FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Li, SM Armstrong, CM Bertin, N Ge, H Milstein, S Boxem, M Vidalain, PO Han, JDJ Chesneau, A Hao, T Goldberg, DS Li, N Martinez, M Rual, JF Lamesch, P Xu, L Tewari, M Wong, SL Zhang, LV Berriz, GF Jacotot, L Vaglio, P Reboul, J Hirozane-Kishikawa, T Li, QR Gabel, HW Elewa, A Baumgartner, B Rose, DJ Yu, HY Bosak, S Sequerra, R Fraser, A Mango, SE Saxton, WM Strome, S van den Heuvel, S Piano, F Vandenhaute, J Sardet, C Gerstein, M Doucette-Stamm, L Gunsalus, KC Harper, JW Cusick, ME Roth, FP Hill, DE Vidal, M AF Li, SM Armstrong, CM Bertin, N Ge, H Milstein, S Boxem, M Vidalain, PO Han, JDJ Chesneau, A Hao, T Goldberg, DS Li, N Martinez, M Rual, JF Lamesch, P Xu, L Tewari, M Wong, SL Zhang, LV Berriz, GF Jacotot, L Vaglio, P Reboul, J Hirozane-Kishikawa, T Li, QR Gabel, HW Elewa, A Baumgartner, B Rose, DJ Yu, HY Bosak, S Sequerra, R Fraser, A Mango, SE Saxton, WM Strome, S van den Heuvel, S Piano, F Vandenhaute, J Sardet, C Gerstein, M Doucette-Stamm, L Gunsalus, KC Harper, JW Cusick, ME Roth, FP Hill, DE Vidal, M TI A map of the interactome network of the metazoan C-elegans SO SCIENCE LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; CAENORHABDITIS-ELEGANS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; EYE DEVELOPMENT; GENOME; IDENTIFICATION; INFORMATION; DROSOPHILA; COMPLEXES AB To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains similar to5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses. C1 Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Inst Genet Mol, CNRS, UMR 5535, F-34293 Montpellier, France. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Fac Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Belgium. Baylor Coll Med, Verna & Marrs Dept Biochem & Mol Biol, Program Cell & Mol Biol Biophys & Biol, Houston, TX 77030 USA. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. Agencourt Biosci Corp, Beverly, MA 01915 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NYU, Dept Biol, New York, NY 10003 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Boxem, Mike/B-8857-2011; van den Heuvel, Sander/B-8892-2011; Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; Reboul, Jerome/P-9103-2016; OI Bertin, Nicolas/0000-0002-9835-9606; Boxem, Mike/0000-0003-3966-4173; Reboul, Jerome/0000-0002-5513-4546; Vaglio, Philippe/0000-0003-2900-5596; Elewa, Ahmed/0000-0002-1988-7970; Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X; Fraser, Andrew/0000-0001-9939-6014 FU NIA NIH HHS [R01 AG011085]; NIGMS NIH HHS [R01 GM034059, R01 GM034059-18] NR 27 TC 1162 Z9 1220 U1 4 U2 80 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 JAN 23 PY 2004 VL 303 IS 5657 BP 540 EP 543 DI 10.1126/science.1091403 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765XM UT WOS:000188316400043 PM 14704431 ER PT J AU MacLaughlin, DT Donahoe, PK AF MacLaughlin, DT Donahoe, PK TI Mechanisms of disease: Sex determination and differentiation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID MULLERIAN-INHIBITING SUBSTANCE; CONGENITAL ADRENAL-HYPERPLASIA; STEROIDOGENIC FACTOR-I; MIXED GONADAL-DYSGENESIS; HUMAN ANDROGEN RECEPTOR; PRIMORDIAL GERM-CELLS; HUMAN Y-CHROMOSOME; TRUE HERMAPHRODITISM; X-CHROMOSOME; 21-HYDROXYLASE DEFICIENCY C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP MacLaughlin, DT (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. EM maclaughlin@helix.mgh.harvard.edu; donahoe.patricia@mgh.harvard.edu FU NCI NIH HHS [CA 17393]; NICHD NIH HHS [HD 32112] NR 89 TC 128 Z9 149 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 2004 VL 350 IS 4 BP 367 EP 378 DI 10.1056/NEJMra022784 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 765EU UT WOS:000188254800009 PM 14736929 ER PT J AU Young, RH McDougal, WS Shipley, WU Kaufman, DS Heney, NM Zietman, AL Sacco, DE AF Young, RH McDougal, WS Shipley, WU Kaufman, DS Heney, NM Zietman, AL Sacco, DE TI A 57-year-old man with invasive transitional-cell carcinoma of the bladder - Transitional-cell carcinoma of the urinary bladder, grade 3 of 3, with invasion of the muscularis propria and involvement of the prostatic urethra (stage T2N0M0 [muscle invasion without nodal or distant metastasis]). Recurrent transitional-cell carcinoma of the urinary bladder, grade 3 of 3, after treatment according to a bladder-sparing protocol, with invasion of the lamina propria. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SELECTIVE ORGAN PRESERVATION; COMBINED-MODALITY PROGRAM; QUALITY-OF-LIFE; TRANSURETHRAL RESECTION; RADIATION-THERAPY; CANCER; CYSTECTOMY; CHEMOTHERAPY; CONSERVATION; RADIOTHERAPY C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, 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 Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Urol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 2004 VL 350 IS 4 BP 394 EP 402 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 765EU UT WOS:000188254800013 ER PT J AU Matejuk, A Dwyer, J Hopke, C Vandenbark, AA Offner, H AF Matejuk, A Dwyer, J Hopke, C Vandenbark, AA Offner, H TI Opposing roles for TGF-beta 1 and TGF-beta 3 isoforms in experimental autoimmune encephalomyelitis SO CYTOKINE LA English DT Article DE EAE; estrogen; TGF-beta 1; TGF-beta 3 ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GROWTH-FACTOR-BETA; MYELIN BASIC-PROTEIN; MESSENGER-RNA EXPRESSION; T-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; TGF-BETA; DIFFERENTIAL EXPRESSION; CYTOKINE RESPONSE; NERVOUS-SYSTEM AB Hormones can exert significant protective effects on autoimmune diseases by activating immunoregulatory mechanisms. One of the possible mechanisms of hormonal protection might be through the anti-inflammatory effects of the TGF-beta molecule. The present study investigated the changes in expression of two TGF-beta isoforms, TGF-beta1 and TGF-beta3, in C57BL/6 and TCR transgenic (T/R+) B10.PL mice that manifested or were protected against clinical signs of experimental autoimmune encephalomyelitis (EAE) with 17beta-estradiol (E2) treatment. We here demonstrate an inverse relationship between expression of TGF-beta1 that is enhanced in mice with EAE, and TGF-beta3 that is enhanced in E2-protected mice. The differential expression of TGF-beta isoforms was observed in spinal cord tissue but not spleen. Additionally TGF-beta1 expression was evident both in whole spinal cord tissue and mononuclear cells isolated from inflamed tissue, in contrast to TGF-beta3 that was only detected in spinal cord tissue but not in mononuclear cells. Further studies revealed that CD3 and especially MAC-1 positive cells were the main source of TGF-beta1 in the mononuclear CNS population. Of crucial importance, the TGF-beta3 isoform displayed anti-proliferative properties towards encephalitogenic cells in vitro. We propose that the TGF-beta1 and TGF-beta3 isoforms play opposing roles in the expression of EAE. (C) 2003 Elsevier Ltd. All rights reserved. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM offnerva@ohsu.edu FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 39 TC 12 Z9 13 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN 21 PY 2004 VL 25 IS 2 BP 45 EP 51 DI 10.1016/j.cyto.2003.09.007 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 765NW UT WOS:000188290900001 PM 14693159 ER PT J AU Lee, SR Tsuji, K Lee, SR Lo, EH AF Lee, SR Tsuji, K Lee, SR Lo, EH TI Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stroke; neuroprotection; hippocampus; mouse; neuroinflammation; MMPs ID TISSUE-PLASMINOGEN ACTIVATOR; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; GENE KNOCK-OUT; CELL-DEATH; EXTRACELLULAR PROTEOLYSIS; HIPPOCAMPAL-FORMATION; FOREBRAIN ISCHEMIA; MOUSE HIPPOCAMPUS; INDUCED APOPTOSIS AB Mechanisms of selective neuronal death in the hippocampus after global cerebral ischemia remain to be clarified. Here, we explored a possible role for matrix metalloproteinases (MMPs) in this phenomenon. Although many studies have demonstrated detrimental roles for the gelatinase MMP-9 in focal cerebral ischemia, how dysregulated MMP proteolysis influences global cerebral ischemia is less well understood. In this study, CD-1 mice were subjected to transient global ischemia. Transient occlusions of common carotid arteries for periods between 20 and 40 min led to increasing hippocampal neuronal death after 3 d. Gel zymography showed elevations in gelatinase (MMP-2 and MMP-9) activity. In situ zymography showed that gelatinase activity was mostly colocalized with neuron-specific nuclear protein-stained pyramidal neurons. Mice treated with the broad-spectrum metalloproteinase inhibitor BB-94 (50 mg/kg, i.p.) showed reduced hippocampal gelatinase activity after transient global cerebral ischemia and suffered significantly reduced hippocampal neuronal damage compared with vehicle-treated controls (p < 0.01). Additionally, hippocampal gelatinase activity and neuronal damage after transient global ischemia were also significantly reduced in MMP-9 knock-out mice compared with wild-type mice (p < 0.05). These data indicate a potential deleterious role for MMP-9 in the pathogenesis of delayed neuronal damage in the hippocampus after global cerebral ischemia. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Lo, EH (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS38731, R01-NS40529] NR 56 TC 171 Z9 185 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 21 PY 2004 VL 24 IS 3 BP 671 EP 678 DI 10.1523/JNEUROSCI.4243-03.2004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 765UK UT WOS:000188302000013 PM 14736853 ER PT J AU Rubenstein, MH Finn, AV Leinbach, RC Hollenbach, S Aretz, HT Virmani, R Gold, HK AF Rubenstein, MH Finn, AV Leinbach, RC Hollenbach, S Aretz, HT Virmani, R Gold, HK TI Short-term intravenous eptifibatide infusion combined with reduced dose recombinant tissue plasminogen activator inhibits platelet recruitment at sites of coronary artery injury SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Scientific Session of the American-College-of-Cardiology CY MAR 17-20, 2002 CL ATLANTA, GEORGIA SP Amer Coll Cardiol ID ANTIPLATELET GPIIB/IIIA ANTIBODY; ACUTE MYOCARDIAL-INFARCTION; SINGLE BOLUS INJECTION; GLYCOPROTEIN-IIB/IIIA; VESSEL WALL; HEPARIN-ANTITHROMBIN; REPERFUSION THERAPY; MONOCLONAL-ANTIBODY; RANDOMIZED TRIAL; BLEEDING-TIME AB OBJECTIVES This study was designed to determine in a dog model of coronary thrombosis whether short-term eptifibatide (Ep) combined with low-dose plasminogen activator (rt-PA) inhibits platelet recruitment at sites of endothelial damage after normalization of platelet function. BACKGROUND Ep plus reduced-dose rt-PA has not previously been shown to render a recanalized coronary artery resistant to platelet recruitment after normalization of platelet function. METHODS Inhibition of platelet recruitment was studied by scanning electron microscopy (SEM) in a canine model of left anterior descending (LAD) thrombosis. In phase I treatment groups were: 1) Ep (n = 6); 2) Ep + rt-PA (n = 6); 3) rt-PA (n = 6); and 4) placebo (n = 4). Coronary blood flow was monitored and LAD segments excised for SEM after 90-min infusion of study drug. In phase 11, dogs were randomized to Ep alone (n = 5) or to Ep + rt-PA (n = 5). Coronary blood flow was monitored during and 120 min after cessation of drug when platelet function had returned to normal and LAD segments were excised. RESULTS All animals except placebo showed reflow. In phase 1, SEM showed an absence of platelet aggregates with Ep alone and with Ep + rt-PA, but not with rt-PA alone. In phase 11, SEM showed an intimal surface devoid of mural thrombus and platelet aggregates only in Ep + rt-PA treated arteries. Ep-alone treated arteries showed new platelet aggregates at sites of residual mural thrombus. CONCLUSIONS Short-term infusion Ep plus low-dose rt-PA acutely neutralizes the ability of damaged endothelial surfaces to recruit new platelets by inhibiting platelet aggregation and eliminating residual mural thrombus. (C) 2004 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Millennium Pharmaceut Inc, Boston, MA USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Gold, HK (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. EM hgold@partners.org NR 31 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 21 PY 2004 VL 43 IS 2 BP 287 EP 294 DI 10.1016/j.jacc.2003.08.039 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765CD UT WOS:000188248800022 PM 14736451 ER PT J AU Berbeco, RI Jiang, SB Sharp, GC Chen, GTY Mostafavi, H Shirato, H AF Berbeco, RI Jiang, SB Sharp, GC Chen, GTY Mostafavi, H Shirato, H TI Integrated radiotherapy imaging system (IRIS): design considerations of tumour tracking with linac gantry-mounted diagnostic x-ray systems with flat-panel detectors SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; ORGAN MOTION; MOVEMENT; LUNG; PANCREAS; LIVER AB The design of an integrated radiotherapy imaging system (IRIS), consisting of gantry mounted diagnostic (kV) x-ray tubes and fast read-out flat-panel amorphous-silicon detectors, has been studied. The system is meant to be capable of three main functions: radiographs for three-dimensional (3D) patient set-up, cone-beam CT and real-time tumour/marker tracking. The goal of the current study is to determine whether one source/panel pair is sufficient for real-time tumour/marker tracking and, if two are needed, the optimal position of each relative to other components and the isocentre. A single gantry-mounted source/imager pair is certainly capable of the first two of the three functions listed above and may also be useful for the third, if combined with prior knowledge of the target's trajectory. This would be necessary because only motion in two dimensions is visible with a single imager/source system. However, with previously collected information about the trajectory, the third coordinate may be derived from the other two with sufficient accuracy to facilitate tracking. This deduction of the third coordinate can only be made if the 3D tumour/marker trajectory is consistent from fraction to fraction. The feasibility of tumour tracking with one source/imager pair has been theoretically examined here using measured lung marker trajectory data for seven patients from multiple treatment fractions. The patients' selection criteria include minimum mean amplitudes of the tumour motions greater than 1 cm peak-to-peak. The marker trajectory for each patient was modelled using the first fraction data. Then for the rest of the data, marker positions were derived from the imager projections at various gantry angles and compared with the measured tumour positions. Our results show that, due to the three dimensionality and irregular trajectory characteristics of tumour motion, on a fraction-to-fraction basis, a 'monoscopic' system (single source/imager) is inadequate for consistent real-time tumour tracking, even with prior knowledge. We found that, among the seven patients studied with peak-to-peak marker motion greater than 1 cm, five cases have mean localization errors greater than 2 mm and two have mean errors greater than 3 mm. Because of this uncertainty associated with a monoscopic system, two source/imager pairs are necessary for robust 3D target localization. Dual orthogonal x-ray source/imager pairs mounted on the linac gantry are chosen for the IRIS. We further studied the placement of the x-ray sources/panel based on the geometric specifications of the Varian 21EX Clinac. The best configuration minimizes the localization error while maintaining a large field of view and avoiding collisions with the floor/ceiling or couch. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Varian Med Syst Inc, Ginzton Technol Ctr, Palo Alto, CA USA. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. RP Berbeco, RI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM rberbeco@partners.org RI Shirato, Hiroki/A-7068-2010 NR 15 TC 111 Z9 117 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 JAN 21 PY 2004 VL 49 IS 2 BP 243 EP 255 AR PII S0031-9155(04)68365-5 DI 10.1088/0031-9155/49/2/005 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 806GF UT WOS:000220421700005 PM 15083669 ER PT J AU Atwood, CS Perry, G Zeng, H Kato, Y Jones, WD Ling, KQ Huang, XD Moir, RD Wang, DD Sayre, LM Smith, MA Chen, SG Bush, AI AF Atwood, CS Perry, G Zeng, H Kato, Y Jones, WD Ling, KQ Huang, XD Moir, RD Wang, DD Sayre, LM Smith, MA Chen, SG Bush, AI TI Copper mediates dityrosine cross-linking of Alzheimer's amyloid-beta SO BIOCHEMISTRY LA English DT Article ID METAL-CATALYZED OXIDATION; REACTION END-PRODUCTS; A-BETA; PROTEIN OXIDATION; CEREBROSPINAL-FLUID; HYDROGEN-PEROXIDE; TRANSITION-METALS; SENILE PLAQUES; FREE-RADICALS; DISEASE AB We have previously reported that amyloid Abeta, the major component of senile plaques in Alzheimer's disease (AD), binds Cu with high affinity via histidine and tyrosine residues [Atwood, C. S., et al. (1998) J. Biol. Chem. 273, 12817-12826; Atwood, C. S., et al. (2000) J. Neurochem. 75, 12191233] and produces H2O2 by catalyzing the reduction of Cu(II) or Fe(III) [Huang, X., et al. (1999) Biochemistry 38, 7609-7616; Huang, X., et al. (1999) J. Biol. Chem. 274, 37111-37116]. Incubation with Cu induces the SDS-resistant oligomerization of Abeta [Atwood, C. S., et al. (2000) J. Neurochem. 75, 1219-1233], a feature characteristic of neurotoxic soluble Abeta extracted from the AD brain. Since residues coordinating Cu are most vulnerable to oxidation, we investigated whether modifications of these residues were responsible for Abeta cross-linking. SDS-resistant oligomerization of Abeta caused by incubation with Cu was found to induce a fluorescence signal characteristic of tyrosine cross-linking. Using ESI-MS and a dityrosine specific antibody, we confirmed that Cu(II) (at concentrations lower than that associated with amyloid plaques) induces the generation of dityrosine-cross-linked, SDS-resistant oligomers of human, but not rat, Abeta peptides. The addition of H2O2 strongly promoted Cu-induced dityrosine cross-linking of Abeta1-28, Abeta1-40, and Abeta1-42, suggesting that the oxidative coupling is initiated by interaction of H2O2 with a Cu(II) tyrosinate. The dityrosine modification is significant since it is highly resistant to proteolysis and is known to play a role in increasing structural strength. Given the elevated concentration of Cu in senile plaques, our results suggest that Cu interactions with Abeta could be responsible for causing the covalent cross-linking of Abeta in these structures. C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Edith Cowan Univ, Sch Biomed & Sports Sci, Ctr Aging & Alzheimers Dis, Joondalup, WA 6027, Australia. Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA. Himeji Inst Technol, Sch Humanities Environm Policy & Technol, Himeji, Hyogo 6700092, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Lab Oxidat Biol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Atwood, CS (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Sch Med, GRECC 11G,2500 Overlook Terrace, Madison, WI 53705 USA. EM csa@medicine.wisc.edu RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009; Jones, Walton/A-2417-2011; Sayre, Lawrence/C-8224-2011; Bush, Ashley/A-1186-2007; Chen, Shu/O-4750-2014 OI Perry, George/0000-0002-6547-0172; Jones, Walton/0000-0001-8642-627X; Bush, Ashley/0000-0001-8259-9069; Chen, Shu/0000-0001-7180-3001 FU NIA NIH HHS [AG19356, P50AG08012, R01 AG14249] NR 63 TC 235 Z9 244 U1 2 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 20 PY 2004 VL 43 IS 2 BP 560 EP 568 DI 10.1021/bi0358824 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763RH UT WOS:000188113900031 PM 14717612 ER PT J AU Diwan, A Dibbs, Z Nemoto, S DeFreitas, G Carabello, BA Sivasubramanian, N Wilson, EM Spinale, FG Mann, DL AF Diwan, A Dibbs, Z Nemoto, S DeFreitas, G Carabello, BA Sivasubramanian, N Wilson, EM Spinale, FG Mann, DL TI Targeted overexpression of noncleavable and secreted forms of tumor necrosis factor provokes disparate cardiac phenotypes SO CIRCULATION LA English DT Article DE hypertrophy; remodeling; metalloproteinases ID MATRIX-METALLOPROTEINASE INHIBITION; FACTOR-ALPHA; HEART-FAILURE; CONVERTING ENZYME; TRANSGENIC MICE; DYSFUNCTION; GEOMETRY AB Background - Recent studies suggest that posttranslation processing or "shedding" (ie, secretion) of tumor necrosis factor (TNF) by tumor necrosis factor-alpha converting enzyme ( TACE) may contribute to the left ventricular (LV) remodeling that occurs in the failing human heart. Methods and Results - To address the functional significance of TNF shedding, we generated lines of transgenic mice with targeted overexpression of secreted wild-type (MHCsTNF2) TNF and overexpression of a mutated noncleavable transmembrane form of TNF (MHCmTNF). Both lines of mice had overlapping levels of myocardial TNF protein; however, the phenotypes of the MHCsTNF2 and MHCmTNF mice were strikingly disparate. Whereas the MHCmTNF mice developed a concentric LV hypertrophy phenotype, the MHCsTNF2 mice developed a dilated LV phenotype. The fibrillar collagen weave in MHCmTNF mice with concentric hypertrophy was characterized by thick collagen fibrils and increased collagen content, whereas the fibrillar collagen weave in the MHCsTNF2 mice with LV dilation was characterized by a diminished collagen content. Inhibition of matrix metalloproteinases with a broad-based matrix metalloproteinase inhibitor prevented LV dilation in the MHCsTNF2 mice. Conclusions - These findings suggest that posttranslational processing of TNF, as opposed to TNF expression per se, is responsible for the adverse cardiac remodeling that occurs after sustained TNF overexpression. C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, Med Serv Care Line, Houston, TX 77030 USA. Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, MS 524,6565 Fannin, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL-42250-10/10, P50 HL-O6H, R01 HL58081-01, R01 HL61543-01] NR 15 TC 48 Z9 48 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 JAN 20 PY 2004 VL 109 IS 2 BP 262 EP 268 DI 10.1161/01.CIR.0000109642.27985.FA PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 765CX UT WOS:000188250500021 PM 14699008 ER PT J AU van den Heuvel, S AF van den Heuvel, S TI Protein degradation: CUL-3 and BTB - Partners in proteolysis SO CURRENT BIOLOGY LA English DT Editorial Material ID CAENORHABDITIS-ELEGANS; UBIQUITIN-LIGASE; SPINDLE COMPONENT; COMPLEX; MEI-1; GENE; ADAPTERS; MEIOSIS; MEL-26 AB In early C. elegrans embryos, the transition from meiosis to mitosis requires degradation of the MEI-1 protein. A novel class of SCF-like ubiquitin ligases has been identified that mediates this process. These ligases contain the CUL-3 scaffold at their core and use a BTB-domain protein in substrate recognition. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP van den Heuvel, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 NR 16 TC 38 Z9 39 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 20 PY 2004 VL 14 IS 2 BP R59 EP R61 DI 10.1016/j.cub.2003.12.044 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 767ZU UT WOS:000188504400008 PM 14738749 ER PT J AU Wei, EK Giovannucci, E Wu, K Rosner, B Fuchs, CS Willett, WC Colditz, GA AF Wei, EK Giovannucci, E Wu, K Rosner, B Fuchs, CS Willett, WC Colditz, GA TI Comparison of risk factors for colon and rectal cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colon cancer; rectal cancer; cohort studies; risk factors ID FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; PHYSICAL-ACTIVITY QUESTIONNAIRE; COLORECTAL-CANCER; CIGARETTE-SMOKING; UNITED-STATES; WOMEN; VALIDITY; ADENOMA; MEN AB Predictors of colorectal cancer have been extensively studied with some evidence suggesting that risk factors vary by subsite. Using data from 2 prospective cohort studies, we examined established risk factors to determine whether they were differentially associated with colon and rectal cancer. Our study population included 87,733 women from the Nurses' Health Study (NHS) and 46,632 men from the Health Professionals Follow Up Study (HPFS). Exposure information was collected via biennial questionnaires (dietary variables were collected every 4 years). During the follow-up period (NHS: 1980 to May 31, 2000; HPFS: 1986 to January 31, 2000), we identified 1, 139 cases of colon cancer and 339 cases of rectal cancer. We used pooled logistic regression to estimate multivariate relative risks for the 2 outcomes separately and then used polytomous logistic regression to compare these estimates. In the combined cohort, age, gender, family history of colon or rectal cancer, height, body mass index, physical activity, folate, intake of beef, pork or lamb as a main dish, intake of processed meat and alcohol were significantly associated with colon cancer risk. However, only age and sex were associated with rectal cancer. In a stepwise polytomous logistic regression procedure, family history and physical activity were associated with statistically significant different relative risks of colon and rectal cancer. Our findings support previous suggestions that family history and physical activity are not strong contributors to the etiology of rectal cancer. Future investigations of colon or rectal cancer should take into consideration risk factor differences by subsite. (C) 2003 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Wei, EK (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [P01 CA087969-01, CA87969, P01 CA087969] NR 41 TC 265 Z9 271 U1 2 U2 18 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 20 PY 2004 VL 108 IS 3 BP 433 EP 442 DI 10.1002/ijc.11540 PG 10 WC Oncology SC Oncology GA 754BK UT WOS:000187282700015 PM 14648711 ER PT J AU Janakiraman, A Goldberg, MB AF Janakiraman, A Goldberg, MB TI Evidence for polar positional information independent of cell division and nucleoid occlusion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIN-BASED MOTILITY; ESCHERICHIA-COLI; FTSZ RING; UNIPOLAR LOCALIZATION; MIN SYSTEM; ICSA; PLACEMENT; MUTANTS; CYTOKINESIS; PROTEIN AB We present evidence that, in Escherichia coli, polar positional information is present at midcell independent of known cell division factors. In filamented cells, IcsA, which is normally polar, localizes at or near potential cell division sites. Because the cell pole is derived from the septum, the sites to which IcsA localizes in filaments correspond to future poles. IcsA localization to these sites is independent of FtsZ, MinCDE, septation, and nucleoid occlusion, indicating that positional information for the future pole is independent of cell division and chromosome positioning. Upon IcsA localization to these sites, septation is inhibited, suggesting that IcsA recognition of this polar positional information may influence cell division. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [AI35817, R01 AI035817] NR 36 TC 37 Z9 38 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 JAN 20 PY 2004 VL 101 IS 3 BP 835 EP 840 DI 10.1073/pnas.0305747101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768VH UT WOS:000188555400027 PM 14715903 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, KW TI Presentation of a self-peptide in two distinct conformations by a disease-associated HLA-B27 subtype SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID ANKYLOSING-SPONDYLITIS; VIRAL PEPTIDES; SUSCEPTIBILITY; COMPLEX C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu NR 17 TC 9 Z9 9 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 JAN 19 PY 2004 VL 199 IS 2 BP 151 EP 154 DI 10.1084/jem.20032050 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 766HC UT WOS:000188369700001 PM 14734520 ER PT J AU Cortes, M Georgopoulos, K AF Cortes, M Georgopoulos, K TI Aiolos is required for the generation of high affinity bone marrow plasma cells responsible for long-term immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE plasma cell subsets; long-term antibody production; immunologic memory; Aiolos; transcription factor ID ANTIBODY-FORMING-CELLS; GERMINAL-CENTERS; IN-SITU; CLONAL SELECTION; B-CELLS; MEMORY; MICE; MATURATION; IKAROS; (4-HYDROXY-3-NITROPHENYL)ACETYL AB Antigenic encounter generates long-term immunity sustained by long-lived high affinity plasma cells resident in the bone marrow (BM). Here we show that the Ikaros family member, Aiolos, is specifically required for the generation of these plasma cells. Failure to generate high affinity plasma cells in the BM and to sustain serum antibody titers is apparent after both primary and secondary immunization of Aiolos(-/-) mice with a range of hapten concentrations. Chimera reconstitutions demonstrate that the BM plasma cell defect is B cell intrinsic. Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation. No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge. These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St,3rd Floor, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu FU NIAID NIH HHS [R01 AI042254, R01-AI/CA42254] NR 33 TC 53 Z9 59 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 19 PY 2004 VL 199 IS 2 BP 209 EP 219 DI 10.1084/jem.20031571 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 766HC UT WOS:000188369700007 PM 14718515 ER PT J AU Pachori, AS Melo, LG Zhang, LN Loda, M Pratt, RE Dzau, VJ AF Pachori, AS Melo, LG Zhang, LN Loda, M Pratt, RE Dzau, VJ TI Potential for germ line transmission after intramyocardial gene delivery by adeno-associated virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AAV; chromosomal integration; ectopic expression; gene transfer; germ cell line transmission; myocardial gene therapy ID MYOCARDIAL-ISCHEMIA; THERAPY; VECTOR; ANGIOGENESIS; TRANSDUCTION; INTEGRATION; EXPRESSION; ADENOVIRUS; INJECTION; HEART AB Intramyocardial injection of adeno-associated virus (AAV) has been shown to be an effective strategy for cardiac gene delivery. This approach leads to long-term gene expression in the heart, offering the possibility of chronic gene therapy. However, the long-term safety of this approach with regard to vector bio-distribution and extracardiac transgene expression has not been evaluated. To examine these issues, 8-week-old male Sprague-Dawley rats were injected intramyocardially with either 4 x 10(11) particles of AAV-2-lacZ or saline at five locations in the anterioposterior apical region of the left ventricle. Animals were sacrificed at 3 and 6 months after gene transfer, tissues were harvested and analyzed for lacZ expression by semi-quantitative RT-PCR and beta-galactosidase activity using X-gal staining. We observed high level of transgene expression in the myocardium at 3 months after gene transfer, which persisted up to 6 months of follow-up. Also, significantly we detected lacZ expression and beta-galactosidase activity in extracardiac tissues such as liver, kidney, and testes at 6 months. More significantly, late transgene expression was detected in cellular elements of the seminiferous tubule, including Sertoli cells and spermatogonia like cells. These data demonstrate the efficacy of AAV-2 delivery for long-term myocardial gene therapy, but raise concerns about the possibility of ectopic transgene expression and germ cell line infection. (C) 2003 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada. RP Dzau, VJ (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM vdzau@partners.org FU NHLBI NIH HHS [HL 058516, HL 072010, HL 073219, HL35610] NR 23 TC 21 Z9 22 U1 1 U2 3 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 JAN 16 PY 2004 VL 313 IS 3 BP 528 EP 533 DI 10.1016/j.bbrc.2003.11.140 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 761HA UT WOS:000187894400012 PM 14697221 ER PT J AU Matthews, BD Overby, DR Alenghat, FJ Karavitis, J Numaguchi, Y Allen, PG Ingber, DE AF Matthews, BD Overby, DR Alenghat, FJ Karavitis, J Numaguchi, Y Allen, PG Ingber, DE TI Mechanical properties of individual focal adhesions probed with a magnetic microneedle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mechanical stress; integrins; focal adhesion; mechanotransduction; cell mechanics; magnetometry ID CELL-SHAPE; ENDOTHELIAL-CELLS; LIVING CELLS; INTEGRIN; CYTOSKELETON; GROWTH; FORCE; CONTRACTILITY; MIGRATION; COMPLEXES AB A permanent magnetic microneedle was developed to apply tensional forces to integrin receptors via ligand-coated magnetic microbeads while optically analyzing the mechanical properties of individual focal adhesions. Force application (130 pN for 3 s) through activated beta1 integrins produced less bead displacement than when unligated integrins were stressed. This strengthening response differed markedly on a bead-by-bead basis, correlated directly with local focal adhesion assembly, and was similar when analyzed at 4 degreesC, indicating that it was due to passive material properties of the cell. Viscoelastic analysis clarified that recruitment of focal adhesion proteins increased the local elastic stiffness of the adhesion complex without changing its viscous behavior. These data indicate that individual focal adhesions exhibit distinct mechanical properties that depend upon local focal adhesion assembly, and that these local variations in micromechanics can be detected and analyzed within living cells using the permanent magnetic microneedle technique. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. RP Ingber, DE (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Pathol, Boston, MA 02115 USA. EM donald.ingber@tch.harvard.edu RI Overby, Darryl/G-1520-2011; OI Overby, Darryl/0000-0001-9894-7515; Alenghat, Francis/0000-0003-4151-9258 NR 36 TC 88 Z9 91 U1 1 U2 31 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 JAN 16 PY 2004 VL 313 IS 3 BP 758 EP 764 DI 10.1016/j.bbrc.2003.12.005 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 761HA UT WOS:000187894400047 PM 14697256 ER PT J AU Amici, R Sanford, LD Kearney, K McInerney, B Ross, RJ Horner, RL Morrison, AR AF Amici, R Sanford, LD Kearney, K McInerney, B Ross, RJ Horner, RL Morrison, AR TI A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus participates in regulating the pattern of rapid-eye-movement sleep occurrence in the rat SO BRAIN RESEARCH LA English DT Article DE REM sleep; serotonin; 5-HT2 receptor; laterodorsal tegmental nucleus; single REM sleep episode; sequential REM sleep episode; REM sleep cluster ID DORSAL RAPHE NUCLEUS; FREELY MOVING CATS; MESOPONTINE CHOLINERGIC NUCLEI; REM-SLEEP; AMBIENT-TEMPERATURE; BEHAVIORAL AROUSAL; WAKING CYCLE; NEURONS; WAKEFULNESS; AGONIST AB Serotonin [5-hydroxytryptamine (5-HT)] plays an inhibitory role in rapid-eye-movement (REM) sleep although the exact mechanism(s) and site(s) of action are not known. It is commonly assumed that 5-HT exerts its influence on REM sleep via input from the dorsal raphe nucleus (DRN) directly onto cholinergic neurons involved in the generation of REM sleep. 5-HT2 receptor sites have been found on cholinergic neurons in the laterodorsal tegmental nucleus (LDT) and pedunculopontine tegmental nucleus (PPT). We locally microinjected the 5-HT2 agonist DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl) and the 5-HT2 antagonist, ketanserin, in LDT in rats to determine whether these receptor sites are involved in the regulation of behavioral states. DOI and ketanserin primarily affected REM sleep, by significantly decreasing or increasing, respectively, the number, but not the duration, of REM sleep episodes. DOI specifically decreased the occurrence of clusters of REM sleep episodes appearing at intervals less than or equal to 3 min (sequential episodes) without affecting single episodes separated by more than 3 min. An opposite effect of ketanserin on REM sleep clusters, although not statistically significant, was observed. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Penn, Sch Vet Med, Dept Biol Anim, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Bologna, Dept Human & Gen Physiol, Bologna, Italy. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Morrison, AR (reprint author), Univ Penn, Sch Vet Med, Dept Biol Anim, Lab Study Brain Sleep, 3800 Spruce St, Philadelphia, PA 19104 USA. EM armsleep@vet.upenn.edu FU NHLBI NIH HHS [HLB42236]; NIMH NIH HHS [MH42903] NR 47 TC 24 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 16 PY 2004 VL 996 IS 1 BP 9 EP 18 DI 10.1016/j.brainres.2003.09.026 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 760XX UT WOS:000187861500002 PM 14670626 ER PT J AU Keresztes, G Martemyanov, KA Krispel, CM Mutai, H Yoo, PJ Maison, SF Burns, ME Arshavsky, VY Heller, S AF Keresztes, G Martemyanov, KA Krispel, CM Mutai, H Yoo, PJ Maison, SF Burns, ME Arshavsky, VY Heller, S TI Absence of the RGS9 center dot G beta 5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN BETA-SUBUNIT; ACCELERATING PROTEIN; ROD PHOTORESPONSE; MEMBRANE ANCHOR; MICE LACKING; RGS9-1; CELLS; DEACTIVATION; ADAPTATION AB Timely termination of the light response in retinal photoreceptors requires rapid inactivation of the G protein transducin. This is achieved through the stimulation of transducin GTPase activity by the complex of the ninth member of the regulator of G protein signaling protein family (RGS9) with type 5 G protein beta subunit (Gbeta5). RGS9.Gbeta5 is anchored to photoreceptor disc membranes by the transmembrane protein, R9AP. In this study, we analyzed visual signaling in the rods of R9AP knockout mice. We found that light responses from R9AP knockout rods were very slow to recover and were indistinguishable from those of RGS9 or Gbeta5 knockout rods. This effect was a consequence of the complete absence of any detectable RGS9 from the retinas of R9AP knockout mice. On the other hand, the level of RGS9 mRNA was not affected by the knockout. These data indicate that in photoreceptors R9AP determines the stability of the RGS9.Gbeta5 complex, and therefore all three proteins, RGS9, Gbeta5, and R9AP, are obligate members of the regulatory complex that speeds the rate at which transducin hydrolyzes GTP. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Labs, Boston, MA 02114 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. RP Heller, S (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM hellers@epl.meei.harvard.edu FU NEI NIH HHS [R01 EY014047-03, EY 12859, EY 14147, R01 EY014047]; NIDCD NIH HHS [DC 04563] NR 20 TC 72 Z9 74 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 16 PY 2004 VL 279 IS 3 BP 1581 EP 1584 DI 10.1074/jbc.C300456200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700003 PM 14625292 ER PT J AU Mukhin, YV Garnovskaya, MN Ullian, ME Raymond, JR AF Mukhin, YV Garnovskaya, MN Ullian, ME Raymond, JR TI ERK is regulated by sodium-proton exchanger in rat aortic vascular smooth muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NA+-H+ EXCHANGER; GROWTH-FACTOR RECEPTOR; RENAL MESANGIAL CELLS; ASCITES TUMOR-CELLS; ANGIOTENSIN-II; INTRACELLULAR PH; COUPLED RECEPTORS; HEART-FAILURE; VENTRICULAR MYOCYTES AB The purposes of this study were to test 1) the relationship between two widely studied mitogenic effector pathways, and 2) the hypothesis that sodium-proton exchanger type 1 (NHE-1) is a regulator of extracellular signal-regulated protein kinase (ERK) activation in rat aortic smooth muscle (RASM) cells. Angiotensin II (Ang II) and 5-hydroxytryptamine (5-HT) stimulated both ERK and NHE-1 activities, with activation of NHE-1 preceding that of ERK. The concentration-response curves for 5-HT and Ang II were superimposable for both processes. Inhibition of NHE-1 with pharmacological agents or by isotonic replacement of sodium in the perfusate with choline or tetramethylammonium greatly attenuated ERK activation by 5-HT or Ang II. Similar maneuvers significantly attenuated 5-HT- or Ang II-mediated activation of MEK and Ras but not transphosphorylation of the epidermal growth factor (EGF) receptor. EGF receptor blockade attenuated ERK activation, but not NHE-1 activation by 5-HT and Ang II, suggesting that the EGF receptor and NHE-1 work in parallel to stimulate ERK activity in RASM cells, converging distal to the EGF receptor but at or above the level of Ras in the Ras-MEK-ERK pathway. Receptor- independent activation of NHE-1 by acute acid loading of RASM cells resulted in the rapid phosphorylation of ERK, which could be blocked by pharmacological inhibitors of NHE-1 or by isotonic replacement of sodium, closely linking the proton transport function of NHE-1 to ERK activation. These studies identify NHE as a new regulator of ERK activity in RASM cells. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Mukhin, YV (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Rm 829 CSB,POB 250623, Charleston, SC 29425 USA. EM mukhinyv@musc.edu FU NCRR NIH HHS [S10 RR 013005]; NIDDK NIH HHS [DK 52448, DK 02694] NR 67 TC 36 Z9 37 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 JAN 16 PY 2004 VL 279 IS 3 BP 1845 EP 1852 DI 10.1074/jbc.M304907200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700035 PM 14600156 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Personal view: going around in circles - circuitous medical management plans SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ANNOTATED ALGORITHMIC APPROACH; BARRETTS-ESOPHAGUS; SURVEILLANCE AB Physicians occasionally embark on a work-up that, after a lengthy path, leads them to a clinical situation similar to that from which they started their original pursuit. This article aims to describe the characteristics of circular medical management and means for its avoidance. The underlying medical problem often presents itself initially as a bewildering array of consecutive outcomes similar to a complex decision tree. On closer inspection, however, few of the outcomes are associated with a high probability, and only one path stands out as the most likely one to take. This path usually ends in such options as expectant management, supportive measures or doing nothing, which are already available at the onset of work-up. If medical management is drawn out and takes a long time to complete, sight of its circular nature is easily lost. If many different specialists care for a patient, little appreciation for circular paths occurs. A prospective outline of the management plan and the elimination of paths with low a priori probability can help to prevent unnecessary medical interventions. The physician may then come to realize that standing still and waiting become as effective and less costly than a lengthy circular work-up. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JAN 15 PY 2004 VL 19 IS 2 BP 191 EP 195 DI 10.1111/j.0269-2813.2004.01849.x PG 5 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 763YJ UT WOS:000188127800005 PM 14723610 ER PT J AU Tobin, MJ AF Tobin, MJ TI Sleep-disordered breathing, control of breathing, respiratory muscles, pulmonary function testing in AJRCCM 2003 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID POSITIVE AIRWAY PRESSURE; INTERMITTENT HYPOXIA; LUNG-CANCER; QUADRICEPS FATIGABILITY; MECHANICAL VENTILATION; ANATOMIC DISORDER; OXIDATIVE STRESS; CYSTIC-FIBROSIS; APNEA SYNDROME; HEART-FAILURE C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Route 111N, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 85 TC 2 Z9 3 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2004 VL 169 IS 2 BP 254 EP 264 DI 10.1164/rccm.2312010 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763RQ UT WOS:000188114600026 PM 14718239 ER PT J AU Tobin, MJ AF Tobin, MJ TI Asthma, airway biology, and nasal disorders in AJRCCM 2003 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID EXERCISE-INDUCED BRONCHOCONSTRICTION; NITRIC-OXIDE; ALLERGEN CHALLENGE; SIGNALING PATHWAY; EPITHELIAL-CELLS; CHILDHOOD ASTHMA; MOUSE MODEL; IN-VIVO; INFLAMMATION; HYPERRESPONSIVENESS C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 86 TC 4 Z9 4 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2004 VL 169 IS 2 BP 265 EP 276 DI 10.1164/rccm.2312011 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763RQ UT WOS:000188114600027 PM 14718240 ER PT J AU Tobin, MJ AF Tobin, MJ TI Pediatrics, surfactant, and cystic fibrosis in AJRCCM 2003 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID RESPIRATORY-DISTRESS-SYNDROME; MECONIUM ASPIRATION SYNDROME; EXHALED BREATH CONDENSATE; OBSTRUCTIVE SLEEP-APNEA; LUNG-FUNCTION; NONTUBERCULOUS-MYCOBACTERIA; BRONCHOPULMONARY-DYSPLASIA; INTERMITTENT HYPOXIA; CHILDHOOD ASTHMA; PROTEIN-A C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 79 TC 1 Z9 1 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2004 VL 169 IS 2 BP 277 EP 287 DI 10.1164/rccm.2312009 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763RQ UT WOS:000188114600028 PM 14718241 ER PT J AU Tobin, MJ AF Tobin, MJ TI Tuberculosis, lung infections, interstitial lung disease, social issues and journalology in AJRCCM 2003 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID IDIOPATHIC PULMONARY-FIBROSIS; ACUTE RESPIRATORY SYNDROME; NECROSIS-FACTOR-ALPHA; DOUBLE-EDGED-SWORD; CYSTIC-FIBROSIS; LATENT TUBERCULOSIS; INTERFERON-GAMMA; GROWTH-FACTOR; HYPERSENSITIVITY PNEUMONITIS; NONTUBERCULOUS-MYCOBACTERIA C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 116 TC 2 Z9 2 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2004 VL 169 IS 2 BP 288 EP 300 DI 10.1164/rccm.2312006 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763RQ UT WOS:000188114600029 PM 14718242 ER PT J AU Tobin, MJ AF Tobin, MJ TI Chronic obstructive pulmonary disease, pollution, pulmonary vascular disease, transplantation, pleural disease, and lung cancer in AJRCCM 2003 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 11IN, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 0 TC 3 Z9 6 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2004 VL 169 IS 2 BP 301 EP 313 DI 10.1164/rccm.2312007 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 763RQ UT WOS:000188114600030 PM 14718243 ER PT J AU Kovalenko, OV Yang, XW Kolesnikova, TV Hemler, ME AF Kovalenko, OV Yang, XW Kolesnikova, TV Hemler, ME TI Evidence for specific tetraspanin homodimers: inhibition of palmitoylation makes cysteine residues available for cross-linking SO BIOCHEMICAL JOURNAL LA English DT Article DE CD9; cross-linking; cysteine; oligomerization; palmitoylation; tetraspanin ID AMINO-ACID-RESIDUES; PROTEIN-KINASE-C; TRANSMEMBRANE-4 SUPERFAMILY; EXTRACELLULAR DOMAIN; PHOTORECEPTOR PERIPHERIN/RDS; ENDOTHELIAL-CELLS; HLA-DR; INTEGRIN; CD81; CD151 AB It is a well-established fact that tetraspanin proteins, a large family of integral membrane proteins involved in cell motility, fusion and signalling. associate extensively with one another and with other transmembrane and membrane-proximal proteins. In this study, we present results strongly suggesting that tetraspanin homodimers are fundamental units within larger tetraspanin complexes. Evidence for constitutive CD9 homodimers was obtained using several cell lines, utilizing the following four methods: (1) spontaneous cross-linking via intermolecular disulphide bonds, (2) use of a cysteine-reactive covalent cross-linking agent, (3) use of an amino-reactive covalent cross-linking agent, and (4) covalent cross-linking via direct intermolecular disulphide bridging between unpalmitoylated membrane-proximal cysteine residues. In the last case, incubation of cells with the palmitoylation inhibitor 2-bromopalmitate exposed membrane-proximal cysteine residues, thus effectively promoting 'zero-length' cross-linking to stabilize homodimers. Similar to CD9, other tetraspanins (CD81 and CD151) also showed a tendency to homodimerize. Tetraspanin homodimers were assembled from newly synthesized proteins in the Golgi, as evidenced by cycloheximide and Brefeldin A inhibition studies. Importantly, tetraspanin homodimers appeared on the cell surface and participated in typical 'tetraspanin web' interactions with other proteins. Whereas homodimers were the predominant cross-linked species, we also observed some higher-order complexes (trimers, tetramers or higher) and a much lower level of cross-linking between different tetraspanins (CD81-CD9, CD9-CD151, CD81-CD151). In conclusion, our results strongly suggest that tetraspanin homodimers, formed in the Golgi and present at the cell surface, serve as building blocks for the assembly of larger, multicomponent tetraspanin protein complexes. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, D-1430,44 Binney St, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu FU NCI NIH HHS [CA86712] NR 46 TC 77 Z9 80 U1 0 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2004 VL 377 BP 407 EP 417 DI 10.1042/BJ20031037 PN 2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769EA UT WOS:000188612400015 PM 14556650 ER PT J AU Wiegand, LC Warfield, SK Levitt, JJ Hirayasu, Y Salisbury, DF Heckers, S Dickey, CC Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Wiegand, LC Warfield, SK Levitt, JJ Hirayasu, Y Salisbury, DF Heckers, S Dickey, CC Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI Prefrontal cortical thickness in first-episode psychosis: A magnetic resonance imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; magnetic resonance imaging; prefrontal cortex; cortical thickness; gray matter; age ID GRAY-MATTER VOLUME; FIRST-EPISODE SCHIZOPHRENIA; NORMAL HUMAN CORTEX; CEREBRAL-CORTEX; CYTOARCHITECTONIC DEFINITION; NEURONAL DENSITY; BRAIN MORPHOLOGY; BLADDER WALL; MRI DATA; AREAS 9 AB Background: Findings from postmortem studies suggest reduced prefrontal cortical thickness in schizophrenia; however, cortical thickness in first-episode schizophrenia has not been evaluated using magnetic resonance imaging (MRI). Methods. Prefrontal cortical thickness was measured using MRI in first-episode schizophrenia patients (n = 17), first-episode affective psychosis patients (n = 17), and normal control subjects (n = 17), subjects were age-matched within 2 years and within a narrow age range (18-29). A previous study using the same subjects reported reducing prefrontal gray matter volume in first-episode schizophrenia. Manual editing was performed on those prefrontal segmentations before cortical thickness was measured. Results: Prefrontal cortical thickness was not significantly different among groups. Prefrontal gray matter volume and thickness were, However, positively correlated in both schizophrenia and control subjects. The product of boundary complexity and thickness, an alternative measure of volume, was positively correlated with volume for all three groups. Finally, age and age at first medication were negatively correlated with prefrontal cortical thickness only in first-episode schizophrenia. Conclusions: This study demonstrates the potential usefulness of MRI for the study of cortical thickness abnormalities in schizophrenia. Correlations between cortical thickness and age and between cortical thickness and age at first medication suggest that the longer the schizophrenic process has been operative, the thinner the prefrontal cortex, although this needs confirmation in a longitudinal study. C1 Harvard Univ, Sch Med, Dept Psychiat 116A, Vet Affairs Boston Hlth Care Syst,Brockton Div, Brockton, MA USA. Harvard Univ, Sch Med, Clin Neurosci Div, Neurosci Lab,Brockton Div, Brockton, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,MRI Div,Surg Planning Lab, Boston, MA USA. Kyorin Univ, Sch Med, Dept Psychiat, Tokyo, Japan. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychot Disorders Unit, Boston, MA 02114 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, Dept Psychiat 116A, Vet Affairs Boston Hlth Care Syst,Brockton Div, 940 Belmont St, Brockton, MA USA. RI Heckers, Stephan/F-3051-2010; Warfield, Simon/B-3352-2009; McCarley, Robert/N-5562-2014; OI Heckers, Stephan/0000-0003-3601-9910; McCarley, Robert/0000-0001-5705-7495; Warfield, Simon/0000-0002-7659-3880 FU NCI NIH HHS [P01 CA067165, P01 CA067165-06, P01 CA67165, R01 CA086879, R01 CA86879]; NCRR NIH HHS [P41 RR013218, P41 RR013218-02, P41 RR13218, R01 RR011747, R01 RR011747-02, R01 RR11747]; NIMH NIH HHS [R01 MH040799, K02 MH01110, K05 MH070047, K05 MH070047-01, R01 MH 40799, R01 MH040799-17, R01 MH050740, R01 MH050740-06, R01 MH50740] NR 65 TC 60 Z9 60 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2004 VL 55 IS 2 BP 131 EP 140 DI 10.1016/j.biopsych.2003.07.009 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764GX UT WOS:000188200100005 PM 14732592 ER PT J AU Gribben, JG AF Gribben, JG TI Death of follicular lymphoma cells - the long and the short of it SO BLOOD LA English DT Editorial Material ID EXPRESSION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 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 JAN 15 PY 2004 VL 103 IS 2 BP 374 EP 374 DI 10.1182/blood-2003-10-3492 PG 1 WC Hematology SC Hematology GA 762CY UT WOS:000187954000011 ER PT J AU Rowe, JM Neuberg, D Friedenberg, W Bennett, JM Paietta, E Makary, AZ Liesveld, JL Abboud, CN Dewald, G Hayes, FA Tallman, MS Wiernik, PH AF Rowe, JM Neuberg, D Friedenberg, W Bennett, JM Paietta, E Makary, AZ Liesveld, JL Abboud, CN Dewald, G Hayes, FA Tallman, MS Wiernik, PH TI A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; COUNCIL AML11 TRIAL; CYTOSINE-ARABINOSIDE; COMPARING IDARUBICIN; REMISSION INDUCTION; III TRIAL; GROUP-B AB The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P=.03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate. C1 Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Haifa, Israel. Dana Farber Canc Inst, Boston, MA 02115 USA. Guthrie Med Ctr, Sayre, PA USA. Univ Rochester, Ctr Canc, Rochester, NY USA. New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. Geisinger Med Ctr, Danville, PA 17822 USA. Mayo Clin, Rochester, MN USA. Immunex Corp, Seattle, WA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Rowe, JM (reprint author), Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, IL-31096 Haifa, Israel. EM rowe@jimmy.harvard.edu FU NCI NIH HHS [CA21115, CA17145, CA66636, CA11083, CA23318] NR 44 TC 174 Z9 181 U1 1 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 JAN 15 PY 2004 VL 103 IS 2 BP 479 EP 485 DI 10.1182/blood-2003-05-1686 PG 7 WC Hematology SC Hematology GA 762CY UT WOS:000187954000026 PM 14512295 ER PT J AU Fujiwara, Y Chang, AN Williams, AM Orkin, SH AF Fujiwara, Y Chang, AN Williams, AM Orkin, SH TI Functional overlap of GATA-1 and GATA-2 in primitive hematopoietic development SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; EMBRYONIC STEM-CELLS; MICE LACKING; DIFFERENTIATION; LINEAGE; RESCUE; DROSOPHILA; PROTEINS; MUTATION; DEFECT AB Transcription factors GATA-1 and GATA-2 are required for normal hematopoiesis. The loss of either leads to embryonic lethality in knockout mice because of the failure of erythroid maturation and the expansion of progenitors, respectively. As the expression of GATA-1 and GATA-2 overlaps within hematopoietic progenitors, the extent to which these factors functionally compensate for each other during embryogenesis is unknown. As shown here, we have analyzed double-knockout embryos at the yolk sac stage of development and have shown that the combined absence of these GATA factors virtually ablates primitive erythroid cell formation. Thus, the function of GATA-1 and GATA-2 overlaps at the yolk sac stage. Moreover, a GATA factor, either GATA-1 or GATA-2, is required to initiate blood formation in the embryo. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Enders 760,300 Longwood Ave, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu NR 19 TC 93 Z9 99 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 JAN 15 PY 2004 VL 103 IS 2 BP 583 EP 585 DI 10.1182/blood-2003-08-2870 PG 3 WC Hematology SC Hematology GA 762CY UT WOS:000187954000041 PM 14504093 ER PT J AU Bellucci, R Wu, CJ Chiaretti, S Weller, E Davies, FE Alyea, EP Dranoff, G Anderson, KC Munshi, NC Ritz, J AF Bellucci, R Wu, CJ Chiaretti, S Weller, E Davies, FE Alyea, EP Dranoff, G Anderson, KC Munshi, NC Ritz, J TI Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; METABOTROPIC GLUTAMATE RECEPTORS; PRIMARY BILIARY-CIRRHOSIS; PYRUVATE-DEHYDROGENASE COMPLEX; CHRONIC MYELOGENOUS LEUKEMIA; MEDIATED TUMOR DESTRUCTION; CELL MATURATION ANTIGEN; IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; E2 COMPONENT AB The ability of donor lymphocyte infusions (DLIs) to induce complete responses (CRs) in patients with relapsed myeloma after allogeneic bone marrow transplantation (BMT) provides clear evidence of an effective graft-versus-myeloma (GVM) response. To identify target antigens of the GVM response, we screened a myeloma cDNA expression library with post-DLI serum from 4 patients with myeloma who achieved CR after DLI and 1 patient who was in CR before DLI. We identified a panel of 13 gene products reactive with post-DLI serum but negative with pre-DLI and pre-BMT serum. Antibodies to these proteins were not detected in the sera of 10 patients who underwent allogeneic BMT without DLI and 5 patients with acute graft-versus-host disease (GVHD). Minimal reactivity with these proteins was detected in the sera of 20 healthy donors and 20 patients with chronic GVHD. In contrast, 5 of these proteins were recognized by more than 1 myeloma DLI responder. Testing of serial serum samples showed an association between antibody response and time of best response after DLI. The expression of these genes was evaluated in primary myeloma cells and in normal plasma cells. This study demonstrates that the GVM response is associated with antibody responses to highly expressed myeloma-associated antigens. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M530,44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA078378]; NIAID NIH HHS [AI29530] NR 54 TC 49 Z9 49 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 JAN 15 PY 2004 VL 103 IS 2 BP 656 EP 663 DI 10.1182/blood-2003-07-2559 PG 8 WC Hematology SC Hematology GA 762CY UT WOS:000187954000052 PM 14563636 ER PT J AU Kim, YM Mapara, MY Down, JD Johnson, KW Boisgerault, F Akiyama, Y Benichou, G Pelot, M Zhao, GL Sykes, M AF Kim, YM Mapara, MY Down, JD Johnson, KW Boisgerault, F Akiyama, Y Benichou, G Pelot, M Zhao, GL Sykes, M TI Graft-versus-host-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning SO BLOOD LA English DT Article ID ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; BONE-MARROW; LYMPHOCYTE INFUSION; THYMIC IRRADIATION; TRANSPLANTATION; DISEASE; MICE; DEPLETION; TOLERANCE AB Murine mixed hematopoietic chimerism can be achieved following nonmyeloablative conditioning with cyclophosphamide, T cell-depleting monoclonal antibodies, and thymic irradiation. Donor lymphocyte infusions (DLIs) 35 days after bone marrow transplantation (BMT) convert mixed to full donor chimerism and mediate graft-versus-lymphoma effects without graft-versus-host disease. We evaluated the role of T-cell subsets in DLIs in converting mixed to full donor chimerism in a fully major histocompatibility complex-mismatched strain combination. Whereas DLIs administered on day 35 converted 100% of mixed chimeras to full donor chimerism, conversion was less frequent when either CD4 or CD8 cells were depleted, indicating that both subsets contribute to the conversion. Surprisingly, administration of CD8-depleted DLIs led to complete loss of donor chimerism in a high proportion (54%) of recipients compared with CD4-plus CD8-depleted DLIs (15%) or CD4-depleted DLIs (0%) (P<.05). DLIs administered at early time points after BMT (eg, day 21) also precipitated rejection of donor marrow by recipient αβ T cells, in association with donor CD4 cell expansion and high production of interleukin 2 (IL-2), IL-4, and interferon-γ. Thus, DLIs can paradoxically induce marrow rejection by residual host αβ T cells. These results have implications for the timing of and use of subset depletion of DLIs in recipients of nonmyeloablative transplants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Biotransplant Inc, Medford, MA USA. Harvard Univ, Sch Med, Schepens Eye Inst, Boston, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01 CA79989]; NEI NIH HHS [R01 EY13310]; NHLBI NIH HHS [R01 HL49915]; NIAID NIH HHS [R01 AI33704] NR 27 TC 9 Z9 9 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 JAN 15 PY 2004 VL 103 IS 2 BP 732 EP 739 DI 10.1182/blood-2003-02-0643 PG 8 WC Hematology SC Hematology GA 762CY UT WOS:000187954000064 PM 14512313 ER PT J AU Milinkovic, M Antin, JH Hergrueter, CA Underhill, CB Sackstein, R AF Milinkovic, M Antin, JH Hergrueter, CA Underhill, CB Sackstein, R TI CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD SO BLOOD LA English DT Article ID T-CELL EXTRAVASATION; HYALURONAN-BINDING; PRIMARY ADHESION; CD44; SURFACE; RECEPTOR; LIGAND; PATHWAY AB For circulating lymphocytes to migrate to inflammatory sites, they must first adhere to the target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence, whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD. C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Georgetown Univ, Sch Med, Dept Oncol, Washington, DC USA. RP Sackstein, R (reprint author), Harvard Inst Med, Rm 671,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA 84156]; NIAMS NIH HHS [P30AR42689] NR 25 TC 25 Z9 25 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 JAN 15 PY 2004 VL 103 IS 2 BP 740 EP 742 DI 10.1182/blood-2003-05-1500 PG 3 WC Hematology SC Hematology GA 762CY UT WOS:000187954000065 PM 14504094 ER PT J AU Anhang, R Stryker, JE Wright, TC Goldie, SJ AF Anhang, R Stryker, JE Wright, TC Goldie, SJ TI News media coverage of human papillomavirus SO CANCER LA English DT Article DE cervical cancer screening; DNA testing; human papillomavirus; sexually transmitted disease; news media ID CERVICAL-CANCER; BREAST-CANCER; SCREENING MAMMOGRAPHY; WOMENS MAGAZINES; POPULAR PRESS; MASS-MEDIA; KNOWLEDGE; HPV; DNA; PREFERENCES AB BACKGROUND. Now that human papillomavirus (HPV) DNA testing is being incorporated into cervical cancer screening programs, salient and accurate media information about HPV will be crucial to inform women's screening choices and to manage psychosocial responses to HPV DNA test results. METHODS. The authors conducted a content analysis of 111 news stories about HPV from the 10 most circulated newspapers and from 3 major television networks for the period from January 1995 through July 2002. Stories were assessed for predominant theme (STD, cancer, or new tests); information about symptoms, transmission, prevention, and cancer-causing properties of HPV; screening test descriptions; and recommended screening guidelines. RESULTS. Thirty-six percent of stories primarily were about new tests for HPV cervical cancer, 30% of stories focused on cervical cancer or its link to HPV, and 27% of stories emphasized sexually transmitted diseases (STDs) or genital warts. Seventy-nine percent of stories mentioned that HPV is an STD, and 50% of stories reported that HPV is very common. Twenty-six percent of stories reported that most women with HPV will not develop cervical carcinoma. Of 81 stories that mentioned a screening test for HPV or cervical carcinoma, 38% reported the sensitivity of the test; 30% mentioned wrong, uncertain, or unnecessary test results; and 25% mentioned consequences of such results. CONCLUSIONS. Media coverage of HPV could better fulfill women's educational needs by including information about low-risk and high-risk types of HPV and their differing links to cervical cancer; describing HPV prevention, transmission, and symptoms; explaining the benefits and consequences of HPV testing; and outlining the latest screening guidelines in every story. (C) 2003 American Cancer Society. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10027 USA. RP Goldie, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, 718 Huntington Ave,Suite 2, Boston, MA 02115 USA. EM sgoldie@hsph.harvard.edu FU NCI NIH HHS [R01 CA 93435-02] NR 41 TC 57 Z9 57 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2004 VL 100 IS 2 BP 308 EP 314 DI 10.1002/cncr.20006 PG 7 WC Oncology SC Oncology GA 769DE UT WOS:000188610500014 PM 14716765 ER PT J AU Miller, AJ Du, JY Rowan, S Hershey, CL Widlund, HR Fisher, DE AF Miller, AJ Du, JY Rowan, S Hershey, CL Widlund, HR Fisher, DE TI Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma SO CANCER RESEARCH LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; MICROPHTHALMIA GENE-PRODUCT; METASTATIC MELANOMA; EXPRESSION; TYROSINASE; DIAGNOSIS; MUTATIONS; CELLS; DIFFERENTIATION; PIGMENTATION AB Determining the metastatic potential of intermediate thickness lesions remains a major challenge in the management of melanoma. Clinical studies have demonstrated that expression of melastatin/TRPM1 strongly predicts nonmetastatic propensity and correlates with improved outcome, leading to a national cooperative prospective study, which is ongoing currently. Similarly, the melanocytic markers MLANA/MART1 and MITF also have been shown to lose relative expression during melanoma progression. Recent studies have revealed that MITF, an essential transcription factor for melanocyte development, directly regulates expression of MLANA. This prompted examination of whether MITF also might transcriptionally regulate TRPM1 expression. The TRPM1 promoter contains multiple MITF consensus binding elements that were seen by chromatin immunoprecipitation to be occupied by endogenous MITF within melanoma cells. Endogenous TRPM1 expression responded strongly to MITF up- or down-regulation, as did TRPM1 promoter-driven reporters. In addition, MITF and TRPM1 mRNA levels were correlated tightly across a series of human melanoma cell lines. Mice homozygously mutated in MITF showed a dramatic decrease in TRPM1 expression. Finally, the slope of TRPM1 induction by MITF was particularly steep compared with other MITF target genes, suggesting it is a sensitive indicator of MITF expression and correspondingly of melanocytic differentiation. These studies identify MITF as a major transcriptional regulator of TRPM1 and suggest that its prognostic value may be linked to MITF-mediated regulation of cellular differentiation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM David_Fisher@dfci.harvard.edu FU NIAMS NIH HHS [AR43369] NR 39 TC 113 Z9 115 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 509 EP 516 DI 10.1158/0008-5472.CAN-03-2440 PG 8 WC Oncology SC Oncology GA 766WX UT WOS:000188399300012 PM 14744763 ER PT J AU Grimm, J Perez, JM Josephson, L Weissleder, R AF Grimm, J Perez, JM Josephson, L Weissleder, R TI Novel nanosensors for rapid analysis of telomerase activity SO CANCER RESEARCH LA English DT Article ID REPEAT AMPLIFICATION PROTOCOL; BREAST-CANCER CELLS; PROTEIN-KINASE; CATALYTIC SUBUNIT; MESSENGER-RNA; LIFE-SPAN; IN-VITRO; ASSAY; PHOSPHORYLATION; PROLIFERATION AB Elevated telomerase levels are found in many malignancies, offering an attractive target for therapeutic intervention and diagnostic or prognostic purposes. Here we describe the use of a novel nanosensor developed for rapid screens of telomerase activity in biological samples. The technique utilizes magnetic nanoparticles that, on annealing with telomerase synthesized TTAGGG repeats, switch their magnet state, a phenomenon readily detectable by magnetic readers. We tested the efficacy of different telomerase inhibitors in crude human and murine samples and show that phosphorylation of telomerase regulates its activity. High-throughput adaptation of the technique by magnetic resonance imaging allowed processing of hundreds of samples within tens of minutes at ultrahigh sensitivities. Together, these studies establish and validate a novel and powerful tool for rapidly sensing telomerase activity and provide the rationale for developing analogous magnetic nanoparticles for in vivo sensing. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA USA. RP Weissleder, R (reprint author), Ctr Mol Imaging Res, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. RI Grimm, Jan/B-1937-2008 NR 55 TC 108 Z9 112 U1 1 U2 14 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 JAN 15 PY 2004 VL 64 IS 2 BP 639 EP 643 DI 10.1158/0008-5472.CAN-03-2798 PG 5 WC Oncology SC Oncology GA 766WX UT WOS:000188399300028 PM 14744779 ER PT J AU Xu, L Pathak, PS Fukumura, D AF Xu, L Pathak, PS Fukumura, D TI Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3 '-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; INDUCIBLE FACTOR-I; INDUCED ELEVATION; AUTOCRINE GROWTH; GENE-EXPRESSION; UP-REGULATION; PC12 CELLS; MAP KINASE; HA-RAS AB Purpose: Overexpression of interleukin 8 (IL-8) is associated with disease progression in human ovarian cancer. Hypoxia, a common feature in solid tumors, induces IL-8 expression in human ovarian carcinoma cells through activation of nuclear factor-kappa B and activating protein-1. Here we show the upstream components of these signal transduction pathways that lead to IL-8 expression under hypoxia. Experimental Design: We incubated Hey-A8 human ovarian carcinoma cells under hypoxic condition (1% O-2) and determined hypoxia regulation of phosphatidylinositol 3'-kinase (PI3K)/Akt pathway, mitogen-activated protein kinases (MAPKs), and effects of ras and vascular endothelial growth factor by Western and Northern blots, the use of specific inhibitors, in vitro kinase assays, luciferase reporter genes, and ELISA. Results: While investigating the upstream signaling pathways, we found that Akt kinase and p38 MAPK are activated by hypoxia. Both hypoxia-induced Akt and p38 MAPK functional activity, and IL-8 mRNA and protein expression were reduced with the inhibition of PI3K and p38 MAPK. Oncogenic ras overexpression resulted in an increase in the hypoxia-induced IL-8 expression, whereas the inhibition of ras by transfection of dominant-negative ras inhibited the hypoxia-induced IL-8 expression. Conclusions: These results show that hypoxia activates ras, PI3K/Akt pathway, and p38 MAPK pathway to enhance IL-8 gene transcription under hypoxia, and suggest these signaling pathways as potential targets for controling IL-8 expression and angiogenesis by human ovarian carcinoma cells. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu FU NCI NIH HHS [P01-CA80124] NR 41 TC 57 Z9 58 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2004 VL 10 IS 2 BP 701 EP 707 DI 10.1158/1078-0432.CCR-0953-03 PG 7 WC Oncology SC Oncology GA 771TA UT WOS:000188801100036 PM 14760093 ER PT J AU Shammas, MA Reis, RJS Li, C Koley, H Hurley, LH Anderson, KC Munshi, NC AF Shammas, MA Reis, RJS Li, C Koley, H Hurley, LH Anderson, KC Munshi, NC TI Telomerase inhibition and cell growth arrest after telomestatin treatment in multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID G-QUADRUPLEX; DNA; CANCER; EXPRESSION AB Purpose: The aim of this study was to test the efficacy of telomestatin, an intramolecular G-quadruplex intercalating drug with specificity for telomeric sequences, as a potential therapeutic agent for multiple myeloma. Experimental Design: We treated ARD, ARP, and MM1S myeloma cells with various concentrations of telomestatin for 7 days and evaluated for telomerase activity. Myeloma cells were treated with the minimal effective telomestatin concentration for 3-5 weeks. Every 7(th) day the fraction of live cells was determined by trypan blue exclusion, aliquots of cells were removed for various molecular assays, and the remaining cells were replated at the same cell number and at the same concentration of telomestatin. Telomere length, apoptosis, and gene expression changes were monitored as described in detail in "Materials and Methods." Results: Telomestatin treatment led to inhibition of telomerase activity, reduction in telomere length, and apoptotic cell death in ARD, MM1S, and ARP myeloma cells. Gene expression profile after 1 and 7 days of telomestatin treatment revealed greater than or equal to2-fold change in only 6 (0.027%) and 51 (0.23%) of 33,000 genes surveyed, respectively. No changes were seen in expression of genes involved in cell cycle, apoptosis, DNA repair, or recombination. Conclusions: These results demonstrate that telomestatin exerts its antiproliferative and proapoptotic effects in myeloma cells via inhibition of telomerase and subsequent reduction in telomere length. We conclude that telomerase is an important potential therapeutic target for multiple myeloma therapy, and G-quadruplex interacting agents with specificity for binding to telomeric sequences can be important agents for additional evaluation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St,M557, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Shmookler Reis, Robert/C-4112-2009 FU PHS HHS [R01-50947, P50-100707, P01-78378] NR 32 TC 82 Z9 87 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2004 VL 10 IS 2 BP 770 EP 776 DI 10.1158/1078-0432.CCR-0793-03 PG 7 WC Oncology SC Oncology GA 771TA UT WOS:000188801100043 PM 14760100 ER PT J AU Argiris, A Li, Y Murphy, BA Langer, CJ Forastiere, AA AF Argiris, A Li, Y Murphy, BA Langer, CJ Forastiere, AA TI Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; CELL LUNG-CANCER; COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; CLINICAL-TRIALS; BREAST-CANCER; OLDER PATIENTS; ADJUVANT CHEMOTHERAPY; PHASE-II AB Purpose To evaluate the outcome of elderly patients with head and neck cancer undergoing palliative chemotherapy. Patients and Methods We analyzed combined data from two mature phase III randomized trials conducted by the Eastern Cooperative Oncology Group (ECOG; trial E1393, which compared cisplatin plus paclitaxel at two dose levels, and trial E1395, which compared cisplatin plus fluorouracil to cisplatin plus paclitaxel) to evaluate the toxicity, objective response rates, and survival of patients 70 years or older versus their younger counterparts. All patients had previously untreated recurrent or metastatic squamous cell carcinoma of the head and neck and ECOG performance status 0 or 1. Results Fifty-three elderly patients were enrolled from a total of 399 eligible participants (13%). Elderly patients had similar objective response rates (28% v 33%) and median time to progression (5.25 v 4.8 months) compared with younger patients. The median survival was 5.3 v 8 months (Wilcoxon P = .06; log-rank P = .17) and the 1-year survival 26% v 33% for elderly and younger patients, respectively. Elderly patients had a significantly higher incidence of severe nephrotoxicity, diarrhea, and thrombocytopenia. A higher rate of toxic deaths was noted in the elderly but did not reach statistical significance (13% v 8%; P = .29). Conclusion Elderly patients were underrepresented in these studies. Fit elderly patients with recurrent or metastatic head and neck cancer sustained increased toxicities with cisplatin-based doublets but had comparable survival outcomes compared with younger patients. Strategies to ameliorate toxicities should be pursued in the elderly. C1 Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. RP Argiris, A (reprint author), Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, 676 N St Clair,Suite 850, Chicago, IL 60611 USA. EM a-argiris@northwestern.edu NR 47 TC 50 Z9 51 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2004 VL 22 IS 2 BP 262 EP 268 DI 10.1200/JCO.2004.08.039 PG 7 WC Oncology SC Oncology GA 764GT UT WOS:000188199700009 PM 14722034 ER PT J AU Loehrer, PJ Wang, W Johnson, DH Ettinger, DS AF Loehrer, PJ Wang, W Johnson, DH Ettinger, DS TI Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: An Eastern Cooperative Oncology Group phase II trial 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, FLORIDA SP Amer Soc Clin Oncol ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; LONG-ACTING RELEASE; EPITHELIAL-CELLS; TYROSINE PHOSPHATASE; MALIGNANT THYMOMA; INTERGROUP TRIAL; ANALOG AN-238; INHIBITION; SUBTYPES; THERAPY AB Purpose To determine the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pretreatment octrectide scan was positive. Patients and Methods Forty-two patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (one patient had inconclusive histology; three patients had negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously tid. At 2 months, patients were evaluated. Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1 year. Results Two complete (5.3%) and 10 partial responses (25%) were observed (four partial responses with octreotide alone; the remainder with octreotide plus prednisone). None of the six patients without pure thymoma responded. The 1- and 2-year survival rates were 86.6% and 75.7%, respectively. Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (P = .031). Conclusion Octreotide alone has modest activity in patients with octrectide scan-positive thymoma. Prednisone improves the overall response rate but is associated with increased toxicity. Additional studies with the agent are warranted. C1 Indiana Univ, Med Ctr, Indianapolis, IN 46204 USA. Walther Canc Inst, Indianapolis, IN USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN USA. Johns Hopkins Univ, Baltimore, MD USA. RP Loehrer, PJ (reprint author), Indiana Canc Pavil,535 Barnhill Dr,Room 473, Indianapolis, IN 46202 USA. EM ploehrer@iupui.edu FU NCI NIH HHS [CA23318, 2 R 35 CA39844-08, P 30 CA 82709-04, R 10 CA 28171-04, U 10 CA 21115] NR 33 TC 91 Z9 92 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2004 VL 22 IS 2 BP 293 EP 299 DI 10.1200/JCO.2004.02.047 PG 7 WC Oncology SC Oncology GA 764GT UT WOS:000188199700013 PM 14722038 ER PT J AU Earle, CC Neville, BA Landrum, MB Ayanian, JZ Block, SD Weeks, JC AF Earle, CC Neville, BA Landrum, MB Ayanian, JZ Block, SD Weeks, JC TI Trends in the aggressiveness of cancer care near the end of life SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, ILLINOIS SP Amer Soc Clin Oncol ID CELL LUNG-CANCER; MEDICARE MANAGED CARE; HOSPICE USE; COMORBIDITY INDEX; QUALITY; DEATH; CHEMOTHERAPY; METHODOLOGY; VALIDATION; INSTITUTE AB Purpose To characterize the aggressiveness of end-of-life cancer treatment for older adults on Medicare, and its relationship to the availability of healthcare resources. Patients and Methods We analyzed Medicare claims of 28,777 patients 65 years and older who died within 1 year of a diagnosis of lung, breast, colorectal, or other gastrointestinal cancer between 1993 and 1996 while living in one of 11 US regions monitored by the Surveillance, Epidemiology, and End Results Program. Results Rates of treatment with chemotherapy increased from 27.9% in 1993 to 29.5% in 1996 (P = .02). Among those who received chemotherapy, 15.7% were still receiving treatment within 2 weeks of death, increasing from 13.8% in 1993 to 18.5% in 1996 (P < .001). From 1993 to 1996, increasing proportions of patients had more than one emergency department visit (7.2% v 9.2%; P < .001), hospitalization (7.8% v 9.1%; P = .008), or were admitted to an intensive care unit (7.1% v 9.4%; P = .009) in the last month of life. Although fewer patients died in acute-care hospitals (32.9% v 29.5%; P < .001) and more used hospice services (28.3% v 38.8%; P < .001), an increasing proportion of patients who received hospice care initiated this service only within the last 3 days of life (14.3% v 17.0%; P = .004). Black patients were more likely than white patients to experience aggressive intervention in nonteaching hospitals but not in teaching hospitals. Greater local availability of hospices was associated with less aggressive treatment near death on multivariate analysis. Conclusion The treatment of cancer patients near death is becoming increasingly aggressive over time. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Psychosocial Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Ctr Outcomes & Policy Res, 44 Binney St,454 STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu FU NCI NIH HHS [CA 91753-02] NR 41 TC 429 Z9 434 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2004 VL 22 IS 2 BP 315 EP 321 DI 10.1200/JCO.2004.08.036 PG 7 WC Oncology SC Oncology GA 764GT UT WOS:000188199700016 PM 14722041 ER PT J AU Abdi, R Means, TK Ito, T Smith, RN Najafian, N Jurewicz, M Tchipachvili, V Charo, I Auchincloss, H Sayegh, MH Luster, AD AF Abdi, R Means, TK Ito, T Smith, RN Najafian, N Jurewicz, M Tchipachvili, V Charo, I Auchincloss, H Sayegh, MH Luster, AD TI Differential role of CCR2 in islet and heart allograft rejection: Tissue specificity of chemokine/chemokine receptor function in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; CHEMOKINE RECEPTORS; CARDIAC ALLOGRAFTS; IFN-GAMMA; MICE; TRANSPLANTATION; RESPONSES; IMMUNITY; COSTIMULATION; CD154-CD40 AB Chemokines have a pivotal role in the mobilization and activation of specific leukocyte subsets in acute allograft rejection. However, the role of specific chemokines and chemokine receptors in islet allograft rejection has not been fully elucidated. We now show that islet allograft rejection is associated with a steady increase in intragraft expression of the chemokines CCL8 (monocyte chemoattractant protein-2), CCL9 (monocyte chemoattractant protein-5), CCL5 (RANTES), CXCL-10 (IFN-gamma-inducible protein-10), and CXCL9 (monokine induced by IFN-gamma) and their corresponding chemokine receptors CCR2, CCR5, CCR1, and CXCR3. Because CCR2 was found to be highly induced, we tested the specific role of CCR2 in islet allograft rejection by transplanting fully MHC mismatched islets from BALB/c mice into C57BL/6 wild-type (WT) and CCR2-deficient mice (CCR2(-/-)). A significant prolongation of islet allograft survival was noted in CCR2(-/-) recipients, with median survival time of 24 and 12 days for CCR2(-/-) and WT recipients, respectively (p < 0.0001). This was associated with reduction in the generation of CD8(+), but not CD4(+) effector alloreactive T cells (CD62L(low)CD44(high)) in CCR2(-/-) compared with WT recipients. In addition, CCR2(-/-) recipients had a reduced Th1 and increased Th2 alloresponse in the periphery (by ELISPOT analysis) as well as in the grafts (by RT-PCR). However, these changes were only transient in CCR2(-/-) recipients that ultimately rejected their grafts. Furthermore, in contrast to the islet transplants, CCR2 deficiency offered only marginal prolongation of heart allograft survival. This study demonstrates the important role for CCR2 in early islet allograft rejection and highlights the tissue specificity of the chemokine/chemokine receptor system in vivo in regulating allograft rejection. The Journal of Immunology, 2004, 172: 767-775. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. RP Abdi, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA 69212]; NHLBI NIH HHS [HL 52773]; NIAID NIH HHS [P01 AI 41521]; NIDDK NIH HHS [P01 DK 50305] NR 30 TC 63 Z9 66 U1 1 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 JAN 15 PY 2004 VL 172 IS 2 BP 767 EP 775 PG 9 WC Immunology SC Immunology GA 762WM UT WOS:000188005200005 PM 14707046 ER PT J AU Nath, N Giri, S Prasad, R Singh, AK Singh, I AF Nath, N Giri, S Prasad, R Singh, AK Singh, I TI Potential targets of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for multiple sclerosis therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; HMG-COA REDUCTASE; T-CELLS; TRANSCRIPTION FACTOR; DENDRITIC CELLS AB The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins are newly identified immunomodulators. In vivo treatment of SJL/J mice with lovastatin reduced the duration and clinical severity of active and passive experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Lovastatin induced the expression of GATA3 and the phosphorylation of STAT6, whereas it inhibited tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT4. Inhibition of the Janus kinase-STAT4 pathway by lovastatin modulated TO to Th1 differentiation and reduced cytokine (IFN-gamma and TNF-alpha) production, thus inducing Th2 cytokines (IL-4, IL-5, and IL-10). It inhibited T-bet (T box transcription factor) and NF-kappaB in activated T cells and significantly reduced infiltration of CD4- and MHC class II-positive cells to CNS. Further, it stabilized IL-4 production and GATA-3 expression in differentiated Th2 cells, whereas in differentiated Th1 cells it inhibited the expression of T-bet and reduced the production of IFN-gamma. Moreover, lovastatin-exposed macrophage and BV2 (microglia) in allogeneic MLRs induced the production of the anti-inflammatory cytokine IL-10. These observations indicate that the antiinflammatory effects of lovastatin are mediated via T cells as well as APCs, because it modulates the polarization patterns of naive T cell activation in an APC-independent system. Together, these findings reveal that lovastatin may have possible therapeutic value involving new targets (in both APCs and T cells) for the treatment of multiple sclerosis and other inflammatory diseases. The Journal of Immunology, 2004, 172: 1273-1286. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 96 Jonathan Lucas St,Clin Sci Bldg,Suite 316, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS 22576, NS 34741, NS 37766, NS 41044] NR 65 TC 106 Z9 118 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2004 VL 172 IS 2 BP 1273 EP 1286 PG 14 WC Immunology SC Immunology GA 762WM UT WOS:000188005200065 PM 14707106 ER PT J AU Jenike, MA AF Jenike, MA TI Obsessive-compulsive disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMPLEX SEGREGATION ANALYSIS; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; PHARMACOLOGICAL-TREATMENTS; BEHAVIOR-THERAPY; CLOMIPRAMINE; AUGMENTATION; EFFICACY; STIMULATION; COMBINATION C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jenike, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 55 TC 97 Z9 103 U1 2 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2004 VL 350 IS 3 BP 259 EP 265 DI 10.1056/NEJMcp031002 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 763HF UT WOS:000188078400009 PM 14724305 ER PT J AU Dodson, TB Caruso, PA Nielsen, GP Clark, HD McIntyre, JF Harmon, DC Kaban, LB Varvares, MA AF Dodson, TB Caruso, PA Nielsen, GP Clark, HD McIntyre, JF Harmon, DC Kaban, LB Varvares, MA TI A man with pain and swelling of the jaw SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OSTEOGENIC-SARCOMA; OSTEOSARCOMA; NECK; HEAD C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2004 VL 350 IS 3 BP 267 EP 275 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 763HF UT WOS:000188078400012 PM 14724307 ER PT J AU Sharpless, NE Ramsey, MR Balasubramanian, P Castrillon, DH DePinho, RA AF Sharpless, NE Ramsey, MR Balasubramanian, P Castrillon, DH DePinho, RA TI The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis SO ONCOGENE LA English DT Article DE Rb; p14(ARF); p53; cdkn2a ID MAMMARY EPITHELIAL-CELLS; HUMAN-DIPLOID FIBROBLASTS; TUMOR SUPPRESSION; INDUCED SENESCENCE; KERATINOCYTE SENESCENCE; GERMLINE MUTATION; FAMILIAL MELANOMA; INK4A LOCUS; IN-VIVO; INACTIVATION AB Mounting genetic evidence suggests that each product of the Ink4/Arf locus, p16(INK4a) and p19(ARF), possesses tumor-suppressor activity (Kamijo et al., 1997; Krimpenfort et al., 2001; Sharpless et al., 2001a). We report the generation and characterization of a p19(ARF)-specific knockout allele (p19(ARF)-/-) and direct comparison with mice and derivative cells deficient for p16(INK4a), both p16(INK4a) and p19(ARF), and p53. Like Ink4/Arf-/- murine embryo fibroblasts (MEFs), p19(ARF)-/- MEFs were highly susceptible to oncogenic transformation, exhibited enhanced subcloning efficiency at low density, and resisted both RAS- and culture-induced growth arrest. In contrast, the biological profile of p16(INK4a)-/- MEFs in these assays more closely resembled that of wild-type cells. In vivo, however, both p19(ARF)-/- and p16(INK4a)-/- animals were significantly more tumor prone than wild-type animals, but each less so than p53-/- or Ink4/Arf-/- animals, and with differing tumor spectra. These data confirm the predominant role of p19(ARF) over p16(INK4a) in cell culture-based assays of MEFs, yet also underscore the importance of the analysis of tumor suppressors across many cell types within the organism. The cancer-prone conditions of mice singly deficient for either p16(INK4a) or p19(ARF) agree with data derived from human cancer genetics, and reinforce the view that both gene products play significant and nonredundant roles in suppressing malignant transformation in vivo. C1 Univ N Carolina, Sch Med, Lineberger Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Lineberger Canc Ctr, Dept Med, CB 7295, Chapel Hill, NC 27599 USA. EM NES@med.unc.edu OI Ramsey, Matthew/0000-0003-2402-8502 NR 46 TC 110 Z9 118 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 15 PY 2004 VL 23 IS 2 BP 379 EP 385 DI 10.1038/sj.onc.1207074 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 763QH UT WOS:000188098300007 PM 14724566 ER PT J AU Dangond, F Hwang, D Camelo, S Pasinelli, P Frosch, MP Stephanopoulos, G Stephanopoulos, G Brown, RH Gullans, SR AF Dangond, F Hwang, D Camelo, S Pasinelli, P Frosch, MP Stephanopoulos, G Stephanopoulos, G Brown, RH Gullans, SR TI Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter SO PHYSIOLOGICAL GENOMICS LA English DT Article DE amyotrophic lateral sclerosis; DNA microarrays; mitochondria; excitotoxicity; apoptosis ID TRANSGENIC MOUSE MODEL; MOTOR-NEURON DISEASE; SUPEROXIDE-DISMUTASE; NEURODEGENERATIVE DISEASE; DIFFERENTIAL EXPRESSION; GLUTAMATE TRANSPORTER; OXIDATIVE STRESS; CDNA MICROARRAYS; GENE-EXPRESSION; SCLEROSIS AB Little is known about global gene expression patterns in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). To address this, we used high-density oligonucleotide microarray technology to compare expression levels of similar to6,800 genes in postmortem spinal cord gray matter obtained from individuals with ALS as well as normal individuals. Using Fisher discriminant analysis (FDA) and leave-one-out cross-validation (LOOCV), we discerned an ALS-specific signature. Moreover, it was possible to distinguish familial ALS (FALS) from sporadic ALS (SALS) gene expression profiles. Characterization of the specific genes significantly altered in ALS uncovered a pro-inflammatory terminal state. Moreover, we found alterations in genes involved in mitochondrial function, oxidative stress, excitotoxicity, apoptosis, cytoskeletal architecture, RNA transcription and translation, proteasomal function, and growth and signaling. It is apparent from this study that DNA microarray analysis and appropriate bioinformatics can reveal distinct phenotypic changes that underlie the terminal stages of neurodegeneration in ALS. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Sch Transcript & Immune Regulat, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. MIT, Dept Chem Engn, Bioinformat & Metab Engn Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol,Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Lab Funct Genom, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Day Neuromuscular Res Lab, Boston, MA 02114 USA. RP Gullans, SR (reprint author), 65 Landsdowne St, Cambridge, MA 02139 USA. EM sgullans@rics.bwh.harvard.edu; sgullans@rics.bwh.harvard.edu FU NCI NIH HHS [1K08-CA-80084]; NINDS NIH HHS [R21-NS-41623, 1P50-NS-38375, 1PO-NS-31248, R01-NS-37812] NR 46 TC 69 Z9 76 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JAN 15 PY 2004 VL 16 IS 2 BP 229 EP 239 DI 10.1152/physiolgenomics.00087.2001 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 809EC UT WOS:000220619000011 PM 14645737 ER PT J AU Cooper, DKC Tseng, YL Saidman, SL AF Cooper, DKC Tseng, YL Saidman, SL TI Alloantibody and xenoantibody cross-reactivity in transplantation SO TRANSPLANTATION LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL-CLONES; SWINE LEUKOCYTE ANTIGENS; HLA-SPECIFIC ANTIBODIES; CLASS-I; SENSITIZED PATIENTS; MINIATURE SWINE; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANT; PIG AB The recent availability of pigs homozygous for alpha1,3-galactosyltransferase gene knockout, and improved immunosuppressive regimens that prevent an elicited antibody response, are expected to contribute to significantly increased survival of pig organs transplanted into primates, bringing clinical trials of xenotransplantation closer. Patients highly sensitized to human leukocyte antigens, who may be precluded from obtaining a human donor organ, would be one group that might benefit from xenotransplantation. However, there have been few studies on whether there is cross-reactivity of anti-human leukocyte antigen antibodies with pig antigens. What data there are suggest that such cross-reactivity exists and that this may be detrimental to the outcome after transplantation of a pig organ. Neither is it known whether sensitization after a pig xenograft would preclude subsequent allotransplantation, although the data available suggest that this will not be the case. Further investigation on allo- and xenoantibody cross-reactivity is required. C1 Harvard Univ, Transplantat Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Histocompatibil Lab, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM David.Cooper@tbrc.mgh.harvard.edu FU PHS HHS [1P01 A145897] NR 45 TC 37 Z9 38 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 JAN 15 PY 2004 VL 77 IS 1 BP 1 EP 5 DI 10.1097/01.TP.0000105116.74032.63 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 766DA UT WOS:000188329100001 PM 14724427 ER PT J AU LeGuern, C AF LeGuern, C TI Potential role of major histocompatibility complex class II peptides in regulatory tolerance to vascularized grafts SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 3rd Beaune Seminar in Transplant Research CY MAY 15-16, 2003 CL BEAUNE, FRANCE ID DISPARATE RENAL-ALLOGRAFTS; CD4(+)CD25(+) T-CELLS; MINIATURE SWINE; AUTOIMMUNE ENCEPHALOMYELITIS; TRANSPLANTATION TOLERANCE; PERIPHERAL-BLOOD; BONE-MARROW; ANTIGEN; SUPPRESSION; SELF AB The inactivation of persisting T lymphocytes reactive to self- and non-self-antigens is a major arm of operational immune tolerance in mammals. Silencing of such T cells proceeds mostly by means of suppression, a process that is mediated by regulatory T-cell subsets and especially by CD4(+)CD25(high) regulatory T cells (Treg). Although Treg activation and ensuing suppressive activity appear to be major histocompatibility complex class II dependent, the fine specificity of Treg T-cell receptors has not yet been elucidated. Recent data from the. author's laboratory on a class II gene therapy induction of tolerance to allogeneic kidney grafts suggest that class II peptides are involved as generic signals for Treg activation. A brief compilation of results that would support this hypothesis it; discussed in the present article. C1 Massachusetts Gen Hosp, TBRC, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Massachusetts Gen Hosp, TBRC, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM leguern@helix.mgh.harvard.edu NR 31 TC 8 Z9 10 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 JAN 15 PY 2004 VL 77 IS 1 SU S BP S35 EP S37 DI 10.1097/01.TP.0000106472.91343.8D PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 767CV UT WOS:000188423400013 PM 14726769 ER PT J AU Marneros, AG Keene, DR Hansen, U Fukai, N Moulton, K Goletz, PL Moiseyev, G Pawlyk, BS Halfter, W Dong, SC Shibata, M Li, TS Crouch, RK Bruckner, P Olsen, BR AF Marneros, AG Keene, DR Hansen, U Fukai, N Moulton, K Goletz, PL Moiseyev, G Pawlyk, BS Halfter, W Dong, SC Shibata, M Li, TS Crouch, RK Bruckner, P Olsen, BR TI Collagen XVIII endostatin is essential for vision and retinal pigment epithelial function SO EMBO JOURNAL LA English DT Article DE age-related macular degeneration; collagen XVIII; endostatin; retinal pigment epithelium ID ENDOGENOUS INHIBITOR; KNOBLOCH-SYNDROME; DEFICIENT MICE; TUMOR-GROWTH; MEMBRANE; ANGIOGENESIS; RPE65; ABNORMALITIES; DEGENERATION; MICROFIBRILS AB Age-related macular degeneration (ARMD) with abnormal deposit formation under the retinal pigment epithelium (RPE) is the major cause of blindness in the Western world. basal laminar deposits are found in early ARMD and are composed of excess basement membrane material produced by the RPE. Here, we demonstrate that mice lacking the basement membrane component collagen XVIII/endostatin have massive accumulation of sub-RPE deposits with striking similarities to basal laminar deposits, abnormal RPE, and age-dependent loss of vision. The progressive attenuation of visual function results from decreased retinal rhodopsin content as a consequence of abnormal vitamin A metabolism in the RPE. In addition, aged mutant mice show photoreceptor abnormalities and increased expression of glial fibrillary acidic protein in the neural retina. Our data demonstrate that collagen XVIII/ endostatin is essential for RPE function, and suggest an important role of this collagen in Bruch's membrane. Consistent with such a role, the ultrastructural organization of collagen XVIII/ endostatin in basement membranes, including Bruch's membrane, shows that it is part of basement membrane molecular networks. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Shriners Hosp Children, Portland Res Ctr, Portland, OR 97201 USA. Univ Munster, Dept Physiol Chem & Pathophysiol, D-4400 Munster, Germany. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. Med & Biol Labs Co, Ina, Saitama, Japan. RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM alexander_marneros@hms.harvard.edu FU NEI NIH HHS [EY04939, EY12231, R01 EY004939, R01 EY012231]; NHLBI NIH HHS [R01 HL067255]; NIAMS NIH HHS [AR36819, AR36820, R01 AR036819, R01 AR036820, R37 AR036819]; NINDS NIH HHS [R01 NS033981, NS33981-02] NR 27 TC 75 Z9 77 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 14 PY 2004 VL 23 IS 1 BP 89 EP 99 DI 10.1038/sj.emboj.7600014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 773JW UT WOS:000188921500009 PM 14685281 ER PT J AU Surks, MI Ortiz, E Daniels, GH Sawin, CT Col, NF Cobin, RH Franklyn, JA Hershman, JM Burman, KD Denke, MA Gorman, C Cooper, RS Weissman, NJ AF Surks, MI Ortiz, E Daniels, GH Sawin, CT Col, NF Cobin, RH Franklyn, JA Hershman, JM Burman, KD Denke, MA Gorman, C Cooper, RS Weissman, NJ TI Subclinical thyroid disease - Scientific review and guidelines for diagnosis and management SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the American-Thyroid-Association CY OCT 09-13, 2002 CL LOS ANGELES, CALIFORNIA SP Amer Thyroid Assoc ID PLACEBO-CONTROLLED TRIAL; SICK EUTHYROID SYNDROME; L-THYROXINE TREATMENT; SERUM THYROTROPIN; STIMULATING HORMONE; ATRIAL-FIBRILLATION; DOUBLE-BLIND; RISK-FACTOR; FOLLOW-UP; NONTHYROIDAL ILLNESS AB Context Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T-3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. Objectives To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. Data Sources MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) data bases were searched for articles on subdinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. Study Selection and Data Extraction A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. Data Synthesis The strength of the evidence that untreated subdinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subdinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subdinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. Conclusions Data supporting associations of subdinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subdinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction. C1 Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Agcy Healthcare Res & Qual, Ctr Primary Care Prevent & Clin Partnerships, Rockville, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Vet Adm, Washington, DC USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Univ Birmingham, Div Med Sci, Birmingham, W Midlands, England. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90024 USA. Washington Hosp Ctr, Endocrine Sect, Washington, DC 20010 USA. Univ Texas, SW Med Ctr Dallas, Dept Med, Dallas, TX 75235 USA. Mayo Clin & Mayo Fdn, Res Dev, Rochester, MN 55905 USA. Loyola Univ, Sch Med, Chicago, IL 60611 USA. Georgetown Univ, Coll Med, Dept Med, Washington, DC USA. RP Surks, MI (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. NR 96 TC 885 Z9 984 U1 6 U2 58 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 14 PY 2004 VL 291 IS 2 BP 228 EP 238 DI 10.1001/jama.291.2.228 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 762YZ UT WOS:000188040900032 PM 14722150 ER PT J AU Col, NF Surks, MI Daniels, GH AF Col, NF Surks, MI Daniels, GH TI Subclinical thyroid disease - Clinical applications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID FOLLOW-UP; HYPOTHYROIDISM; HYPERTHYROIDISM; COMMUNITY; BONE; DEFICIENCY; PREVALENCE; THERAPY AB Subclinical hypothyroidism and hyperthyroidism are diagnoses based on laboratory evaluation with few if any clinical signs or symptoms. Subclinical hypothyroidism is defined as an elevation in serum thyroid-stimulating hormone (TSH) above the upper limit of the reference range (0.45-4.5 mIU/L). with normal serum FT4 concentration; subclinical hyperthyroidism is defined as a decrease in serum TSH below the reference range with normal serum FT4- and T-3 Concentrations. Though these conditions represent the earliest stages of thyroid dysfunction, the benefits of detecting and treating subclinical thyroid disease are not well established. Most persons found to have subclinical thyroid disease will have TSH values between 0.1 and 0.45 mIU/L or between 4.5 and 10 mIU/L, for which the benefits of treatment are not clearly established; treatment may be beneficial in individuals with serum TSH lower than 0.1 mIU/L or higher than 10 mIU/L. This article illustrates approaches to managing patients with subclinical hypothyroidism and hyperthyroidism through 5 case scenarios that apply the principles of evidence-based medicine. Because of the substantial uncertainty concerning the consequences of untreated subclinical hypothyroidism and hyperthyroidism, as well as the benefit of initiating treatment, patient preferences are important in deciding, on management of subclinical disease. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Montefiore Med Ctr, Dept Pathol & Med, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Surks, MI (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. NR 21 TC 81 Z9 89 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 14 PY 2004 VL 291 IS 2 BP 239 EP 243 DI 10.1001/jama.291.2.239 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 762YZ UT WOS:000188040900033 PM 14722151 ER PT J AU Smith, AC Frank, LM Wirth, S Yanike, M Hu, D Kubota, Y Graybiel, AM Suzuki, WA Brown, EN AF Smith, AC Frank, LM Wirth, S Yanike, M Hu, D Kubota, Y Graybiel, AM Suzuki, WA Brown, EN TI Dynamic analysis of learning in behavioral experiments SO JOURNAL OF NEUROSCIENCE LA English DT Article DE learning; behavior; state-space model; hidden Markov model; change-point test; association task; EM algorithm ID PREFRONTAL CORTEX; RATS; SET; HIPPOCAMPUS; ACQUISITION; LESIONS; REWARD; MEMORY; MONKEY; MODELS AB Understanding how an animal's ability to learn relates to neural activity or is altered by lesions, different attentional states, pharmacological interventions, or genetic manipulations are central questions in neuroscience. Although learning is a dynamic process, current analyses do not use dynamic estimation methods, require many trials across many animals to establish the occurrence of learning, and provide no consensus as how best to identify when learning has occurred. We develop a state-space model paradigm to characterize learning as the probability of a correct response as a function of trial number (learning curve). We compute the learning curve and its confidence intervals using a state-space smoothing algorithm and define the learning trial as the first trial on which there is reasonable certainty (>0.95) that a subject performs better than chance for the balance of the experiment. For a range of simulated learning experiments, the smoothing algorithm estimated learning curves with smaller mean integrated squared error and identified the learning trials with greater reliability than commonly used methods. The smoothing algorithm tracked easily the rapid learning of a monkey during a single session of an association learning experiment and identified learning 2 to 4 d earlier than accepted criteria for a rat in a 47 d procedural learning experiment. Our state-space paradigm estimates learning curves for single animals, gives a precise definition of learning, and suggests a coherent statistical framework for the design and analysis of learning experiments that could reduce the number of animals and trials per animal that these studies require. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM brown@neurostat.mgh.harvard.edu OI Frank, Loren/0000-0002-1752-5677 FU NIDA NIH HHS [DA015644, R01 DA015644]; NIMH NIH HHS [F32 MH065108, K02 MH061637, MH58847, MH59733, MH60379, MH61637, MH65108, R01 MH058847, R01 MH059733] NR 33 TC 124 Z9 125 U1 1 U2 10 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 JAN 14 PY 2004 VL 24 IS 2 BP 447 EP 461 DI 10.1523/JNEUROSCI.2908-03.2004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 763QE UT WOS:000188098000016 PM 14724243 ER PT J AU Giri, S Nath, N Smith, B Viollet, B Singh, AK Singh, I AF Giri, S Nath, N Smith, B Viollet, B Singh, AK Singh, I TI 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: A possible role of AMP-activated protein kinase SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glia; AICAR; NF-kappa B; inflammation; C/EBP; AMPK ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; RAT-LIVER; PERMEABLE ACTIVATOR; AICA-RIBOSIDE; FATTY-ACID; C/EBP; PHOSPHORYLATION; EXPRESSION; INDUCTION AB AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in the regulation of energy homeostasis and metabolic stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR) inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin-1beta, and interleukin-6) and inducible nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages. AICAR attenuates the LPS-induced activation of nuclear factor kappaB via downregulation of IkappaB kinase alpha/beta activity. It also inhibits nuclear translocation of CCAAT/enhancer-binding protein (C/EBP) transcription factor by inhibiting the expression of C/EBP-delta in brain glial cells. The dominant negative form of AMPKalpha(2) (D157A) and its antisense documents a possible role of AMPK in the regulation of the cellular proinflammatory process. AICAR also inhibited the production of inflammatory mediators in serum and their expression in CNS of rats injected with a sublethal dose of LPS by intraperitoneal injection. These observations in cultured cells as well as in the animal model suggest that AICAR may be of therapeutic value in treating inflammatory diseases. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Univ Paris 05, CNRS, INSERM, Dept Genet Dev & Mol Pathol,Inst Cochin, F-75014 Paris, France. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 316 Clin Sci Bldg, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS 37766, NS-22576, NS-34741, NS-40144, NS-40810] NR 45 TC 174 Z9 184 U1 3 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 JAN 14 PY 2004 VL 24 IS 2 BP 479 EP 487 DI 10.1523/JNEUROSCI.4288-03.2004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 763QE UT WOS:000188098000019 PM 14724246 ER PT J AU Birbeck, GL Gifford, DR Song, J Belin, TR Mittman, BS Vickrey, BG AF Birbeck, GL Gifford, DR Song, J Belin, TR Mittman, BS Vickrey, BG TI Do malpractice concerns, payment mechanisms, and attitudes influence test-ordering decisions? SO NEUROLOGY LA English DT Article ID PHYSICIAN ATTITUDES; UNCERTAINTY AB Greater understanding is needed of nonclinical factors that determine neurologists' decisions to order tests. The authors surveyed 595 US neurologists and utilized demographic information, attitude scales, and clinical scenarios to evaluate the influence of nonclinical factors on test-ordering decisions. Greater test reliance, higher malpractice concerns, and receiving reimbursement for testing were all associated with a higher likelihood of test ordering. These findings have implications for training needs and suggest malpractice worries may inflate health care costs. C1 Michigan State Univ, Dept Neurol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. Brown Univ, Dept Med, Providence, RI 02912 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Alzheimers Dis Res Ctr, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90406 USA. RP Birbeck, GL (reprint author), 138 Serv Rd,A-217, E Lansing, MI 48824 USA. EM Gretchen.Birbeck@ht.msu.edu NR 10 TC 28 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 13 PY 2004 VL 62 IS 1 BP 119 EP 121 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 762XR UT WOS:000188010100031 PM 14718712 ER PT J AU Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Akiyama, M Chauhan, D Munshi, N Gu, XS Bailey, C Joseph, M Libermann, TA Richon, VM Marks, PA Anderson, KC AF Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Shringarpure, R Hideshima, T Akiyama, M Chauhan, D Munshi, N Gu, XS Bailey, C Joseph, M Libermann, TA Richon, VM Marks, PA Anderson, KC TI Transcriptional signature of histone deacetylase inhibition in multiple myeloma: Biological and clinical implications SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oligonucleotide microarrays; cell signaling; drug resistance ID SUBEROYLANILIDE HYDROXAMIC ACID; THERAPEUTIC APPLICATIONS; GROWTH-FACTOR; MOLECULAR SEQUELAE; CANCER-CELLS; KAPPA-B; GENE; EXPRESSION; APOPTOSIS; LEUKEMIA AB Histone deacetylases (HDACs) affect cell growth at the transcriptional level by regulating the acetylation status of nucleosomal histories. HDAC inhibition induces differentiation and/or apoptosis in transformed cells. We recently showed that HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), potently induce apoptosis of human multiple myeloma (MM) cells. In this study, we focused on MM as a model to study the transcriptional profile of HDAC inhibitor treatment on tumor cells and to address their pathophysiological implications with confirmatory mechanistic and functional assays. We found that MM cells are irreversibly committed to cell death within few hours of incubation with SAHA. The molecular profile of MM cells before their commitment to SAHA-induced cell death is hallmarked by a constellation of anti proliferative and/or proapoptotic molecular events, including down-regulation of transcripts for members of the insulin-like growth factor (IGF)/IGF-1 receptor (IGF-IR) and IL-6 receptor (IL-6R) signaling cascades, antiapoptotic molecules (e.g., caspase inhibitors), oncogenic kinases, DNA synthesis/repair enzymes, and transcription factors (e.g., XBP-1, E2F-1) implicated in MM pathophysiology. Importantly, SAHA treatment suppresses the activity of the proteasome and expression of its subunits, and enhances MM cell sensitivity to proteasome inhibition by bortezomib (PS-341). SAHA also enhances the anti-MM activity of other proapoptotic agents, including dexamethasone, cytotoxic chemotherapy, and thalidomide analogs. These findings highlight the pleiotropic antitumor effects of HDAC inhibition, and provide the framework for future clinical applications of SAHA to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02115 USA. Aton Pharma Inc, Tarrytown, NY 10591 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI Libermann, Towia/F-9866-2010 FU PHS HHS [P0-1 78378, R0-1 50947] NR 54 TC 403 Z9 414 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2004 VL 101 IS 2 BP 540 EP 545 DI 10.1073/pnas.2536759100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764MJ UT WOS:000188210400024 PM 14695887 ER PT J AU Fang, MC Stafford, RS Ruskin, JN Singer, DE AF Fang, MC Stafford, RS Ruskin, JN Singer, DE TI National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GEORGIA SP Soc Gen Internal Med ID SINUS RHYTHM; WARFARIN USE; RISK-FACTORS; HEART-ASSOCIATION; STROKE PREVENTION; MANAGEMENT; THERAPY; AMIODARONE; EFFICACY; TRIALS AB Background: Atrial fibrillation is the most common cardiac arrhythmia associated with significant medical complications. We examined trends in the medical therapy of atrial fibrillation in the United States from 1991 through 2000. Methods: Data from 1355 visits among patients with atrial fibrillation were obtained from the National Ambulatory Medical Care Survey, a nationally representative assessment of office-based practice. We assessed trends in medication use for ventricular rate control (digoxin, beta-blockers, and calcium channel blockers), sinus rhythm maintenance (class IA, IC, and III antiarrhythmics), and thromboembolism prevention (oral anticoagulants and aspirin). Results: Overall rate control medication use decreased from 72% of visits in 1991-1992 to 56% in 1999-2000 (P = .01 for trend) due to declining digoxin use (64% to 37%, P < .001 for trend). β-Blocker and calcium channel blocker use remained unchanged. Although there was no change in overall sinus rhythm medication use over time, armodarone hydrochloride use increased from 0.2% to 6.4% (P < .001 for trend), while quinidine use decreased from 5.0% to 0.0% (P = .01 for trend). Oral anticoagulant use increased (28% to 41%, P = .01 for trend), with the greatest increase in patients aged 80 years and older (14% to 48%, P < .001 for trend). Despite this, only 46.5% of patients at high risk for stroke were taking anticoagulants in 1999-2000. Conclusions: Digoxin use in atrial fibrillation decreased over time, without concomitant increases in β-blocker or calcium channel blocker use. Antiodarone replaced quinidine as the dominant sinus rhythm medication. Although oral anticoagulant use increased over time, particularly in the oldest patients, fewer than half of the patients at high risk for stroke were anticoagulated. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. RP Fang, MC (reprint author), Univ Calif San Francisco, Dept Med, 533 Parnassus Ave,Campus Box 0131, San Francisco, CA 94143 USA. EM mfang@medicine.ucsf.edu FU BHP HRSA HHS [5T32 PE11001-13] NR 30 TC 136 Z9 139 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 12 PY 2004 VL 164 IS 1 BP 55 EP 60 DI 10.1001/archinte.164.1.55 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 763AF UT WOS:000188045200006 PM 14718322 ER PT J AU Harris, JE Thun, MJ Mondul, AM Calle, EE AF Harris, JE Thun, MJ Mondul, AM Calle, EE TI Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8 SO BRITISH MEDICAL JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; FRENCH CASE-CONTROL; CARDIORESPIRATORY DISEASE; SMOKING-CESSATION; FILTER CIGARETTES; RISK FACTOR; SMOKERS; WOMEN; TOBACCO; MEN AB Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar cigarettes. Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day. Setting Cancer prevention study H (CPS-II). Participants 364 239 men and 576 535 women, aged greater than or equal to 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study. Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (less than or equal to 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (greater than or equal to 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg). Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (greater than or equal to 22 mg) non-filter brands (hazard ratio 1.44 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively). Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (less than or equal to 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings greater than or equal to 22 mg have an even higher risk of lung cancer. C1 MIT, Dept Econ, Cambridge, MA 02139 USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Harris, JE (reprint author), Massachusetts Gen Hosp, Internal Med Associates, Boston, MA 02114 USA. NR 75 TC 65 Z9 70 U1 4 U2 17 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JAN 10 PY 2004 VL 328 IS 7431 BP 72 EP 76 DI 10.1136/bmj.37936.585382.44 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 762MP UT WOS:000187976400013 PM 14715602 ER PT J AU Tagami, H Ray-Gallet, D Almouzni, G Nakatani, Y AF Tagami, H Ray-Gallet, D Almouzni, G Nakatani, Y TI Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis SO CELL LA English DT Article ID SYNDROME CRITICAL REGION; VARIANT SYNTHESIS; CHROMATIN STATES; REPLICATION FORK; MESSENGER-RNA; HUMAN HOMOLOG; CELL-CYCLE; HUMAN ASF1; IN-VITRO; S-PHASE AB Deposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA replication and possibly DNA repair, whereas histone variant H3.3 serves as the replacement variant for the DNA-synthesis-independent deposition pathway. To address how histories H3.1 and H3.3 are deposited into chromatin through distinct pathways, we have purified deposition machineries for these histories. The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively. Notably, these complexes possess one molecule each of H3.1/H3.3 and H4, suggesting that histories H3 and H4 exist as dimeric units that are important intermediates in nucleosome formation. This finding provides new insights into possible mechanisms for maintenance of epigenetic information after chromatin duplication. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CNRS, UMR 218, Inst Curie, Sect Rech, F-75248 Paris, France. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM yoshihiro_nakatani@dfci.harvard.edu FU NIGMS NIH HHS [GM065939-02] NR 52 TC 705 Z9 733 U1 9 U2 42 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 9 PY 2004 VL 116 IS 1 BP 51 EP 61 DI 10.1016/S0092-8674(03)01064-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762FL UT WOS:000187960800008 PM 14718166 ER PT J AU Murthy, V Han, SY Beauchamp, RL Smith, N Haddad, LA Ito, N Ramesh, V AF Murthy, V Han, SY Beauchamp, RL Smith, N Haddad, LA Ito, N Ramesh, V TI Pam and its ortholog highwire interact with and may negatively regulate the TSC1 center dot TSC2 complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUBEROUS SCLEROSIS GENE; TUMOR-SUPPRESSOR PROTEINS; CELL-GROWTH; DEVELOPMENTAL EXPRESSION; 3-KINASE/AKT PATHWAY; EMBRYONIC LETHALITY; MAMMALIAN TARGET; SYNAPTIC GROWTH; TSC2 MUTATION; C-ELEGANS AB Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder associated with mutations in TSC1, which codes for hamartin, or TSC2, which codes for tuberin. The brain is one of the most severely affected organs, and CNS lesions include cortical tubers and subependymal giant cell astrocytomas, resulting in mental retardation and seizures. Tuberin and hamartin function together as a complex in mammals and Drosophila. We report here the association of Pam, a protein identified as an interactor of Myc, with the tuberin-hamartin complex in the brain. The C terminus of Pam containing the RING zinc finger motif binds to tuberin. Pam is expressed in embryonic and adult brain as well as in cultured neurons. Pam has two forms in the rat CNS, an similar to 450-kDa form expressed in early embryonic stages and an similar to 350-kDa form observed in the postnatal period. In cortical neurons, Pam co-localizes with tuberin and hamartin in neurites and growth cones. Although Pam function(s) are yet to be defined, the highly conserved Pam homologs, HIW ( Drosophila) and RPM-1 ( Caenorhabditis elegans), are neuron-specific proteins that regulate synaptic growth. Here we show that HIW can genetically interact with the Tsc1.Tsc2 complex in Drosophila and could negatively regulate Tsc1.Tsc2 activity. Based on genetic studies, HIW has been implicated in ubiquitination, possibly functioning as an E3 ubiquitin ligase through the RING zinc finger domain. Therefore, we hypothesize that Pam, through its interaction with tuberin, could regulate the ubiquitination and proteasomal degradation of the tuberin-hamartin complex particularly in the CNS. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St,Rm 6222, Charlestown, MA 02129 USA. RI Haddad, Luciana/D-8002-2012 FU NINDS NIH HHS [NS24279, NS41917] NR 45 TC 56 Z9 58 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 9 PY 2004 VL 279 IS 2 BP 1351 EP 1358 DI 10.1074/jbc.M310208200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759DJ UT WOS:000187722800063 PM 14559897 ER PT J AU Geijsen, N Horoschak, M Kim, K Gribnau, J Eggan, K Daley, GQ AF Geijsen, N Horoschak, M Kim, K Gribnau, J Eggan, K Daley, GQ TI Derivation of embryonic germ cells and male gametes from embryonic stem cells SO NATURE LA English DT Article ID MALE-STERILITY GENE; RET FINGER PROTEIN; IN-VITRO; YOLK-SAC; MOUSE; EXPRESSION; DAZ; DIFFERENTIATION; SPERMATOGENESIS; PROLIFERATION AB Egg and sperm cells ( gametes) of the mouse are derived from a founder population of primordial germ cells that are set aside early in embryogenesis. Primordial germ cells arise from the proximal epiblast, a region of the early mouse embryo that also contributes to the first blood lineages of the embryonic yolk sac(1). Embryonic stem cells differentiate in vitro into cystic structures called embryoid bodies consisting of tissue lineages typical of the early mouse embryo(2,3). Because embryoid bodies sustain blood development, we reasoned that they might also support primordial germ cell formation. Here we isolate primordial germ cells from embryoid bodies, and derive continuously growing lines of embryonic germ cells. Embryonic germ cells show erasure of the methylation markers ( imprints) of the Igf2r and H19 genes, a property characteristic of the germlineage. We show that embryoid bodies support maturation of the primordial germ cells into haploid male gametes, which when injected into oocytes restore the somatic diploid chromosome complement and develop into blastocysts. Our ability to derive germ cells from embryonic stem cells provides an accessible in vitro model system for studies of germline epigenetic modification and mammalian gametogenesis. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM george.daley@childrens.harvard.edu NR 31 TC 478 Z9 546 U1 6 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 8 PY 2004 VL 427 IS 6970 BP 148 EP 154 DI 10.1038/nature02247 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 760YY UT WOS:000187863900034 PM 14668819 ER PT J AU Mempel, TR Henrickson, SE von Andrian, UH AF Mempel, TR Henrickson, SE von Andrian, UH TI T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases SO NATURE LA English DT Article ID IMMUNOLOGICAL SYNAPSE FORMATION; ANTIGEN PRESENTATION; IN-VIVO; ACTIVATION; LYMPHOCYTES; EXPRESSION; CHEMOKINE; INDUCTION; DYNAMICS AB Primary T-cell responses in lymph nodes (LNs) require contact-dependent information exchange between T cells and dendritic cells (DCs). Because lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool is composed of nonsynchronized cells with different dwell times that display heterogeneous behaviour in mouse LNs in vitro(1-3). Here we employ two-photon microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell time in LNs was synchronized. During the first 8 h after entering from the blood, T cells underwent multiple short encounters with DCs, progressively decreased their motility, and upregulated activation markers. During the subsequent 12 h T cells formed long-lasting stable conjugates with DCs and began to secrete interleukin-2 and interferon-gamma. On the second day, coinciding with the onset of proliferation, T cells resumed their rapid migration and short DC contacts. Thus, T-cell priming by DCs occurs in three successive stages: transient serial encounters during the first activation phase are followed by a second phase of stable contacts culminating in cytokine production, which makes a transition into a third phase of high motility and rapid proliferation. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NIGMS NIH HHS [T32 GM007753] NR 30 TC 924 Z9 947 U1 9 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 8 PY 2004 VL 427 IS 6970 BP 154 EP 159 DI 10.1038/nature02238 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 760YY UT WOS:000187863900035 PM 14712275 ER PT J AU Chad, DA Hedley-Whyte, ET Dawson, KT Amato, A Basgoz, N AF Chad, DA Hedley-Whyte, ET Dawson, KT Amato, A Basgoz, N TI A 49-year-old woman with asymmetric painful neuropathy - Borderline leprosy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MIGRANT SENSORY NEURITIS; PERIPHERAL NEUROPATHY; PERINEURITIS; DIAGNOSIS C1 UMass Mem Hlth Care, Dept Neurol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Chad, DA (reprint author), UMass Mem Hlth Care, Dept Neurol, Worcester, MA 01605 USA. NR 24 TC 7 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 2004 VL 350 IS 2 BP 166 EP 176 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 760WP UT WOS:000187858500012 PM 14711916 ER PT J AU Greene, MF Ecker, JL AF Greene, MF Ecker, JL TI Abortion, health, and the law SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 8 Z9 8 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 2004 VL 350 IS 2 BP 184 EP 186 DI 10.1056/NEJMsb035739 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 760WP UT WOS:000187858500016 PM 14711920 ER PT J AU Baer, JS Rosengren, DB Dunn, CW Wells, EA Ogle, RL Hartzler, B AF Baer, JS Rosengren, DB Dunn, CW Wells, EA Ogle, RL Hartzler, B TI An evaluation of workshop training in motivational interviewing for addiction and mental health clinicians SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE motivational interviewing; training evaluation; skill acquisition ID STANDARDIZED PATIENTS; SIMULATED PATIENTS; INTERVENTIONS; SKILLS AB We evaluated a 2-day training workshop on motivational interviewing (MI) for addiction and mental health clinicians (n = 22). Clinicians completed the helpful responses questionnaire (HRQ) and taped interactions with a standardized patient (SP). Independent, blinded coders rated the tapes using the motivational interviewing skills code (MISC). Post-training assessment showed significant increase on the HRQ and two of four MISC summary scores for SP interviews. At 2-month follow-up, means of the HRQ and two MISC summary scores remained higher than baseline, but declined from post-training. Some MI skills improved to a greater degree than others, and a subset of clinicians (>40%) showed continued improvement at follow-up. Results were consistent across interviews with different SPs, supporting the use of this assessment method. Findings highlight the need for additional research on the use of standardized patients, alternative assessment techniques, and effective methods of technology transfer for MI skill acquisition and retention. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Univ Washington, Dept Psychol, Seattle, WA 98108 USA. VA Med Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Social Work, Seattle, WA 98195 USA. Univ N Carolina, Dept Psychol, Wilmington, NC 28403 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Baer, JS (reprint author), Univ Washington, Dept Psychol, S-116-ATC,1660 S Colombian Way, Seattle, WA 98108 USA. EM jsbaer@u.washington.edu NR 22 TC 106 Z9 106 U1 0 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 7 PY 2004 VL 73 IS 1 BP 99 EP 106 DI 10.1016/j.drugalcdep.2003.10.001 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 763VV UT WOS:000188121900011 PM 14687964 ER PT J AU Qin, ZH Wang, YM Sapp, E Cuiffo, B Wanker, E Hayden, MR Kegel, KB Aronin, N DiFiglia, M AF Qin, ZH Wang, YM Sapp, E Cuiffo, B Wanker, E Hayden, MR Kegel, KB Aronin, N DiFiglia, M TI Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; huntingtin; autophagy; vesicle trafficking; dynamin; protein aggregates; protein interactions ID NEURONAL INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; BINDING PROTEIN; DISEASE BRAINS; HEAT REPEATS; WILD-TYPE; IN-VIVO; POLYGLUTAMINE; EXPRESSION; AUTOPHAGY AB Polyglutamine expansion in the N terminus of huntingtin (htt) causes selective neuronal dysfunction and cell death by unknown mechanisms. Truncated htt expressed in vitro produced htt immunoreactive cytoplasmic bodies ( htt bodies). The fibrillar core of the mutant htt body resisted protease treatment and contained cathepsin D, ubiquitin, and heat shock protein (HSP) 40. The shell of the htt body was composed of globules 14 - 34 nm in diameter and was protease sensitive. HSP70, proteasome, dynamin, and the htt binding partners htt interacting protein 1 (HIP1), SH3-containing Grb2-like protein (SH3GL3), and 14.7K-interacting protein were reduced in their normal location and redistributed to the shell. Removal of a series of prolines adjacent to the polyglutamine region in htt blocked formation of the shell of the htt body and redistribution of dynamin, HIP1, SH3GL3, and proteasome to it. Internalization of transferrin was impaired in cells that formed htt bodies. In cortical neurons of Huntington's disease patients with early stage pathology, dynamin immunoreactivity accumulated in cytoplasmic bodies. Results suggest that accumulation of a nonfibrillar form of mutant htt in the cytoplasm contributes to neuronal dysfunction by sequestering proteins involved in vesicle trafficking. C1 Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. Univ British Columbia, Dept Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. RP Qin, ZH (reprint author), Massachusetts Gen Hosp, Lab Cellular Neurobiol, 114 16th St,Room 2125, Charlestown, MA 02129 USA. RI Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Wanker, Erich/0000-0001-8072-1630 FU NINDS NIH HHS [NS13579, NS16367, NS38194] NR 53 TC 100 Z9 105 U1 3 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 7 PY 2004 VL 24 IS 1 BP 269 EP 281 DI 10.1523/JNEUROSCI.1409-03.2004 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 761EW UT WOS:000187888700028 PM 14715959 ER PT J AU Tong, AT Roudaut, R Ozkan, M Sagie, A Shahid, MSA Pontes, SC Carreras, F Girard, SE Arnaout, S Stainback, RF Thadhani, R Zoghbi, WA AF Tong, AT Roudaut, R Ozkan, M Sagie, A Shahid, MSA Pontes, SC Carreras, F Girard, SE Arnaout, S Stainback, RF Thadhani, R Zoghbi, WA CA PRO-TEE Registry Investigators TI Transesophageal echocardiography improves risk assessment of thrombolysis of prosthetic valve thrombosis: Results of the International PRO-TEE Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIAC VALVULAR PROSTHESES; SURGICAL-MANAGEMENT; HEART-VALVES; THERAPY; OBSTRUCTION; DIAGNOSIS; REOPERATION; OPERATION; LINE; TERM AB Objectives The goal of this study was to evaluate whether quantitation of thrombus burden with transesophageal echocardiography (TEE) can help risk-stratify patients undergoing thrombolysis of prosthetic valve thrombosis (PVT). Background Thrombolytic therapy of PVT has an unpredictable risk of embolization and complications. Methods An international registry of patients with suspected PVT undergoing two-dimensional/Doppler and TEE before thrombolysis was established. All TEE studies were reviewed and quantitated by a single observer blinded to all data. Results From 1985 to 2001, 107 patients (71 females; age 24 to 86 years) from 14 centers (6 in the U.S.) were identified. The majority of cases involved the mitral valve (79 mitral, 13 aortic, and 15 tricuspid). Hemodynamic success rate was achieved in 85% and was similar across valves. Overall complications were observed in 17.8%, and death in 5.6%. Predictors of complications were: New York Heart Association (NYHA) functional class, presence of shock, sinus tachycardia, hypotension, previous history of stroke, thrombus extension beyond the valve ring, and thrombus area. Multivariate analysis demonstrated that two variables were independent predictors of complications: thrombus area by TEE (odds ratio [OR] 2.41 per 1 cm(2) increment, 95% confidence interval [CI] 1.12 to 5.19) and prior history of stroke (OR 4.55, 95% CI 1.35 to 15.38). A thrombus area <0.8 cm(2) identified patients at lower risk for complications from thrombolysis, irrespective of NYHA functional class. Conclusions In PVT, the thrombus size imaged with TEE is a significant independent predictor of outcome. Transesophageal echocardiography can identify low-risk groups for thrombolysis irrespective of symptom severity and is therefore recommended in the management of prosthetic valve thrombosis. C1 Baylor Coll Med, Houston, TX 77030 USA. Hop Cardiol Du Haut Leveque, Pessac, France. Kosuyolu Heart & Res Hosp, Istanbul, Turkey. Rabin Med Ctr, Petah Tiqwa, Israel. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. Inst Dante Pazzanes E Cardiol, Sao Paulo, Brazil. Hosp Santa Creu & Sant Pau, Barcelona, Spain. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Amer Univ Beirut, Beirut, Lebanon. Texas Heart Inst, Houston, TX 77025 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zoghbi, WA (reprint author), Methodist DeBakey Heart Ctr, Echocardiog Lab, 6550 Fannin,SM-677, Houston, TX 77030 USA. OI Stainback, Raymond/0000-0002-2089-6508 NR 31 TC 104 Z9 108 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 7 PY 2004 VL 43 IS 1 BP 77 EP 84 DI 10.1016/j.jacc.2003.08.028 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 760DB UT WOS:000187795400016 PM 14715187 ER PT J AU Garber, JE Syngal, S AF Garber, JE Syngal, S TI One less thing to worry about: The shrinking spectrum of tumors in BRCA founder mutation carriers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; COLORECTAL-CANCER; PHEOCHROMOCYTOMA; ASSOCIATION; PREVENTION; CARCINOMA; COLON; RISKS C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,SM 209, Boston, MA 02115 USA. EM judy_garber@dfci.harvard.edu NR 17 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 7 PY 2004 VL 96 IS 1 BP 2 EP 3 DI 10.1093/jnci/djh021 PG 2 WC Oncology SC Oncology GA 765ED UT WOS:000188253400001 PM 14709725 ER PT J AU Schernhammer, ES Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, ES Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS TI A prospective study of aspirin use and the risk of pancreatic cancer in women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BREAST-CANCER; CELL-LINES; EXPRESSION; CYCLOOXYGENASE-2; CARCINOGENESIS; INHIBITION; WEIGHT AB Background: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses' Health Study. Methods: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. Results: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] = 1.20, 95% confidence interval [CI] = 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR = 1.58, 95% CI = 1.03 to 2.43; P-trend = .01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR = 1.11, 95% CI = 0.70 to 1.76; four to six tablets per week: RR = 1.29, 95% CI = 0.70 to 2.40; seven to 13 tablets per week: RR = 1.41, 95% CI = 0.76 to 2.61; and 2:14 tablets per week: RR = 1.86, 95% CI = 1.03 to 3.35) (P-trend = .02). Conclusion: Extended periods of regular aspirin use appear to be associated with a statistically significantly increased risk of pancreatic cancer among women. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. 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 Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA86102, CA/ES62984, CA40356, CA55075, CA87969] NR 30 TC 88 Z9 94 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 7 PY 2004 VL 96 IS 1 BP 22 EP 28 DI 10.1093/jnci/djh001 PG 7 WC Oncology SC Oncology GA 765ED UT WOS:000188253400008 PM 14709735 ER PT J AU Achenbach, S Moselewski, F Ropers, D Ferencik, M Hoffmann, U MacNeill, B Pohle, K Baum, U Anders, K Jang, I Daniel, WG Brady, TJ AF Achenbach, S Moselewski, F Ropers, D Ferencik, M Hoffmann, U MacNeill, B Pohle, K Baum, U Anders, K Jang, I Daniel, WG Brady, TJ TI Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography - A segment-based comparison with intravascular ultrasound SO CIRCULATION LA English DT Article DE tomography; atherosclerosis; coronary disease ID CT; ARTERIES AB Background - We investigated the ability of multidetector spiral computed tomography (MDCT) to detect atherosclerotic plaque in nonstenotic coronary arteries. Methods and Results - In 22 patients without significant coronary stenoses, contrast-enhanced MDCT (0.75-mm collimation, 420-ms rotation) and intravascular ultrasound (IVUS) of one coronary artery were performed. A total of 83 coronary segments were imaged by IVUS ( left main, 19; left anterior descending, 51; left circumflex, 4; right coronary, 9). MDCT data sets were evaluated for the presence and volume of plaque in the coronary artery segments. Results were compared with IVUS in a blinded fashion. For the detection of segments with any plaque, MDCT had a sensitivity of 82% (41 of 50) and specificity of 88% (29 of 33). For calcified plaque, sensitivity was 94% (33 of 36) and specificity 94% ( 45 of 47). Coronary segments containing noncalcified plaque were detected with a sensitivity of 78% (35 of 45) and specificity of 87% (33 of 38), but presence of exclusively noncalcified plaque was detected with only 53% sensitivity ( 8 of 15). If analysis was limited to the 41 proximal segments ( segments 1, 5, 6, and 11 according to American Heart Association classification), sensitivity and specificity were 92% and 88% for any plaque, 95% and 91% for calcified plaque, and 91% and 89% for noncalcified plaque. MDCT substantially underestimated plaque volume per segment as compared with IVUS (24 +/- 35 mm(3) versus 43 +/- 60 mm(3), P < 0.001). Conclusions - The results indicate the potential of MDCT to detect coronary atherosclerotic plaque in patients without significant coronary stenoses. However, further improvements in image quality will be necessary to achieve reliable assessment, especially of noncalcified plaque throughout the coronary tree. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-8520 Erlangen, Germany. RP Achenbach, S (reprint author), Univ Erlangen Nurnberg, Dept Internal Med 2, Ulmenweg 18, D-91054 Erlangen, Germany. NR 11 TC 495 Z9 521 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 6 PY 2004 VL 109 IS 1 BP 14 EP 17 DI 10.1161/01.CIR.0000111517.69230.0F PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 760BY UT WOS:000187791900005 PM 14691045 ER PT J AU Rivera, GM Briceno, CA Takeshima, F Snapper, SB Mayer, BJ AF Rivera, GM Briceno, CA Takeshima, F Snapper, SB Mayer, BJ TI Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck triggers localized actin polymerization SO CURRENT BIOLOGY LA English DT Article ID ALDRICH-SYNDROME PROTEIN; N-WASP; ARP2/3 COMPLEX; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; FILOPODIUM FORMATION; SURFACE-RECEPTORS; TYROSINE KINASES; FOCAL ADHESIONS; CELL ACTIVATION; 3T3 FIBROBLASTS AB Background: SH2/SH3 adaptor proteins play a critical role in tyrosine kinase signaling pathways, regulating essential cell functions by increasing the local concentration or altering the subcellular localization of downstream effectors. The SH2 domain of the Nck adaptor can bind tyrosine-phosphorylated proteins, while its SH3 domains can modulate actin polymerization by interacting with effectors such as WASP/Scar family proteins. Although several studies have implicated Nck in regulating actin polymerization, its role in living cells is not well understood. Results: We used an antibody-based system to experimentally modulate the local concentration of Nck SH3 domains on the plasma membrane of living cells. Clustering of fusion proteins containing all three Nck SH3 domains induced localized polymerization of actin, including the formation of actin tails and spots, accompanied by general cytoskeletal rearrangements. All three Nck SH3 domains were required, as clustering of individual SH3 domains or a combination of the two N-terminal Nck SH3 domains failed to promote significant local polymerization of actin in vivo. Changes in actin dynamics induced by Nck SH3 domain clustering required the recruitment of N-WASp, but not WAVE1, and were unaffected by downregulation of Cdc42. Conclusions: We show that high local concentrations of Nck SH3 domains are sufficient to stimulate localized, Cdc42-independent actin polymerization in living cells. This study provides strong evidence of a pivotal role for Nck in directly coupling ligand-induced tyrosine phosphorylation at the plasma membrane to localized changes in organization of the actin cytoskeleton through a signaling pathway that requires N-WASP. C1 Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. Harvard Univ, Dept Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mayer, BJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, 263 Farmington Ave, Farmington, CT 06030 USA. EM bmayer@neuron.uchc.edu FU NCI NIH HHS [CA82258] NR 59 TC 72 Z9 73 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 6 PY 2004 VL 14 IS 1 BP 11 EP 22 DI 10.1016/j.cub.2003.12.033 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 763UH UT WOS:000188118500019 PM 14711409 ER PT J AU Boulton, SJ Martin, JS Polanowska, J Hill, DE Gartner, A Vidal, M AF Boulton, SJ Martin, JS Polanowska, J Hill, DE Gartner, A Vidal, M TI BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans SO CURRENT BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR; DAMAGE RESPONSE; MEIOTIC CELLS; BRCA1; PROTEIN; COMPLEX; UBIQUITIN; CLONING; LIGASE; BARD1 AB Inherited germline mutations in the tumor suppressor gene BRCA1 predispose individuals to early onset breast and ovarian cancer [1]. BRCA1 together with its structurally related partner BARD1 is required for homologous recombination and DNA double-strand break repair, but how they perform these functions remains elusive [2, 3]. As part of a comprehensive search for DNA repair genes in C. elegans, we identified a BARD1 ortholog. In protein interaction screens, Ce-BRD-1 was found to interact with components of the sumoylation pathway, the TACC domain protein TAC-1, and most importantly, a homolog of mammalian BRCA1. We show that animals depleted for either Ce-brc-1 or Ce-brd-1 display similar abnormalities, including a high incidence of males, elevated levels of p53-dependent germ cell death before and after irradiation, and impaired progeny survival and chromosome fragmentation after irradiation. Furthermore, depletion of ubc-9 and tac-1 leads to radiation sensitivity and a high incidence of males, respectively, potentially linking these genes to the C. elegans BRCA1 pathway. Our findings support a shared role for Ce-BRC-1 and Ce-BRD-1 in C. elegans DNA repair processes, and this role will permit studies of the BRCA1 pathway in an organism amenable to rapid genetic and biochemical analysis. C1 London Res Inst, Canc Res UK, Clare Hall Labs, DNA Damage Response Lab, S Mimms EN6 3LD, Herts, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. RP Boulton, SJ (reprint author), London Res Inst, Canc Res UK, Clare Hall Labs, DNA Damage Response Lab, S Mimms EN6 3LD, Herts, England. EM simon.boulton@cancer.org.uk RI Hill, David/B-6617-2011; Polanowska, Jolanta/P-9117-2016; OI Polanowska, Jolanta/0000-0001-7666-7010; Gartner, Anton/0000-0003-4639-9902 FU NCI NIH HHS [7 R33 CA81658-02, P01CA80111-02]; NHGRI NIH HHS [5R01HG0715-02] NR 33 TC 86 Z9 94 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 6 PY 2004 VL 14 IS 1 BP 33 EP 39 DI 10.1016/j.cub.2003.11.029 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 763UH UT WOS:000188118500021 PM 14711411 ER PT J AU Luftig, M Yasui, T Soni, V Kang, MS Jacobson, N Cahir-McFarland, E Seed, B Kieff, E AF Luftig, M Yasui, T Soni, V Kang, MS Jacobson, N Cahir-McFarland, E Seed, B Kieff, E TI Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappa B activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOTOXIN-BETA-RECEPTOR; LYMPHOCYTE GROWTH TRANSFORMATION; SEVERE LIVER DEGENERATION; NECROSIS-FACTOR-ALPHA; GAMMA-DEFICIENT MICE; PROTEIN 1 ENGAGES; MEMBRANE-PROTEIN; IKK-ALPHA; DEFECTIVE INTERLEUKIN-1; NF-KAPPA-B2 P100 AB Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-kappaB activation is important for infected cell survival. LMP1 activates NF-kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40. LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha-dependent and IKKbeta/IKKgamma independent. In the experiments described here, we found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was required for p100 processing and p52 nuclear localization, whereas the LMP1 death domain binding site was not. Moreover, the LMP1 TRAF-binding site preferentially caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a role for IKKalpha in down-modulating canonical IKKbeta activation or its effects. In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore, LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent, whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent. Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical canonical IKKbeta/IKKgamma-independent, and noncanonical NIK/IKKalpha-dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is principally mediated by the LMP1 TRAF-binding site. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Program Virol,Brigham & Womens Hosp,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kieff, E (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Program Virol,Brigham & Womens Hosp,Channing Lab, 181 Longwood Ave,8th Floor, Boston, MA 02115 USA. EM ekieff@rics.bwh.harvard.edu FU NCI NIH HHS [CA47006, CA85180, R01 CA047006, R01 CA085180, R35 CA047006] NR 65 TC 116 Z9 125 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2004 VL 101 IS 1 BP 141 EP 146 DI 10.1073/pnas.2237183100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200028 PM 14691250 ER PT J AU Kissler, S Lu, LR Cantor, H AF Kissler, S Lu, LR Cantor, H TI Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Bcl-x gamma; TCR; thymus; CD5 ID POSITIVE SELECTION; DEFICIENT MICE; SELF-PEPTIDE; TCR SIGNALS; IN-VIVO; INDUCTION; TOLERANCE; ISOFORM; CD5 AB Thymic selection adjusts the reactivity of the peripheral T cell repertoire to maximize recognition of pathogens and minimize stimulation by innocuous substances and self-antigen. The study of molecules implicated in T cell activation often involves the generation of knockout(-/-) mice. in many instances, knockout animals display revealing phenotypes. But should a lack of phenotype be interpreted as a lack of function? Bcl-xgamma was shown previously to affect T cell activation in vitro, and here we note that overexpression of this molecule increases cell cycling after T cell receptor ligation by antibody. It was therefore surprising that Bcl-xgamma(-/-), Bcl-xgamma transgenic, and WT T cells displayed similar levels of sensitivity to antigen according to ex vivo stimulation. Bcl-xgamma could be demonstrated to influence competitiveness and selection of thymocytes in a manner that counteracted the effects of Bcl-xgamma mutation on T cell activation. These findings suggest that thymic selection can overcome genetic defects in T cell activation to generate a T cell repertoire of normal reactivity. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013; OI , /0000-0003-3062-7800; Lu, Linrong/0000-0002-0171-4115 NR 18 TC 4 Z9 4 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2004 VL 101 IS 1 BP 210 EP 214 DI 10.1073/pnas.0307202101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200040 PM 14694195 ER PT J AU Yang, H Ochani, M Li, JH Qiang, XL Tanovic, M Harris, HE Susarla, SM Ulloa, L Wang, H DiRaimo, R Czura, CJ Wang, HC Roth, J Warren, HS Fink, MP Fenton, MJ Andersson, U Tracey, KJ AF Yang, H Ochani, M Li, JH Qiang, XL Tanovic, M Harris, HE Susarla, SM Ulloa, L Wang, H DiRaimo, R Czura, CJ Wang, HC Roth, J Warren, HS Fink, MP Fenton, MJ Andersson, U Tracey, KJ TI Reversing established sepsis with antagonists of endogenous high-mobility group box 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; PROINFLAMMATORY CYTOKINES; SYSTEMIC INFLAMMATION; LETHAL BACTEREMIA; PROTEIN; MICE; CACHECTIN; MEDIATOR; HMG-1 AB Despite significant advances in intensive care therapy and antibiotics, severe sepsis accounts for 9% of all deaths in the United States annually. The pathological sequelae of sepsis are characterized by a systemic inflammatory response, but experimental therapeutics that target specific early inflammatory mediators [tumor necrosis factor (TNF) and IL-1beta] have not proven efficacious in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late mediator of endotoxin-induced lethality that exhibits significantly delayed kinetics relative to TNF and IL-1beta. Here, we report that serum HMGB1 levels are increased significantly in a standardized model of murine sepsis, beginning 18 h after surgical induction of peritonitis. Specific inhibition of HMGB1 activity [with either anti-HMGB1 antibody (600 mug per mouse) or the DNA-binding A box (600 mug per mouse)] beginning as late as 24 h after surgical induction of peritonitis significantly increased survival (nonimmune IgG-treated controls = 28% vs. anti-HMGB1 antibody group = 72%, P < 0.03; GST control protein = 28% vs. A box = 68%, P < 0.03). Animals treated with either HMGB1 antagonist were protected against the development of organ injury, as evidenced by improved levels of serum creatinine and blood urea nitrogen. These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame. C1 N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, Manhasset, NY 11030 USA. Karolinska Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA. Univ Maryland, Sch Med, Div Pulm & Crit Care, Baltimore, MD 21201 USA. Karolinska Inst, Dept Woman & Child Hlth, S-17176 Stockholm, Sweden. RP Tracey, KJ (reprint author), N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, 350 Community Dr, Manhasset, NY 11030 USA. EM kjtracey@sprynet.com RI Wang, Haichao/K-6310-2012; OI Wang, Haichao/0000-0002-0211-9000; Ulloa, Luis/0000-0002-7702-7549; Tracey, Kevin J/0000-0003-1884-6314; Andersson, Ulf/0000-0003-0316-3860; Susarla, Srinivas/0000-0003-0155-8260 NR 30 TC 704 Z9 759 U1 6 U2 36 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 JAN 6 PY 2004 VL 101 IS 1 BP 296 EP 301 DI 10.1073/pnas.2434651100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200055 PM 14695889 ER PT J AU Kim, J Krichevsky, A Grad, Y Hayes, GD Kosik, KS Church, GM Ruvkun, G AF Kim, J Krichevsky, A Grad, Y Hayes, GD Kosik, KS Church, GM Ruvkun, G TI Identification of many microRNAs that copurify with polyribosomes in mammalian neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE translational control; noncoding RNA; messenger ribonucleoprotein complex (mRNP) ID LOCAL PROTEIN-SYNTHESIS; RNA INTERFERENCE MACHINERY; NERVOUS-SYSTEM LINEAGES; C-ELEGANS; CAENORHABDITIS-ELEGANS; MESSENGER-RNAS; HIPPOCAMPAL-NEURONS; DROSOPHILA-MELANOGASTER; REGULATORY RNA; SYNAPTIC SITES AB Localized translation in mammalian dendrites may play a role in synaptic plasticity and contribute to the molecular basis for learning and memory. The regulatory mechanisms that control localized translation in neurons are not well understood. We propose a role for microRNAs (miRNAs), a class of noncoding RNAs, as mediators of neuronal translational regulation. We have identified 86 miRNAs expressed in mammalian neurons, of which 40 have not previously been reported. A subset of these miRNAs exhibits temporally regulated expression in cortical cultures. Moreover, all of the miRNAs that were tested cofractionate with polyribosomes, the sites of active translation. These findings indicate that a large, diverse population of miRNAs may function to regulate translation in mammalian neurons. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8,50 Blossom St, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu RI Hayes, Gabriel/B-9816-2012 FU NIGMS NIH HHS [GM44619, R01 GM044619] NR 69 TC 364 Z9 526 U1 0 U2 10 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 JAN 6 PY 2004 VL 101 IS 1 BP 360 EP 365 DI 10.1073/pnas.2333854100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200066 PM 14691248 ER PT J AU Francis, JW Figueiredo, D vanderSpek, JC Ayala, LM Kim, YS Remington, MP Young, PJ Lorson, CL Ikebe, S Fishman, PS Brown, RH AF Francis, JW Figueiredo, D vanderSpek, JC Ayala, LM Kim, YS Remington, MP Young, PJ Lorson, CL Ikebe, S Fishman, PS Brown, RH TI A survival motor neuron : tetanus toxin fragment C fusion protein for the targeted delivery of SMN protein to neurons SO BRAIN RESEARCH LA English DT Article DE spinal muscular atrophy; survival motor neuron (SMN) protein; tetanus toxin fragment C; diphtheria toxin; protein delivery ID SPINAL MUSCULAR-ATROPHY; RETROGRADE AXONAL-TRANSPORT; CENTRAL-NERVOUS-SYSTEM; DISEASE GENE-PRODUCT; DIPHTHERIA-TOXIN; MEMBRANE TRANSLOCATION; ESCHERICHIA-COLI; CELL-LINE; BINDING; INTERNALIZATION AB Spinal muscular atrophy (SMA) is a degenerative disorder of spinal motor neurons caused by homozygous mutations in the survival motor neuron (SMN1) gene. Because increased tissue levels of human SMN protein (hSMN) in transgenic mice reduce the motor neuron loss caused by murine SMN knockout, we engineered a recombinant SMN fusion protein to deliver exogenous hSMN to the cytosolic compartment of motor neurons. The fusion protein, SDT, is comprised of hSMN linked to the catalytic and transmembrane domains of diphtheria toxin (DTx) followed by fragment C of tetanus toxin (TTC). Following overexpression in Escherichia coli, SDT possessed a subunit molecular weight of approximately 130 kDa as revealed by both SDS-PAGE and immunoblot analyses with anti-SMN, anti-DTx, and anti-TTC antibodies. Like wild-type SMN, purified SDT showed specific binding in vitro to an RG peptide derived from Ewing's sarcoma protein. The fusion protein also bound to cultured primary neurons in amounts similar to those achieved by TTC. Unlike the case with TTC, however, immunolabeling of SDT-treated neurons with anti-TTC and anti-SM antibodies showed staining restricted to the cell surface. Results from cytotoxicity studies in which the DTx catalytic domain of SDT was used as a reporter protein for internalization and membrane translocation activity suggest that the SMN moiety of the fusion protein is interfering with one or both of these processes. While these studies indicate that SDT may not be useful for SMA therapy, the use of the TTC:DTx fusion construct to deliver other passenger proteins to the neuronal cytosol should not be ruled out. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Francis, JW (reprint author), Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Bldg 114,16th St,Room 3003, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA60934]; NINDS NIH HHS [P01NS31248, P01NS37912, R01 NS38679-04, R01 NS41584-01, R21NS41660-02] NR 56 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 2 PY 2004 VL 995 IS 1 BP 84 EP 96 DI 10.1016/j.brainres.2003.09.063 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 759QB UT WOS:000187747400011 PM 14644474 ER PT J AU Lutz, EP Kako, Y Yagyu, H Heeren, J Marks, S Wright, T Melford, K Ben-Zeev, O Radner, H Merkel, M Bensadoun, A Wong, H Goldberg, IJ AF Lutz, EP Kako, Y Yagyu, H Heeren, J Marks, S Wright, T Melford, K Ben-Zeev, O Radner, H Merkel, M Bensadoun, A Wong, H Goldberg, IJ TI Mice expressing only covalent dimeric heparin binding-deficient lipoprotein lipase - Muscles inefficiently secrete dimeric enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; TRANSGENIC MICE; SULFATE; TISSUES; INVOLVEMENT; SITE AB Lipoprotein lipase (LpL) hydrolyzes triglycerides of circulating lipoproteins while bound as homodimers to endothelial cell surface heparan sulfate proteoglycans. This primarily occurs in the capillary beds of muscle and adipose tissue. By creating a mouse line that expresses covalent dimers of heparin-binding deficient LpL (hLpL(HBM-Dimer)) in muscle, we confirmed in vivo that linking two LpL monomers in a head to tail configuration creates a functional LpL. The hLpL(HBM-Dimer) transgene produced abundant activity and protein in muscle, and the LpL was the expected size of a dimer (similar to110 kDa). Unlike the heparin-binding mutant monomer, hLpL(HBM-Dimer) had the same stability as nonmutated LpL. The hLpL(HBM-Dimer) transgene prevented the neonatal demise of LpL knockout mice; however, these mice were hypertriglyceridemic. Postheparin plasma LpL activity was lower than expected with the robust expression in muscle and was no longer covalently linked. Studies in transfected cells showed that Chinese hamster lung cells, but not COS cells, also degraded tandem repeated LpL into monomers. Thus, although muscle can synthesize tethered, dimeric LpL, efficient production of this enzyme leading to secretion, and physiological function appears to favor secretion of a noncovalent dimer composed of monomeric subunits. C1 Columbia Univ, Dept Med, New York, NY 10032 USA. Univ Hamburg, Hosp Eppendorf, Dept Med, D-20246 Hamburg, Germany. Univ Hamburg, Hosp Eppendorf, Dept Med Biochem & Mol Biol, D-20246 Hamburg, Germany. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Med, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Mainz, Inst Pathol, D-55101 Mainz, Germany. RP Goldberg, IJ (reprint author), Columbia Univ, Dept Med, 630 W 168th St, New York, NY 10032 USA. OI Merkel, Martin/0000-0002-2850-5110 FU NHLBI NIH HHS [HL028481, HL45095, HL014990] NR 21 TC 3 Z9 3 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 JAN 2 PY 2004 VL 279 IS 1 BP 238 EP 244 DI 10.1074/jbc.M310559200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757GU UT WOS:000187555300029 PM 14570890 ER PT J AU Gennari, F Mehta, S Wang, Y Tallarico, AS Palu, G Marasco, WA AF Gennari, F Mehta, S Wang, Y Tallarico, AS Palu, G Marasco, WA TI Direct phage to intrabody screening (DPIS): Demonstration by isolation of cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane protein 1 (LMP1) that block NF-kappa B transactivation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE intracellular antibodies; high-throughput screen; functional genomics; cancer; signalling ID LYMPHOCYTE GROWTH TRANSFORMATION; SINGLE-CHAIN ANTIBODIES; MEMBRANE-PROTEIN 1; TERMINAL CYTOPLASMIC DOMAIN; INTRACELLULAR ANTIBODIES; HIGH-AFFINITY; DISPLAY LIBRARY; ESCHERICHIA-COLI; CELL-LINES; CANONICAL STRUCTURES AB The expression of intracellular antibodies (intrabodies) in eukaryotic cells has provided a powerful tool to manipulate microbial and cellular signaling pathways in a highly precise manner. However, there have been several technical issues that have restricted their more widespread use. In particular, single-chain antibodies (sFv) have been reported to fold poorly in the reducing environment of the cytoplasm and as such there has been a reluctance to use sFv-phage libraries as a source of intrabodies unless a pre-selection step to identify these rare sFvs from natural libraries or libraries of engineering sFvs that could fold properly in the absence of disulfide bonds were used. Here, we investigated whether target specific sFvs that are isolated from a 15 billion member non-immune human sFv-phage display library could be directly screened in pools as intrabodies without prior knowledge of their individual identity or purity within pools of antigen-specific sFvs. As the target, we used a synthetic transformation effector site 1 (TES1) polypeptide comprising the membrane-most proximal 34 amino acid residues of the carboxyterminal cytoplasmic tail of the oncogenic latent membrane protein I (LMP1) of Epstein Barr virus, which serves as a docking site for adapter proteins of the tumor necrosis factor (TNF) receptor (TNFR)-associated factor (TRAF) family. Anti-TES1 sFvs, initially identified by phage ELISA screens, were grouped into pools according to the absorbance reading of the antigen-specific phage ELISA assays and then transferred as pools into eukaryotic expression vectors and expressed as cytoplasmic intrabodies. Using the pooling strategy, there was no loss of individual antiTES1 sFvs in the transfer from prokaryotic to eukaryotic expression vectors. In addition, the initial assignments into sFv pools based on phage ELISA readings allowed the segregation of individual anti-TES1 sFvs into discrete or minimally overlapping intrabody pools. Further assessment of the biological activity of the anti-TES1 intrabody pools demonstrated that they were all able to selectively block F-LMP1-induced NFkappaB activity that was mediated through the TES1-site and to bind LMP1 protein with high efficiency. This direct phage to intrabody screening (DPIS) strategy should allow investigators to bypass much of the in vitro sFv characterization that is often not predictive of in vivo intrabody function and provide a more efficient use of large native and synthetic sFv phage libraries already in existence to identify intrabodies that are active in vivo. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Padua, Sch Med, Dept Histol Microbiol & Med Biotechnol, I-35121 Padua, Italy. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB824, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU NIAID NIH HHS [AI28785] NR 81 TC 25 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 2 PY 2004 VL 335 IS 1 BP 193 EP 207 DI 10.1016/j.jmb.2003.09.073 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 761BP UT WOS:000187879600015 PM 14659750 ER PT J AU Holschneider, DP Maarek, JMI Yang, J Harimoto, J Scremin, OU AF Holschneider, DP Maarek, JMI Yang, J Harimoto, J Scremin, OU TI Activation of cerebral cortex during acoustic challenge or acute foot-shock in freely moving, nontethered rats SO NEUROSCIENCE LETTERS LA English DT Article DE brain mapping; cerebral blood flow; infusion pump; autoradiography; auditory cortex; electroshock; stress ID BLOOD-FLOW; INDICATOR FRACTIONATION; CONSCIOUS RAT; STRESS AB Most brain mapping techniques require immobilization of the subject, which extinguishes all but the simplest behaviors. We applied in freely moving rats an implantable microbolus infusion pump (MIP) which can be triggered by remote activation for the injection of the cerebral blood flow tracer [C-14]iodoantipyrine during behavioral activation. Consistent with previous electrophysiological, metabolic and brain anatomic studies, CBF-related tissue radioactivity (CBF-TR) increased in acoustic cortex during a 1000 Hz/8000 Hz alternating tone. In response to an acute foot-shock, CBF-TR increased in visual cortex, parietal association cortex, and extended into primary motor cortex, and primary somatosensory cortex mapping the trunk. These results support the utility of implantable pumps as adjunct tools for studying cerebral activation during behavioral challenges in nontethered, nonrestrained animals. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. RP Holschneider, DP (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. EM holschne@usc.edu FU NIA NIH HHS [K12 AG000521]; NIBIB NIH HHS [R01 EB000300, R01 EB-00300-03] NR 15 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 2 PY 2004 VL 354 IS 1 BP 74 EP 78 DI 10.1016/j.neulet.2003.09.078 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 765TA UT WOS:000188298500019 PM 14698485 ER PT S AU Correia, JA Burnham, CA Kaufman, D Fischman, A AF Correia, JA Burnham, CA Kaufman, D Fischman, A BE Metzler, SD TI Quasi-continous detector module design for high-resolution small animal PET SO 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2003 CL Portland, OR SP IEEE, Nucl & Plasma Sci Soc AB The purpose of the work reported here was to carry out design and development of a high-resolution volumetric PET detector module based on a generalization of our single-plane design. The design evaluated consists of an array of ten 1.2 x 7 x 50mm LSO crystals viewed by an array of eight photomultipliers. In general this design is extendable to larger axial dimension using longer crystals and additional photomultiplier tubes. The optical boundary pattern between crystals mimics a block detector in the radial direction while the optics relates to a continuous detector in the axial direction with the crystal boundaries enhancing uniformity of response. Results of singles measurements on a test block indicate that all crystals are identified radially and singles resolution on the order of 2 mm can be achieved axially over the central 80% axially. The advantages of this design include ease of fabrication, continuous axial sampling and lower light losses than modules constructed of individual crystal elements. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Correia, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8257-9 J9 IEEE NUCL SCI CONF R PY 2004 BP 2063 EP 2066 PG 4 WC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAS86 UT WOS:000223398000458 ER PT S AU Holdsworth, CH Badawi, RD Santos, P Van den Abbeele, AD Hoffman, EJ El Fakhri, G AF Holdsworth, CH Badawi, RD Santos, P Van den Abbeele, AD Hoffman, EJ El Fakhri, G BE Metzler, SD TI Evaluation of a Monte Carlo scatter correction in clinical 3D PET SO 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2003 CL Portland, OR SP IEEE, Nucl & Plasma Sci Soc AB Phantom and patient data were used to compare performance of a one-iteration Monte Carlo scatter correction (MC-SC-1i) for 3D PET [1], a vendor-supplied one-iteration single scatter model-based correction (SSS-1i) for 3D PET [2,3], unscatter-corrected 3D PET (No-SC), a SSS-1i followed by Monte Carlo scatter correction as a second iteration (MC-SSS) for 3D PET, and a convolution-subtraction scatter correction for 2D PET in terms of quantitative accuracy and lesion detectabitity [4]. ROI analysis showed 2D PET images were more accurate than 3D, particularly for large phantoms, and MC-SSS corrected 3D PET images were more accurate than SSS-1i corrected 3D PET images for this data set. 2D and 3D PET images were reconstructed from 59 patient data sets. Bias of 3D PET images with respect to 2D images was determined using Corresponding Intensity Variance [5]. 3D PET uncorrected images overestimated activity by similar to50% (smallest patients) to similar to150% (largest patients). The average absolute bias of SSS-1i corrected images (16%) was twice that of MC-SSS (8%) and more dependent on patient size. Lesion detection sensitivity in these patient images was evaluated using a Channelized Hotelling Observer. Scatter corrected 3D PET images performed similar to10% better than uncorrected 3D PET images for smaller patients. Slightly better lesion sensitivity was seen for large patients in images reconstructed using SSS-1i (CHO-SNR=2.23+/-0.29) compared to MC-SSS (2.08+/-0.27) and uncorrected images (2.02+/-0.23). C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Holdsworth, CH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8257-9 J9 IEEE NUCL SCI CONF R PY 2004 BP 2540 EP 2544 DI 10.1109/NSSMIC.2003.1352408 PG 5 WC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAS86 UT WOS:000223398000561 ER PT S AU Badawi, RD Surti, S Kemp, B Zimmerman, RE El Fakhri, G Holdsworth, CH Worstell, WA AF Badawi, RD Surti, S Kemp, B Zimmerman, RE El Fakhri, G Holdsworth, CH Worstell, WA BE Metzler, SD TI The effects of pulse pile-up on point-source measurements performed on different PET scanning devices SO 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2003 CL Portland, OR SP IEEE, Nucl & Plasma Sci Soc AB We have quantified resolution and contrast loss as a function of noise-equivalent count rate on the GSO-based Philips Allegro and the pixelated NaI CPET2 using previously developed methodology involving the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source. We found that at peak NEC, neither system showed significant loss of resolution. However., after accounting for event loss due to dead time, loss of contrast was seen in both systems. C1 Harvard Univ, Sch Med, Div Nucl Med, Dana Farber Canc Inst,Joint Program Nucl Med, Boston, MA 02115 USA. RP Badawi, RD (reprint author), Harvard Univ, Sch Med, Div Nucl Med, Dana Farber Canc Inst,Joint Program Nucl Med, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8257-9 J9 IEEE NUCL SCI CONF R PY 2004 BP 2581 EP 2583 DI 10.1109/NSSMIC.2003.1352418 PG 3 WC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAS86 UT WOS:000223398000571 ER PT B AU Ntziachristos, V Graves, E Schultz, RF Ripoll, J AF Ntziachristos, V Graves, E Schultz, RF Ripoll, J GP IEEE TI Fluorescence Molecular Tomography: New detection schemes for acquiring high information content measurements SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 AND 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE ID 3-DIMENSIONAL OPTICAL TOMOGRAPHY; SYSTEM; MEDIA AB We describe the implementation of new detection concepts based on highly spatial sampling and non-contact measurements for obtaining tomographic reconstructions of targeted fluorochromes with phantoms and in-vivo. This new approach can enable unprecedented experimental performance and simplicity compared to conventional tomographic systems. C1 Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA USA. RP Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, CNY 149 13th St, Charlestown, MA USA. RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 12 TC 0 Z9 0 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 1475 EP 1478 PG 4 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671301109 ER PT B AU Saha, S Long, CJ Brown, E Aminoff, E Bar, M Solo, V AF Saha, S Long, CJ Brown, E Aminoff, E Bar, M Solo, V GP IEEE TI Hemodynamic transfer function estimation with Laguerre polynomials and confidence intervals construction, from functional magnetic resonance imaging (FMRI) data SO 2004 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOL III, PROCEEDINGS: IMAGE AND MULTIDIMENSIONAL SIGNAL PROCESSING SPECIAL SESSIONS LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAY 17-21, 2004 CL Montreal, CANADA SP IEEE Signal Proc Soc, IEEE AB In order to construct spatial activation plots from functional magnetic resonance imaging (fMRI) data, a complex spatio-temporal modeling problem must be solved. A crucial part of this process is the estimation of the hemodynamic response (HR) function, an impulse response relating the stimulus signal to the measured noisy response. The estimation of the HR is complicated by the presence of low frequency colored noise. The standard approach to modeling the HR is to use simple parametric models, although FIR models have been used. We offer two contributions here. Firstly we pursue a nonparametric approach using orthonormal causal Laguerre polynomials which have become popular in the system identification literature It also happens that the shape of the basis elements is similar to that of a typical HR. We thus expect to achieve a compact and so bias reduced and low noise representation of the HR. Additionally we develop a procedure for providing confidence intervals for the whole HR function. This feature is completely lacking in all previous work. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Saha, S (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA PY 2004 BP 109 EP 112 PG 4 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Telecommunications SC Engineering; Imaging Science & Photographic Technology; Telecommunications GA BAH05 UT WOS:000222177700028 ER PT B AU Cascio, EW Sisterson, JM Gottschalk, B Sarkar, S AF Cascio, EW Sisterson, JM Gottschalk, B Sarkar, S GP ieee TI Measurements of the energy spectrum of degraded proton beams at NPTC SO 2004 IEEE RADIATION EFFECTS DATA WORKSHOP, WORKSHOP RECORD LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop ( REDW) held in conjunction with the IEEE Nuclear and Space Radiation Effects Conference (NSREC) CY JUL 22, 2004 CL Atlanta, GA SP IEEE Nucl & Plasma Sci Soc, IEEE AB The results of NaI scintillator measurements of the energy spectrum of degraded proton beams at the Northeast Proton Therapy Center at Massachusetts General Hospital are described. Measurements are presented for both the typical radiation test beams presently in use and for a configuration that results in a smaller energy spread at low energies. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8697-3 PY 2004 BP 151 EP 155 DI 10.1109/REDW.2004.1352922 PG 5 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BBN14 UT WOS:000226254000028 ER PT J AU Marill, KA AF Marill, KA TI Advanced statistics: Linear regression, Part I: Simple linear regression SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE regression analysis; linear models; least-squares analysis; statistics; models; statistical; epidemiologic methods AB Simple linear regression is a mathematical technique used to model the relationship between a single independent predictor variable and a single dependent outcome variable. In this, the first of a two-part series exploring concepts in linear regression analysis, the four fundamental assumptions and the mechanics of simple linear regression are reviewed. The most common technique used to derive the regression line, the method of least squares, is described. The reader will be acquainted with other important concepts in simple linear regression, including: variable transformations, dummy variables, relationship to inference testing, and leverage. Simplified clinical examples with small datasets and graphic models are used to illustrate the points. This will provide a foundation for the second article in this series: a discussion of multiple linear regression, in which there are multiple predictor variables. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin 11,Div Emergency Med, Boston, MA 02114 USA. RP Marill, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin 11,Div Emergency Med, 55 Fruit St, Boston, MA 02114 USA. EM kmarill@partners.org NR 5 TC 5 Z9 5 U1 0 U2 8 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 JAN PY 2004 VL 11 IS 1 BP 87 EP 93 DI 10.1197/S1069-6563(03)00600-6 PG 7 WC Emergency Medicine SC Emergency Medicine GA 760VQ UT WOS:000187856300015 PM 14709436 ER PT J AU Marill, KA AF Marill, KA TI Advanced statistics: Linear regression, Part II: Multiple linear regression SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE regression analysis; linear models; least-squares analysis; statistics; models; statistical; epidemiologic methods ID NONORTHOGONAL PROBLEMS; RIDGE REGRESSION; MODELS; RISK AB The applications of simple linear regression in medical research are limited, because in most situations, there are multiple relevant predictor variables. Univariate statistical techniques such as simple linear regression use a single predictor variable, and they often may be mathematically correct but clinically misleading. Multiple linear regression is a mathematical technique used to model the relationship between multiple independent predictor variables and a single dependent outcome variable. It is used in medical research to model observational data, as well as in diagnostic and therapeutic studies in which the outcome is dependent on more than one factor. Although the technique generally is limited to data that can be expressed with a linear function, it benefits from a well-developed mathematical framework that yields unique solutions and exact confidence intervals for regression coefficients. Building on Part I of this series, this article acquaints the reader with some of the important concepts in multiple regression analysis. These include multicollinearity, interaction effects, and an expansion of the discussion of inference testing, leverage, and variable transformations to multivariate models. Examples from the first article in this series are expanded on using a primarily graphic, rather than mathematical, approach. The importance of the relationships among the predictor variables and the dependence of the multivariate model coefficients on the choice of these variables are stressed. Finally, concepts in regression model building are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Med,Clin 115, Boston, MA 02114 USA. RP Marill, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Med,Clin 115, 55 Fruit St, Boston, MA 02114 USA. EM kmarill@partners.org NR 14 TC 23 Z9 25 U1 1 U2 12 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 JAN PY 2004 VL 11 IS 1 BP 94 EP 102 DI 10.1197/S1069-6563(03)00601-8 PG 9 WC Emergency Medicine SC Emergency Medicine GA 760VQ UT WOS:000187856300016 PM 14709437 ER PT J AU Gordon, JA Oriol, NE Cooper, JB AF Gordon, JA Oriol, NE Cooper, JB TI Bringing good teaching cases "to life": A simulator-based medical education service SO ACADEMIC MEDICINE LA English DT Article AB Realistic medical simulation has expanded worldwide over the last decade. Such technology is playing an increasing role in medical education not merely because simulator sessions are enjoyable, but because they can provide an enhanced environment for experiential learning and reflective thought. High-fidelity patient simulators allow students of all levels to "practice" medicine without risk, providing a natural framework for the integration of basic and clinical science in a safe environment. Often described as "flight simulation for doctors," the rationale, utility, and range of medical simulations have been described elsewhere, yet the challenges of integrating this technology into the medical school curriculum have received little attention. The authors report how Harvard Medical School established an on-campus simulator program for students in 2001, building on the work of the Center for Medical Simulation in Boston. As an overarching structure for the process, faculty and residents developed a simulator-based "medical education service"-like any other medical teaching service, but designed exclusively to help students learn on the simulator alongside a clinician-mentor, on demand. Initial evaluations among both preclinical and clinical students suggest that simulation is highly accepted and increasingly demanded. For some learners, simulation may allow complex information to be understood and retained more efficiently than can occur with traditional methods. Moreover, the process outlined here suggests that simulation can be integrated into existing curricula of almost any medical school or teaching hospital in an efficient and cost-effective manner. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. GS Beckwith Gilbert & Katharine S Gilbert Med Edu, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Anaesthesia, Boston, MA 02215 USA. Partners HealthCare Syst, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Clin 115, Boston, MA 02114 USA. EM jgordon3@partners.org NR 25 TC 67 Z9 70 U1 0 U2 6 PU ASSOC AMER MEDICAL COLLEGES PI WASHINGTON PA 2450 N ST N W, WASHINGTON, DC 20037-1126 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2004 VL 79 IS 1 BP 23 EP 27 DI 10.1097/00001888-200401000-00007 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 801BL UT WOS:000220071300005 PM 14690993 ER PT J AU Pham, HH Simonson, L Elnicki, M Fried, LP Goroll, AH Bass, EB AF Pham, HH Simonson, L Elnicki, M Fried, LP Goroll, AH Bass, EB TI Training US medical students to care for the chronically ill SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the Clerkship Directors of Internal Medicine CY 2002 CL Washington, DC ID INTERNAL-MEDICINE; CHRONIC ILLNESS; CORE CLERKSHIP; EDUCATION; HEALTH; HOME; EXPERIENCES; MANAGEMENT; ATTITUDES AB Purpose. The growing prevalence of chronic illness has important implications for the training of all physicians. The authors assessed the degree to which undergraduate medical curricula explicitly address chronic care competencies selected through literature and expert review. Method. In 2001, trained student assistants interviewed directors of required medical school courses (internal medicine, pediatrics, family practice, and ambulatory care clerkships; longitudinal care; and other relevant courses) at 16 representative U.S. medical schools sampled by geography, curriculum reform activity, and primary care orientation of graduates. Course directors were asked whether chronic care competencies were addressed using specific curricular methods (written objectives, course materials, observational evaluations, written/oral examinations, other required course activities), and to rate the importance (1 = not important; 5 = essential) of each competency for their course and for the overall undergraduate curriculum. Results. All 70 eligible course directors responded. Of 49 chronic care competencies, 29 (59%) received mean importance ratings for a course of greater than or equal to3, but only 14 (29%) were addressed using two or more specific curricular, methods. Course directors gave highest importance ratings (mean >3.9) to screening for abuse, awareness of patients' sociocultural perspectives, and protecting patients' confidentiality. They gave lowest importance ratings (mean less than or equal to2.6) to knowing strategies to maximize patients' potential, ability to discuss alternative information sources, and ability to assess equipment needs. Their importance ratings correlated only moderately with the number of curricular methods used to address each competency (r(2) = 0.27-0.80, p < .05). Conclusion. Course directors agreed about the importance of many competencies in chronic care but reported considerable variation in how they addressed competencies in their courses. Medical schools can improve training in chronic care by paying greater attention to specific methods for addressing important chronic care competencies. C1 Ctr Studying Hlth Syst Change, Washington, DC 20024 USA. Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pham, HH (reprint author), Ctr Studying Hlth Syst Change, 600 Maryland Ave SW,Suite 550, Washington, DC 20024 USA. EM mpham@hschange.org FU NHLBI NIH HHS [HL07180] NR 25 TC 29 Z9 29 U1 2 U2 2 PU ASSOC AMER MEDICAL COLLEGES PI WASHINGTON PA 2450 N ST N W, WASHINGTON, DC 20037-1126 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2004 VL 79 IS 1 BP 32 EP 41 DI 10.1097/00001888-200401000-00009 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 801BL UT WOS:000220071300007 PM 14690995 ER PT J AU Greig, NH Giordano, T Zhu, XX Yu, QS Perry, TA Holloway, HW Brossi, A Rogers, JT Sambamurti, K Lahiri, DK AF Greig, NH Giordano, T Zhu, XX Yu, QS Perry, TA Holloway, HW Brossi, A Rogers, JT Sambamurti, K Lahiri, DK TI Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases SO ACTA NEUROBIOLOGIAE EXPERIMENTALIS LA English DT Article DE thalidomide; thalidomide analogues; TNF-alpha inhibitors; Alzheimer's disease; amyloid precursor protein; amyloid-beta peptide; lipopolysacharide (LPS); peripheral blood mononuclear cells (PBMC); rheumatoid arthritis; erythema nodosum leprosum (ENL); amyotrophic lateral sclerosis (ALS); translational regulation ID AMYLOID PRECURSOR PROTEIN; NECROSIS-FACTOR-ALPHA; AU-RICH ELEMENTS; MESSENGER-RNA DEGRADATION; NF-KAPPA-B; ALZHEIMERS-DISEASE; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; HUMAN BRAIN; INTERLEUKIN-1 AB Inflammatory processes associated with the over-production of cytokines, particularly of TNF-alpha, accompany numerous neurodegenerative diseases, such as Alzheimer's disease, in addition to numerous systemic conditions, exemplified by rheumatoid arthritis and erythema nodosum leprosum (ENL). TNF-alpha has been validated as a drug target with Remicade and Enbrel available as prescription medications. Both, however, are large macromolecules, require injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of diseases. As its clinical value in treating ENL derives from its TNF-alpha inhibitory activity, thalidomide was chosen for structural modification for the discovery of novel and more potent isosteric analogues with appropriate lipophilicity to insure high brain penetration. TNF-alpha inhibitory activity was evaluated against lipopolysacharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in cell culture, whose viability was quantified to differentiate reductions in TNF-alpha secretion from that associated with cellular toxicity. Specific analogues potently inhibited TNF-alpha secretion, compared to thalidomide. This involved a post-transcriptional mechanism, as they decreased TNF-alpha rnRNA stability via its 3'-untranslated region (UTR), as determined by luciferase activity in stably transfected cells with and without the 3'-UTR of human TNF-alpha. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Prog,NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Dept Mol Biol & Biochem, Shreveport, LA 71130 USA. Univ N Carolina, Sch Pharm, Dept Chem, Chapel Hill, NC 27599 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit,Dept Neurol, Charlestown, MA 02129 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Prog,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@vax.grc.nia.nih.gov NR 63 TC 30 Z9 34 U1 0 U2 0 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1400 J9 ACTA NEUROBIOL EXP JI Acta Neurobiol. Exp. PY 2004 VL 64 IS 1 BP 1 EP 9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 805KZ UT WOS:000220366500002 PM 15190675 ER PT J AU Hoh, BL Carter, BS Ogilvy, CS AF Hoh, BL Carter, BS Ogilvy, CS TI Incidence of residual intracranial AVMs after surgical resection and efficacy of immediate surgical re-exploration SO ACTA NEUROCHIRURGICA LA English DT Article DE angiography; AVM; embolization; hemorrhage; reoperation; surgery ID CEREBRAL ARTERIOVENOUS-MALFORMATIONS; DIGITAL-SUBTRACTION-ANGIOGRAPHY; INTRAOPERATIVE ANGIOGRAPHY; POSTOPERATIVE ANGIOGRAPHY; STEREOTAXIC RADIOSURGERY; DYSPLASTIC VESSELS; MANAGEMENT; RISK; HEMORRHAGE; ANEURYSMS AB Background. The true incidence of residual lesions after surgical resection of AVMs is not well documented in the literature. Partial surgical resection is thought to not confer any improvement over the natural history risk of hemorrhage of AVMs, and in certain cases may actually increase the risk of hemorrhage. Over the past 11 years, we have adopted a policy of immediate postoperative angiography with immediate surgical re-exploration if a residual lesion is seen. The purpose of the present study was to review our experience to determine the incidence of residual lesions and subsequent outcome. Methods. From June 1991 to June 2002, 324 patients underwent craniotomy and surgical AVM resection. As per protocol, all patients underwent immediate postoperative angiography. We have a protocol for immediate surgical re-exploration if a residual lesion is seen on postoperative angiographic exam. Findings. There were total six patients (1.8% of patients operated with intracranial AVMs) with residual lesions on postoperative angiography. All six patients underwent immediate surgical re-exploration with complete 100% obliteration; two patients required two re-exploration procedures. There was one operative complication: posterior cerebral artery and superior cerebellar artery infarcts after re-exploration of residual lesion after surgical resection of a large occipito-temperal-parietal AVM. There were no other morbidities and no mortalities. Conclusions. The incidence of residual lesions seen on postoperative angiography after AVM surgery at an experienced center is 1.8%. Because of the potential imminent danger of hemorrhage from a residual lesion, we recommend a policy of immediate postoperative angiography (or intraoperative angiography if image quality is satisfactory) for all AVM surgery and early surgical re-exploration if a residual lesion is seen. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Brain Aneurysm AVM Ctr, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Brain Aneurysm AVM Ctr, VBK-710,55 Fruit St, Boston, MA 02114 USA. EM cogilvy@partners.org NR 17 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PD JAN PY 2004 VL 146 IS 1 BP 1 EP 7 DI 10.1007/s00701-003-0164-5 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 774RL UT WOS:000188998300001 PM 14740259 ER PT J AU Sachs, GS AF Sachs, GS TI Strategies for improving treatment of bipolar disorder: integration of measurement and management SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder, clinical management; assessment; treatment; clinical outcomes ID MANIC EPISODES; MOOD DISORDERS; CARE COSTS; DIAGNOSIS; SYMPTOMS AB Objective: Bipolar disorder is a common and complex condition associated with high rates of disability and high health care costs. The aim of this article is to provide an overview of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Method: The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to an NIMH request for proposals to study the effectiveness of treatments for Bipolar Disorder. Aspects of this program have been adapted and enriched for presentation in this paper. Result: Designed for implementation in routine practice across a variety of settings, STEP-BD offers a disease management program in which standardized assessments are linked to critical decision points in clinical management pathways. Conclusion: This paper describes strategies used in STEP-BD to improve the treatment of Bipolar disorder: a simple conceptual model, which integrates assessments and management, and several specialized elements, used in the STEP-BD assessment package. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. EM SachsG@aol.com NR 23 TC 30 Z9 33 U1 3 U2 6 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. PY 2004 VL 110 SU 422 BP 7 EP 17 DI 10.1111/j.1600-0447.2004.00409.x PG 11 WC Psychiatry SC Psychiatry GA 859VW UT WOS:000224297000002 ER PT J AU Bauer, M Blumentritt, H Berghofer, A Bschor, T Glenn, T Adli, M Schlattmann, P Baethge, C AF Bauer, M Blumentritt, H Berghofer, A Bschor, T Glenn, T Adli, M Schlattmann, P Baethge, C TI Long-term lithium treatment and thyroid antibodies - a study of 100 patients with affective disorders and 100 normal controls SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Med Berlin, Charite, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. Tech Univ Dresden, Carl Gustav Carus Hosp, Dept Psychiat, D-8027 Dresden, Germany. ChronoRecord Assoc Inc, Fullerton, CA USA. Inst Med Informat Epidemiol & Biometry, Charite, Berlin, Germany. Harvard Univ, McLean Div, Sch Med,Dept Psychiat, Massachusetts Gen Hosp, Belmont, MA USA. Harvard Univ, McLean Div, Sch Med,Bipolar & Psychot Disorders Program, Massachusetts Gen Hosp, Belmont, MA USA. RI Schlattmann, Peter/B-5289-2008 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 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 16 EP 16 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100029 ER PT J AU Mick, E Biederman, J Aleardi, M Dougherty, M AF Mick, E Biederman, J Aleardi, M Dougherty, M TI Open trial of atypical antipsychotics in preschoolers with bipolar disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 29 EP 29 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100072 ER PT J AU Mick, E Biederman, J Dougherty, M Aleardi, M AF Mick, E Biederman, J Dougherty, M Aleardi, M TI Comparative efficacy of atypical antipsychotics for paediatric bipolar disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 29 EP 29 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100071 ER PT S AU Schiff, I AF Schiff, I BE Daya, S Harrison, RF Kempers, RD TI Treating menopause in the 21st century - where do we go from here? SO ADVANCES IN FERTILITY AND REPRODUCTIVE MEDICINE SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 18th World Congress on Fertility and Sterility CY MAY 23-28, 2004 CL Montreal, CANADA SP Canadian Fertil & Androl Soc, Int Federat Fertils Soc DE estrogen; breast cancer; heart disease ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE-REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN/PROGESTIN REPLACEMENT; DISEASE OUTCOMES; BREAST-CANCER; HEART; PREVENTION; RALOXIFENE AB Introduction: The history of estrogen replacement therapy has changed dramatically during the past 40 years or so. At first it was thought that estrogens represented the fountain of youth but in the 1970s it was shown that unopposed estrogens could result in endometrial cancer. With the utilization of progestins, this particular risk disappeared. In the 1980s and 1990s, numerous observational trials found that estrogens could prevent chronic diseases such as heart disease, osteoporosis, colon cancer and even dementia. However, when prospective randomized trials were carried out in the late 1990s and published in the early 21st century, this potential benefit disappeared. And in fact we learned more about the risks of estrogen and breast cancer. When one identifies the major medical risks for not taking estrogen replacement therapy, it appears to be the development of osteoporosis. If a woman desires or requires treatment to prevent or treat osteoporosis there are other medications such as bisphosphonates or selective estrogen receptor modulators (SERMs) which are available and they may have a better benefit/risk profile. Treatment of symptoms such as vaginal atrophy can be carried out successfully with the use of vaginal estrogen tablets or a vaginal ring which is associated with minimal systemic absorption. As for the treatment of vasomotor flushes when estrogens are contraindicated one can consider the use of selective serotonin reuptake inhibitors (SSRIs). Complementary medicines such as phytoestrogens have had disappointing results. Although estrogens have received a lot of negative publicity, health care providers should continue to prescribe them because they do provide a lot of benefit predominantly symptomatic to patients. As long as the patients are fully aware of the risks, then it is reasonable to prescribe them for the appropriate patient. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51545-3 J9 INT CONGR SER PY 2004 VL 1266 BP 3 EP 9 DI 10.1016/j.ics.2004.02.015 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BAP70 UT WOS:000223166200001 ER PT J AU Monach, PA Benoist, C Mathis, D AF Monach, PA Benoist, C Mathis, D TI The role of antibodies in mouse models of rheumatoid arthritis, and relevance to human disease SO ADVANCES IN IMMUNOLOGY, VOL 82 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID COLLAGEN-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; ANTIGEN-INDUCED ARTHRITIS; PRISTANE-INDUCED ARTHRITIS; PROTEOGLYCAN-INDUCED ARTHRITIS; SYNOVIAL LINING CELLS; LEUKEMIA-VIRUS TYPE-1; RECEIVING CONCOMITANT METHOTREXATE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; TERMINAL COMPLEMENT COMPLEX C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Monach, PA (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. NR 175 TC 67 Z9 69 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 82 BP 217 EP 248 DI 10.1016/S0065-2776(04)82005-4 PG 32 WC Immunology SC Immunology GA BY74H UT WOS:000189452400005 PM 14975258 ER PT J AU Davis, AE Cai, SH Liu, DX AF Davis, AE Cai, SH Liu, DX TI The biological role of the C1 inhibitor in regulation of vascular permeability and modulation of inflammation SO ADVANCES IN IMMUNOLOGY, VOL 82 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID MOLECULAR-WEIGHT KININOGEN; HEREDITARY ANGIONEUROTIC-EDEMA; HUMAN HAGEMAN-FACTOR; HUMAN-ENDOTHELIAL-CELLS; MANNAN-BINDING LECTIN; FACTOR FACTOR-XII; PLASMINOGEN-ACTIVATOR RECEPTOR; PLASMA KALLIKREIN/KININ SYSTEM; DENSITY-LIPOPROTEIN-RECEPTOR; ANTIBODY IMMUNOSORBENT-ASSAY C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 188 TC 13 Z9 14 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 82 BP 331 EP 363 DI 10.1016/S0065-2776(04)82008-X PG 33 WC Immunology SC Immunology GA BY74H UT WOS:000189452400008 PM 14975261 ER PT J AU Traver, D Akashi, K AF Traver, D Akashi, K TI Lineage commitment and developmental plasticity in early lymphoid progenitor subsets SO ADVANCES IN IMMUNOLOGY, VOL 83 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; GREEN FLUORESCENT PROTEIN; RECEPTOR-GAMMA CHAIN; MURINE FETAL LIVER; PLASMACYTOID DENDRITIC CELLS/; TRANSCRIPTION FACTOR GATA-1; COMMON MYELOID PROGENITOR; NECROSIS-FACTOR-ALPHA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Traver, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 257 TC 12 Z9 12 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 83 BP 1 EP 54 PG 54 WC Immunology SC Immunology GA BAK35 UT WOS:000222633600001 PM 15135627 ER PT J AU Von Boehmer, H AF Von Boehmer, H TI Selection of the T-cell repertoire: Receptor-controlled checkpoints in T-cell development SO ADVANCES IN IMMUNOLOGY, VOL 84 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID DETERMINE IMMUNE RESPONSIVENESS; PROMISCUOUS GENE-EXPRESSION; COMMON LYMPHOID PROGENITORS; DIFFERENTIAL AVIDITY MODEL; HEMATOPOIETIC STEM-CELLS; THYMIC EPITHELIAL-CELLS; BONE-MARROW CHIMERAS; TCR ALPHA-CHAIN; NF-KAPPA-B; POSITIVE SELECTION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 211 TC 90 Z9 93 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 84 BP 201 EP 238 DI 10.1016/S0065-2776(04)84006-9 PG 38 WC Immunology SC Immunology GA BAU07 UT WOS:000223554500006 PM 15246254 ER PT J AU Hinkin, CH Hardy, DJ Mason, KI Castellon, SA Durvasula, RS Lam, MN Stefaniak, M AF Hinkin, CH Hardy, DJ Mason, KI Castellon, SA Durvasula, RS Lam, MN Stefaniak, M TI Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse SO AIDS LA English DT Article; Proceedings Paper CT Workshop on Mental Health Research Issues in HIV Infection and Aging CY APR, 2002 CL WASHINGTON, DC SP Natl Inst Mental Hlth DE aging; alcohol abuse; drug abuse; electronic monitoring; medication adherence; neuropsychology ID SELF-REPORTED ADHERENCE; ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; PROTEASE INHIBITORS; AIDS; OLDER; PERFORMANCE; DYSFUNCTION; PREDICTORS; OUTCOMES AB Objective: To examine the predictors of antiretroviral adherence among HIV-infected adults, with a particular focus on advancing age, neuropsychological dysfunction, and substance abuse. Design: Prospective observational design. Methods: Participants were 148 HIV-infected adults between the ages of 25 and 69 years, all on a self-administered antiretroviral regimen. Medication adherence was tracked over a one-month period using an electronic monitoring device (medication event monitoring system caps). All participants completed a comprehensive battery of neuropsychological tests as well as a structured psychiatric interview. Results: The mean adherence rate for the entire cohort was 80.7%, with older patients (greater than or equal to50 years) demonstrating significantly better medication adherence than younger patients (87.5 versus 78.3%). Logistic regression analyses found that older patients were three times more likely to be classified as good adherers (defined as greater than or equal to95% adherent). Neurocognitive impairment conferred a 2.5 times greater risk of poor adherence. Among the older patients, those who were classified as poor adherers performed significantly worse on neuropsychological testing, particularly on measures of executive function and psychomotor speed. Current drug abuse/dependence, but not current alcohol abuse/dependence, was also associated with sub-optimal medication adherence. Conclusion: Although older age is associated with higher rates of antiretroviral adherence, older participants who were cognitively impaired showed disproportionate difficulty in adequately adhering to their medication regimen. As such, efforts to detect neuropsychological dysfunction, particularly among older patients, and a thorough assessment of substance abuse, appear to be essential for the effective treatment of HIV-infected adults. (C) 2004 Lippincott Williams Wilkins. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Psychol Serv, Los Angeles, CA USA. Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. EM chinkin@ucla.edu FU NIMH NIH HHS [R01 MH058552, R01 MH058552-02, R01 MH58552, T32 MH019535] NR 37 TC 263 Z9 269 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN PY 2004 VL 18 SU 1 BP S19 EP S25 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 805OL UT WOS:000220375500004 PM 15075494 ER PT J AU Justice, AC McGinnis, KA Atkinson, JH Heaton, RK Young, C Sadek, J Madenwald, T Becker, JT Conigliaro, J Brown, ST Rimland, D Crystal, S Simberkoff, M AF Justice, AC McGinnis, KA Atkinson, JH Heaton, RK Young, C Sadek, J Madenwald, T Becker, JT Conigliaro, J Brown, ST Rimland, D Crystal, S Simberkoff, M CA VACS 5 Project Team TI Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study SO AIDS LA English DT Article; Proceedings Paper CT Workshop on Mental Health Research Issues in HIV Infection and Aging CY APR, 2002 CL WASHINGTON, DC SP Natl Inst Mental Hlth DE HIV; cognitive function; depression; substance abuse; symptoms ID DEMOGRAPHICALLY CORRECTED NORMS; VERBAL-LEARNING-TEST; DIAGNOSTIC INTERVIEW; AIDS; AGE; EPIDEMIOLOGY; DEPRESSION; INFECTION; VALIDITY; DEMENTIA AB Background: The risk for psychiatric and neurocognitive disorders among middle-aged and older individuals with HIV infection has not been well characterized. Methods: The Veterans Aging Cohort 5-Site Study enrolled 1803 patients (1047 HIV-positive) from VA infectious disease and general medicine clinics from September 2001 to June 2002. A convenience subset of 10 patients from each site (n=50) was consented for formal neurocognitive and psychiatric (NCP) testing. Data from this subset were linked to the larger sample. Results: Kappa scores for agreement beyond chance were fair for available measures when compared with formal NCP testing. Using available measures, depressive symptoms (PHQ-9 and provider reported), alcohol abuse or dependence (ICD-9 codes), and drug abuse or dependence (DAST-10) decreased with age in HIV-negative subjects (P trend <0.05) but did not among HIV-positive subjects (P>0.05). HIV-positive subjects demonstrated higher prevalence of these conditions with increasing age when compared to HIV-negative subjects. Patient report of memory problems increased with age among both groups after excluding those reporting symptoms of depression (PHQ-9egreater than or equal to10). Conclusion: Available measures were no substitute for formal NCP testing. Older HIV-positive veterans demonstrate greater prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence than age-matched, HIV-negative veterans. Both groups reported increased memory problems with advancing age. This preliminary work suggests a substantial prevalence of psychiatric and neurocognitive problems among middle-aged and older HIV-infected individuals. (C) 2004 Lippincott Williams Wilkins. C1 VA Pittsburgh Healthcare Syst, Vet Aging Cohort Ctr, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, HIB Neurobehav Res Ctr, San Diego, CA 92103 USA. Univ Pittsburgh, Western Psychiat Inst, Pittsburgh, PA USA. CUNY Mt Sinai Sch Med, Bromx VA Med Ctr, New York, NY 10029 USA. VA Med Program, HIV Program, Atlanta, GA USA. Rutgers State Univ, Div Aging, New Brunswick, NJ 08903 USA. VA New Harbor Helathcare Syst, New York, NY USA. RP Justice, AC (reprint author), W Haven VA Healthcare Syst, 950 Campbell Ave,11-ACSLG, W Haven, CT 06516 USA. EM amy.justice2@med.va.gov FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [3U01 AA 13566]; NIMH NIH HHS [5P30 MH062512, MH01011] NR 35 TC 73 Z9 74 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 JAN PY 2004 VL 18 SU 1 BP S49 EP S59 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 805OL UT WOS:000220375500008 PM 15075498 ER PT J AU Brief, DJ Bollinger, AR Vielhauer, MJ Berger-Greenstein, JA Morgan, EE Brady, SM Buondonno, LM Keane, TM AF Brief, DJ Bollinger, AR Vielhauer, MJ Berger-Greenstein, JA Morgan, EE Brady, SM Buondonno, LM Keane, TM CA HIVAIDS Treatment Adherence Hlth O TI Understanding the interface of HIV, trauma, post-traumatic stress disorder, and substance use and its implications for health outcomes SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHILDHOOD SEXUAL-ABUSE; INJECTION-DRUG USERS; COGNITIVE-BEHAVIORAL TREATMENT; ANTIRETROVIRAL THERAPY; ALCOHOL-CONSUMPTION; RISK BEHAVIORS; INFECTED PATIENTS; ASSAULT VICTIMS; MENTAL-HEALTH AB Many individuals living with HIV have been exposed to some type of traumatic event during their lives and may be living with symptoms of post-traumatic stress disorder (PTSD). A substantial number of these individuals are also likely to show evidence of a co-morbid substance use disorder (SUD). There is reason to believe that the co-occurrence of HIV and PTSD or co-morbid PTSD and SUD (PTSD/SUD) may predict poorer health outcomes. There are several pathways through which PTSD or PTSD/SUD might adversely impact the health of individuals living with HIV, including participation in negative health behaviours, low levels of adherence to antiretroviral medications, and/or a direct, deleterious effect on immune function. Psychological interventions are needed to treat PTSD and PTSD/SUD in HIV-positive individuals, and reduce the negative impact of these conditions on health outcomes. This article will explore data on the prevalence of trauma exposure, PTSD, and PTSD/SUD among individuals living with HIV, the pathways through which these conditions might affect health, possible interventions for PTSD and PTSD/SUD for individuals living with HIV, and methods for integrating care for individuals with these disorders. Future directions for research related to HIV, PTSD, and PTSD/SUD will also be discussed. C1 VA Boston Healthcare Syst, Psychol 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. RP Brief, DJ (reprint author), VA Boston Healthcare Syst, Psychol 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM deborah.brief@med.va.gov NR 154 TC 42 Z9 42 U1 5 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2004 VL 16 SU 1 BP S97 EP S120 DI 10.1080/09540120412301315259 PG 24 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 879QR UT WOS:000225732800007 PM 15736824 ER PT J AU Cayabyab, M Rohne, D Pollakis, G Mische, C Messele, T Abebe, A Etemad-Moghadam, B Yang, P Henson, S Axthelm, M Goudsmit, J Letvin, NL Sodroski, J AF Cayabyab, M Rohne, D Pollakis, G Mische, C Messele, T Abebe, A Etemad-Moghadam, B Yang, P Henson, S Axthelm, M Goudsmit, J Letvin, NL Sodroski, J TI Rapid CD4(+) T-lymphocyte depletion in rhesus monkeys infected with a simian-human immunodeficiency virus expressing the envelope glycoproteins of a primary dual-tropic Ethiopian clade C HIV type 1 isolate SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CHEMOKINE CORECEPTOR USAGE; PROTEIN-COUPLED RECEPTOR; BRAIN-DERIVED CELLS; PIG-TAILED MACAQUES; SUBTYPE-E ENVELOPE; DISEASE PROGRESSION; PERSISTENT INFECTION; BIOLOGICAL PHENOTYPE; MACROPHAGE TROPISM; GENETIC SUBTYPES AB Simian - human immunodeficiency virus (SHIV) chimerae with the envelope glycoproteins of X4 or R5/X4 HIV-1 isolates from clade B can cause rapid and severe CD4(+) T cell depletion and AIDS-like illness in infected monkeys. We created a SHIV (SHIV-MCGP1.3) expressing the envelope glycoproteins of a primary R5/X4, clade C HIV-1 isolate. Infection of a rhesus monkey with SHIV-MCGP1.3 resulted in a low level of viremia and no significant alteration in CD4(+) T- lymphocyte counts. However, serial intravenous passage of the virus resulted in the emergence of SHIV-MCGP1.3 variants that replicated efficiently and caused profound CD4(+) T cell depletion during the acute phase of infection. The CD4(+) T cell counts in the infected monkeys gradually returned to normal, and the animals remained healthy. The ability to cause rapid and profound loss of CD4(+) T lymphocytes in vivo is a property shared by passaged, CXCR4-using SHIVs, irrespective of the clade of origin of the HIV-1 envelope glycoproteins. C1 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. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02215 USA. Univ Amsterdam, Acad Med Ctr, Fac Med, Dept Human Retrovirol, NL-1105 AZ Amsterdam, Netherlands. Ethiopian Hlth & Nutr Res Inst, Addis Ababa, Ethiopia. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Acad Med Ctr Amsterdam, Ctr Poverty Related Communicable Dis, Leiden, Netherlands. Acad Med Ctr Crucell, Ctr Poverty Related Communicable Dis, Leiden, Netherlands. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI33832, AI42848] NR 91 TC 18 Z9 19 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2004 VL 20 IS 1 BP 27 EP 40 DI 10.1089/088922204322749477 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 772VD UT WOS:000188861700004 PM 15000696 ER PT J AU Schneider, A Barmada, MM Slivka, A Martin, JA Whitcomb, DC AF Schneider, A Barmada, MM Slivka, A Martin, JA Whitcomb, DC TI Analysis of tumor necrosis factor-alpha, transforming growth factor-beta(1), interleukin-10, and interferon-gamma polymorphisms in patients with alcoholic chronic pancreatitis SO ALCOHOL LA English DT Article DE alcohol; chronic pancreatitis; cytokines; polymorphisms ID IDIOPATHIC CHRONIC-PANCREATITIS; GROWTH-FACTOR-BETA-1 GENE; STELLATE CELLS; TNF-ALPHA; PROMOTER REGION; FIBROSIS; IDENTIFICATION; ASSOCIATION; EXPRESSION; MUTATIONS AB The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at positions -308 and -238; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1082; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with alcoholic chronic pancreatitis. We investigated 42 patients with alcoholic chronic pancreatitis. We studied 94 control subjects for the TNF-alpha polymorphisms and 73 control subjects for the remaining polymorphisms. Mutation analysis was performed by direct DNA sequencing or by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype frequencies were similar between patients and control subjects for all investigated cytokine polymorphisms (P > .05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Genom Sci, Pittsburgh, PA 15213 USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. EM whitcomb@pitt.edu OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 45 TC 30 Z9 32 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JAN PY 2004 VL 32 IS 1 BP 19 EP 24 DI 10.1016/j.alcohol.2003.09.006 PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 814DO UT WOS:000220955600002 PM 15066699 ER PT J AU Bearer, CF Stoler, JM Cook, JD Carpenter, SJ AF Bearer, CF Stoler, JM Cook, JD Carpenter, SJ TI Biomarkers of alcohol use in pregnancy SO ALCOHOL RESEARCH & HEALTH LA English DT Article ID HEMOGLOBIN-ACETALDEHYDE ADDUCTS; ACID ETHYL-ESTERS; ETHANOL EXPOSURE; RISK-DRINKING; WOMEN; RECOGNITION; MECONIUM; INFANTS; MARKERS C1 Case Western Reserve Univ, Univ Hosp Cleveland, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Neurosci, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Maryland, Sch Med, Dept Med & Res Technol, Baltimore, MD 21201 USA. RP Bearer, CF (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. FU NIAAA NIH HHS [R01-AA-11839]; NIEHS NIH HHS [P01-ES-11261]; PHS HHS [MM-0122-02/02] NR 27 TC 9 Z9 9 U1 0 U2 2 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2004 VL 28 IS 1 BP 38 EP 43 PG 6 WC Substance Abuse SC Substance Abuse GA 988MY UT WOS:000233606500005 PM 19006990 ER PT S AU Nagler-Anderson, C Walker, WA AF Nagler-Anderson, C Walker, WA BE Isolauri, E Walker, WA TI Mechanisms governing non-responsiveness to food proteins SO Allergic Diseases and the Environment SE NESTLE NUTRITION WORKSHOP SERIES PEDIATRIC PROGRAM LA English DT Proceedings Paper CT 53rd Nestle Pediatric Nutrition Workshop CY APR 06-10, 2003 CL Lausanne, SWITZERLAND C1 Massachusetts Gen Hosp, Charlestown, MA USA. RP Nagler-Anderson, C (reprint author), Massachusetts Gen Hosp, Charlestown, MA USA. NR 48 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0742-2806 BN 3-8055-7649-8 J9 NESTLE NUTR WORKS SE PY 2004 VL 53 BP 117 EP 132 PG 16 WC Allergy; Immunology; Nutrition & Dietetics; Pediatrics SC Allergy; Immunology; Nutrition & Dietetics; Pediatrics GA BDC00 UT WOS:000232488700007 ER PT J AU Snow, AL Norris, MP Doody, R Molinari, VA Orengo, CA Kunik, ME AF Snow, AL Norris, MP Doody, R Molinari, VA Orengo, CA Kunik, ME TI Dementia deficits scale rating self-awareness of deficits SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; deficit awareness; insight ID GERIATRIC DEPRESSION SCALE; ALZHEIMERS-DISEASE; COGNITIVE DEFICITS; CAREGIVER BURDEN; IMPAIRED INSIGHT; MEMORY DEFICIT; ANOSOGNOSIA; UNAWARENESS; PERFORMANCE; BEHAVIOR AB Impaired deficit awareness is important to detect because of its clinical implications; for example, patients with impaired awareness are more likely to engage in potentially dangerous activities, such as operating the stove. This study evaluated the reliability and validity of the Dementia Deficits Scale (DDS), a new multidimensional instrument for the assessment of self-awareness of cognitive, emotional, and functional deficits associated with dementia. Three parallel forms of the DDS were independently completed by the patient, clinician, and informant. The DDS yields two measures of deficit awareness: the discrepancy between clinician and patient assessments of the patient's deficits, and the discrepancy between informant and patient assessments. The DDS demonstrated adequate reliability and good divergent and convergent validity. Clinician and informant reports each added unique information, highlighting the importance of including both perspectives in the awareness assessment process. The DDS is recommended as a reliable and valid tool for the clinical and empirical assessment of deficit awareness in patients with dementia. C1 Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Houston VA Med Ctr, Mental Hlth Serv Line, Houston, TX 77030 USA. Houston VA Med Ctr, Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Baylor Alzheimers Dis Ctr, Houston, TX 77030 USA. Univ S Florida, Dept Aging & Mental Hlth, Tampa, FL 33620 USA. RP Snow, AL (reprint author), Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM asnow@bcm.tme.edu FU NIA NIH HHS [AGO 8664, P50-AG00149] NR 39 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2004 VL 18 IS 1 BP 22 EP 31 DI 10.1097/00002093-200401000-00005 PG 10 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 801PK UT WOS:000220107600005 PM 15198084 ER PT J AU Co, JPT AF Co, JPT TI Assessing resident performance: Commentary on latent class analysis SO AMBULATORY PEDIATRICS LA English DT Editorial Material ID OTITIS-MEDIA; COMPETENCES; EDUCATION C1 Harvard Univ, Ctr Child & Adolescent Hlth Policy, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Co, JPT (reprint author), Harvard Univ, Ctr Child & Adolescent Hlth Policy, Sch Med, Massachusetts Gen Hosp, 50 Staniford St,901, Boston, MA 02114 USA. EM jco@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JAN-FEB PY 2004 VL 4 IS 1 BP 11 EP 12 DI 10.1367/1539-4409(2004)004<0011:ARPCOL>2.0.CO;2 PG 2 WC Pediatrics SC Pediatrics GA 766RR UT WOS:000188389800004 PM 14731099 ER PT J AU Raitt, MH Kusumoto, W Giraud, GD McAnulty, JH AF Raitt, MH Kusumoto, W Giraud, GD McAnulty, JH TI Electrophysiologic predictors of the recurrence of persistent atrial fibrillation within 30 days of cardioversion SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AVERAGED P-WAVE; DURATION; RISK AB Patients with recurrence of persistent atrial fibrillation within 30 days. of cardioversion had slower atrial conduction, a slower sinus rate, no difference in the absolute value of the effective refractory period, greater early reverse remodeling of the effective refractory period, and more premature atrial contractions than those who did not. These findings highlight the role of slow conduction and premature atrial contractions in the pathophysiology of atrial fibrillation and suggest a possible proarrhythmic effect of reverse remodeling. (C) 2003 by Excerpta Medica, Inc. C1 Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Kaiser Permanente, Denver, CO USA. RP Raitt, MH (reprint author), P-3 CARD,3710 SW US Vet Rd, Portland, OR 97239 USA. OI Raitt, Merritt/0000-0001-5638-7732 NR 15 TC 27 Z9 27 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2004 VL 93 IS 1 BP 107 EP 110 DI 10.1016/j.amjcard.2003.08.079 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 760GT UT WOS:000187803800026 PM 14697481 ER PT J AU Sesso, HD Buring, JE Norkus, EP Gaziano, JM AF Sesso, HD Buring, JE Norkus, EP Gaziano, JM TI Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE lycopene; cardiovascular disease; women; prospective studies; nutrition ID CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; BETA-CAROTENE; MYOCARDIAL-INFARCTION; SERUM CAROTENOIDS; ENZYMATIC DETERMINATION; ALPHA-TOCOPHEROL; PROSTATE-CANCER; ADIPOSE-TISSUE; ATHEROSCLEROSIS AB Background: Growing evidence suggests that lycopene has significant in vitro antioxidant potential. Lycopene has rarely been tested in prospective studies for its role in cardiovascular disease (CVD) prevention. Objective: We examined the association between plasma lycopene and the risk of CVD, in middle-aged and elderly women. Design: A prospective, nested, case-control study was conducted in 39 876 women initially free of CVD and cancer in the Women's Health Study. Baseline blood samples were collected from 28 345 (71%) of the women. During a mean of 4.8 y of follow-up, we identified 483 CVD cases and 483 control subjects matched by age, smoking status, and follow-up time. Plasma lycopene, other carotenoids, retinol, and total cholesterol were measured. Results: In analyses matched for age and smoking, with adjustment for plasma cholesterol, the relative risks (RRs) and 95% CIs of CVD in increasing quartiles of plasma lycopene were 1.00 (referent), 0.78 (95% CI: 0.55, 1.11), 0.56 (0.39, 0.82), and 0.62 (0.43, 0.90). In multivariate models, the RRs were 1.00 (referent), 0.94 (0.60, 1.49), 0.62 (0.39, 1.00), and 0.67 (0.41, 1.11); those in the upper compared with the lower half of plasma lycopene had an RR of 0.66 (0.47, 0.95). For CVD, exclusive of angina, women in the upper 3 quartiles had a significant multivariate 50% risk reduction compared with those in the lowest quartile. The stepwise addition of individual plasma carotenoids did not affect the RRs. Conclusions: Higher plasma lycopene concentrations are associated with a lower risk of CVD in women. These findings require confirmation in other cohorts, and the determinants of plasma lycopene concentrations need to be better understood. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Our Lady Mercy Med Ctr, Dept Med Res, Bronx, NY USA. New York Med Coll, Bronx, NY USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-43851] NR 45 TC 115 Z9 133 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2004 VL 79 IS 1 BP 47 EP 53 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 757NZ UT WOS:000187569500008 PM 14684396 ER PT J AU Smith, EY Charles, LA Van Cott, EM AF Smith, EY Charles, LA Van Cott, EM TI Biphasic activated partial thromboplastin time waveform and adverse events in non-intensive care unit patients SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE biphasic aPTT waveform; DIC; disseminated intravascular coagulation; activated partial thromboplastin time; aPTT ID DISSEMINATED INTRAVASCULAR COAGULATION; C-REACTIVE PROTEIN; EARLY IDENTIFICATION; LIPOPROTEIN AB The purpose of the present study was to determine whether the presence of a biphasic activated partial thromboplastin time (aPTT) waveform (BPW) is associated with adverse clinical outcomes among patients not in an intensive care unit (ICU). Consecutive patients from the emergency department or non-ICU inpatient floors with a BPW (n = 24) were enrolled prospectively, along with 24 matched control subjects with a normal aPTT waveform. Patients with a BPW had a significantly longer hospital stay (mean [median], 16.9 [11] vs 4.9 [2.5] days; P =. 011), were more likely to have a positive microbial culture (16/24 [67%] vs 3/24 [13%]; P < .001), were transferred more often to an ICU (6/24 [25%] vs 0/24 [0%]; P = .010), and were more likely to receive an RBC transfusion (11/24 [46%] vs 5/24 [21%]; P = .047) or a fresh frozen plasma transfusion (5/24 [21%] vs 0124 [0%]; P = .025). Emergency department patients with a BPW were more likely to be admitted (11/11/ vs 5/11; P = .018). These results suggest that the BPW is associated with an increased rate of adverse events among non-ICU patients. Further study in this population is warranted. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Coagulat Lab, Boston, MA 02114 USA. Charles Biopharm Associates, Durham, NC USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Coagulat Lab, Jackson 235,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2004 VL 121 IS 1 BP 138 EP 141 DI 10.1309/W4F7892WJE6Y1W7Y PG 4 WC Pathology SC Pathology GA 761XF UT WOS:000187940200018 PM 14750251 ER PT J AU Harris, DS Batki, SL Berger, SP AF Harris, DS Batki, SL Berger, SP TI Fluoxetine attenuates adrenocortical but not subjective responses to cocaine cues SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE cocaine; cues; craving; fluoxetine; cortisol; adrenocortical ID CORTICOTROPIN-RELEASING-FACTOR; INDUCED REINSTATEMENT; SEEKING BEHAVIOR; RATS; SEROTONIN; CORTICOSTERONE; RELAPSE; STRESS; DRUG; ANTIDEPRESSANT AB Preclinical data suggest a link between stress reactivity and cocaine self-administration by rodents. Serotonin appears to modulate the hypothalamic-pituitary -adrenal (HPA) axis. We studied the effects of chronic treatment with the scrotonin reuptake inhibitor fluoxetine 40 mg/day on subjective and hormonal responses to cocaine cues in 22 subjects participating in a controlled clinical trial for cocaine dependence. Fluoxetine antagonized the cue-induced increase in cortisol but increased subjects' ratings of the likelihood of cocaine use in response to cocaine cues. Cortisol response to cocaine cues was not related to subjective craving. Activation of the HPA axis by cocaine cues does not appear to be a necessary mediator of cue-induced craving. C1 Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45220 USA. Vet Adm Med Ctr, Cincinnati, OH 45220 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Syracuse VA Med Ctr, Syracuse, NY USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Psychiat, Portland, OR 97201 USA. RP Harris, DS (reprint author), Univ Cincinnati, Dept Psychiat, 3200 Vine St, Cincinnati, OH 45220 USA. EM debra.harris4@med.va.gov FU NCRR NIH HHS [5-M01-RR00083]; NIDA NIH HHS [P50-DA09253] NR 42 TC 7 Z9 7 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2004 VL 30 IS 4 BP 765 EP 782 DI 10.1081/ADA-200037542 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 877LQ UT WOS:000225572500004 PM 15624548 ER PT J AU Lai, L Brugge, WR AF Lai, L Brugge, WR TI Endoscopic ultra sound is a sensitive and specific test to diagnose portal venous system thrombosis (PVST) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VEIN-THROMBOSIS; COLOR DOPPLER; LIVER-TRANSPLANTATION; ULTRASONOGRAPHY; RISK; INVASION; ADULTS; EUS AB OBJECTIVES: Thrombosis of the portal venous system (PVS) may complicate cirrhosis, pancreatitis, malignancies, and hypercoagulable states. Computed tomography (CT) scanning can diagnose thrombi present in the lumen of the PVS, but is probably insensitive. Endoscopic ultrasound (EUS) may be a more sensitive test for diagnosing PVS thrombosis (PVST). We sought to determine the accuracy of EUS for the diagnosis of PVST. METHODS: Using a retrospective analysis of patients' studies retrieved from a database at Massachusetts General Hospital, we determined the sensitivity and specificity of EUS in 16 patients with PVST and 29 without PVST as proven by surgery and/or CT scanning. All patients underwent a linear EUS exam of the PVS and the results of the EUS report were used as the basis of the study. RESULTS: The sensitivity of EUS for the finding of PVST was 81% in 13 of 16 patients and the specificity was 93% in 27 of 29 patients with an overall accuracy of 89% (40/45). In an additional group of 11 patients, EUS demonstrated the presence of a PVST that was not detected by CT scanning. CONCLUSION: Linear EUS is a highly sensitive and specific test for PVST. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. NR 18 TC 25 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2004 VL 99 IS 1 BP 40 EP 44 DI 10.1046/j.1572-0241.2003.04020.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 763AV UT WOS:000188047200010 PM 14687139 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Decision analysis in clinical gastroenterology SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID COST-EFFECTIVENESS; MANAGEMENT; DISEASE; STRATEGY; DILATION; THERAPY AB OBJECTIVES: Although the tools of medical decision analysis have been mostly used to address complex issues of healthcare and management policies, an important role remains for decision analysis to play in solving mundane medical problems of daily practice. The present article alms to restate the origins of decision analysis and to demonstrate the utility of decision models in clinical gastroenterology. METHODS: Three clinical scenarios are presented to illustrate the applicability of decision analysis in clinical gastroenterology. The examples are modeled as simple decision trees and phrased in terms of threshold analysis. RESULTS: In spite of its striking simplicity, the framework of threshold analysis is able to capture a large variety of heterogeneous and often perplexing medical problems. Rather than calculate a cost-effectiveness or cost-benefit ratio, the result of the analysis is expressed as a probability value, which forms the threshold between the two choices against or in favor of a particular medical action. For most analyses little if any calculation is needed to solve the decision tree, and the final outcome of the analysis can be derived based on comparative estimates and considerations of magnitude only. CONCLUSIONS: The study demonstrates that threshold analysis can serve as a simple and convenient instrument to solve a large variety of problems in clinical gastroenterology. C1 Portland VA Med Ctr P3 G1, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 G1, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 18 TC 12 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2004 VL 99 IS 1 BP 163 EP 169 DI 10.1046/j.1572-0241.2003.04011.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 763AV UT WOS:000188047200030 PM 14687159 ER PT J AU Johnson, RA Teran, FJ Durante, W Peyton, KJ Johnson, FK AF Johnson, RA Teran, FJ Durante, W Peyton, KJ Johnson, FK TI Enhanced heme oxygenase-mediated coronary vasodilation in Dahl salt-sensitive hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE heme oxygenase; heart; coronary vessels; hypertension; Dahl rats ID CARBON-MONOXIDE; NITRIC-OXIDE; RAT-HEART; ANGIOTENSIN-II; EXPRESSION; INHIBITOR; REPERFUSION; RELAXATION; INDUCTION; MECHANISM AB Background: Cardiovascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Carbon monoxide promotes relaxation of coronary vascular smooth muscle. Increased HO-I expression provides cardioprotection during certain pathologic conditions. On a high salt (HS) diet Dahl salt-sensitive (DS) rats develop hypertension that is accompanied by left ventricular hypertrophy, whereas Dahl salt-resistant rats (DR) do not. This study tests the hypothesis that cardiac HO-1 expression is increased in DS rats with salt-induced hypertension and provides cardioprotection by promoting coronary vasodilation. Methods: Male DS and DR rats were placed on a HS (8% NaCl) or low salt (LS, 0.3% NaCl) diet for 4 weeks. Cardiac HO isoform expression were determined by immunohistochemistry. Experiments used isolated paced Langendorff-hearts perfused at a constant flow. Changes in coronary perfusion pressure and left ventricular contractility (dP/dt(max)) were measured in response to an inhibitor of HO, chromium mesoporphyrin (CrMP). Results: With respect to the LS group, DS rats on HS diet showed elevated mean arterial pressure and increased heart weight. Coronary arterial HO-1 immunostaining was enhanced in HS rats, but HO-2 staining was similar in both groups. In isolated Langendorff-hearts the HO inhibitor CrMP increased coronary perfusion pressure and calculated coronary resistance, and decreased left ventricular contractility (dP/dt(max)) in both groups, but the response was exaggerated in HS rat hearts. In the DR strain, HS diet did not augment CrMP responses and had no effect on any of the parameters measured with respect to the LS diet. Conclusions: These findings suggest that coronary HO-1 expression is increased to promote enhanced coronary vasodilation in DS rats with salt-induced hypertension. (C) 2004 American Journal of Hypertension, Ltd. C1 Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Johnson, RA (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Physiol, 1430 Tulane Ave,SL39, New Orleans, LA 70112 USA. FU NCRR NIH HHS [P20 RR017659]; NHLBI NIH HHS [R01 HL59976, R01 HL64577] NR 25 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2004 VL 17 IS 1 BP 25 EP 30 DI 10.1016/j.amjhyper.2003.08.009 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 760GQ UT WOS:000187803600005 PM 14700508 ER PT J AU Singh, H Kalavar, J AF Singh, H Kalavar, J TI Quality of care for hypertension and diabetes in federal- versus commercial-managed care organizations SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE health care quality; HEDIS measures; primary care; veterans affairs ID ACUTE MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; UNITED-STATES; VETERANS; MEDICARE; DISEASE; SYSTEM; TRIAL; MEN; VA AB Initiatives to improve quality in primary care include use of performance measures to benchmark health care organizations. We looked for an objective way to compare primary care quality in the Veterans Affairs (VA) with that of private sector. We analyzed performance measures of the Health Plan and Employer Data Information Set (HEDIS) used in ambulatory care for hypertension and diabetes and compared a sample data from a network of VA hospitals with those from National Committee for Quality Assurance's The State of Health Care Quality 2002 Report. The VA data were comparable to the national data. Performance on the hypertension control measure was slightly below the HEDIS national average but better than the regional commercial average. VA's performance on all diabetes measures was higher. Although the VA network had a large influx in patient base recently, the quality of outpatient care in hypertension and diabetes as measured by standardized performance indicators in the network compared favorably with commercial Health Maintenance Organizations in the private sector. C1 VA Med Ctr, Sect Primary Care, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Singh, H (reprint author), VA Med Ctr, Sect Primary Care, 111PC,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu NR 22 TC 9 Z9 9 U1 0 U2 0 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2004 VL 19 IS 1 BP 19 EP 24 DI 10.1177/106286060401900104 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 767JW UT WOS:000188437300003 PM 14977021 ER PT J AU Diamond, LH Kliger, AS Goldman, RS Palevsky, PM AF Diamond, LH Kliger, AS Goldman, RS Palevsky, PM TI Commentary: Quality improvement projects: How do we protect patients' rights? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Editorial Material DE accountability; clinical practice; clinical research; informed consent; quality improvement AB A recent ruling by the Office of Human Research Protection (OHRP) has renewed an ongoing debate over whether Institutional Review Boards (IRBs) should have oversight not only over clinical research but also over quality improvement projects (QIPs). The authors discussed the similarities and differences among clinical practice, QIPs, and clinical research, pointing out issues to consider when identifying the most appropriate method for QIP oversight and accountability. They note that potential solutions must address ethical issues (eg, patient safety, privacy, and self-determination) and weigh the effect of the underlying QIP goal (administrative versus clinical improvement) on an individual patient and patient populations. They conclude that because QIPs are an extension of clinical practice and have elements of clinical research, it too should have an oversight system. Institutional or regional quality improvement boards, operating parallel to current IRBs, are suggested as 1 means of ensuring that QIP participants are offered the same protections as those who take part in clinical research. C1 Medstat, Washington, DC 20008 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Hosp St Raphael, Dept Med, New Haven, CT USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Diamond, LH (reprint author), Medstat, 4301 Connecticut Ave,NW,Suite 330, Washington, DC 20008 USA. EM louis.diamond@medstat.com OI Palevsky, Paul/0000-0002-7334-5400 NR 2 TC 7 Z9 7 U1 0 U2 0 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2004 VL 19 IS 1 BP 25 EP 27 DI 10.1177/106286060401900105 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 767JW UT WOS:000188437300004 PM 14977022 ER PT J AU Frayne, SM Freund, KM Skinner, KM Ash, AS Moskowitz, MA AF Frayne, SM Freund, KM Skinner, KM Ash, AS Moskowitz, MA TI Depression management in medical clinics: Does healthcare sector make a difference? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Gen Internal Med DE depression; models, organizational; physician's practice patterns; primary health care; quality assurance, health care; veterans ID LATE-LIFE DEPRESSION; OF-VETERANS-AFFAIRS; MENTAL-HEALTH; MYOCARDIAL-INFARCTION; FINANCIAL INCENTIVES; COMPETING DEMANDS; DECISION-MAKING; UNITED-STATES; PHYSICIANS; SERVICES AB Medical providers often fail to treat depression. We examined whether treatment is more aggressive in a setting with accessible mental health resources, the Veterans Health Administration (VA). VA and non-VA primary care physicians and medical specialists viewed a videotape vignette portraying a patient meeting criteria for major depression and then answered interviewer-administered questions about management. We found that 24% of VA versus 15% of non-VA physicians would initiate guideline-recommended treatment (antidepressants or mental health referral, or both) (P = .09). Among those who identified depression as likely, 42% of VA versus 19% of non-VA physicians would treat (P = .002): 23% versus 3% recommended mental health referral (P < .001) and 21% versus 17% an antidepressant (P = .67). Although many patients with major depression may not receive guideline-recommended management, VA physicians do initiate mental health referral more often than do non-VA physicians. Access to mental health services may prove valuable in the campaign to increase physician adherence to depression clinical guidelines. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Med Ctr, Evans Dept Med, Womens Hlth Unit, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RP Frayne, SM (reprint author), VA Palo Alto, Ctr Hlth Care Evaluat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM sfrayne@stanford.edu OI Freund, Karen/0000-0002-9049-5574 FU NIA NIH HHS [AG12437-03] NR 58 TC 7 Z9 7 U1 4 U2 6 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD JAN-FEB PY 2004 VL 19 IS 1 BP 28 EP 36 DI 10.1177/106286060401900106 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 767JW UT WOS:000188437300005 PM 14977023 ER PT J AU Nowbar, S Burkart, KM Gonzales, R Gozansky, WS Gaudio, JC Taylor, MRG Zwillich, CW AF Nowbar, S Burkart, KM Gonzales, R Gozansky, WS Gaudio, JC Taylor, MRG Zwillich, CW TI Obesity-associated hypoventilation in hospitalized patients: Prevalence, effects, and outcome SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; PICKWICKIAN-SYNDROME; MORTALITY; COMPLICATIONS; HYPERCAPNIA; ALTITUDE; FAILURE; DISEASE; LEVEL AB BACKGROUND: Severe obesity is associated with hypoventilation, a disorder that may adversely affect morbidity and mortality. We sought to determine the prevalence and effects of obesity-associated hypoventilation in hospitalized patients. METHODS: Consecutive admissions to internal medicine services were screened over a 6-month period. In all eligible subjects with severe obesity (body mass index greater than or equal to35 kg/m(2)), we administered a sleep questionnaire, and performed neuropsychological, arterial blood gas, and pulmonary function testing. Hospital course and mortality at 18 months was also determined. RESULTS: Of 4332 admissions, 6% (n = 277) of patients were severely obese, of whom 150 were enrolled, 75 refused to participate, and 52 met the exclusion criteria. Hypoventilation (mean [+/- SD] arterial partial pressure of carbon dioxide [PaCO2], 52 +/- 7 mm Hg) was present in 31% (n = 47) of subjects who did not have, other reasons for hypercapnia. Decreased objective attention/concentration and increased subjective sleepiness were present in patients with obesity-associated hypoventilation compared with in severely obese hospitalized patients without hypoventilation (simple obesity group; mean PaCO2, 37 +/- 6 mm Hg). There were higher rates of intensive care (P = 0.08), long-term care at discharge (P = 0.01), and mechanical ventilation (P = 0.01) among subjects with obesity-associated hypoventilation. Therapy for hypoventilation at discharge was initiated in only 6 (13%) of the patients with obesity-associated hypoventilation. At 18 months following. hospital discharge, mortality was 23% in the obesity-associated hypoventilation group as compared with 9% in the simple obesity group (hazard ratio = 4.0; 95% confidence interval: 1.5 to 10.4]. CONCLUSION: Hypoventilation frequently complicates severe obesity among hospitalized adults and is associated with excess morbidity and mortality. (C) 2004 by Excerpta Medica Inc. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. Denver Hlth Med Ctr, Denver, CO 80220 USA. Univ Calif San Francisco, Sch Med, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. Rose Med Ctr, Denver, CO USA. Brown Univ, Providence, RI 02912 USA. RP Zwillich, CW (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St,111, Denver, CO 80220 USA. EM clifford.zwillich@med.va.gov NR 24 TC 165 Z9 175 U1 0 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 JAN 1 PY 2004 VL 116 IS 1 BP 1 EP 7 DI 10.1016/j.amjmed.2003.08.022 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 763AY UT WOS:000188047900001 PM 14706658 ER PT J AU Adams, JR Elting, LS Lyman, GH George, JN Lembersky, BC Armitage, JO Demetri, GD Bennett, CL AF Adams, JR Elting, LS Lyman, GH George, JN Lembersky, BC Armitage, JO Demetri, GD Bennett, CL TI Use of erythropoietin in cancer patients: Assessment of oncologists' practice patterns in the United States and other countries SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID COLONY-STIMULATING FACTORS; CLINICAL-PRACTICE GUIDELINES; PEGYLATED LIPOSOMAL DOXORUBICIN; 1997 AMERICAN SOCIETY; THERAPY; EPOETIN; CHEMOTHERAPY; TOPOTECAN AB PURPOSE: To assess physician use of erythropoietin in cancer patients before publication of the American Society of Clinical Oncology/American Society of Hematology guidelines. METHODS: Questionnaires about erythropoietin use in practice and 12 hypothetical clinical scenarios involving patients with cancer were mailed to 2000 oncologists/hematologists in the United States and 19 other countries. Response rates were 30% in the United States and 25% internationally. Data on erythropoietin use for ovarian cancer were obtained from one clinical trial. Multivariate regression models assessed predictors of erythropoietin prescription. RESULTS: Most physicians selected a hemoglobin level less than or equal to10 g/dL as an upper threshold for erythropoietin use (36% to 51% of U.S. physicians and 21% to 3% of foreign physicians). Frequent erythropoietin use (defined as use in at least 10% of cancer patients) was higher in the United States than elsewhere (adjusted odds ratio [OR] 5.8; 95% confidence interval [CI]: 2.5 to 13.4). Among U.S. physicians, those who said they used erythropoietin frequently we re more likely to be in fee-for-service than managed care settings (OR = 2.2; 95% CI: 1.3 to 3.7). Those who reported never using erythropoietin practiced in countries that had lower annual per capita health care,expenditures, lower proportions of privately funded health care, and a national health service (P <0.05 for all comparisons). Of 235 ovarian cancer patients who received topotecan, 38% (45/118) of U.S. patients and 2% (2/117) of European patients who developed grade 1 anemia (hemoglobin level between 10 and 12 g/dL) were treated with erythropoietin (P <0.01). CONCLUSION: Financial considerations and a hemoglobin level <10 g/dL appear to influence erythropoietin use in the United States, whereas financial considerations alone determine erythropoietin use abroad. (C) 2004 by Excerpta Medica Inc. C1 MidW Ctr Hlth Serv & Policy Res, Dept Vet Affairs, Chicago, IL USA. Vet Affairs Chicago Healthcare Syst, Lakeside Div, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Ctr Hlth Studies, Chicago, IL 60611 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73190 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Univ Nebraska, Sch Med, Omaha, NE 68182 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bennett, CL (reprint author), VA Med Sci Bldg,400 E Ontario,Suite 204, Chicago, IL 60611 USA. EM cbenne@northwestern.edu RI Bennett, Charles/C-2050-2008 FU AHRQ HHS [HS 10370] NR 18 TC 16 Z9 16 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 JAN 1 PY 2004 VL 116 IS 1 BP 28 EP 34 DI 10.1016/j.amjmed.2003.06.004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 763AY UT WOS:000188047900006 PM 14706663 ER PT J AU Rook, MS Delach, SM Deyneko, G Worlock, A Wolfe, JL AF Rook, MS Delach, SM Deyneko, G Worlock, A Wolfe, JL TI Whole genome amplification of DNA from laser capture-microdissected tissue for high-throughput single nucleotide polymorphism and short tandem repeat genotyping SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; HYBRIDIZATION; CANCER; CELLS; PCR; HETEROZYGOSITY; SAMPLES; TUMORS AB Genome-wide screening of genetic alterations between normal and cancer cells, as well as among subgroups of tumors, is important for establishing molecular mechanism and classification of cancer. Gene silencing through loss of heterozygosity is widely observed in cancer cells and detectable by analyzing allelic loss of single nucleotide polymorphism and/or short tandem repeat markers. To use minute quantities of DNA that are available through laser capture microdissection (LCM) of cancer cells, a whole genome amplification method that maintains locus and allele balance is essential. We have successfully used a phi29 polymerase-based isothermal whole genome amplification method to amplify LCM DNA using a proteinase K lysis procedure coupled with a pooling strategy. Through single nucleotide polymorphism and short tandem repeat genotype analysis we demonstrate that using pooled DNA from two or three separate amplification reactions significantly reduces any allele bias introduced during amplification. This strategy is especially effective when using small quantities of source DNA. Although a convenient alkaline lysis DNA extraction procedure provided satisfactory results from using 1500 to 3000 LCM cells, proteinase K digestion was superior for lower cell numbers. Accurate genotyping is achieved with as few as 100 cells when both proteinase K extraction and pooling are applied. C1 Nuvelo Inc, Cambridge, MA USA. RP Wolfe, JL (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. NR 26 TC 70 Z9 78 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2004 VL 164 IS 1 BP 23 EP 33 DI 10.1016/S0002-9440(10)63092-1 PG 11 WC Pathology SC Pathology GA 757KB UT WOS:000187560600004 PM 14695315 ER PT J AU Kemmer, K Corless, CL Fletcher, JA McGreevey, L Haley, A Griffith, D Cummings, OW Wait, C Town, A Heinrich, MC AF Kemmer, K Corless, CL Fletcher, JA McGreevey, L Haley, A Griffith, D Cummings, OW Wait, C Town, A Heinrich, MC TI KIT mutations are common in testicular seminomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GERM-CELL TUMORS; GASTROINTESTINAL STROMAL TUMORS; PROTOONCOGENE C-KIT; TYROSINE KINASE-ACTIVITY; ACUTE MYELOID-LEUKEMIA; FACTOR RECEPTOR; URTICARIA PIGMENTOSA; ACTIVATING MUTATIONS; HUMAN MASTOCYTOSIS; CATALYTIC DOMAIN AB Expression of KIT tyrosine kinase is critical for normal germ cell development and is observed in the majority of seminomas. Activating mutations in KIT are common in gastrointestinal stromal tumors and mastocytosis. In this study we examined the frequency and spectrum of KIT mutations in 54 testicular seminomas, 1 ovarian dysgerminoma and 37 non-seminomatous germ cell tumors (NSGCT). Fourteen seminomas (25.9%) contained exon 17 point mutations including D816V (6 cases), D816H (3 cases), Y823D (2 cases), and single examples of Y823C, N822K, and T801I. No KIT mutations were found in the ovarian dysgerminoma or the NSGCTs. In transient transfection assays, mutant isoforms D816V, DK16H, Y823D, and N822K were constitutively phosphorylated in the absence of the natural ligand for KIT, stem cell factor (SCF). In contrast, activation of T801I and wild-type KIT required SCF. Mutants N822K and Y823D were inhibited by imatinib mesylate (Gleevec, previously STI571) whereas D816V and D816H were both resistant to imatinib mesylate. Biochemical evidence of KIT activation, as assessed by KIT phosphorylation and KIT association with phosphatidylinositol (PI) 3-kinase in tumor cell lysates, was largely confined to seminomas with a genomic KIT mutation. These findings suggest that activating KIT mutations may contribute to tumorigenesis in a subset of seminomas, but are not involved in NSGCT. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Oncol, Dept Pathol, Portland, OR 97201 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, R&D19,3710 US Vet Hosp Rd, Portland, OR 97239 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 49 TC 208 Z9 216 U1 1 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 JAN PY 2004 VL 164 IS 1 BP 305 EP 313 DI 10.1016/S0002-9440(10)63120-3 PG 9 WC Pathology SC Pathology GA 757KB UT WOS:000187560600032 PM 14695343 ER PT J AU Bertocci, GE Munin, MC Frost, KL Burdett, R Wassinger, CA Fitzgerald, SG AF Bertocci, GE Munin, MC Frost, KL Burdett, R Wassinger, CA Fitzgerald, SG TI Isokinetic performance after total hip replacement SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE total hip replacement; isokinetic performance; endurance; rehabilitation; biomechanical performance; muscle strength ID ARTHROPLASTY; RECOVERY; KNEE AB Objective: To evaluate differences in isokinetic hip flexion, extension, and abduction muscle performance of operated vs. nonoperated hips in older adults who have undergone elective, unilateral, total hip replacement (THR) surgery and completed rehabilitation. Design: Quasi-experimental study using a nonequivalent posttestonly control group design, comprising 20 unilateral THR patients and a convenience sample of 22 healthy older adults. THR patients participated between 4 and 5 mos after surgery. THR subjects received an average of 13 outpatient or home-based physical therapy sessions, Isokinetic muscle strength and fatigue was assessed through measurement of hip peak torque per body weight, total work, and average power using a robotic dynamometer. Results: Comparisons of THR subjects' operated vs. nonoperated hips showed no significant differences in isokinetic performance for any of the examined variables. THR subjects' operated hips generated significantly less peak torque per body weight, total work, and average power across all exercises as compared with a population of healthy subjects. Conclusions: THR subjects' operated and nonoperated hips showed similar blomechanical performance. THR patients are not being restored to the same level of strength and muscular endurance as compared with a population of healthy adults. These findings may be useful in providing a preliminary rationale for revising current approaches in THR rehabilitation protocols. C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Univ Pittsburgh, 5044 Forbes Tower, Pittsburgh, PA 15260 USA. NR 22 TC 35 Z9 42 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2004 VL 83 IS 1 BP 1 EP 9 DI 10.1097/01.PHM.0000098047.26314.93 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 758FM UT WOS:000187623100001 PM 14709968 ER PT J AU Otani, K Kulkarni, RN Baldwin, AC Krutzfeldt, J Ueki, K Stoffel, M Kahn, CR Polonsky, KS AF Otani, K Kulkarni, RN Baldwin, AC Krutzfeldt, J Ueki, K Stoffel, M Kahn, CR Polonsky, KS TI Reduced beta-cell mass and altered glucose sensing impair insulin-secretory function in beta IRKO mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE beta-cell insulin receptor knockout; insulin secretion; insulin resistance; glucose transporter 2; glucokinase ID DEPENDENT DIABETES-MELLITUS; PANCREATIC B-CELL; GROWTH-FACTOR-I; P70 S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-TRANSCRIPTION; RECEPTOR SUBSTRATE-1; MOLECULAR MECHANISMS; INTRACELLULAR CA2+; PROTEIN-SYNTHESIS AB Pancreatic beta-cell-restricted knockout of the insulin receptor results in hyperglycemia due to impaired insulin secretion, suggesting that this cell is an important target of insulin action. The present studies were undertaken in beta-cell insulin receptor knockout (betaIRKO) mice to define the mechanisms underlying the defect in insulin secretion. On the basis of responses to intraperitoneal glucose, similar to7-mo-old betaIRKO mice were either diabetic (25%) or normally glucose tolerant (75%). Total insulin content was profoundly reduced in pancreata of mutant mice compared with controls. Both groups also exhibited reduced beta-cell mass and islet number. However, insulin mRNA and protein were similar in islets of diabetic and normoglycemic betaIRKO mice compared with controls. Insulin secretion in response to insulin secretagogues from the isolated perfused pancreas was markedly reduced in the diabetic betaIRKOs and to a lesser degree in the nondiabetic betaIRKO group. Pancreatic islets of nondiabetic betaIRKO animals also exhibited defects in glyceraldehyde- and KCl-stimulated insulin release that were milder than in the diabetic animals. Gene expression analysis of islets revealed a modest reduction of GLUT2 and glucokinase gene expression in both the nondiabetic and diabetic mutants. Taken together, these data indicate that loss of functional receptors for insulin in beta-cells leads primarily to profound defects in postnatal beta-cell growth. In addition, altered glucose sensing may also contribute to defective insulin secretion in mutant animals that develop diabetes. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA. RP Polonsky, KS (reprint author), Washington Univ, Sch Med, Dept Med, 660 S Euclid Ave,Campus Box 8066, St Louis, MO 63110 USA. FU NIDDK NIH HHS [K08 DK 02885, DK 31842, DK 31036, DK 20579] NR 51 TC 104 Z9 110 U1 0 U2 0 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 JAN 1 PY 2004 VL 286 IS 1 BP E41 EP E49 DI 10.1152/ajpendo.00533.2001 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 751ND UT WOS:000187072700007 PM 14519599 ER PT J AU Beck, PL Xavier, R Wong, J Ezedi, I Mashimo, H Mizoguchi, A Mizoguchi, E Bhan, AK Podolsky, DK AF Beck, PL Xavier, R Wong, J Ezedi, I Mashimo, H Mizoguchi, A Mizoguchi, E Bhan, AK Podolsky, DK TI Paradoxical roles of different nitric oxide synthase isoforms in colonic injury SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE inducible nitric oxide synthase; endothelial nitric oxide synthase; neuronal nitric oxide synthase; dextran sodium sulfate ID ENDOTHELIAL GROWTH-FACTOR; PEROXYNITRITE-INDUCED APOPTOSIS; INFLAMMATORY-BOWEL-DISEASE; MICE LACKING; GENE-EXPRESSION; LEUKOCYTE ADHESION; ULCERATIVE-COLITIS; EPITHELIAL-CELLS; SKELETAL-MUSCLE; DOWN-REGULATION AB Nitric oxide (NO) is a free radical that is largely produced by three isoforms of NO synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). NO regulates numerous processes in the gastrointestinal tract; however, the overall role that NO plays in intestinal inflammation is unclear. NO is upregulated in both ulcerative colitis and Crohn's disease as well as in animal models of colitis. There have been conflicting reports on whether NO protects or exacerbates injury in colitis or is simply a marker of inflammation. To determine whether the site, timing, and level of NO production modulate the effect on the inflammatory responses, the dextran sodium sulfate model of colitis was assessed in murine lines rendered deficient in iNOS, nNOS, eNOS, or e/nNOS by targeted gene disruption. The loss of nNOS resulted in more severe disease and increased mortality, whereas the loss of eNOS or iNOS was protective. Furthermore, concomitant loss of eNOS reversed the susceptibility found in nNOS-/- mice. Deficiencies in specific NOS isoforms led to distinctive alterations of inflammatory responses, including changes in leukocyte recruitment and alterations in colonic lymphocyte populations. The present studies indicate that NO produced by individual NOS isoforms plays different roles in modulating an inflammatory process. C1 Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Calgary, Gastrointestinal Res Grp, Calgary, AB T2N 4N1, Canada. Vet Affairs Boston Healthcare, Boston, MA 02131 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [P30-DK-43351, R37-DK-41557] NR 58 TC 64 Z9 65 U1 0 U2 1 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 JAN 1 PY 2004 VL 286 IS 1 BP G137 EP G147 DI 10.1152/ajpgi.00309.2003 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 751YQ UT WOS:000187118600018 PM 14665440 ER PT J AU Furukawa, O Bi, LC Guth, PH Engel, E Hirokawa, M Kaunitz, JD AF Furukawa, O Bi, LC Guth, PH Engel, E Hirokawa, M Kaunitz, JD TI NHE3 inhibition activates duodenal bicarbonate secretion in the rat SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE epithelial cells; cystic fibrosis transmembrane conductance regulator; back titration; S3226 ID TRANSMEMBRANE CONDUCTANCE REGULATOR; BORDER NA+/H+ EXCHANGER; EPITHELIAL-CELLS; MEDIATED INHIBITION; CARBONIC-ANHYDRASE; CL-/HCO3-EXCHANGE; INTRACELLULAR PH; APICAL SURFACE; ADENOMA DRA; IN-VIVO AB We examined the effect of inhibition of Na+/H+ exchange (NHE) on duodenal bicarbonate secretion (DBS) in rats to further understand DBS regulation. DBS was measured by using the pH-stat method and by using CO2-sensitive electrodes. 5-(N,N-dimethyl)-amiloride (50 muM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS. Nevertheless, 3 mM DMA, a higher concentration that inhibits NHE1, NHE2, and NHE3, significantly increased DBS. Moreover, S1611 and S3226, both specific inhibitors of NHE3 only, or perfusion with Na+-free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH. Coperfusion with 0.1 muM indomethacin, 0.5 mM DIDS, or 1 mM methazolamide did not affect S3226-induced DBS. Nevertheless, coperfusion with 0.1 and 0.3 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid, which inhibits the cystic fibrosis transmembrane conductor regulator (CFTR), dose dependently inhibited S3226-induced DBS. In conclusion, only specific apical NHE3 inhibition increased DBS, whereas prostaglandin synthesis, Na+-HCO3- cotransporter activation, or intracellular HCO3- formation by carbonic anhydrase was not involved. Because NHE3 inhibition-increased DBS was inhibited by an anion channel inhibitor and because reciprocal CFTR regulation has been previously shown between NHE3 and apical membrane anion transporters, we speculate that NHE3 inhibition increased DBS by altering anion transporter function. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90024 USA. CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [2-R01-DK-54221] NR 45 TC 30 Z9 31 U1 0 U2 1 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 JAN 1 PY 2004 VL 286 IS 1 BP G102 EP G109 DI 10.1152/ajpgi.00092.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 751YQ UT WOS:000187118600014 PM 12881227 ER PT J AU Hinnebusch, BF Siddique, A Henderson, JW Malo, MS Zhang, WY Athaide, CP Abedrapo, MA Chen, XM Yang, VW Hodin, RA AF Hinnebusch, BF Siddique, A Henderson, JW Malo, MS Zhang, WY Athaide, CP Abedrapo, MA Chen, XM Yang, VW Hodin, RA TI Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestine; transcription factor; gene regulation ID FINGER TRANSCRIPTION FACTOR; CELL-CYCLE REGULATION; EPITHELIAL-CELLS; GROWTH-STATE; EXPRESSION; CANCER; SUPPRESSION; PROMOTER; EKLF; MICE AB We have examined the role that the transcription factor gut-enriched Kruppel-like factor (KLF4 or GKLF) plays in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase (IAP). A yeast one-hybrid screen was used to identify proteins interacting with a previously identified cis-element (IF-III) located within the human IAP gene promoter. DNA-protein interactions were determined by using EMSA. Northern blot analysis was used to study RNA expression in human colon cancer RKO cells engineered to overexpress KLF4. Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription. The yeast one-hybrid screen and EMSA identified KLF4 as binding to IF-III. RKO cells induced to overexpress KLF4 demonstrated a corresponding dose-dependent increase in IAP expression, and EMSA with nuclear extract from these cells confirmed that KLF4 binds to the IF-III element. Transient transfections revealed that KLF4 transactivated the IAP gene largely via a critical segment in the IAP promoter that includes the IF-III cis-element. Mutant KLF4 constructs failed to fully activate IAP. We have identified the enterocyte differentiation marker IAP as a KLF4 target gene. IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. RP Hodin, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Gray Bigelow 504,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA-84196]; NIDDK NIH HHS [DK-47186, DK-50623, DK-52230] NR 45 TC 64 Z9 67 U1 1 U2 1 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 JAN 1 PY 2004 VL 286 IS 1 BP G23 EP G30 DI 10.1152/ajpgi.00203.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 751YQ UT WOS:000187118600003 PM 12919939 ER PT J AU McLaughlin, JT Ai, WD Sinclair, NF Colucci, R Raychowdhury, R Koh, TJ Wang, TC AF McLaughlin, JT Ai, WD Sinclair, NF Colucci, R Raychowdhury, R Koh, TJ Wang, TC TI PACAP and gastrin regulate the histidine decarboxylase promoter via distinct mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE histamine ID CYCLASE-ACTIVATING POLYPEPTIDE; PHORBOL 12-MYRISTATE 13-ACETATE; PROTEIN-KINASE-A; PC12 CELLS; ACID-SECRETION; SIGNALING PATHWAYS; GASTROINTESTINAL-TRACT; GENE-EXPRESSION; ECL CELLS; RAT AB The enterochromaffin-like (ECL) cell controls gastric acid secretion via histamine, generated by L-histidine decarboxylase (HDC). HDC expression is regulated by gastrin. However, gastrin is not alone in controlling ECL cell function. For example, the neural peptide pituitary adenylate cyclase-activating polypeptide (PACAP) also increases ECL cell proliferation. To investigate a potential role of PACAP in regulating HDC expression, we generated a series of HDC promoter-luciferase reporter constructs and transiently transfected them into PC12 cells (stably expressing the gastrin-CCK-2 receptor). We found that PACAP regulates HDC promoter activity. This is temporally biphasic, involving both adenyl cyclase and phospholipase C-dependent pathways. Deletional analysis, block mutation, and EMSA demonstrated a PACAP-response element at -177 to -170, wholly necessary for the effects of PACAP and discrete from known gastrin-responsive elements. Discrete neural and endocrine pathways regulate ECL cells through different patterns of postreceptor signaling and promoter activation, which may be appropriate to their functions in vivo. C1 Univ Manchester, Hope Hosp, Salford M6 8HD, Lancs, England. Univ Massachusetts, Mem Med Ctr, Div Digest Dis & Nutr, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Wang, TC (reprint author), Univ Massachusetts, Med Ctr, Div Gastroenterol, Lazare Res Bldg,Rm 208,364 Plantat St, Worcester, MA 01605 USA. FU NIDDK NIH HHS [5 R01 DK-48077-06, K08 DK-02545-05, R03-DK60225-02] NR 43 TC 11 Z9 11 U1 2 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 JAN 1 PY 2004 VL 286 IS 1 BP G51 EP G59 DI 10.1152/ajpgi.00169.2002 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 751YQ UT WOS:000187118600007 PM 12816760 ER PT J AU Evans, SB Wilkinson, CW Gronbeck, P Bennett, JL Zavosh, A Taborsky, GJ Figlewicz, DP AF Evans, SB Wilkinson, CW Gronbeck, P Bennett, JL Zavosh, A Taborsky, GJ Figlewicz, DP TI Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE dorsomedial hypothalamus; stress; rat; lidocaine; hypothalamic-pituitary-adrenal axis ID DORSOMEDIAL HYPOTHALAMIC NUCLEUS; PARAVENTRICULAR NUCLEUS; COUNTERREGULATORY RESPONSES; CHEMICAL-STIMULATION; LOCAL-ANESTHETICS; AUTONOMIC FAILURE; EFFECTIVE SPREAD; FOS EXPRESSION; NERVE ACTIVITY; RAT AB We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls (n = 9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50 +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 +/- 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Figlewicz, DP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK-50154, DK-40963, DK-62446] NR 44 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN 1 PY 2004 VL 286 IS 1 BP R123 EP R128 DI 10.1152/ajpregu.00328.2003 PG 6 WC Physiology SC Physiology GA 751BX UT WOS:000187033900022 PM 14660476 ER PT J AU Martis, B Wright, CI McMullin, KG Shin, LM Rauch, SL AF Martis, B Wright, CI McMullin, KG Shin, LM Rauch, SL TI Functional magnetic resonance imaging evidence for a lack of striatal dysfunction during implicit sequence learning in individuals with animal phobia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID REGISTRATION; INVENTORY; FEAR; PET; MRI AB Objective: This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia, in a follow-up to analogous studies of obsessive-compulsive disorder (OCD). Method: Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging. Results: A main effect of condition (implicit sequence learning versus random sequence) was observed across diagnostic groups in the right striatum, as well as in other regions. In the striaturn, the a priori region of interest, there were no significant effects of diagnosis or the interaction of diagnosis and condition. Conclusions: Brain activation in the striaturn of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning. This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD, in which deficient striatal recruitment has been reproducibly found with this paradigm. This approach offers promise for demonstrating diagnostic specificity across different neuro psychiatric disorders based on the presence or absence of deficient striatal activation. C1 Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Tufts Univ, Medford, MA 02155 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Bldg 149,Rm 9130,13th St, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu FU NIMH NIH HHS [MH-60219, MH-64806] NR 23 TC 16 Z9 16 U1 4 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 67 EP 71 DI 10.1176/appi.ajp.161.1.67 PG 5 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700012 PM 14702252 ER PT J AU Rohan, M Parow, A Stoll, AL Demopulos, C Friedman, S Dager, S Hennen, J Cohen, BM Renshaw, PF AF Rohan, M Parow, A Stoll, AL Demopulos, C Friedman, S Dager, S Hennen, J Cohen, BM Renshaw, PF TI Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LEFT PREFRONTAL CORTEX; MAJOR DEPRESSION; ELECTRIC-FIELD; RATING-SCALE; RTMS; MODEL; TRIAL; MOOD; SLOW; TMS AB Objective: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. Method: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect: Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. Results: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1-500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. Conclusions: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is Warranted. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Washington, Sch Med, Dept Radiol & Bioengn, Seattle, WA 98195 USA. RP Rohan, M (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM mrohan@mclean.harvard.edu FU NIMH NIH HHS [MH-58681] NR 25 TC 46 Z9 47 U1 1 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 93 EP 98 DI 10.1176/appi.ajp.161.1.93 PG 6 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700016 PM 14702256 ER PT J AU Ghaemi, SN Rosenquist, KJ Ko, JY Baldassano, CF Kontos, NJ Baldessarini, RJ AF Ghaemi, SN Rosenquist, KJ Ko, JY Baldassano, CF Kontos, NJ Baldessarini, RJ TI Antidepressant treatment in bipolar versus unipolar depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; DISORDER; SAFETY AB Objective: Antidepressant responses were compared in DSM-IV bipolar and unipolar depression. Method: The authors analyzed clinical records for outcomes of antidepressant trials for 41 patients with bipolar depression and 37 with unipolar depression, similar in age and sex distribution. Results: Short-term nonresponse was more frequent in bipolar (51.3%) than unipolar (31.6%) depression. Manic switching occurred only in bipolar depression but happened less in patients taking mood stabilizers (31.6% versus 84.2%). Cycle acceleration occurred only in bipolar depression (25.6%), with new rapid cycling in 32.1%. Late response loss (tolerance) was 3.4 times as frequent, and withdrawal relapse into depression was 4.7 times less frequent, in bipolar as in unipolar depression. Mood stabilizers did not prevent cycle acceleration, rapid cycling, or response loss. Modern antidepressants, in general, did not have lower rates of negative outcomes than tricyclic antidepressants. Conclusions: The findings suggest an unfavorable cost/benefit ratio for antidepressant treatment of bipolar depression. C1 Cambridge Hosp, Bipolar Disorder Res Program, Cambridge, MA 02139 USA. Cambridge Hosp, Dept Psychiat, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Penn, Dept Psychiat, Bipolar Outpatient Program, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA USA. RP Ghaemi, SN (reprint author), Cambridge Hosp, Bipolar Disorder Res Program, 1493 Cambridge St, Cambridge, MA 02139 USA. EM ghaemi@hms.harvard.edu FU NIMH NIH HHS [MH-64189] NR 9 TC 171 Z9 176 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 163 EP 165 DI 10.1176/appi.ajp.161.1.163 PG 3 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700027 PM 14702267 ER PT J AU Mascarenhas, MM Day, RM Ochoa, CD Choi, WI Yu, LY Bin, OY Garg, HG Hales, CA Quinn, DA AF Mascarenhas, MM Day, RM Ochoa, CD Choi, WI Yu, LY Bin, OY Garg, HG Hales, CA Quinn, DA TI Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID MECHANICAL STRAIN; DIFFERENTIAL REGULATION; ELECTROPHORETIC METHOD; INTERFERON-GAMMA; GENE-EXPRESSION; CELLS; ACID; MACROPHAGES; SYNTHASES; INJURY AB Mechanical ventilation has been shown to cause ventilator induced lung injury (VILI), probably by overdistending or stretching the lung. Hyaluronan (HA), a component of the extracellular matrix, in low molecular weight (LMW) forms has been shown to induce cytokine production. LMW HA is produced by hyaluronan synthase 3 (HAS 3). We found that HAS 3 mRNA expression was upregulated and that LMW HA accumulated in an animal model of VILI We hypothesized that stretch induced LMW HA production that causes cytokine release in VILI was dependent on HAS 3 mRNA expression. We explored this hypothesis with in vitro lung cell stretch. Cell stretch induced HAS 3 mRNA expression and LMW HA in fibroblasts. Nonspecific inhibitors of HAS 3 (cyclohexamide and dexamethasone), a nonspecific inhibitor of protein tyrosine kinases (genistein), and a janus kinase 2 inhibitor (AG490) blocked stretch-induced HAS 3 expression and synthesis of LMW HA. Stretch-induced LMW HA from fibroblasts caused a significant dose-dependent increase in interleukin-8 production both in static and stretched epithelial cells. These results indicated that de novo synthesis of LMW HA was induced in lung fibroblasts by stretch via tyrosine kinase signaling pathways, and may play a role in augmenting induction of proinflammatory cytokines in VILI. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, New England Med Ctr, Div Pulm & Crit Care, Boston, MA USA. Medellin Gen Hosp, Div Crit Care Med, Medellin, Colombia. Pontif Bolivarian Univ, Medellin, Colombia. RP Mascarenhas, MM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, 55 Fruit St Bulfinch 148, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03920-01, 5T32 HL07874-05, HL39150-13] NR 35 TC 73 Z9 77 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2004 VL 30 IS 1 BP 51 EP 60 DI 10.1165/rcmb.2002-0167OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 760UE UT WOS:000187852800007 PM 12738686 ER PT J AU Shamsi, K Sorensen, AG AF Shamsi, K Sorensen, AG TI Results of four multicenter Phase III magnetic resonance angiography (MRA) trials with MS-325, a blood pool contrast agent, for the detection of vascular disease in the Aortoiliac, Renal, and Pedal regions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Berlex Labs Inc, Montville, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EPIX Med, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 2 EP 2 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100008 ER PT J AU Rastogi, N Sahani, D Ko, D Saini, S Mueller, P AF Rastogi, N Sahani, D Ko, D Saini, S Mueller, P TI Presurgical evaluation of living related renal donors: Evaluation with 3D 4-MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 5 EP 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100018 ER PT J AU Zacharia, TT O'Neill, MJ Hahn, PF Lee, SL Mueller, PR AF Zacharia, TT O'Neill, MJ Hahn, PF Lee, SL Mueller, PR TI Incidence and distribution of adnexal findings suggesting endometriosis in patients with MR diagnosis of adenomyosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 17 EP 18 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100067 ER PT J AU Digumarthy, SR Lee, SI Duska, LR Blake, MA O'Neill, MJ Hahn, PF AF Digumarthy, SR Lee, SI Duska, LR Blake, MA O'Neill, MJ Hahn, PF TI Endometriosis: How sensitive is magnetic resonance imaging? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 18 EP 18 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100070 ER PT J AU Zacharia, TT O'Neill, MJ Hahn, PF Lee, SL Mueller, PR AF Zacharia, TT O'Neill, MJ Hahn, PF Lee, SL Mueller, PR TI Transvaginal ultrasound vs. MRI for the diagnosis of adenomyosis: Does the expertise of the interpreter affect diagnostic accuracy? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 18 EP 18 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100068 ER PT J AU Uppot, RN Lee, S Singh, AK Sahani, D Saini, S Hahn, P Mueller, P AF Uppot, RN Lee, S Singh, AK Sahani, D Saini, S Hahn, P Mueller, P TI Value of viewing coronal reformatted multidetector CT images in the evaluation of metastatic ovarian malignancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 19 EP 19 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100073 ER PT J AU Singh, AK Gervais, D Hahn, P Mueller, P AF Singh, AK Gervais, D Hahn, P Mueller, P TI Acute appendagitis: CT appearance SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 24 EP 25 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100093 ER PT J AU Pomerantz, SR Schaefer, PW Lev, MH AF Pomerantz, SR Schaefer, PW Lev, MH TI Diffusion-weighted imaging of orbital lymphoproliferative disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 31 EP 32 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100120 ER PT J AU Boyajian, DA Mullins, ME Ryan, DP Purdy, DR Doody, DP Rhea, JT Novelline, RA Wang, LT AF Boyajian, DA Mullins, ME Ryan, DP Purdy, DR Doody, DP Rhea, JT Novelline, RA Wang, LT TI The utility of abdominal plain films in the evaluation of acute abdominal pain in children, with comparison to CT and sonography (part II) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 37 EP 38 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100143 ER PT J AU Sahani, DV Krishnamoorthy, V Kalva, S D'souza, R Cusack, C Singh, A Saini, S Mueller, P AF Sahani, DV Krishnamoorthy, V Kalva, S D'souza, R Cusack, C Singh, A Saini, S Mueller, P TI Multidetector-row CT angiography for planning intraaterial chemotherapy pump placement in patients with colorectal metastases to the liver SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 46 EP 46 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100175 ER PT J AU Aquino, SL Fischman, AJ AF Aquino, SL Fischman, AJ TI Significance between whole body PET and thoracic PET in the staging of patients with newly diagnosed lung cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 50 EP 50 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100191 ER PT J AU Kwek, BH Fischman, AJ Aquino, SL AF Kwek, BH Fischman, AJ Aquino, SL TI Patterns of pleural disease on FDG-PET and CT following talc pleurodesis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 50 EP 50 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100190 ER PT J AU Kalva, SP Sahani, DV Saini, S Fischmann, AJ Kadavigere, R Ryan, D Hahn, PF Mueller, PR AF Kalva, SP Sahani, DV Saini, S Fischmann, AJ Kadavigere, R Ryan, D Hahn, PF Mueller, PR TI Detection of liver metastases: Comparative study of dual contrast-enhanced MRI and FDG PET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 56 EP 56 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100215 ER PT J AU Kadavigere, R Sahani, DV Kalva, SP D'Souza, R Mueller, P Castillo, F AF Kadavigere, R Sahani, DV Kalva, SP D'Souza, R Mueller, P Castillo, F TI Intraductal papillary mucinous neoplasms: Comparative evaluation of MRCP and curved 2D reformations on MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 64 EP 64 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100246 ER PT J AU Singh, AK Gervais, D Alhilali, L Uppot, R Hahn, P Mueller, P AF Singh, AK Gervais, D Alhilali, L Uppot, R Hahn, P Mueller, P TI Image-guided catheter drainage of abdominal collections with pancreatobiliary communication SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 64 EP 64 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100245 ER PT J AU Zacharia, TT Shah, JR Kale, HR Patkar, D AF Zacharia, TT Shah, JR Kale, HR Patkar, D TI MR imaging in ankle tuberculosis: A review of 14 patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Nanavati Hosp, Bombay, Maharashtra, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 72 EP 72 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100277 ER PT J AU Zalis, ME Perumpillichira, JJ Blake, MA Hahn, PF Sahani, DV Mueller, PR AF Zalis, ME Perumpillichira, JJ Blake, MA Hahn, PF Sahani, DV Mueller, PR TI A comparison of the compliance of research vs. clinical patients with preparation and exam requirements in CT colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 76 EP 76 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100289 ER PT J AU Turner, BG Rhea, JT Novelline, RA AF Turner, BG Rhea, JT Novelline, RA TI Utilization of imaging in the evaluation of facial trauma: Comparison of 1992 vs. 2002 SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 79 EP 80 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100304 ER PT J AU Georgian-Smith, D Rafferty, EA Kricun, B Yeh, E D'Alessandro, HA Staffa, M Kopans, DB AF Georgian-Smith, D Rafferty, EA Kricun, B Yeh, E D'Alessandro, HA Staffa, M Kopans, DB TI ACR BIRADS breast ultrasound lexicon: A computerized display SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 82 EP 82 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100309 ER PT J AU Lee, JC Chantra, PK Chen, L Larsen, LH Bassett, LW AF Lee, JC Chantra, PK Chen, L Larsen, LH Bassett, LW TI The role of sonography in male breast imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 83 EP 83 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100314 ER PT J AU Kalva, SP Sahani, DV Hahn, PF Kadavigere, R Willett, CG Bendell, J Mueller, PR AF Kalva, SP Sahani, DV Hahn, PF Kadavigere, R Willett, CG Bendell, J Mueller, PR TI Rectal cancer imaging: What do the surgeons and oncologists need? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 89 EP 89 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100343 ER PT J AU Blake, MA Sweeney, AT Sahani, D Kalra, MK Maher, M Boland, GW Hahn, PF Mueller, PR AF Blake, MA Sweeney, AT Sahani, D Kalra, MK Maher, M Boland, GW Hahn, PF Mueller, PR TI The imaging spectrum of pheochromocytomas SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. St Elizabeths Med Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 96 EP 96 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100381 ER PT J AU Rastogi, N Sahani, D Ko, D Blake, M Uppot, R Mercer, J Mueller, P AF Rastogi, N Sahani, D Ko, D Blake, M Uppot, R Mercer, J Mueller, P TI MDCT or MRA imaging for renal vascular and excretory realm as key selling points prior to laparoscopic donor nephrectomy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 96 EP 97 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100382 ER PT J AU Oeppen, RS Connolly, SA Bencardino, JT Jaramillo, D AF Oeppen, RS Connolly, SA Bencardino, JT Jaramillo, D TI Acute injury of the articular cartilage and subchondral bone: A common but unrecognized lesion in the immature knee SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HYALINE CARTILAGE; SPORTS INJURIES; CHILDREN; ARTHROSCOPY; ADOLESCENTS; THICKNESS; ACCURACY; MRI AB OBJECTIVE. We studied the prevalence of injuries of the articular cartilage and subchondral bone after acute trauma in skeletally immature knees using high-resolution MRI. MATERIALS AND METHODS. We reviewed knee MRIs of 126 young children and adolescents suspected to have internal knee derangement, including 82 with open physes and a control group of 44 who were skeletally mature. High-resolution proton density and T2-weighted pulse sequences were used in all patients. The prevalence of common injuries in the two groups was compared using chi-square analysis. Levels of interobserver agreement for evaluation of chondral lesions in the skeletally immature group were determined using the kappa statistic. RESULTS. In the skeletally immature group, chondral lesions were the most prevalent injuries (prevalence = 0.34, p = 0.009) followed by meniscal and anterior cruciate ligament injuries (prevalence = 0.23 and 0.24, respectively). No significant difference in the prevalence of chondral injury before and after physeal closure was seen (P = 0.45). There was no significant difference in the prevalence of anterior cruciate ligament injuries between the two groups, but meniscal injuries were more prevalent in the skeletally mature patients (prevalence = 0.41, p = 0.037). Interobserver agreement for chondral injuries in the group with open physes was good (weighted kappa = 0.45-0.51). CONCLUSION. The most common injuries occurring as a result of acute trauma to the immature knee were chondral. In patients with open physes, chondral injuries were significantly more prevalent than anterior cruciate ligament and meniscal injuries. C1 Massachusetts Gen Hosp, Dept Pediat Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Huntington Hosp, Dept Radiol, Huntington, NY 11743 USA. RP Jaramillo, D (reprint author), Massachusetts Gen Hosp, Dept Pediat Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 23 TC 42 Z9 47 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2004 VL 182 IS 1 BP 111 EP 117 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767WB UT WOS:000188495900029 PM 14684522 ER PT J AU Mehta, AA Sahani, D Uppot, R Hertl, M Kim, J Saini, S Hahn, P Mueller, P AF Mehta, AA Sahani, D Uppot, R Hertl, M Kim, J Saini, S Hahn, P Mueller, P TI Postoperative anatomic and functional evaluation of a biliary tree with contrast-enhanced MRCP SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 114 EP 114 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100467 ER PT J AU Sahani, DV Kadavigere, R Fernandez, C Warsha, A D'Souza, R AF Sahani, DV Kadavigere, R Fernandez, C Warsha, A D'Souza, R TI Comprehensive imaging evaluation of intraductal papillary mucinous tumor (IPMT) of the pancreas with MDCT and 2D curved reformations: Comparison with MRCP and pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 114 EP 115 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100468 ER PT J AU Sahani, DV Kadavigere, R Fernandez, C Brugge, W Lauwers, G Warsha, W Kalva, SP Mueller, P AF Sahani, DV Kadavigere, R Fernandez, C Brugge, W Lauwers, G Warsha, W Kalva, SP Mueller, P TI Current concepts in diagnosis and management of cystic lesions of the pancreas SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 115 EP 115 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100469 ER PT J AU Uppot, RN Sahani, D Lee, S Saini, S Mueller, P AF Uppot, RN Sahani, D Lee, S Saini, S Mueller, P TI Coronal vs. axial: A pictoral exhibit of bowel pathology on coronally reformatted images using 16 slice multidetector CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 116 EP 116 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100478 ER PT J AU Uppot, RN Sahani, D Lee, S Mueller, P AF Uppot, RN Sahani, D Lee, S Mueller, P TI Coronal vs. axial: A pictoral exhibit of genitourinary pathology on coronally reformatted images using 16 slice multidetector CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 117 EP 117 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100484 ER PT J AU Gill, TJ DeFrate, LE Wang, C Carey, CT Zayontz, S Zarins, B Li, G AF Gill, TJ DeFrate, LE Wang, C Carey, CT Zayontz, S Zarins, B Li, G TI The effect of posterior cruciate ligament reconstruction on patellofemoral contact pressures in the knee joint under simulated muscle loads SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Conference of the American-Orthopaedic-Society-for-Sports-Medicine-Specialty-Day CY 2002 CL Dallas, TX SP Amer Orthopaed Soc Sports Med Specialty Day DE posterior cruciate ligament; patellofemoral joint; contact pressures; ligament reconstruction; knee biomechanics ID TERM FOLLOW-UP; DEFICIENT KNEE; IN-VITRO; NATURAL-HISTORY; GRAFT; INJURIES; RUPTURE; INSTABILITY; KINEMATICS; STABILITY AB Background: The mechanism of cartilage degeneration in the patellofemoral joint (PFJ) and medial compartment of the knee following posterior cruciate ligament (PCL) injury remains unclear. PCL reconstruction has been recommended to restore kinematics and prevent long-term degeneration. The effect of current reconstruction techniques on PFJ contact pressures is unknown. Purpose: To measure PFJ contact pressures after PCL deficiency and reconstruction. Method: Eight cadaveric knees were tested with the PCL intact, deficient, and reconstructed. Contact pressures were measured at 30degrees, 60degrees, 90degrees, and 120degrees of flexion under simulated muscle loads. Knee kinematics were measured by a robotic testing. system, and the PFJ contact pressures were measured using a thin film transducer. A single bundle achilles tendon allograft was used in the reconstruction. Results: PCL deficiency significantly increased the peak contact pressures measured in the PFJ relative to the intact knee under both an isolated quadriceps load of 400 N and a combined quadriceps/hamstrings load of 400 N/200 N. Reconstruction did not significantly reduce the increased contact pressures observed in the PCL-deficient knee. Conclusion: The elevated contact pressures observed in the PCL-deficient knee and reconstructed knee might contribute to the long-term degeneration observed in both the non-operatively treated and PCL-reconstructed knees. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. NR 45 TC 34 Z9 39 U1 0 U2 1 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JAN-FEB PY 2004 VL 32 IS 1 BP 109 EP 115 DI 10.1177/0095399703258794 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 810NP UT WOS:000220711300014 PM 14754732 ER PT J AU Peretti, GM Gill, TJ Xu, JW Randolph, MA Morse, KR Zaleske, DJ AF Peretti, GM Gill, TJ Xu, JW Randolph, MA Morse, KR Zaleske, DJ TI Cell-based therapy for meniscal repair - A large animal study SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT 2nd Meeting of the Italian-Argentinean-Brazilian-Orthopaedic-and-Traumatology-Society CY DEC 02-06, 2001 CL Buenos Aires, ARGENTINA SP Italian Argentinean Brazilian Orthopaed & Traumatol Soc DE meniscus; repair; tissue engineering; chondrocytes; knee ID ARTICULAR-CARTILAGE; PARTIAL MENISCECTOMY; DEGENERATIVE CHANGES; CANINE MENISCECTOMY; AVASCULAR ZONE; RABBIT MODEL; KNEE; OSTEOARTHRITIS; REGENERATION; DOGS AB Background: The avascular portion of the meniscus cartilage in the knee does not have the ability to repair spontaneously. Hypothesis: Cell-based therapy is able to repair a lesion in the swine meniscus. Study Design: Controlled laboratory study. Methods: Sixteen Yorkshire pigs were divided into four groups. A longitudinal tear was produced in the avascular portion of the left medial meniscus of 4 pigs. Autologous chondrocytes were seeded onto devitalized allogenic meniscal slices and were secured inside the lesion with two sutures. Identical incisions were created in 12 other pigs, which were used as three separate control groups: 4 animals treated with an unseeded scaffold, 4 were simply sutured, and 4 were left untreated. Meniscal samples were collected after 9 weeks, and the samples were analyzed grossly, histologically, and histomorphometrically. Results: Gross results showed bonding of the lesion margins in the specimens of the experimental group, whereas no repair was noted in any of the control group specimens. Histological and histomorphometrical analysis showed multiple areas of healing in the specimens of the experimental group. Conclusions: This study demonstrated the ability of seeded chondrocytes to heal a meniscal tear. Clinical Relevance: Cell-based therapy could be a potential tool for avascular meniscus repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Univ Vita Salute, Hosp San Raffaele, Dept Orthopaed, Milan, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Labs, Boston, MA 02115 USA. Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. Fudan Univ, Shanghai 200433, Peoples R China. RP Gill, TJ (reprint author), Sports Med Serv, WACC 531,15 Parkman St, Boston, MA 02114 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 61 TC 88 Z9 90 U1 1 U2 9 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JAN-FEB PY 2004 VL 32 IS 1 BP 146 EP 158 DI 10.1177/0095399703258790 PG 13 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 810NP UT WOS:000220711300020 PM 14754738 ER PT J AU Folpe, AL Fanburg-Smith, JC Billings, SD Bisceglia, M Bertoni, F Cho, JY Econs, MJ Inwards, CY de Beur, SMJ Mentzel, T Montgomery, E Michal, M Miettinen, M Mills, SE Reith, JD O'Connell, JX Rosenberg, AE Rubin, BP Sweet, DE Vinh, TN Wold, LE Wehrli, BM White, FKE Zaino, RJ Weiss, SW AF Folpe, AL Fanburg-Smith, JC Billings, SD Bisceglia, M Bertoni, F Cho, JY Econs, MJ Inwards, CY de Beur, SMJ Mentzel, T Montgomery, E Michal, M Miettinen, M Mills, SE Reith, JD O'Connell, JX Rosenberg, AE Rubin, BP Sweet, DE Vinh, TN Wold, LE Wehrli, BM White, FKE Zaino, RJ Weiss, SW TI Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity - An analysis of 32 cases and a comprehensive review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE oncogenic osteomalacia; phosphaturia; mesenchymal tumors; sarcoma; hemangiopericytoma; immunohistochemistry ID ONCOGENIC HYPOPHOSPHATEMIC OSTEOMALACIA; METASTATIC PROSTATE CARCINOMA; FINE-NEEDLE-ASPIRATION; D-RESISTANT RICKETS; SOFT-TISSUE TUMORS; GIANT-CELL TUMOR; HYPERCALCEMIC HYPERPARATHYROIDISM; TERTIARY HYPERPARATHYROIDISM; PHOSPHATE SUPPLEMENTATION; SKELETAL SURVEY AB Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMT-MCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of 00 was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known 00 were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and I sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serumchernistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrurn, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should a] low distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO. C1 Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. IRCCS Casa Sollievo della Sofferenza Hosp, Dept Pathol, San Giovanni Rotondo, Italy. Univ Bologna, Dept Pathol, Rizzoli Inst, Bologna, Italy. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Mayo Clin, Dept Anat Pathol, Rochester, MN USA. Dermatopathol Gemeinschaftspraxis, Friedrichshafen, Germany. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Charles Univ, Fac Hosp, Dept Pathol, Plzen, Czech Republic. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA. Surrey Mem Hosp, Dept Pathol, Surrey, BC, Canada. Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Lab, Boston, MA 02114 USA. Univ Washington, Med Ctr, Dept Pathol Anat, Seattle, WA 98195 USA. Armed Forces Inst Pathol, Dept Orthoped Surg, Washington, DC 20306 USA. London Hlth Sci Ctr, Dept Pathol, London, ON, Canada. Penn State Hershey Med Ctr, Dept Pathol, Hershey, PA USA. Univ Virginia, Med Ctr, Dept Pathol, Charlottesville, VA USA. RP Folpe, AL (reprint author), Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. EM afolpe@emory.edu NR 113 TC 222 Z9 244 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2004 VL 28 IS 1 BP 1 EP 30 DI 10.1097/00000478-200401000-00001 PG 30 WC Pathology; Surgery SC Pathology; Surgery GA 774JB UT WOS:000188975400001 PM 14707860 ER PT J AU Zembowicz, A Carney, JA Mihm, MC AF Zembowicz, A Carney, JA Mihm, MC TI Pigmented epithelioid melanocytoma - A low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE melanoma; equine melanotic disease; sentinel lymph node; epithelioid blue nevus; metastases; Carney complex ID PILAR NEUROCRISTIC HAMARTOMA; DEEP PENETRATING NEVUS; CARNEY COMPLEX; MALIGNANT-MELANOMA; NEOPLASMS; DISEASE; CELL; SKIN; SCHWANNOMA; MUTATIONS AB In the course of a study of borderline melanocytic tumors, we observed a distinctive group of lesions characterized by features very similar to those previously described in the literature as "animal-type melanoma" and epithelioid blue nevus of Carney complex. We have designated these lesions as pigmented epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis of 41 consecutive PEM from 40 patients and compare them with I I epithelioid blue nevi from patients with Carney complex. PEM occurred in both sexes of different ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide distribution with extremities being the most common site. The tumors were formed by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily pigmented epithelioid and/or spindled melanocytes. Five lesions were part of combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in 1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph nodes contained metastases (46%). Liver metastases occurred in 1 case. None of the patients died of disease. Clinical follow-up of more than a year (mean 32 months, range up to 67 months) was available in 27 cases (67%). We found no histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration was the only feature more common in PEM than epithelioid blue nevi of Carney complex. Otherwise, they were histologically indistinguishable. Our data show that PEM is a unique low-grade variant of melanoma with frequent lymph node metastases but indolent clinical course. We suggest that PEM be considered as a provisional histologic entity encompassing both animal-type melanoma and epithelioid blue nevus. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Dermatol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 53 TC 123 Z9 126 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2004 VL 28 IS 1 BP 31 EP 40 DI 10.1097/00000478-200401000-00002 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 774JB UT WOS:000188975400002 PM 14707861 ER PT J AU Skinnider, BF Young, RH AF Skinnider, BF Young, RH TI Infarcted adenomatoid tumor - A report of five cases of a facet of a benign neoplasm that may cause diagnostic difficulty SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE adenomatoid tumor; infarction; epididymis; testis; fallopian tube ID PSEUDOTUMOR; EPIDIDYMIS; TESTIS AB We describe five cases in which adenomatoid tumors showed extensive necrosis, presumably due to infarction, and posed diagnostic difficulty. The tumors occurred in four males (three with epididymal tumors and one with an intratesticular tumor) and one female (with a parafallopian tube tumor) 35 to 44 years of age. Two of the men presented with acute scrotal pain simulating epididymitis, and two with a palpable mass. The parafallopian tube tumor was an incidental finding. The tumors were solitary, grossly well-circumscribed, uniformly solid masses that ranged in size from 1.1 to 3.5 cm. Microscopically, they were all characterized by central necrosis with pate mummified adenomatoid tumor identified at least focally but often overshadowed by nondescript necrotic tissue. Viable adenomatoid tumor was identified in all cases but was minor in amount in two of them. The necrosis was surrounded by a florid reactive process of fibroblasts and myofibroblasts that had plump nuclei often with prominent nucleoli, and occasional mitoses. Two of the epididymal cases had adjacent rete testis showing epithelial hyperplasia with hyaline globule formation. The microscopic appearance often suggested the possibility of a malignant neoplasm because of. 1) blurring of the normal relatively easily identifiable junction between adenomatoid tumor and adjacent tissue; 2) irregular pseudo-infiltration of fat by reactive tissue and adenomatoid tumor; 3) paucity of typical adenomatoid turnor due to the infarction and the fact that viable tumor usually showed a solid pattern;, and 4) atypia of the associated reactive cells. This unemphasized feature of adenomatoid tumors may potentially lead to more aggressive therapy than warranted if it is not correctly interpreted. C1 Vancouver Hosp & Hlth Sci Ctr, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Skinnider, BF (reprint author), Vancouver Hosp & Hlth Sci Ctr, Dept Pathol & Lab Med, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. EM bskinnid@vanhosp.bc.ca NR 18 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2004 VL 28 IS 1 BP 77 EP 83 DI 10.1097/00000478-200401000-00008 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 774JB UT WOS:000188975400008 PM 14707867 ER PT J AU Zhou, M Epstein, JI Young, RH AF Zhou, M Epstein, JI Young, RH TI Paragangliorna of the urinary bladder - A lesion that may be misdiagnosed as urothelial carcinoma in transurethral resection specimens SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE paraganglioma; urotbelial carcinoma; urinary bladder ID MELANOTIC PARAGANGLIOMA; CELL-CARCINOMA; PHEOCHROMOCYTOMA AB Paraganglioma of the urinary bladder is a rare tumor with characteristic histologic and immunohistochemical features. However, in our experience, it may be misdiagnosed as urothelial cancer because of 1) its frequent involvement of the muscularis propria; 2) morphology that may suggest urothelial cancer in transurethral resection specimens, particularly if there are artifactual changes induced by that procedure; 3) failure of pathologists to include it in their differential diagnosis when evaluating a bladder tumor; and 4) only a minority of the cases are associated with symptoms that might prompt consideration of the diagnosis. Distinction between paraganglioma and urothelial cancer is important because of likely different therapeutic options. In this report, we describe our experience with the histopathology of paragangliomas of the urinary bladder with emphasis on the histologic features that have led to their being misdiagnosed as conventional urothelial cancer and, most importantly, those that will help pathologists recognize this rare tumor of the bladder. Fifteen cases of paraganglioma of the urinary bladder were studied, 11 of them consult cases. They affected patients (8 male, 7 female) with a mean age of 49.5 years; only two had symptoms suggestive of the diagnosis, including hypertension during cystoscopy and episodic headache. Three consult cases were submitted with a diagnosis of "transitional cell carcinoma" and 4 with a diagnosis only of "bladder tumor." Histologically, "zellballen" and diffuse patterns were present in 12 (80%) and 3 (20%) of the cases. A delicate fibrovascular stroma was obvious in 14 (93%) cases. Other patterns included irregular nests and pseudorosette formation. Tumor necrosis, significant cautery artifact, and muscularis propria invasion were present in 1 (7%), 3 (20%) cases, and 10 (67%) cases, respectively. All 15 tumors were composed of large polygonal cells with abundant granular cytoplasm. Focal clear cells were present in 3 (20%). The nuclei were mostly uniform, although occasional pleomorphic nuclei were seen in 6 (40%) cases, and 2 (13%) had frequent pleomorphic nuclei. Mitoses were rare overall, and no abnormal mitotic figures were found. The major histologic features that led to misdiagnosis included a diffuse growth pattern, focal clear cells, necrosis, and muscularis propria invasion, with significant cautery artifact compounding the diagnostic problems. Immunohistochemically, 2 of 2 tumors were positive for neuron-specific enolase, 9 of 10 tumors for chromogranin, and 2 of 3 tumors for synaptophysin; 3 of 3 tumors were negative for cytokeratin and 1 of 1 tumor negative for HMB-45. Paraganglioma of the urinary bladder may be misdiagnosed as urothelial cancer, but a careful search for the characteristic histologic features and, if necessary, supportive immunohistochemical studies, should lead to a correct diagnosis. C1 Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Young, RH (reprint author), Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,WRN 215, Boston, MA 02114 USA. NR 21 TC 35 Z9 42 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2004 VL 28 IS 1 BP 94 EP 100 DI 10.1097/00000478-200401000-00011 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 774JB UT WOS:000188975400011 PM 14707870 ER PT J AU Leaf, DA Kleinman, MT Deitrick, RW AF Leaf, DA Kleinman, MT Deitrick, RW TI The effects of exercise on markers of lipid peroxidation in renal dialysis patients compared with control subjects SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE renal dialysis; exercise; oxidative stress; lipids ID CORONARY-ARTERY DISEASE; HEMODIALYSIS-PATIENTS; OXIDATIVE STRESS; VITAMIN-E; ACCELERATED ATHEROSCLEROSIS; MAINTENANCE HEMODIALYSIS; UREMIC PATIENTS; OXIDANT STRESS; FREE-RADICALS; FATTY-ACIDS AB Purpose: The purpose of this study was to compare the susceptibility to exercise-induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and non-CMD control subjects. Design: Cross-sectional comparison of exercise-induced changes in breath ethane and pentane flux between patients on CMD (group A) and an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched comparison group (group B). Breath ethane and pentane were measured at rest before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic acidosis threshold (Vo(2)LAT), and 5 minutes after CPX. Results: Group comparisons of clinical characteristics reveal that the groups were similar in terms of age, ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors. All subjects successfully completed the CPX protocol achieving Vo(2)LAT. There were significant differences in breath ethane flux between group A and B subjects, with greater pre-exercise, Vo(2)LAT, and postexercise ethane levels in group A compared with group B subjects, and significant group differences, with lower breath ethane/pentane flux ratios at rest, Vo(2)LAT, and recovery with lower ratios in group B than group A subjects. Discussion/Conclusions: This study shows that patients on CMD have greater lipid peroxidation compared with control subjects at rest and during and after physical exercise. In addition, compared with control subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty acids at rest and during physical exercise and recovery. The lipid peroxidation profile may result in an unfavorable endoperoxide shift and should be evaluated further, along with modalities to reduce oxidative stress among patients on CMD. C1 Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Irvine, Dept Community & Environm Med, Irvine, CA 92717 USA. Univ Scranton, Dept Exercise Sci & Sport, Scranton, PA 18510 USA. RP Leaf, DA (reprint author), Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, Dept Med, 111G,Wiltshire & Sawtelle Blvds, Los Angeles, CA 90073 USA. EM david.leaf@med.va.gov NR 48 TC 9 Z9 10 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 JAN PY 2004 VL 327 IS 1 BP 9 EP 14 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 764FQ UT WOS:000188197100004 PM 14722390 ER PT J AU Ojo, AO Heinrichs, D Emond, JC McGowan, JJ Guidinger, MK Delmonico, FL Metzger, RA AF Ojo, AO Heinrichs, D Emond, JC McGowan, JJ Guidinger, MK Delmonico, FL Metzger, RA TI Organ donation and utilization in the USA SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE deceased donors; donation rates; living; donors; OPOs; organ donation; organ procurement; SRTR ID UNITED-STATES; DONORS; TRANSPLANTATION AB The processes leading to donor identification, consent, organ procurement, and allocation continue to dominate debates and efforts in the field of transplantation. A considerable shortage of donors remains while the number of patients needing organ transplantation increases. This article reviews the main trends in organ donation practices and procurement patterns from both deceased and living sources in the USA. Although there have been increases in living donation in recent years, 2002 witnessed a much more modest growth of 1%. Absolute declines in living liver and lung donation were also noted in 2002. In 2002, the number of deceased donors increased by only 1.6% (101 donors). Increased donation from deceased donors provides more organs for transplantation than a comparable increase in living donation, because on average 3.6 organs are recovered from each deceased donor. The total number of organs recovered from deceased donors increased by 2.1% (462 organs). Poor organ quality continued to be the major reason given for nonrecovery of consented organs from deceased donors. The kidney is the organ most likely to be discarded after recovery. Over the past decade the discard rate of recovered kidneys has increased from 6% to 11%. Many of these are expanded criteria donor kidneys. C1 Univ Michigan, Sci Registry Transplant Recipients, Ann Arbor, MI 48109 USA. LifeLink Fdn, Tampa, FL USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Renal Res & Educ Assoc, Sci Registry Transplant Recipients, Ann Arbor, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. TransLife Florida Hosp Med Ctr, Orlando, FL USA. RP Ojo, AO (reprint author), Univ Michigan, Sci Registry Transplant Recipients, Ann Arbor, MI 48109 USA. EM aojo@umich.edu NR 20 TC 45 Z9 49 U1 0 U2 5 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. PY 2004 VL 4 SU 9 BP 27 EP 37 DI 10.1111/j.1600-6135.2004.00396.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 837ZP UT WOS:000222680500004 PM 15113353 ER PT J AU Takeuchi, Y Ito, H Kurtz, J Wekerle, T Ho, L Sykes, M AF Takeuchi, Y Ito, H Kurtz, J Wekerle, T Ho, L Sykes, M TI Earlier low-dose TBI or DST overcomes CD8(+) T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE bone marrow transplantation; costimulatory blockades; donor-specific transfusion; evaluation; mixed chimerism; tolerance ID VERSUS-HOST DISEASE; DONOR-SPECIFIC TOLERANCE; TOTAL-BODY IRRADIATION; BONE-MARROW; CD40 LIGAND; TRANSPLANTATION TOLERANCE; ALLOGRAFT-REJECTION; MONOCLONAL-ANTIBODY; MIXED CHIMERISM; CUTTING EDGE AB Treatment with a single injection of anti- CD40L (CD154) monoclonal antibody (mAb) and fully mismatched allogeneic bone marrow transplant (BMT) allows rapid tolerization of CD4 (+) T cells to the donor. The addition of in vivo CD8 T- cell depletion leads to permanent mixed hematopoietic chimerism and tolerance. We now describe two approaches that obviate the requirement for CD8 T- cell depletion by rapidly tolerizing recipient CD8 T cells in addition to CD4 cells. Administration of donor- specific transfusion (DST) to mice receiving 3 Gy total body irradiation (TBI), BMT and anti- CD40L mAb on day 0 uniformly led to permanent mixed chimerism and tolerance, compared with only 40% of mice receiving similar treatment without DST. In the absence of DST, moving the timing of 3 Gy TBI to day -1 or day -2 instead of day 0 led to rapid (by 2 weeks) induction of CD8(+) cell tolerance, and also permitted uniform achievement of permanent mixed chimerism and donor- specific tolerance in recipients of anti- CD40L and BMT on day 0. These nontoxic regimens overcome CD8(+) and CD4(+) T- cell- mediated alloresistance without requiring host T- cell depletion, permitting the induction of permanent mixed chimerism and tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Univ Vienna, Vienna Gen Hosp, Dept Surg, Div Transplantat, Vienna, Austria. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02114 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL 49915] NR 50 TC 49 Z9 50 U1 0 U2 0 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 JAN PY 2004 VL 4 IS 1 BP 31 EP 40 DI 10.1046/j.1600-6135.2003.00272.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 753QU UT WOS:000187242700007 PM 14678032 ER PT J AU Menard, MT Schwarze, ML Allan, JS Johnston, DR Mawulawde, K Shimizu, A Yamada, K Houser, SL Allison, KS Sachs, DH Madsen, JC AF Menard, MT Schwarze, ML Allan, JS Johnston, DR Mawulawde, K Shimizu, A Yamada, K Houser, SL Allison, KS Sachs, DH Madsen, JC TI Composite 'thymoheart' transplantation improves cardiac allograft survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE heart; swine; thymus; tolerance; transplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; THYMIC TRANSPLANTATION; T-CELLS; TOLERANCE INDUCTION; DENDRITIC CELLS; VASCULOPATHY; HEART; EPITHELIUM; COTRANSPLANTATION AB We have generated a novel composite organ, the thymoheart, which facilitates the contemporaneous transfer of fully vascularized and functional donor thymic tissue to the host at the time of cardiac transplantation. Composite thymoheart allografts were prepared in MHC- inbred miniature swine by implanting autologous thymic tissue into donor hearts 60- 90 days before organ procurement. Thymoheart allografts and unmanipulated control hearts were then transplanted into three groups, each treated with the same 12 days of cyclosporine. MHC- matched thymohearts transplanted into euthymic recipients had a minimum survival ranging between 72 and 194 days vs. 42- 64 days for unmanipulated control hearts (p = 0.02). MHC class I- disparate thymohearts transplanted into euthymic recipients had a minimum survival ranging between 64 and 191 days vs. 30- 55 days for unmanipulated control hearts (p = 0.01). MHC class I- disparate thymohearts transplanted into thymectomized recipients survived between 41 and 70 days vs. 8- 27 days for unmanipulated control hearts (p = 0.01). Cellular and humoral functional assays, and skin grafting, confirmed the presence of donor- specific hyporesponsiveness in long- term thymoheart allografts recipients. The transfer of vascularized, functional donor thymic tissue to the host at the time of cardiac transplantation may provide a novel approach to the induction of tolerance in human heart transplant recipients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL 18646, F32 HL 69645]; NIAID NIH HHS [P01 AI 50157] NR 30 TC 11 Z9 11 U1 0 U2 0 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 JAN PY 2004 VL 4 IS 1 BP 79 EP 86 DI 10.1046/j.1600-6143.2003.00295.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 753QU UT WOS:000187242700012 PM 14678037 ER PT J AU Guidinger, MK Sung, RS Lake, CD McBride, MA Greenstein, SM Delmonico, FL Port, FK Merion, RM Leichtman, AB AF Guidinger, MK Sung, RS Lake, CD McBride, MA Greenstein, SM Delmonico, FL Port, FK Merion, RM Leichtman, AB TI Initial experience with the Expanded Criteria Donor kidney allocation system: Impact on utilization. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 URREA, SRTR, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. UNOS, OPTN, Richmond, VA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 3 BP 160 EP 160 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500004 ER PT J AU Shinoda, M Tilles, AW Wakabayashi, G Kobayashi, N Berthiaume, F Shimazu, M Shimizu, N Tanaka, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML AF Shinoda, M Tilles, AW Wakabayashi, G Kobayashi, N Berthiaume, F Shimazu, M Shimizu, N Tanaka, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML TI Interleukin-1 receptor antagonist secreting hepatocytes for the treatment of fulminant hepatic failure. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Keio Univ, Sch Med, Tokyo 108, Japan. Okayama Univ, Grad Sch Med & Dent, Okayama 7008530, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 72 BP 178 EP 179 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500073 ER PT J AU Wong, WC Hirsch, HH Fujimoto, K Pascual, M Doran, MT Delvecchio, AM Cosimi, AB Tolkoff-Rubin, N AF Wong, WC Hirsch, HH Fujimoto, K Pascual, M Doran, MT Delvecchio, AM Cosimi, AB Tolkoff-Rubin, N TI Thymoglobulin induction therapy does not increase risk of BK virus replication in kidney transplant recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Univ Basel Hosp, Div Infect Dis, CH-4031 Basel, Switzerland. CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 141 BP 197 EP 197 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500142 ER PT J AU Kauffman, HM Cheng, Y Cherikh, WS McBride, MA Hanto, DW Delmonico, FL AF Kauffman, HM Cheng, Y Cherikh, WS McBride, MA Hanto, DW Delmonico, FL TI Recipient history of cancer is independently associated with increased post-transplant de novo malignancies and decreased survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 United Network Organ Sharing, Richmond, VA USA. Beth Israel Deaconess Med Ctr, Dept Transplantat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 171 BP 205 EP 205 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500172 ER PT J AU Tseng, YL Dor, FJMF Kuwaki, K Prabharasuth, D Alt, A Ryan, D Denaro, M Giovino, M Wood, J Yamada, K Hawley, R Awwad, M Patience, C Schuurman, HJ Sachs, DH Cooper, DKC AF Tseng, YL Dor, FJMF Kuwaki, K Prabharasuth, D Alt, A Ryan, D Denaro, M Giovino, M Wood, J Yamada, K Hawley, R Awwad, M Patience, C Schuurman, HJ Sachs, DH Cooper, DKC TI Transplantation of alpha 1,3-galactosyltransferase gene-knockout pig bone marrow in baboons. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, TBRC, Boston, MA 02114 USA. Immerge Biotherapeut, Cambridge, MA USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 313 BP 243 EP 243 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500313 ER PT J AU Shimizu, I Kawahara, Y Bardwell, PD Sykes, M AF Shimizu, I Kawahara, Y Bardwell, PD Sykes, M TI Critiacl role for CR2 in the mechanism of B cell tolerance to alpha Gal in GalT knockout mice via induction of mixed chimerism. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02114 USA. RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 319 BP 245 EP 245 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500319 ER PT J AU McBride, MA Delmonico, FL Kauffman, HM AF McBride, MA Delmonico, FL Kauffman, HM TI Risk factors for early mortality following deceased donor kidney transplant. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 United Network Organ Sharing, Res Dept, Richmond, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 438 BP 278 EP 278 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500438 ER PT J AU Shaffer, JM Kawai, T Fudaba, Y Cosimi, AB Saidman, S Preffer, F Dombkowski, D Delmonico, F McAfee, S Rubin-Tolkoff, N Dey, B Spitzer, TR Sachs, DH Sykes, M AF Shaffer, JM Kawai, T Fudaba, Y Cosimi, AB Saidman, S Preffer, F Dombkowski, D Delmonico, F McAfee, S Rubin-Tolkoff, N Dey, B Spitzer, TR Sachs, DH Sykes, M TI Mechanisms of donor-specific unresponsiveness in tolerant recipient of combined non-myeloablative HLA-mismatched bone marrow and kidney transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 526 BP 303 EP 303 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500526 ER PT J AU McDonald, RA Ashby, VB Rosendale, J Harmon, WE Williams, WW Sommers, CM Wolfe, RA Port, FK AF McDonald, RA Ashby, VB Rosendale, J Harmon, WE Williams, WW Sommers, CM Wolfe, RA Port, FK TI Impact of expanded criteria donor kidney transplantation on young minority patients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Childrens Hosp, Seattle, WA USA. Univ Michigan, Ann Arbor, MI 48109 USA. SRTR, URREA, Ann Arbor, MI USA. OPTN, UNOS, Richmond, VA USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 533 BP 304 EP 304 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500533 ER PT J AU Izawa, A Clarkson, MR Salama, AD Ueno, T Yagita, H Sharpe, AH Freeman, GJ Sayegh, MH Najafian, N AF Izawa, A Clarkson, MR Salama, AD Ueno, T Yagita, H Sharpe, AH Freeman, GJ Sayegh, MH Najafian, N TI Generation of regulatory CD8(+) T cells by ICOS-B7h signal blockade in vivo. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 538 BP 306 EP 306 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500538 ER PT J AU Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA AF Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA TI Time-dependent changes in gene expression in a rat cardiac transplant model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 546 BP 308 EP 308 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500546 ER PT J AU Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA AF Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA TI Gene expression profiles in a rat heart transplant model of acute cellular rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 545 BP 308 EP 308 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500545 ER PT J AU Nadazdin, O Wee, S Kawai, T Boskovic, S Koyama, I Winn, H Sachs, D Cosimi, AB AF Nadazdin, O Wee, S Kawai, T Boskovic, S Koyama, I Winn, H Sachs, D Cosimi, AB TI Lack of indirect alloreactivity is associated with renal allograft tolerance in a nonhuman primate model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 576 BP 316 EP 316 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500576 ER PT J AU Shoji, T Johnston, DR Hoerbelt, R Wain, JC Houser, SL Benjamin, LC Lee, RS Guenther, DA Muniappan, A Hasse, RS Ledgerwood, LG Bravard, MA Sayegh, MH Madsen, JC Allan, JS AF Shoji, T Johnston, DR Hoerbelt, R Wain, JC Houser, SL Benjamin, LC Lee, RS Guenther, DA Muniappan, A Hasse, RS Ledgerwood, LG Bravard, MA Sayegh, MH Madsen, JC Allan, JS TI Indirect allorecognition of MHC class I peptides accelerates pulmonary allograft rejection in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2004 VL 4 SU 8 MA 579 BP 316 EP 316 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500579 ER PT J AU Whiting, JF Delmonico, F Morrissey, P Basadonna, G Johnson, S Lewis, WD Rohrer, R O'Connor, K Bradley, J Lovewell, TD Lipkowitz, G AF Whiting, JF Delmonico, F Morrissey, P Basadonna, G Johnson, S Lewis, WD Rohrer, R O'Connor, K Bradley, J Lovewell, TD Lipkowitz, G TI Clinical results of a region-wide program to increase utilization of donors after cardiac death (DCD). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Maine Med Ctr, Portland, ME 04102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rhode Isl Hosp, Providence, RI 02903 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Lahey Clin Fdn, Burlington, MA USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. New England Organ Bank Inc, Newton, MA USA. Baystate Med Ctr, Springfield, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 594 BP 320 EP 320 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500594 ER PT J AU Koporc, Z Bigenzahn, S Blaha, P Wrba, F Muehlbacher, F Sykes, M Wekerle, T AF Koporc, Z Bigenzahn, S Blaha, P Wrba, F Muehlbacher, F Sykes, M Wekerle, T TI Mobilized peripheral blood stem cells show lower tolerogenic potential than bone marrow cells in recipients of costimulation blockade SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Vienna, Vienna Gen Hosp, Div Transplantat, A-1010 Vienna, Austria. Univ Vienna, Vienna Gen Hosp, Inst Clin Pathol, A-1010 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 610 BP 324 EP 324 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500610 ER PT J AU McBride, MA Delmonico, FL Kauffman, HM AF McBride, MA Delmonico, FL Kauffman, HM TI Risk factors for death on the kidney waiting list. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 United Network Organ Sharing, Res Dept, Richmond, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 608 BP 324 EP 324 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500608 ER PT J AU Forman, D Kang, ES Tian, CR Iacomini, J AF Forman, D Kang, ES Tian, CR Iacomini, J TI Peripheral CD4 T cell tolerance induced by gene therapy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 617 BP 326 EP 326 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500617 ER PT J AU Fehr, T Takeuchi, Y Kurtz, J Sykes, M AF Fehr, T Takeuchi, Y Kurtz, J Sykes, M TI Mechanisms of CD8(+) T cell tolerance after bone marrow transplantation with non-myeloablative conditioning using anti-CD40 ligand and day-1 TBI. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 622 BP 327 EP 327 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500622 ER PT J AU Hong, HZ Yamada, K Shimizu, A Kamano, C Arakawa, H Samelson-Jones, E Moran, S Sachs, DH Hertl, M AF Hong, HZ Yamada, K Shimizu, A Kamano, C Arakawa, H Samelson-Jones, E Moran, S Sachs, DH Hertl, M TI The role of host thymic function in the induction of tolerance across full MHC barriers by FK506 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 619 BP 327 EP 327 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500619 ER PT J AU Kaye, J Cretin, N Malkowski, D Iacomini, J AF Kaye, J Cretin, N Malkowski, D Iacomini, J TI Determining the developmental fate of B cells producing anti-alpha Gal antibodies using immunoglobulin knock-in mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 623 BP 328 EP 328 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500623 ER PT J AU Koyama, I Kawai, T Wee, SL Boskovic, S Nadazdin, O Smith, RN Sykes, M Colvin, RB Sachs, DH Cosimi, AB AF Koyama, I Kawai, T Wee, SL Boskovic, S Nadazdin, O Smith, RN Sykes, M Colvin, RB Sachs, DH Cosimi, AB TI Development of a mixed chimerism-tolerance inducing nonmyeloablative regimen relevant to cadaver donor transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 633 BP 330 EP 330 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500633 ER PT J AU Elias, N Hertl, M Kawai, T Ko, DSC Thiim, M Chung, RT Cosimi, AB AF Elias, N Hertl, M Kawai, T Ko, DSC Thiim, M Chung, RT Cosimi, AB TI Steroid-free immunosupression results in decreased HCV recurrence in liver transplant recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 731 BP 357 EP 357 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500730 ER PT J AU Soule, JL Olyaei, AJ Busch, AMH Schwartz, JM Rosen, HR Ham, JM Orloff, SL AF Soule, JL Olyaei, AJ Busch, AMH Schwartz, JM Rosen, HR Ham, JM Orloff, SL TI Vancomycin-resistant Enterococcus in liver transplant recipients: A dramatic improvement in outcomes with new anti-VRE antibiotics. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Oregon Hlth Sci Univ, Dept Surg, Div Transplantat, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Surg, Div Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Hepatol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 737 BP 358 EP 359 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500736 ER PT J AU Cagliero, E Chandraker, AK Dea, A Fritz, S Omer, K Pavlakis, M Weir, GC Auchincloss, H Nathan, DM AF Cagliero, E Chandraker, AK Dea, A Fritz, S Omer, K Pavlakis, M Weir, GC Auchincloss, H Nathan, DM TI Sirolimus and tacrolimus in preparation for islet cell transplantation in type 1 diabetic patients recipient of renal allografts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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. PY 2004 VL 4 SU 8 MA 805 BP 377 EP 377 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500804 ER PT J AU Mandal, AK Drew, N Tableman, M Lapidus, JA AF Mandal, AK Drew, N Tableman, M Lapidus, JA TI Transplantation of renal allografts from hepatitis C seropositive deceased donors into elderly hepatitis C seronegative recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Portland State Univ, Dept Math & Stat, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 874 BP 396 EP 396 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500873 ER PT J AU Port, FK Ashby, VB Leichtman, AB McBride, MA Wynn, JJ Williams, WW Roberts, JP Rush, SH Wolfe, RA AF Port, FK Ashby, VB Leichtman, AB McBride, MA Wynn, JJ Williams, WW Roberts, JP Rush, SH Wolfe, RA TI Eliminating points for HLA-B similarity increased kidney allocation to minority, pediatric, sensitized, and zero MM candidates. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 SRTR, URREA, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. OPTN, UNOS, Richmond, VA USA. Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA. Massachusetts Gen Hosp, Multicultural Affairs Off, Boston, MA 02114 USA. Univ Calif San Francisco, Liver & Kidney Transplant Serv, San Francisco, CA 94143 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 939 BP 414 EP 415 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500938 ER PT J AU Maki, T Ogawa, N List, JF Habener, JF AF Maki, T Ogawa, N List, JF Habener, JF TI Transient short course of polyclonal anti-T cell antibody for cure of full blown diabetes. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 998 BP 431 EP 431 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500996 ER PT J AU Tseng, YL Kuwaki, K Dor, FJMF Shimizu, A Houser, SL Sanderson, TM Lancos, CJ Prabharasuth, DD Yamada, K Hawley, R Patience, C Awwad, M Fishman, JA Robson, SC Sachs, DH Schuurman, HJ Cooper, DKC AF Tseng, YL Kuwaki, K Dor, FJMF Shimizu, A Houser, SL Sanderson, TM Lancos, CJ Prabharasuth, DD Yamada, K Hawley, R Patience, C Awwad, M Fishman, JA Robson, SC Sachs, DH Schuurman, HJ Cooper, DKC TI Transplantation (Tx) of hearts from alpha 1,3-galactosyl-transferase gene-knockout (GalT-KO) pigs into baboons SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, TBRC, Boston, MA 02114 USA. Immerge Biotherapeut, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA 02215 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 3 Z9 3 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1068 BP 450 EP 451 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501066 ER PT J AU Yamada, K Yazawa, K Shimizu, A Nuhn, M Moran, S Iwanaga, T O'Malley, P Vagefi, PA Fishman, J Cooper, DKC Patience, C Hawley, R Greenstein, J Schuurman, HJ Awwad, M Sykes, M Sachs, DH AF Yamada, K Yazawa, K Shimizu, A Nuhn, M Moran, S Iwanaga, T O'Malley, P Vagefi, PA Fishman, J Cooper, DKC Patience, C Hawley, R Greenstein, J Schuurman, HJ Awwad, M Sykes, M Sachs, DH TI Pig-to-baboon life-supporting kidney plus thymus transplantation using GalT-KO donors SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge BioTherapeut, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1067 BP 450 EP 450 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501065 ER PT J AU Yazawa, K Iwanaga, T Shimizu, A Nuhn, M Moran, S Nobori, S Vagefi, PA Cooper, DKC Hawley, R Schuurman, HJ Greenstein, J Sachs, DH Yamada, K AF Yazawa, K Iwanaga, T Shimizu, A Nuhn, M Moran, S Nobori, S Vagefi, PA Cooper, DKC Hawley, R Schuurman, HJ Greenstein, J Sachs, DH Yamada, K TI Use of GalT-KO donors avoids both hyperacute and accelerated humoral xenograft rejection following miniature swine-to-baboon renal transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge BioTherapeut, Cambridge, England. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1066 BP 450 EP 450 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501064 ER PT J AU Houser, SL Shimizu, A Kuwaki, K Dor, FJMF Tseng, YL Knosalla, C Cheng, J Schuurman, HJ Sachs, DH Cooper, DKC AF Houser, SL Shimizu, A Kuwaki, K Dor, FJMF Tseng, YL Knosalla, C Cheng, J Schuurman, HJ Sachs, DH Cooper, DKC TI Thrombotic microangiopathy in HDAF and GalT-knockout pig hearts following transplantation into baboons SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 5th American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplant C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge Biotherapeut, Cambridge, MA USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1069 BP 451 EP 451 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501067 ER PT J AU Shimizu, A Yamada, K Yazawa, K Cheng, J Robson, SC Schuurman, HJ Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Yazawa, K Cheng, J Robson, SC Schuurman, HJ Sachs, DH Colvin, RB TI Injury of kidney xenografts from alpha 1,3-galactosyl-transferase gene-knockout (GalT-KO) pigs into baboons is characterized by glomerular thrombotic microangiopathy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge BioTherapeut, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1094 BP 458 EP 458 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501092 ER PT J AU Dor, FJMF Doucette, KE Mueller, NJ Wilkinson, RA Bajwa, JA McMorrow, IM Tseng, YL Kuwaki, K Houser, SL Sachs, DH Fishman, JA Huang, CA Cooper, DKC AF Dor, FJMF Doucette, KE Mueller, NJ Wilkinson, RA Bajwa, JA McMorrow, IM Tseng, YL Kuwaki, K Houser, SL Sachs, DH Fishman, JA Huang, CA Cooper, DKC TI Post-transplant lymhpoproliferative disease after allogeneic spleen transplantation in miniature swine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RI Dor, Frank/E-1032-2013; Mueller, Nicolas/B-6864-2013 OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1110 BP 462 EP 462 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501108 ER PT J AU Bagley, J Iacomini, J AF Bagley, J Iacomini, J TI Hematopoietic stem cell transplantation prevents lymphoma in Atm deficient mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1122 BP 465 EP 465 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501120 ER PT J AU Ansari, MJI Khosroshahi, A Guleria, I Yagita, H Auchincloss, H Sayegh, MH AF Ansari, MJI Khosroshahi, A Guleria, I Yagita, H Auchincloss, H Sayegh, MH TI Marked prolongation of islet allograft survival in NOD mice with high dose rapamycin and CD154 plus ICOSL blockade. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Juntendo Univ, Tokyo, Japan. Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1131 BP 467 EP 467 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501129 ER PT J AU Nuhn, M Samelson-Jones, E Kamano, C Tchipashvili, V Yazawa, K Nobori, S Vagefi, PA Sachs, DH Yamada, K AF Nuhn, M Samelson-Jones, E Kamano, C Tchipashvili, V Yazawa, K Nobori, S Vagefi, PA Sachs, DH Yamada, K TI Islet-kidney transplantation: Determining the minimum number of islet equivalents needed to cure diabetes in inbred miniature swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1134 BP 468 EP 468 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501132 ER PT J AU Kawai, T Sachs, DH Spitzer, T Sykes, M Tolkoff-Rubin, N Delmonico, F Saidman, S Shaffer, J Dey, B McAfee, S Williams, W Ko, D Hertl, M Goes, N Wong, WC Colvin, RB Cosimi, AB AF Kawai, T Sachs, DH Spitzer, T Sykes, M Tolkoff-Rubin, N Delmonico, F Saidman, S Shaffer, J Dey, B McAfee, S Williams, W Ko, D Hertl, M Goes, N Wong, WC Colvin, RB Cosimi, AB TI Combined kidney and bone marrow transplantation for induction of mixed chimerism and renal allograft tolerance in HLA mismatched transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1217 BP 491 EP 491 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501214 ER PT J AU Bagley, J Iacomini, J AF Bagley, J Iacomini, J TI Hematopoietic stem cell transplantation restores immune system function in Atm deficient mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1278 BP 508 EP 508 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501274 ER PT J AU El Essawy, B Otu, HH Manuel, A Kim, YS Libermann, T Strom, T AF El Essawy, B Otu, HH Manuel, A Kim, YS Libermann, T Strom, T TI Proteomic analysis of the allograft response SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Inst Med, BIDMC Genom Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1294 BP 512 EP 512 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501290 ER PT J AU Shapiro, J Ricordi, C Hering, B DiMercurio, B Lindblad, R Cagliero, E Brendel, M Robertson, P Berney, T Secchi, A Brennan, D Ramos, E Viviano, L Ryan, E Close, N Lakey, J AF Shapiro, J Ricordi, C Hering, B DiMercurio, B Lindblad, R Cagliero, E Brendel, M Robertson, P Berney, T Secchi, A Brennan, D Ramos, E Viviano, L Ryan, E Close, N Lakey, J TI International multicenter trial of islet transplantation using the Edmonton Protocol in patients with Type 1 diabetes SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Alberta, Edmonton, AB T6G 2M7, Canada. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Miami, Miami, FL 33152 USA. NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Giessen, D-35390 Giessen, Germany. Pacific NW Res Inst, Seattle, WA USA. Univ Geneva, CH-1211 Geneva 4, Switzerland. Univ Milan, I-20122 Milan, Italy. Washington Univ, St Louis, MO 63130 USA. Immune Tolerance Network, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1434 BP 552 EP 552 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501430 ER PT J AU Yamashita, K McDaid, J Ollinger, R Wang, HJ Csizmadia, E Smith, RN Soares, MP Bach, FH AF Yamashita, K McDaid, J Ollinger, R Wang, HJ Csizmadia, E Smith, RN Soares, MP Bach, FH TI Induced heme oxygenase-1 plus donor specific transfusion yields antigen specific tolerance mediated by regulatory CD4(+)CD25(+) T cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Immunobiol Res Ctr, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RI Ollinger, Robert/D-1538-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2004 VL 4 SU 8 MA 1447 BP 555 EP 555 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501443 ER PT J AU Tian, CR Bagley, J Forman, D Sachs, DH Iacomini, J AF Tian, CR Bagley, J Forman, D Sachs, DH Iacomini, J TI Prevent Type I diabetes in NOD mice by gene therapy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1536 BP 580 EP 580 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501532 ER PT J AU Vagefi, PA Kamano, C Yamamoto, S Teranishi, K Houser, SL Madsen, JC Samelson-Jones, E Shimizu, A Sachs, DH Yamada, K AF Vagefi, PA Kamano, C Yamamoto, S Teranishi, K Houser, SL Madsen, JC Samelson-Jones, E Shimizu, A Sachs, DH Yamada, K TI Long-term acceptance of heterotopic cardiac allografts by co-transplantation of vascularized thymic lobes in fully MHC-mismatched miniature swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1541 BP 581 EP 581 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501537 ER PT J AU Chandraker, A Ali, S Drachenberg, CB Wali, R Hirsch, H DeCaprio, J Ramos, E AF Chandraker, A Ali, S Drachenberg, CB Wali, R Hirsch, H DeCaprio, J Ramos, E TI Use of fluoroquinolones to treat BK infection in renal transplant recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Basel, Dept Internal Med, CH-4003 Basel, Switzerland. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 21 Z9 22 U1 1 U2 1 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. PY 2004 VL 4 SU 8 MA 1564 BP 587 EP 587 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501560 ER PT J AU Delmonico, FL McGowan, J Ojo, A AF Delmonico, FL McGowan, J Ojo, A TI Comparative outcomes of unrelated live donor and ideal deceased donor kidney transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Univ Renal Res & Educ Res Assoc, Sci Registry Transplant Recipients, Ann Arbor, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1586 BP 593 EP 593 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501582 ER PT J AU Dor, FJMF Tseng, YL Cheng, J Moran, K Sanderson, TM Lancos, CJ Shimizu, A Awwad, M Sachs, DH Schuurman, HJ Hawley, R Cooper, DKC AF Dor, FJMF Tseng, YL Cheng, J Moran, K Sanderson, TM Lancos, CJ Shimizu, A Awwad, M Sachs, DH Schuurman, HJ Hawley, R Cooper, DKC TI Pigs lacking the alpha-1,3galactosyltraxsferase gene develop anti-Gal antibodies that are cytotoxic to wild-type (Gal(+/+)) MHC-matched pig cells: A potential model to study accommodation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge Biotherapeut, Cambridge, MA USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1605 BP 599 EP 599 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501601 ER PT J AU Boskovic, S Kawai, T Andrews, D Koyama, I Nadazdin, O Colvin, RB Sachs, DH Cosimi, AB AF Boskovic, S Kawai, T Andrews, D Koyama, I Nadazdin, O Colvin, RB Sachs, DH Cosimi, AB TI Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its prophylaxis in nonhuman primates. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Univ Miami, Dept Blood Transfus, Miami, FL 33152 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2004 VL 4 SU 8 MA 1609 BP 600 EP 600 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501605 ER PT J AU Ueno, T Najafian, N Yamada, A Glimcher, LH Sayegh, MH Auchincloss, H AF Ueno, T Najafian, N Yamada, A Glimcher, LH Sayegh, MH Auchincloss, H TI Role of NFAT transcription factors in skin and vascularized cardiac allograft rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 4 SU 8 MA 1608 BP 600 EP 600 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501604 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Bridge, P Mintz, J AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Bridge, P Mintz, J TI Cortical gray matter volumes are associated with subjective responses to cocaine infusion SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MAGNETIC-RESONANCE; BRAIN MORPHOLOGY; IN-VIVO; AGE; ABUSERS; LOBE; ADDICTS; MRI; ABNORMALITIES; HIPPOCAMPUS AB We analyzed the relationship between cocaine-induced euphoria and measures of frontal and temporal gray matter volumes in eleven cocaine-dependent (CD) patients who underwent magnetic resonance imaging (MRI). Self-reported ratings of the intensity of euphoric response to cocaine infusion were obtained from the CD subjects at 3, 10, and 30 minutes after cocaine infusion. Significant positive correlation between frontal and temporal cortical gray matter volume and the intensity of euphoria was observed at 10 minutes after IV cocaine. The data suggest that frontal and temporal lobe gray matter volume is associated with some of the reinforcing effects of cocaine. Given the well-established negative linear relationship between cortical gray matter volume and age, cortical gray matter volume may be a marker for the neurobiological substrate of the age-related reduction in addiction rates. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. NIDA, Medicat Dev Div, Rockville, MD USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 NR 30 TC 13 Z9 16 U1 1 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2004 VL 13 IS 1 BP 64 EP 73 DI 10.1080/10550490490265352 PG 10 WC Substance Abuse SC Substance Abuse GA 771EH UT WOS:000188772300006 PM 14766439 ER PT J AU Kampman, KM Pettinati, HM Volpicelli, JR Oslin, DM Lipkin, C Sparkman, T O'Brien, CP AF Kampman, KM Pettinati, HM Volpicelli, JR Oslin, DM Lipkin, C Sparkman, T O'Brien, CP TI Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID TREATMENT ATTRITION; WITHDRAWAL; DISORDERS; ABUSE AB This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity. C1 Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman_k@mail.trc.upenn.edu FU NIDA NIH HHS [P60 DA 051186] NR 20 TC 28 Z9 28 U1 2 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2004 VL 13 IS 1 BP 74 EP 82 DI 10.1080/10550490490265389 PG 9 WC Substance Abuse SC Substance Abuse GA 771EH UT WOS:000188772300007 PM 14766440 ER PT J AU Kier, FJ Davenport, DS AF Kier, FJ Davenport, DS TI Unaddressed problems in the study of spirituality and health SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material ID RELIGION C1 VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Texas A&M Univ, College Stn, TX 77843 USA. RP Kier, FJ (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div, Behav Hlth 116 A-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM frederick.kier@med.va.gov NR 8 TC 10 Z9 10 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2004 VL 59 IS 1 BP 53 EP 54 DI 10.1037/0003.066X.59.1.53 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 765LP UT WOS:000188285300016 PM 14736330 ER PT J AU Williams, JH Hepner, DL AF Williams, JH Hepner, DL TI Risperidone and exaggerated hypotension during a spinal anesthetic SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANTIPSYCHOTIC AGENTS; DRUGS AB Antipsychotic medications are often continued through pregnancy and may have important anesthetic interactions. For example, risperidone is an antipsychotic medication with therapeutic effects mediated by dopaminergic and serotonergic antagonism. However, it also possesses potent alpha-1 adrenergic antagonism. Here we report a case of a parturient with bipolar disease, controlled with lithium. and risperidone, undergoing a spinal anesthetic for a cesarean delivery. The parturient developed exaggerated hypotension, refractory to conventional treatment with ephedrine and IV fluids, that eventually responded to large doses of phenylephrine. Risperidone a-antagonism should be a consideration for any patient receiving this medication during neuraxial anesthesia. Treatment of significant and refractory hypotension with an alpha-1 agonist such as phenylephrine may be warranted. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Hepner, DL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 8 Z9 8 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 JAN PY 2004 VL 98 IS 1 BP 240 EP 241 DI 10.1213/01.ANE.0000094335.82824.F3 PG 2 WC Anesthesiology SC Anesthesiology GA 757KK UT WOS:000187561400056 PM 14693627 ER PT J AU Schumacher, SD Brockwell, RC Andrews, J Ogles, D AF Schumacher, SD Brockwell, RC Andrews, J Ogles, D TI Bulk liquid oxygen supply failure SO ANESTHESIOLOGY LA English DT Article C1 Univ Alabama, Sch Med, Dept Anesthesiol, Birmingham, AL 35249 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama Hosp & Clin, Dept Bldg & Engn Serv, Birmingham, AL USA. RP Brockwell, RC (reprint author), Univ Alabama, Sch Med, Dept Anesthesiol, 619 S 19th St,Jefferson Tower 964, Birmingham, AL 35249 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2004 VL 100 IS 1 BP 186 EP 189 DI 10.1097/00000542-200401000-00032 PG 4 WC Anesthesiology SC Anesthesiology GA 758FN UT WOS:000187623200030 PM 14695744 ER PT J AU Tsourkas, A Hofstetter, O Hofstetter, H Weissleder, R Josephson, L AF Tsourkas, A Hofstetter, O Hofstetter, H Weissleder, R Josephson, L TI Magnetic relaxation switch immunosensors detect enantiomeric impurities SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE enantiomers; immunoassays; NMR spectroscopy; sensors; sterectselectivity ID ENANTIOSELECTIVE CATALYSTS; CHIRAL DRUGS; ANTIBODIES; SAMPLES; SENSORS; EXCESS; PROBES; NMR C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Boston, MA 02129 USA. EM josephso@helix.mgh.harvard.edu RI Tsourkas, Andrew/A-1074-2007 OI Tsourkas, Andrew/0000-0001-7758-1753 FU NCI NIH HHS [T32CA79443, P50CA86355, R24CA92782] NR 40 TC 77 Z9 80 U1 1 U2 22 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2004 VL 43 IS 18 BP 2395 EP 2399 DI 10.1002/anie.200352998 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 819HY UT WOS:000221307200011 PM 15114571 ER PT J AU TePas, EC Hoyte, EG McIntire, JJ Umetsu, DT AF TePas, EC Hoyte, EG McIntire, JJ Umetsu, DT TI Clinical efficacy of microencapsulated Timothy grass pollen extract in grass-allergic individuals SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SHORT RAGWEED EXTRACT; ORAL TOLERANCE; DOUBLE-BLIND; AUTOIMMUNE-DISEASES; SUBLINGUAL IMMUNOTHERAPY; INTERLEUKIN-4 PRODUCTION; IMMUNOLOGICAL CHANGES; DENDRITIC CELLS; T-CELLS AB Background: Conventional allergen immunotherapy is clinically effective in reducing the symptoms of allergic rhinitis and asthma. It differs from other pharmacotherapies in that it can induce long-term clinical remission of these diseases. However, it requires years of treatment and is associated with serious allergic reactions. Objective: To evaluate the safety, clinical efficacy, and immunologic mechanisms of immunotherapy with an oral, microencapsulated form of timothy grass allergen. Methods: In this double-blind, placebo-controlled study, 24 patients aged 19 to 55 years with grass pollen allergy were randomized to receive either microencapsulated timothy grass pollen extract or placebo once a day for 10 weeks. The dose of study drug was doubled weekly. Safety was evaluated through weekly visits, daily symptom diaries, and routine laboratory tests. Efficacy was evaluated by comparing medication use and symptoms scores during peak grass pollen season before and after treatment. Allergen-specific T-cell responses, cytokine production, and IgG, IgE, and skin reactivity were measured to evaluate immunologic mechanisms. Results: Eleven of 12 patients in the active treatment group had a decrease in the combined medication and symptom score, but only 4 of 10 patients in the placebo group had a decrease in scores. The proliferative response to timothy grass was reduced by at least 30% in 9 of the 12 grass-treated patients, but only 3 of 11 placebo patients had a proliferative response reduction. Timothy grass-induced interieukin-5 messenger RNA was reduced in the active group, but not in the placebo group. There were no significant changes in either group in IgG, IgE, and skin reactivity. Conclusions: Oral immunotherapy with microencapsulated allergen induces a(.)form of immunologic tolerance to the allergen and is a safe, efficient, and effective method of allergen immunotherapy. C1 Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. RP TePas, EC (reprint author), Massachusetts Gen Hosp, 15 Parkman St ACC 712, Boston, MA 02114 USA. EM etepas@partners.org RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 NR 38 TC 25 Z9 26 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JAN PY 2004 VL 92 IS 1 BP 25 EP 31 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 766VY UT WOS:000188397100007 PM 14756461 ER PT J AU Meinel, L Karageorgiou, V Fajardo, R Snyder, B Shinde-Patil, V Zichner, L Kaplan, D Langer, R Vunjak-Novakovic, G AF Meinel, L Karageorgiou, V Fajardo, R Snyder, B Shinde-Patil, V Zichner, L Kaplan, D Langer, R Vunjak-Novakovic, G TI Bone tissue engineering using human mesenchymal stem cells: Effects of scaffold material and medium flow SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE collagen; silk; scaffold; flow; bioreactor; mu-computerized tomography ID OSTEOBLAST-LIKE CELLS; IN-VITRO; FLUID-FLOW; TRABECULAR BONE; STROMAL CELLS; MARROW; CULTURE; EXPRESSION; MOUSE; DIFFERENTIATION AB We report studies of bone tissue engineering using human mesenchymal stem cells (MSCs), a protein substrate (film or scaffold; fast degrading unmodified collagen, or slowly degrading cross-linked collagen and silk), and a bioreactor (static culture, spinner flask, or perfused cartridge). MSCs were isolated from human bone marrow, characterized for the expression of cell surface markers and the ability to undergo chondrogenesis and osteogenesis in vitro, and cultured for 5 weeks. MSCs were positive for CD105/endoglin, and had a potential for chondrogenic and osteogenic differentiation. In static culture, calcium deposition was similar for MSC grown on collagen scaffolds and films. Under medium flow, MSC on collagen scaffolds deposited more calcium and had a higher alcaline phosphatase (AP) activity than MSC on collagen films. The amounts of DNA were markedly higher in constructs based on slowly degrading (modified collagen and silk) scaffolds than on fast degrading (unmodified collagen) scaffolds. In spinner flasks, medium flow around constructs resulted in the formation of bone rods within the peripheral region, that were interconnected and perpendicular to the construct surface, whereas in perfused constructs, individual bone rods oriented in the direction of fluid flow formed throughout the construct volume. These results suggest that osteogenesis in cultured MSC can be modulated by scaffold properties and flow environment. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Frankfurt, Dept Orthopaed, D-6000 Frankfurt, Germany. Tufts Univ, Dept Chem & Biol Engn, Medford, MA 02155 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA USA. RP Vunjak-Novakovic, G (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, MIT E25-330,45 Carleton St, Cambridge, MA 02139 USA. EM gordana@mit.edu RI Meinel, Lorenz/D-9997-2015; OI Meinel, Lorenz/0000-0002-7549-7627; Karageorgiou, Vassilis/0000-0002-0892-510X; Vunjak-Novakovic, Gordana/0000-0002-9382-1574 NR 53 TC 336 Z9 355 U1 10 U2 76 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JAN PY 2004 VL 32 IS 1 BP 112 EP 122 DI 10.1023/B:ABME.0000007796.48329.b4 PG 11 WC Engineering, Biomedical SC Engineering GA 771PA UT WOS:000188794100012 PM 14964727 ER PT J AU Richardson, PG Hideshima, T Mitsiades, C Anderson, K AF Richardson, PG Hideshima, T Mitsiades, C Anderson, K TI Proteasome inhibition in hematologic malignancies SO ANNALS OF MEDICINE LA English DT Article DE bortezomib; combined modality therapy; dexamethasone; doxorubicin; leukemia; lymphoma; non-Hodgkin; melphalan; multiple myeloma; proteasome inhibition; thalidomide ID MULTIPLE-MYELOMA CELLS; OVERCOMES DRUG-RESISTANCE; FACTOR-KAPPA-B; PHASE-I TRIAL; THERAPEUTIC APPLICATIONS; GENE-EXPRESSION; PS-341; APOPTOSIS; GROWTH; CANCER AB Hematologic malignancies, including multiple myeloma (MM), will account for more than 100,000 new cases of cancer and over 57,000 deaths in the United States in 2003. Treatment of MM is a serious challenge, because despite a variety of available therapies, median survival is short. A new therapeutic area focuses on inhibiting the activity of the proteasome, a 26S protease complex involved in cell cycle regulation, cell adhesion, inflammation, and protein turnover. The novel proteasome inhibitor, bortezomib (Velcade(R)), was recently approved for use in patients with refractory and relapsed MM and to date is the only proteasome inhibitor to have entered clinical trials. Bortezomib has demonstrated activity with manageable toxicity in a variety of hematologic malignancies in addition to MM. including leukemia and non-Hodgkin's lymphoma. This article reviews clinical information on bortezomib in hematologic malignancies both as monotherapy and in combination with dexamethasone. Preliminary reports of bortezomib in combination with Doxil (pegylated liposomal doxorubicin), melphalan, and thalidomide are discussed, and current trials are described. Available data suggest that bortezomib will be useful in the treatment of a variety of hematologic malignancies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM Paul_Richardson@dfci.harvard.edu NR 43 TC 40 Z9 43 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2004 VL 36 IS 4 BP 304 EP 314 DI 10.1080/07853890410030877 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 828GC UT WOS:000221960800008 PM 15224657 ER PT J AU Burstein, H Storniolo, AM Franco, S Salazar, VM Sorensen, MJ Stein, SH AF Burstein, Harold Storniolo, Anna Marie Franco, Sandro Salazar, Vanessa M. Sorensen, Mel J. Stein, Stven H. TI A phase II, open-label, multicenter study of lapatinib in two cohorts of patients with advanced or metastatic breast cancer who have progressed while receiving trastuzumab-containing regimens SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Burstein, Harold] Dana Farber Canc Inst, Boston, MA 02115 USA. [Storniolo, Anna Marie] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Franco, Sandro] Canc Res Network Inc, Oncol, Plantation, FL USA. [Salazar, Vanessa M.; Sorensen, Mel J.; Stein, Stven H.] GSK, Oncol, Collegeville, PA USA. NR 0 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 27 EP 28 PG 3 WC Oncology SC Oncology GA V14FS UT WOS:000207720900105 ER PT J AU Enzinger, PC Earle, C Zhu, A Blaskowsky, L Kulke, M Ryan, D Langford, L Michelini, A Meyerhardt, J AF Enzinger, Peter C. Earle, Craig Zhu, Andrew Blaskowsky, Lawrence Kulke, Matthew Ryan, David Langford, Lauren Michelini, Ann Meyerhardt, Jeffrey TI Phase I dose-finding and pharmacologic study of cisplatin (P), irinotecan (C), and either capecitabine (X) or infusional 5-FU (F) in patients (pts) with advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Enzinger, Peter C.; Earle, Craig; Zhu, Andrew; Blaskowsky, Lawrence; Kulke, Matthew; Ryan, David; Langford, Lauren; Michelini, Ann; Meyerhardt, Jeffrey] Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 106 EP 106 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900396 ER PT J AU Johnson, BE Lucca, J Rabin, MS Lynch, TJ Ostier, P Skarin, AT Temel, J Liu, G Janne, PA AF Johnson, Bruce E. Lucca, Joan Rabin, Michael S. Lynch, Thomas J. Ostier, Patricia Skarin, Arthur T. Temel, Jennifer Liu, Geoffrey Jaenne, Pasi A. TI A phase II trial of eriotinib in previously untreated elderly patients (>= 70 yrs) with advanced NSCLC: Preliminary results SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Johnson, Bruce E.; Rabin, Michael S.; Skarin, Arthur T.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lynch, Thomas J.; Ostier, Patricia; Temel, Jennifer; Liu, Geoffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 169 EP 169 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900640 ER PT J AU Fanucchi, M Belt, R Fossella, F Natale, R Robert, F Fidias, P Kelly, K Kashala, O Schenkein, D Schiller, J AF Fanucchi, Michael Belt, Robert Fossella, Frank Natale, Ronald Robert, Francisco Fidias, Panos Kelly, Karen Kashala, Oscar Schenkein, David Schiller, Joan TI Bortezomib +/- docetaxel in previously treated advanced non-small cell lung cancer: Interim analysis of a phase 2 study SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Fanucchi, Michael] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Belt, Robert] Kansas City Oncol Hematol Grp, Kansas City, MO USA. [Fossella, Frank] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Natale, Ronald] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. [Robert, Francisco] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Fidias, Panos] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, Karen] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Kashala, Oscar; Schenkein, David] Millennium Pharmaceut Inc, Cambridge, MA USA. [Schiller, Joan] Univ Wisconsin, Ctr Canc, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 170 EP 170 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900643 ER PT J AU Finketstein, SN Huse, DM Glendenning, GA Blanke, CD Joensuu, H von Mehren, M Demetri, GD AF Finketstein, Stan N. Huse, Daniel M. Glendenning, G. A. Blanke, Charles D. Joensuu, Heikki von Mehren, Margaret Demetri, George D. TI Imatinib: Cost-effective in the treatment of gastrointestinal stromal tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Finketstein, Stan N.] Harvard Mit Div Hlth Sci & Technol, MIT Sloan Sch Management, Cambridge, MA USA. [Huse, Daniel M.] Thomson Medstat, Market Scan Studies, Cambridge, MA USA. [Glendenning, G. A.] Novartis Pharmaceut, Florham Pk, NJ USA. [Blanke, Charles D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Blanke, Charles D.] Portland Vet Med Ctr, Dept Oncol, Portland, OR USA. [Joensuu, Heikki] Univ Helsinki, Dept Oncol, Helsinki, Finland. [von Mehren, Margaret] Fox Chase Canc Ctr, Dept Oncol, Philadelphia, PA 19111 USA. [Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 201 EP 201 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900763 ER PT J AU Demetri, G von Mehren, M Joensuu, H Finketstein, S Huse, D Kiese, B McDougali, K Dimitrijevic, S Glendenning, GA Blanke, C AF Demetri, George von Mehren, Margaret Joensuu, Heikki Finketstein, Stan Huse, Daniel Kiese, Beate McDougali, Karen Dimitrijevic, Sasa Glendenning, G. A. Blanke, Charles TI Lack of progression is the most clinically significant measure of a patients's clinical benefit: Correlating the effects of imatinib mesylate therapy in gastrointestinal stromal tumor (GIST) with survival benefits SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Demetri, George] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Dept Oncol, Philadelphia, PA 19111 USA. [Joensuu, Heikki] Univ Helsinki, Dept Oncol, Helsinki, Finland. [Finketstein, Stan] Harvard Mit Div Hlth Sci & Technol, MIT Sloan Sch Management, Cambridge, MA USA. [Huse, Daniel] Thomson Medstat, Market Scan Studies, Cambridge, MA USA. [Kiese, Beate; McDougali, Karen; Dimitrijevic, Sasa] Novartis Pharmaceut, Basel, Switzerland. [Glendenning, G. A.] Novartis Pharmaceut, Florham Pk, NJ USA. [Blanke, Charles] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Blanke, Charles] Portland Vet Med Ctr, Dept Oncol, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 202 EP 202 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900765 ER PT J AU Zeitels, SM Burns, JA Dailey, SH AF Zeitels, SM Burns, JA Dailey, SH TI Suspension laryngoscopy revisited SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 02-03, 2003 CL NASHVILLE, TENNESSEE SP Amer Broncho Esophagol Assoc DE dysphoma; glottis; hoarseness; laryngoscope; laryngoscopy; microlaryngoscopy; phonomicrosurgery; phonosurgery; vocal cord; vocal fold ID CLINICAL EXPERIENCE; LASER SURGERY; CO2-LASER; POSITION; EXPOSURE AB Every critical advancement in direct laryngoscopic surgical technique has enhanced its precision. Among the most notable was Killian's seminal description of suspension laryngoscopy 90 years ago, which allowed for bimanual direct laryngoscopic surgery. Because of the technical difficulties encountered while performing suspension laryngoscopy, Brunings and Seiffert designed fulcrum laryngoscope holder-stabilizers for spatula laryngoscopes from Killian's original instrument design. Their devices, which were easier to use and better tolerated by patients, were supported from the laryngeal cartilage framework or chest wall. Laryngoscope holder-stabilizers were retrofitted to tubular laryngoscope specula in the 1940s and 1950s, whereupon they became very popular. Suspension laryngoscopy should have become more common subsequent to the introduction of general endotracheal anesthesia with paralysis in the 1960s. However, laryngoscope holder-stabilizers were entrenched as the device preferred by most, and they remain so today. This entrenchment occurred despite the fact that suspension laryngoscopy allows for positioning a larger examining speculum , which in turn allows for enhanced exposure and endolaryngeal procedural precision. The applied vector forces on the mandible, maxilla, oral cavity, pharynx, and larynx associated with suspension laryngoscopy are preferable to those associated with holder-stabilizers. A prospective assessment of 120 cases revealed effective use of suspension laryngoscopy in all. We believe that only a minority of surgeons has actually seen true suspension laryngoscopy and that its merits are worthy of reexamination. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 44 TC 25 Z9 26 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2004 VL 113 IS 1 BP 16 EP 22 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 762TH UT WOS:000187997900004 PM 14763566 ER PT J AU Arpino, PA Hallisey, RK AF Arpino, PA Hallisey, RK TI Effect of renal function on the pharmacodynamics of argatroban SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE argatroban; heparin-induced thrombocytopenia; renal insufficiency ID HEPARIN-INDUCED THROMBOCYTOPENIA; VENOUS THROMBOEMBOLISM; SERUM CREATININE; FVIII-C; MANAGEMENT; PREDICTION; ELEVATION AB BACKGROUND: Argatroban is a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia (HIT). Argatroban is primarily cleared by hepatic mechanisms, with only small amounts of unchanged drug cleared by the kidneys. OBJECTIVE: To assess the effects of renal function on argatroban dose and activated partial thromboplastin time (aPTT). METHODS: Patients treated with argatroban were identified and prospectively screened. Patients with liver dysfunction were excluded from the analysis. Charts and laboratory data were reviewed daily until a therapeutic aPTT was reached or argatroban was discontinued. Data points collected included age, weight, gender, admitting diagnosis, past medical history, indication for anticoagulation, indication for argatroban, initial dose, goal aPTT, titration instructions, liver function tests, serum creatinine (S,,), blood urea nitrogen, and estimated creatinine clearance (Cl-cr). RESULTS: A total of 66 patients were evaluated and 44 met criteria for inclusion. Baseline S-cr was elevated at 1.5 mg/dL (0.9, 2.3; median 25th, 75th percentile), with an estimated Cl-cr 40 mL/min/1.73 m(2) (26, 74). The median dose of argatroban to reach the predefined therapeutic range was 1 mug/kg/min (0.68, 2), with a corresponding aPTT of 60 seconds (54, 66). After univariate analysis, Cl-cr significantly predicted the therapeutic dose (coefficient b +/- SE 0.019 +/- 0.004; r(2) 0.35; p < 0.001). Covariates that predicted dose were the presence of HIT (coefficient b +/- SE -0.61 +/- 0.3; p = 0.045), history of myocardial infarction (coefficient b +/- SE -0.74 +/- 0.3; p = 0.02), and an indication for anticoagulation of deep-vein thrombosis/pulmonary embolism (coefficient b +/- SE 0.69 +/- 0.3; p = 0.03). CONCLUSIONS: Estimated Cl-cr significantly predicted the dose of argatroban needed to reach a therapeutic aPTT. C1 Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP Arpino, PA (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 31 Z9 31 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2004 VL 38 IS 1 BP 25 EP 29 DI 10.1345/aph.1D163 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 757PE UT WOS:000187570000004 PM 14742788 ER PT J AU Holman, WL Sansom, M Kiefe, CI Peterson, ED Hubbard, SG Delong, DF Allman, RM AF Holman, WL Sansom, M Kiefe, CI Peterson, ED Hubbard, SG Delong, DF Allman, RM TI Alabama coronary artery bypass grafting project - Results from Phase II of a Statewide quality improvement initiative SO ANNALS OF SURGERY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; INTERNAL MAMMARY ARTERY; ACHIEVABLE BENCHMARKS; HOSPITAL MORTALITY; EARLY EXTUBATION; EARLY DISCHARGE; CABG SURGERY; MORBIDITY; OUTCOMES; LENGTH AB Objective/Background: This report describes the first round of results for Phase II of the Alabama CABG Project, a regional quality improvement initiative. Methods: Charts submitted by all hospitals in Alabama performing CABG (ICD-9 codes 36.10-36.20) were reviewed by a Clinical Data Abstraction Center (CDAC) (preintervention 1999-2000; postintervention 2000-2001). Variables that described quality in Phase I were abstracted for Phase II and data describing the new variables of beta-blocker use and lipid management were collected. Data samples collected onsite by participating hospitals were used for rapid cycle improvement in Phase II. Results: CDAC data (n = 1927 cases in 1999; n = 2001 cases in 2000) showed that improvements from Phase I in aspirin prescription, internal mammary artery use, and duration of intubation persisted in Phase II. During Phase II, use of beta-blockers before, during, or after CABG increased from 65% to 76% of patients (P < 0.05). Appropriate lipid management, an aggregate variable, occurred in 91% of patients before and 91% after the educational intervention. However. there were improvements in 3 of 5 subcategories for lipid management (documenting a lipid disorder [52%-57%], initiating drug therapy [45%-53%], and dietary counseling [74%-91%]; P < 0.05). Conclusions: In Phase II, this statewide process-oriented quality improvement program added two new measures of quality. Achievements of quality improvement from Phase I persisted in Phase II, and improvements were seen in the new variables of lipid management and perioperative use of beta-blockers. C1 Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Alabama Qual Assurance Fdn, Birmingham, AL USA. UAB, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. E Alabama Med Ctr, Opelika, AL USA. RP Holman, WL (reprint author), Dept Surg, ZRB 719,703 S 19th St, Birmingham, AL 35294 USA. EM wholman@its.uab.edu NR 25 TC 14 Z9 15 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2004 VL 239 IS 1 BP 99 EP 109 DI 10.1097/01.sla.0000103065.17661.8f PG 11 WC Surgery SC Surgery GA 774FK UT WOS:000188968900016 PM 14685107 ER PT J AU Rathore, SS Epstein, AJ Vopp, KGM Krumholz, HM AF Rathore, SS Epstein, AJ Vopp, KGM Krumholz, HM TI Hospital coronary artery bypass graft surgery volume and patient mortality, 1998-2000 SO ANNALS OF SURGERY LA English DT Article ID NEW-YORK-STATE; SURGICAL VOLUME; OUTCOME RELATIONSHIPS; INHOSPITAL MORTALITY; POTENTIAL BENEFITS; CARDIAC-SURGERY; UNITED-STATES; RISK-FACTORS; OPERATIONS; QUALITY AB Objective: To evaluate the association between annual hospital coronary artery bypass graft (CABG) surgery volume and in-hospital mortality. Summary Background Data: The Leapfrog Group recommends health care purchasers contract for CABG services only with hospitals that perform greater than or equal to500 CABGs annually to reduce mortality; it is unclear whether this standard applies to current practice. Methods: We conducted a retrospective analysis of the National Inpatient Sample database for patients who underwent CABG in 1998-2000 (n = 228,738) at low (12-249 cases/year), medium (250-499 cases/year), and high (greater than or equal to500 cases/year) CABG volume hospitals. Crude in-hospital mortality rates were 4.21% in low-volume hospitals, 3.74% in medium-volume hospitals, and 3.54% in high-volume hospitals (trend P < 0.001). Compared with patients at high-volume hospitals (odds ratio 1.00, referent), patients at low-volume hospitals remained at increased risk of mortality after multivariable adjustment (odds ratio 1.26, 95% confidence interval = 1.15-1.39). The mortality risk for patients at medium-volume hospitals was of borderline significance (odds ratio 1.11, 95% confidence interval = 1.01-1.21). However, 207 of 243 (85%) of low-volume and 151 of 169 (89%) of medium-volume hospital-years had risk-standardized mortality rates that were statistically lower or comparable to those expected. In contrast, only 11 of 169 (6%) of high-volume hospital-years had outcomes that were statistically better than expected. Conclusions: Patients at high-volume CABG hospitals were, on average, at a lower mortality risk than patients at lower-volume hospitals. However, the small size of the volume-associated mortality difference and the heterogeneity in outcomes within all CABG volume groups suggest individual hospital CABG volume is not a reliable marker of hospital CABG quality. C1 Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med,MD PhD Program, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06520 USA. Univ Penn, Wharton Sch Buiness, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Gen Internal Med Sect, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Rathore, SS (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med,MD PhD Program, New Haven, CT 06520 USA. FU AHRQ HHS [T32 HS000009, T32-HS00009] NR 46 TC 67 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2004 VL 239 IS 1 BP 110 EP 117 DI 10.1097/01.sla.0000103066.22732.b8 PG 8 WC Surgery SC Surgery GA 774FK UT WOS:000188968900017 PM 14685108 ER PT J AU Esserman, L Sepucha, K Ozanne, E Hwang, ES AF Esserman, L Sepucha, K Ozanne, E Hwang, ES TI Applying the neoadjuvant paradigm to ductal carcinoma in situ SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cutting Edge Strategies: Optimizing Surgical and Medical Treatment of Breast Cancer CY MAR 06, 2003 CL LOS ANGELES, CALIFORNIA DE DCIS; magnetic resonance imaging; risk assessment; biomarkers ID SURGICAL-ADJUVANT-BREAST; BOWEL-PROJECT P-1; PROPHYLACTIC MASTECTOMY; RADIATION-THERAPY; LOCAL RECURRENCE; CONTROLLED-TRIAL; CANCER RISK; WOMEN; TAMOXIFEN; BIOPSY AB Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk, In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women. C1 Univ Calif San Francisco, Ctr Med, Carol Franc Buck Breast Care Ctr, Dept Surg, San Francisco, CA 94115 USA. Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Esserman, L (reprint author), Univ Calif San Francisco, Ctr Med, Carol Franc Buck Breast Care Ctr, Dept Surg, 1600 Divisadero,Floos 2,Box 1710, San Francisco, CA 94115 USA. EM laura.esserman@ucsfmedctr.org NR 45 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2004 VL 11 IS 1 SU S BP 28S EP 36S DI 10.1245/ASO.2004.11.932 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 761BY UT WOS:000187880600006 PM 15015707 ER PT J AU Allan, JS AF Allan, JS TI The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung - Commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2004 VL 77 IS 1 BP 252 EP 253 DI 10.1016/S0003-4975(03)01646-1 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 759KA UT WOS:000187735800054 ER PT J AU Raut, CP Cambria, RP LaMuraglia, GM Brewster, DC Moncure, AC Abbott, WM AF Raut, CP Cambria, RP LaMuraglia, GM Brewster, DC Moncure, AC Abbott, WM TI Surgical management of popliteal artery embolism at the turn of the millennium SO ANNALS OF VASCULAR SURGERY LA English DT Article ID LOWER-LIMBS; EMBOLECTOMY; THROMBECTOMY; HEPARIN AB Popliteal artery embolism has been a focus of study at the Massachusetts General Hospital for over 60 years. It is a formidable vascular problem with significant limb loss and mortality. To assess the impact of advances in cardiac and vascular therapies, we reviewed our outcomes over 12 years. A retrospective review from our databases identified 66 patients with 72 popliteal artery emboli between January 1989 and October 2000. Patients undergoing nonsurgical therapy or with in situ atherosclerotic thrombosis were excluded. Demographics, comorbidities, presentation, duration, etiology, treatment, and outcomes were analyzed. Patients were classified into. those with acute (AP; symptoms <7 days; 59 of 72, 82%) or delayed (DP; symptoms >7 days;,l 3 of 72, 18%) presentation. The presentation was typically acute ischemia (85%) in the AP group and claudication (69%), rest pain (15.5%), or gangrene (15.5%) in the DP group. The most common etiology was embolism secondary to atrial fibrillation (17 of 72, 24%). Femoral artery access (15 of 72, 21%) was more prevalent than in our prior experience. In the AP group, 9 of 59 (15%) were treated with a femoral artery approach, 44 of 59 (75%) with a popliteal artery approach, and 6 of 59 (10%) with bypass. In the DP group, 11 of 13 (85%) were treated with a popliteal approach and 2 of 13 (15%) with bypass. Completion angiography was done in 17 cases (24%). Limb salvage rate was 88% (88% AP, 85% DP); the rate was 94% with angiography and 85% without it (p > 0.1). There were seven deaths (10%). The mortality rate was 33% after amputation and 7% after limb salvage (p < 0.05). Except for a greater prevalence of femoral artery access as an etiology, the demographics of patients with popliteal embolism were similar to those of prior reports. Although a femoral approach may be appropriate in select A.P cases, a popliteal approach is preferred in most patients and is necessary in DP cases. Completion angiography should be performed to ensure adequacy of the embolectomy. Outcomes arc, unchanged. Future therapies should aim to improve limb salvage and mortality rates. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 275 Charles St,Warren 901, Boston, MA 02114 USA. EM wabbott@partners.org NR 25 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JAN PY 2004 VL 18 IS 1 BP 79 EP 85 DI 10.1007/s10016-003-0057-3 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 800ZC UT WOS:000220065200015 PM 14508664 ER PT J AU Rot, A von Andrian, UH AF Rot, A von Andrian, UH TI Chemokines in innate and adaptive host defense: Basic chemokinese grammar for immune cells SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE chemokine receptors; chemotaxis; endothelial cells; lymphocyte trafficking ID HIGH ENDOTHELIAL VENULES; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SECONDARY LYMPHOID ORGANS; RECEPTOR-DEFICIENT MICE; TOLL-LIKE RECEPTOR-4; BLOOD-GROUP ANTIGEN; CD8(+) T-CELLS; DENDRITIC CELLS; IN-VIVO; CC-CHEMOKINE AB Chemokines compose a sophisticated communication system used by all our cell types, including immune cells. Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular. Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via "silent" chemokine receptors (interceptors) leading either to their transcytosis or to degradation. These regulatory mechanisms of chemokine histotopography, as well as the promiscuous and overlapping receptor specificities of inflammation-induced chemokines, shape innate responses to infections and tissue damage. Conversely, the specific patterns of homeostatic chemokines, where each chemokine is perceived by a single receptor, are charting lymphocyte navigation routes for immune surveillance. This review presents our current understanding of the mechanisms that regulate the cellular perception and pathophysiologic meaning of chemokines. C1 Novartis Inst Biomed Res, A-1235 Vienna, Austria. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rot, A (reprint author), Novartis Inst Biomed Res, A-1235 Vienna, Austria. EM antal.rot@pharma.novartis.com; uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; OI Rot, Antal/0000-0002-9730-6166 FU NHLBI NIH HHS [HL54936, HL56949, HL62524]; NIAMS NIH HHS [AR42689] NR 256 TC 731 Z9 758 U1 7 U2 44 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2004 VL 22 BP 891 EP 928 DI 10.1146/annurev.immunol.22.012703.104543 PG 42 WC Immunology SC Immunology GA 823HP UT WOS:000221601500029 PM 15032599 ER PT J AU Koutkia, P Grinspoon, S AF Koutkia, P Grinspoon, S TI HIV-associated lipodystrophy: Pathogenesis, prognosis, treatment, and controversies SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE lipodystrophy; insulin resistance; HIV ID IMMUNODEFICIENCY-VIRUS-INFECTION; INHIBITOR-ASSOCIATED LIPODYSTROPHY; SUBCUTANEOUS ADIPOCYTE APOPTOSIS; ACTIVE ANTIRETROVIRAL THERAPY; CORONARY-HEART-DISEASE; PROTEASE INHIBITORS; INSULIN-RESISTANCE; FAT REDISTRIBUTION; BODY-COMPOSITION; METABOLIC ABNORMALITIES AB Potent antiretroviral agents markedly suppress HIV and have dramatically improved the clinical course, prognosis, and survival of HIV-infected patients. Unfortunately, highly active antiretroviral therapy is often compromised by metabolic complications, including insulin resistance, dyslipidemia, and fat redistribution. Together these changes have been termed the HlV-lipodystrophy syndrome, which is estimated to affect a majority of patients treated with potent combination antiretroviral therapy. Routine testing of fasting glucose is recommended for all HIV-infected patients, particularly those who are obese, have a family history of diabetes mellitus, or are receiving protease inhibitor therapy. Preliminary investigations have demonstrated the potential utility of insulin-sensitizing agents and lipid-lowering therapies to ameliorate these metabolic disturbances. Patients with HIV infection who demonstrate fat redistribution and develop hyperinsulinemia and dyslipidemia may be at increased risk of cardiovascular disease. However, the long-term effects on cardiovascular disease have not yet been determined. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutrit Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. RP Koutkia, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutrit Med, 55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 75 TC 50 Z9 51 U1 0 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 303 EP 317 DI 10.1146/annurev.med.55.091902.104412 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000018 PM 14746523 ER PT J AU Gaasch, WH Zile, MR AF Gaasch, WH Zile, MR TI Left ventricular diastolic dysfunction and diastolic heart failure SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE cardiac function; congestive heart failure; diastole; ejection fraction ID NORMAL EJECTION FRACTION; NORMAL SYSTOLIC FUNCTION; PRESSURE-VOLUME CURVE; HYPERTROPHIC CARDIOMYOPATHY; PULMONARY-EDEMA; DOPPLER-ECHOCARDIOGRAPHY; NATRIURETIC PEPTIDE; ELDERLY-PATIENTS; CORONARY REVASCULARIZATION; ESSENTIAL-HYPERTENSION AB Thirty to fifty percent of patients presenting with signs and symptoms of heart failure have a normal left ventricular (LV) systolic ejection fraction. The clinical examination cannot distinguish these patients (diastolic heart failure) from those with a depressed ejection fraction (systolic heart failure), but echocardiography can. The management of diastolic heart failure has two major objectives. The first is to reverse the consequences of diastolic dysfunction (e.g., venous congestion), and the second is to eliminate or reduce the factors responsible for diastolic dysfunction (e.g., myocardial hypertrophy, fibrosis, and ischemia). C1 Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA 01805 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. RP Gaasch, WH (reprint author), Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA 01805 USA. EM William.H.Gaasch@Lahey.org NR 84 TC 137 Z9 146 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 373 EP 394 DI 10.1146/annurev.55.091902.104417 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000022 PM 14746527 ER PT J AU Siegel, JM AF Siegel, JM TI Hypocretin (orexin): Role in normal behavior and neuropathology SO ANNUAL REVIEW OF PSYCHOLOGY LA English DT Review DE REM sleep; hypothalamus; narcolepsy; cataplexy; feeding; motor; alertness ID LOCUS-COERULEUS NEURONS; IN-VIVO MICRODIALYSIS; DORSAL RAPHE NUCLEUS; AMINO-ACID RELEASE; HUMAN NARCOLEPSY; RETICULAR-FORMATION; GABA RELEASE; MUSCLE TONE; RAT-BRAIN; HISTAMINERGIC NEURONS AB The hypocretins (Hcrts, also known as orexins) are two peptides, both synthesized by a small group of neurons, most of which are in the lateral hypothalamic and perifornical regions of the hypothalamus. The hypothalamic Hcrt system directly and strongly innervates and potently excites noradrenergic, dopaminergic, serotonergic, histaminergic, and cholinergic neurons. Hcrt also has a major role in modulating the release of glutamate and other amino acid transmitters. Behavioral investigations have revealed that Hcrt is released at high levels in active waking and rapid eye movement (REM) sleep and at minimal levels in non-REM sleep. Hcrt release in waking is increased markedly during periods of increased motor activity relative to levels in quiet, alert waking. Evidence for a role for Hcrt in food intake regulation is inconsistent. I hypothesize that Hcrt's major role is to facilitate motor activity tonically and phasically in association with motivated behaviors and to coordinate this facilitation with the activation of attentional and sensory systems. Degeneration of Hcrt neurons or genetic mutations that prevent the normal synthesis of Hcrt or of its receptors causes human and animal narcolepsy. Narcolepsy is characterized by an impaired ability to maintain alertness for long periods and by sudden losses of muscle tone (cataplexy). Administration of Hcrt can reverse symptoms of narcolepsy in animals, may be effective in treating human narcolepsy, and may affect a broad range of motivated behaviors. C1 Univ Calif Los Angeles, Ctr Sleep Res, Vet Affairs Greater Los Angeles Healthcare Syst S, North Hills, CA 91343 USA. Univ Calif Los Angeles, Ctr Sleep Res, Dept Psychiat & Biobehav Sci, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Ctr Sleep Res, Vet Affairs Greater Los Angeles Healthcare Syst S, North Hills, CA 91343 USA. EM jsiegel@ucla.edu FU NHLBI NIH HHS [HL060246]; NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610, NS64109] NR 100 TC 151 Z9 157 U1 1 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4308 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol. PY 2004 VL 55 BP 125 EP 148 DI 10.1146/annurev.psych.55.090902.141545 PG 28 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 780BK UT WOS:000189351100005 PM 14744212 ER PT J AU Mukohara, T Kudoh, S Matsuura, K Yamauchi, S Kimura, T Yoshimura, N Kanazawa, H Hirata, K Inoue, K Wanibuchi, H Fukushima, S Yoshikawa, J AF Mukohara, T Kudoh, S Matsuura, K Yamauchi, S Kimura, T Yoshimura, N Kanazawa, H Hirata, K Inoue, K Wanibuchi, H Fukushima, S Yoshikawa, J TI Activated Akt expression has significant correlation with EGFR and TGF-alpha expressions in stage INSCLC SO ANTICANCER RESEARCH LA English DT Article DE Akt; EGFR; HER-2; NSCLC; TGF-alpha; immunohistochemistry ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; BREAST-CANCER; MOLECULAR MARKERS; PROTEIN-KINASE; SURVIVAL; PHOSPHORYLATION; OVEREXPRESSION; ADENOCARCINOMA; CARCINOMAS AB Background: In vitro studies have indicated that epidermal growth factor receptor (EGFR) may intensify signaling output by the receptor's overexpression, heterodimerization with HER-2, or autocrine expression of ligands. The purpose of the present study was to evaluate the correlation between EGTR and its related proteins and to explore the prognostic value of the proteins. Materials and Methods: Immunohistochemical staining of transforming growth factor alpha (TGF-alpha), EGFR, HER-2, and phosphorylated (p-)Akt was performed in specimens surgically excised from 91 consecutive patients with p-stage I non-small cell lung cancer (NSCLC). Expression or coexpression of TGF-a and the receptors were related to etpression of p-Akt. The prognostic impact of these peptides was also tested. Results: TGF-a, EGFR and HER-2 overexpressions were detected in 32%, 79% and 13% of tumors, respectively. Coexpressions of TGF-alpha & EGFR and EGFR & HER-2 were observed in 29% and 11% of tumors, respectively. P-Akt expression was found in 73% of tumors. Significant correlations between EGFR, TGF-alpha or coexpression of TGF-a & EGFR and p-Akt expression were found (p=0.006, 0.008 and 0.010 respectively). No proteins examined had an impact on relapse-free survival. Conclusion: The Akt pathway is frequently involved in NSCLC and overexpression of EGFR and autocrine expression of TGF-alpha may increase the potency of Akt activation. C1 Osaka City Univ, Sch Med, Dept Internal Med 1, Osaka 545, Japan. Osaka City Univ, Sch Med, Dept Surg, Osaka 545, Japan. Osaka City Univ, Sch Med, Dept Pathol 1, Osaka 545, Japan. RP Mukohara, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D820D, Boston, MA 02115 USA. EM toru_mukohara@dfci.harvard.edu NR 35 TC 35 Z9 36 U1 1 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2004 VL 24 IS 1 BP 11 EP 17 PG 7 WC Oncology SC Oncology GA 778ZV UT WOS:000189271900002 PM 15015570 ER PT J AU Andes, D Marchillo, K Conklin, R Krishna, G Ezzet, F Cacciapuoti, A Loebenberg, D AF Andes, D Marchillo, K Conklin, R Krishna, G Ezzet, F Cacciapuoti, A Loebenberg, D TI Pharmacodynamics of a new triazole, posaconazole, in a murine model of disseminated candidiasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VIVO ACTIVITIES; OROPHARYNGEAL CANDIDIASIS; STREPTOCOCCUS-PNEUMONIAE; AMPHOTERICIN-B; OTITIS-MEDIA; FLUCONAZOLE; ALBICANS; INFECTIONS; RESISTANCE; VITRO AB Previous in vivo studies have characterized the pharmacodynamic characteristics of two triazole compounds, fluconazole and ravuconazole. These investigations demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic-pharmacodynamic (PK-PD) parameter associated with treatment efficacy. Further analysis demonstrated that a free-drug triazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success in both experimental models and clinical trials. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the time course activity of the new triazole, posaconazole. The PK-PD parameters (percent time above MIC, AUC/MIC ratio, and peak serum drug level/MIC ratio) were correlated with in vivo efficacy, as measured by organism number in kidney cultures after 48 h of therapy. Kinetics and protein binding following oral posaconazole dosing were performed in neutropenic infected mice. Peak levels and AUC from 0 h to infinity values were nonlinear over the 16-fold dose range studied. Serum drug elimination half-life ranged from 12.0 to 17.7 h. Protein binding was 99%. Single dose postantifungal effect studies demonstrated prolonged suppression of organism regrowth after serum posaconazole levels had fallen below the MIC. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (AUC/MIC ratio R-2 = 83%; peak serum drug/MIC ratio R-2 = 85%; time that serum levels of posaconazole remained above the MIC R-2 = 65%). Similar studies were conducted with 11 additional C albicans isolates with various posaconazole susceptibilities (MIC, 0.015 to 0.12 mug/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The posaconazole free-drug AUC/MIC ratios were similar for all of the organisms studied (6.12 to 26.7, mean +/- SD = 16.9 +/- 7.8, P value, 0.42). These free-drug AUC/MIC ratios are similar to those observed for other triazoles in this model. C1 Univ Wisconsin, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Andes, D (reprint author), Univ Wisconsin, 600 Highland Ave,Room H4-572, Madison, WI 53792 USA. NR 27 TC 107 Z9 112 U1 1 U2 3 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 JAN PY 2004 VL 48 IS 1 BP 137 EP 142 DI 10.1128/AAC.48.1.137-142.2004 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 759FW UT WOS:000187728500020 PM 14693531 ER PT J AU Pena, JA Li, SY Wilson, PH Thibodeau, SA Szary, AJ Versalovic, J AF Pena, JA Li, SY Wilson, PH Thibodeau, SA Szary, AJ Versalovic, J TI Genotypic and phenotypic studies of murine intestinal lactobacilli: Species differences in mice with and without colitis SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTERGENIC SPACER REGION; 16S-23S RIBOSOMAL-RNA; LACTIC-ACID BACTERIA; PCR-BASED METHODS; GASTROINTESTINAL-TRACT; ACIDOPHILUS GROUP; DIGESTIVE-TRACT; RHAMNOSUS GG; IDENTIFICATION AB Lactobacilli represent components of the commensal mammalian gastrointestinal microbiota and are useful as probiotics, functional foods, and dairy products. This study includes systematic polyphasic analyses of murine intestinal Lactobacillus isolates and correlation of taxonomic findings with data from cytokine production assays. Lactobacilli were recovered from mice with microbiota-dependent colitis (interleukin-10 [IL-10] deficient C57BL/6 mice) and from mice without colitis (Swiss Webster and inducible nitric oxide synthetase-deficient C57BL/6 mice). Polyphasic analyses were performed to elucidate taxonomic relationships among 88 reference and murine gastrointestinal lactobacilli. Genotypic tests included single-locus analyses (16S ribosomal DNA sequencing and 16S-23S rRNA intergenic spacer region PCR) and genomic DNA profiling (repetitive DNA element-based PCR), and phenotypic analyses encompassed more than 50 tests for carbohydrate utilization, enzyme production, and antimicrobial resistance. From 20 mice without colitis, six Lactobacillus species were recovered; the majority of the mice were colonized with L. reuteri or L. murinus (72% of isolates). In contrast, only, L. johnsonii was isolated from 14 IL-10-deficient mice. Using an in vitro assay, we screened murine isolates for their ability to inhibit tumor necrosis factor alpha (TNF-alpha) secretion by lipopolysaccharide-activated macrophages. Interestingly, a subpopulation of lactobacilli recovered from mice without colitis displayed TNF-alpha inhibitory properties, whereas none of the L. johnsonii isolates from IL-10-deficient mice exhibited this effect. We propose that differences among intestinal Lactobacillus populations in mammals, combined with host genetic susceptibilities, may account partly for variations in host mucosal responses. C1 Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Versalovic, J (reprint author), Texas Childrens Hosp, Dept Pathol, 6621 Fannin St,MC 1-2261, Houston, TX 77030 USA. EM jxversal@texaschildrenshospital.org FU NIDDK NIH HHS [DK56338, P30 DK056338, K08 DK002705, K08-DK02705] NR 42 TC 49 Z9 52 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2004 VL 70 IS 1 BP 558 EP 568 DI 10.1128/AEM.70.1.558-568.2004 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 763RY UT WOS:000188115300070 PM 14711688 ER PT S AU Sundback, CA Shyu, JY Wu, AJ Sheahan, TP Wang, YD Faquin, WC Langer, RS Vacanti, JP Hadlock, TA AF Sundback, CA Shyu, JY Wu, AJ Sheahan, TP Wang, YD Faquin, WC Langer, RS Vacanti, JP Hadlock, TA BE Wong, JY Plant, AL Schmidt, CE Shea, L Coury, AJ Chen, CS Barron, AE Klok, HA Saltzman, WM Chilkoti,A Luo, D Uhrich, K TI In vitro and in vivo biocompatibility analysis of poly (glycerol sebacate) as a potential nerve guide material SO ARCHITECTURE AND APPLICATION OF BIOMATERIALS AND BIOMOLECULAR MATERIALS SE MATERIALS RESEARCH SOCIETY SYMPOSIUM PROCEEDINGS LA English DT Proceedings Paper CT Symposium on Architecture and Application of Biomaterials and Biomolecular Materials held at the 2003 MRS Fall Meeting CY DEC 01-04, 2003 CL Boston, MA ID REGENERATION; COLLAGEN AB Aligned guiding structures within nerve repair conduits have been shown to enhance peripheral nerve regeneration. The recently developed poly (glycerol sebacate) (PGS) is a biodegradable tough elastomer with good mechanical properties, unlike many biomaterials and hydrogels. The potential use of PGS in nerve guide repairs has been assessed and compared to that of poly (lactic-co-glycolic) acid (50:50) (PLGA) through in vitro and in vivo. bioconipatibility tests. Ill vitro tests were Conducted With Schwann cells on PGS and PLGA to assess cell attachment at 1 and 3 h, as well as metabolic activity and apoptosis on days 1, 3, 5, 7. and 9. PGS presented minimal cytotoxic effects and compared, favorably with PLGA. PGS and PLGA pieces were implanted in direct apposition to the sciatic nerve in Fisher rats; inflammatory response (H&E), fibrous capsule formation (Masson's trichrome), and the soft tissue response to ED1. Subclass macrophages were evaluated on days 7, 21, 35, and 60. For PGS implanted tissue, fibrosis and inflammation gradually decreased throughout the test period, except for a mild spike between 21 and 35 days during the period of significant degradation and mass loss. PLGA showed a similar trend; however the fibrosis and inflammation levels were comparable or higher at all time points and the spike between 21 and 35 days was significantly greater. ED1 cell density decreased throughout the test period for both biomaterials, but was still higher for PLGA. Based on these data, PGS is a potential nerve guidance conduit material. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sundback, CA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. OI Wang, Yadong/0000-0003-2067-382X NR 5 TC 2 Z9 2 U1 0 U2 5 PU MATERIALS RESEARCH SOCIETY PI WARRENDALE PA 506 KEYSTONE DRIVE, WARRENDALE, PA 15088-7563 USA SN 0272-9172 BN 1-55899-745-8 J9 MATER RES SOC SYMP P PY 2004 VL 1 BP 37 EP 39 PG 3 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA BAB22 UT WOS:000221434200008 ER PT J AU Wright, JH AF Wright, JH TI Protozoa in a case of tropical ulcer ("Alep-Po Boil"). SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Clinicopathol Lab, Boston, MA 02114 USA. RP Wright, JH (reprint author), Massachusetts Gen Hosp, Clinicopathol Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2004 VL 140 IS 1 BP 9 EP 9 PG 1 WC Dermatology SC Dermatology GA 763DT UT WOS:000188060200001 ER PT J AU Piacquadio, DJ Chen, DM Farber, HF Fowler, JF Glazer, SD AF Piacquadio, DJ Chen, DM Farber, HF Fowler, JF Glazer, SD TI Photodynamic therapy with aminolevulinic acid topical solution and visible blue, light in the treatment of multiple actinic keratoses of the face and scalp - Investigator-blinded, phase 3, multicenter trials SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; 5-AMINOLEVULINIC ACID; SOLAR KERATOSES; 5-FLUOROURACIL AB Objective: To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter "ALA") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp. Design: Randomized, placebo-con trolled, uneven parallel-group study. Interventions: Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated. Main Outcome Measure: Clinical response based on lesion clearing by week 8. Results: Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P < .001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment. Conclusion: Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp. C1 Univ Calif San Diego, Dept Med, Div Dermatol, San Diego, CA 92103 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Columbia Univ, New York, NY USA. Univ Louisville, Sch Med, Div Dermatol, Louisville, KY 40292 USA. Washington Univ, Sch Med, Div Dermatol, St Louis, MO USA. Radiant Res, Div Dermatol, W Palm Beach, FL USA. Medaphase Inc, Atlanta, GA USA. RP Piacquadio, DJ (reprint author), Therapeut Inc, 4180 La Jolla Village Dr,Suite 255, La Jolla, CA 92037 USA. EM danp@therapeuticsinc.com NR 19 TC 129 Z9 133 U1 1 U2 6 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 JAN PY 2004 VL 140 IS 1 BP 41 EP 46 DI 10.1001/archderm.140.1.41 PG 6 WC Dermatology SC Dermatology GA 763DT UT WOS:000188060200006 PM 14732659 ER PT J AU Tsao, H Feldman, M Fullerton, JE Sober, AJ Rosenthal, D Goggins, W AF Tsao, H Feldman, M Fullerton, JE Sober, AJ Rosenthal, D Goggins, W TI Early detection of asymptomatic pulmonary melanoma metastases by routine chest radiographs is not associated with improved survival SO ARCHIVES OF DERMATOLOGY LA English DT Article ID FOLLOW-UP TESTS; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; STAGE-I; CANCER PATIENTS; BREAST-CANCER; RESECTION; SURVEILLANCE; MANAGEMENT; GUIDELINES AB Objective: To determine if earlier detection of pulmonary metastasis by routine chest radiography (CR) is associated with a prolonged survival. Design: A computer-assisted search of all CR reports on patients with melanoma between 1990 and 1994 at the Massachusetts General Hospital, Boston. Positive or suspicious findings for pulmonary metastasis were further pursued through review of medical records and tumor registry files. Setting and Patients: A hospital-based population of patients with melanoma undergoing routine CR at Massachusetts General Hospital. Results: Overall, of 994 patients, 75 were identified as having pulmonary metastases by CR (1937 total chest radiographs). In addition, there were 63 patients with suspicious findings that were later shown to be false positive. Chest radiographs provided the initial evidence of metastases in 41 asymptomatic individuals. Thirty-four patients had known melanoma metastases to other sites at the time of the first abnormal chest radiograph. Survival after identification of pulmonary metastasis did not differ significantly between the 2 groups. Conclusions: In this study, there was no evidence to support the notion that earlier detection of pulmonary metastasis in other-wise asymptomatic individuals confers a survival advantage in an unselected melanoma population. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. Hong Kong Baptist Univ, Dept Math, Hong Kong, Hong Kong, Peoples R China. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 21 TC 25 Z9 26 U1 0 U2 0 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 JAN PY 2004 VL 140 IS 1 BP 67 EP 70 DI 10.1001/archderm.140.1.67 PG 4 WC Dermatology SC Dermatology GA 763DT UT WOS:000188060200009 PM 14732662 ER PT J AU Linfante, I Hirsch, JA Selim, M Schlaug, G Caplan, LR Reddy, AS AF Linfante, I Hirsch, JA Selim, M Schlaug, G Caplan, LR Reddy, AS TI Safety of latest-generation self-expanding stents in patients with NASCET-ineligible severe symptomatic extracranial internal carotid artery stenosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID ANGIOPLASTY; ENDARTERECTOMY; TRIAL; RISK; NITINOL AB Background: Patients with symptomatic extracranial internal carotid artery stenosis (greater than or equal to70%) benefit from carotid endarterectomy when compared with medical management. However, independent risk factors can significantly increase the combined stroke and death risk after carotid endarterectomy. Carotid angioplasty and stenting (CAS) is a therapeutic option in patients who are otherwise at high risk or ineligible for carotid endarterectomy. Previous-generation self-expanding stents were hampered by length foreshortening, which limited their application in multifactorial occlusive extracranial internal carotid artery stenosis. Methods: This is a single-center, prospective, open-label, safety study of CAS with the latest-generation self-expanding stents in patients with extracranial internal carotid artery symptomatic stenosis ( greater than or equal to70%). All patients included were adjudicated to be ineligible for carotid endarterectomy by a vascular surgeon and/or a neurologist according to the exclusion criteria. Primary adverse events included death and all strokes (ipsilateral and contralateral). Secondary adverse events included transient ischemic attack, myocardial infarction, stent thrombosis, need for reintervention, and presence of hematomas. All adverse events were recorded at 24 hours, 30 days, and 6 months after CAS. Results: Between June 1, 2001, and January 30, 2003, 23 consecutive patients (14 women and 9 men; mean age, 65 years; age range, 48-85 years) underwent 24 extracranial CAS procedures with the latest-generation self-expanding stents. All patients had one or multiple criteria for ineligibility according to the North American Symptomatic Carotid Endarterectomy Trial. Extracranial CAS was successful in all patients, with average residual stenosis of less than 20%. One patient (4%) experienced a stroke by the 30-day periprocedure examination. The total number of primary adverse events at 6 months after CAS was 2 strokes (9%), 1 of which was contralateral to the stent placement; there were no deaths. Twenty-two patients were asymptornatic at 6 months, with a modified Rankin scale score of 1 or less. Of the 2 patients who had a stroke, I had a follow-up modified Rankin scale score of 3. Conclusion: Extracranial CAS with the latest-generation self-expanding stents is a valid alternative treatment in high-risk or North American Symptomatic Carotid Endarterectomy Trial-ineligible patients. C1 Univ Miami, Jackson Mem Hosp, Dept Radiol, Div NeuroEndovasc Surg & Intervent Neuroradiol, Miami, FL 33136 USA. Beth Israel Med Ctr, Dept Neurol, Boston, MA USA. Beth Israel Med Ctr, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Linfante, I (reprint author), Univ Miami, Jackson Mem Hosp, Dept Radiol, Div NeuroEndovasc Surg & Intervent Neuroradiol, 1611 NW 12th Ave,W Wing 279, Miami, FL 33136 USA. EM ilinfant@med.miami.edu NR 17 TC 17 Z9 17 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 JAN PY 2004 VL 61 IS 1 BP 39 EP 43 DI 10.1001/archneur.61.1.39 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 763BV UT WOS:000188050900007 PM 14732618 ER PT J AU Zandi, PP Anthony, JC Khachaturian, AS Stone, SV Gustafson, D Tschanz, JT Norton, MC Welsh-Bohmer, KA Breitner, JCS AF Zandi, PP Anthony, JC Khachaturian, AS Stone, SV Gustafson, D Tschanz, JT Norton, MC Welsh-Bohmer, KA Breitner, JCS CA Cache Cty Study Grp TI Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements - The Cache County Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID COGNITIVE FUNCTION; NUTRITIONAL-STATUS; OXIDATIVE STRESS; DIETARY-INTAKE; ASSOCIATION; POPULATION; SAMPLE; PERFORMANCE; DEMENTIA; HEALTH AB Background: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). Objective: To examine the relationship between antioxidant supplement use and risk of AD. Design: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. Setting: Cache County, Utah. Participants: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. Main Outcome Measure: Diagnosis of AD by means of multistage assessment procedures. Results: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. Conclusions: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD. C1 Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Adv Acad Programs, Baltimore, MD USA. Utah State Univ, Dept Food Sci & Nutr, Logan, UT USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Stat, Logan, UT 84322 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27710 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. RP Zandi, PP (reprint author), Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [R01 AG 11380]; NIDA NIH HHS [K05 DA015799]; NIMH NIH HHS [T32 MH 14592] NR 35 TC 368 Z9 399 U1 4 U2 24 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 JAN PY 2004 VL 61 IS 1 BP 82 EP 88 DI 10.1001/archneur.61.1.82 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 763BV UT WOS:000188050900013 PM 14732624 ER PT J AU Fishman, GA Roberts, MF Derlacki, DJ Grimsby, JL Yamamoto, H Sharon, D Nishiguchi, KM Dryja, TP AF Fishman, GA Roberts, MF Derlacki, DJ Grimsby, JL Yamamoto, H Sharon, D Nishiguchi, KM Dryja, TP TI Novel muytations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens - Evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID BOTHNIA DYSTROPHY; CONE DYSTROPHY; MUTATIONS; PIGMENTOSA; ALBIPUNCTATUS; ROD AB Objective: To evaluate the molecular genetic defects associated with retinitis punctata albescens (RPA) in 5 patients from 3 families with this disease. Methods: We examined 3 probands and 2 clinically affected relatives with RPA. Clinical examinations included best-corrected visual acuity, visual field testing, electroretinography, dilated fundus examination, and fundus photography. Leukocyte DNA was analyzed for mutations in the exons of the genes encoding cellular retinaldehyde-binding protein I (RLBP1), 11-cis-retinol dehydrogenase (RDH5), interphotoreceptor retinoid-binding protein (RBP3), and photoreceptor all-trans-retinol dehydrogenase (RDH8). Not all patients were evaluated for mutations in each gene. The exons were individually amplified and screened for mutations by single-stranded conformational polymorphism analysis or direct genomic sequencing. Results: The 3 probands had similar clinical findings, including a history of poor night vision, the presence of punctate white deposits in the retina, and substantially reduced or absent rod responses on electroretinogram testing. One of the probands (patient 2:111:2) had 2 novel mutations in the RLBP1 gene (Arg151Trp and Gly31. [2-base pair deletion], [GGA-->G-]). Segregation analysis showed that the 2 mutations were allelic and that the patient was a compound heterozygote. Both parents of the proband manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in RLBP1 or in the other 3 genes evaluated.. Conclusions: The identification of novel RLBP1 mutations in 1 of our 3 probands, all with RPA, is further evidence of genetic (nonallelic) heterogeneity in this disease. The presence of round white deposits in the retina may be observed in those heterozygous for RLBP1. Clinical Relevance: Patients with a clinical presentation of RPA can have genetically different mutations. Drusen-like lesions may be observed in heterozygotes in families with this disease and a mutation in RLBP1. C1 Univ Illinois, Dept Ophthalmol & Visual Sci, UIC, Ctr Eye, Chicago, IL 60612 USA. Illinois Coll Optomerty, Illinois Eye Inst, Chicago, IL USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Fishman, GA (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, UIC, Ctr Eye, Mail Code 648,1855 W Taylor St, Chicago, IL 60612 USA. EM gerafish@uic.edu RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 FU NEI NIH HHS [EY01792, EY08683] NR 22 TC 34 Z9 34 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 JAN PY 2004 VL 122 IS 1 BP 70 EP 75 DI 10.1001/archopht.122.1.70 PG 6 WC Ophthalmology SC Ophthalmology GA 762AF UT WOS:000187947100011 PM 14718298 ER PT J AU Barouch, FC Benson, MD Mukai, S AF Barouch, FC Benson, MD Mukai, S TI Isolated vitreoretinal amyioidosis in the absence of transthyretin mutations SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID AMYLOIDOSIS; INVOLVEMENT C1 Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol, Boston, MA 02114 USA. RP Mukai, S (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM shizuo_mukai@meei.harvard.edu NR 6 TC 5 Z9 5 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 JAN PY 2004 VL 122 IS 1 BP 123 EP 125 DI 10.1001/archopht.122.1.123 PG 3 WC Ophthalmology SC Ophthalmology GA 762AF UT WOS:000187947100024 PM 14718311 ER PT J AU Shin, JJ Katayama, T Michaud, WA Rocco, JW AF Shin, JJ Katayama, T Michaud, WA Rocco, JW TI Short hairpin RNA system to inhibit human p16 in squamous cell carcinoma SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Head-and-Neck-Society CY MAY 04, 2003 CL NASHVILLE, TENNESSEE SP Amer Head Neck Soc ID REPLICATIVE SENESCENCE; GENE; P16(INK4A); CANCER; HEAD; EXPRESSION; DNA; INACTIVATION; P19(ARF); MELANOMA AB Objective: To develop short hairpin RNA (shRNA) vectors and virions to trigger RNA interference against human p16. Design and Interventions: A modular vector-based shRNA system was used to construct multiple distinct shRNA vectors against the unique exon 1alpha of p16. Target sequences were designed using rigid criteria for length and GC content, along with basic local alignment search tool (BLAST) evaluation to ensure targeting specificity. Individual shRNA-p16 cassettes were then cotransfected with a p16 expression vector and evaluated by Western blot. Cassettes showing a high level of p16 repression were used to construct shRNA-p16 expressing adenoviral and retroviral vectors and tested in a human head and neck squamous cell carcinoma line expressing endogenous and exogenous p16. Results: Adenoviral and retroviral transfer of shRNA-p16 significantly reduced p16 protein levels, while control constructs left p16 expression unchanged. Conclusions: Although p16 is a common target of inactivation in head and neck cancer, its biological role remains ill defined. RNA interference is rapidly becoming the standard to target selected genes of interest for inactivation. We have successfully inhibited p16 expression using shRNA cassettes with strong activity against human p16 and integrated these constructs into adenoviral and retroviral vectors for transient and integrated expression in human cells. Application of this novel modular system to primary human cells will allow the biological consequences of p16 loss to be examined both in vitro and in vivo. C1 Massachusetts Gen Hosp, Div Head & Neck Surg, Massachusetts Eye & Ear Infirm, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Harvard Program Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Div Head & Neck Surg, Massachusetts Eye & Ear Infirm, Div Surg Oncol, 243 Charles St, Boston, MA 02114 USA. EM jrocco@partners.org RI Shin, Jennifer/A-3169-2016 NR 32 TC 13 Z9 16 U1 0 U2 0 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 JAN PY 2004 VL 130 IS 1 BP 68 EP 73 DI 10.1001/archotol.130.1.68 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 763DV UT WOS:000188060400011 PM 14732771 ER PT J AU Cai, YC Roggli, V Mark, E Cagle, PT Fraire, AE AF Cai, YC Roggli, V Mark, E Cagle, PT Fraire, AE TI Transforming growth factor alpha and epidermal growth factor receptor in reactive and malignant mesothelial proliferations SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CANCER-CELLS; EXPRESSION; ANTIBODY AB Background.-Growth factors such as transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) play an important role in cell proliferation. The immunohistochemical expression of these factors has been extensively studied in malignant tumors including mesothelioma. However, the comparative expression of these growth factors in mesothelioma and reactive mesothelial proliferations has been less well studied. Objective.-To evaluate the possible role of TGF-alpha and EGFR in the clinically important distinction between reactive mesothelial proliferations and malignant mesothelioma. Methods.-The expression of TGF-alpha and EGFR was studied in 39 cases of mesothelioma and 30 cases of reactive mesothelial proliferations by means of immunohistochemistry. Results.-Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29 (76%) of 38 mesotheliornas tested expressed TGF-alpha. One (3%) of 30 reactive mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR. Conclusions.-These results suggest an up-regulation of EGFR in mesothelioma as compared with reactive mesothelial proliferations. This up-regulation further suggests a possible use of EGFR as an adjunct immunohistochemical test in the differential diagnosis of mesothelioma and reactive mesothelial proliferations. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Duke Univ, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Houston, TX 77030 USA. Mercy Hosp, Pittsburgh, PA 15219 USA. RP Fraire, AE (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. EM fraire@ummhc.org NR 17 TC 15 Z9 15 U1 0 U2 0 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 JAN PY 2004 VL 128 IS 1 BP 68 EP 70 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 762AQ UT WOS:000187948000014 PM 14692808 ER PT J AU Wayne, PM Krebs, DE Wolf, SL Gill-Body, KM Scarborough, DM McGibbon, CA Kaptchuk, TJ Parker, SW AF Wayne, PM Krebs, DE Wolf, SL Gill-Body, KM Scarborough, DM McGibbon, CA Kaptchuk, TJ Parker, SW TI Can Tai Chi improve vestibulopathic postural control? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE balance; posture; rehabilitation; Tai Chi ID QUALITY-OF-LIFE; OLDER ADULTS; CARDIORESPIRATORY FUNCTION; AEROBIC EXERCISE; VESTIBULAR REHABILITATION; RHEUMATOID-ARTHRITIS; ALTERNATIVE MEDICINE; CHUAN PRACTITIONERS; ACOUSTIC NEUROMA; PHYSICAL THERAPY AB Wayne PM, Krebs DE, Wolf SL, Gill-Body KM, Scarborough DM, McGibbon CA, Kaptchuk TJ, Parker SW. Can Tai Chi improve vestibulopathic postural control? Arch Phys Med Rehabil 2004;85:142-52. Objectives: To evaluate the rationale and scientific support for Tai Chi as an intervention for vestibulopathy and to offer recommendations for future studies. Data Sources: A computer-aided search, including MEDLINE and Science Citation Index, to identify original Tai Chi studies published in English; relevant references cited in the retrieved articles were also included. Study Selection: A preliminary screening selected all randomized controlled trials (RCTs), non-RCTs, case-control studies, and case series that included Tai Chi as an intervention and had at least 1 outcome variable relevant to postural stability. Data Extraction: Authors critically reviewed studies and summarized study designs and outcomes in a summary table. Data Synthesis: Twenty-four Tai Chi studies met screening criteria. No studies specifically studying Tai Chi for vestibulopathy were found. Collectively, the 24 studies provide sometimes contradictory but generally supportive evidence that Tai Chi may have beneficial effects for balance and postural impairments, especially those associated with aging. Ten RCTs were found, of which 8 provide support that Tai Chi practiced alone, or in combination with other therapies, can reduce risk of falls, and/or impact factors associated with postural control, including improved balance and dynamic stability, increased musculoskeletal strength and flexibility, improved performance of activities of daily living (ADLs), reduced fear of falling, and general improvement in psychologic well-being. Studies using other designs support the results observed in RCTs. Conclusions: At present, few data exist to support the contention that Tai Chi specifically targets the impairments, functional limitations, disability, and quality of life associated with peripheral vestibulopathy. There are, however, compelling reasons to further investigate Tai Chi for vestibulopathy, in part because Tai Chi appears useful for a variety of nonvestibulopathy etiologic balance disorders, and is safe. Especially needed are studies that integrate measures of balance relevant to ADLs with other psychologic and cognitive measures; these might help identify specific mechanisms whereby Tai Chi can remedy balance disorders. C1 New England Sch Acupuncture, Dept Res, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA USA. Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wayne, PM (reprint author), New England Sch Acupuncture, Dept Res, 40 Belmont St, Watertown, MA 02472 USA. EM pwayne@nesa.edu RI Wolf, Steven/F-6588-2010 OI Wolf, Steven/0000-0002-9446-8995 FU NCCIH NIH HHS [5R25AT0(0)714-02, R21AT000553] NR 98 TC 47 Z9 47 U1 3 U2 16 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2004 VL 85 IS 1 BP 142 EP 152 DI 10.1016/S0003-9993(03)00652-X PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 761GH UT WOS:000187892800023 PM 14970982 ER PT J AU Boninger, ML Cooper, RA Koontz, AM Souza, AL Towers, JD DiCianno, BE AF Boninger, ML Cooper, RA Koontz, AM Souza, AL Towers, JD DiCianno, BE TI Shoulder magnetic resonance imaging abnormalities, wheelchair propulsion, and gender (vol 84, pg 1615, 2003) SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Correction C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. OI Boninger, Michael/0000-0001-6966-919X NR 1 TC 1 Z9 1 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2004 VL 85 IS 1 BP 172 EP 172 DI 10.1016/j.apmr.2003.11.006 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 761GH UT WOS:000187892800029 ER PT J AU Williams, TN Zhang, CX Game, BA He, L Huang, Y AF Williams, TN Zhang, CX Game, BA He, L Huang, Y TI C-reactive protein stimulates MMP-1 expression in U937 histiocytes through Fc gamma RII and extracellular signal-regulated kinase pathway: An implication of CRP involvement in plaque destabilization SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE C-reactive protein; matrix metalloproteinase; arteriosclerosis; gene expression ID MATRIX METALLOPROTEINASE-1 EXPRESSION; CORONARY-ARTERY-DISEASE; HUMAN ENDOTHELIAL-CELLS; ATHEROSCLEROTIC PLAQUE; CROSS-LINKING; RECEPTOR; COMPLEMENT; INFLAMMATION; SYNTHESIZE; MONOCYTES AB Objective-It has been shown that plasma level of C-reactive protein (CRP) is an independent predictor for acute coronary syndromes and is associated with plaque weakening. However, the underlying mechanisms are not well understood. In this study, we investigated the effect of CRP on the expression of matrix metalloproteinase-1 (MMP-1) that has been implicated in plaque vulnerability by human U937 histiocytes and monocyte-derived macrophages. Methods and Results-Enzyme-linked immunosorbent assay of MMP-1 in conditioned medium showed that treatment of U937 cells with 100 mug/mL of CRP for 24 hour led to a 3- to 5-fold increase in MMP-1 secretion. CRP also markedly stimulated MMP-1 release from human monocyte-derived macrophages. In contrast, CRP had no effect on tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion. Northern blot showed that CRP upregulated MMP-1 mRNA expression. Collagenase activity assay showed that CRP increased collagen-degrading activity in cell-conditioned medium. Furthermore, results showed that the stimulation of MMP-1 secretion by CRP was inhibited by anti-CD32, but not by anti-CD64 antibody, and by mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor PD98059. Finally, Western blot showed that CRP stimulated phosphorylation of extracellular signal-regulated kinase. Conclusions-This study demonstrates that CRP stimulates MMP-1 expression by U937 cells through FcgammaRII and extracellular signal-regulated kinase pathway. These findings suggest that CRP may promote matrix degradation and thus contribute to plaque vulnerability. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. NR 37 TC 85 Z9 103 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2004 VL 24 IS 1 BP 61 EP 66 DI 10.1161/01.ATV.0000104014.24367.16 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 760BV UT WOS:000187791600010 PM 14592848 ER PT J AU Studer, RK Bergman, R Stubbs, T Decker, K AF Studer, RK Bergman, R Stubbs, T Decker, K TI Chondrocyte response to growth factors is modulated by p38 mitogen-activated protein kinase inhibition SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE chondrocytes; interleukin-1; nitric oxide; p38 mitogen-activated protein kinase; transforming growth factor beta ID N-TERMINAL KINASE; NITRIC-OXIDE; ARTICULAR CHONDROCYTES; GENE-EXPRESSION; CULTURED CHONDROCYTES; RHEUMATOID-ARTHRITIS; SELECTIVE INHIBITOR; CELL-PROLIFERATION; ATDC5 CELLS; MAP KINASE AB Inhibitors of p38 mitogen-activated protein kinase ( MAPK) diminish inflammatory arthritis in experimental animals. This may be effected by diminishing the production of inflammatory mediators, but this kinase is also part of the IL-1 signal pathway in articular chondrocytes. We determined the effect of p38 MAPK inhibition on proliferative and synthetic responses of lapine chondrocytes, cartilage, and synovial fibroblasts under basal and IL-1-activated conditions. Basal and growth factor-stimulated proliferation and proteoglycan synthesis were determined in primary cultures of rabbit articular chondrocytes, first-passage synovial fibroblasts, and cartilage organ cultures. Studies were performed with or without p38 MAPK inhibitors, in IL-1-activated and control cultures. Media nitric oxide and prostaglandin E(2) were assayed. p38 MAPK inhibitors blunt chondrocyte and cartilage proteoglycan synthesis in response to transforming growth factor beta; responses to insulin-like growth factor 1 (IGF-1) and fetal calf serum (FCS) are unaffected. p38 MAPK inhibitors significantly reverse inhibition of cartilage organ culture proteoglycan synthesis by IL-1. p38 MAPK inhibition potentiated basal, IGF-1-stimulated and FCS-stimulated chondrocyte proliferation, and reversed IL-1 inhibition of IGF-1-stimulated and FCS-stimulated DNA synthesis. Decreases in nitric oxide but not prostaglandin E(2) synthesis in IL-1-activated chondrocytes treated with p38 MAPK inhibitors are partly responsible for this restoration of response. Synovial fibroblast proliferation is minimally affected by p38 MAPK inhibition. p38 MAPK activity modulates chondrocyte proliferation under basal and IL-1-activated conditions. Inhibition of p38 MAPK enhances the ability of growth factors to overcome the inhibitory actions of IL-1 on proliferation, and thus could facilitate restoration and repair of diseased and damaged cartilage. C1 Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. RP Studer, RK (reprint author), VA Med Ctr, Res & Dev, Univ Dr C, Pittsburgh, PA 15240 USA. EM rstuder@pitt.edu NR 34 TC 21 Z9 22 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 1 BP R56 EP R64 DI 10.1186/ar1022 PG 9 WC Rheumatology SC Rheumatology GA 750WM UT WOS:000187021500010 ER PT S AU Reche, PA Reinherz, EL AF Reche, PA Reinherz, EL BE Nicosia, G Cutello, V Bentley, PJ Timmis, J TI Definition of MHC supertypes through clustering of MHC peptide binding repertoires SO ARTIFICIAL IMMUNE SYSTEMS, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 3rd International Conference on Artificial Immune Systems CY SEP 13-16, 2004 CL Catania, ITALY SP Univ Catania, Fac Sci, Acad Network ARTIST, Univ Catania, Dept Math & Comp Sci ID CLASS-I; HLA-A; MOLECULES; POLYMORPHISM; MOTIFS; AMINO AB MHC molecules, also known in the human as human leukocyte antigens (HLA), display peptides on antigen presenting cell surfaces for subsequent T cell recognition. Identification of these antigenic peptides is especially important for developing peptide-based vaccines. Consequently experimental and computational approaches have been developed for their identification. A major impediment to such an approach is the extreme polymorphism of HLA, which is in fact the basis for differential peptide binding. This problem can be mitigated by the observation that despite such polymorphisms, HLA molecules bind overlapping set of peptides, and therefore, may be grouped accordingly into supertypes. Here we describe a method of grouping HLA alleles into supertypes based on analysis and subsequent clustering of their peptide binding repertoires. Combining this method with the known allele and haplotype gene frequencies of HLA I molecules for five major American ethnic groups (Black, Caucasian, Hispanic, Native American, and Asian), it is now feasible to identify supertypic combinations for prediction of antigenic peptide, offering the potential to generate peptide-vaccines with a population coverage greater than or equal to 95%, regardless of ethnicity. One combination including five distinct supertypes is available online at our PEPVAC web server (http://immunax.dfci.harvard.edu/PEPVAC/). Promiscuous peptides predicted to bind to these five supertypes represent around 5% of all possible peptide binders from a given genome. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reche, PA (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM reche@research.dfci.havard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 NR 21 TC 13 Z9 13 U1 0 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-23097-1 J9 LECT NOTES COMPUT SC PY 2004 VL 3239 BP 189 EP 196 PG 8 WC Computer Science, Theory & Methods SC Computer Science GA BAX50 UT WOS:000224093300015 ER PT J AU Kurland, J Naeser, MA Baker, EH Doron, K Martin, PI Seekins, HE Bogdan, A Renshaw, P Yurgelun-Todd, D AF Kurland, J Naeser, MA Baker, EH Doron, K Martin, PI Seekins, HE Bogdan, A Renshaw, P Yurgelun-Todd, D TI Test-retest reliability of fMRI during nonverbal semantic decisions in moderate-severe nonfluent aphasia patients SO BEHAVIOURAL NEUROLOGY LA English DT Article DE nonfluent aphasia; fMRI reliability; nonverbal semantic decisions ID BRAIN PLASTICITY; FUNCTIONAL MRI; RECOVERY; STROKE; RETRIEVAL; THERAPY; SPEECH; PET AB Cortical reorganization in poststroke aphasia is not well understood. Few studies have investigated neural mechanisms underlying language recovery in severe aphasia patients, who are typically viewed as having a poor prognosis for language recovery. Although test-retest reliability is routinely demonstrated during collection of language data in single-subject aphasia research, this is rarely examined in tMRI studies investigating the underlying neural mechanisms in aphasia recovery. The purpose of this study was to acquire fMRI test-retest data examining semantic decisions both within and between two aphasia patients. Functional MRI was utilized to image individuals with chronic, moderate-severe nonfluent aphasia during nonverbal, yes/no button-box semantic judgments of iconic sentences presented in the Computer-assisted Visual Communication (C-ViC) program. We investigated the critical issue of intra-subject reliability by exploring similarities and differences in regions of activation during participants' performance of identical tasks twice on the same day. Each participant demonstrated high intra-subject reliability, with response decrements typical of task familiarity. Differences between participants included greater left hemisphere perilesional activation in the individual with better response to C-ViC training. This study provides fMRI reliability in chronic nonfluent aphasia, and adds to evidence supporting differences in individual cortical reorganization in aphasia recovery. C1 VA Boston Healthcare Syst, Aphasia Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Harold Goodglass Boston Univ Aphasia Res Ctr, Boston, MA 02215 USA. Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. Univ Colorado, Dept Neurosci, Boulder, CO 80309 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. RP Kurland, J (reprint author), VA Boston Healthcare Syst, Aphasia Res Ctr, 12-A,150 S Huntington Ave, Boston, MA 02130 USA. EM kurlandji@bu.edu FU NIDCD NIH HHS [R01 DC005672, R01 DC05672, P30 DC005207, P30 DC05207] NR 41 TC 25 Z9 28 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2004 VL 15 IS 3-4 BP 87 EP 97 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 903XQ UT WOS:000227459300005 PM 15706052 ER PT S AU Goodman, M New, A Siever, L AF Goodman, M New, A Siever, L BE Yehuda, R McEwen, B TI Trauma, genes, and the neurobiology of personality disorders SO BIOBEHAVIORAL STRESS RESPONSE: PROTECTIVE AND DAMAGING EFFECTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protective and Damaging Effects of the Biobehavioral Stress Response CY SEP 07-09, 2003 CL New York, NY SP Glaxosmithkline, Janssen Pharmaceut, Pfizer Inc, Solvay, Bristol Myers Squibb, Novartis Pharmaceut, Astrazeneca, Eli Lilly & Co, Johnson & Johnson, Merck, Ortho McNeil Pharmaceut Inc DE trauma; genes; personality disorder; impulsive aggression; neurobiology ID SEROTONIN TRANSPORTER GENE; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; TRYPTOPHAN-HYDROXYLASE GENE; BORDERLINE PERSONALITY; MONOAMINE-OXIDASE; PROMOTER REGION; ANTISOCIAL PERSONALITY; IMPULSIVE-AGGRESSION; SUICIDAL-BEHAVIOR AB A model for personality dysfunction posits an interaction between inherited susceptibility and environmental factors such as childhood trauma. Core biological vulnerabilities in personality include dimensions of affective instability, impulsive aggression, and cognition/perceptual domains. For the dimension of impulsive aggression, often seen in borderline personality disorder (BPD), the underlying neurobiology involves deficits in central serotonin function and alterations in specific brain regions in the cingulate and the medial and orbital prefrontal cortex. The role of trauma in the development of personality disorder and especially for BPD remains unclear. Although recent studies suggest that BPD is not a trauma-spectrum disorder and that it is biologically distinct from posttraumatic stress disorder, high rates of childhood abuse and neglect do exist for individuals with personality dysfunction. Personality symptom clusters seem to be unrelated to specific abuses, but they may relate to more enduring aspects of interpersonal and family environments in childhood. Whereas twin and family studies indicate a partially heritable basis for impulsive aggression, studies of serotonin-related genes to date suggest only modest contributions to behavior. Gene-environment interactions involving childhood maltreatment are demonstrated in recent studies on antisocial behaviors and aggressive rhesus monkeys and highlight the need for further research in this important area. C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Goodman, M (reprint author), Bronx Vet Adm Med Ctr, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM marianne.goodman@med.va.gov NR 86 TC 71 Z9 72 U1 9 U2 25 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-518-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1032 BP 104 EP 116 DI 10.1196/annals.1314.008 PG 13 WC Behavioral Sciences; Endocrinology & Metabolism; Multidisciplinary Sciences; Physiology; Psychology SC Behavioral Sciences; Endocrinology & Metabolism; Science & Technology - Other Topics; Physiology; Psychology GA BBW44 UT WOS:000228129700009 PM 15677398 ER PT J AU Brody, AL Mandelkern, MA Jarvik, ME Lee, GS Smith, EC Huang, JC Bota, RG Bartzokis, G London, ED AF Brody, AL Mandelkern, MA Jarvik, ME Lee, GS Smith, EC Huang, JC Bota, RG Bartzokis, G London, ED TI Differences between smokers and nonsmokers in regional gray matter volumes and densities SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the European-Society-for-Research-on-Nicotine-and-Tobacco CY OCT 05, 2002 CL SANTANDER, SPAIN SP European Soc Res Nicotine Tobacco DE magnetic resonance imaging; nicotine dependence; voxel-based morphometry; prefrontal cortex; anterior cingulate cortex; ventral striatum ID VOXEL-BASED MORPHOMETRY; NICOTINIC ACETYLCHOLINE-RECEPTORS; QUANTITATIVE CEREBRAL ANATOMY; SILENT BRAIN INFARCTION; AGE-RELATED-CHANGES; CIGARETTE-SMOKING; SEX-DIFFERENCES; IN-VIVO; COGNITIVE PERFORMANCE; CARDIOVASCULAR HEALTH AB Background: Magnetic resonance imaging (MRI) studies have demonstrated large-scale brain abnormalities in cigarette smokers, such as ventricular enlargement and atrophy. Converging lines of evidence point to functional differences between smokers and nonsmokers in specific brain regions, namely the lateral prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and thalamus. Using MRI, we examined these regions for differences in gray matter between smokers and nonsmokers. Metbods: Thirty-six otherwise bealthy adults (19 smokers and 17 nonsmoking control subjects) underwent three-dimensional Fourier-transform spoiled-gradient-recalled acquisition MRI of the brain. Both band-drawn regions of interest and the computer program voxel-based morphometry were used to assess group differences in regional gray matter volumes and densities, respectively. Results: Smokets hadsmallergray mattervolumes andlowergray matter densities than nonsmokers in the PFC bilaterally, along with smaller volumes in the left dorsal ACC and lower gray matter densities in the right cerebellum. Smokers also bad negative associations between pack-year smoking history and PFC gray matter densities. Conclusions: Smokers and nonsmokers differed in regional gray matter in brain areas previously linked with nicotine dependence. These findings might reflect effects of chronic smoking, predisposing traits that lead to smoking, or some combination of these factors. (C) 2004 Society of Biological Psychiatry. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Lab Neuroimaging, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [R01 DA14093, R01 DA15059] NR 116 TC 208 Z9 215 U1 4 U2 19 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 JAN 1 PY 2004 VL 55 IS 1 BP 77 EP 84 DI 10.1016/S0006-3223(03)00610-3 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 759NH UT WOS:000187743400010 PM 14706428 ER PT J AU Schneyer, A Xia, Y Mukherjee, A Sidis, Y AF Schneyer, A Xia, Y Mukherjee, A Sidis, Y TI Regulation of gonadal activin/BMPs. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA MS9 BP 83 EP 84 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400022 ER PT J AU Geijsen, N Horoschak, M Kim, K Gribnau, J Eggan, K Daley, GQ AF Geijsen, N Horoschak, M Kim, K Gribnau, J Eggan, K Daley, GQ TI In vitro generation of male germ cells from embryonic stem cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA MS24 BP 87 EP 87 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400037 ER PT J AU Pru, JK Kaneko-Tarui, T Johnson, J Skaznik-Wikiel, ME AF Pru, JK Kaneko-Tarui, T Johnson, J Skaznik-Wikiel, ME TI Regulation of sphingosine kinases during deciduailization: A role for sphingosine-1-phosphate in uterine prostanoid production SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 5 BP 94 EP 94 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400065 ER PT J AU Martin-DeLeon, PA Morales, CR Badran, H El-Alfy, M Zhang, H Men, HS AF Martin-DeLeon, PA Morales, CR Badran, H El-Alfy, M Zhang, H Men, HS TI Arachidonate 15-lipoxygenase (15-LOX) in the sperm cytoplasmic droplet is a potential fertility marker in boars. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Univ Missouri, Dept Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Obstet & Gynecol, Columbia, MO 65211 USA. Smithfield Premium Genet Grp, Roanoke Rapids, NC USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. RI Morales, Carlos/H-1055-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 142 BP 125 EP 125 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400202 ER PT J AU Hou, XY Arvisais, EW Hansen, TR Rueda, BR McDonald, CA Davis, JS AF Hou, XY Arvisais, EW Hansen, TR Rueda, BR McDonald, CA Davis, JS TI The expression of early growth response transcription factor-1 (EGR-1) during prostaglandin F2 alpha (PGF)-induced luteolysis in the bovine corpus luteum (CL) SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Univ Nebraska, Med Ctr, Olson Ctr Womens Hlth, Omaha, NE USA. Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. VA Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 340 BP 171 EP 171 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400400 ER PT J AU Johnson, J Tilly, JC Tilly, JL AF Johnson, J Tilly, JC Tilly, JL TI Expression of Bmi-1, a polycomb group gene family member, in the postnatal mouse ovary. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv,Dept Obstet &, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 413 BP 187 EP 187 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400472 ER PT J AU Lee, HJ Perez, GI Tilly, JL AF Lee, HJ Perez, GI Tilly, JL TI Sphingosine-1-phosphate attenuates chemotherapy-induced depletion of primordial and primary follicles in vivo. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 420 BP 188 EP 189 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400479 ER PT J AU Rueda, BR Jablonski, EM Oliva, E Huet-Hudson, Y Hughes, FM AF Rueda, BR Jablonski, EM Oliva, E Huet-Hudson, Y Hughes, FM TI Estrogen regulation of AQP-2 expression in human uterine epithelium SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 435 BP 192 EP 192 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400494 ER PT J AU Styer, AK Rueda, BR AF Styer, AK Rueda, BR TI Optimizing mouse models to mimic human disease? Are immunocompetent mouse models appropriate for endometriosis? SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 438 BP 192 EP 193 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400497 ER PT J AU Kaneko-Tarui, T Johnson, J Tilly, JL AF Kaneko-Tarui, T Johnson, J Tilly, JL TI Inhibitor of differentiation (Id) protein expression in the mouse ovary SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv,Vincent Ctr Reprod, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 452 BP 196 EP 196 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400511 ER PT J AU Salli, U Mitalipov, S Meshul, CK Pau, FKY Thomson, JA Wolf, DP AF Salli, U Mitalipov, S Meshul, CK Pau, FKY Thomson, JA Wolf, DP TI Neuronal differentiation of GFP-expressing rhesus monkey embryonic stem cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod Sci, Beaverton, OR USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Behav Neurobiol, Portland, OR 97201 USA. Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Dept Anat, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 545 BP 217 EP 218 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400604 ER PT J AU Sidis, Y Mukherjee, A Schneyer, A AF Sidis, Y Mukherjee, A Schneyer, A TI Differential binding and neutralization of TGF beta family ligands by follistatin isoforms. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 669 BP 246 EP 247 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400728 ER PT J AU Lin, AJ Chen, HJ Gonzalez, E Yacono, PW Michel, T Golan, DE AF Lin, AJ Chen, HJ Gonzalez, E Yacono, PW Michel, T Golan, DE TI Regulation of protein-protein interactions involving endothelial nitric oxide synthase in living cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Harvard Univ, Med Sch, Boston, MA USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 11A EP 11A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200052 ER PT J AU Zhang, BX Ma, XY Shu, ZJ Yeh, CK Swerdlow, RH Katz, MS AF Zhang, BX Ma, XY Shu, ZJ Yeh, CK Swerdlow, RH Katz, MS TI Differential regulation of intracellular calcium oscillations by mitochondria and gap junctions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA 22908 USA. S Texas Vet Hlth Care Syst, Grecc, Almd, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Res Serv 151, ALMD, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 27A EP 27A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200132 ER PT J AU Hadlock, TA Gent, A Strichartz, G AF Hadlock, TA Gent, A Strichartz, G TI Interactions of a local anesthetic, tetracaine, with model membranes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Pain Res Ctr, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 31A EP 32A PN 2 PG 2 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200155 ER PT J AU Zhu, XS Bernecker, OY Manohar, NS Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U AF Zhu, XS Bernecker, OY Manohar, NS Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U TI Abnormal Ca2+ homeostasis and contractility in rat heart in sepsis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med & Dent, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Wisconsin, Sch Med, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 182A EP 182A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200939 ER PT J AU Donnet, C Jia, LG Moorman, JR Tucker, AL Sweadner, KJ AF Donnet, C Jia, LG Moorman, JR Tucker, AL Sweadner, KJ TI Reduced Na,K-ATPase activity and cardiac hypertrophy in phospholemman-deficient mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 245A EP 245A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971201258 ER PT J AU Stevens, RJ Ruesch, D Davies, PA Raines, DE AF Stevens, RJ Ruesch, D Davies, PA Raines, DE TI Modulation of 5-HT3A receptors by n-alcohols and volatile anesthetics is dependent on molecular volume. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 288A EP 288A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971201478 ER PT J AU Axmann, M Huppa, JB Moertelmaier, M Kieberger, N Sumen, C Davis, MM Schuetz, GJ AF Axmann, M Huppa, JB Moertelmaier, M Kieberger, N Sumen, C Davis, MM Schuetz, GJ TI In situ detection of the interaction between single T cell receptors and their antigenic ligands by Total Internal Reflection Fluorescence Microscopy (TIRFM) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Univ Linz, Inst Biophys, Linz, Austria. Stanford Univ, Beckman Ctr, Dept Microbiol & Immunol, Palo Alto, CA USA. Howard Hughes Med Inst, Palo Alto, CA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 445A EP 445A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971202291 ER PT J AU Das, J Stehle, T Miller, KW AF Das, J Stehle, T Miller, KW TI Identification of an alcohol-binding site in the second cysteine-rich domain of protein kinase C delta by X-ray crystallography SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 508A EP 508A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971202627 ER PT J AU Cheng, EHY Sheiko, TV Fisher, JK Craigen, WJ Korsmeyer, SJ AF Cheng, EHY Sheiko, TV Fisher, JK Craigen, WJ Korsmeyer, SJ TI VDAC2 inhibits BAK activation and mitochondrial apoptosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 516A EP 516A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971202667 ER PT J AU Tung, CH AF Tung, CH TI Fluorescent peptide probes for in vivo diagnostic imaging SO BIOPOLYMERS LA English DT Article DE fluorescence probe; peptide; imaging; near-infrared; enzyme activation ID NEAR-INFRARED FLUORESCENCE; FLUOROCHROME-LABELED INHIBITORS; CONTRAST AGENTS; INDOCYANINE GREEN; PROTEOLYTIC ACTIVITY; MOLECULAR BEACONS; PROTEASE ACTIVITY; BREAST-CANCER; CATHEPSIN-B; RECEPTOR AB Recently, many novel peptide-based near-infrared (NIR) fluorescent molecular probes have been developed for in vivo biomedical imaging. To report specific information of biological targets, the probes were individually designed according to the unique property or functions of their targets. These peptide-based probes can be classified into targeting, crosslinking, and enzyme-activatable probes. Several of them have been tested in various in vitro and in vivo models, and the obtained imaging information has been applied to disease detection, medical diagnosis, and drug evaluations. (C) 2004 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 85 TC 134 Z9 139 U1 4 U2 31 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2004 VL 76 IS 5 BP 391 EP 403 DI 10.1002/bip.20139 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 868UE UT WOS:000224937700003 PM 15389488 ER PT J AU Hashimoto, JG Beadles-Bohling, AS Wiren, KM AF Hashimoto, JG Beadles-Bohling, AS Wiren, KM TI Comparison of RiboGreen (R) and 18S rRNA quantitation for normalizing real-time RT-PCR expression analysis SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; QUANTIFICATION; VALIDATION C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Wiren, KM (reprint author), Portland VA Med Ctr, P3-R&D39,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 NR 9 TC 71 Z9 73 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2004 VL 36 IS 1 BP 54 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763KF UT WOS:000188083600007 PM 14740484 ER PT J AU Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, PT AF Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, PT TI Deformation field morphometry findings in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT Conference of the International-Society-for-Bipolar-Disorders CY FEB 05-07, 2004 CL Sydney, AUSTRALIA SP Int Soc Bipolar Disorders C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Div, San Antonio, TX 78284 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. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Verona, Sch Med, Dept Med & Publ Hlth, I-37100 Verona, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. RI Kochunov, Peter/E-4711-2010; brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2004 VL 6 SU 1 MA 124 BP 16 EP 17 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 778RR UT WOS:000189255000024 ER PT J AU Wang, ZY Cohen, K Shao, Y Mole, P Dombkowski, D Scadden, DT AF Wang, ZY Cohen, K Shao, Y Mole, P Dombkowski, D Scadden, DT TI Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels SO BLOOD LA English DT Article ID EMBRYONIC STEM-CELLS; IN-VITRO DIFFERENTIATION; YOLK-SAC; HEMATOPOIETIC-CELLS; ENDOTHELIAL-CELLS; CARDIOVASCULAR DEVELOPMENT; DEFINITIVE HEMATOPOIESIS; SPROUTING ANGIOGENESIS; COMMON PRECURSOR; TYROSINE KINASES AB Differentiation of pluripotent embryonic stem (ES) cells is associated with expression of fate-specifying gene products. Coordinated development, however, must involve modifying factors that enable differentiation and growth to adjust in response to local microenvironmental determinants. We report here that the ephrin receptor, EphB4, known to be spatially restricted in expression and critical for organized vessel formation, modifies the rate and magnitude of ES cells acquiring genotypic and phenotypic characteristics of mesodermal tissues. Hemangioblast, blood cell, cardiomyocyte, and vascular differentiation was impaired in EphB4(-/-) ES cells in conjunction with decreased expression of mesoderm-associated, but not neuroectoderm-associated, genes. Therefore, EphB4 modulates the response to mesoderm induction signals. These data add differentiation kinetics to the known effects of ephrin receptors on mammalian cell migration and adhesion. We propose that modifying sensitivity to differentiation cues is a further means for ephrin receptors to contribute to tissue patterning and organization. C1 Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 5212, Charlestown, MA 02129 USA. NR 53 TC 37 Z9 44 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 JAN 1 PY 2004 VL 103 IS 1 BP 100 EP 109 DI 10.1182/blood-2003-04-1063 PG 10 WC Hematology SC Hematology GA 757QM UT WOS:000187573000024 PM 12958066 ER PT J AU Miklos, DB Kim, HT Zorn, E Hochberg, EP Guo, LX Mattes-Ritz, A Viatte, S Soiffer, RJ Antin, JH Ritz, J AF Miklos, DB Kim, HT Zorn, E Hochberg, EP Guo, LX Mattes-Ritz, A Viatte, S Soiffer, RJ Antin, JH Ritz, J TI Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors SO BLOOD LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol ID VERSUS-HOST-DISEASE; H-Y-ANTIGEN; BONE-MARROW GRAFT; T-LYMPHOCYTES; GENE CODES; IDENTIFICATION; REJECTION; MICE; HLA; IMMUNOTHERAPY AB Minor histocompatibility antigens (mHAs) recognized by donor T cells play a central role as immunologic targets of graft-versus-host disease (GVHD) and graft versus leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Men who have undergone sex-mismatched allogeneic HSCT are at high risk for GVHD because of immune responses directed against mHAs encoded by genes on the Y chromosome (termed H-Y antigens). We hypothesized that the immunogenicity of mHAs results in a coordinated response involving B cells as well as T cells. To test this, we measured antibody responses to a well-characterized H-Y antigen, dead box RNA helicase Y(DBY), and its homolog, DBX, in 150 HSCT patients. Using Western blot and enzyme-linked immunosorbent assay (ELISA), we found that 50% of male patients who received stem cell grafts from female donors developed antibody responses to recombinant DBY protein. Antibodies to DBY were also detected in 17% of healthy women, but not in healthy men. Antibody responses were directed primarily against areas of amino acid disparity between DBY and DBX. These studies demonstrate that the immune response to mHA includes the generation of specific antibodies and suggests that the serologic response to these antigens may also be useful in the identification of new mHAs. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Dana Farber Canc Inst,Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St,M530, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [HL69132, HL70149, K08 HL069132, K08 HL69132, P01 HL070149]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 40 TC 106 Z9 110 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 JAN 1 PY 2004 VL 103 IS 1 BP 353 EP 359 DI 10.1182/blood-2003-03-0984 PG 7 WC Hematology SC Hematology GA 757QM UT WOS:000187573000060 PM 14512314 ER PT J AU Elfenbein, GJ Sackstein, R Oblon, DJ AF Elfenbein, GJ Sackstein, R Oblon, DJ TI Do G-CSF mobilized, peripheral blood-derived stem cells from healthy, HLA-identical donors really engraft more rapidly than do G-CSF primed, bone marrow-derived stem cells? No! SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article; Proceedings Paper CT Workshop on Stem Cell Plasticity CY APR 08-11, 2003 CL PROVIDENCE, RHODE ISLAND SP Leukemia & Lymphoma Soc, Univ Nevada, Roger Williams Med Ctr DE G-CSF; stem cells; peripheral blood-derived; bone marrow-derived ID COLONY-STIMULATING FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST DISEASE; MYELOABLATIVE THERAPY; PROGENITOR CELLS; RANDOMIZED-TRIAL; TRANSPLANTATION; LYMPHOCYTES; LYMPHOMA; RESCUE AB For more than a decade, the notion that peripheral blood-derived stem cells engraft more rapidly than bone marrow-derived stem cells after high-dose therapy has dominated our thinking. Recently, reports that granulocyte colony-stimulating factor (G-CSF) induces a proteolytic marrow microenvironment have provided mechanistic support for that belief, compelling us to review our own experience of 29 consecutive transplants with HLA-identical blood and marrow stem cells. In contrast to several reported randomized controlled trials, we found marrow stem cells engraft just as rapidly (median day 11 for granulocytes over 500/mul and median day 17 for platelets over 20,000/mul) as blood stem cells (median day 12 and median day 19, respectively) if the donor is treated with G-CSF in the same manner before marrow harvest as the donor is treated with G-CSF before leukapheresis. These observations with healthy HLA-identical donors confirm the results of our prior randomized autotransplant study. We propose the concept that the level of activation of the stem cells (induced by G-CSF) determines engraftment kinetics and not the anatomical site of derivation. (C) 2003 Elsevier Inc. All rights reserved. C1 Roger Williams Med Ctr, Adele R Decof Canc Ctr, Blood & Marrow Transplant Program, Providence, RI 02908 USA. Univ S Florida, Div Bone Marrow Transplantat, Tampa, FL 33612 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Elfenbein, GJ (reprint author), Roger Williams Med Ctr, Adele R Decof Canc Ctr, Blood & Marrow Transplant Program, 825 Chalkstone Ave, Providence, RI 02908 USA. EM gelfenbein@rwmc.org NR 25 TC 13 Z9 13 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN-FEB PY 2004 VL 32 IS 1 BP 106 EP 111 DI 10.1016/j.bcmd.2003.09.024 PG 6 WC Hematology SC Hematology GA 773DT UT WOS:000188883000020 PM 14757423 ER PT J AU Pisani, D Poling, LL Lyons-Weiler, M Hedges, SB AF Pisani, Davide Poling, Laura L. Lyons-Weiler, Maureen Hedges, S. Blair TI The colonization of land by animals: molecular phylogeny and divergence times among arthropods SO BMC BIOLOGY LA English DT Article AB Background: The earliest fossil evidence of terrestrial animal activity is from the Ordovician, similar to 450 million years ago (Ma). However, there are earlier animal fossils, and most molecular clocks suggest a deep origin of animal phyla in the Precambrian, leaving open the possibility that animals colonized land much earlier than the Ordovician. To further investigate the time of colonization of land by animals, we sequenced two nuclear genes, glyceraldehyde-3-phosphate dehydrogenase and enolase, in representative arthropods and conducted phylogenetic and molecular clock analyses of those and other available DNA and protein sequence data. To assess the robustness of animal molecular clocks, we estimated the deuterostome-arthropod divergence using the arthropod fossil record for calibration and tunicate instead of vertebrate sequences to represent Deuterostomia. Nine nuclear and 15 mitochondrial genes were used in phylogenetic analyses and 61 genes were used in molecular clock analyses. Results: Significant support was found for the unconventional pairing of myriapods (millipedes and centipedes) with chelicerates (spiders, scorpions, horseshoe crabs, etc.) using nuclear and mitochondrial genes. Our estimated time for the divergence of millipedes (Diplopoda) and centipedes (Chilopoda) was 442 +/- 50 Ma, and the divergence of insects and crustaceans was estimated as 666 +/- 58 Ma. Our results also agree with previous studies suggesting a deep divergence (similar to 1100 - 900 Ma) for arthropods and deuterostomes, considerably predating the Cambrian Explosion seen in the animal fossil record. Conclusions: The consistent support for a close relationship between myriapods and chelicerates, using mitochondrial and nuclear genes and different methods of analysis, suggests that this unexpected result is not an artefact of analysis. We propose the name Myriochelata for this group of animals, which includes many that immobilize prey with venom. Our molecular clock analyses using arthropod fossil calibrations support earlier studies using vertebrate calibrations in finding that deuterostomes and arthropods diverged hundreds of millions of years before the Cambrian explosion. However, our molecular time estimate for the divergence of millipedes and centipedes is close to the divergence time inferred from fossils. This suggests that arthropods may have adapted to the terrestrial environment relatively late in their evolutionary history. C1 [Pisani, Davide; Poling, Laura L.; Lyons-Weiler, Maureen; Hedges, S. Blair] Penn State Univ, NASA, Astrobiol Inst, University Pk, PA 16802 USA. [Pisani, Davide; Poling, Laura L.; Lyons-Weiler, Maureen; Hedges, S. Blair] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Poling, Laura L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lyons-Weiler, Maureen] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15232 USA. RP Hedges, SB (reprint author), Penn State Univ, NASA, Astrobiol Inst, University Pk, PA 16802 USA. EM D.Pisani@nhm.ac.uk; Laura_Poling@student.hms.harvard.edu; mal26@pitt.edu; sbh1@psu.edu FU National Science Foundation [DBI-0112670]; National Aeronautics and Space Administration [NCC2-1057] FX We thank Frederick Schram for helpful advice concerning arthropod taxonomy and literature. This work was supported by grants to S.B.H. from the National Science Foundation (DBI-0112670) and the National Aeronautics and Space Administration (NCC2-1057). NR 57 TC 141 Z9 151 U1 8 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PY 2004 VL 2 AR 1 DI 10.1186/1741-7007-2-1 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA V40AM UT WOS:000209451500001 PM 14731304 ER PT J AU Herndon, TO Gonzalez, S Gowrishankar, TR Anderson, RR Weaver, JC AF Herndon, Terry O. Gonzalez, Salvador Gowrishankar, T. R. Anderson, R. Rox Weaver, James C. TI Transdermal microconduits by microscission for drug delivery and sample acquisition SO BMC MEDICINE LA English DT Article AB Background: Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 mu m diameter areas of human skin in vivo. Methods: Microscissioning is achieved by a limited flux of accelerated gas: 25 mu m inert particles passing through the aperture in a mask held against the stratum corneum. The particles scize (cut) tissue, which is removed by the gas flow with the sensation of a gentle stream of air against the skin. The resulting microconduit is fully open and may be between 50 and 200 mu m deep. Results: In vivo adult human tests show that microconduits reduce the electrical impedance between two ECG electrodes from approximately 4,000 Omega to 500 Omega. Drug delivery has been demonstrated in vivo by applying lidocaine to a microconduit from a cotton swab. Sharp point probing demonstrated full anaesthesia around the site within three minutes. Topical application without the microconduit required approximately 1.5 hours. Approximately 180 mu m deep microconduits in vivo yielded blood sample volumes of several mu l, with a faint pricking sensation as blood enters tissue. Blood glucose measurements were taken with two commercial monitoring systems. Microconduits are invisible to the unaided eye, developing a slight erythematous macule that disappears over days. Conclusion: Microscissioned microconduits may provide a minimally invasive basis for delivery of any size molecule, and for extraction of interstitial fluid and blood samples. Such microconduits reduce through-skin electrical impedance, have controllable diameter and depth, are fully open and, after healing, no foreign bodies were visible using through-skin confocal microscopy. In subjects to date, microscissioning is painless and rapid. C1 [Herndon, Terry O.; Gowrishankar, T. R.; Anderson, R. Rox; Weaver, James C.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gonzalez, Salvador; Anderson, R. Rox] Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Weaver, JC (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM herndon@mit.edu; sgonzalez3@partners.org; tgowrish@mit.edu; rranderson@partners.org; jcw@mit.edu FU Massachusetts Institute of Technology Lincoln Laboratory; NIH; Massachusetts General Hospital; CIMIT FX The authors are grateful to Rieko Tachihara and Milind Rajadhyaksha of the M.G.H Wellman Laboratory of Photomedicine, Department of Dermatology for their assistance and cooperation with in vivo testing, useful discussions and assistance in using the Lucid Vivascope 1000. We thank James Howard of MIT Lincoln Laboratory for the many experiments he performed in perfecting the scission process. This research was supported by grants from Massachusetts Institute of Technology Lincoln Laboratory, and NIH, with additional support from Massachusetts General Hospital and CIMIT. NR 18 TC 11 Z9 15 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PY 2004 VL 2 AR 12 DI 10.1186/1741-7015-2-12 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA V22MX UT WOS:000208280400012 PM 15090063 ER PT J AU Shao, WL Brown, M AF Shao, WL Brown, M TI Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy SO BREAST CANCER RESEARCH LA English DT Review DE coregulators; estrogen receptor; growth factors; SERM; tamoxifen resistance ID STEROID-HORMONE RECEPTORS; ACTIVATED PROTEIN-KINASE; ALPHA TRANSCRIPTIONAL ACTIVITY; CARDIOVASCULAR RISK-FACTORS; SURGICAL-ADJUVANT-BREAST; LIGAND-BINDING DOMAIN; GROWTH FACTOR-I; NUCLEAR-RECEPTOR; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL AB Estrogen receptor ( ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These include targeting the level of estrogen, blocking estrogen action at the ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is limited by either intrinsic or acquired resistance. Identifying the factors and pathways responsible for sensitivity and resistance remains a challenge in improving the treatment of breast cancer. With a better understanding of coordinated action of ER, its coregulatory factors, and the influence of other intracellular signaling cascades, improvements in breast cancer therapy are emerging. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, 44 Binney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 NR 178 TC 108 Z9 114 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2004 VL 6 IS 1 BP 39 EP 52 DI 10.1186/bcr742 PG 14 WC Oncology SC Oncology GA 751WA UT WOS:000187112000010 PM 14680484 ER PT J AU Piccart, M Winer, E AF Piccart, M Winer, E TI Introducing Breast Cancer Research's updates on clinical trials SO BREAST CANCER RESEARCH LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Jules Bordet, B-1000 Brussels, Belgium. RP Winer, E (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Eric_Winer@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2004 VL 6 IS 4 BP 164 EP 164 DI 10.1186/bcr810 PG 1 WC Oncology SC Oncology GA 840AA UT WOS:000222828200006 ER PT J AU Yao, J Polyak, K AF Yao, J Polyak, K TI EMSY links breast cancer gene 2 to the 'Royal Family' SO BREAST CANCER RESEARCH LA English DT Review DE BRCA2; breast cancer; EMSY; familiar; sporadic ID TRANSCRIPTIONAL ACTIVATION; IONIZING-RADIATION; SPORADIC BREAST; OVARIAN-CANCER; DNA-DAMAGE; BRCA1; SUSCEPTIBILITY; COMPLEX; RAD51; AMPLIFICATION AB Although the role of the breast cancer gene 2 (BRCA2) tumor suppressor gene is well established in inherited breast and ovarian carcinomas, its involvement in sporadic disease is still uncertain. The recent identification of a novel BRCA2 binding protein, EMSY, as a putative oncogene implicates the BRCA2 pathway in sporadic tumors. Furthermore, EMSY's binding to members of the 'Royal Family' of chromatin remodeling proteins may lead to a better understanding of the physiological function of BRCA2 and its role in chromatin remodeling. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu NR 27 TC 6 Z9 6 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2004 VL 6 IS 5 BP 201 EP 203 DI 10.1186/bcr916 PG 3 WC Oncology SC Oncology GA 853YH UT WOS:000223866400004 PM 15318925 ER PT J AU Lin, NU Winer, EP AF Lin, NU Winer, EP TI New targets for therapy in breast cancer - Small molecule tyrosine kinase inhibitors SO BREAST CANCER RESEARCH LA English DT Review DE breast cancer; EGFR; HER2; targeted therapy; tyrosine kinase inhibitors ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR EGFR; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; LUNG-CANCER; GEFITINIB; MULTICENTER; EXPRESSION; ZD1839; CHEMOTHERAPY AB Over the past several years many advances have been made in our understanding of critical pathways involved in carcinogenesis and tumor growth. These advances have led to the investigation of small molecule inhibitors of the ErbB family of receptor tyrosine kinases across a broad spectrum of malignancies. In this article we summarize the rationale for targeting members of the ErbB family in breast cancer, and review the preclinical and clinical data for the agents that are furthest in development. In addition, we highlight directions for future research, such as exploration of the potential crosstalk between the ErbB and hormone receptor signal transduction pathways, identification of predictive markers for tumor sensitivity, and development of rational combination regimens that include the tyrosine kinase inhibitors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ewiner@partners.org FU NCI NIH HHS [T32 CA009172] NR 41 TC 40 Z9 40 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2004 VL 6 IS 5 BP 204 EP 210 DI 10.1186/bcr919 PG 7 WC Oncology SC Oncology GA 853YH UT WOS:000223866400005 PM 15318926 ER PT J AU Burstein, HJ Parker, LM Doherty, J Partridge, AH Schapira, L Ryan, PD Younger, J Harris, LN Moy, B Bunnell, CA AF Burstein, HJ Parker, LM Doherty, J Partridge, AH Schapira, L Ryan, PD Younger, J Harris, LN Moy, B Bunnell, CA TI Use of the long-acting hematopoietic growth factors pegfilgrastim and darbepoetin alfa in support of dose-dense adjuvant chemotherapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S60 EP S60 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600163 ER PT J AU Chang, SB Miron, P Kung, AL Miron, A Iglehart, JD AF Chang, SB Miron, P Kung, AL Miron, A Iglehart, JD TI New treatments for ER plus breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S251 EP S251 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600713 ER PT J AU Duda, RB Hill, AG AF Duda, RB Hill, AG TI Breast health in developing countries. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Hill Ag, BIDMC, HMS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S101 EP S101 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600287 ER PT J AU Goss, PE AF Goss, PE TI The rise and current status of aromatase inhibitors in breast cancer treatment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S1 EP S1 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600003 ER PT J AU Hartman, AR Kurian, AW Mills, MA Ford, JM Smith, DN Daniel, BL AF Hartman, AR Kurian, AW Mills, MA Ford, JM Smith, DN Daniel, BL TI Magnetic resonance galactography: a new technique for localization of ductal atypia. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S190 EP S190 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600539 ER PT J AU Jones, JL Lesnikoski, BA Howard-McNatt, M Kaelin, C Rhei, E Christian, RL Colbert, JA Michaelson, JS Hughes, KS Gadd, MA Barbara, SL AF Jones, JL Lesnikoski, BA Howard-McNatt, M Kaelin, C Rhei, E Christian, RL Colbert, JA Michaelson, JS Hughes, KS Gadd, MA Barbara, SL TI Sentinel node biopsy (SNB) in patients with ductal carcinoma-in-situ (DCIS) and ductal carcinoma-in-situ with microinvasion (DCISM). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S70 EP S70 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600192 ER PT J AU Kim, J Overmoyer, B Silverman, P Cooper, B Shenk, R Lyons, J AF Kim, J Overmoyer, B Silverman, P Cooper, B Shenk, R Lyons, J TI The acute and late cosmetic outcomes from the use of concurrent paclitaxel (Taxol) and definitive breast radiation therapy in early stage breast cancer following four cycles of adriamycin/cyclophosphamide chemotherapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S172 EP S173 PG 2 WC Oncology SC Oncology GA 877SE UT WOS:000225589600490 ER PT J AU Leining, MG Gelber, S Rosenberg, R Przypyszny, M Rein, A Winer, E Partridge, A AF Leining, MG Gelber, S Rosenberg, R Przypyszny, M Rein, A Winer, E Partridge, A TI Menopausal symptoms in very young breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Young Survival Coalit, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S139 EP S140 PG 2 WC Oncology SC Oncology GA 877SE UT WOS:000225589600393 ER PT J AU Punglia, RS Kuntz, KM Winer, E Weeks, JC Burstein, HJ AF Punglia, RS Kuntz, KM Winer, E Weeks, JC Burstein, HJ TI Optimizing adjuvant endocrine therapy in postmenopausal women with early stage breast cancer: a decision analysis. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S58 EP S59 PG 2 WC Oncology SC Oncology GA 877SE UT WOS:000225589600160 ER PT J AU Rauch, PK AF Rauch, PK TI Impact of breast cancer on parents and children SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600016 ER PT J AU Rincon, M Harris, L Broadwater, G Crocker, A Dressler, L Berry, D Winer, E Hudis, C Norton, L Appel, S Muss, H AF Rincon, M Harris, L Broadwater, G Crocker, A Dressler, L Berry, D Winer, E Hudis, C Norton, L Appel, S Muss, H TI Interleukin-6 (IL-6) expression does not predict response rate to paclitaxel in women with metastatic breast cancer (MBC): Cancer and Leukemia Group B (CALGB) trial 159806. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 VT Canc Ctr, Burlington, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CALGB, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S51 EP S51 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600139 ER PT J AU Sacchini, V Costa, A Vanel, D Crowe, JP Hughes, KS AF Sacchini, V Costa, A Vanel, D Crowe, JP Hughes, KS TI Report of the validation task force on the biofield electropotential test for breast cancer diagnosis SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Maugeri Fdn, Pavia, Italy. Inst Gustave Roussy, Villejuif, France. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. TAsk Force, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S221 EP S222 PG 2 WC Oncology SC Oncology GA 877SE UT WOS:000225589600628 ER PT J AU Walker, SR Frank, DA AF Walker, SR Frank, DA TI Her2 amplifies the opposing roles of STAT3 and STAT5 in breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S215 EP S215 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600613 ER PT J AU Woff, AC Wang, M Sparano, JA Pins, MR Thor, AD Davidson, NE AF Woff, AC Wang, M Sparano, JA Pins, MR Thor, AD Davidson, NE TI Cardiac safety and clinical activity of pegylated liposomal doxorubicin (D) and docetaxel (T) with and without trastuzumab (H) as 1(st) line chemotherapy in HER2-positive and HER2-negative metastatic breast cancer (MBC): Eastern Cooperative Oncology Group (ECOG) trial E3198. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S125 EP S125 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600354 ER PT J AU You, F Wittner, B Gentleman, R Petkovska, A Ngo, T Kamma, M Smith, D Richardson, A Iglehart, JD Winer, E Sgroi, D Harris, LN AF You, F Wittner, B Gentleman, R Petkovska, A Ngo, T Kamma, M Smith, D Richardson, A Iglehart, JD Winer, E Sgroi, D Harris, LN TI Gene profiling and response to Herceptin and Vinorelbine (H&N) in HER2 3+/FISH+ early breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 27th Annual Charles A Colman San Antonio Breast Cancer Symposium CY DEC 08-11, 2004 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Brigham & Womens Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2004 VL 88 SU 1 BP S48 EP S48 PG 1 WC Oncology SC Oncology GA 877SE UT WOS:000225589600130 ER PT J AU Ballantyne, JC AF Ballantyne, JC TI Does epidural analgesia improve surgical outcome? SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Editorial Material ID REGIONAL ANESTHESIA; CONTROLLED-TRIALS; RANDOMIZED TRIAL; SURGERY; ANTICOAGULATION; METAANALYSES; MORTALITY; PATIENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr, Boston, MA 02114 USA. RP Ballantyne, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr, 15 Parkman St,WACC 333, Boston, MA 02114 USA. NR 29 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JAN PY 2004 VL 92 IS 1 BP 4 EP 6 DI 10.1093/bja/aeh005 PG 3 WC Anesthesiology SC Anesthesiology GA 753ED UT WOS:000187218400002 PM 14665544 ER PT J AU Rosen, LS Gordon, DH Dugan, W Major, P Eisenberg, PD Provencher, L Kaminski, M Simeone, J Seaman, J Chen, BL Coleman, RE AF Rosen, LS Gordon, DH Dugan, W Major, P Eisenberg, PD Provencher, L Kaminski, M Simeone, J Seaman, J Chen, BL Coleman, RE TI Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion SO CANCER LA English DT Article DE bisphosphonates; breast neoplasms; neoplasm metastasis; zoledronic acid ID PLACEBO-CONTROLLED TRIAL; SKELETAL COMPLICATIONS; PROSTATE-CANCER; MARKERS; BISPHOSPHONATES; MALIGNANCY; TURNOVER; WOMEN AB BACKGROUND. Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial. METHODS. Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3-4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone. RESULTS. Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least I osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]). CONCLUSIONS. The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least I osteolytic lesion at study entry. (C) 2003 American Cancer Society. C1 Canc Inst Med Grp, Santa Monica, CA USA. US Oncol, Dept Med Oncol Hematol, San Antonio, TX USA. Community Canc Care, Indianapolis, IN USA. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. Calif Canc Care, Greenbrae, CA USA. Hop St Sacrement, Quebec City, PQ, Canada. Amer Med Res Inst, Cumming, GA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Nova Pharmaceut Corp, E Hanover, NJ USA. Western Pk Hosp, Canc Res Ctr, Sheffield, S Yorkshire, England. RP Rosen, LS (reprint author), Canc Inst Med Grp, 11818 Wilshire Blvd,Suite 200, Los Angeles, CA 90025 USA. NR 17 TC 183 Z9 204 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2004 VL 100 IS 1 BP 36 EP 43 DI 10.1002/cncr.11892 PG 8 WC Oncology SC Oncology GA 756LV UT WOS:000187467400006 PM 14692022 ER PT J AU Arnold, CN Goel, A Compton, C Marcus, V Niedzwiecki, D Dowell, JM Wasserman, L Inoue, T Mayer, RJ Bertagnolli, MM Boland, CR AF Arnold, CN Goel, A Compton, C Marcus, V Niedzwiecki, D Dowell, JM Wasserman, L Inoue, T Mayer, RJ Bertagnolli, MM Boland, CR TI Evaluation of microsatellite instability, hMLH1 expression and hMLH1 promoter hypermethylation in defining the MSI phenotype of colorectal cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE hMLH1; microsatellite instability; promoter methylation; colorectal cancer; immunohistochemistry ID DNA MISMATCH REPAIR; COLON-CANCER; MUTATOR PATHWAYS; GENE-EXPRESSION; PROXIMAL COLON; CELL-LINES; METHYLATION; TUMORS; HEREDITARY; IMMUNOHISTOCHEMISTRY AB Introduction: About 15% of all colorectal cancers (CRCs) demonstrate high levels of microsatellite instability (MSI-H) and are currently best identified by molecular analysis of microsatellite markers. Most sporadic CRCs with MSI-H are known to be associated with the methylation of the hMLH1 promoter. Promoter methylation coincided with lack of hMLH1 expression. We aimed to investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter, and to determine the usefulness of each method in defining the MSI phenotype in sporadic CRCs. Materials and Methods: CRCs from 173 patients from the Cancer and Leukemia Group B (CALGB) were assessed for their MSI status. An additional cohort of 18 MSI-H tumors from the University of California San Diego (UCSD) was included in the analysis of the MSI-H subgroup. MSI testing was performed by PCR using five standard MSI markers. hMLH1 promoter analysis was investigated by methylation specific PCR (MSP), and expression of the MMR genes hMLH1 and hMSH2 was examined by immunohistochemistry (IHC). Results: Of the 173 CALGB tumors, 111 (64%) were MSS, 35 (20%) were MSI-L and 27 (16%) MSI-H, respectively. Data on hMLH1 protein expression, hMSH2 protein expression and hMLH1 methylation are available on 128, 173 and 81 of these tumors, respectively. Presence of hMLH1 and hMSH2 protein expression was significantly associated with MSI status. Four of 45 (8.9%) MSI-H tumors and 0 of 146 (0%) MSS/MSI-L tumors did not express hMSH2 (p = 0.0028). hMLH1 protein expression was present in 107 of 108 (99%) MSS and MSI-L tumors versus 11 of 20 (55%) MSI-H tumors (p < 0.0001). Of 61 MSS and MSI-L cancers studied for methylation, 11 (18%) were methylated at the hMLH1 promoter whereas 14 of 20 (70%) MSI-H cancers were methylated (p = 0.0001). In 27 MSI-H tumors studied for hMLH1 protein expression and methylation, 93% of tumors with loss of expression (93%) were also methylated while 42% (5/12) with positive immunostaining for hMLH1 were methylated at the hMLH1 promoter (p = 0.009). Conclusions: Promoter methylation and hMLH1 expression are significantly associated with the MSI-H phenotype in CRC. Promoter methylation analysis provides a useful means to screen for MSI-H tumors. Our data further suggests that hMLH1 promoter methylation analysis alone cannot replace MSI testing, as a significant number of MSI-H tumors could be potentially overseen by such an approach. We suggest that phenotypic evaluation of CRC is performed most reliably with MSI testing, although expression analysis and investigation of the promoter methylation status may complement the screening process. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Duke Univ, CALGB Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. RP Boland, CR (reprint author), Baylor Univ, Med Ctr, 2 Hoblitzelle,3500 Gaston Ave, Dallas, TX USA. EM RickBo@BaylorHealth.Edu FU NCI NIH HHS [R01-CA 72851, CA31946] NR 34 TC 22 Z9 24 U1 0 U2 3 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 JAN PY 2004 VL 3 IS 1 BP 73 EP 78 DI 10.4161/cbt.3.1.590 PG 6 WC Oncology SC Oncology GA 805QF UT WOS:000220380100014 PM 14726676 ER PT J AU Campling, B AF Campling, B TI Topotecan in small cell lung cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE small cell lung cancer; chemotherapy; topotecan ID COOPERATIVE-ONCOLOGY-GROUP; PHASE-II; CYCLOPHOSPHAMIDE; CAMPTOTHECIN; TRIAL C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Campling, B (reprint author), Univ Penn, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM complinb@mail.med.upenn.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2004 VL 3 IS 1 BP 94 EP 95 DI 10.4161/cbt.3.1.713 PG 2 WC Oncology SC Oncology GA 805QF UT WOS:000220380100019 PM 14739785 ER PT J AU Lepourcelet, M Chen, YNP France, DS Wang, HS Crews, P Petersen, F Bruseo, C Wood, AW Shivdasani, RA AF Lepourcelet, M Chen, YNP France, DS Wang, HS Crews, P Petersen, F Bruseo, C Wood, AW Shivdasani, RA TI Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex SO CANCER CELL LA English DT Article ID ADENOMATOUS POLYPOSIS-COLI; GLYCOGEN-SYNTHASE KINASE-3; BETA-CATENIN; COLORECTAL-CANCER; XENOPUS EMBRYOS; CYCLIN D1; HEPATOCELLULAR CARCINOMAS; SUBCELLULAR-DISTRIBUTION; SIGNALING PATHWAY; HIGHLY POTENT AB Key molecular lesions in colorectal and other cancers cause beta-catenin-dependent transactivation of T cell factor (Tcf)dependent genes. Disruption of this signal represents an opportunity for rational cancer therapy. To identify compounds that inhibit association between Tcf4 and beta-catenin, we screened libraries of natural compounds in a high-throughput assay for immunoenzymatic detection of the protein-protein interaction. Selected compounds disrupt Tcf/beta-catenin complexes in several independent in vitro assays and potently antagonize cellular effects of beta-catenin-dependent activities, including reporter gene activation, c-myc or cyclin D1 expression, cell proliferation, and duplication of the Xenopus embryonic dorsal axis. These compounds thus meet predicted criteria for disrupting Tcf/beta-catenin complexes and define a general standard to establish mechanism-based activity of small molecule inhibitors of this pathogenic protein-protein interaction. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Novartis Inst Biomed Res, Dept Oncol, Cambridge, MA 02139 USA. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. Univ Calif Santa Cruz, Inst Marine Sci, Santa Cruz, CA 95064 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NCI NIH HHS [CA52955] NR 68 TC 419 Z9 434 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2004 VL 5 IS 1 BP 91 EP 102 DI 10.1016/S1535-6108(03)00334-9 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 766XH UT WOS:000188400300012 PM 14749129 ER PT J AU Frahm, S Kurtz, A Kluwe, L Farassati, F Friedrich, RE Mautner, VF AF Frahm, Silke Kurtz, Andreas Kluwe, Lan Farassati, Faris Friedrich, Reinhard E. Mautner, Victor F. TI Sulindac derivatives inhibit cell growth and induce apoptosis in primary cells from malignant peripheral nerve sheath tumors of NF1-patients SO CANCER CELL INTERNATIONAL LA English DT Article AB Background: Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms leading to death in most cases. Patients with Neurofibromatosis type 1 have an increased risk of developing this malignancy. The metabolites of the inactive prodrug Sulindac, Sulindac Sulfide and Sulindac Sulfone (Exisulind) are new chemopreventive agents that show promising results in the treatment of different cancer types. In this study we examined the antineoplastic effect of these compounds on primary cells derived from two MPNSTs of Neurofibromatosis type 1 patients. Results: Exisulind and Sulindac Sulfide showed a dramatic time- and dose-dependent growth inhibitory effect with IC50-values of 120 mu M and 63 mu M, respectively. The decrease in viability of the tested cells correlated with induction of apoptosis. Treatment with 500 mu M Exisulind and 125 mu M Sulindac Sulfide for a period of 2 days increased the rate of apoptosis 21-27-fold compared to untreated cells. Reduced expression of RAS-GTP and phosphorylated ERK1/2 was detected in treated MPNST cells. Moreover, elevated levels of phosphorylated SAPK/JNK were found after drug treatment, and low activation of cleaved caspase-3 was seen. Conclusions: Our results suggest that this class of compounds may be of therapeutic benefit for Neurofibromatosis type 1 patients with MPNST. C1 [Frahm, Silke] Univ Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, Hamburg, Germany. [Kurtz, Andreas; Farassati, Faris] Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA USA. [Kluwe, Lan; Friedrich, Reinhard E.; Mautner, Victor F.] Univ Hosp Eppendorf, Dept Maxillofacial Surg, Hamburg, Germany. RP Frahm, S (reprint author), Univ Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, Hamburg, Germany. EM sfrahm@uke.uni-hamburg.de; KurtzA@rki.de; kluwe@uke.uni-hamburg.de; Farassati.Faris@mayo.edu; rfriedri@uke.uni-hamburg.de; vrges@aol.com FU department of neurosurgery at University Hospital Eppendorf, Hamburg; Deutsche Krebshilfe [70-2653-Ma3, 70-3072-Ma4]; NIH [NS37895] FX We thank Prof. M. Westphal of the department of neurosurgery at University Hospital Eppendorf, Hamburg for his support. This study was supported by the Deutsche Krebshilfe 70-2653-Ma3, 70-3072-Ma4 and NIH grant NS37895. NR 35 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2867 J9 CANCER CELL INT JI Cancer Cell Int. PY 2004 VL 4 AR 4 DI 10.1186/1475-2867-4-4 PG 11 WC Oncology SC Oncology GA V24IT UT WOS:000208404800004 ER PT J AU Kane, MA AF Kane, MA TI The role of folates in squamous cell carcinoma of the head and neck SO CANCER DETECTION AND PREVENTION LA English DT Article DE folate; head and neck cancer; squamous cell carcinoma; chemoprevention ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISMS; LUNG-CANCER PATIENTS; NEURAL-TUBE DEFECTS; DNA EXCISION-REPAIR; ESOPHAGEAL CANCER; STRAND BREAKS; RISK-FACTORS; PROMOTER METHYLATION; CHINESE POPULATION; EPITHELIAL-CELLS AB The primary objective of this review is to explore the hypothesis that folate insufficiency may be important in the pathogenesis of squamous cell carcinomas of the head and neck (SCCHN) and that folate repletion may be an effective component of chemoprevention. The main results are that folate insufficiency disrupts DNA global and specific gene methylation patterns such that the activity of certain tumor suppressor genes such as p16 and possibly p53 may be lost. Folate pool imbalance and impaired repair mechanisms may contribute to DNA instability and strand breaks. Sensitive methods exist for identification of individuals with folate insufficiency in contrast to the relatively insensitive conventional serum or red cell folate assays with broad "normal" ranges. The impact of folate supplementation can thus be quantified. Folate imbalance may result from alterations in folate cellular uptake by the reduced folate carrier (RFC) and/or the folate receptor (FR) and polymorphisms in enzymes important in folate retention such as folylpolyglutamate synthetase and in folate modification such as methylene tetrahydrofolate reductase (MTHFR). Known predisposing factors for SCCHN such as alcohol and tobacco carcinogens may influence folate balance. Folate supplementation may reduce primary or secondary risk of cancer. Formal studies of folate sufficiency in persons at risk for or diagnosed and treated for SCCHN are needed to define the role of folate supplementation in the prevention of these cancers. (c) 2004 lnternational Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Kane, MA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Med Oncol, 1055 Clermont St, Denver, CO 80220 USA. EM madeleine.kane@uchsc.edu NR 75 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2004 VL 29 IS 1 BP 46 EP 53 DI 10.1016/j.cdp.2004.08.002 PG 8 WC Oncology SC Oncology GA 906SS UT WOS:000227664000007 ER PT J AU Kulke, MH Kim, H Stuart, K Clark, JW Ryan, DP Vincitore, M Mayer, RJ Fuchs, CS AF Kulke, MH Kim, H Stuart, K Clark, JW Ryan, DP Vincitore, M Mayer, RJ Fuchs, CS TI A phase II study of docetaxel in patients with metastatic carcinoid tumors SO CANCER INVESTIGATION LA English DT Article DE carcinoid tumors; neuroendocrine tumors; docetaxel; chemotherapy ID NEUROENDOCRINE TUMORS; ONCOLOGY-GROUP; OCTREOTIDE; CANCER AB Twenty-one patients with metastatic carcinoid tumors were treated with docetaxel. Although the treatment was well tolerated, no objective radiologic responses were observed. Novel, more effective agents are needed for this disease. Background. Traditional combination chemotherapy regimens containing streptozocin, doxorubicin, and 5-fluorouracil have yielded disappointing results in patients with metastatic carcinoid tumors. The lack of efficacy of these combinations, together with their toxicity, has led to efforts to investigate therapeutic agents that are potentially more active and tolerable. We, therefore, assessed the efficacy of docetaxel in the treatment of patients with metastatic carcinoid tumors. Methods. Twenty-one patients with metastatic carcinoid tumors were treated with docetaxel, administered at a dose of 75 mg/m(2) every three weeks. Patients were followed for evidence of toxicity, response, and survival. Results. Docetaxel was well tolerated in this patient population. However, no objective radiologic responses were noted in any of the 21 patients. Of the 13 patients who were evaluable for biochemical responses to therapy, four (31%) experienced decreases in 24-hour urinary 5-hydroxyindole acetic acid (5HIAA) excretion of greater than 50%. The clinical course of the patients enrolled ill this study was marked by a high incidence of radiologically stable disease (81%), a median progression-free survival time of 10 months, and a median overall survival time of 24 months. Conclusion. Although treatment with docetaxel results in biochemical responses in patients with metastatic carcinoid tumors, the lack of more significant antitumor activity demonstrates the need for novel, more effective agents in this disease. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu NR 19 TC 35 Z9 35 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2004 VL 22 IS 3 BP 353 EP 359 DI 10.1081/CNV-200029058 PG 7 WC Oncology SC Oncology GA 860TJ UT WOS:000224365800004 PM 15493355 ER PT J AU Langer, CJ Li, Y Jennings, T DeConti, RC Nair, S Cohen, RB Forastiere, AA AF Langer, CJ Li, Y Jennings, T DeConti, RC Nair, S Cohen, RB Forastiere, AA TI Phase II evaluation of 96-hour paclitaxel infusion in advanced (recurrent or metastatic) squamous cell carcinoma of the head and neck (E3395): A trial of the Eastern Cooperative Oncology Group SO CANCER INVESTIGATION LA English DT Article DE 96-Hr paclitaxel; metastatic squamous cell carcinoma of head and neck (SCCHN); relapsed SCCHN; SCCHN ID BREAST-CANCER; CHEMOTHERAPY; CISPLATIN; COMBINATION; RADIATION; INDUCTION AB Background: Paclitaxel (24-hour infusion) has yielded activity in advanced squamous cell carcinoma of the head and neck (SCCHN). Protracted exposure to paclitaxel may overcome resistance observed by using shorter infusions. Therefore we sought to evaluate paclitaxel by 96-hour infusion in both treatment-naive and previously treated patients with SCCHN. Materials and Methods: Eligibility stipulated bi-dimensionally measurable, biopsy-documented, incurable SCCHN, Eastern Cooperative Oncology Group performance Status (PS) 0-1, and adequate physiological indices. Patients were divided into three cohorts: 1) chemotherapy-naive; 2) chemotherapy-ex posed, paclitaxel-naive; and 3) chemotherapy and paclitaxel exposed. Paclitaxel was dosed at 140 mg/m(2) (96-hour infusion) every 3 weeks in treatment-naive patients and at 120 mg/m2 (96 hours) every 3 weeks in previously treated patients. Results: Fifty patients were accrued between February 1997 and July 2000. The study was terminated because of low response rate. Eighty percent of patients were mate, 75% PS 1. Nearly half the patients had oropharyngeal or hypopharyngeal primary sites. There was one treatment-related death due to neutropenic fever/pneumonia. Grade 4 toxicities included granulocytopenia in eight patients (20%), thrombocytopenia, and stomatitis in one patient each. Grade 3 or greater anemia occurred in 10 patients. There was no grade 2 or 3 peripheral sensory neuropathy. In 15 chemotherapy-naive patients, two responses (13%) were observed. There were no responses in treatment-exposed patients. The overall median survival was 5.5 months, and 1-year survival rate 10%. Treatment-naive patients had a median survival of 8.2 months and 1-year survival rate of 20%. Conclusions: Paclitaxel by 96-hour infusion at a dose of 120-140 mg/m(2)/96 hours is only marginally active in the treatment of SCCHN. This dose and schedule cannot be recommended for further evaluation. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Albany Med Coll, Albany, NY 12208 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Geisinger Med Ctr, Danville, PA USA. Johns Hopkins Univ, Baltimore, MD USA. RP Langer, CJ (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM cj_langer@fccc.edu FU NCI NIH HHS [CA21115, CA73590, CA16116, CA13650, CA27525, CA66636, CA23318, CA49957] NR 27 TC 12 Z9 12 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2004 VL 22 IS 6 BP 823 EP 831 DI 10.1081/CNV-200039628 PG 9 WC Oncology SC Oncology GA 882AN UT WOS:000225910900001 PM 15641479 ER PT J AU Wang, ZGC Lin, M Wei, LJ Li, C Miron, A Lodeiro, G Harris, L Ramaswamy, S Tanenbaum, DM Meyerson, M Iglehart, JD Richardson, A AF Wang, ZGC Lin, M Wei, LJ Li, C Miron, A Lodeiro, G Harris, L Ramaswamy, S Tanenbaum, DM Meyerson, M Iglehart, JD Richardson, A TI Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; NUCLEOTIDE POLYMORPHISM ARRAYS; OVARIAN-CANCER; DNA AMPLIFICATION; ALLELIC IMBALANCE; ANALYSIS REVEALS; WIDE DETECTION; CGH ANALYSIS; CARCINOMAS; TUMORS AB Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. The present study attempted to correlate genomic alterations (loss of heterozygosity; LOH) with subclasses of breast cancers having distinct gene expression signatures. Hierarchical clustering of expression array data from 89 invasive breast cancers identified four major expression subclasses. Thirty-four of these cases representative of the four subclasses were microdissected and allelotyped using genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.). LOH was determined by comparing tumor and normal single nucleotide polymorphism allelotypes. A newly developed statistical tool was used to determine the chromosomal regions of frequent LOH. We found that breast cancers were highly heterogeneous, with the proportion of LOH ranging widely from 0.3% to > 60% of heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q, and 14q, sites reported in previous LOH studies. Signature LOH events were discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p marked a subclass of breast cancers with "basal-like" expression profiles, distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a subclass of estrogen receptor-positive breast cancers. Finding unique LOH patterns in different groups of breast cancer, in part defined by expression signatures, adds confidence to newer schemes of molecular classification. Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genom Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Richardson, A (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM arichardson@partners.org RI Meyerson, Matthew/E-7123-2012 NR 42 TC 157 Z9 167 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2004 VL 64 IS 1 BP 64 EP 71 DI 10.1158/0008-5472.CAN-03-2570 PG 8 WC Oncology SC Oncology GA 765QA UT WOS:000188293900012 PM 14729609 ER PT J AU Chen, TT Brown, EJ Huang, EJ Seaman, WE AF Chen, TT Brown, EJ Huang, EJ Seaman, WE TI Expression and activation of signal regulatory protein alpha on astrocytomas SO CANCER RESEARCH LA English DT Article ID TYROSINE-PHOSPHATASE SHP-2; T-CELL; SIRP-ALPHA; NEGATIVE REGULATION; ADHESION MOLECULE; NEURITE OUTGROWTH; NERVOUS-SYSTEM; MYELOID CELLS; SHPS-1; CD47 AB High-grade astrocytomas and glioblastomas are usually unresectable because they extensively invade surrounding brain tissue. Here, we report the expression and function of a receptor on many astrocytomas that may alter both the proliferative and invasive potential of these tumors. Signal regulatory protein (SIRP) alpha1 is an immunoglobulin superfamily transmembrane glycoprotein that is normally expressed in subsets of myeloid and neuronal cells. Transfection of many cell types with SIRPalpha1, including glioblastomas, has been shown to inhibit their proliferation in response to a range of growth factors. Furthermore, the expression of a murine SIRPalpha1 mutant has been shown to enhance cell adhesion and initial cell spreading but to inhibit cell extension and movement. The extracellular portion of SIRPalpha1 binds CD47 (integrin-associated protein), although this interaction is not required for integrin-mediated activation of SIRPalpha1. On phosphorylation, SIRPalpha1 recruits the tyrosine phosphatases SHP-1 and SHP-2, which are important in its functions. Although SHP-1 is uniquely expressed on hematopoietic cells, SHP-2 is ubiquitously expressed, so that SIRPalpha1 has the potential to function in many cell types, including astrocytomas. Because SIRPalpha1 regulates cell functions that may contribute to the malignancy of these tumors, we examined the expression of SIRPs in astrocytoma cell lines by flow cytometry using a monoclonal antibody against all SIRPs. Screening of nine cell lines revealed clear cell surface expression of SIRPs on five cell lines, whereas Northern blotting for SIRPalpha transcripts showed mRNA present in eight of nine cell lines. All nine cell lines expressed the ligand for SIRPalpha1, CD47. To further examine the expression and function of SIRPs, we studied the SF126 and U373MG astrocytoma cell lines, both of which express SIRPs, in greater detail. SHIP transcripts in these cells are identical in sequence to SIRPalpha1. The expressed deglycosylated protein is the same size as SIRPalpha1, but in the astrocytoma cells, it is underglycosylated compared with SIRPalpha1 produced in transfected Chinese hamster ovary cells. It is nonetheless still capable of binding soluble CD47. Moreover, SIRPalpha1 in each of the two cell lines recruited SHP-2 on phosphorylation, and SIRPalpha1 phosphorylation in cultured cells is CD47 dependent. Finally, examination of frozen sections from 10 primary brain tumor biopsies by immunohistochemistry revealed expression of SIRPs on seven of the specimens, some of which expressed high levels of SIRPs. Most of the tumors also expressed CD47. This is the first demonstration that astrocytomas can express SIRPa. Given the known role of SIRPa in regulating cell adhesion and responses to mitogenic growth factors, the expression of SIRPalpha1 on astrocytomas may, be of considerable importance in brain tumor biology, and it offers the potential of a new avenue for therapeutic intervention. C1 San Francisco VA Med Ctr, Dept Immunol, San Francisco, CA USA. San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. RP Chen, TT (reprint author), San Francisco VA Hosp, Dept Arthritis Immunol, 4150 Clement St,111R, San Francisco, CA 94121 USA. EM thochen@itsa.ucsf.edu FU NIDDK NIH HHS [5T32 DK-7636-19] NR 65 TC 9 Z9 11 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2004 VL 64 IS 1 BP 117 EP 127 DI 10.1158/0008-5472.CAN-3455-2 PG 11 WC Oncology SC Oncology GA 765QA UT WOS:000188293900018 PM 14729615 ER PT J AU Zukerberg, LR DeBernardo, RL Kirley, SD D'Apuzzo, M Lynch, MP Littell, RD Duska, LR Boring, L Rueda, BR AF Zukerberg, LR DeBernardo, RL Kirley, SD D'Apuzzo, M Lynch, MP Littell, RD Duska, LR Boring, L Rueda, BR TI Loss of cables, a cyclin-dependent kinase regulatory protein, is associated with the development of endometrial hyperplasia and endometrial cancer SO CANCER RESEARCH LA English DT Article ID CORPUS-LUTEUM; CELL-DEATH; P53 GENE; EXPRESSION; CARCINOMA; PHOSPHORYLATION; ACCELERATION; PROGRESSION; CASPASE-3; MUTATIONS AB Endometrial cancer is the most common gynecological cancer in Western industrialized countries. Cables, a cyclin-dependent kinase binding protein, plays a role in proliferation and/or differentiation. Cables mutant mice are viable, but develop endometrial hyperplasia and carcinoma in situ at a young age. Exposure to chronic low levels of estrogen results in development of endometrial cancer, similar to that observed in the postmenopausal female. In vitro and in vivo studies demonstrate that levels of Cables mRNA in benign human endometrial epithelium are up-regulated by progesterone and down-regulated by estrogen. Furthermore, nuclear immunostaining for Cables is lost in a high percentage of cases of human endometrial hyperplasia and adenocarcinoma, which are likely the product of unopposed estrogen. The loss of Cables immunostaining in the human endometrial cancer samples correlates with a marked decrease in Cables mRNA. Ectopic expression of Cables in human endometrial cells dramatically slows cell proliferation. Collectively, these data provide evidence that Cables is hormonally regulated and is involved in regulating endometrial cell proliferation. In addition, loss or suppression of Cables may be an early step in the development of endometrial cancer. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Xenogen Biosci, Cranbury, NJ USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU NCI NIH HHS [CA098333] NR 22 TC 30 Z9 31 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2004 VL 64 IS 1 BP 202 EP 208 DI 10.1158/0008-5472.CAN-03-2833 PG 7 WC Oncology SC Oncology GA 765QA UT WOS:000188293900028 PM 14729625 ER PT J AU Shah, K Tung, CH Chang, CH Slootweg, E O'Loughlin, T Breakefield, XO Weissleder, R AF Shah, K Tung, CH Chang, CH Slootweg, E O'Loughlin, T Breakefield, XO Weissleder, R TI In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas SO CANCER RESEARCH LA English DT Article ID PROBES; INHIBITORS; SYSTEM; TUMORS AB (I)n vivo imaging of endogenously expressed mammalian proteases has been useful for the detection of cancer and preneoplastic lesions, for staging of inflammatory and autoimmune diseases, and for testing the efficacy of novel protease inhibitors. Here we report on the synthesis of a novel imaging probe that is specific for HIV-1 protease (PR). The probe was designed to be biocompatible, i.v. injectable, and detectable by fluorescence imaging. Human Gli36 glioblastoma cells infected with an human simplex virus amplicon vector expressing HIV-1PR showed specific fluorescence activation, an effect that could be inhibited by the HIV-1PR inhibitor, indinavir. The transfer of the HIV-1PR marker gene could be detected in vivo after intratumoral delivery of the human simplex virusamplicon vector. These results are the first proof of principle that viral proteases can directly be imaged in vivo. These findings may be directly applicable in using viral protease expression as a transgene marker in tumor therapy and may have implications in testing the efficacy of HIV-1PR inhibitors in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit,Dept Neurol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 13th St,Bldg 149,Room 5403, Charlestown, MA 02129 USA. EM Weissleder@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA6924, CAP5086355, R24CA92782, R33CA88365] NR 30 TC 33 Z9 33 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2004 VL 64 IS 1 BP 273 EP 278 DI 10.1158/0008-5472.CAN-03-1123 PG 6 WC Oncology SC Oncology GA 765QA UT WOS:000188293900037 PM 14729634 ER PT J AU Kogai, T Kanamoto, Y Che, LH Taki, K Moatamed, F Schultz, JJ Brent, GA AF Kogai, T Kanamoto, Y Che, LH Taki, K Moatamed, F Schultz, JJ Brent, GA TI Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models SO CANCER RESEARCH LA English DT Article ID SODIUM-IODIDE SYMPORTER; THYROID NA+/I-SYMPORTER; PROSTATE-CANCER; GENE-EXPRESSION; MAMMARY-GLAND; UPSTREAM ENHANCER; RECEPTOR-ALPHA; CELL-LINE; HORMONE; THERAPY AB Lactating breast tissue and some breast cancers express the sodium/iodide symporter (NIS) and concentrate iodide. We recently demonstrated that all-trans retinoic acid (tRA) induces both NIS gene expression and iodide accumulation in vitro in well-differentiated human breast cancer cells (MCF-7). In the present study, we investigated the in vivo efficacy and specificity of tRA-stimulated iodide accumulation in mouse breast cancer models. Immunodeficient mice with MCF-7 xenograft tumors were treated with systemic tRA for 5 days. Iodide accumulation in the xenograft tumors was markedly increased, similar to15-fold greater than levels without treatment, and the effects were tRA dose dependent. Iodide accumulation in other organs was not significantly influenced by tRA treatment. Significant induction of NIS mRNA and protein in the xenograft tumors was observed after tRA treatment. Iodide accumulation and NIS mRNA expression were also selectively induced in breast cancer tissues in transgenic mice expressing the oncogene, polyoma virus middle T antigen. These data demonstrate selective induction of functional NIS in breast cancer by tRA. Treatment with short-term systemic retinoic acid, followed by radioiodide administration, is a potential tool in the diagnosis and treatment of some differentiated breast cancer. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Dept Med & Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NCI NIH HHS [CA8936401] NR 50 TC 46 Z9 46 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2004 VL 64 IS 1 BP 415 EP 422 DI 10.1158/0008-5472.CAN-03-2285 PG 8 WC Oncology SC Oncology GA 765QA UT WOS:000188293900056 PM 14729653 ER PT J AU Stone, JR AF Stone, JR TI Intimal hyperplasia in the distal ulnar artery influence of gender and implications for the hypothenar hammer syndrome SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE neointima; intima; intimal thickening; atherosclerosis; vascular injury ID UPPER EXTREMITY; FIBROMUSCULAR DYSPLASIA; OCCUPATIONAL TRAUMA; RAYNAUDS-PHENOMENON; DIGITAL ISCHEMIA; BLUNT TRAUMA; HAND; ATHEROSCLEROSIS; ANEURYSMS; DISEASE AB Introduction: The distal ulnar artery in the hand is subjected to trauma when the hypothenar eminence is used as a hammer. The clinical presentation of arterial obstruction or aneurysm formation at this site with a history of trauma to the hypothenar eminence is termed the hypothenar hammer syndrome (HHS) and is most commonly observed in the right. hands of men. Since the trauma-inducing activities associated with the HHS are common, the histopathology of this arterial segment in our autopsy population was evaluated. Methods: The distal ulnar artery in the hand was examined in 21 randomly selected autopsies. Formalin-fixed paraffin-embedded cross sections of artery were assessed using hematoxylin and eosin (H&E), trichrome and elastic stains as well as immunohistochemistry for CD34 and a-smooth muscle actin. Results: Intimal hyperplasia is common at this site in the vasculature. The degree of intimal hyperplasia, as assessed by the intima/media ratio, is significantly greater in the right hands of men than in either their corresponding left hands or in women. None of the arterial segments examined contained foam cells or extracellular lipid deposits indicative of atherosclerosis. Conclusions: In the injury-prone segment of the distal ulnar artery, intimal hyperplasia is common but is particularly severe in the right hands of men, correlating with the demographics of the HHS. Although, this arterial segment frequently develops intimal hyperplasia, it is resistant to the development of atherosclerosis. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Warren 501B,55 Fruit St, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [R01 HL074324] NR 53 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JAN-FEB PY 2004 VL 13 IS 1 BP 20 EP 25 DI 10.1016/S1054-8807(03)00110-8 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 774WR UT WOS:000189009800003 PM 14761781 ER PT J AU Russell, MW Childers, NK Michalek, SM Smith, DJ Taubman, MA AF Russell, MW Childers, NK Michalek, SM Smith, DJ Taubman, MA TI A caries vaccine? The state of the science of immunization against dental caries SO CARIES RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Cariology in the 21st Century - State of the Art and Future Perspectives CY JUL 02-06, 2003 CL Konstanz, GERMANY SP ORCA DE mutans streptococci; salivary IgA antibodies; vaccine antigen; mucosal immunization ID BACTERIAL PROTEIN ANTIGEN; STREPTOCOCCUS-SOBRINUS GLUCOSYLTRANSFERASE; SALIVARY ANTIBODY-RESPONSES; LOCAL PASSIVE-IMMUNIZATION; TOXIN-B-SUBUNIT; CHOLERA-TOXIN; MUTANS STREPTOCOCCI; MUCOSAL IMMUNIZATION; ORAL IMMUNIZATION; GLUCAN-BINDING AB Studies performed in numerous laboratories over several decades have demonstrated the feasibility of immunizing experimental rodents or primates with protein antigens derived from Streptococcus mutans or Streptococcus sobrinus against oral colonization by mutans streptococci and the development of dental caries. Protection has been attributed to salivary IgA antibodies which can inhibit sucrose-independent or sucrose-dependent mechanisms of streptococcal accumulation on tooth surfaces according to the choice of vaccine antigen. Strategies of mucosal immunization have been developed to induce high levels of salivary antibodies that can persist for prolonged periods and to establish immune memory. Studies in humans show that salivary antibodies to mutans streptococci can be induced by similar approaches, and that passively applied antibodies can also suppress oral re-colonization by mutans streptococci. Progress towards practical vaccine development requires evaluation of candidate vaccines in clinical trials. Promising strategies of passive immunization also require further clinical evaluation. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Buffalo, Dept Oral Biol, Buffalo, NY 14214 USA. Univ Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. Univ Alabama, Dept Oral Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Russell, MW (reprint author), Univ Buffalo, Dept Microbiol, Farber 138,3435 Main St, Buffalo, NY 14214 USA. EM russellm@buffalo.edu OI Russell, Michael/0000-0002-1303-4061 FU NIDCR NIH HHS [DE04733, DE06153, DE06746, DE07026, DE08182, DE09081, DE09846] NR 52 TC 37 Z9 42 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PY 2004 VL 38 IS 3 BP 230 EP 235 DI 10.1159/000077759 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 822YB UT WOS:000221575700010 PM 15153693 ER PT J AU [Anonymous] AF [Anonymous] TI IRS-proteins and development of beta-cell dysfunction SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Meeting Abstract RP Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2004 SU S BP 226 EP 227 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 853SC UT WOS:000223846900033 ER PT J AU Goldmann, WH Isenberg, G AF Goldmann, WH Isenberg, G TI Signal transmission forces at the cell membrane under debate SO CELL BIOLOGY INTERNATIONAL LA English DT Editorial Material ID KINETIC DETERMINATION; TALIN; ACTIN; BINDING; FIBRONECTIN; DOMAIN C1 Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Tech Univ Munich, Dept Biophys, D-8046 Garching, Germany. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Rm 8200,Bldg 149,13th St, Charlestown, MA 02129 USA. EM goldmann@receptor.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013 NR 23 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2004 VL 28 IS 4 BP 327 EP 328 DI 10.1016/j.cellbi.2003.11.021 PG 2 WC Cell Biology SC Cell Biology GA 820YB UT WOS:000221424800013 PM 15109991 ER PT J AU Goldmann, WH Isenberg, G AF Goldmann, WH Isenberg, G TI Signal transmission forces at the cell membrane under debate (vol 28, pg 327, 2004) SO CELL BIOLOGY INTERNATIONAL LA English DT Correction C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich, Dept Biophys, Garching, Germany. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM goldmann@receptor.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2004 VL 28 IS 10 BP 727 EP 727 DI 10.1016/j.cellbi.2004.05.002 PG 1 WC Cell Biology SC Cell Biology GA 871SC UT WOS:000225152600009 ER PT J AU Sharma, CP Goldmann, WH AF Sharma, CP Goldmann, WH TI Phosphorylation of actin-binding protein (ABP-280; filamin) by tyrosine kinase p56(lck) modulates actin filament cross-linking SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE ABP-280; phosphorylation; dynamic light scattering; actin filament cross-linking ID KINASE-C; ACTIVATION; CELLS; MOLECULES; P56(LCK); PATHWAY; DOMAIN AB Actin-binding protein (ABP-280; filamin) is a phosphoprotein present in the periphery of the cytoplasm where it can cross-link actin filaments, associate with lipid membranes, and bind to membrane surface receptors. Given its function and localization in the cell, we decided to investigate the possibility of whether it serves as substrate for p56(lck), a lymphocyte-specific member of the src family of protein tyrosine kinases associated with cell surface glycoproteins. The interaction of p56(lck) with membrane glycoproteins is important for cell development and functional activation. Here, we show that purified p56(lck) interacts and catalyzes in vitro kinase reactions. Tyrosine phosphorylation by p56(lck) is restricted to a single peptide of labeled ABP-280 shown by protease digest. The addition of phorbol ester to cells results in the inhibition of phosphorylation of ABP-280 by p56(lck). These results show a decrease in phosphorylation suggesting conformationally induced regulation. Dynamic light scattering confirmed increased actin filament cross-linking due to phosphorylation of ABP-280 by p56(lck). (C) 2004 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 Univ Erlangen Nurnberg, Zent Inst Biomed Tech, D-91052 Erlangen, Germany. Boston Bioprod Inc, Worcester, MA 01604 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Zent Inst Biomed Tech, Henkestr 91, D-91052 Erlangen, Germany. EM wgoldmann@biomed.uni-erlangen.de RI Goldmann, Wolfgang/H-5572-2013 NR 26 TC 20 Z9 20 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2004 VL 28 IS 12 BP 935 EP 941 DI 10.1016/j.cellbi.2004.09.006 PG 7 WC Cell Biology SC Cell Biology GA 879YL UT WOS:000225755200010 ER PT J AU Green, JBA AF Green, JBA TI Lkb1 and GSK3 beta - Kinases at the center and poles of the action SO CELL CYCLE LA English DT Article DE Wnt; beta eta-catenin; cell polarity; Xenopus; embryo ID PEUTZ-JEGHERS-SYNDROME; GLYCOGEN-SYNTHASE KINASE-3; SERINE-THREONINE KINASE; CELL-POLARITY; PROTEIN-KINASE; TUMOR-SUPPRESSOR; ASYMMETRIC DIVISIONS; GROWTH ARREST; GENE; POLYPOSIS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Green, JBA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jeremy_green@dfci.harvard.edu RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 NR 48 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN PY 2004 VL 3 IS 1 BP E14 EP E16 PG 3 WC Cell Biology SC Cell Biology GA 833RB UT WOS:000222354900005 ER PT J AU Kobori, M Yang, Z Gong, D Heissmeyer, V Zhu, H Jung, YK Gakidis, MAM Rao, A Sekine, T Ikegami, F Yuan, C Yuan, J AF Kobori, M Yang, Z Gong, D Heissmeyer, V Zhu, H Jung, YK Gakidis, MAM Rao, A Sekine, T Ikegami, F Yuan, C Yuan, J TI Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK Complex SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE wedelolactone; caspase-11; LPS; NF-kappa B; IKK ID KAPPA-B-ALPHA; KINASE-ACTIVITY; INTERFERON-GAMMA; PROTEIN-KINASE; ACTIVATION; LIPOPOLYSACCHARIDE; SIGNAL; BETA; PHOSPHORYLATION; UBIQUITINATION AB Caspase-11 is a key regulator of proinflammatory cytokine IL-1beta maturation and pathological apoptosis. Caspase-11 is not expressed in most tissues under normal condition, but highly inducible upon pathological stimulation such as in the presence of lipopolysaccharide (LPS). Here, we describe the identification and characterization of wedelolactone, a natural compound that inhibits LPS-induced caspase-11 expression in cultured cells by inhibiting NF-kappaB-mediated transcription. We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-kappaB by mediating phosphorylation and degradation of IkappaBalpha. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Natl Food Res Inst, Tsukuba, Ibaraki 305, Japan. Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China. Ctr Blood Res, Boston, MA 02115 USA. Chiba Univ, Grad Sch Pharmaceut Sci, Inage Ku, Chiba, Japan. RP Yuan, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kobori@nfri.affrc.go.jp; jyuan@hms.harvard.edu OI Jung, Yong-Keun/0000-0002-9686-3120 NR 26 TC 118 Z9 127 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2004 VL 11 IS 1 BP 123 EP 130 DI 10.1038/sj.cdd.4401325 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762PY UT WOS:000187992400017 PM 14526390 ER PT J AU Springer, TA Wang, JH AF Springer, TA Wang, JH TI The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion SO CELL SURFACE RECEPTORS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID GLYCOPROTEIN-IIB-IIIA; I-LIKE DOMAIN; HUMAN MATRIX METALLOPROTEINASE-2; FUNCTION-ASSOCIATED ANTIGEN-1; INSIDE-OUT ACTIVATION; NIDOGEN-BINDING-SITE; BETA-A DOMAIN; CRYSTAL-STRUCTURE; HIGH-AFFINITY; EXTRACELLULAR SEGMENT AB Integrins are a structurally elaborate family of adhesion molecules that transmit signals bidirectionally across the plasma membrane by undergoing large-scale structural rearrangements. By regulating cell-cell and cell-matrix contacts, integrins participate in a wide-range of biological interactions including development, tissue repair, angiogenesis, inflammation and hemostasis. From a therapeutic standpoint, integrins are probably the most important class of cell adhesion receptors. Structural investigations on integrin-ligand interactions reveal remarkable features in molecular detail. These details include the atomic basis for divalent cation-dependent ligand binding and how conformational signals are propagated long distances from one domain to another between the cytoplasm and the extracellular ligand binding site that regulate affinity for ligand, and conversely, cytosolic signaling pathways. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. NR 109 TC 95 Z9 104 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2004 VL 68 BP 29 EP + PG 43 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBK04 UT WOS:000225856800002 PM 15500858 ER PT J AU Warden, S Zaleske, DJ Glowacki, J AF Warden, S Zaleske, DJ Glowacki, J TI Fate of a chimeric joint construct in an ectopic site in SCID mice SO CELL TRANSPLANTATION LA English DT Article DE bioengineering; joints; in vivo; knee ID 3-DIMENSIONAL COLLAGEN SPONGES; HUMAN DERMAL FIBROBLASTS; BOVINE CHONDROCYTES; DEMINERALIZED BONE; MATRIX PRODUCTION; MEDIUM PERFUSION; CULTURE; CHONDROINDUCTION; GROWTH; CELLS AB This study examines the use of a devitalized biological knee as a scaffold for repopulation with chondrocytes and tests the hypothesis that the devitalized scaffold would become repopulated with the foreign chondrocytes when placed in a suitable environment. Chimeric knee constructs were engineered in vitro and their ectopic in vivo fate was examined in SCID mice. The constructs were made by applying porous collagen sponges that contained viable bovine articular chondrocytes to shaved articular surfaces of devitalized embryonic chick knees. The chimeric joints were cultured for 1 week and were subsequently transplanted into dorsal subcutaneous pouches of 5-week-old mice. Specimens were prepared for histological analysis at 1, 3, 6, or 8 weeks after transplantation. Controls included empty collagen sponges, collagen sponges seeded with viable bovine chondrocytes, and devitalized chick knees without collagen sponge inserts. One week after in vitro incubation of the constructs, the porous collagen sponges with viable bovine chondrocytes were adherent to the shaved articular surfaces of the devitalized chick joints. There was abundant metachromatic neo-matrix around the chondrocytes in the collagen sponges. During maintenance of the constructs in vivo, the chimeric joints exhibited dramatic changes. Bovine chondrocytes proliferated in the collagen sponges and formed abundant new matrix. Bovine chondrocytes migrated into preexisting chick cartilage canals at 1 week. Subsequently, bovine chondrocytes invaded the matrix of the devitalized chick knees. Bovine neocartilage obliterated the interface between the collagen sponge and the devitalized chick cartilage. With time in vivo, the bovine neocartilage expanded and replaced the chick matrix. The devitalized cartilage appears to provide a framework for supporting chondrogenesis in a chimeric joint. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Glowacki, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM jglowacki@partners.org FU NIAMS NIH HHS [AR 45870] NR 15 TC 6 Z9 6 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2004 VL 13 IS 2 BP 161 EP 168 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 813MD UT WOS:000220910300008 PM 15129762 ER PT J AU Sugimachi, K Sosef, MN Baust, JM Fowler, A Tompkins, RG Toner, M AF Sugimachi, K Sosef, MN Baust, JM Fowler, A Tompkins, RG Toner, M TI Long-term function of cryopreserved rat hepatocytes in a coculture system SO CELL TRANSPLANTATION LA English DT Article DE cryopreservation; primary hepatocyte; coculture; connexin-32; albumin; cytochrome P450; HypoThermosol ID PRIMARY PORCINE HEPATOCYTES; FLAT-PLATE BIOREACTOR; BIOARTIFICIAL LIVER; XENOBIOTIC METABOLISM; NONPARENCHYMAL CELLS; ADULT HEPATOCYTES; IN-VITRO; VIABILITY; MAINTENANCE; DRUG AB The goal of this study was to investigate postpreservation long-term function of cryopreserved primary rat hepatocytes using the hepatocyte/3T3-J2 fibroblast coculture system. The long-term function of thawed hepatocytes cocultured with fibroblasts was evaluated and compared with hepatocytes cultured without fibroblasts. Fresh isolated primary rat hepatocytes were frozen at a controlled rate (-1degreesC/min) up to -80degreesC, and then stored in liquid nitrogen for up to 90 days. Thawed hepatocytes were thereafter cocultured with 3T3-J2 murine fibroblasts and cocultivation was monitored for 14 days. The viability of fresh isolated hepatocytes was 91.4%, and that of cryopreserved hepatocytes was 82.1%. Cellular morphology and polarity, which were determined by the localization of actin filaments and connexin-32, were successfully maintained in cryopreserved hepatocytes following cryopreservation. Albumin and urea synthesis reached the maximum level and became stable after day 7 in coculture in both fresh and cryopreserved hepatocytes. Urea synthesis of cryopreserved hepatocytes was maintained 89.0% of nonfrozen fresh control, and albumin production of cryopreserved hepatocytes was 63.7% of control in coculture. Cytochrome P450 activity, which was measured by deethylation of ethoxyresorufin, was also maintained in cryopreserved hepatocytes at 88.6% of nonfrozen fresh control in coculture. The retention of synthetic and detoxification activities was verified to be well preserved during extended low-temperature storage (90 days). Both fresh control and cryopreserved hepatocytes cultured without fibroblast did not retain their synthetic and detoxification functions in long-term culture. These data illustrate that, through the utilization of our cryopreservation procedure, primary hepatocyte function was successfully maintained when placed into coculture configuration following thawing. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org RI Yu, weiting/I-7417-2013 FU NIDDK NIH HHS [DK46270] NR 36 TC 22 Z9 23 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2004 VL 13 IS 2 BP 187 EP 195 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 813MD UT WOS:000220910300011 PM 15129765 ER PT J AU Erdag, G Morgan, JR AF Erdag, G Morgan, JR TI Allogeneic versus xenogeneic immune reaction to bioengineered skin grafts SO CELL TRANSPLANTATION LA English DT Article DE cultured skin substitute; rejection; allograft; xenograft; keratinocyte growth factor ID CULTURED KERATINOCYTE ALLOGRAFTS; HUMAN EPIDERMAL-CELLS; PROLONGED SURVIVAL; MOUSE MODEL; T-CELLS; HLA-DR; REJECTION; EQUIVALENT; MICE; REPLACEMENT AB There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a hyperproliferative epidermis. CSS (control and KGF modified) and neonatal human foreskins were evaluated by immunohistochemistry for the expression of MHC class I and II. To study allograft rejection, grafts were transplanted to human peripheral blood mononuclear cell (huPBMC)-reconstituted SCID mice. To study xenograft rejection, grafts were transplanted to immunocompetent mice. Graft survival and immune reaction were assessed visually and microscopically. After transplantation, control CSS formed a normal differentiated epidermis, whereas KGF CSS formed a hyperproliferative epidermis. Control and KGF CSS expressed class I similar to neonatal foreskin, but did not express class II. In the allograft model, rejection of neonatal foreskins was between 5 and 9 days. In contrast, neither control nor KGF CSS was rejected by huPBMC-SCID mice. Histology showed dense mononuclear cell infiltration in human foreskins, with few, if any, mononuclear cells in control or KGF CSS. In contrast to the allogeneic reaction, CSS (control and KGF) were rejected in the xenograft model, but rejection was delayed (9-21 days) compared with neonatal skin (5-8 days). Humanized SCID mice rejected allografts of human neonatal foreskins, but did not reject control CSS or KGF CSS, even though the KGF CSS formed a hyperproliferative epidermis. Rejection of control and KGF CSS by immunocompetent mice in a xenograft model was comparable and their survival was significantly prolonged compared with neonatal skin. These results demonstrate that control CSS and hyperproliferative KGF CSS are less immunogenic than normal human skin and that sustained hyperproliferation of the epidermis does not accelerate rejection. C1 Brown Univ, Ctr Biomed, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Brown Univ, Ctr Biomed, G-B 393,171 Meeting St, Providence, RI 02912 USA. EM Jeffrey_Morgan@Brown.edu OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 30 TC 20 Z9 20 U1 0 U2 4 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2004 VL 13 IS 6 BP 701 EP 712 DI 10.3727/000000004783983594 PG 12 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 880TX UT WOS:000225813500010 PM 15648740 ER PT S AU Cantiello, HF Montalbetti, N Timpanaro, GA Gonzalez-Perrett, S AF Cantiello, HF Montalbetti, N Timpanaro, GA Gonzalez-Perrett, S BE Lauf, PK Adragna, NC TI Polycystin-2 as a signal transducer SO CELL VOLUME AND SIGNALING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Cell Volume and Signaling CY SEP 20-24, 2003 CL Wright State Univ, Dayton, OH SP Natl Inst Hlth, Natl Inst Diabetes Digest & Kidney Dis HO Wright State Univ ID NONSELECTIVE CATION CHANNEL; HUMAN PLACENTAL MICROVILLI; EPITHELIAL NA+ CHANNEL; ACTIN CYTOSKELETON; ALPHA-ACTININ; CELL-VOLUME; LECITHIN BILAYERS; HUMAN TROPHOBLAST; CHLORIDE CHANNEL; TROPONIN-I C1 Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. Univ Buenos Aires, Fac Med, Dept Fisiol, RA-1121 Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. EM cantiell@helix.mgh.harvard.edu NR 54 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-23299-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2004 VL 559 BP 235 EP 244 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA BDB39 UT WOS:000232359300022 PM 18727244 ER PT J AU Perrino, MA Yelick, PC AF Perrino, MA Yelick, PC TI Immunolocalization of Alk8 during replacement tooth development in zebrafish SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 32nd Annual Meeting and Exhibition of the American-Association-for-Dental-Research CY MAR 12-15, 2003 CL SAN ANTONIO, TX SP Amer Assoc Dent Res DE replacement teeth; activin-like kinase receptors; TGF-beta family member signaling; zebrafish ID SERINE/THREONINE KINASE RECEPTOR; BRANCHIAL ARCH MUTANTS; TGF-BETA; CRANIOFACIAL DEVELOPMENT; DANIO-RERIO; MUTAGENESIS; EPITHELIUM; CYPRINIDAE; TELEOSTEI; GENES AB The novel type I transforming growth factor-beta (TGF-beta) family member receptor Alk8 was previously identified in a degenerate RT-PCR screen for zebrafish type I and II TGF-beta family member receptors. Functional analyses revealed that Alk8 acts through Bmp signaling pathways in early embryonic dorsoventral patterning, in neural crest cell specification, and in patterning and differentiation of neural crest cell-derived pharyngeal arch cartilages. In addition, Alk8 forms active signaling complexes with TGF-beta1 and the TGF-beta RII receptor, suggesting that Alk8 mediates cross talk between Bmp and TGF-beta subfamily members. In this study, immunohistochemical analysis was performed on zebrafish aged 2 days postfertilization to 1 year, revealing immunolocalization of Alk8 to tissues of the tooth-bearing ceratobranchial 5 (cb5) arch including dental epithelial and mesenchymal tooth tissues of developing primary and replacement teeth, mucous-producing crypt epithelium, keratinized bite plate, and developing taste buds. These results suggest roles for Alk8 in patterning tooth-bearing pharyngeal epithelium, in the initiation of tooth development, in odontoblast and ameloblast differentiation, and in osteoblast maturation. The ability for zebrafish to continuously form teeth throughout their lives allows for the comparison of Alk8 expression in both primary and replacement tooth development, revealing identical Alk8 expression profiles. This study advances our current understanding of the functions of Alk8, particularly with respect to primary and replacement tooth formation, reveals additional roles for Alk8 in dental epithelial patterning and in odontoblast, ameloblast and osteoblast differentiation, and demonstrates the utility of the zebrafish as a model for primary and replacement tooth development. Copyright (C) 2004 S. Karger AG, Basel. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org FU NIDCR NIH HHS [DE12024, DE12076] NR 25 TC 9 Z9 11 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2004 VL 176 IS 1-3 BP 17 EP 27 DI 10.1159/000075024 PG 11 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 816LL UT WOS:000221111300003 PM 14745232 ER PT S AU Casal, A Sumen, C Reddy, T Alber, M Lee, PP AF Casal, A Sumen, C Reddy, T Alber, M Lee, PP BE Sloot, PMA Chopard, B Hoekstra, AG TI A cellular automata model of early T cell recognition SO CELLULAR AUTOMATA, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Cellular Automata for Research and Industry CY OCT 25-27, 2004 CL Amsterdam, NETHERLANDS SP Univ Amsterdam, Dutch Sci Fdn NWO ID LIGANDS; AGONIST AB T cells are key components of the immune system, recognizing the presence of foreign antigens by coming in direct contact with specialized antigen-presenting cells (APCs) and scanning the array of surface molecules presented by the APC. During the first 60 seconds of contact, thousands of molecules on both cell surfaces interact. Based on these interactions the T cell makes a first crucial decision to either sustain contact, eventually leading to activation, or to disengage and move on. This paper presents a Cellular Automata model to study how a T cell integrates a varied array of positive and negative signals into its first activation decision. Our simulations use available biological data and support the notion that complex behaviors, such as the signal processing function of a cell, can emerge from the varied local interactions of many cellular receptors. C1 Stanford Univ, Sch Med, Div Hematol, Palo Alto, CA 94305 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. Univ Notre Dame, Dept Math, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Biocomplex, Notre Dame, IN 46556 USA. RP Casal, A (reprint author), Stanford Univ, Sch Med, Div Hematol, Palo Alto, CA 94305 USA. EM cas@stanford.edu; sumen@cbr.harvard.edu; treddy@bu.edu; malber@nd.edu; ppl@stanford.edu NR 8 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-23596-5 J9 LECT NOTES COMPUT SC PY 2004 VL 3305 BP 553 EP 560 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BBC99 UT WOS:000224949700057 ER PT J AU Choudhury, GG Abboud, HE AF Choudhury, GG Abboud, HE TI Tyrosine phosphorylation-dependent PI 3 kinase/Akt signal transduction regulates TGF beta-induced fibronectin expression in mesangial cells SO CELLULAR SIGNALLING LA English DT Article DE mesangial cell; TGF beta; tyrosine phosphorylation; Akt; fibronectin ID GROWTH-FACTOR-BETA; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; SERINE-THREONINE KINASE; CAMP RESPONSE ELEMENT; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-EXPRESSION; DNA-SYNTHESIS; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTION FACTOR AB TGFbeta stimulates expression of fibronectin in various cells, including mesangial cells. The mechanism by which TGFbeta exerts this effect is not fully understood. We investigated the involvement of tyrosine phosphorylation and the phosphatidylinositol (PI) 3 kinase/Akt signalling pathway in this process. TGFbeta increased tyrosine phosphorylation, resulting in activation of PI 3 kinase in mesangial cells. Inhibition of tyrosine phosphorylation blocked TGFbeta-induced fibronectin expression. Inhibition of PI 3 kinase activity also prevented fibronectin expression induced by TGFbeta. Furthermore, expression of constitutively active PI 3 kinase by adenovirus-mediated gene transfer increased fibronectin expression similar to TGFbeta. TGFbeta stimulated Akt serine threonine kinase in a tyrosine kinase- and PI 3 kinase-dependent manner. Inhibition of TGFbeta-induced Akt activity by adenovirus-mediated expression of a dominant-negative mutant of Akt abolished expression of fibronectin. Dominant-negative PI 3 kinase or dominant-negative Akt inhibited TGFbeta-induced fibronectin transcription. In contrast, and similarly to TGFbeta, expression of constitutively active PI 3 kinase or constitutively active Akt increased transcription of fibronectin, confirming a prominent role of these kinases in expression of fibronectin. These data provide the evidence that activation of TGFbeta receptor serine threonine kinase stimulates the PI 3 kinase/Akt pathway in a tyrosine phosphorylation-dependent manner and define a role for the same signal transduction pathway in TGFbeta-induced fibronectin expression. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. NR 67 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2004 VL 16 IS 1 BP 31 EP 41 DI 10.1016/S0898-6568(03)00094-9 PG 11 WC Cell Biology SC Cell Biology GA 748KU UT WOS:000186861700004 ER PT J AU Fischl, B van der Kouwe, A Destrieux, C Halgren, E Segonne, F Salat, DH Busa, E Seidman, LJ Goldstein, J Kennedy, D Caviness, V Makris, N Rosen, B Dale, AM AF Fischl, B van der Kouwe, A Destrieux, C Halgren, E Segonne, F Salat, DH Busa, E Seidman, LJ Goldstein, J Kennedy, D Caviness, V Makris, N Rosen, B Dale, AM TI Automatically parcellating the human cerebral cortex SO CEREBRAL CORTEX LA English DT Article ID 3-DIMENSIONAL STATISTICAL-ANALYSIS; SURFACE-BASED ANALYSIS; HUMAN BRAIN; CORTICAL SURFACE; PLANUM TEMPORALE; SULCAL VARIABILITY; COORDINATE SYSTEM; MR-IMAGES; SCHIZOPHRENIA; SEGMENTATION AB We present a technique for automatically assigning a neuroanatomical label to each location on a cortical surface model based on probabilistic information estimated from a manually labeled training set. This procedure incorporates both geometric information derived from the cortical model, and neuroanatomical convention, as found in the training set. The result is a complete labeling of cortical sulci and gyri. Examples are given from two different training sets generated using different neuroanatomical conventions, illustrating the flexibility of the algorithm. The technique is shown to be comparable in accuracy to manual labeling. C1 MGH MIT Harvard Med Sch, Athnoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. MIT, Artificial Intelligence Lab, Charlestown, MA 02129 USA. CHRU, Fac Med, Lab Anat, Tours, France. INSERM, U316, Tours, France. Massachusetts Mental Hlth Ctr, Harvard Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Harvard Dept Psychiat, Charlestown, MA 02129 USA. Harvard Inst Psychiat Epidemiol & Genet, Charlestown, MA 02129 USA. MGH, Dept Neurol, Ctr Morphometr Anal, Charlestown, MA 02129 USA. RP Fischl, B (reprint author), MGH MIT Harvard Med Sch, Athnoula A Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Kennedy, David/H-3627-2012; Destrieux, Christophe/K-1190-2012 FU NCRR NIH HHS [R01 RR016594, P41 RR 14075, P41 RR014075, R01 RR 13609, R01 RR 16594-01A1]; NEI NIH HHS [R01 EY013609]; NIMH NIH HHS [MH 56956, R01 MH056956]; NINDS NIH HHS [R01 NS 34189, R01 NS 39581, R01 NS034189] NR 64 TC 1449 Z9 1457 U1 5 U2 47 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2004 VL 14 IS 1 BP 11 EP 22 DI 10.1093/cercor/bhg087 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 753EV UT WOS:000187219900002 PM 14654453 ER PT J AU Hiroki, M Miyashita, K Oe, H Takaya, S Hirai, S Fukuyama, H AF Hiroki, M Miyashita, K Oe, H Takaya, S Hirai, S Fukuyama, H TI Link between linear hyperintensity objects in cerebral white matter and hypertensive intracerebral hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Article DE linear hyperintensity objects; cerebral white matter; MRI; intracerebral hemorrhage; hypertension ID BLOOD-FLOW; RISK-FACTOR; STROKE; MICROBLEEDS; PRESSURE; MRI; CT AB Background: We retrospectively studied the relationship between linear hyperintensity objects (LHOs) on T-2-weighted magnetic resonance images (MRI) in the cerebral white matter and the occurrence of hypertensive intracerebral hemorrhage (HIH). Methods: Forty-nine hypertensive patients with a fixed imaging condition MRI were classified into three groups: HIH (n = 17), ischemic stroke due to hypertensive vasculopathy ( n = 19), and hypertension only ( n = 13). After assessing clinical and radiological background information among these groups and the reliability of LHO measurements, polynomial logistic regression analysis was used to identify the factors relating to HIH. Results: HIH had a significantly higher LHO number (p = 0.002) and larger diameter (p = 0.007). The LHO number showed an excellent interrater (kappa = 0.91, 95% CI = 0.87-0.94, SEM = 6.2%) and intrarater reliability (kappa = 0.95, 95% CI = 0.92-0.97, SEM = 4.8%), and was the most significant independent indicator of HIH (OR = 1.29, 95% CI = 1.05-1.60, p = 0.017). The number of microbleeds was an additional indicator ( OR = 3.73, 95% CI = 1.10-12.65, p = 0.034). Conclusions: LHOs are closely linked to HIH. A prospective, longitudinal study is needed to clarify whether LHOs can predict HIH. Copyright (C) 2004 S. Karger AG, Basel. C1 Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. Natl Cardiovasc Ctr, Dept Med, Cerebrovasc Div, Suita, Osaka 565, Japan. Tokyo Metropolitan Neurol Hosp, Dept Neurol, Fuchu, Tokyo, Japan. RP Hiroki, M (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM CYI01752@nifty.com RI Takaya, Shigetoshi/M-2718-2013 NR 27 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2004 VL 18 IS 2 BP 166 EP 173 DI 10.1159/000079737 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 844BK UT WOS:000223131700013 PM 15256792 ER PT J AU Law, B Curino, A Bugge, TH Weissleder, R Tung, CH AF Law, B Curino, A Bugge, TH Weissleder, R Tung, CH TI Design, synthesis, and characterization of urokinase plasminogen-activator-sensitive near-infrared reporter SO CHEMISTRY & BIOLOGY LA English DT Article ID BREAST-CANCER; TUMOR INVASION; SYSTEM; METASTASIS; INHIBITOR; MICE; ANGIOGENESIS; PROTEASES; RECEPTOR; TISSUE AB The urokinase-type plasminogen activator (uPA) plays a critical role in malignancies, and its overexpression has been linked to poor clinical prognosis in breast cancer. The ability to noninvasively and serially map uPA expression as a biomarker would thus have significant potential in improving novel cancer therapies. Here, we describe the development of a selective uPA activatable near-infrared (NIR) fluorescent imaging probe. The probe consists of multiple peptide motifs, GGSGRSANAKC-NH2, terminally capped with different NIR fluorochromes (Cy5.5 or Cy7) and a pegylated poly-L-lysine graft copolymer. Upon addition of recombinant human uPA to the probe, significant fluorescence amplification was observed, up to 680% with the optimized preparation. No activation with negative control compounds and uPA inhibitors could be measured. These data indicate that the optimized preparation should be useful for imaging uPA in cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [N01-CO17016, P50-CA86355, R01 CA99385] NR 31 TC 64 Z9 68 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 2004 VL 11 IS 1 BP 99 EP 106 DI 10.1016/j.chembiol.2003.12.017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 768NQ UT WOS:000188549400017 PM 15112999 ER PT J AU Patel, SR Karmpaliotis, D Ayas, NT Mark, EJ Wain, J Thompson, BT Malhotra, A AF Patel, SR Karmpaliotis, D Ayas, NT Mark, EJ Wain, J Thompson, BT Malhotra, A TI The role of open-lung biopsy in ARDS SO CHEST LA English DT Article DE ARDS; open-lung biopsy; pulmonary surgical procedures ID RESPIRATORY-DISTRESS-SYNDROME; EUROPEAN CONSENSUS CONFERENCE; TRIAL; VENTILATION; STRATEGIES; SURVIVAL; THERAPY AB Study objectives: The role of open-lung biopsy in ARDS has been questioned due to potentially high morbidity and low diagnostic yield. The goals of this study were to better define the frequency of unexpected diagnoses made by open-lung biopsy, the frequency biopsy results lead to a change in clinical management, and the frequency of procedural complications. Design: Case series. Setting: A large tertiary referral center. Patients: All individuals with available records undergoing open-lung biopsy between 1989 and 2000 for evaluation of ARDS based on the American-European Consensus Conference definition. Interventions: None. Measurements and results: The mean age in this cohort of 57 patients was 53 years (SD, 18 years) with Pao(2)/fraction of inspired oxygen ratio of 145 min Hg (SD, 61 min Hg) at the time of biopsy. A pathologic diagnosis other than diffuse alveolar damage or fibroproliferation was found in 60% of patients. The most common alternative diagnoses were infection (n = 8), alveolar hemorrhage (n = 5), and bronchiolitis obliterans organizing pneumonia (n = 5). Alternative diagnoses were as frequent in immunocompetent as immunosuppressed hosts (60% vs 59%, respectively). Biopsy results led to a change in management in the majority of patients, with addition of specific therapy in 60% and withdrawal of unneeded therapy in 37%. Although the overall complication rate was 39%, major complications occurred in only 7% of cases. No deaths were attributable to the procedure. Conclusions: In selected patients with clinical ARDS, open-lung biopsy can be performed safely, often reveals an unsuspected diagnosis, and frequently leads to alterations in therapy. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Patel, SR (reprint author), 221 Longwood Ave,RFB-486, Boston, MA 02115 USA. EM spatel@partners.org NR 14 TC 73 Z9 81 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2004 VL 125 IS 1 BP 197 EP 202 DI 10.1378/chest.125.1.197 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 764QN UT WOS:000188217700034 PM 14718441 ER PT J AU Gong, MN Wei, Z Xu, LL Miller, DP Thompson, BT Christiani, DC AF Gong, MN Wei, Z Xu, LL Miller, DP Thompson, BT Christiani, DC TI Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS SO CHEST LA English DT Article DE ARDS; genetic susceptibility; surfactant ID RESPIRATORY-DISTRESS-SYNDROME; CONSENSUS CONFERENCE; LUNG SURFACTANT; DEFICIENT MICE; SUSCEPTIBILITY; ASSOCIATION; OUTCOMES; SEPSIS; FAILURE; SMOKING AB Study objective: Major risk factors for ARDS have been identified. However, only a minority of patients with such risks develops ARDS. It is likely that, given the same type and degree of insult, there are heritable determinants of susceptibility to ARDS. To investigate the possibility of variable genetic susceptibility to ARDS, we examined the association between ARDS and a polymorphism in intron 4 of the surfactant protein-B (SP-B) gene. Design: Nested case-control study conducted from September 1999 to March 2001. Setting: Four adult medical and surgical ICUs at a tertiary academic center. Patients: One hundred eighty-nine patients meeting study criteria for a defined risk factor for ARDS were enrolled and prospectively followed. Measurements and results: Seventy-two patients (38%) developed ARDS. After stratification by gender and adjustment for potential confounders, there was a significantly increased odds for women with the variant SP-B gene to develop ARDS compared to women homozygous for the wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to 18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly increased odds of having a direct pulmonary injury such as aspiration or pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or direct pulmonary injury was found for men. Conclusion: The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women, but not in men. Further study is needed to confirm the association between the variant SP-B gene, and gender, ARDS, and direct pulmonary injury. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu FU NHLBI NIH HHS [HL60710, K23 HL67197]; NIEHS NIH HHS [ES00002, T32 ES07069] NR 45 TC 75 Z9 87 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2004 VL 125 IS 1 BP 203 EP 211 DI 10.1378/chest.125.1.203 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 764QN UT WOS:000188217700035 PM 14718442 ER PT J AU Ciccone, DN Morshead, KB Oettinger, MA AF Ciccone, DN Morshead, KB Oettinger, MA TI Chromatin Immunoprecipitation in the analysis of large chromatin domains across murine antigen receptor loci SO CHROMATIN AND CHROMATIN REMODELING ENZYMES, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID DNA INTERACTIONS INVIVO; TIME QUANTITATIVE PCR; IN-VIVO; HISTONE; GENE; PROTEIN; FORMALDEHYDE; METHYLATION C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Ciccone, DN (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM48026] NR 16 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2004 VL 376 BP 334 EP + PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY68Z UT WOS:000189439600022 PM 14975316 ER PT J AU Sasaki, H Balto, K Kawashima, N Eastcott, J Hoshino, K Akira, S Stashenko, P AF Sasaki, H Balto, K Kawashima, N Eastcott, J Hoshino, K Akira, S Stashenko, P TI Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resorption in vivo SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INHIBITS OSTEOCLAST FORMATION; PERIAPICAL LESIONS; DESTRUCTION; MICE; RAT; CELLS; PATHOGENESIS; EXPRESSION; SYNERGY; IMMUNE AB Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12(-/-), IL-18(-/-), and IFN-gamma(-/-) mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12(-/-), IL-18(-/-), and IFN-gamma(-/-) mice bad similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-gamma(-/-) mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1alpha levels. Recombinant IL-12, IL-18, and IFN-gamma individually failed to consistently modulate macrophage IL-1alpha production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-gamma do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. King Abdulaziz Univ, Fac Dent, Div Endodont, Jeddah 21413, Saudi Arabia. Tokyo Med & Dent Univ, Grad Sch, Dept Restorat Sci, Tokyo, Japan. Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 565, Japan. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pstashenk@forsyth.org RI Akira, Shizuo/C-3134-2009; Hoshino, Katsuaki/L-9162-2014 OI Hoshino, Katsuaki/0000-0003-0493-4815 FU NIDCR NIH HHS [DE-13747, DE-09018, R01 DE009018, R01 DE013747] NR 25 TC 36 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 2004 VL 11 IS 1 BP 106 EP 110 DI 10.1128/CDLI.11.1.106-110.2004 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 764HL UT WOS:000188201400018 PM 14715554 ER PT J AU Feikin, DR Elie, CM Goetz, MB Lennox, JL Carlone, GM Romero-Steiner, S Holder, PF O'Brien, WA Whitney, CG Butler, JC Breiman, RF AF Feikin, DR Elie, CM Goetz, MB Lennox, JL Carlone, GM Romero-Steiner, S Holder, PF O'Brien, WA Whitney, CG Butler, JC Breiman, RF TI Specificity of the antibody response to the pneumococcal polysaccharide and conjugate vaccines in human immunodeficiency virus-infected adults SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; CAPSULAR POLYSACCHARIDES; STREPTOCOCCUS-PNEUMONIAE; RANDOMIZED TRIAL; CHILDREN; DISEASE; HIV; VACCINATION; ACTIVATION; EFFICACY AB Nonspecific antibodies, which are thought to be nonprotective, have been shown to contribute a substantial proportion of the measured concentration in the standardized immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for pneumococcal polysaccharide capsular antibodies. The presence of such antibodies in human immunodeficiency virus (HIV)-infected persons has not been evaluated. The amount of nonspecific antibodies is proportional to the reduction in IgG antibody concentration that occurs with serum absorption with the heterologous polysaccharide 22F. We measured the amount of nonspecific antibodies before and after vaccination with the pneumococcal conjugate vaccine (PCV; n = 33) or the pneumococcal polysaccharide vaccine (PPV; n = 34) in HIV-infected adults with CD4 counts of greater than or equal to200 cells/mm(3). Blood was drawn before and 2 months after vaccination. For prevaccination sera, we found a substantial amount of nonspecific antibodies for serotypes 4, 6B, 9V, and 23F (23 to 47% of measured IgG concentration), but not for serotype 14. There tended to be proportionately less nonspecific antibodies in postvaccine sera than prevaccine sera for PCV, but not for PPV. Subjects with a low HIV viral load (less than or equal to400 copies/ml) had proportionately more nonspecific antibodies than those with higher viral load before and after both vaccines. After 22F absorption, the geometric mean concentrations of antibodies were significantly higher post-PCV than post-PPV for the high viral load group for all five serotypes, but for no serotypes in the low viral load group. These findings confirm that absorption with a heterologous pneumococcal polysaccharide (e.g., 22F) is necessary to remove nonspecific antibodies in a standardized IgG ELISA for pneumococcal capsular antibodies in HIV-infected adults. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Grady Infect Dis Program, Atlanta, GA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Feikin, DR (reprint author), 1600 Clifton Rd,Mailstop C23, Atlanta, GA 30333 USA. EM dfeikin@cdc.gov RI Lennox, Jeffrey/D-1654-2014; OI Lennox, Jeffrey/0000-0002-2064-5565; Romero-Steiner, Sandra/0000-0003-4128-7768; Goetz, Matthew/0000-0003-4542-992X NR 27 TC 29 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 2004 VL 11 IS 1 BP 137 EP 141 DI 10.1128/CDLI.11.1.137-141.2004 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 764HL UT WOS:000188201400024 PM 14715560 ER PT J AU DeAngelo, DJ Ritz, J AF DeAngelo, DJ Ritz, J TI Imatinib therapy for patients with chronic myelogenous leukemia: Are patients living longer? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; INTERFERON-ALPHA; CYTARABINE; RESPONSES; CELLS C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Hematol Malignancies, Cambridge, MA 02138 USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM ddeangelo@partners.org RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2004 VL 10 IS 1 BP 1 EP 3 DI 10.1158/1078-0432.CCR-1218-3 PN 1 PG 3 WC Oncology SC Oncology GA 765YM UT WOS:000188318700001 PM 14734443 ER PT J AU Batchelor, TT Betensky, RA Esposito, JM Pham, LDD Dorfman, MV Piscatelli, N Jhung, S Rhee, D Louis, DN AF Batchelor, TT Betensky, RA Esposito, JM Pham, LDD Dorfman, MV Piscatelli, N Jhung, S Rhee, D Louis, DN TI Age-dependent prognostic effects of genetic alterations in glioblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID BRAIN-TUMOR SPECIMENS; ASTROCYTOMAS; CARCINOMA; SURVIVAL; RECEPTOR; P53 AB Purpose: Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent. Experimental Design: In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as loss of chromosome 1p, chromosome 10q, and chromosome 19q. The complete set of genetic alterations was available on 60 of 140 patients. Results: In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. The prognostic effects of TP53 mutation, EGFR amplification, CDKN2A/p16 alterations, and loss of chromosome 1p were dependent on the age of the patient. Conclusions: This is the first observation that the prognostic effects of TP53, 1p, and CDKN2A/p16 alterations are dependent on patient age. These observations concerning the interactions of age and genetic changes in glioblastoma suggest that tumorigenic pathways to glioblastoma vary with the age of the patient and that future molecular marker studies should carefully evaluate the potential age-dependent prognostic effects of these biological variables. The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp E, Mol Neurooncol Lab, Charlestown Navy Yark,Bldg 149,Room 6008, Charlestown, MA 02129 USA. EM tbatchelor@partners.org FU NCI NIH HHS [CA57683] NR 18 TC 114 Z9 122 U1 0 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 JAN 1 PY 2004 VL 10 IS 1 BP 228 EP 233 DI 10.1158/1078-0432.CCR-0841-3 PN 1 PG 6 WC Oncology SC Oncology GA 765YM UT WOS:000188318700032 PM 14734474 ER PT J AU Come, SE Buzdar, AU Arteaga, CL Bissell, MJ Brown, MA Ellis, MJ Goss, PE Green, JE Ingle, JN Lee, AV Medina, D Nicholson, RI Santen, RJ Schiff, R Hart, CS AF Come, SE Buzdar, AU Arteaga, CL Bissell, MJ Brown, MA Ellis, MJ Goss, PE Green, JE Ingle, JN Lee, AV Medina, D Nicholson, RI Santen, RJ Schiff, R Hart, CS TI Proceedings of the Third International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: Conference summary statement SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Breast Canc Program, Boston, MA 02215 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Princess Margaret Hosp, Breast Canc Prevent Program, Toronto, ON M4X 1K9, Canada. NIH, Transgen Oncogenes Grp, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Baylor Coll Med, Baylor Breast Canc, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Wales Coll Cardiff, Welsh Sch Pharm, Tenovus Ctr Canc Res, Cardiff CF1 3XF, S Glam, Wales. Univ Virginia, Hlth Sci Syst, Dept Med, Charlottesville, VA USA. InforMED, Narberth, PA USA. RP Come, SE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Breast Canc Program, 330 Brookline Ave, Boston, MA 02215 USA. EM scome@bidmc.harvard.edu NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2004 VL 10 IS 1 SU S BP 327S EP 330S DI 10.1158/1078-0432.CCR-031213 PN 2 PG 4 WC Oncology SC Oncology GA 767DB UT WOS:000188424000001 PM 14734487 ER PT J AU Miyamoto, A Prieto, AR Friedl, SE Lin, FC Muller, JE Nesto, RW Abela, GS AF Miyamoto, A Prieto, AR Friedl, SE Lin, FC Muller, JE Nesto, RW Abela, GS TI Atheromatous plaque cap thickness can be determined by quantitative color analysis during angioscopy: Implications for identifying the vulnerable plaque SO CLINICAL CARDIOLOGY LA English DT Article DE angioscopy; colorimetry; lipid-rich plaque; vulnerable plaques ID ACUTE MYOCARDIAL-INFARCTION; HUMAN ATHEROSCLEROTIC PLAQUES; CORONARY-ARTERY LESIONS; UNSTABLE ANGINA; ANGIOGRAPHIC MORPHOLOGY; RISK-FACTORS; THROMBOSIS; PATHOGENESIS; ANGIOPLASTY; ULTRASOUND AB Background: Coronary angioscopy in acute myocardial infarction has frequently revealed disrupted yellow lesions. Furthermore, postmortem studies have demonstrated that these lesions have thin collagenous caps with underlying lipid-rich cores. Hypothesis: We hypothesized that the yellow color is due to visualization of reflected light from the lipid-rich yellow core through a thin fibrous cap. Thus, quantification of yellow color saturation may estimate plaque cap thickness and identify vulnerable plaques. Methods: To test this hypothesis, the feasibility of detecting cap thickness was tested using both a model of lipid-rich plaque and human atherosclerotic plaque. The model was constructed by injecting a yellow beta-carotene-lipid emulsion subendothelially into normal bovine aorta. Human plaque was obtained from cadaver aorta. Digitized images were obtained by angioscopy, and percent yellow saturation was analyzed using a custom computer program. Plaque cap thickness was measured by planimetry of digitized images on stained tissue sections. Percent yellow saturation was then correlated with plaque cap thickness. Results: In the bovine model, plaque cap thickness and percent yellow saturation correlated inversely (r(2) = 0.91; p = 0.0001). In human plaques, yellow saturation was significantly greater in atheromatous than in white plaques (p<0.0004). Also, there was a high correlation between plaque cap thickness and yellow saturation at various angles of view between 40degrees and 90degrees, the greatest between 50degrees and 80degrees (r(2) = 0.75 to 0.88). Conclusion: Plaque cap thickness is a determinant of plaque color, and this can be assessed by quantitative colorimetry. Thus, plaque color by angioscopy may be useful for detecting vulnerable plaques. C1 Michigan State Univ, Dept Med, Div Cardiol, Clin Ctr B208, E Lansing, MI 48824 USA. Harvard Univ, Sch Med, Deaconess Hosp, Dept Med,Cardiovasc Div,Inst Prevent Cardiovasc D, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. RP Abela, GS (reprint author), Michigan State Univ, Dept Med, Div Cardiol, Clin Ctr B208, E Lansing, MI 48824 USA. EM george.abela@ht.msu.edu FU NHLBI NIH HHS [R01-HL36320] NR 32 TC 26 Z9 27 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JAN PY 2004 VL 27 IS 1 BP 9 EP 15 DI 10.1002/clc.4960270104 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 760WC UT WOS:000187857400003 PM 14743849 ER PT J AU Merchant, SN Naimi, TS Khan, A Nadol, JB Holmes, LB AF Merchant, SN Naimi, TS Khan, A Nadol, JB Holmes, LB TI Axial mesodermal dysplasia sequence: autopsy findings SO CLINICAL DYSMORPHOLOGY LA English DT Article DE axial mesodermal dysplasia sequence (AMDS); oculo-auriculovertebral (OAV) sequence; caudal dysgenesis ID OCULOAURICULOVERTEBRAL DYSPLASIA; GOLDENHARS-SYNDROME; TEMPORAL BONE; SPECTRUM; COMPLEX AB We describe an infant with the phenotype of the "axial mesodermal dysplasia spectrum" who had the oculo-auriculo-vertebral sequence and caudal dysgenesis. Postmortem studies identified anomalies of the middle ear ossicles, and muscles, in association with microtia and atresia of the external auditory canals, but no cerebral abnormalities. C1 MassGen Hosp Children, Genet & Teratol Unit, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. EM holmes.lewis@MGH.harvard.edu NR 15 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD JAN PY 2004 VL 13 IS 1 BP 21 EP 24 DI 10.1097/01.mcd.0000112295.81160.aa PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 809WT UT WOS:000220667500005 PM 15127759 ER PT J AU Tritos, NA Kissinger, KV Manning, WJ Danias, PG AF Tritos, NA Kissinger, KV Manning, WJ Danias, PG TI Association between ghrelin and cardiovascular indexes in healthy obese and lean men SO CLINICAL ENDOCRINOLOGY LA English DT Article ID LEFT-VENTRICULAR MASS; PLASMA LEPTIN; MAGNETIC-RESONANCE; MORBID-OBESITY; WEIGHT-LOSS; HEART-RATE; ESSENTIAL-HYPERTENSION; EJECTION FRACTION; SYSTOLIC FUNCTION; NERVOUS-SYSTEM AB OBJECTIVE Obesity is an increasingly common condition and is associated with excess morbidity and mortality, including clinical and subclinical cardiac dysfunction. The role of hormones involved in energy homeostasis, including ghrelin and leptin, in cardiovascular function remains incompletely understood. Therefore, we sought to evaluate the association between systemic ghrelin and leptin levels with indexes of cardiovascular structure and function. DESIGN AND MEASUREMENTS We measured serum ghrelin and leptin levels in 25 clinically healthy obese men and 25 lean controls, using commercially available immunoassays. We also assessed right and left ventricular structure and function using cardiac magnetic resonance imaging. We then investigated the association between serum ghrelin and leptin levels with cardiac indexes, using univariate and multivariate analysis. RESULTS There was an independent association between serum ghrelin levels and height-adjusted right ventricular mass (r = -0.324, P = 0.026), right ventricular end-diastolic volume (r = -0.363, P = 0.017) and right ventricular end-systolic volume (r = -0.398, P = 0.009) as well as right ventricular ejection fraction (r = 0.317, P = 0.050). There was no significant association between serum ghrelin and indexes of left ventricular structure or function. We also identified an association between serum leptin levels and resting heart rate (r = 0.391, P = 0.002). There was an association between serum leptin and height-adjusted left ventricular mass on univariate, but not on multivariate, analysis. CONCLUSIONS Serum ghrelin is associated with right ventricular cardiovascular indexes and serum leptin is associated with resting heart rate. These associations indicate a close interaction between the endocrine and cardiovascular systems in obesity. C1 Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc & Endocrinol Div, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Danias, PG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc & Endocrinol Div, 330 Brookline Ave, Boston, MA 02215 USA. NR 50 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2004 VL 60 IS 1 BP 60 EP 66 DI 10.1046/j.1365-2265.2003.01944.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 755MT UT WOS:000187407200009 PM 14678289 ER PT J AU Romashko, AA Young, MRI AF Romashko, AA Young, MRI TI Protein phosphatase-2A maintains focal adhesion complexes in keratinocytes and the loss of this regulation in squamous cell carcinomas SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE cytoskeleton; focal adhesions; HNSCC; keratinocytes; paxillin; PP-2A; squamous cell carcinoma ID CYTOSKELETAL ORGANIZATION; TYROSINE PHOSPHORYLATION; HUMAN HEAD; PAXILLIN; MOTILITY; KINASE; ASSOCIATION; MICROTUBULES; METASTASIS; MIGRATION AB Studies assessed if the serine/threonine protein phosphatase-2A (PP-2A) maintains cytoskeletal integrity of normal keratinocytes and if this differs in malignant cells. Murine and human keratinocyte cell lines contained more PP-2A activity than did the murine SCC VII/SF squamous cell carcinoma cells or primary cultures of human head and neck squamous cell carcinoma (HNSCC) cells. Since tyrosine phosphorylation of the focal adhesion proteins paxillin and FAK is indicative of more stable focal adhesions, cells were immunostained for phosphotyrosine plus either paxillin or FAK, and then examined by confocal microscopy. In non-malignant keratinocytes, phosphotyrosine staining co-localized with paxillin and FAK. This co-localization occurred at the cell periphery in a pattern resembling focal adhesions. In contrast, the co-localization of phosphotyrosine with either paxillin or FAK along the cell periphery was almost absent in the SCC cells or in keratinocytes that were treated with okadaic acid to inhibit PP-2A activity. Consistent with this was a rounded cellular morphology with less extended processes as compared to control keratinocytes. These studies indicate PP-2A maintains the organization and tyro si ne-phosphorylated state of the focal adhesion proteins FAK and paxillin, and that the loss of PP-2A activity results in a loss of cytoskeletal organization, as is seen in SCC. C1 Loyola Univ, Stritch Sch Med, Dept Otolaryngol, Maywood, IL 60153 USA. Ralph H Johnson VA Med Ctr, Res Serv, Dept Otolaryngol, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [CA45080, CA79768, CA85266] NR 25 TC 13 Z9 13 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2004 VL 21 IS 4 BP 371 EP 379 DI 10.1023/B:CLIN.0000046178.08043.f8 PG 9 WC Oncology SC Oncology GA 869ND UT WOS:000224990400011 PM 15554394 ER PT J AU Mitsiades, C Lembessis, P Sourla, A Milathianakis, C Tsintavis, A Koutsilieris, M AF Mitsiades, C Lembessis, P Sourla, A Milathianakis, C Tsintavis, A Koutsilieris, M TI Molecular staging by RT-PCR analysis for PSA and PSMA in peripheral blood and bone marrow samples is an independent predictor of time to biochemical failure following radical prostatectomy for clinically localized prostate cancer SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE pre-operative risk stratification; prostate cancer; PSA; PSMA; RT-PCR ID POLYMERASE-CHAIN-REACTION; DIGITAL RECTAL EXAMINATION; HORMONAL-THERAPY PRIOR; MEMBRANE ANTIGEN; PATHOLOGICAL STAGE; GLEASON SCORE; PROGNOSTIC-SIGNIFICANCE; NEOADJUVANT THERAPY; EUROPEAN EXPERIENCE; DISEASE RECURRENCE AB Radical prostatectomy should ideally be curative for all patients with clinically localized prostate cancer (PrCa), yet a sizeable proportion of them eventually relapse. We examined in this setting the feasibility of pre-operative risk stratification for early post-operative relapse using reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts in pre-operative bone marrow (BM) biopsies and peripheral blood (PBL) samples. Nested RT-PCR for PSA and PSMA transcripts were performed in RNA from BM biopsies and PBL samples prospectively obtained from 111 men newly diagnosed, by trans-rectal ultrasound (TRUS)-guided biopsy, with clinically localized PrCa and scheduled to undergo radical prostatectomy, according to their respective doctors' recommendation. Molecular analysis for each sample (PBL or BM) was considered positive only if both PSA and PSMA transcripts were detectable. Serial serum PSA level measurements served for biochemical follow-up and detection of biochemical failure (PSA >0.2 ng/ml). PBL and BM RT-PCR molecular staging delineated three groups of patients (a) PBL-BM- (72 patients, 65%), (b) PBL+BM+ (29 patients, 26%), and (c) PBL+BM- (10 patients, 9%). These three groups corresponded to low, high, and intermediate risk for early post-prostatectomy recurrence (median time to biochemical failure of >38, 8, and >28 months, respectively). Multivariate analysis confirmed that molecular staging status was independent predictor of disease-free survival, after adjusting for PSA levels and Gleason score. In clinically localized PrCa, combined PSA/PSMA RT-PCR in PBL and BM is an independent predictor of time to biochemical failure following radical prostatectomy. C1 Univ Athens, Sch Med, Dept Expt Physiol, Goudi 11527, Greece. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Diagnost & Therapeut Med Ctr, Endo OncoRes Labs, Athens, Greece. Metaxa Anticanc Hosp, Dept Urol, Piraeus, Greece. RP Koutsilieris, M (reprint author), Univ Athens, Sch Med, Dept Expt Physiol, 75 Micras Asias St, Goudi 11527, Greece. EM mkouts@medscape.com NR 59 TC 33 Z9 36 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2004 VL 21 IS 6 BP 495 EP 505 DI 10.1007/s10585-004-3217-0 PG 11 WC Oncology SC Oncology GA 884TC UT WOS:000226108100003 PM 15679047 ER PT J AU Sasaki, H Ide, N Yukiue, H Kobayashi, Y Fukai, I Yamakawa, Y Fujii, Y AF Sasaki, H Ide, N Yukiue, H Kobayashi, Y Fukai, I Yamakawa, Y Fujii, Y TI Arg and DAP3 expression was correlated with human thymoma stage SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Arg; chromosome 1q; DAP3; microarray; progression; thymoma ID THYMIC EPITHELIAL NEOPLASMS; TYROSINE KINASE EXPRESSION; DEATH-ASSOCIATED PROTEIN-3; INDUCED CELL-DEATH; GENE-EXPRESSION; CANCER; CLASSIFICATION; HYBRIDIZATION; LYMPHOCYTE; DIAGNOSIS AB Thymoma is one of the most common solid tumors in the mediastinum. As there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular genetic analysis of patients' tissues. The recent reports showed that the gain of chromosome 1q regions was frequent in thymoma. We investigated the use of oligonucleotide arrays to monitor in vivo gene expression levels at chromosome 1q regions in the early- (stage I or II) and late-stage (stage IVa) thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 36 thymoma patients. Using both the methods, candidate genes were come up. These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins. The Arg/GAPDH mRNA level in stage IV thymoma (90.716 +/- 177.851) was significantly higher than in stage I thymoma (10.335 +/- 25.744, P = 0.0465). The DAP3/GAPDH mRNA level in stage IV thymoma (17.424 +/- 20.649) was significantly higher than in stage I thymoma (5.184 +/- 3.878, P = 0.0305). DAP3 expression was also correlated with the WHO classification. The combined use of oligonucleotide microarray and real-time RT-PCR analyses provided a candidate molecular marker surrounding the development and progression of thymoma correlated with chromosome 1q. C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Natl Kinki Cent Hosp Chest Dis, Dept Surg, Sakai, Osaka, Japan. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Kawasumi 1,Mizuho Cho, Nagoya, Aichi 4678601, Japan. EM hisasaki@med.nagoya-cu.ac.jp NR 31 TC 10 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2004 VL 21 IS 6 BP 507 EP 513 DI 10.1007/s10585-004-2153-3 PG 7 WC Oncology SC Oncology GA 884TC UT WOS:000226108100004 PM 15679048 ER PT J AU Suarez-Cuervo, C Merrell, MA Watson, L Harris, KW Rosenthal, EL Vaananen, HK Selander, K AF Suarez-Cuervo, C Merrell, MA Watson, L Harris, KW Rosenthal, EL Vaananen, HK Selander, K TI Breast cancer cells with inhibition of p38 alpha have decreased MMP-9 activity and exhibit decreased bone metastasis in mice SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE bone metastasis; breast cancer; MMP-9; motility; p38 alpha; urokinase plasminogen activator ID ACTIVATED PROTEIN-KINASE; UROKINASE PLASMINOGEN-ACTIVATOR; ENDOTHELIAL GROWTH-FACTOR; MESSENGER-RNA STABILITY; P38 MAPK PATHWAY; TRANSFORMING GROWTH-FACTOR-BETA-1; MATRIX METALLOPROTEINASES; SUPPRESSOR GENE; UP-REGULATION; EXPRESSION AB p38 belongs to a family of mitogen-activated protein kinases, which transfer extracellular signals into intracellular responses. p38 is also frequently detected in clinical breast cancer specimens, but its role as a prognostic factor is not known. Of the various p38 isoforms, p38alpha has been shown to mediate the in vitro invasiveness of breast cancer cells through up-regulation of urokinase plasminogen activator (uPA). We studied the role of p38alpha in breast cancer bone metastases, using dominant negative blockade approach. Human MDA-MB-231 breast cancer clones stably expressing dominant negative p38alpha (p38/AF) exhibited decreased basal MMP-9 activity. TGF-beta(1)-induced MMP-9 activity was also blunted in these clones, as compared with controls in which TGF-beta(1) up-regulated MMP-9 activity. Consistent with these findings, SB202190, a specific p38 inhibitor, also inhibited TGF-beta(1)-induced MMP-9 activity in parental cells. The p38/AF clones exhibited also reduced uPA production after growth on vitronectin and decreased cell motility, as compared with controls. VEGF production levels in all the studied clones were similar. The p38/AF clone, which had similar in vitro growth rate as the control pcDNA3 clone, formed significantly less bone metastases in a mouse model, as compared with the control clone. In conclusion, inhibition of the p38alpha pathway results in decreased MMP-9 activity, impaired uPA expression and decreased motility, all of which may contribute to the decreased formation of bone metastasis. C1 Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. Univ Alabama, Div Otolaryngol, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Turku, Dept Anat, Inst Biomed, SF-20500 Turku, Finland. RP Selander, K (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA. EM katri.selander@ccc.uab.edu FU NCI NIH HHS [P50 CA 89019] NR 49 TC 38 Z9 44 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2004 VL 21 IS 6 BP 525 EP 533 DI 10.1007/s10585-004-3503-x PG 9 WC Oncology SC Oncology GA 884TC UT WOS:000226108100006 PM 15679050 ER PT J AU Giordano, TP Soini, H Teeter, LD Adams, GJ Musser, JM Graviss, EA AF Giordano, TP Soini, H Teeter, LD Adams, GJ Musser, JM Graviss, EA TI Relating the size of molecularly defined clusters of tuberculosis to the duration of symptoms SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 06-11, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID NEW-YORK-CITY; DRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; NOSOCOMIAL TRANSMISSION; SAN-FRANCISCO; OUTBREAK; EPIDEMIOLOGY; STRAIN; POPULATION; VIRULENT AB Molecular profiling of Mycobacterium tuberculosis isolates has improved recognition of tuberculosis case clusters, but the determinants of cluster size are unknown. We hypothesized that longer duration of symptoms prior to initiation of tuberculosis therapy would be associated with increased cluster size. All patients with tuberculosis in Harris County, Texas, identified between 10/1/95 and 12/31/97 through a prospective population-based project were interviewed, had their medical records reviewed, and had M. tuberculosis isolates molecularly characterized. There were 506 symptomatic, evaluable patients in 74 clusters, ranging in size from 2 patients (32 clusters) to 61 patients (1 cluster). The median duration of symptoms was 46 days (range, 1-471 days). There was no association between the log-transformed duration of symptoms and cluster size in univariate or multivariate analysis. In multivariate analysis, age and HIV coinfection were inversely related to cluster size, but only weakly. The size of molecularly defined clusters of tuberculosis was not related to the duration of symptoms of most patients who belonged to clusters. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Giordano, TP (reprint author), Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. FU NIAID NIH HHS [N01-AO-02738, 5T32AI07456-10]; NIMH NIH HHS [1K23MH67505-01] NR 35 TC 7 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2004 VL 38 IS 1 BP 10 EP 16 DI 10.1086/380454 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754PF UT WOS:000187325000002 PM 14679442 ER PT J AU Lipsky, BA Itani, K Norden, C AF Lipsky, BA Itani, K Norden, C CA Linezolid Diabet Foot Infect Study TI Treating foot infections in diabetic patients: A randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 24-27, 2002 CL CHICAGO, ILLINOIS SP Infectious Dis Soc Amer ID RESISTANT STAPHYLOCOCCUS-AUREUS; PERIPHERAL VASCULAR-DISEASE; LOWER-EXTREMITY INFECTIONS; THERAPY; EPIDEMIOLOGY; MELLITUS; CIPROFLOXACIN; PENETRATION; PNU-100766; VANCOMYCIN AB Foot infections in diabetic patients are predominantly caused by gram-positive cocci, many of which are now antibiotic resistant. Because linezolid is active against these pathogens, we compared the efficacy and safety of intravenous and oral formulations with that of intravenous ampicillin-sulbactam and intravenous and oral amoxicillin-clavulanate given for 7-28 days in a randomized, open-label, multicenter study of all types of foot infection in diabetic patients ( ratio of linezolid to comparator drug recipients, 2: 1). Among 371 patients, the clinical cure rates associated with linezolid and the comparators were statistically equivalent overall (81% vs. 71%, respectively) but were significantly higher for linezolid-treated patients with infected foot ulcers (81% vs. 68%;) and for patients without osteomyelitis (87% vs. 72%; P = .03). Cure rates were comparable for inpatients and outpatients and for both oral and intravenous formulations. Drug-related adverse events were significantly more common in the linezolid group, but they were generally mild and reversible. Linezolid was at least as effective as aminopenicillin/beta-lactamase inhibitors for treating foot infections in diabetic patients. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Antibiot Res Clin, Seattle, WA 98108 USA. Vet Affairs Med Ctr, Dept Gen Surg, Houston, TX 77030 USA. Pfizer Inc, Peapack, NJ USA. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Antibiot Res Clin, S-111-GIMC,1660 S Columbian Wy, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 30 TC 159 Z9 165 U1 1 U2 12 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 JAN 1 PY 2004 VL 38 IS 1 BP 17 EP 24 DI 10.1086/380449 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754PF UT WOS:000187325000003 PM 14679443 ER PT J AU Uribarri, J Prabhakar, S Kahn, T AF Uribarri, J Prabhakar, S Kahn, T TI Hyponatremia in peritoneal dialysis patients SO CLINICAL NEPHROLOGY LA English DT Article DE hyponatremia; peritoneal dialysis; sodium dialysate loss; salt intake ID REMOVAL; SODIUM; FLUID; CAPD AB Background: Low serum sodium is uncommon. m peritoneal dialysis (PD), which is surprising in view of the important role of normal kidney function to regulate water and sodium balance. Methods: We report 2 cases of persistent hyponatremia with balance studies in Case 1. We performed measurements of dialysate sodium and volume output over 24 hours in a group of chronic PD patients. Results: The low serum sodium concentration did not vary too much with overall fluid removal via dialysis in patient 1, mainly because large quantities of sodium were removed in the dialysate. In the 24-hour studies, a significant relationship was found between net daily PD sodium removal and net daily dialysate volume removed (r=0.65). There was no relationship between net daily PD sodium removal and serum sodium concentration. There was a linear direct correlation between serum and dialysate sodium concentration (r=0.8) as shown by others previously. Conclusions: These results suggest that the main determinant of PD sodium loss is net dialysate ultrafiltration volume. Water loss via dialysis is necessarily associated with sodium loss. In order to maintain a normal serum sodium concentration salt intake must be proportional to the water loss induced by dialysis. The stimuli that allow dialysis patients to maintain this delicate balance between water and salt intake are of considerable interest but remain undetermined. C1 Mt Sinai Sch Med, Div Renal, New York, NY USA. Texas Tech Univ, Hlth Sci Ctr, Div Renal, Lubbock, TX 79430 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Uribarri, J (reprint author), Mt Sinai Med Ctr, 1 Gustave Levy Pl, New York, NY 10029 USA. EM jaime.uribarri@mssm.edu NR 10 TC 2 Z9 2 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JAN PY 2004 VL 61 IS 1 BP 54 EP 58 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 762YD UT WOS:000188030700008 PM 14964458 ER PT J AU Soriano, SG Martyn, JAJ AF Soriano, SG Martyn, JAJ TI Antiepileptic-induced resistance to neuromuscular blockers - Mechanisms and clinical significance SO CLINICAL PHARMACOKINETICS LA English DT Review ID CHRONIC ANTICONVULSANT THERAPY; ACUTELY ADMINISTERED PHENYTOIN; CHRONIC CARBAMAZEPINE THERAPY; ACETYLCHOLINE-RECEPTORS; DRUG-INTERACTIONS; PROTEIN-BINDING; CEREBRAL-PALSY; D-TUBOCURARINE; ALPHA-1-ACID GLYCOPROTEIN; DECREASED SENSITIVITY AB Prolonged administration of antiepileptic drugs is associated with several drug interactions. In the field of anaesthesia and critical care, patients exhibit both sensitivity and resistance to non-depolarising neuromuscular blockers (NDNMBs) after acute and long-term administration of antiepileptic drugs, respectively. Although antiepileptic therapy alone has only mild neuromuscular effects, acutely administered antiepileptic drugs can potentiate the neuromuscular effects of NDNMBs as a result of direct pre- and post-junctional effects. Resistance to NDNMBs during long-term antiepileptic therapy is due to multiple factors operating alone or in combination, including induction of hepatic drug metabolism, increased protein binding of the NDNMBs and/or upregulation of acetylcholine receptors. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02115 USA. RP Soriano, SG (reprint author), Harvard Univ, Sch Med, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM sulpicio.soriano@tch.harvard.edu FU NIGMS NIH HHS [GM 61411-4, GM 31569-20, GM55082-6] NR 63 TC 15 Z9 16 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2004 VL 43 IS 2 BP 71 EP 81 DI 10.2165/00003088-200443020-00001 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779EH UT WOS:000189282000001 PM 14748617 ER PT J AU Robertson, JFR Erikstein, B Osborne, KC Pippen, J Come, SE Parker, LM Gertler, S Harrison, MP Clarke, DA AF Robertson, JFR Erikstein, B Osborne, KC Pippen, J Come, SE Parker, LM Gertler, S Harrison, MP Clarke, DA TI Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer SO CLINICAL PHARMACOKINETICS LA English DT Review ID POSTMENOPAUSAL WOMEN; PURE-ANTIESTROGEN; ANASTROZOLE AB Objective: To characterise the pharmacokinetics of a long-acting formulation of fulvestrant following intramuscular administration of single and multiple doses. Study design: Pharmacokinetic investigations of single and multiple doses of fulvestrant were conducted within two global phase III efficacy studies that compared intramuscular fulvestrant with oral anastrozole in postmenopausal women with hormone-sensitive advanced breast cancer (study 0020, conducted in Europe, Australia and South Africa, and study 0021, conducted in North America). Methods: Patients received once-monthly intramuscular injections of fulvestrant 250mg (1 x 5mL for less than or equal to21 months in study 0020; 2 x 2.5mL for less than or equal to30 months in study 0021). Serial blood samples were collected for the first 28 days after the initial dose and immediately prior to all subsequent monthly doses. Plasma fulvestrant concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry. Patients: Twenty-six (study 0020) and 193 (study 0021) postmenopausal women, comprising the pharmacokinetic subgroups of the phase III efficacy trials, were studied. Patients had shown disease progression or recurrence following previous hormonal therapy for advanced disease or had relapsed after adjuvant endocrine therapy with a nonsteroidal antiestrogen. Outcome measures and results: For single-dose fulvestrant 250mg, area under the concentration-time curve from time zero to 28 days (AUC(28)), maximum observed plasma concentration (C-max), minimum observed plasma concentration at 28 days (C-min) and time to maximum plasma concentration (t(max)) were determined. For multiple-dose fulvestrant 250mg once monthly, steady-state trough concentrations (C-trough) were determined. Plasma fulvestrant concentrations reached a peak at a median of 7 days (range 2-8 days) postdose, and declined biexponentially with a slower phase commencing approximately 2-3 weeks postdose. Intersubject variability in C-max, and AUC(28) was approximately 6-fold and 4-fold, respectively. Mean parameters for single-dose fulvestrant were: AUC28, 148 mug (.) day/L; Cmax, 8.2 mug/L; C-min, 2.6 mug/L; t(max), 7.0 days. Geometric mean C-trough increased from 2.57 to 6.15 mug/L (study 0020) and from 2.38 to 6.52 mug/L (study 0021) over the first 6 months, reaching steady-state concentrations of approximately 6-7 mug/L (study 0020) or 9 mug/L (study 002 1). Preliminary pharmacokinetic analysis, using a naive pooled data approach, suggests that observed single- and multiple-dose plasma profiles can be adequately described with a two-Compartment kinetic model. Model-generated steady-state AUC28 values were approximately 300 mug (.) day/L. Conclusions: The intramuscular formulation of fulvestrant displays predictable kinetics and approximately 2-fold accumulation on administration once monthly. At the proposed therapeutic dosage (250mg once monthly), plasma fulvestrant concentrations are maintained within a narrow range throughout the administration interval, thus ensuring stable systemic drug exposure during long-term treatment. C1 Astra Zeneca Pharmaceut, Macclesfield SK10 4TG, Cheshire, England. City Hosp Nottingham, Nottingham, England. Norwegian Radium Hosp, N-0310 Oslo, Norway. Baylor Coll Med, Houston, TX 77030 USA. Texas Oncol, Dallas, TX USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. RP Harrison, MP (reprint author), Astra Zeneca Pharmaceut, Mereside,Alderley Pk, Macclesfield SK10 4TG, Cheshire, England. EM Mike.P.Harrison@astrazeneca.com NR 14 TC 49 Z9 50 U1 0 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2004 VL 43 IS 8 BP 529 EP 538 DI 10.2165/00003088-200443080-00003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 834HU UT WOS:000222403000003 PM 15170367 ER PT J AU Montoya, ID Gorelick, DA Preston, KL Schroeder, JR Umbricht, A Cheskin, LJ Lange, R Contoreggi, C Johnson, RE Fudala, PJ AF Montoya, ID Gorelick, DA Preston, KL Schroeder, JR Umbricht, A Cheskin, LJ Lange, R Contoreggi, C Johnson, RE Fudala, PJ TI Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID METHADONE-MAINTENANCE TREATMENT; OPIOID DEPENDENCE; RHESUS-MONKEYS; CLINICAL-TRIAL; INTRAVENOUS COCAINE; MAINTAINED PATIENTS; ABUSE; USERS; IMPACT; HUMANS AB Background: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Methods: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. Results: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P = .0135 for 8 mg and P < .001 for 16 mg) or benzoylecgonine concentrations (P = .0277 for 8 mg and P = .006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. Conclusions: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use. C1 NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Div Treatment Res & Dev, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z99 DA999999] NR 51 TC 80 Z9 81 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2004 VL 75 IS 1 BP 34 EP 48 DI 10.1016/j.clpt.2003.09.004 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 765YJ UT WOS:000188318400003 PM 14749690 ER PT J AU Melo, MFV Barazanji, K Winga, E Johnson, RL AF Melo, MFV Barazanji, K Winga, E Johnson, RL TI Estimate of pulmonary diffusing capacity for oxygen during exercise in humans from routine O-2 and CO2 measurements SO CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING LA English DT Article DE V-A/Q heterogeneity; alveolar-arterial O-2 gradients; diffusion limitation; lung resection; mathematical modelling; sarcoidosis ID VENTILATION-PERFUSION INEQUALITY; INTERSTITIAL LUNG-DISEASE; GAS-EXCHANGE; SEA-LEVEL; SIMULATED ALTITUDE; HEAVY EXERCISE; LIMITATION; O2; INHOMOGENEITIES; MISMATCH AB A method to estimate pulmonary diffusing capacity for O-2 (D-LO2) during exercise based on routine O-2 and CO2 transport variables is presented. It is based on the fitting of a mathematical model to gas exchange data. The model includes (V)over dot(A)/(Q)over dot heterogeneity (described as two exchanging compartments), diffusion limitation and right-to-left shunt. Mass conservation equations and Bohr integration were solved to calculate partial pressures in each compartment. Diffusion was distributed with perfusion. Two-compartment ventilation and perfusion distributions were estimated at rest during conditions of negligible diffusion limitation. These distributions were used during hypoxic and normoxic exercise to obtain the D-LO2 from the model computations (D(LO2)2C) compatible with experimental data. Three normals, four sarcoid patients and four patients after lung resection were studied. An independent technique for carbon monoxide was used to provide experimental estimates of D-LO2 (DLO2EXP, rebreathing technique for sarcoid patients and single breath for lung resection). D(LO2)2C was highly correlated with DLO2EXP (r(2) = 0.95, P<0.001) and the slope of the regression line was not statistically different from 1. The mean (DLO2EXP - D(LO2)2C) difference was -1.0 +/- 7.4 ml min(-1) mmHg(-1). The results suggest that use of a refined analytical procedure allows for assessment of D-LO2 from routine O-2 and CO2 measurements comparable with those obtained from independent carbon monoxide techniques. The method may be an alternative for estimates of D-LO2 during exercise. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02461 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Pulm Res, Dallas, TX USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Furit St, Boston, MA 02461 USA. EM mvidalmelo@partners.org NR 42 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1475-0961 J9 CLIN PHYSIOL FUNCT I JI Clin. Physiol. Funct. Imaging PD JAN PY 2004 VL 24 IS 1 BP 46 EP 57 PG 12 WC Physiology SC Physiology GA 763AM UT WOS:000188046100007 ER PT J AU Nishimori, M Ballantyne, JC Low, JHS AF Nishimori, M. Ballantyne, J. C. Low, J. H. S. TI Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review AB This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this systematic review is to assess the benefits and harm of postoperative epidural pain relief in comparison with postoperative systemic opioid-based pain relief for adult patients who underwent elective abdominal aortic surgery. By conducting selective cumulative meta-analysis, we would also be able to show decreased surgical mortality over the previous two decades, and demonstrate the change of the role of the epidurals. This review will allow a more balanced perspective of the potential benefit for the patient compared to the increase in medical and nursing costs that it incurs. C1 [Nishimori, M.] Massachusetts Gen Hosp, Pain Ctr, 15 Parkman St Suite WAC 324, Boston, MA 02114 USA. RP Nishimori, M (reprint author), Massachusetts Gen Hosp, Pain Ctr, 15 Parkman St Suite WAC 324, Boston, MA 02114 USA. EM mnishimori@partners.org FU Japan Society for Promotion of Science JAPAN FX Japan Society for Promotion of Science JAPAN NR 21 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2004 IS 3 AR CD005059 DI 10.1002/14651858.CD005059 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA V46YM UT WOS:000209919500228 ER PT S AU Park, BH Pierce, MC Cense, B de Boer, JF AF Park, BH Pierce, MC Cense, B de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Speckle averaging for optical coherence tomography by vibration of a thin water film SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE VIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine VIII CY JAN 26-28, 2004 CL San Jose, CA SP SPIE DE speckle; reduction; OCT ID REDUCTION AB A novel method for reducing the appearance of speckle within a single image acquisition in optical coherence tomography is presented. Local variations in the optical path length of beamlets within the beam diameter are introduced by vibrating a thin water film placed in a collimated section of the sample arm beam path. Consequent averaging of small numbers of adjacent depth scans results in a reduced appearance of speckle with no change in the axial point spread function. Reduced speckle images of a layered agar sample and thin reflective surfaces are shown. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St,BAR 714, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5224-6 J9 P SOC PHOTO-OPT INS PY 2004 VL 5316 BP 391 EP 396 DI 10.1117/12.531400 PG 6 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BAP46 UT WOS:000223125200056 ER PT S AU Park, BH Pierce, MC Cense, B de Boer, JF AF Park, BH Pierce, MC Cense, B de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Vector-based analysis for polarization-sensitive optical coherence tomography SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE VIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine VIII CY JAN 26-28, 2004 CL San Jose, CA SP SPIE DE polarization; diattenuation; birefringence; optic axis; OCT; PS-OCT ID BIOLOGICAL TISSUE; MUELLER MATRIX; BIREFRINGENCE; PARAMETERS AB A vector-based analysis is presented for polarization-sensitive optical coherence tomography (PS-OCT) that yields diattenuation, birefringence, and relative optic axis orientation. Experimental confirmation is demonstrated by comparing the calculated diattenuation of chicken tendon and muscle to independent measurement. The diattenuation of the retinal nerve fiber layer of the superior region of a human retina is also calculated. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,BAR 7, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5224-6 J9 P SOC PHOTO-OPT INS PY 2004 VL 5316 BP 397 EP 403 DI 10.1117/12.531395 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BAP46 UT WOS:000223125200057 ER PT S AU Pierce, MC Shishkov, M Park, BH Nassif, NA Cense, B Bouma, BE Tearney, GJ de Boer, JF AF Pierce, MC Shishkov, M Park, BH Nassif, NA Cense, B Bouma, BE Tearney, GJ de Boer, JF BE Tuchin, VV Izatt, JA Fujimoto, JG TI Polarization-sensitive optical coherence tomography with a scanning fiber-optic probe SO COHERENCE DOMAIN OPTICAL METHODS AND OPTICAL COHERENCE TOMOGRAPHY IN BIOMEDICINE VIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine VIII CY JAN 26-28, 2004 CL San Jose, CA SP SPIE DE endoscopic imaging; birefringence; collagen; cartilage ID INTERFEROMETER; CATHETER AB We have developed a scanning fiber-optic probe compatible with high-speed polarization-sensitive OCT imaging. The effect of sample arm fiber motion on the polarization state of light incident on a sample is demonstrated by the evolution of incident Stokes vectors during the course of acquiring a single image. By referencing the polarization state of light backscattered from within a sample to the measured surface state, effects of motion-induced birefringence can be isolated. Conventional and polatization-sensitive images of human tissues are presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 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 0-8194-5224-6 J9 P SOC PHOTO-OPT INS PY 2004 VL 5316 BP 404 EP 407 DI 10.1117/12.531397 PG 4 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BAP46 UT WOS:000223125200058 ER PT J AU Huynh, KD Lee, JT AF Huynh, KD Lee, JT TI A continuity of X-chromosome silence from gamete to zygote SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID EARLY MOUSE DEVELOPMENT; DOSAGE COMPENSATION; PREIMPLANTATION EMBRYOS; INACTIVATION CENTER; CHORIONIC VILLI; PARENTAL ORIGIN; XIST EXPRESSION; HUMAN-PLACENTA; LINKED GENES; GERM-CELLS C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Huynh, KD (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM58839] NR 82 TC 2 Z9 3 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 103 EP 112 DI 10.1101/sqb.2004.69.103 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200013 PM 16117638 ER PT J AU Kaneda, M Sado, T Hata, K Okano, M Tsujimoto, N Li, E Sasaki, H AF Kaneda, M Sado, T Hata, K Okano, M Tsujimoto, N Li, E Sasaki, H TI Role of de novo DNA methyltransferases in initiation of genomic imprinting and X-chromosome inactivation SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID MOUSE EMBRYOS; GENE; METHYLATION; HYPOMETHYLATION; IMPLANTATION; EXPRESSION; LETHALITY; DNMT3L; GROWTH; CELLS C1 Res Org Informat & Syst, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. Grad Univ Adv Studies, Dept Genet, Sch Life Sci, Mishima, Shizuoka 4118540, Japan. Japan Sci & Technol Agcy, PRESTO, Kawaguchi 3320012, Japan. RIKEN, Ctr Dev Biol, Lab Mammalian Epigenet Studies, Kobe, Hyogo 6500047, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02139 USA. RP Kaneda, M (reprint author), Res Org Informat & Syst, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. RI Kaneda, Masahiro/E-3117-2010 OI Kaneda, Masahiro/0000-0003-0660-7156 NR 29 TC 14 Z9 17 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 125 EP 129 DI 10.1101/sqb.2004.69.125 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200016 PM 16117641 ER PT J AU Fan, HY Narlikar, GJ Kingston, RE AF Fan, HY Narlikar, GJ Kingston, RE TI Noncovalent modification of chromatin: Different remodeled products with different ATPase domains SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID YEAST SWI/SNF COMPLEX; SWI-SNF COMPLEX; NUCLEOSOMAL DNA; CELLULAR MEMORY; H2A/H2B DIMER; POLYCOMB; HISTONE; TRANSCRIPTION; GENE; BINDING C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Fan, HY (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 43 TC 11 Z9 12 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 183 EP 192 DI 10.1101/sqb.2004.69.183 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200023 PM 16117648 ER PT J AU Felsenfeld, G Burgess-Beusse, B Farrell, C Gaszner, M Ghirlando, R Huang, S Jin, C Litt, M Magdinier, F Mutskov, V Nakatani, Y Tagami, H West, A Yusufzai, T AF Felsenfeld, G Burgess-Beusse, B Farrell, C Gaszner, M Ghirlando, R Huang, S Jin, C Litt, M Magdinier, F Mutskov, V Nakatani, Y Tagami, H West, A Yusufzai, T TI Chromatin boundaries and chromatin domains SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID ENHANCER-BLOCKING ACTIVITY; BETA-GLOBIN LOCUS; PROMOTER DNA; DAD1 GENES; CTCF; INSULATOR; METHYLATION; REGION; MOUSE; MECHANISMS C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009; Magdinier, Frederique/I-4735-2016; OI Magdinier, Frederique/0000-0002-0159-9559; West, Adam/0000-0003-3502-7804 NR 28 TC 66 Z9 70 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 245 EP 250 DI 10.1101/sqb.2004.69.245 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200030 PM 16117655 ER PT J AU Nakatani, Y Ray-Gallet, D Quivy, JP Tagami, H Almouzni, G AF Nakatani, Y Ray-Gallet, D Quivy, JP Tagami, H Almouzni, G TI Two distinct nucleosome assembly pathways: Dependent or independent of DNA synthesis promoted by histone H3.1 and H3.3 complexes SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; ACTIVE CHROMATIN; CORE HISTONES; HUMAN HOMOLOG; HUMAN ASF1; REPLICATION; PROTEIN; TRANSCRIPTION; INHERITANCE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Curie, CNRS, Sect Rech, UMR 218, F-75248 Paris, France. RP Nakatani, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM065939-02] NR 57 TC 30 Z9 32 U1 2 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 273 EP 280 DI 10.1101/sqb.2004.69.273 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200034 PM 16117659 ER PT J AU Wang, D Ruvkun, G AF Wang, D Ruvkun, G TI Regulation of Caenorhabditis elegans RNA interference by the daf-2 insulin stress and longevity signaling pathway SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID AGE-1 PI3 KINASE; C-ELEGANS; LIFE-SPAN; TRANSCRIPTION FACTOR; GENES; EXPRESSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Wang, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK070147] NR 23 TC 14 Z9 14 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 429 EP 431 DI 10.1101/sqb.2004.69.429 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200052 PM 16117677 ER PT J AU Neves, G Chess, A AF Neves, G Chess, A TI Dscam-mediated self-versus non-self-recognition by individual neurons SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 69th Cold Spring Harbor Symsposium on Quantitative Biology CY JUN 02-07, 2004 CL Cold Spring Harbor, NY SP NCI, Natl Inst Environm Hlth Sci, Amgen Inc, Aventis Pharma AG, Bristol Myers Squibb Co, Eli Lilly, GlaxoSmithKline, Novartis Inst BioMed Res, Pfizer, Appl Biosyst, AstraZeneca, BioVentures, Cogene BioTech Ventures, Diagnost Prod Corp, Forest Labs, Genentech Inc, Hoffmann La Roche, Johnson & Johnson Pharmaceut Res & Dev LLC, Kyowa Hakko Kogyo Co Ltd, Lexicon Genet Inc, Merck Res Labs, New England BioLabs, OSI Pharmaceut, Pall Corp, Schering Plough Res Inst, Wyeth Genet Inst ID DROSOPHILA DSCAM; EXPRESSION; RECEPTORS; ADHESION C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Cambridge, MA 02142 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Neves, G (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Cambridge, MA 02142 USA. RI Neves, Guilherme/G-8957-2011 OI Neves, Guilherme/0000-0001-6463-6997 NR 13 TC 10 Z9 10 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2004 VL 69 BP 485 EP 488 DI 10.1101/sqb.2004.69.485 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 969IG UT WOS:000232227200059 PM 16117684 ER PT S AU Nam, DS Youn, CH Lee, BH Clifford, G Healey, J AF Nam, DS Youn, CH Lee, BH Clifford, G Healey, J BE Lagana, A Gavrilova, ML Kumar, V Mun, Y Tan, CJK TI QoS-constrained resource allocation for a Grid-based multiple source electrocardiogram application SO COMPUTATIONAL SCIENCE AND ITS APPLICATIONS - ICCSA 2004, PT 1 SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT International Conference on Computational Science and Its Applications (ICCSA 2004) CY MAY 14-17, 2004 CL Assisi, ITALY SP Univ Perugia, Univ Calgary, Univ Minnesota, Queens Univ Belfast, Heuchera Technologies, Minist Sci & Educ Italy, GRID IT Project, COST AB QoS-constrained policy has an advantage to guarantee QoS requirements requested by users. Quorum systems can ensure the consistency and availability of replicated data despite the benign failure of data repositories. We propose a Quorum based resource management scheme, which resource Quorum includes middleware entity and network entity, both can satisfy requirements of application QoS. We also suggest a heuristic configuration algorithm in order to optimize performance and usage cost of Resource Quorum. We evaluate both simulations and experiments based on the electrocardiogram (ECG) application for health care, because this application requires transferring giga-bytes of data and analyzing complicated signal of ECG. Simulation results show that network capabilities are more important than computing capabilities, as both sizes of transferred data and computation task increases. Experimental results show that our scheme can reduce the total execution time of ECG application by using proposed heuristic algorithm compared to policy based management scheme. C1 Informat & Commun Univ, Sch Engn, Taejon 305732, South Korea. Daejeon Univ, Dept Informat & Commun Engn, Taejon 300716, South Korea. Harvard Univ, MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, BIDMC, Dept Translat Med, Boston, MA 02215 USA. Natl Secur Res Inst, Dept Informat Assurance, Taejon 305348, South Korea. RP Informat & Commun Univ, Sch Engn, 103-6 Munji Dong, Taejon 305732, South Korea. EM dsnam@icu.ac.kr; chyoun@icu.ac.kr; blee@dju.ac.kr; gari@mit.edu; jhealey@bidmc.harvard.edu RI Youn, Chan-Hyun/C-1729-2011 NR 8 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22054-2 J9 LECT NOTES COMPUT SC PY 2004 VL 3043 BP 352 EP 359 PG 8 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Telecommunications SC Computer Science; Telecommunications GA BAE82 UT WOS:000221909000044 ER PT J AU Behnam, K Brochmann, EJ Murray, SS AF Behnam, K Brochmann, EJ Murray, SS TI Alkali-urea extraction of demineralized bone matrix removes noggin, an inhibitor of bone morphogenetic proteins SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE bone; bone morphogenetic proteins; noggin; osteogenesis ID VENTRALIZING FACTOR; SPEMANN ORGANIZER; XENOPUS MESODERM; INDUCTION; OSSIFICATION; MUTATIONS; CHORDIN; GENE AB Demineralized bone matrix (DBM) and native bone morphogenetic protein (nBMP) are complex mixtures of non-collagenous bone proteins. These mixtures contain many of the BMPs that are available as recombinant molecules. Information regarding the presence in these materials of molecules that may affect the availability and activity of the BMPs is very limited. We have devised a simple chemical extraction of DBM using alkali-urea that produces a water soluble extractate that inhibits the osteogenic activity of DBM. We have demonstrated the presence of noggin, an extracellular BMP ligand antagonist, in this material. We conclude that differential chemical extraction may be a useful means of removing inhibitory molecules from DBM and nBMP. C1 Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Murray, SS (reprint author), Vet Adm Med Ctr, GRECC 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. EM murrayes@ucla.edu NR 21 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2004 VL 45 IS 4-5 BP 257 EP 260 DI 10.1080/03008200490903048 PG 4 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 897XX UT WOS:000227041300008 PM 15763935 ER PT B AU Potts, JT Schwartz, WB AF Potts, JT Schwartz, WB BE Aaron, HJ Schwartz, WB TI The impact of the revolution in biomedical research on life expectancy by 2050 SO COPING WITH METHUSELAH: THE IMPACT OF MOLECULAR BIOLOGY ON MEDICINE AND SOCIETY LA English DT Proceedings Paper CT Conference on Coping with Methuselah - The Impact of Molecular Biology on Medicine and Society CY APR, 2002 CL Brookings Inst, Washington, DC HO Brookings Inst ID SINGLE NUCLEOTIDE POLYMORPHISMS; SEVERE COMBINED IMMUNODEFICIENCY; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; MESENCHYMAL STEM-CELLS; CASSETTE TRANSPORTER 1; GENE-THERAPY; ALZHEIMERS-DISEASE; TANGIER-DISEASE; EX-VIVO C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 151 TC 3 Z9 3 U1 0 U2 0 PU BROOKINGS INST PI WASHINGTON PA 1775 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA BN 0-8157-0039-3 PY 2004 BP 16 EP 65 PG 50 WC Demography; Social Issues SC Demography; Social Issues GA BAD15 UT WOS:000221625600002 ER PT J AU Watson, D Grover, R Anzueto, A Lorente, J Smithies, M Bellomo, R Guntupalli, K Grossman, S Donaldson, J Le Gall, JR AF Watson, D Grover, R Anzueto, A Lorente, J Smithies, M Bellomo, R Guntupalli, K Grossman, S Donaldson, J Le Gall, JR CA Glaxo Wellcome Int Septic Shock St TI Cardiovascular effects of the nitric oxide synthase inhibitor N-G-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: Results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002) SO CRITICAL CARE MEDICINE LA English DT Article DE human; severe sepsis; septic shock; nitric oxide; nitric oxide synthase inhibitor; N-G-methyl-L-arginine hydrochloride; randomized; placebo-controlled trial; norepinephrine; dopamine; dobutamine; arginine; nitrate; hemodynamics ID IMPROVES SURVIVAL; SEPSIS SYNDROME; CLINICAL-TRIAL; DYSFUNCTION; PRESSURE; HUMANS; INVIVO; MODEL AB Objective: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period. Design: Multicentered, randomized, placebo-controlled, safety and efficacy study. Setting. Forty-eight intensive care units in Europe, North America, and Australia. Patients: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. Interventions: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). Measurements and Main Results: Requirement for vasopressors, systemic and pulmonary hemodynamics, indices of oxygen transport, and plasma concentrations of arginine and nitrate were assessed over time. The median mean arterial pressure for both groups was maintained greater than or equal to70 mm Hg. There was an early increase in systemic and pulmonary vascular tone and oxygen extraction, whereas both cardiac index and oxygen delivery decreased for patients in the 546C88 cohort. Although these parameters subsequently returned toward baseline values, the observed differences between the treatment groups, except for pulmonary vascular resistance and oxygen extraction, persisted throughout the treatment period, despite a reduced requirement for vasopressors in the 546C88 cohort. These changes were associaled with a reduction in plasma nitrate concentrations, which were elevated in both groups before the start of therapy. Conclusions. The nitric oxide synthase inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed in patients with septic shock. In this study, treatment with 546C88 for up to 72 hrs was associated with an increase in vascular tone and a reduction in both cardiac index and oxygen delivery. The successful maintenance of a target mean arterial blood pressure :70 mm Hg was achieved with a reduction in the requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents (i.e., dopamine and norepinephrine). There were no substantive untoward consequences accompanying these hemodynamic effects. An international, randomized, double-blind, placebo-controlled phase III study has since been conducted in patients with septic shock. Recruitment into the study was discontinued due to the emergence of increased mortality in the 546C88-treated group. C1 Hop St Louis, Dept Intens Care, Paris, France. Homerton Hosp, Dept Intens Care, London, England. Glaxo Wellcome Res & Dev Ltd, Int Dept Cardiovasc Crit Care & Anesthesia Clin D, Greenford, Middx, England. Audie L Murphy Mem Vet Adm Med Ctr, Dept Med Intens Care, San Antonio, TX 78284 USA. Hop Getafe, Dept Intens Care, Madrid, Spain. Univ Wales Hosp, Intens Care Unit, Cardiff CF4 4XW, S Glam, Wales. Austin Med Ctr, Dept Intens Care, Melbourne, Vic, Australia. Ben Taub Gen Hosp, Dept Med Intens Care, Houston, TX 77030 USA. RP Le Gall, JR (reprint author), Hop St Louis, Dept Intens Care, Paris, France. NR 25 TC 70 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2004 VL 32 IS 1 BP 13 EP 20 DI 10.1097/01.CCM.0000104209.07273.FC PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 765YN UT WOS:000188318800002 PM 14707555 ER PT J AU Lopez, A Lorente, JA Steingrub, J Bakker, J McLuckie, A Willatts, S Brockway, M Anzueto, A Holzapfel, L Breen, D Silverman, MS Takala, J Donaldson, J Arneson, C Grove, G Grossman, S Grover, R AF Lopez, A Lorente, JA Steingrub, J Bakker, J McLuckie, A Willatts, S Brockway, M Anzueto, A Holzapfel, L Breen, D Silverman, MS Takala, J Donaldson, J Arneson, C Grove, G Grossman, S Grover, R TI Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: Effect on survival in patients with septic shock SO CRITICAL CARE MEDICINE LA English DT Article DE human; severe sepsis; septic shock; nitric oxide; nitric oxide synthase inhibitor; N-G-methyl-L-arginine hydrochloride; placebo-controlled study; norepinephrine; dopamine; dobutamine; nitrate; resolution of shock ID SMOOTH-MUSCLE CELLS; L-ARGININE PATHWAY; METHYL-L-ARGININE; SEPSIS SYNDROME; ENDOTOXIN; PATHOGENESIS; MECHANISMS; DISEASE; DOGS AB Objective: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was survival at day 28. Design: Multiple-center, randomized, two-stage, double-blind, placebo-controlled, safety and efficacy study. Setting: A total of 124 intensive care units in Europe, North America, South America, South Africa, and Australasia. Patients: A total of 797 patients with septic shock diagnosed for <24 hrs. Interventions: Patients with septic shock were allocated to receive 546C88 or placebo (5% dextrose) for up to 7 days (stage 1) or 14 days (stage 2) in addition to conventional therapy. Study drug was initiated at 0.05 mL(.)kg(-1.)hr(-1) (2.5 mg(.)kg(-1.)hr(-1) 546C88) and titrated up to a maximum rate of 0.4 mL(.)kg(-1.)hr(-1) to maintain mean arterial pressure between 70 and 90 mm Hg while attempting to withdraw concurrent vasopressors. Measurements and Main Results: Hemodynamic variables, organ function data, microbiological data, concomitant therapy, and adverse event data were recorded at baseline, throughout treatment, and at follow-up. The primary end point was day-28 survival. The trial was stopped early after review by the independent data safety monitoring board. Day-28 mortality was 59% (259/439) in the 546C88 group and 49% (174/358) in the placebo group (p < .001). The overall incidence of adverse events was similar in both groups, although a higher proportion of the events was considered possibly attributable to study drug in the 546C88 group. Most of the events accounting for the disparity between the groups were associated with the cardiovascular system (e.g., decreased cardiac output, pulmonary hypertension, systemic arterial hypertension, heart failure). The causes of death in the study were consistent with those expected in patients with septic shock, although there was a higher proportion of cardiovascular deaths and a lower incidence of deaths caused by multiple organ failure in the 546C88 group. Conclusions: In this study, the nonselective nitric oxide synthase inhibitor 546C88 increased mortality in patients with septic shock. C1 Hosp Infanta Cristinam, Badajoz, Spain. Hosp Getafe, Madrid, Spain. Baystate Med Ctr, Crit Care Sect, Springfield, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Ziekenhuisctr Apeldoorn, Afdeling Intens Care, Apeldoorn, Netherlands. Guys Hosp, Intens Care Unit, London SE1 9RT, England. Bristol Royal Infirm & Gen Hosp, Bristol BS2 8HW, Avon, England. St Johns Hosp, Livingston EH54 6PP, W Lothian, Scotland. Audie L Murphy Mem Vet Adm Med Ctr, Pulm Dis Sect, San Antonio, TX 78284 USA. SAMU, Serv Reanimat Urgences, Hop Fleyriat, Bourg en Bresse, France. Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. Oshawa Gen Hosp, Oshawa, ON, Canada. Kuopio Univ Hosp, Intens Care Unit, SF-70210 Kuopio, Finland. Glaxo Wellcome Inc, Greenford, Middx, England. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Lopez, A (reprint author), Hosp Infanta Cristinam, Badajoz, Spain. RI Bakker, Jan/A-4011-2009; Silverman, Michael/J-3776-2014 OI Bakker, Jan/0000-0003-2236-7391; Silverman, Michael/0000-0002-0389-7656 NR 30 TC 434 Z9 452 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2004 VL 32 IS 1 BP 21 EP 30 DI 10.1097/01.CCM.0000105581.01815.C6 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 765YN UT WOS:000188318800003 PM 14707556 ER PT J AU Rauch, PK Muriel, AC AF Rauch, PK Muriel, AC TI The importance of parenting concerns among patients with cancer SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE cancer; parenting; quality of life; patient-doctor communication ID MATERNAL BREAST-CANCER; OF-LIFE INSTRUMENT; PSYCHOSOCIAL ADJUSTMENT; PSYCHOLOGICAL DISTRESS; QUALITATIVE INTERVIEW; TELLING CHILDREN; CLINICAL-TRIALS; TERMINAL CANCER; COMMUNICATION; ADOLESCENTS AB Almost one quarter of all cancer patients in the United States is estimated to have children under 18-years-old living with them. However, there is limited research on how children's functioning is affected by parental cancer, and the impact of parenting concerns on treatment decisions. This paper will review the literature and hypothesize about why addressing the needs of the children has not been part of routine cancer care. In addition, we will make a case for the importance of including parenting issues in cancer care, and in assessments of treatment decision-making and quality of life. We also describe a clinical program that is attempting to address these issues, and offer practical recommendations for oncologists who want to help parents with cancer and their partners support their children through the challenges of cancer treatment. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Rauch, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM prauch@partners.org NR 44 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JAN PY 2004 VL 49 IS 1 BP 37 EP 42 DI 10.1016/S1040-8428(03)00095-7 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 775YV UT WOS:000189089000002 PM 14734153 ER PT S AU Bragdon, CR O'Connor, D Muratoglu, OK Harris, WH AF Bragdon, CR O'Connor, D Muratoglu, OK Harris, WH BE Kurtz, SM Gsell, RA Martell, J TI Development of a model for testing third body wear of UHMWPE acetabular components SO CROSSLINKED AND THERMALLLY TREATED ULTRA-HIGH MOLECULAR WEIGHT POLYETHYLENE FOR JOINT REPLACEMENTS SE AMERICAN SOCIETY FOR TESTING AND MATERIALS SPECIAL TECHNICAL PUBLICATION LA English DT Proceedings Paper CT Symposium on Crosslinked and Thermally Treated Ultra-High Molecular Weight Polyethylene for Joint Replacements CY NOV 05-06, 2002 CL Miami Beach, FL SP Amer Soc Testing & Mat Int Comm F04 DE polyethylene; crosslinked; wear; third body; simulator; debris ID POLYETHYLENE; PROSTHESES; DEBRIS AB The purpose of this paper is to describe the development of a new wear test protocol utilizing third body particulate debris in order to assess conventional and highly cross-linked polyethylene components. A series of tests were performed using the Boston Hip Simulator to evaluate different types of particles for possible use. Modifications to the simulator are described which ensure that the third body particles can be maintained in suspension. In this series of studies, alumina particles in a concentration of 0.15 mg/cc appeared to provide the most effective challenge to the wear resistance of UHMWPE while at the same time not creating unrealistic destruction to the femoral head. In all of the experiments, under all conditions, the WIAM highly crosslinked polyethylene acetabular components resisted the effects of the third body particles and the concomitant changes in the femoral heads distinctly better than the conventional UHMWPE. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMERICAN SOCIETY TESTING AND MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DRIVE, W CONSHOHOCKEN, PA 19428-2959 USA SN 1040-1695 BN 0-8031-3474-6 J9 AM SOC TEST MATER PY 2004 VL 1445 BP 240 EP 247 DI 10.1520/STP11935S PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials; Orthopedics; Polymer Science SC Engineering; Materials Science; Orthopedics; Polymer Science GA BY62J UT WOS:000189423700018 ER PT J AU Nardi, V Azam, M Daley, GQ AF Nardi, V Azam, M Daley, GQ TI Mechanisms and implications of imatinib resistance mutations in BCR-ABL SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE BCR-ABL kinase; target-directed chemotherapy; imatinib; STI-571; drug resistance; point mutations ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; CHROMOSOME-POSITIVE LEUKEMIA; TYROSINE KINASE INHIBITORS; REGULATES C-ABL; PHILADELPHIA-CHROMOSOME; CLINICAL RESISTANCE; CYTOGENETIC RESPONSES; ARSENIC TRIOXIDE AB Purpose of review Aside from bone marrow transplantation, a definitive cure for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) has yet to be developed. Although Imatinib, the first molecularly targeted drug developed for CML has achieved a remarkable success, the emergence of resistance to this agent mitigates the prospect of a cure for this leukemia. Though a variety of resistance mechanisms can arise, in the majority of patients resistance coincides with reactivation of the tyrosine kinase activity of the BCR-ABL fusion oncoprotein. This can result from gene amplification and, more importantly, point mutations that disrupt the bind of imatinib to BCR-ABL itself. In this review, we aim to define and illuminate mechanisms of resistance and describe how drug resistance is shedding new light on kinase domain regulation. Recent findings In light of recent studies and publications, it is now clear that Imatinib exerts its inhibitory action by stabilizing the inactive non ATP-binding conformation of BCR-ABL and that mutations even outside the kinase domain can lead to enhanced autophosphorylation of the kinase, thereby stabilizing the active conformation that resists imatinib binding. So far, 25 different substitutions of 21 amino acid residues of BCR-ABL have been detected in CML patients. In addition, it has been recently illustrated that mutations preexist the onset of treatment and that some confer a more aggressive disease phenotype. Finally it has been shown that molecular remission is almost never reached through Imatinib therapy. Summary The most common mechanism of relapse for CML patients treated with Imatinib is the appearance of point mutations in the BCR-ABL oncogene that confer resistance to this drug. Insights into the emerging problem of resistance should promote the rational development of alternative, synergistic, and potentially curative treatment strategies. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. 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 Daley, GQ (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 76 TC 137 Z9 150 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2004 VL 11 IS 1 BP 35 EP 43 DI 10.1097/00062752-200401000-00006 PG 9 WC Hematology SC Hematology GA 871GB UT WOS:000225116700005 PM 14676625 ER PT J AU Shimaoka, M Springer, TA AF Shimaoka, M Springer, TA TI Therapeutic antagonists and the conformational regulation of the beta 2 integrins SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID FUNCTION-ASSOCIATED ANTIGEN-1; I-LIKE DOMAIN; GLYCOPROTEIN-IIB-IIIA; INSIDE-OUT ACTIVATION; BETA-A DOMAIN; LIGAND-BINDING; SMALL-MOLECULE; INTEGRIN ANTAGONISTS; CRYSTAL-STRUCTURE; EXTRACELLULAR SEGMENT AB The beta(2) integrins are validated therapeutic targets for inflammatory disorders. Two distinct mechanistic classes of small molecule inhibitors, termed alpha I allosteric and alpha/beta I-like allosteric antagonist, have recently been developed. The alpha I allosteric antagonists bind underneath the C-terminal helix of the I domain and stabilize the I domain in the inactive closed conformation. By contrast, the alpha/beta I-like allosteric antagonists bind to the beta(2) I-like domain MIDAS and disrupt conformational signal transmission between the I and the I-like domain, leaving the I domain in a default inactive form. Furthermore, the two classes of the antagonists have opposite effects on integrin conformation; the alpha I allosteric antagonists stabilize the bent conformation, whereas the alpha/beta I-like allosteric antagonists induce the extended conformation with inactive I domain. The small molecule antagonists to the beta(2) integrin highlight the importance of the structural linkages within and between integrin domains for transmission of the conformational signals and regulation of the overall conformation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Anesthesia & Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Anesthesia & Pathol, 200 Longwood, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu NR 74 TC 34 Z9 35 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2004 VL 4 IS 14 BP 1485 EP 1495 DI 10.2174/1568026043387575 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 858DP UT WOS:000224170800003 PM 15544539 ER PT J AU Kormeili, T Neel, V Moy, RL AF Kormeili, T Neel, V Moy, RL TI Cutaneous sarcoidosis at sites of previous laser surgery SO CUTIS LA English DT Article ID SCAR SARCOIDOSIS; VENIPUNCTURE SITES AB A 33-year-old patient was referred for evaluation and treatment of enlarging scars in areas where full-face carbon dioxide (CO2) laser resurfacing had been performed previously. The patient denied any systemic illness and was in good health at the time of presentation. This is a case report of isolated sarcoidosis limited to the skin associated with CO2 laser resurfacing. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Div Dermatol Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Adm Med Ctr, Los Angeles, CA 91343 USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90073 USA. EM rmoy@ucla.edu NR 19 TC 12 Z9 12 U1 1 U2 1 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD JAN PY 2004 VL 73 IS 1 BP 53 EP 55 PG 3 WC Dermatology SC Dermatology GA 765QD UT WOS:000188294200006 PM 14964632 ER PT J AU Solky, BA Pincus, L Horan, RF AF Solky, BA Pincus, L Horan, RF TI Vancomycin-induced linear IgA bullous dermatosis: Morphology is a key to diagnosis SO CUTIS LA English DT Article ID DISEASE AB Vancomycin-induced linear IgA bullous dermatosis (LABD) previously has been described; however, past reports have suggested that the clinical presentation is nonspecific. We present a case of vancomycin-induced LABD with a suggestive clinical presentation; specifically, groups of annularly arranged vesicles. We propose that this clinical presentation strongly suggests drug-induced LABD and should raise a clinician's suspicion of vancomycin as the offending agent. This awareness may guide the antibiotic management of the patient while the clinician awaits histopathologic correlation. C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Solky, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bsolky@partners.org NR 13 TC 9 Z9 9 U1 1 U2 1 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 EI 2326-6929 J9 CUTIS JI Cutis PD JAN PY 2004 VL 73 IS 1 BP 65 EP 67 PG 3 WC Dermatology SC Dermatology GA 765QD UT WOS:000188294200008 PM 14964634 ER PT J AU Leach, NT Bruns, GAP Donovan, DJ Eisenman, R Ferguson, HL Gusella, JF Harris, DJ Herrick, SR Higgins, AW Ligon, AH Kim, HG Kocher, KM Lu, W Maas, RL MacDonald, ME Michaud, S Michelson, AM Moore, SD Peters, RE Quade, BJ Quintero-Rivera, F Saadi, I Williamson, RE Morton, CC AF Leach, NT Bruns, GAP Donovan, DJ Eisenman, R Ferguson, HL Gusella, JF Harris, DJ Herrick, SR Higgins, AW Ligon, AH Kim, HG Kocher, KM Lu, W Maas, RL MacDonald, ME Michaud, S Michelson, AM Moore, SD Peters, RE Quade, BJ Quintero-Rivera, F Saadi, I Williamson, RE Morton, CC TI Developmental genome anatomy project (DGAP): Cytogenetic approaches to gene identification SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 16th European Colloquium on Animal Cytogenetics and Gene Mapping (16th ECACGM) CY JUL 06-09, 2004 CL Jouy en Josas, FRANCE SP Natl Inst Agron Res C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Donovan, Diana/A-1256-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2004 VL 106 IS 1 MA 18 BP 130 EP 130 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 859DU UT WOS:000224243600112 ER PT J AU Sachs, RK Levy, D Hahnfeldt, P Hlatky, L AF Sachs, RK Levy, D Hahnfeldt, P Hlatky, L TI Quantitative analysis of radiation-induced chromosome aberrations SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article; Proceedings Paper CT 6th International Symposium on Chromosome Aberrations CY SEP 10-13, 2003 CL Univ Duisburg-Essen, Duisburg-Essen, GERMANY HO Univ Duisburg-Essen ID LOW-LET RADIATION; INDUCED GENOMIC INSTABILITY; IN-SITU HYBRIDIZATION; M-FISH ANALYSIS; HUMAN-LYMPHOCYTES; INTERPHASE CHROMOSOMES; EXCHANGE ABERRATIONS; IONIZING-RADIATION; HUMAN FIBROBLASTS; ALPHA-PARTICLES AB We review chromosome aberration modeling and its applications, especially to biodosimetry and to characterizing chromosome geometry. Standard results on aberration formation pathways, randomness, dose-response, proximity effects, transmissibility, kinetics, and relations to other radiobiological endpoints are summarized. We also outline recent work on graph-theoretical descriptions of aberrations, Monte-Carlo computer simulations of aberration spectra, software for quantifying aberration complexity, and systematic links of apparently incomplete with complete or truly incomplete aberrations. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Calif Berkeley, Dept Math, Main Math Off, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Main Math Off, 9th Floor,Evans Hall,MC 3840, Berkeley, CA 94720 USA. EM sachs@math.berkeley.edu FU NCI NIH HHS [CA78496]; NIGMS NIH HHS [GM68423] NR 95 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2004 VL 104 IS 1-4 BP 142 EP 148 DI 10.1159/000077479 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 835XX UT WOS:000222519900021 PM 15162028 ER PT J AU Boehm, JS Hahn, WC AF Boehm, JS Hahn, WC TI Immortalized cells as experimental models to study cancer SO CYTOTECHNOLOGY LA English DT Review DE cancer; hTERT; immortalization; model systems; oncogenes; telomerase; telomeres; transformation; tumor suppressor genes ID SMALL-T-ANTIGEN; MAMMARY EPITHELIAL-CELLS; HUMAN-DIPLOID FIBROBLASTS; RAS-INDUCED SENESCENCE; TELOMERASE ACTIVITY; PROTEIN PHOSPHATASE-2A; MOUSE CELLS; LIFE-SPAN; ONCOGENIC TRANSFORMATION; MEDIATED TRANSFORMATION AB The development of cancer is a multi-step process in which normal cells sustain a series of genetic alterations that together program the malignant phenotype. Much of our knowledge of cancer biology results from the detailed study of specimens and cell lines derived from patient tumors. While these approaches continue to yield critical information regarding the identity, number, and types of alterations found in human tumors, further progress in understanding the molecular basis of malignant transformation depends upon the generation and use of increasingly sophisticated experimental models of cancer. Over the past several years, the recognition that telomeres and telomerase play essential roles in regulating cell lifespan now permits the development of new models of human cancer. Here we review recent progress in the use of immortalized human cells as a foundation for understanding the molecular basis of cancer. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Hahn, WC (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu OI Boehm, Jesse/0000-0002-6795-6336 NR 104 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PD JAN PY 2004 VL 45 IS 1-2 BP 47 EP 59 DI 10.1007/s10616-004-5125-1 PG 13 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 907GA UT WOS:000227702700007 PM 19003243 ER PT J AU Duda, JE AF Duda, JE TI Pathology and neurotransmitter abnormalities of dementia with Lewy bodies SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Review DE dementia with Lewy bodies; neuropathology; alpha-synuclein; neurotransmitters ID SLEEP BEHAVIOR DISORDER; ANTI-UBIQUITIN IMMUNOCYTOCHEMISTRY; NICOTINIC ACETYLCHOLINE-RECEPTORS; ALPHA-SYNUCLEIN IMMUNOREACTIVITY; SPORADIC ALZHEIMERS-DISEASE; PURE AUTONOMIC FAILURE; PARKINSONS-DISEASE; BODY DISEASE; CHOLINERGIC DYSFUNCTION; PROGRESSIVE DEMENTIA AB The neuropathology of dementia with Lewy bodies (DLB) is characterized by the presence of Lewy bodies (LBs) and Lewy neurites (LNs) in specific systems throughout the brainstem, diencephalon, basal ganglia and neocortex. DLB shares many features with Parkinson's disease (PD) with respect to LB distribution in the brainstem, and there is recent evidence that Lewy pathology (LP), which consists of LBs and LNs, may progress in a systematic fashion through the brain regardless of clinical phenotype. Increasing evidence supports a central role for LNs in Lewy neurodegeneration and engenders a 'neuritic dystrophy hypothesis' described herein. LP formation also occurs in Alzheimer's disease (AD) and other dementias, and it is unclear whether there is a common underlying pathophysiology in these diseases or if the LP merely represents a common final pathway. Cholinergic deficits are evident in both DLB and AD, with reductions in acetylcholine and abnormalities in nicotinic and muscarinic receptor expression in both diseases. Cholinergic deficits are greater in DLB than in AD, although generally there is less brain atrophy in DLB. The lower neurodegeneration and preservation of cholinergic receptors in DLB has important therapeutic implications because patients with DLB (vs. AD) may receive greater benefits from cholinergic pharmacologic therapy. Patients with DLB who display parkinsonian signs have severe dopamine neurotransmitter deficiencies similar to those in patients with PD, although the manifestation of these deficiencies is different. Both groups have striatal dopamine transporter deficiencies, but the striatal dopamine D2 receptors are reduced in DLB patients compared with PD and control subjects. D2 receptor deficiencies in DLB may be the cause of the relative lack of response to levodopa treatment and the severe adverse reaction to neuroleptics in these patients. Copyright (C) 2004 S. Karger AG, Basel. C1 Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Duda, JE (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. NR 102 TC 36 Z9 39 U1 3 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2004 VL 17 SU 1 BP 3 EP 14 DI 10.1159/000074677 PG 12 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 754DD UT WOS:000187286700002 PM 14676464 ER PT J AU Sultzer, DL AF Sultzer, DL TI Psychosis and antipsychotic medications in Alzheimer's disease: Clinical management and research perspectives SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; psychosis; treatment; antipsychotic medications ID PLACEBO-CONTROLLED-TRIAL; SEROTONIN REUPTAKE INHIBITORS; NURSING-HOME PATIENTS; BEHAVIORAL DISTURBANCES; PARKINSONS-DISEASE; DOUBLE-BLIND; LEWY BODIES; NEUROPSYCHIATRIC SYMPTOMS; GENETIC-VARIATION; RANDOMIZED TRIAL AB Psychosis is common in patients with Alzheimer's disease (AD) and contributes substantially to patient morbidity and caregiver distress. Antipsychotic medications are used to treat psychosis and other psychiatric or behavioral symptoms in AD, although optimal treatment guidelines have been elusive. Choosing the most advantageous medication for an individual patient is challenging. This article provides an overview of clinical management principles and medication treatment strategies for patients with AD and psychosis. Effects of individual medications are also described. Medications in the conventional neuroleptic, atypical antipsychotic, cholinesterase inhibitor, and serotonergic classes have been shown to ameliorate psychosis and behavioral symptoms in patients with AD, although the evidence is not conclusive for many medications. Side effects vary substantially across medication classes and modestly among individual patients. Improvement in agitation, aggression, or other behaviors with antipsychotic medication treatment may not depend on distinct antipsychotic effects. In contrast, there is preliminary evidence that delusions and hallucinations may respond to treatment with medications outside the antipsychotic class. Many important clinical questions warrant further research study. In particular, studies to compare how individual symptoms respond to different medications, and to examine how to best manage overlapping symptoms or incomplete treatment response are needed. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Gero Neuropsychiat Div, Los Angeles, CA 90073 USA. RP Sultzer, DL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, 3 South,116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH56031] NR 88 TC 14 Z9 14 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2004 VL 17 IS 1-2 BP 78 EP 90 DI 10.1159/000074279 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 747XY UT WOS:000186832600012 PM 14566100 ER PT J AU Li, XB Nahas, Z Anderson, B Kozel, EA George, MS AF Li, XB Nahas, Z Anderson, B Kozel, EA George, MS TI Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression? SO DEPRESSION AND ANXIETY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; RATING-SCALE; TMS AB Numerous studies have examined the acute antidepressant effects of prefrontal transcranial magnetic stimulation (TMS). However, there is little information on whether TMS can be used as a maintenance treatment to maintain normal mood once subjects have responded. We describe seven adults with bipolar depression who responded acutely to TMS and were then treated with TMS weekly for up to 1 year. TMS was carried out over the left prefrontal cortex at 110% motor threshold, 5 Hz for 8 s for 40 trains. Three subjects completed 1 full year of weekly TMS with an average Hamilton Rating Scale for Depression of 13 (sd = 5.9) over the year. These data suggest but do not prove that TMS might eventually be used as an adjunctive maintenance treatment for at least some patients with bipolar depression. Much work remains. (C) 2004 Wiley-Liss, Inc. C1 Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, 67 President St,Room 502 N,POB 250861, Charleston, SC 29425 USA. EM lixi@musc.edu NR 6 TC 52 Z9 53 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 20 IS 2 BP 98 EP 100 DI 10.1002/da.20027 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 865ZF UT WOS:000224742000007 PM 15390210 ER PT J AU Cassano, P Lattanzi, L Soldani, F Navari, S Battistini, G Gemignani, A Cassano, GB AF Cassano, P Lattanzi, L Soldani, F Navari, S Battistini, G Gemignani, A Cassano, GB TI Pramipexole in treatment-resistant depression: An extended follow-up SO DEPRESSION AND ANXIETY LA English DT Article DE mood disorders; dopamine agonists; treatment outcome; adverse effects; investigational therapies ID DOPAMINE AGONISTS; MAJOR DEPRESSION; DOUBLE-BLIND; SLEEP ATTACKS; LONG-TERM; PLACEBO; COMBINATION; PREVENTION; FLUOXETINE; SYMPTOMS AB We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score = < 2 at LIFE for at least 8 weeks) and recurrence (after remission score > = 3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 bad bipolar depression (16 women; mean age = 52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects bad at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 2 8 weeks. Mean baseline MADRS and CGI-S scores were 33.7 +/- 8.4 (sd) and 4.6 +/- 0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression. (C) 2004 Wiley-Liss, Inc. C1 Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,4th Floor,Suite 401, Boston, MA 02114 USA. EM pcassano@partners.org RI Cassano, Paolo/I-6959-2012 NR 25 TC 66 Z9 68 U1 4 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 20 IS 3 BP 131 EP 138 DI 10.1002/da.20038 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 876BV UT WOS:000225471500005 PM 15549689 ER PT J AU Carter, AS Pollock, RA Suvak, MK Paul, DL AF Carter, AS Pollock, RA Suvak, MK Paul, DL TI Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder SO DEPRESSION AND ANXIETY LA English DT Article; Proceedings Paper CT Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 1998 CL Washington, DC SP Assoc Adv Behav Therapy DE obsessive-compulsive disorder; comorbidity; anxiety; depression; panic disorder; family studies ID ATTENTION-DEFICIT DISORDER; PSYCHIATRIC-DISORDERS; GENETIC-RELATIONSHIP; TOURETTES-SYNDROME; EPIDEMIOLOGY; DIAGNOSIS; VALIDITY; HISTORY; PHENOMENOLOGY; ADOLESCENTS AB To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD bad at least one comorbid anxiety disorder. Early age at onset (< 10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants. Depression and Anxiety 20:165-174, 2004. (C)(C) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. Univ Massachusetts, Dept Psychol, Boston, MA USA. VA Boston Hlth Care Syst, Natl Ctr Post Traumat Stress Disorder, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA USA. RP Paul, DL (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Psychiat & Neurodev Genet Unit, 149 13th St,10th Floor, Charlestown, MA 02129 USA. EM dpauls@partners.org FU NIMH NIH HHS [MH 00508]; NINDS NIH HHS [NS 16648] NR 43 TC 36 Z9 38 U1 2 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 20 IS 4 BP 165 EP 174 DI 10.1002/da.20042 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 891XI UT WOS:000226613900002 PM 15643633 ER PT J AU Chen, HH Nicoletti, M Sanches, M Hatch, JP Sassi, RB Axelson, D Brambilla, P Keshavan, MS Ryan, N Birmaher, B Soares, JC AF Chen, HH Nicoletti, M Sanches, M Hatch, JP Sassi, RB Axelson, D Brambilla, P Keshavan, MS Ryan, N Birmaher, B Soares, JC TI Normal pituitary volumes in children and adolescents with bipolar disorder: A magnetic resonance imaging study SO DEPRESSION AND ANXIETY LA English DT Article DE magnetic resonance imaging; bipolar disorder; pituitary; adolescents ID MAJOR DEPRESSION; GLAND; AGE; CORTISOL AB The volume of the pituitary gland in adults with bipolar disorder has previously been reported to be smaller than that of healthy controls. Such abnormalities would be consistent with the HPA dysfunction reported in this illness. We conducted a study of children and adolescents with bipolar disorder to determine whether size abnormalities in the pituitary gland are already present early in illness course. Magnetic resonance imaging (MRI) morphometric analysis of the pituitary gland was carried out in 16 DSM-IV children and adolescents with bipolar disorder (mean age +/- sd = 15.5 +/- 3.4 years) and 21 healthy controls (mean age +/- sd = 16.9 +/- 3. 8 years). Subjects underwent a 1.5 T MRI, with 3-D Spoiled Gradient Recalled (SPGR) acquisition. There was no statistically significant difference between pituitary gland volumes of bipolar patients compared to healthy controls (ANCOVA, age, gender, and ICV as covariates; F = 1.77, df = 1,32, P = .19). There was a statistically significant direct relationship between age and pituitary gland volume in both groups (r =. 59, df = 17, P = .007 for healthy controls; r = .61, df = 12, P = .008 for bipolar patients). No evidence of size abnormalities in the pituitary gland was found in child and adolescent bipolar patients, contrary to reports involving adult bipolar patients. This suggests that anatomical abnormalities in this structure may develop later in illness course as a result of continued HPA dysfunction. Depression and Anxiety 20:182-186, 2004. (C) 2005 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychait, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Ctr Med, Dept Psychiat, Pittsburgh, PA USA. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, Udine, Italy. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychait, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 01736, MH 30915, MH 55123, MH 59929] NR 21 TC 27 Z9 27 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 20 IS 4 BP 182 EP 186 DI 10.1002/da.20044 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 891XI UT WOS:000226613900004 PM 15643632 ER PT J AU Mischoulon, D Opitz, G Kelly, K Fava, M Rosenbaum, JF AF Mischoulon, D Opitz, G Kelly, K Fava, M Rosenbaum, JF TI A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder: Comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment SO DEPRESSION AND ANXIETY LA English DT Article DE nefazodone; depression; SSRI; effectiveness; clinical services; antidepressant; tolerability ID SEROTONIN RECEPTOR HYPERSENSITIVITY; TREATMENT-RESISTANT DEPRESSION; PANIC DISORDER; META-CHLOROPHENYLPIPERAZINE; CYTOCHROME-P450 SYSTEM; HEALTHY-SUBJECTS; CLINICAL-TRIAL; RATING-SCALE; DOUBLE-BLIND; IN-VITRO AB Anecdotal evidence suggests that the recent discontinuation of an SSRI may confound the tolerability of the initiation of nefazodone treatment. We sought to determine whether recent discontinuation of an SSRI interferes with effectiveness and/or tolerability of nefazodone. Twenty-six depressed subjects, 21-63 years old, were recruited at the Massachusetts General Hospital. Thirteen subjects (50%) had discontinued an SSRI within 1-4 weeks due to ineffectiveness and/or side effects. Thirteen subjects (50%) had not taken antidepressants for the previous 6 months. Subjects were administered open nefazodone 50 mg p.o. b.i.d., and doses were increased as tolerated to a maximum of 600 mg/day. Subjects were followed for 12 weeks and were assessed for response and side effects using HAM-D-6 and clinical interviews. Both groups improved significantly on nefazodone; however, there was no statistically significant difference in response (greater than or equal to50% decrease in HAM-D-6) rates between completers with prior SSRI treatment (80%) and completers without recent exposure to antidepressants (67%). Response rates based on intent-to-treat (ITT) analysis were 31% for both groups. Association between prior SSRI treatment and discontinuation of nefazodone due to side effects or non-response was not statistically significant. Our study suggests that the rate of negative outcomes with nefazodone is no different whether patients have recently failed an SSRI. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Dept Clin & Res Program, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM dmischoulon@partners.org NR 50 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 19 IS 1 BP 43 EP 50 DI 10.1002/da.10127 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 775LJ UT WOS:000189041700007 PM 14978785 ER PT J AU Roy-Byrne, PP Russo, J Michelson, E Zatzick, D Pitman, RK Berliner, L AF Roy-Byrne, PP Russo, J Michelson, E Zatzick, D Pitman, RK Berliner, L TI Risk factors and outcome in ambulatory assault victims presenting to the acute emergency department setting: Implications for secondary prevention studies in PTSD SO DEPRESSION AND ANXIETY LA English DT Article DE trauma; anxiety; violence; rape; treatment ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; URBAN-POPULATION; YOUNG-ADULTS; TRAUMA; PREVALENCE; SURVIVORS; SYMPTOMS; DISTRESS; INJURY AB Prevention of post-traumatic stress disorder (PTSD) in trauma victims is an important public health goal. Planning for the studies required to validate prevention strategies requires identification of subjects at high risk and recruitment of unbiased samples that represent the larger high-risk population (difficult because of the avoidance of many trauma victims). This study recruited high-risk victims of interpersonal violence (sexual or physical assault) presenting to an urban emergency department for prospective 1- and 3-month follow-up. Of 546 victims who were approached about participating, only 56 agreed to be contacted and only 46 participated in either the 1- or 3-month interviews. Of the 46, 43 had been previously victimized with a mean of over six traumas in the group; 21% bad prior PTSD, 85% had prior psychiatric illness, and 37% had prior substance abuse. Sixty-seven percent had positive urine for alcohol or drugs on presentation. Fifty-six percent developed PTSD at 1 or 3 months with the rate declining between 1 and 3 months. There was high use of medical and psychiatric services. These findings document both the difficulty of recruiting large samples of high-risk assault victims to participate in research, and the high rate of prior traumatization, PTSD, substance use, and psychiatric morbidity in these subjects which, if still active at the time of victimization, may complicate efforts to document preventive treatment effects. (C) 2004 Wiley-Liss, Inc. C1 Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Roy-Byrne, PP (reprint author), Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, 325 9Th Ave,Box 359911, Seattle, WA 98104 USA. EM roybyrne@u.washington.edu NR 40 TC 22 Z9 22 U1 4 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 19 IS 2 BP 77 EP 84 DI 10.1002/da.10132 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 803KP UT WOS:000220230300002 PM 15022142 ER PT J AU Hirshfeld-Becker, DR Biederman, J Faraone, SV Robin, JA Friedman, D Rosenthal, JM Rosenbaum, JE AF Hirshfeld-Becker, DR Biederman, J Faraone, SV Robin, JA Friedman, D Rosenthal, JM Rosenbaum, JE TI Pregnancy complications associated with childhood anxiety disorders SO DEPRESSION AND ANXIETY LA English DT Article DE prenatal influences; anxiety disorders; risk factors; psychopathology; child psychopathology ID OBSTETRIC COMPLICATIONS; PERINATAL COMPLICATIONS; PANIC DISORDER; PSYCHIATRIC-DIAGNOSIS; MATERNAL ANXIETY; MAJOR DEPRESSION; FETAL ASPHYXIA; RISK-FACTORS; CHILDREN; PSYCHOPATHOLOGY AB To determine whether perinatal complications predict childhood anxiety disorders independently of parental psychopathology, we systematically assessed pregnancy and delivery complications and psychopathology in a sample of children (mean age = 6.8 years) at high risk for anxiety disorders whose parents bad panic disorder with (n = 138) or without (n = 26) major depression, and in contrast groups of offspring of parents with major depression alone (n = 47), or no mood or anxiety disorders (n = 95; total N = 306). Psychopathology in the children was assessed by structured diagnostic interviews (K-SADS), and pregnancy and delivery complications were assessed using the developmental history module of the DICA-R Number of pregnancy complications predicted multiple childhood anxiety disorders independently of parental diagnosis (odds ratio = 1.6 [1.4-2.0]). This effect was accounted for by heavy bleeding requiting bed-rest, hypertension, illness requiting medical attention, and serious family problems. Associations remained significant when lifetime child mood and disruptive behavior disorders were covaried. Results suggest that prenatal stressors may increase a child's fisk for anxiety disorders beyond the risk conferred by parental psychopathology alone. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 185 Alewife Brook Parkway,Suite 2100, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08 MH001538-02, R01 MH-47077-05] NR 45 TC 30 Z9 31 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2004 VL 19 IS 3 BP 152 EP 162 DI 10.1002/da.20007 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 824DJ UT WOS:000221664200003 PM 15129417 ER PT J AU Gu, GQ Wells, JM Dombkowski, D Preffer, F Aronow, B Melton, DA AF Gu, GQ Wells, JM Dombkowski, D Preffer, F Aronow, B Melton, DA TI Global expression analysis of gene regulatory pathways during endocrine pancreatic development SO DEVELOPMENT LA English DT Article DE Myt1; endoderm; pancreas; endocrine; islets; microarray ID EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; DIABETES RESEARCH; PROGENITOR CELLS; ZINC-FINGER; IN-VITRO; C-KIT; MOUSE; INSULIN; DIFFERENTIATION AB To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. RP Melton, DA (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM dmelton@biohp.harvard.edu RI Aronow, Bruce/F-8438-2012 NR 62 TC 165 Z9 173 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 2004 VL 131 IS 1 BP 165 EP 179 DI 10.1242/dev.00921 PG 15 WC Developmental Biology SC Developmental Biology GA 768UR UT WOS:000188553900016 PM 14660441 ER PT J AU Kenney, AM Widlund, HR Rowitch, DH AF Kenney, AM Widlund, HR Rowitch, DH TI Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors SO DEVELOPMENT LA English DT Article DE cerebellum; Sonic hedgehog; proliferation; GSK3; medulloblastoma; Myc; neural precursor; mouse; Nmyc1 (N-myc) ID GROWTH-FACTOR-I; MYC TRANSACTIVATION DOMAIN; N-TERMINAL DOMAIN; SONIC HEDGEHOG; C-MYC; EMBRYONIC LETHALITY; TRANSCRIPTIONAL REPRESSORS; CUBITUS INTERRUPTUS; BURKITTS-LYMPHOMA; PROTEIN STABILITY AB Neuronal precursor cells in the developing cerebellum require activity of the sonic hedgehog (Shh) and phosphoinositide-3-kinase (PI3K) pathways for growth and survival. Synergy between the Shh and PI3K signaling pathways are implicated in the cerebellar tumor medulloblastoma. Here, we describe a mechanism through which these disparate signaling pathways cooperate to promote proliferation of cerebellar granule neuron precursors. Shh signaling drives expression of mRNA encoding the Nmyc1 oncoprotein (previously N-myc), which is essential for expansion of cerebellar granule neuron precursors. The PI3K pathway stabilizes Nmyc1 protein via inhibition of GSK3-dependent Nmyc1 phosphorylation and degradation. The effects of PI3K activity on Nmyc1 stabilization are mimicked by insulin-like growth factor, a PI3K agonist with roles in central nervous system precursor growth and tumorigenesis. These findings indicate that Shh and PI3K signaling pathways converge on N-Myc to regulate neuronal precursor cell cycle progression. Furthermore, they provide a rationale for therapeutic targeting of PI3K signaling in medulloblastoma. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu FU NINDS NIH HHS [R01 NS4051, R21 NS41764-01] NR 59 TC 155 Z9 157 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 2004 VL 131 IS 1 BP 217 EP 228 DI 10.1242/dev.00891 PG 12 WC Developmental Biology SC Developmental Biology GA 768UR UT WOS:000188553900020 PM 14660435 ER PT J AU Bhide, PG Nowakowski, RS AF Bhide, PG Nowakowski, RS TI Neural stem cells: A perspective and synopsis of the current status SO DEVELOPMENTAL NEUROSCIENCE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM bhide@helix.mgh.harvard.edu RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670; Bhide, Pradeep/0000-0003-4236-9415 NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2004 VL 26 IS 2-4 BP 81 EP 81 DI 10.1159/000083931 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 897BH UT WOS:000226978500001 ER PT J AU Mitchell, BD Emsley, JG Magavi, SSP Arlotta, P Macklis, JD AF Mitchell, BD Emsley, JG Magavi, SSP Arlotta, P Macklis, JD TI Constitutive and induced neurogenesis in the adult mammalian brain: Manipulation of endogenous precursors toward CNS repair SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE neurogenesis; neocortex; neural precursors; neural stem cells; neuronal recruitment ID NEURAL STEM-CELLS; MARROW STROMAL CELLS; FIBROBLAST GROWTH FACTOR-2; TARGETED APOPTOTIC DEGENERATION; MOUSE SUBVENTRICULAR ZONE; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; DENTATE GYRUS NEURONS; GLOBOSE BASAL-CELLS; BONE-MARROW AB Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. During the past 3 decades, research exploring potential neuronal replacement therapies has focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent advances in our understanding of related events of neural development and plasticity, including the role of radial glia in developmental neurogenesis and the ability of endogenous precursors present in the adult brain to be induced to produce neurons and partially repopulate brain regions affected by neurodegenerative processes, have led to fundamental changes in the views about how the brain develops as well as to approaches by which endogenous precursors might be recruited to repair the adult brain. Recruitment of new neurons can be induced in a region-specific, layer-specific and neuronal-type-specific manner, and, in some cases, newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells. Copyright (C) 2004 S. Karger AG, Basel. C1 MGH HMS, Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA 02114 USA. MGH HMS, Ctr Nervous Syst Repair, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci, Boston, MA USA. RP Macklis, JD (reprint author), MGH HMS, Ctr Nervous Syst Repair, Dept Neurosurg, Edwards 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NICHD NIH HHS [HD28478, HD18655]; NINDS NIH HHS [NS41590, NS42190] NR 170 TC 36 Z9 38 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2004 VL 26 IS 2-4 BP 101 EP 117 DI 10.1159/000082131 PG 17 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 897BH UT WOS:000226978500004 PM 15711054 ER PT J AU Shah, K Hsich, G Breakefield, XO AF Shah, K Hsich, G Breakefield, XO TI Neural precursor cells and their role in neuro-oncology SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE brain; glioma; gene therapy; virus vectors; stem cells ID APOPTOSIS-INDUCING LIGAND; CENTRAL-NERVOUS-SYSTEM; EPIDERMAL-GROWTH-FACTOR; TRAIL-INDUCED APOPTOSIS; ADULT MAMMALIAN BRAIN; CNS STEM-CELLS; IN-VIVO; PROGENITOR CELLS; DENTATE GYRUS; GENE-TRANSFER AB Neural precursor cells (NPCs) provide a new mode for delivery of genes and proteins to brain tumors. These cells exist both in the developing and the adult nervous systems of all mammalian organisms. They have the ability to self-renew, migrate to diseased areas of the brain and differentiate into neurons, astrocytes and oligodendrocytes. The migratory ability of NPCs and their capacity to differentiate into all neural phenotypes provides a powerful tool for the treatment of both diffuse and localized neurological disorders. NPCs have been used in transplantation to replace damaged cells and in cancer therapy to provide therapeutic proteins and vectors to eliminate malignant cells in the brain. This review focuses on the characteristics of NPCs and their experimental use in the therapy for brain tumors. Examples are provided of monitoring migration of NPCs by bioluminescence imaging in living animals and of using them to deliver the apoptotic protein, TRAIL, to kill tumor cells. Copyright (C) 2004 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, 13th St,Bldg 149,Room 6216, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu FU NCI NIH HHS [CA6924] NR 126 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2004 VL 26 IS 2-4 BP 118 EP 130 DI 10.1159/000082132 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 897BH UT WOS:000226978500005 PM 15711055 ER PT J AU Popolo, M McCarthy, DM Bhide, PG AF Popolo, M McCarthy, DM Bhide, PG TI Influence of dopamine on precursor cell proliferation and differentiation in the embryonic mouse telencephalon SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE ganglionic eminence; dopamine; cell cycle; striatum; prefrontal cortex; D-1 receptor; D-2 receptor ID LATERAL GANGLIONIC EMINENCE; DEVELOPING CEREBRAL-CORTEX; CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; CORPUS STRIATUM; MESSENGER-RNA; RAT-BRAIN; S-PHASE; CYCLE; RECEPTOR AB Dopamine and its receptor binding sites appear in the brain early in the embryonic period raising the possibility that dopamine may influence brain development. We show that one component of dopamine's role in brain development is its ability to influence proliferation and differentiation of progenitor cells in the neostriatum and the dorsomedial prefrontal cortex on embryonic day 15 in mice. Dopamine and a D-1-like receptor agonist reduce the relative proportion of progenitor cells incorporating the S phase marker bromodeoxyuridine. A D-2-like agonist produces the opposite effect. Both the effects are evident in the lateral ganglionic eminence, neuroepithelial precursor of the neostriatum and in the neuroepithelium of the dorsomedial prefrontal cortex. Neostriatal progenitor cells are more responsive than cortical progenitor cells to the effects of dopamine receptor activation. Furthermore, progenitor cells in the ventricular zone are more responsive to D-1-like agonists and progenitors in the subventricular zone more so to D-2-like agonists. Thus, dopamine's developmental effects show regional and progenitor cell type specificity, presumably due to heterogeneity in the distribution of its receptor binding sites. Copyright (C) 2004 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM Bhide@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU NICHD NIH HHS [HD 05515, P01 HD005515]; NINDS NIH HHS [NS 43426, R01 NS043426] NR 43 TC 56 Z9 60 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2004 VL 26 IS 2-4 BP 229 EP 244 DI 10.1159/000082140 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 897BH UT WOS:000226978500013 PM 15711063 ER PT J AU Kushner, JA Haj, FG Klaman, LD Dow, MA Kahn, BB Neel, BG White, MF AF Kushner, JA Haj, FG Klaman, LD Dow, MA Kahn, BB Neel, BG White, MF TI Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice SO DIABETES LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-2; ENDOPLASMIC-RETICULUM; 1B; RESISTANCE; GROWTH; SENSITIVITY; DISRUPTION; PATHWAY; LACKING; PTP1B AB Protein tyrosine phosphatase-1b (Ptp1b) inhibits insulin and leptin signaling by dephosphorylating specific tyrosine residues in their activated receptor complexes. Insulin signals are mediated by tyrosine phosphorylation of the insulin receptor and its downstream targets, such as Irs1 and Irs2. Irs2 plays an especially important role in glucose homeostasis because it mediates some peripheral actions of insulin and promotes pancreatic beta-cell function. To determine whether the deletion of Ptp1b compensates for the absence of Irs2, we analyzed mice deficient in both Ptp1b and Irs2. Pancreatic beta-cell area decreased in Ptp1b(-/-) mice, consistent with decreased insulin requirements owing to increased peripheral insulin sensitivity. By contrast, peripheral insulin sensitivity and beta-cell area increased in Irs2(-/-)::Ptp1b(-/-) mice, which improved glucose tolerance in Irs2(-/-)::PtP1b(-/-) mice and delayed diabetes until 3 months of age. However, beta-cell function eventually failed to compensate for absence of Irs2. Our studies demonstrate a novel role for Ptp1b in regulating beta-cell homeostasis and indicate that Ptp1b deficiency can partially compensate for lack of Irs2. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Biol Program,Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NCI NIH HHS [CA 49152]; NIDDK NIH HHS [DK38712, DK43808, DK55326, DK60838, DK60839] NR 34 TC 48 Z9 51 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 JAN PY 2004 VL 53 IS 1 BP 61 EP 66 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JZ UT WOS:000187632400009 PM 14693698 ER PT J AU Bluher, S Ziotopoulou, M Bullen, JW Moschos, SJ Ungsunan, L Kokkotou, E Maratos-Flier, E Mantzoros, CS AF Bluher, S Ziotopoulou, M Bullen, JW Moschos, SJ Ungsunan, L Kokkotou, E Maratos-Flier, E Mantzoros, CS TI Responsiveness to peripherally administered melanocortins in lean and obese mice SO DIABETES LA English DT Article ID DIET-INDUCED OBESITY; MELANOCYTE-STIMULATING HORMONE; NEUROPEPTIDE-Y; FOOD-INTAKE; LEPTIN RESISTANCE; ARCUATE NUCLEUS; EXPRESSION; RATS; AGONIST; FAT AB To elucidate mechanisms of melanocortin action, we investigated the effects of a melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 mug q.i.d. i.p.) for 24 h results in similar weight loss but a more pronounced decrease of food intake in DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both food intake and body weight is more pronounced in DIO mice than in lean mice. MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med, RN 325,99 Brookline Ave, Boston, MA 02215 USA. NR 38 TC 54 Z9 56 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 JAN PY 2004 VL 53 IS 1 BP 82 EP 90 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JZ UT WOS:000187632400012 PM 14693701 ER PT J AU Hu, FB Doria, A Li, T Meigs, JB Liu, SM Memisoglu, A Hunter, D Manson, JE AF Hu, FB Doria, A Li, T Meigs, JB Liu, SM Memisoglu, A Hunter, D Manson, JE TI Genetic variation at the adiponectin locus and risk of type 2 diabetes in women SO DIABETES LA English DT Article ID ADIPOSE-SPECIFIC GENE; POLYMORPHISM; MELLITUS; OBESITY; CLASSIFICATION; DIAGNOSIS; PROTEIN AB Previous data suggesting that polymorphisms in the adiponectin gene were associated with insulin resistance or type 2 diabetes have been inconsistent. We assessed the relationship between five common haplotype-tagging single nucleotide polymorphisms (SNPs) in the adiponectin gene (-11365C>G, -4034A>C, -3964A>G, +45T>G, and +276G>T), haplotypes defined by these SNPs, and the risk of type 2 diabetes by conducting a nested case-control study of 642 incident cases of type 2 diabetes and 995 matching control subjects in the Nurses' Health Study. Overall, we did not observe significant differences in genotype or allele frequencies for the five SNPs between the case and control subjects. After adjustment for diabetes risk factors, the -4034 C/C genotype was associated with a reduced risk of diabetes (odds ratio [OR] compared with the A/A genotype = 0.70, 95% CI 0.50-0.99, P = 0.04). In subgroup analyses, the +276 genotype was significantly associated with diabetes risk only among subjects with peroxisome proliferator-activated receptor-gamma (PPARgamma) variant 12Ala allele (OR comparing +276 T alleles with the G/G genotype = 1.69, 1.04-2.75, P = 0.035) or among obese subjects (1.46, 1.03-2.08, P = 0.03). These data suggest a potential interaction between the adiponectin genotype and PPARgamma genotype or obesity, but these analyses should be considered exploratory and require further investigation in larger studies. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK55523, DK58845] NR 17 TC 84 Z9 90 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2004 VL 53 IS 1 BP 209 EP 213 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JZ UT WOS:000187632400028 PM 14693717 ER PT J AU Wolf, M Sauk, J Shah, A Smirnakis, KV Jimenez-Kimble, R Ecker, JL Thadhani, R AF Wolf, M Sauk, J Shah, A Smirnakis, KV Jimenez-Kimble, R Ecker, JL Thadhani, R TI Inflammation and glucose intolerance - A prospective study of gestational diabetes mellitus SO DIABETES CARE LA English DT Article ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE SYNDROME; INNATE IMMUNE-SYSTEM; INHIBITOR-KAPPA-B; BLOOD-CELL COUNT; METABOLIC SYNDROME; OBESE WOMEN; ENDOTHELIAL DYSFUNCTION; LEUKOCYTE COUNT AB OBJECTIVE - Increased leukocyte count is a marker of inflammation that has been associated with the development of type 2 diabetes in prospective studies. Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain pathophysiological mechanisms, few studies have examined inflammation and risk of GDM. RESEARCH DESIGN AND METHODS - We prospectively examined routine leukocyte counts collected at the first prenatal visit in a cohort of 2,753 nulliparous euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were divided into quartiles of leukocyte count, and the results of third-trimester glucose screening tests and the incidence of GDM among these quartiles were compared. Logistic regression was used to calculate univariate and multivariable-adjusted relative risks (RRs) of GDM according to leukocyte quartiles. RESULTS - Leukocyte counts were increased among women who subsequently developed GDM compared with those who remained free of GDM (10.5 +/- 2.2 vs. 9.2 +/- 2.2 X 10(3) cells/ml; P < 0.01). There was a linear increase in postloading mean glucose levels (P for trend <0.01), the area under the glucose tolerance test curves (P for trend <0.01), and the incidence of GDM (quartite 1, 1.1; quartile 2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend <0.01) with increasing leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in the RR of GDM with increasing leukocyte quartiles remained statistically significant (quartile 1, reference; quartile 2, RR 2.3 [95% Cl 0.9-5.7]; quartile 3, 3.3 [1.4-7.8]; quartile 4, 4.9 [2.1-11.2], P for trend <0.01). CONCLUSIONS - Increased leukocyte count early in pregnancy is independently and linearly associated with the results of GDM screening tests and the risk of GDM. Although overlap in the leukocyte count distributions precludes it from being a clinically useful biomarker, these data suggest that inflammation is associated with the development of GDM and may be another pathophysiological link between GDM and future type 2 diabetes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Dept Med, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03804]; NICHD NIH HHS [HD39223] NR 46 TC 61 Z9 70 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2004 VL 27 IS 1 BP 21 EP 27 DI 10.2337/diacare.27.1.21 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JX UT WOS:000187632200006 PM 14693961 ER PT J AU McNeely, MJ Boyko, EJ AF McNeely, MJ Boyko, EJ TI Type 2 diabetes prevalence in Asian Americans SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; FASTING GLUCOSE; RISK; MELLITUS; COHORTS; HEALTH AB OBJECTIVE - Asians are thought to be at high risk for diabetes, yet there is little population-based information about diabetes in Asian Americans. The purpose of this study was to directly compare the prevalence of type 2 diabetes in Asian Americans with other racial and ethnic groups in the U.S. using data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS). RESEARCH DESIGN AND METHODS - The BRFSS is a population-based telephone survey of the health status and health behaviors of Americans in all 50 states, Guam, Puerto Rico, and the U.S. Virgin Islands. Subjects included 3,071 Asians, 12,561 blacks, 12,153 Hispanics, 2,299 Native Americans, 626 Pacific Islanders, and 129,116 non-Hispanic whites aged greater than or equal to30 years. Subjects who reported a physician-diagnosis of diabetes were considered to have type 2 diabetes unless they were diagnosed before age 30. RESULTS - Compared with whites, odds ratios (95% CIS) for diabetes, adjusted for age and sex, were 1.0 (0.7-1.4) for Asians, 2.3 (2.1-2.6) for blacks, 2.0 (1.8-2.3) for Hispanics, 2.2 (1.6-2.9) for Native Americans, and 3.1 (1.4-6.8) for Pacific Islanders. Results adjusted for BMI, age, and sex were 1.6 (1.2-2.3) for Asians, 1.9 (1.7-2.2) for blacks, 1.9 (1.6-2.1) for Hispanics, 1.8 (1.3-2.5) for Native Americans, and 3.0 (1.4-6.7) for Pacific Islanders. CONCLUSIONS - Similar proportions of Asian and non-Hispanic white Americans report having diabetes, but after accounting for the lower BMI of Asians, the adjusted prevalence of diabetes is 60% higher in Asian Americans. C1 Univ Washington, Div Internal Med, Dept Med, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. RP McNeely, MJ (reprint author), Univ Washington, Div Internal Med, Dept Med, 4311 11th Ave NE,Suite 230, Seattle, WA 98105 USA. NR 19 TC 153 Z9 156 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2004 VL 27 IS 1 BP 66 EP 69 DI 10.2337/diacare.27.1.66 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JX UT WOS:000187632200013 PM 14693968 ER PT J AU Arroyo, C Hu, FB Ryan, LM Kawachi, I Colditz, GA Speizer, FE Manson, J AF Arroyo, C Hu, FB Ryan, LM Kawachi, I Colditz, GA Speizer, FE Manson, J TI Depressive symptoms and risk of type 2 diabetes in women SO DIABETES CARE LA English DT Article ID PITUITARY-ADRENAL-AXIS; HEALTH SURVEY SF-36; MELLITUS; NOREPINEPHRINE; CLASSIFICATION; POPULATION; DIAGNOSIS; VALIDITY; PLASMA AB OBJECTIVE - To explore the relationship between depressive symptoms and incidence of type 2 diabetes in women. RESEARCH DESIGN AND METHODS - We conducted an analysis of 72,178 female nurses aged 45-72 years who did not have diagnosed diabetes and who answered the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) at baseline in 1992. We calculated relative risks (RR) of type 2 diabetes for women with presence of depressive symptoms (i.e., Five-Item Mental Health Index [MHI-5] score >52). RESULTS - During 4 years of follow-up (282,317 person-years), 973 incident cases of type 2 diabetes were documented. Age-adjusted RR of developing type 2 diabetes for women with presence of depressive symptoms was 1.55 (95% CI 1.27-1.90). Additional adjustment for BMI resulted in a RR of developing type 2 diabetes of 1.36 (1.11-1.67). The muitivariate RR of developing type 2 diabetes was 1.22 (1.00-1.50). After ex eluding women diagnosed with diabetes between 1992 and 1994, 472 incident cases of type 2 diabetes were documented for the follow-up period from 1994 to 1996 (148,889 person-years). The multivariate RR of developing type 2 diabetes for women with depressive symptoms was 1.29 (0.96-1.72). CONCLUSIONS- Our data suggest that depressive symptoms are associated with a modest increase in the risk of type 2 diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Arroyo, C (reprint author), Morehouse Sch Med, Social Epidemiol Res Div, 720 Westview Dr,SW,NCPC Room 313, Atlanta, GA 30310 USA. RI Ryan, Louise/A-4562-2009; Colditz, Graham/A-3963-2009; OI Ryan, Louise/0000-0001-5957-2490; Colditz, Graham/0000-0002-7307-0291; Arroyo-Johnson, Cassandra/0000-0002-5449-7652 FU NCI NIH HHS [CA87969, P01 CA087969]; NIDDK NIH HHS [F31 DK009949, F31 DK09949, R01 DK036798]; NIGMS NIH HHS [R25 GM055353, R25 GM55353] NR 22 TC 83 Z9 88 U1 2 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2004 VL 27 IS 1 BP 129 EP 133 DI 10.2337/diacare.27.1.129 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JX UT WOS:000187632200023 PM 14693978 ER PT J AU Leonard, DR Farooqi, MH Myers, S AF Leonard, DR Farooqi, MH Myers, S TI Restoration of sensation, reduced pain, and improved balance in subjects with diabetic peripheral neuropathy SO DIABETES CARE LA English DT Article ID FOOT ULCERATION; NERVE FUNCTION AB OBJECTIVE - Diabetic peripheral neuropathy (DPN) has been thought to be progressive and irreversible. Recently, symptomatic reversal of DPN was reported after treatments with a near-infrared medical device, the Anodyne Therapy System (ATS). However, the study was not controlled nor was the investigator blinded. We initiated this study to determine whether treatments with the ATS would decrease pain and/or improve sensation diminished due to DPN under a sham-controlled, double-blind protocol. RESEARCH DESIGN AND METHODS - Tests involved the use of the 5.07 and 6.65 Semmes Weinstein monofilament (SWM) and a modified Michigan Neuropathy Screening Instrument (MNSI). Twenty-seven patients, nine of whom were insensitive to the 6.65 SWM and 18 who were sensitive to this filament but insensitive to the 5.07 SWM, were Studied. Each lower extremity was. treated for 2 weeks with sham or active ATS, and then both received active treatments for an additional 2 weeks. RESULTS The group of 18 patients who could sense the 6.65 SWM but were insensitive to the 5.07 SWM at baseline obtained a significant decrease in the number of sites insensate after both 6 and 12 active treatments (P < 0.02 and 0.001). Sham treatments did not improve sensitivity to the SW but subsequent active treatments did (P < 0.002). The MNSI measures of neuropatic symptoms decreased significantly (from 4.7 to 3.1; P < 0.001). Pain reported on the. 10-point visual analog scale decreased progressively from 4.2 at entry to 3.2 after 6 treatments and to 2.3 after 12 treatments (both P < 0.03). At entry, 90% of subjects reported substantial balance impairment; after treatment, this decreased to 17%. However, among the group of nine patients with greater sensory impairment measured by insensitivity to the 6.65 SWM at baseline, improvements in sensation, neuropathic symptoms, and pain reduction were not significant. CONCLUSIONS- ATS treatments improve sensation in the feet of subjects with DPN, improve balance, and reduce pain. C1 Joslin Diabet Ctr, Morton Plant Mease Helathcare, Clearwater, FL 33756 USA. RP Myers, S (reprint author), Joslin Diabet Ctr, Morton Plant Mease Helathcare, 455 Pinellas St, Clearwater, FL 33756 USA. NR 12 TC 54 Z9 66 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2004 VL 27 IS 1 BP 168 EP 172 DI 10.2337/diacare.27.1.168 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758JX UT WOS:000187632200029 PM 14693984 ER PT J AU Horio, N Clermont, AC Abiko, A Abiko, T Shoelson, BD Bursell, SE Feener, EP AF Horio, N Clermont, AC Abiko, A Abiko, T Shoelson, BD Bursell, SE Feener, EP TI Angiotensin AT(1) receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodiliation in normotensive diabetic rats SO DIABETOLOGIA LA English DT Article DE acetylcholine; angiography; angiotensin-converting enzyme; angiotensin type 1 receptor; blood flow; diabetes; diacylglycerol; rats; retina; vasodilatation ID ENDOTHELIAL GROWTH-FACTOR; CONVERTING ENZYME-INHIBITION; VIDEO FLUORESCEIN ANGIOGRAPHY; NITRIC-OXIDE; INCREASED EXPRESSION; TROPONIN-I; LONG-TERM; HEMODYNAMICS; CIRCULATION; RETINOPATHY AB Aims/hypothesis. The renin angiotensin system is emerging as a potential therapeutic target for diabetic retinopathy. This study examines the effects of angiotensin-converting-enzyme inhibition by captopril and angiotensin AT, receptor antagonism using candesartan-cilexetil on retinal blood flow and acetylcholine-stimulated vasodilatation in normotensive diabetic rats. Methods. Non-diabetic or streptozotocin-induced diabetic rats were treated for 2 weeks with captopril (100 mg/kg/day) or candesartan cilexetil (2 mg/kg/day). Retinal haemodynamics were measured using video fluorescein angiography. Effects of exogenous acetylcholine on retinal haemodynamics were examined following intravitreal injection. Total retinal diacylglycerol was labelled using diacylglycerol kinase, separated by thin-layer chromatography, and quantified using autoradiography. Results. Diabetic rats had prolonged retinal mean circulation time and decreased retinal blood flow compared with non-diabetic rats. Treatment of diabetic rats with either captopril or candesartan blocked the development of these blood flow abnormalities. Intraviteral. injection of acetylcholine (10(-5) mol/l) in non-diabetic rats increased retinal blood flow by 53.9 +/- 22.0% relative to baseline whereas this response to acetylcholine was blunted in diabetic rats (4.4 +/- 19.6%, p < 0.001). Candesartan treatment of diabetic rats restored the acetylcholine-stimulated retinal blood flow response to 60.0 &PLUSMN; 18.7% compared with a 56.2 + 20.1% response in candesartan-treated non-diabetic rats. Total retinal diacylglycerol levels were increased in diabetic rats (3.75 &PLUSMN; 0.98 nmol/mg, p < 0.05) compared with non-diabetic rats (2.13 +/- 0.25 nmol/mg) and candesartan-treatment of diabetic rats normalized diacylglycerol levels (2.10 +/- 0.25 nmol/mg, p < 0.05). Conclusion/interpretation. This report provides evidence that angiotensin-converting enzyme inhibition and AT, receptor antagonism ameliorates retinal haemodynamic dysfunctions in normotensive diabetic rats. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Edward.Feener@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, DK 60165, DK 36836] NR 53 TC 51 Z9 55 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2004 VL 47 IS 1 BP 113 EP 123 DI 10.1007/s00125-003-1262-x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770WA UT WOS:000188753300015 PM 14618237 ER PT J AU Zalis, M Singh, AK AF Zalis, M Singh, AK TI Imaging of inflammatory bowel disease: CT and MR SO DIGESTIVE DISEASES LA English DT Review DE inflammatory bowel disease; CT; MRI; cross-sectional imaging ID ORAL CONTRAST MATERIAL; CROHN-DISEASE; COMPUTED-TOMOGRAPHY; SIGN; ENTEROGRAPHY; COLONOGRAPHY; ENTEROCLYSIS; DIAGNOSIS; ENDOSCOPY; BARIUM AB Cross-sectional imaging has come to play a central role in the imaging of the abdomen. Concurrent to this, the role of CT and MRI in the imaging of inflammatory bowel disease has also increased in importance. These modalities offer numerous advantages over more traditonal methods of radiologic diagnosis, and provide essential information not only for initial diagnosis, but for management, follow-up and detection of potential complications. On the horizon are several derivative techniques involving CT and MRI, potentially in combination with PET imaging; these may further improve the specificity and sensitivity of imaging modalities for diagnosis of inflammatory bowel disease. Copyright (C) 2004 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Zalis, M (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Fruit St, Boston, MA 02114 USA. EM mzalis@partners.org NR 26 TC 13 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2004 VL 22 IS 1 BP 56 EP 62 DI 10.1159/000078735 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 842LA UT WOS:000223004400007 PM 15292695 ER PT J AU Gopal, DV Reichelderfer, M Gaumnitz, EA Harter, J Jobe, BA AF Gopal, DV Reichelderfer, M Gaumnitz, EA Harter, J Jobe, BA TI Barrett's Esophagus - Is screening and surveillance justified? SO DISEASE MANAGEMENT & HEALTH OUTCOMES LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; ENDOSCOPIC SURVEILLANCE; OBSERVER VARIATION; PRACTICE PATTERNS; CANCER-RISK; ADENOCARCINOMA; DYSPLASIA; DIAGNOSIS; CHEMOPREVENTION; PREVALENCE AB Barrett's esophagus is a condition that develops in approximately 10-15% of patients with chronic gastroesophageal reflux disease and is the only known major risk factor for esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has increased by 350% over the last 3 decades and the reasons for this dramatic increase are unclear. At the time of cancer diagnosis up to 50% of patients will have advanced regional or distant metastatic disease, with little or no chance of cure. The overall 5-year survival rate with advanced disease remains poor at <10%. Several studies have demonstrated an early stage of diagnosis and a marked improvement in the survival of patients with esophageal cancer detected by routine endoscopic surveillance in patients known to have pre-existing Barrett's esophagus. The aim of endoscopic surveillance in patients with Barrett's esophagus is the early diagnosis of esophageal cancer, when it is still potentially curable. The desired outcome is to further decrease the mortality rate associated with esophageal adenocarcinoma and identify and screen populations at risk for the development of dysplasia arising from Barrett's esophagus. This is the principle of the current screening and surveillance guidelines set out by several societies, including the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the European Society of Gastrointestinal Endoscopy. However, as most patients with Barrett's esophagus do not develop adenocarcinoma, the cost effectiveness of endoscopic screening and surveillance strategies is questionable. To date, no prospective, randomized trials have been performed to evaluate the effectiveness of surveillance, the survival benefit in patients undergoing surveillance or the subsequent impact on healthcare costs. In this article, we focus on the basic principles and reasoning underlying the surveillance guidelines for Barrett's esophagus. In particular, that the disease is clinically important and has a high prevalence; the transition to adenocarcinoma could have a high death and/or disability rate; early diagnosis of adenocarcinoma should reduce mortality; and the screening method should be easily applied, safe, relatively inexpensive, and applicable to a large number of patients. We then review arguments for and against screening and surveillance as they apply to these principles and discuss the current literature that reviews the effectiveness of such surveillance strategies, including an outline of cost analysis. C1 Univ Wisconsin Hosp & Clin, Sect Gastroenterol & Hepatol, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, Dept Pathol & Lab Med, Madison, WI 53792 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Gopal, DV (reprint author), Univ Wisconsin Hosp & Clin, Sect Gastroenterol & Hepatol, H6-516,600 Highland Ave, Madison, WI 53792 USA. EM dvg@medicine.wisc.edu NR 41 TC 2 Z9 2 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8790 J9 DIS MANAG HEALTH OUT JI Dis. Manag. Health Outcomes PY 2004 VL 12 IS 6 BP 353 EP 361 DI 10.2165/00115677-200412060-00002 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 882SV UT WOS:000225959500001 ER PT J AU Terry, KL Sluss, PM Skates, SJ Mok, SC Ye, B Vitonis, AF Cramer, DW AF Terry, KL Sluss, PM Skates, SJ Mok, SC Ye, B Vitonis, AF Cramer, DW TI Blood and urine markers for ovarian cancer: A comprehensive review SO DISEASE MARKERS LA English DT Review ID PLACENTAL ALKALINE-PHOSPHATASE; TISSUE POLYPEPTIDE ANTIGEN; COLONY-STIMULATING FACTOR; IMMUNOSUPPRESSIVE ACIDIC PROTEIN; TUMOR-ASSOCIATED GLYCOPROTEIN-72; INTERLEUKIN-2 RECEPTOR-ALPHA; HUMAN CHORIONIC-GONADOTROPIN; POTENTIAL SERUM BIOMARKER; CARCINOEMBRYONIC ANTIGEN; HUMAN KALLIKREIN-10 C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Ob Gyn Ctr Epidemiol Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrinol Unit Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, Boston, MA 02115 USA. RP Terry, KL (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Ob Gyn Ctr Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [U01CA086381] NR 119 TC 38 Z9 40 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2004 VL 20 IS 2 BP 53 EP 70 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 852EW UT WOS:000223739000003 PM 15322314 ER PT B AU Curtin, HD AF Curtin, HD BE Schulthess, GKV Zollikofere, CL TI Imaging of the larynx SO DISEASES OF THE BRAIN, HEAD AND NECK, SPINE: DIAGNOSTIC IMAGING AND INTERVENTIONAL TECHNIQUES LA English DT Proceedings Paper CT 36th International Diagnostic Meeting CY MAR 27-APR 02, 2004 CL Davos, SWITZERLAND SP Fdn Adv Educ Med Radiol ID CARTILAGE; INVASION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Curtin, HD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG ITALIA PI MILAN PA MILAN, ITALY BN 88-470-0251-6 PY 2004 BP 146 EP 148 PG 3 WC Clinical Neurology; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BAG80 UT WOS:000222135900023 ER PT J AU Ellis, FH Loda, M AF Ellis, FH Loda, M TI p27 and Barrett's esophagus: a review SO DISEASES OF THE ESOPHAGUS LA English DT Article; Proceedings Paper CT 7th Triannual Meeting of the World-Organization-for-Specialized-Studies on Diseases of the Esophague CY AUG 31-SEP 04, 2003 CL Paris, FRANCE SP World Org Speccialized Studies DE adenocarcinoma; Barrett's esophagus; p27 ID DEPENDENT KINASE INHIBITOR; MALIGNANT-TRANSFORMATION; REFLUX ESOPHAGITIS; MOLECULAR-BIOLOGY; SURGICAL MODEL; ADENOCARCINOMA; CANCER; METAPLASIA; EXPRESSION; CARCINOMA AB The rising prevalence of Barrett's esophagus and Barrett's associated adenocarcinoma in the Western world has stimulated increasing interest in this disease. This has resulted in a plethora of articles concerning its molecular biology, but the tumor suppressor gene, p27, has received little attention. In this article, we review the literature concerning the role of p27 in Barrett's esophagus and its malignant transformation, and we evaluate its possible role as an important clinical biomarker, as well as potential chemopreventive clinical agents aimed at substituting its antitumoral activity. C1 Harvard Univ, Sch Med, Div Cardiovasc Surg, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Ellis, FH (reprint author), Harvard Univ, Sch Med, Div Cardiovasc Surg, Beth Israel Deaconess Med Ctr, West Campus, Boston, MA 02215 USA. EM mjwe@rcn.com NR 48 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2004 VL 17 IS 2 BP 113 EP 117 DI 10.1111/j.1442-2050.2004.00402.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 832ID UT WOS:000222259900001 PM 15230722 ER PT S AU Yao, JK van Kammen, DP AF Yao, JK van Kammen, DP BE Smythies, J TI Membrane phospholipids and cytokine interaction in schizophrenia SO DISORDERS OF SYNAPTIC PLASTICITY AND SCHIZOPHRENIA SE International Review of Neurobiology LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; MAGNETIC-RESONANCE-SPECTROSCOPY; SOLUBLE INTERLEUKIN-2 RECEPTORS; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; INFLAMMATORY RESPONSE SYSTEM; MESSENGER-RNA EXPRESSION; EXCITOTOXIC CELL-DEATH; POSTMORTEM HUMAN BRAIN; ACUTE-PHASE PROTEINS C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. Aventis Inc, Bridgewater, NJ 08807 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH43742, MH44841, MH58141] NR 230 TC 39 Z9 41 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-366860-3 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2004 VL 59 BP 297 EP 326 PG 30 WC Neurosciences SC Neurosciences & Neurology GA BY85B UT WOS:000189478200013 PM 15006493 ER PT J AU Yates, KE AF Yates, KE TI Inferred functions of "novel" genes identified in fibroblasts chondroinduced by demineralized bone SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN DERMAL FIBROBLASTS; EXPRESSED SEQUENCE TAGS; PROFILE; LOCALIZATION; CYTOSKELETON; GENERATION; IMPLANTS; ENCODES; MARROW; BLAST AB Little is known about the cellular mechanisms that control postnatal chondrocyte differentiation. As a first step towards identifying those mechanisms, gene expression shift's were characterized in an in vitro model of chondroinduction. In previous studies, several functional classes of genes (cytoskeletal and matrix elements, cell adhesion proteins, peptide growth factors, and signal transduction proteins) were found to be altered in human dermal fibroblasts (hDFs) cultured in porous collagen sponges with chondroinductive demineralized bone powder (DBP) for 3 days. In addition, a number of "novel" sequences were identified. In this study, molecular techniques were combined with computational methods to characterize those sequences. Gene expression of all 10 novel sequences tested was found in hDFs by RT-PCR. The sequences were compared to the human genome, and their cellular functions were inferred from genes that mapped to the same chromosomal coordinates. Only one of the novel sequences contained a protein-coding region (kinesin superfamily protein 26B). The others contained 3' untranslated (osteonectin, alpha-V integrin, RAM) or other untranslated regions (PTPN21, GAS6) of mRNAs. The cellular functions of the DBP-regulated genes described in this study fall into similar categories as those previously identified. These results provide new details on the cellular response of hDFs exposed to DBP. C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Yates, KE (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM kyates@partners.org FU NIAMS NIH HHS [AR44873] NR 40 TC 0 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN PY 2004 VL 23 IS 1 BP 15 EP 24 DI 10.1089/104454904322745899 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 767UU UT WOS:000188486500002 PM 14965469 ER PT J AU Rogers, SJ Willliams, CS Roman, GC AF Rogers, SJ Willliams, CS Roman, GC TI Myelopathy in Sjogren's syndrome - Role of nonsteroidal immunosuppressants SO DRUGS LA English DT Article ID NERVOUS-SYSTEM DISEASE; SYNDROME CNS-SS; ANTI-RO(SS-A) AUTOANTIBODIES; CLASSIFICATION CRITERIA; PREDNISONE; IMMUNOPATHOGENESIS; PATHOGENESIS; INVOLVEMENT; MANIFESTATIONS; AZATHIOPRINE AB The incidence, aetiology and optimal treatment of CNS Sjogren's syndrome, including myelopathy associated with Sjogren's syndrome, are unknown at the present time. CNS Sjogren's syndrome is thought to be the result of an autoimmune vasculitis, but other mechanisms may be important. Spinal cord involvement in CNS Sjogren's syndrome may present as acute transverse myelitis, progressive myelitis, Brown-Sequard syndrome, neurogenic bladder or lower motor neurone disease. Optic nerve pathology frequently accompanies spinal cord involvement. Acute transverse myelitis has a high mortality and appears to be the most frequent form of spinal cord involvement in CNS Sjogren's syndrome, occurring in about 1% of all patients with Sjogren's syndrome. The patient's symptomatology and clinical course dictate current treatment of myelopathy. First-line treatment appears to be corticosteroid therapy. However, when the patient's condition fails to improve or deteriorates a nonsteroidal immunosuppressant agent should be considered. Agents used to treat myelopathy include cyclophosphamide, chlorambucil, azathioprine, ciclosporin (cyclosporin) and methotrexate in conjunction with corticosteroids. Most data exist as anecdotal reports. The agent of first choice, based on adverse effect profile and efficacy, appears to be cyclophosphamide given intravenously in pulse doses. Other nonsteroidal immunosuppressant agents should be considered, especially when lack of efficacy of, or intolerance to, cyclophosphamide exists in the patient's history. Glandular and other extraglandular symptoms may benefit concomitantly from the immunosuppressant treatment. In addition, when acute relief of symptomatology is needed, the patient may benefit from a trial of plasmapheresis or intravenous immunoglobulin. Infliximab (anti-tumour necrosis factor-alpha antibodies) has not been used as a treatment modality for myelopathy, but has shown some usefulness in the treatment of extraglandular symptoms, as well as peripheral nervous system manifestations of Sjogren's syndrome. This agent might be considered when all other treatment modalities have failed given the presumed importance of tumour necrosis factor in the pathogenesis of Sjogren's syndrome. C1 Univ Texas, Hlth Sci Ctr, Coll Pharm, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, San Antonio, TX USA. RP Univ Texas, Hlth Sci Ctr, Coll Pharm, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM rogerss@uthscsa.edu NR 44 TC 25 Z9 29 U1 0 U2 3 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0012-6667 EI 1179-1950 J9 DRUGS JI Drugs PY 2004 VL 64 IS 2 BP 123 EP 132 DI 10.2165/00003495-200464020-00001 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 771WQ UT WOS:000188809400001 PM 14717615 ER PT J AU Chan, SE Schwartz, JM Rosen, HR AF Chan, SE Schwartz, JM Rosen, HR TI Treatment of hepatitis C in solid organ transplantation SO DRUGS LA English DT Article ID CHRONIC VIRAL-HEPATITIS; STAGE RENAL-DISEASE; ORTHOTOPIC LIVER-TRANSPLANTATION; INTERFERON-ALPHA THERAPY; VIRUS-INFECTION; HEMODIALYSIS-PATIENTS; PLUS RIBAVIRIN; HCV INFECTION; HEART-TRANSPLANTATION; ANTIVIRAL THERAPY AB Hepatitis C virus (HCV) infection is highly prevalent worldwide, and results in significant morbidity and mortality. HCV frequently infects haemodialysis patients and appears to impact on long-term survival of kidney transplant recipients. Therefore, treatment is recommended for kidney transplant candidates before transplantation and should be avoided following transplantation because of a high risk of allograft rejection. HCV infection does not appear to influence survival in cardiac transplant recipients and cardiac transplant recipients should also not be treated. In general, HCV-infected patients with cirrhosis are not considered as candidates for either kidney or cardiac transplantation given their risk of decompensation. HCV is the most common indication for liver transplantation and re-infection with varying degrees of liver injury is universal. Survival after liver transplantation is reduced among HCV-infected patients when compared with uninfected controls. Therefore, treatment using interferon and ribavirin is advocated; however, such therapy is frequently limited by adverse effects. Thus, improved antiviral treatment modalities are eagerly awaited in the transplant setting. C1 Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97201 USA. EM hugo.rosen@med.va.gov NR 75 TC 6 Z9 6 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2004 VL 64 IS 5 BP 489 EP 498 DI 10.2165/00003495-200464050-00003 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 802XU UT WOS:000220197000003 PM 14977386 ER PT J AU Grant, RW Meigs, JB AF Grant, RW Meigs, JB TI Should the insulin resistance syndrome be treated in the elderly? SO DRUGS & AGING LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE RISK; IMPAIRED GLUCOSE-TOLERANCE; CORONARY-HEART-DISEASE; PLASMINOGEN-ACTIVATOR INHIBITOR-1; DENSITY-LIPOPROTEIN CHOLESTEROL; ISOLATED SYSTOLIC HYPERTENSION; NUTRITION EXAMINATION SURVEY; MULTIPLE METABOLIC SYNDROME; RANDOMIZED CONTROLLED-TRIAL AB The insulin resistance syndrome represents the co-occurrence of hyperglycaemia, hypertension, central and overall obesity, and dyslipidaemia characterised by low high density lipoprotein-cholesterol (HDL-C) and high triglyceride levels. Epidemiologic studies have revealed an increasing prevalence of the insulin resistance syndrome in elderly populations. Indeed, recent data indicate that over 40% of US adults aged greater than or equal to60. years meet current criteria for the insulin resistance syndrome. Patients with this syndrome are at increased risk for the development of both cardiovascular disease (CVD) and type 2 diabetes mellitus, two of the most significant health problems among people >65 years of age. Identification and treatment of the insulin resistance syndrome may thus represent an important approach to reducing the overall burden of morbidity and mortality in the elderly. While development of the insulin resistance syndrome is partly determined by modifiable environmental factors, there may be a genetic basis for the syndrome, with high levels of concordance among monozygotic twins. Ongoing research focusing on the pathophysiology of this syndrome has implicated insulin resistance as the central disorder underlying both the development of diabetes as well as the pro-thrombotic endothelial dysfunction characteristic of CVD. Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes. However, although insulin sensitisation may be beneficial for preventing type 2 diabetes, there are no data yet available to show whether this strategy will reduce the incidence of CVD. Increased exercise and other healthy lifestyle changes form the cornerstone of therapy for elderly patients with the insulin resistance syndrome. In addition, active identification and aggressive management of traditional cardiovascular risk factors are the current standard of care. For elderly patients, recent studies have conclusively demonstrated the safety and efficacy of pharmacological management of elevated blood pressure and cholesterol levels. Cardiovascular disease (CVD) is the leading cause of death among people >65 years of age in developed countries([1]) The insulin resistance syndrome (defined as the co-occurrence of hyperglycaemia, hypertension, obesity [both central and overall], elevated levels of triglycerides and low levels of high density lipoprotein-cholesterol [HDL-C]) may play an important role in the development of type 2 diabetes mellitus and CVD.([2,3]) Thus, recognition and appropriate treatment of this syndrome is critical for the effective care of older patients. In this article, we review the pathophysiology and epidemiology of the insulin resistance syndrome and present the evidence for treatment among the elderly, defined as patients >65 years of age. Both peripheral insulin resistance and failure of pancreatic cells to produce enough insulin to overcome peripheral insulin resistance precede the development of type 2 diabetes([4]) Insulin resistance also predicts the development of hypertension and low HDL-C/high triglycerides dyslipidaemia characteristic of diabetes. Thus, insulin resistance constitutes the central element of the insulin resistance syndrome (also called syndrome X or the metabolic syndrome)([5]) Over the past two decades, the prevalence of diabetes has increased dramatically; among US adults aged 40-74 years the prevalence increased from 8.9% to 12.3% by 1994.([6]) This figure is even higher among older adults. During 1988-1994, 13.2% of adults >74 years of age had physician-diagnosed diabetes; these figures are doubled if undiagnosed diabetes is included.([6]) Among people destined to develop diabetes, the prevalence of CVD risk factors is greatest in the most insulin-resistant subjects compared with relatively insulin-sensitive subjects([7-10]) These multiple risk factors confer independent, additive risk with diabetes for CVD-related mortality([11]) Long-time exposure to the risk factors present in the insulin resistance syndrome is an important determinant for developing CVD complications in the elderly.([12]) C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 NR 80 TC 10 Z9 14 U1 2 U2 6 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2004 VL 21 IS 3 BP 141 EP 151 DI 10.2165/00002512-200421030-00001 PG 11 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 802YA UT WOS:000220197600001 PM 14979733 ER PT J AU Menzin, J Lang, K Earle, CC Glendenning, A AF Menzin, J Lang, K Earle, CC Glendenning, A TI Treatment patterns, outcomes and costs among elderly patients with chronic myeloid leukaemia - A population-based analysis SO DRUGS & AGING LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; MEDICARE CLAIMS DATA; BREAST-CANCER; COLORECTAL-CARCINOMA; GEOGRAPHIC-VARIATION; INTERFERON-ALPHA; LINKED MEDICARE; CHRONIC-PHASE; OLDER WOMEN; HOSPICE USE AB Background and objective: Chronic myeloid leukaemia (CML) affects approximately 3000-5000 Americans each year, with the American Cancer Society expecting 4600 new cases in 2004. The incidence of CML increases with age; median age at diagnosis is 67 years. Long-term data on the economic burden associated with CML among the elderly are sparse. To fill this void, our study uses population-based data to evaluate longer-term treatment patterns, outcomes and costs among elderly Medicare beneficiaries following their diagnosis of CML. Patients and methods: This retrospective cohort analysis used linked data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and Medicare claims. Study cohorts included 567 patients aged greater than or equal to65 years newly diagnosed with CML between 1991 and 1993 in a SEER registry and followed for 5 years or until death, whichever occurred first. In addition, 567 control patients without CML matched I : I by age and sex (average age 78 years, 52% male) were included. The costs of care were based on total Medicare payments (in constant 1998 dollars). Groups were generally similar in terms of nonmatched variables. Results: Five years following diagnosis, 13% of CML patients were still alive versus 68% of the control patients (median survival: 14 months vs >60 months, respectively). The average total Medicare payments were $US35 785 for CML patients versus $US21 161 for control subjects (monthly payments: $US1688 vs $ US428, respectively; p < 0.001). Approximately 25% of CML patients underwent Medicare-covered cancer treatment (11% outpatient chemotherapy, 6% inpatient chemotherapy and 8% outpatient interferon-a therapy). Younger patients and those diagnosed in the later years were most likely to be treated. Costs for treated patients were higher, and they lived longer. Conclusion: Our findings suggest low treatment rates, and substantial excess mortality and costs associated with CML among the elderly. The recent introduction of imatinib has dramatically changed the treatment of CML, which is likely to cause important changes to the economic burden of CML. Our results can be used as a baseline for evaluating the impact of such new therapies as data from clinical trials become available. Further work is needed to characterise this disease and the complex factors that influence treatment decisions and associated health outcomes in elderly patients. C1 Boston Hlth Econ Inc, Waltham, MA 02451 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. RP Menzin, J (reprint author), Boston Hlth Econ Inc, 20 Fox Rd, Waltham, MA 02451 USA. EM jmenzin@bhei.com NR 45 TC 8 Z9 9 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2004 VL 21 IS 11 BP 737 EP 746 DI 10.2165/00002512-200421110-00004 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 855BX UT WOS:000223949000004 PM 15323579 ER PT J AU Shuster, DL Farley, KA Sisterson, JM Burnett, DS AF Shuster, DL Farley, KA Sisterson, JM Burnett, DS TI Quantifying the diffusion kinetics and spatial distributions of radiogenic He-4 in minerals containing proton-induced He-3 SO EARTH AND PLANETARY SCIENCE LETTERS LA English DT Article DE helium; diffusion; thermochronometry; isotope; proton beam; (U-Th)/He ID HELIUM DIFFUSION; THERMOCHRONOMETRY; APATITE; ISOTOPES; TITANITE; OLIVINE; SILICON; ROCKS; AGES AB Apatite, titanite and olivine samples were bombarded with a similar to150 MeV proton beam to produce similar to10(8) atoms/mg of spallation He-3. High-precision stepped-heating experiments were then performed in which the artificial He-3 and, for apatite and titanite, the natural radiogenic He-4 were measured to characterize the diffusive behavior of each isotope. Helium-3 diffusion coefficients are in excellent agreement with concurrently and/or previously determined He diffusion coefficients for each mineral. Our results indicate that proton-induced He-3 is uniformly distributed and that radiation damage associated with a proton fluence of similar to5x10(14) protons/cm(2) does not cause noticeable changes in He-4 diffusion behavior in at least apatite and titanite. Proton-induced He-3 can therefore be used to establish He diffusion coefficients in minerals with insufficient natural helium for analysis or those in which the natural He-4 distribution is inhomogeneous. In addition, step-heating He-4/He-3 analysis of a mineral with a uniform synthetic He-3 concentration provides a means by which a natural 4He distribution can be determined. (C) 2003 Elsevier B.V. All rights reserved. C1 CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Shuster, DL (reprint author), CALTECH, Div Geol & Planetary Sci, MC 100-23, Pasadena, CA 91125 USA. RI Shuster, David/A-4838-2011 NR 33 TC 79 Z9 82 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0012-821X J9 EARTH PLANET SC LETT JI Earth Planet. Sci. Lett. PD JAN 1 PY 2004 VL 217 IS 1-2 BP 19 EP 32 DI 10.1016/S0012-821X(03)00594-6 PG 14 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 759YC UT WOS:000187781600002 ER PT J AU Gregory, SA O'Byrne, WT Fan, P AF Gregory, SA O'Byrne, WT Fan, P TI Infected cardiac myxoma SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE myxoma; infected myxoma; echocardiography; endocarditis AB Infected cardiac myxomas are extremely rare with only forty cases described in the literature. We report a case of an infected cardiac myxoma that presented in a manner similar to bacterial endocarditis. Our case is the first to be diagnosed using previously defined criteria, and is unusual in that transesophageal echocardiography was required to make the diagnosis. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02115 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Gregory, SA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, 3rd Floor Prof Off Bldg,275 Cambridge St, Boston, MA 02115 USA. EM sagregory@partners.org NR 4 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2004 VL 21 IS 1 BP 65 EP 67 DI 10.1111/j.0742-2822.2004.02177.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 770RP UT WOS:000188744900012 PM 14717724 ER PT S AU Ruvkun, G AF Ruvkun, G BE Chanson, P Lamberts, S Epelbaum, J Christen, Y TI Regulation of C. elegans life span by insulin-like signaling SO ENDOCRINE ASPECTS OF SUCCESSFUL AGING: GENES, HORMONES AND LIFESTYTLES SE RESEARCH AND PERSPECTIVES IN ENDOCRINE INTERACTIONS LA English DT Proceedings Paper CT 2nd Meeting on Endocrine Aspects of Successful Aging CY DEC 03, 2002 CL PARIS, FRANCE SP Fdn IPSEN ID PROTEIN-KINASE B; TRANSCRIPTION FACTOR FKHR; DAUER LARVA DEVELOPMENT; CAENORHABDITIS-ELEGANS; FORKHEAD TRANSCRIPTION; GENE-EXPRESSION; PHOSPHOENOLPYRUVATE CARBOXYKINASE; SUPEROXIDE-DISMUTASE; PROMOTER ACTIVITY; WILD-TYPE C1 Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, 50 Blossom St,Wellman 901, Boston, MA 02114 USA. NR 48 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1861-2253 BN 3-540-40573-9 J9 RES PERSPECT END INT JI Res. Perspect. End. Int. PY 2004 BP 1 EP 17 PG 17 WC Endocrinology & Metabolism; Genetics & Heredity; Geriatrics & Gerontology; Neurosciences SC Endocrinology & Metabolism; Genetics & Heredity; Geriatrics & Gerontology; Neurosciences & Neurology GA BY49E UT WOS:000189351600001 ER PT J AU Dulai, GS Jensen, DM Kovacs, TOG Gralnek, IM Jutabha, R AF Dulai, GS Jensen, DM Kovacs, TOG Gralnek, IM Jutabha, R TI Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension SO ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Society-for-Gastrointestinal-Endoscopy CY MAY 23, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Soc Gastrointestinal Endoscopy ID ANTRAL VASCULAR ECTASIA; ND-YAG LASER; CIRRHOSIS; GASTROPATHY; FEATURES AB Background and Study Aims: Watermelon stomach is a source of recurrent gastrointestinal hemorrhage and anemia. The aims of this study were to describe the endoscopic appearance and treatment outcomes in watermelon stomach patients with and without portal hypertension. Patients and Methods: All patients with watermelon stomach enrolled in a hemostasis research group's prospective studies from 1991 to 1999 were identified. Investigators collected data using standardized forms. Comparisons were made using the chi-squared test, Wilcoxon rank-sum test, and Wilcoxon signed-rank test. Results: Twenty-six of 744 (4%) consecutively enrolled patients with nonvariceal upper gastrointestinal hemorrhage had watermelon stomach as the cause. Eight of these 26 patients (31%) also had portal hypertension. These patients had diffuse antral angiomas, as opposed to the classic linear arrays seen in those without portal hypertension. The demographic data and clinical presentations of the two groups were otherwise similar. Palliative endoscopic treatment was associated with a significant rise in hematocrit and a decrease in the need for blood transfusion or hospitalization in watermelon stomach patients with and without portal hypertension. Conclusions: Watermelon stomach patients with and without portal hypertension had similar clinical presentations. The endoscopic findings differed in that those with portal hypertension had more diffuse gastric angiomas. Bleeding was effectively palliated by endoscopic treatment, regardless of the presence of portal hypertension. C1 CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Digest Dis Res Ctr,Ctr Study Digest Healthcare Qu, Los Angeles, CA 90024 USA. RP Dulai, GS (reprint author), CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 215C,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gdulai@mednet.ucla.edu FU NCRR NIH HHS [K23 RR 1618801]; NIDDK NIH HHS [DK 41301, K24 DK 02650] NR 26 TC 39 Z9 45 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JAN PY 2004 VL 36 IS 1 BP 68 EP 72 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 762LP UT WOS:000187973700010 PM 14722858 ER PT J AU Cole, AJ Devinsky, O AF Cole, AJ Devinsky, O TI Neuroimaging: Advances and Applications - 2003 Annual Course - Sponsored by the American Epilepsy Society - December 7, 2003 - Boston, Massachusetts, USA - Introduction SO EPILEPSIA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02115 USA. NYU, Sch Med, NYU Epilepsy Ctr, Dept Neurol, New York, NY USA. NYU, Sch Med, NYU Epilepsy Ctr, Dept Neurosurg & Psychiat, New York, NY USA. RP Cole, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 4 BP 1 EP 1 DI 10.1111/j.0013-9580.2004.04001.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 845SY UT WOS:000223265800001 ER PT J AU Grant, PE AF Grant, PE TI Structural MR imaging SO EPILEPSIA LA English DT Article; Proceedings Paper CT Annual Course on Neuroimaging - Advances and Applications held at the Annual Meeting of the American-Epilepsy-Society CY DEC 07, 2003 CL Boston, MA SP Amer Epilepsy Soc DE epilepsy; MRI; phased array; high resolution; 3T; image analysis; sementation; diffusion tensor imaging; multimodatity; MEG ID TEMPORAL-LOBE EPILEPSY; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; REFRACTORY EPILEPSY; COORDINATE SYSTEM; HUMAN BRAIN; SEGMENTATION; COMPLEX; SURGERY AB Phased-array imaging at 1.5 and 3 T significantly improves image quality compared with that in routine 1.5-T head coil studies. These improvements significantly increase lesion detection in patients with focal epilepsy. Semiautomated image-analysis techniques have the potential to improve lesion detection, assess lesion burden more accurately, characterize cortical abnormalities, and determine the location and extent of associated cortical and deep gray nuclei involvement. With increasing interest in understanding the role white matter plays in epileptogenesis and seizure propagation, diffusion tensor imaging may yield useful information about changes in white matter organization. Our current multimodality imaging combines these structural imaging advances with coregistered neurophysiological information obtained with magneto-encephalography and with simultaneous EEG recordings. Our initial experience suggests that multimodality imaging will improve our ability to detect and define the extent of epileptogenic lesions. C1 Massachusetts Gen Hosp, Dept Radiol & Pediat Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Grant, PE (reprint author), Grant At Grey 2 B285,55 Fruit St, Boston, MA 02114 USA. EM ellen@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [K23 NS42758, NS18741, NS44623] NR 23 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 4 BP 4 EP 16 DI 10.1111/j.0013-9580.2004.04003.x PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 845SY UT WOS:000223265800003 PM 15281951 ER PT J AU Thompson, KW Suchomelova, LM AF Thompson, KW Suchomelova, LM TI Transplants of cells engineered to produce GABA suppress spontaneous seizures SO EPILEPSIA LA English DT Article DE transplantation; epilepsy; seizures; genetic engineering; GAD; GABA; tetracycline ID SPONTANEOUS RECURRENT SEIZURES; INDUCED STATUS EPILEPTICUS; SUBSTANTIA-NIGRA; KINDLING EPILEPSY; NEURAL TRANSPLANTATION; PARKINSONS-DISEASE; PIRIFORM CORTEX; PILOCARPINE; RATS; HIPPOCAMPUS AB Purpose: Cell transplantation into the brain is an aggressive clinical alternative. The hopes of treating diseases like intractable temporal lobe epilepsy have been subdued because the preclinical successes thus far have shown only slowing of epileptogenesis, or suppression of electrically induced seizures. Because the hallmark of epilepsy is spontaneous seizures, the clinical relevance of these studies has been questioned. The purpose of this study was to establish that cells genetically engineered to produce gamma-aminobutyric acid (GABA) could suppress spontaneous seizures in an accepted model of temporal lobe epilepsy. Methods: Conditionally immortalized neurons were engineered to produce GABA under the control of tetracycline. These cells were transplanted into the substantia nigra of spontaneously seizing animals. After transplantation, the animals were monitored for 3 days immediately after surgery and again for 3 days beginning 7-8 days after surgery. Seizures and epileptiform spikes were recorded and later analyzed with detection software combined with video monitoring. Results: Animals that received genetically engineered GABA-producing cells had significantly fewer spontaneous seizures than did animals that received control cells, or animals that received GABA-producing cells plus doxycycline at the observation period starting 1 week after transplantation. A significant suppression of epileptiform spikes also was noted between the group that received GABA-producing cells and the group that received the same cells but were given doxycycline. The engineered cells show evidence of integration with the host but limited survival. Conclusions: These data demonstrate that genetically engineered cells have the ability to suppress spontaneous seizures when transplanted into seizure-modulating nuclei. This is an important step toward defining a clinical potential for this approach in epilepsy. The fact that the gene of interest can be regulated suggests that individualizing transplant therapy may be possible. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Acad Sci Czech Republ, Inst Physiol, Prague, Czech Republic. RP Thompson, KW (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 114,Rm 137,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM kthompso@ucla.edu NR 38 TC 53 Z9 57 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2004 VL 45 IS 1 BP 4 EP 12 DI 10.1111/j.0013-9580.2004.29503.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 762GQ UT WOS:000187964000002 PM 14692901 ER PT J AU Houser, CR Huang, C Peng, ZC AF Houser, CR Huang, C Peng, ZC TI Increased expression of the delta subunit of the GABA(A) receptor in hippocampal interneurons during postnatal development SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 19 EP 19 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100060 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, RA Panizzon, KL TI Neuroprotective efficacy of the mitochondrial ATP-sensitive potassium channel opener, diazoxide, against depolarization injury to CA1 pyramidal neurons in rat hippocampal slices SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Healthcare, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 28 EP 28 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100085 ER PT J AU Ulbert, T Heit, G Madsen, J Karmos, T Halgren, F AF Ulbert, T Heit, G Madsen, J Karmos, T Halgren, F TI Laminar analysis of human neocortical interictal spike generation and propagation: Current source density and multiunit analysis in vivo SO EPILEPSIA LA English DT Article; Proceedings Paper CT Annual Course on Neuroimaging held at the Annual Meeting of the American-Epilepsy-Society CY DEC 07, 2003 CL Boston, MA SP Amer Epilepsy Soc DE current source density; epilepsy; human neocortex; interictal spikes; multiple unit activity ID INDUCED EPILEPTIC PHENOMENA; VOLTAGE-SENSITIVE DYES; RAT PIRIFORM CORTEX; PYRAMIDAL CELLS; CEREBRAL-CORTEX; FAST COMPONENTS; WAVE COMPLEXES; MEDIATED INHIBITION; RABBIT NEOCORTEX; VISUAL-CORTEX AB Multicontact microelectrodes were chronically implanted in epilepsy patients undergoing subdural grid implantation for seizure localization. Current source density and multiple unit activity of interictal spikes (IISs) were sampled every similar to150 mum in a line traversing all layers of a cortical column. Our data suggest that interictal epileptiform events in humans are initiated by large postsynaptic depotarizations, consistent with the hypothesis that human IISs correspond to animal paroxysmal depolarization shifts. Furthermore, the cortical layer where the initial depolarization occurs may differ according to whether the IIS is locally generated or propagated from a distant location, and among the propagated IISs, whether the IIS is in the direct path of propagation or on the periphery of that path. C1 Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02138 USA. MIT, Charlestown, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. INSERM, F-13258 Marseille, France. RP Halgren, F (reprint author), MGH-NMR,Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM halgren@nmr.mgh.harvard.edu NR 67 TC 24 Z9 24 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 4 BP 48 EP 56 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 845SY UT WOS:000223265800011 ER PT J AU Wyszynski, DF Holmes, LB AF Wyszynski, DF Holmes, LB TI The AED (antiepileptic drug) pregnancy registry: a six-year experience SO EPILEPSIA LA English DT Meeting Abstract CT 6th European Congress on Epileptology CY MAY 30-JUN 03, 2004 CL Vienna, AUSTRIA SP Int League Against Epilepsy, Austrian League Against Epilepsy C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 3 BP 56 EP 57 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 829BZ UT WOS:000222019500183 ER PT J AU Cole, AJ AF Cole, AJ TI Status epilepticus and periictal imaging SO EPILEPSIA LA English DT Article; Proceedings Paper CT Annual Course on Neuroimaging - Advances and Applications held at the Annual Meeting of the American-Epilepsy-Society CY DEC 07, 2003 CL Boston, MA SP Amer Epilepsy Soc DE MRI; DWI; ADC; diaschesis; PET; SPECT ID CORPUS-CALLOSUM; TRANSIENT LESION; SPLENIUM; ABNORMALITIES; EPILEPSY AB Peri- and postictal changes on both anatomic and functional imaging examinations have been recognized for many years. With the wide availability of magnetic resonance imaging and positron emission tomography, a growing range of recognized acute imaging findings have been described. Periictal and postictal findings can be classified as either local or remote, with respect to the site of maximal ictal EEG abnormality. Although many of the findings described are reversible, the factors that determine whether findings will resolve are incompletely understood. This article considers the range of findings that have been described, places them into the context of known or hypothesized pathophysiologic mechanisms, and considers their clinical significance. A framework is proposed for considering the relation between ictal duration and severity, the characteristics of imaging abnormalities, and the mechanism of their underlying pathophysiology. C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, VBK-830,Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu NR 13 TC 72 Z9 73 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 4 BP 72 EP 77 DI 10.1111/j.0013-9580.2004.04014.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 845SY UT WOS:000223265800014 PM 15281962 ER PT J AU Licht, EA Shewmon, DA Azen, SP Fujikawa, DG AF Licht, EA Shewmon, DA Azen, SP Fujikawa, DG TI Identifying risk factors for nonconvulsive status epilepticus: Tracking severity of subclinical epileptiform discharges suggests athreshold effect SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Olive View UCLA, Med Ctr, Dept Neurol, Los Angeles, CA USA. USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 82 EP 82 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100243 ER PT J AU Lotfizadeh, H Thakore, M Montouris, GD AF Lotfizadeh, H Thakore, M Montouris, GD TI Bone health in males with epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Boston Univ, Ctr Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 124 EP 124 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100366 ER PT J AU Bar, M Borgohain, R Hayes, F Warnock, CR Conklin, H Whitehouse, H Morrell, M AF Bar, M Borgohain, R Hayes, F Warnock, CR Conklin, H Whitehouse, H Morrell, M TI Reproductive endocrine characteristics of women with newly diagnosed or inadequately controlled epilepsy: a preliminary analysis. SO EPILEPSIA LA English DT Meeting Abstract CT 6th European Congress on Epileptology CY MAY 30-JUN 03, 2004 CL Vienna, AUSTRIA SP Int League Against Epilepsy, Austrian League Against Epilepsy C1 FN Poruba, Ostrava, Czech Republic. Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India. Massachusetts Gen Hosp, Boston, MA 02114 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. GlaxoSmithKline, Greenford, Middx, England. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 3 BP 162 EP 162 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 829BZ UT WOS:000222019500600 ER PT J AU Pfeifer, HH Thiele, EA AF Pfeifer, HH Thiele, EA TI Low glycemic index diet as an alternative to the ketogenic diet in the treatment of intractable epilepsy in childhood SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Massachussets Gen Hosp Children, Dept Neurol, Pediat Epilepsy Program, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 184 EP 184 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100539 ER PT J AU Holmes, LB Wyszynski, DF AF Holmes, LB Wyszynski, DF TI The AED (antiepileptic drug) pregnancy registry: A seven-year experience SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 187 EP 187 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100548 ER PT J AU Fujikawa, DG Trinidad, LB Ke, XG AF Fujikawa, DG Trinidad, LB Ke, XG TI Both mild and more severe insults produce caspase-independent necrotic neurons: In vivo evidence from 60-minute lithium-pilocarpine-induced seizures SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 VA Greater Los Angeles Hlthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Utah, Sch Med, Div Neonatol, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 196 EP 197 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100576 ER PT J AU Kim, DY van Brederode, H Sullivan, PG Spain, NJ Rho, JM AF Kim, DY van Brederode, H Sullivan, PG Spain, NJ Rho, JM TI Ketone bodies protect neocortical neurons against acute oxidative stress SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ 85013 USA. Med Ctr, Phoenix, AZ USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Kentucky, Med Ctr, SCoBIRC, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 199 EP 199 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100584 ER PT J AU Huerter, VA Thiele, EA AF Huerter, VA Thiele, EA TI Gabapentin monotherapy in pediatric epilepsy: A retrospective review SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 250 EP 250 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100736 ER PT J AU Doherty, CP Ronan, L Fitzsimons, M Grant, PE Thiele, EA AF Doherty, CP Ronan, L Fitzsimons, M Grant, PE Thiele, EA TI Stereologic estimation of cortical surface area in Tuberous Sclerosis Complex: An MRI-based imaging study SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. Massachusetts Gen Hosp, Pediat Epilepsy Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, MGH,HMS, Athinoula A Martinos Ctr Biomed Imaging, MGH NMR Facil, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 298 EP 298 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100880 ER PT J AU Goldenholz, DM Stufflebeam, SM AF Goldenholz, DM Stufflebeam, SM TI Method for automatic generation of clinical report for seizure focus localization after imaging with MEG, EEG, and MRI SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 299 EP 299 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100881 ER PT J AU Rowan, AJ Ramsay, RE Collins, JF Pryor, F AF Rowan, AJ Ramsay, RE Collins, JF Pryor, F CA VACS 428 Study Grp TI Influence of initial seizure frequency on prognosis for seizure control in the elderly SO EPILEPSIA LA English DT Meeting Abstract CT Annual Meeting of the American-Epilepsy-Society CY DEC 03-07, 2004 CL New Orlands, LA SP Amer Epilepsy Soc C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Miami VA Med Ctr, Miami, FL USA. VA Med Ctr, VA Cooperat Studies Coordinating Ctr, Perry Point, MD USA. RI Ramsay, R. Eugene/D-4491-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2004 VL 45 SU 7 BP 312 EP 312 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 861MG UT WOS:000224420100918 ER PT B AU Delmonico, FL AF Delmonico, FL BE Gutmann, T Daar, AS Sells, RA Land, W TI No payments for organs SO ETHICAL, LEGAL, AND SOCIAL ISSUES IN ORGAN TRANSPLANTATION LA English DT Proceedings Paper CT 1st International Congress of the German-Academy-of-Transplantation-Medicine on Ethics in Organ Transplantation CY DEC 10-13, 2002 CL Munich, GERMANY SP German Acad Transplatat Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PABST SCIENCE PUBLISHERS PI D-49525 LENGERICH PA EICHENGRUND 28, D-49525 LENGERICH, GERMANY BN 1-59326-063-6 PY 2004 BP 294 EP 297 PG 4 WC Medical Ethics; Transplantation SC Medical Ethics; Transplantation GA BBP81 UT WOS:000226965300037 ER PT J AU Rumsfeld, JS Masoudi, FA AF Rumsfeld, JS Masoudi, FA TI Sex differences: implications for heart failure care SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID CLINICAL-TRIALS; GENDER C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver Hlth Med Ctr, Denver, CO 80220 USA. RP Rumsfeld, JS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver Hlth Med Ctr, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM John.Rumsfeld@med.va.gov NR 13 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2004 VL 25 IS 2 BP 101 EP 103 DI 10.1016/j.ehj.2003.11.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 768NG UT WOS:000188548600002 PM 14720524 ER PT J AU Rangone, H Poizat, G Troncoso, J Ross, CA MacDonald, ME Saudou, F Humbert, S AF Rangone, H Poizat, G Troncoso, J Ross, CA MacDonald, ME Saudou, F Humbert, S TI The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE CAG expansion; Huntington's disease; IGF-1; neuronal death; polyglutamine disorders ID INDUCIBLE PROTEIN-KINASE; POLYGLUTAMINE-EXPANDED HUNTINGTIN; NEURONAL INTRANUCLEAR INCLUSIONS; SCA1 TRANSGENIC MICE; NUCLEAR-LOCALIZATION; SURVIVAL SIGNALS; INDUCED DISEASE; STRIATAL CELLS; MESSENGER-RNA; HD MUTATION AB Huntington's disease (HD) is caused by abnormal polyglutamine (polyQ) expansion in the protein huntingtin. We have previously demonstrated the importance of the insulin-like growth factor I (IGF-1)/Akt pathway in HD. Indeed, upon IGF-1 activation, Akt phosphorylates polyQ-huntingtin at serine 421 and abrogates its toxicity. In addition, we have demonstrated that Akt is altered in the brain of HD patients. Here, we investigate the role of the serum- and glucocorticoid-induced kinase (SGK) in HD. We show that SGK phosphorylates huntingtin at serine 421 and that phosphorylation can protect striatal neurons against polyQ-huntingtin-induced toxicity. We find that SGK levels are increased in the brain of HD patients. Using a cellular model of HD, we demonstrate that the SGK dysregulation induced by polyQ-huntingtin occurs via the p38/MAPK pathway. Collectively, our results strongly suggest the involvement of SGK in HD and further imply that IGF-1 downstream signalling is a key transduction pathway that regulates the toxicity of huntingtin. C1 Inst Curie, UMR 146, CNRS, F-91405 Orsay, France. Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Neurobiol, Dept Psychiat, Baltimore, MD USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Humbert, S (reprint author), Inst Curie, UMR 146, CNRS, Bldg 110,Ctr Univ, F-91405 Orsay, France. EM sandrine.humbert@curie.u-psud.fr RI Ross, Christopher/H-8395-2013; SAUDOU, Frederic/L-3454-2014; Humbert, Sandrine/S-2981-2016 OI SAUDOU, Frederic/0000-0001-6107-1046; FU NINDS NIH HHS [NS16375] NR 50 TC 82 Z9 84 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2004 VL 19 IS 2 BP 273 EP 279 DI 10.1111/j.1460-9568.2003.03131.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 764UQ UT WOS:000188224800006 PM 14725621 ER PT J AU Zanzonico, P O'Donoghue, J Chapman, JD Schneider, R Cai, S Larson, SD Wen, BX Chen, YC Finn, R Ruan, ST Gerweck, L Humm, J Ling, C AF Zanzonico, P O'Donoghue, J Chapman, JD Schneider, R Cai, S Larson, SD Wen, BX Chen, YC Finn, R Ruan, ST Gerweck, L Humm, J Ling, C TI Iodine-124-labeled iodo-azomycin-galactoside imaging of tumor hypoxia in mice with serial microPET scanning SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE IAZG; FMISO; tumor hypoxia; microPET ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; OXYGENATION PREDICTS; BLOOD-FLOW; CANCER; CU-60-ATSM; SURVIVAL; I-124; HEAD; NECK AB Tumor hypoxia, present in many human cancers, can lead to resistance to radiation and chemotherapy, is associated with a more aggressive tumor phenotype and is an independent prognostic factor of clinical outcome. It is therefore important to identify and localize tumor hypoxia in cancer patients. In the current study, serial microPET imaging was used to evaluate iodine-124-labeled iodo-azomycin-galactoside ((124)I-IAZG) (4.2-day physical half-life) as a hypoxia imaging agent in 17 MCa breast tumors and six FSaII fibrosarcomas implanted in mice. For comparison, another promising hypoxic-cell PET radiotracer, fluorine-18-labeled fluoro-misonidazole ((18)F-FMISO), was also imaged in the same tumor-bearing animals. Twelve animals were also imaged with (18)F-labeled fluoro-deoxyglucose ((18)F-FDG). In addition, histological examination was performed, and direct measurement of tumor oxygenation status carried out with the Oxylite probe system. Two size groups were used, relatively well-oxygenated tumors in the range of 80-180 mg were designated as small, and those >300 mg and highly hypoxic, as large. Based on the data from 11 MCa and six FSaII tumors, both (124)I-IAZG and (18)F-FMISO images showed high tracer uptake in the large tumors. In (18)F-FMISO images at 1, 3-4, and 6-8 h post-injection (p.i.), there was considerable whole-body background activity. In contrast, (124)I-IAZG imaging was optimal when performed at 24-48 h p.i., when the whole-body background had dissipated considerably. As a result, the (124)I-IAZG images at 24-48 h p.i. had higher tumor to whole-body activity contrast than the (18)F-FMISO images at 3-6 h p.i. Region-of-interest analysis was performed as a function of time p.i. and indicated a tumor uptake of 5-10% (of total-body activity) for FMISO at 3-6 h p.i., and of similar to17% for IAZG at 48 h p.i. This was corroborated by biodistribution data in that the tumor-to-normal tissue (T/N, normal tissues of blood, heart, lung, liver, spleen, kidney, intestine, and muscle) activity ratios of IAZG at 24 h p.i. was 1.5-2 times higher than those of FMISO at 3 h p.i., with the exception of stomach. Statistical analysis indicated that these differences in T/N ratios were significant. The small tumors were visualized in the (18)F-FDG images, but not in the (124)I-IAZG or (18)F-FMISO images. This was perhaps due to the combined effect of a smaller tumor volume and a lower hypoxic fraction. Oxylite probe measurement indicated a lesser proportion of regions with pO(2)<2.5 mmHg in the small tumors (e.g., pO(2) was <2.5 mmHg in 28% and 67% of the data in small and large FSaII tumors, respectively), and the biodistribution data showed lower uptake of the tracers in the small tumors than in the large tumors. In the first study of its kind, using serial microPET imaging in conjunction with biodistribution analysis and direct probe measurements of local pO(2) to evaluate tumor hypoxia markers, we have provided data showing the potential of (124)I-IAZG for hypoxia imaging. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ling, C (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM lingc@mskcc.org OI O'Donoghue, Joseph A/0000-0002-2761-0015 FU NCI NIH HHS [R01 CA84596, R24 CA83084] NR 28 TC 81 Z9 83 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JAN PY 2004 VL 31 IS 1 BP 117 EP 128 DI 10.1007/s00259-003-1322-y PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 754HH UT WOS:000187309700017 PM 14523586 ER PT J AU Vucic, S Chong, PST Dawson, KT Cudkowicz, M Cros, D AF Vucic, S Chong, PST Dawson, KT Cudkowicz, M Cros, D TI Thromboembolic complications of intravenous immunoglobulin treatment SO EUROPEAN NEUROLOGY LA English DT Article DE thromboembolic complications; intravenous immunoglobulin; stroke; myocardial infarction; deep venous thrombosis ID IMMUNE GLOBULIN; MYOCARDIAL-INFARCTION; MYASTHENIA-GRAVIS; THERAPY; INFUSION; DISEASES; IVIG; THROMBOSIS AB Intravenous immunoglobulin (IVIg) preparations are increasingly being used in the treatment of neuroautoimmune diseases. Although for most part this treatment is safe, serious side effects such as thromboembolic events have been reported. We report on 7 patients who suffered a thromboembolic event while being treated with IVIg. Four patients suffered a stroke or transient ischemic attack, 1 an inferior wall myocardial infarction, 1 a deep venous thrombosis, and 1 a retinal artery infarct. The age range of the patients was 57-81 and most had underlying risk factors, such as hypertension, hypercholesterolemia, atrial fibrillation, history of vascular disease and stroke, and deep venous thrombosis. Three patients received multiple IVIg infusions before suffering a thromboembolic complication. Therefore, the clinicians should be vigilant about the possibility of thromboembolic complications with each IVIg infusion and be especially judicious with the use of IVIg in patients with underlying risk factors. Copyright (C) 2004 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. EM dcros@partners.org NR 20 TC 29 Z9 30 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2004 VL 52 IS 3 BP 141 EP 144 DI 10.1159/000081465 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 886QQ UT WOS:000226243800004 PM 15479982 ER PT J AU Huisman, TAGM Sorensen, AG AF Huisman, TAGM Sorensen, AG TI Perfusion-weighted magnetic resonance imaging of the brain: techniques and application in children SO EUROPEAN RADIOLOGY LA English DT Article DE perfusion-weighted imaging; dynamic susceptibility contrast imaging; haemodynamic parameter; children ID CEREBRAL BLOOD-VOLUME; CEREBROVASCULAR-DISEASE; POTENTIAL IMPLICATIONS; TUMOR ANGIOGENESIS; MOYAMOYA DISEASE; CONTRAST AGENTS; TRANSIT-TIME; FLOW; MRI; DIFFUSION AB Perfusion-weighted magnetic resonance imaging (PWI) has been proposed as an attractive non-invasive tool for evaluating cerebral haemodynamics. Quantitative maps of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and various other haemodynamic parameters can be obtained. Recent advances in hard- and software made PWI available for clinical routine. Although PWI became common in adult neuroradiology, it remains challenging in pediatric neuroradiology. In this article, the different PWI techniques that render haemodynamic maps of the brain are presented and discussed. The normal developmental changes of the cerebral haemodynamics in children as measured by PWI are presented as well as the application of PWI in cerebral ischaemia, primary and secondary cerebral vasculopathies and in cerebral tumours. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Huisman, TAGM (reprint author), Univ Zurich, Childrens Hosp, Dept Radiol, Steinwiesstr 75, CH-8032 Zurich, Switzerland. EM thierry.huisman@kispi.unizh.ch NR 50 TC 33 Z9 33 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2004 VL 14 IS 1 BP 59 EP 72 DI 10.1007/s00330-003-1972-y PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 764LN UT WOS:000188208500007 PM 12827431 ER PT J AU Roman, GC Rogers, SJ AF Roman, GC Rogers, SJ TI Donepezil: a clinical review of current and emerging indications SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE aphasia; Alzheimer's disease; autism; cholinesterase inhibitors; cholinergic transmission; dementia; donepezil; drowsiness; Down's syndrome; head injury; Lewy body; memory; migraine; opioid drowsiness; Parkinson's disease; schizophrenia; seizures; stroke; tardive dyskinesia; vascular dementia ID MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; CEREBRAL BLOOD-FLOW; PROGRESSIVE SUPRANUCLEAR PALSY; SEVERE ALZHEIMERS-DISEASE; TRAUMATIC BRAIN INJURY; HUMAN BASAL FOREBRAIN; LEWY BODY DEMENTIA; VASCULAR DEMENTIA; DOUBLE-BLIND AB This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept(R)), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. in addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions. C1 Univ Texas, Hlth Sci Ctr, Coll Pharm, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Coll Pharm, 7703 Floyd Curl Dr,Mail Code 7883, San Antonio, TX 78229 USA. NR 216 TC 25 Z9 26 U1 3 U2 16 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JAN PY 2004 VL 5 IS 1 BP 161 EP 180 DI 10.1517/14656566.5.1.161 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 759YG UT WOS:000187782000017 PM 14680445 ER PT J AU Ogino, S Wilson, RB AF Ogino, S Wilson, RB TI Spinal muscular atrophy: molecular genetics and diagnostics SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE carrier; conversion; deletion; gene dosage; genetic counselling; genetic testing; risk assessment; SMN; SMN1; SMN2 ID MOTOR-NEURON GENE; ARTHROGRYPOSIS MULTIPLEX CONGENITA; WERDNIG-HOFFMANN DISEASE; SMN GENE; DE-NOVO; SINGLE NUCLEOTIDE; COPY NUMBER; DIAPHRAGMATIC PARALYSIS; RESPIRATORY-DISTRESS; SPLICING ENHANCER AB Spinal muscular atrophy is one of the most common autosomal recessive diseases, affecting approximately one in 10,000 live births and with a carrier frequency of approximately one in 50. Spinal muscular atrophy is caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN genes, SMN1 and SMN2. Due to a single nucleotide polymorphism (840C>T), SMN2 produces less full-length transcript than SMN1 and cannot entirely prevent neuronal cell death at physiologic gene dosages. The 38-kDa SMN protein comprises 294 amino acids and is involved in the biogenesis of uridine-rich small nuclear ribonucleoproteins, facilitating their cytoplasmic assembly into the spliceosome. Various animal models have been developed to study the pathogenesis of spinal muscular atrophy, as well as to test novel therapeutics. Common PCR-restriction fragment length polymorphism assays can detect the homozygous absence of SMN1 in approximately 94% of patients with clinically typical spinal muscular atrophy. SMN gene dosage analysis can determine the copy number of SMN1 to detect carriers and patients heterozygous for the absence of SMN1. Due to the genetic complexity and the high carrier frequency, accurate risk assessment and genetic counseling are particularly important. Comprehensive SMA genetic testing, combined with appropriate genetic counseling and risk assessment, provides the most complete evaluation of patients and their families at this time. New technologies, such as monosomal analysis techniques, may be widely available in the future. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM sogino@partners.org NR 121 TC 63 Z9 75 U1 0 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JAN PY 2004 VL 4 IS 1 BP 15 EP 29 DI 10.1586/14737159.4.1.15 PG 15 WC Pathology SC Pathology GA 768EW UT WOS:000188531500002 PM 14711346 ER PT J AU Krysan, K Merchant, FH Zhu, L Dohadwala, M Luo, J Lin, Y Heuze-Vourc'h, N Pold, M Seligson, D Chia, D Goodglick, L Wang, HJ Strieter, R Sharma, S Dubinett, S AF Krysan, K Merchant, FH Zhu, L Dohadwala, M Luo, J Lin, Y Heuze-Vourc'h, N Pold, M Seligson, D Chia, D Goodglick, L Wang, HJ Strieter, R Sharma, S Dubinett, S TI COX-2-dependent stabilization of survivin in non-small cell lung cancer SO FASEB JOURNAL LA English DT Article DE cyclooxygenase 2; prostaglandin; NSCLC cells ID CASPASE ACTIVATION; PROSTAGLANDIN E-2; PROSTATE-CANCER; CYTOCHROME-C; APOPTOSIS; CYCLOOXYGENASE-2; EXPRESSION; PROTEIN; INHIBITOR; INVOLVEMENT AB Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. The mechanism(s) by which COX-2 exerts its cytoprotective effects are not completely understood but may be due to an imbalance of pro- and anti-apoptotic gene expression. To analyze COX-2-dependent gene expression and apoptosis, we created cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations. Whereas COX-2 sense cells have significantly heightened resistance to radiation and drug-induced apoptosis, COX-2 antisense cells are highly sensitive to apoptosis induction. We found that the expression of the anti-apoptotic protein survivin correlated positively with COX-2 expression. A COX-2-dependent modulation of survivin ubiquitination led to its stabilization in COX-2 overexpressing cells, and this effect was replicated by exogenous PGE2 treatment of parental tumor cells. In contrast to previous studies in other cell types, in nonsmall cell lung cancer cells survivin was expressed in a cell cycle-independent manner. When established in SCID mice in vivo, COX-2 antisense-derived tumors had significantly decreased survivin levels while COX-2 sense-derived tumors demonstrated elevated levels compared with controls. In accord with these findings, survivin and COX-2 were frequently upregulated and co-expressed in human lung cancers in situ. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Defined Tumor Marker Evaluat Ctr, Los Angeles, CA 90024 USA. RP Dubinett, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU UCLA SPORE In Lung Cancer NIH [P50 CA90388]; TRDRP grant [12FT-0061]; Early Detection Research Network [NCI CA-99-008] FX This study was supported by the UCLA SPORE In Lung Cancer NIH P50 CA90388, TRDRP grant #12FT-0061 (K. Krysan) and the Early Detection Research Network (NCI CA-99-008; L. Goodglick, D. Chia, D. Seligson, and F. Merchant). NR 45 TC 103 Z9 129 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2004 VL 18 IS 1 BP 205 EP 206 DI 10.1096/fj.03-0369fje PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 772EX UT WOS:000188829300075 PM 14597555 ER PT J AU Strowski, MZ Cramer, T Schafer, G Juttner, S Walduck, A Schipani, E Kemmner, W Wessler, S Wunder, C Weber, M Meyer, TF Wiedenmann, B Jons, T Naumann, M Hocker, M AF Strowski, MZ Cramer, T Schafer, G Juttner, S Walduck, A Schipani, E Kemmner, W Wessler, S Wunder, C Weber, M Meyer, TF Wiedenmann, B Jons, T Naumann, M Hocker, M TI Helicobacter pylori stimulates host vascular endothelial growth factor-A (vegf-A) gene expression via MEK/ERK-dependent activation of Sp1 and Sp3 SO FASEB JOURNAL LA English DT Article DE angiogenesis; Sp1/Sp3 transcription factors; gastric epithelial cells ID CAG PATHOGENICITY ISLAND; HISTIDINE-DECARBOXYLASE PROMOTER; GASTRIC-CANCER; TRANSCRIPTIONAL ACTIVATION; OXIDATIVE STRESS; EPITHELIAL-CELLS; PROTEIN-KINASE; FACTOR-ALPHA; ANGIOGENESIS; BINDING AB VEGF-A is a key regulator of inflammatory and tumor-associated angiogenesis. H. pylori plays a critical role in the pathogenesis of benign and malignant gastric diseases. It has been suggested that H. pylori infection is associated with activation of host angiogenesis, however, underlying mechanisms as well as angiogenic growth factors activated by the bacterium have not yet been identified. Therefore, we investigated the influence of the bacterium on VEGF-A as a candidate host target gene in vivo and in vitro. We show that H. pylori potently up-regulates production and release of VEGF-A protein as well as vegf-A mRNA levels, and we provide strong evidence that enhanced recruitment of SpI and Sp3 transcription factors to two proximal GC-rich vegf-A promoter elements mediates H. pylori-triggered vegf-A gene expression. In addition, H. pylori infection increased the transactivating capacity of both SpI and Sp3, which suggests additional mechanism(s) of vegf-A gene regulation by the bacterium. Signaling studies identified the MEK>ERK1/-2 kinase cascade as principal host signaling pathway mediating H. pylori-stimulated vegf-A transcription. By identifying H. pylori as potent activator of vegf-A gene expression and characterization of underlying molecular mechanisms, our results provide novel insights into pathways linking the bacterium to host angiogenesis and may help to develop strategies to influence vegf-A gene expression in the setting of H. pylori infection. C1 Univ Med Berlin, Med Klin Schwerpunkt Hepatol & Gastroenterol, Charite, Sekt Mol Hepatol & Gastroenterol, D-13353 Berlin, Germany. Max Planck Inst Infekt Biol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Free Univ Berlin, Klinikum Rudolf Virchow, Robert Rossle Klin, D-13122 Berlin, Germany. Max Delbruck Ctr, Berlin, Germany. Otto Von Guericke Univ, Inst Expt Innere Med, Magdeburg, Germany. Univ Med Berlin, Inst Anat, Charite, Berlin, Germany. RP Hocker, M (reprint author), Univ Med Berlin, Med Klin Schwerpunkt Hepatol & Gastroenterol, Charite, Sekt Mol Hepatol & Gastroenterol, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. EM hoecker@charite.de RI Meyer, Thomas F./J-2485-2013; Naumann, Michael/B-5285-2011; Wessler, Silja/C-6309-2015; Cramer, Thorsten/S-2479-2016; OI Meyer, Thomas F./0000-0002-6120-8679; Naumann, Michael/0000-0002-8060-2313; Wessler, Silja/0000-0001-7011-6162; Cramer, Thorsten/0000-0002-6462-239X; Wunder, Christian/0000-0001-9091-0080; Walduck, Anna/0000-0002-9624-4370 FU Bundesministerium fur Bildung und Forschung (BMBF) [NBLIII-Schnittstellenlabor Tumormetastasierung]; Deutsche Forschungsgemeinschaft (DFG) [HO1288/6-1, Na292/6-2]; DFG-Graduiertenkolleg [GRK276]; Max-Planck-Gesellschaft(Tandemprojekt-Initiative) FX Grant support of M. H. was provided by the Bundesministerium fur Bildung und Forschung (BMBF; Grant NBLIII-Schnittstellenlabor Tumormetastasierung), the Deutsche Forschungsgemeinschaft (DFG; HO1288/6-1), the DFG-Graduiertenkolleg GRK276, and the Max-Planck-Gesellschaft(Tandemprojekt-Initiative). M. N. was supported by the DFG (Na292/6-2). We express our gratitude to M. Cobb, C. Vinson, M. Karin, and G. Suske for providing plasmid DNA. NR 47 TC 11 Z9 11 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2004 VL 18 IS 1 BP 218 EP 220 DI 10.1096/fj.03-0055fje PG 3 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 772EX UT WOS:000188829300078 PM 14597566 ER PT J AU Choi, W Mitsumoto, A Rajadurai, A Kochevar, I AF Choi, W Mitsumoto, A Rajadurai, A Kochevar, I TI Reactive oxygen species mediate the TGF-B1-induced increase in elastin mRNA in dermal fibroblasts beta SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S66 EP S66 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900190 ER PT J AU Milbury, P Kwak, HK Blumberg, J Ning, MM Furie, K Kelly, P AF Milbury, P Kwak, HK Blumberg, J Ning, MM Furie, K Kelly, P TI Acute ischemic stroke results in early depletion of endogenous antioxidant status in humans SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Tufts Univ, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S162 EP S162 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900493 ER PT J AU Swenberg, JA AF Swenberg, JA TI New approaches for evaluating oxidative DNA damage SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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. PY 2004 VL 37 SU 1 BP S8 EP S8 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900014 ER PT J AU Valencia, A Carle, B Redmond, R Kochevar, IE AF Valencia, A Carle, B Redmond, R Kochevar, IE TI Role of reactive oxygen species in the ultraviolet-A skin photosensitivity of Smith-Lemli-Opitz patients SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S147 EP S148 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900455 ER PT J AU Wang, TW Donahoe, PK AF Wang, TW Donahoe, PK TI The immunophilin FKBP12: A molecular guardian of the TGF-beta family type I receptors SO FRONTIERS IN BIOSCIENCE LA English DT Article DE FKBP12; TGF-beta; type I receptor; type II receptor; farnesyltransferase; review ID CHANNEL RYANODINE RECEPTOR; P70 S6 KINASE; PEPTIDYL-PROLYL ISOMERASE; STAGE HEART-FAILURE; FK506-BINDING PROTEIN; RELEASE CHANNELS; IMMUNOSUPPRESSANT FK506; MAMMALIAN PROTEIN; CARDIAC MYOCYTES; CYCLOSPORINE-A AB FKBP12 as an immunophilin that binds to two well-known immunosuppressive macrolides, FK506 and rapamycin, has attracted immense attention and its role in mediating the immunosuppressive functions of these macrolides has been extensively studied. Since FKBP12 is a well-conserved protein among many species and is also highly expressed in almost all cells, it must play important roles in cellular function in the absence of macrolides. In one such a role, FKBP12 interacts with and regulates the functional state of the ryanodine Ca2+ channel receptor by altering protein conformation and coordinating multiprotein complex formation. This review summarizes another physiological role of FKBP12 as an interactor and a regulator of the type I serine/threonine kinase receptors of TGF-beta superfamily. Current data, derived from detailed biochemical studies as well as from functional studies in various systems, suggest that FKBP12 functions as a "guardian" for the type I receptors to prevent them from leaky signaling under sub-optimal ligand concentrations, thereby providing a molecular "gradient reader" for TGF-beta family morphogens. This aspect of FKBP12 function may be critical for cellular responsiveness to morphogenetic gradients of the TGF-beta family members during early development, serving to assure the translation of different ligand concentrations into different signaling readouts. C1 Virginia Mason, Benaroya Res Inst, Seattle, WA 98101 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Wang, TW (reprint author), Virginia Mason, Benaroya Res Inst, 1201 9th Ave, Seattle, WA 98101 USA. NR 76 TC 40 Z9 42 U1 0 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2004 VL 9 BP 619 EP 631 DI 10.2741/1095 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746XW UT WOS:000186773800059 PM 14766396 ER PT S AU Iwaki, S Bonmassar, G Belliveau, JW AF Iwaki, S Bonmassar, G Belliveau, JW BE Nakagawa, M Hirata, K Koga, Y Nagata, K TI Spatiotemporal imaging of the brain activities during 3-D structure perception from motion SO FRONTIERS IN HUMAN BRAIN TOPOGRAPHY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th World Congress of the International-Society-for-Brain-Electromagnetic-Topography CY APR 11-14, 2004 CL Tokyo, JAPAN SP Int Soc Brain Electromagnet Topog DE 3-D structure perception from random-dot motion; MEG; fMRI; spatio-temporal source modeling; weighted minimum-nonn estimate ID FMRI AB Here, we used both MEG and fMRI to detect dynamic brain responses to 3-D structure perception from random-dot motion in humans. The visual stimuli consisted of 1000 random dots, which started to move 500 ins after the onset of presentation. The coherence of the motion was controlled from 0 to 100%. A stimulus that is fully coherent had all the dots moving as if they belonged to a rotating spherical surface. On the other hand, the 80, 60, 40, 20, and 0% coherence stimuli contain dots having the same speed as the fully coherent stimuli, but the directions of the 20, 40, 60, 80, and 100% of the dots were randomized, respectively. Neuromagnetic signals were measured with a 306-channel MEG system. More than 60 stimulus-related epochs of 2000 ms, including a 1000 ms pre-stimulus baseline, were recorded and averaged for each condition with a sampling rate of 600 Hz. FMRI experiments were conducted using a 3 Testa scanner covering the entire brain using blocked design, in which 12 s blocks were presented in pseudo-randomized order. The results of the fMRI analysis were used to impose plausible constraints on the MEG inverse calculation using a "weighted" minimum-norm approach to improve spatial resolution of the spatiotemporal activity estimates. The bilateral occipito-temporal and the intra-parietal regions showed increased neural activity in the fully coherent motion condition around the latencies of 180 ms and 240 ms after the onset of motion, respectively. These results indicate that the bilateral occipito-temporal and intra-parietal regions play an important role in the perception of 3-D structure from random-dot motion. Also, the present study adds further insight into the temporal characteristics of the neural activities in these regions. (C) 2004 Published by Elsevier B.V. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Iwaki, S (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 NR 3 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51655-7 J9 INT CONGR SER PY 2004 VL 1270 BP 209 EP 212 DI 10.1016/j.ics.2004.04.036 PG 4 WC Multidisciplinary Sciences; Clinical Neurology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBH13 UT WOS:000225483000043 ER PT J AU Brambilla, P Hardan, AY di Nemi, SU Caverzasi, E Soares, JC Perez, J Barale, F AF Brambilla, P Hardan, AY di Nemi, SU Caverzasi, E Soares, JC Perez, J Barale, F TI The functional neuroanatomy of autism SO FUNCTIONAL NEUROLOGY LA English DT Article DE brain imaging; fMRI; MRS; neuroimaging; PET; SPECT ID CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE; ASPERGER-SYNDROME; CHILDHOOD AUTISM; FACIAL EXPRESSIONS; NEURAL MECHANISMS; CORTICAL ACTIVITY; FACE RECOGNITION; HUMAN BRAIN; MIND AB Autism is a neurodevelopmental syndrome characterized by impaired social and executive functions. Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows investigation of the neural networks underlying cognitive impairments in autism. In this article, brain imaging studies investigating the functional brain anatomy of autism are reviewed. Face recognition, theory of mind and executive functions have all been explored in functional neuroimaging studies involving autistic patients. The available literature suggests an involvement of abnormal functional mechanisms in face recognition, mentalization and executive functions in adults with high-functioning autism or Asperger's syndrome, possibly due to brain maturation abnormalities, and resulting in dysfunctional reciprocal cortico-subcortical connections. Future functional neuroimaging research should investigate subgroups of autistic children and adolescents longitudinally and attempt to integrate genetic, cognitive and empirical approaches. Such studies will be instrumental in furthering understanding of the pathophysiology of autism and in exploring the importance of dimensional measures of the broader phenotype currently defined as autism. C1 IRCCS S Giovanni Dio Fatebenefratelli, Biol Psychiat Unit, Brescia, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Pavia, S Matteo Hosp, IRCCS, Dept Psychiat, I-27100 Pavia, Italy. Cascina Rossago Rehabil Ctr Autism, Pavia, Italy. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Brambilla, P (reprint author), Univ Udine, Policlin Univ, Sez Psichiatria, Dipartimento Patol & Med Sperimentale & Clin, Via Colugna 50, I-33100 Udine, Italy. EM brambillapf@tiscali.it RI brambilla, paolo/B-4184-2010; OI brambilla, paolo/0000-0002-4021-8456; BARALE, FRANCESCO/0000-0001-7820-6736 FU NIMH NIH HHS [MH 01736]; PHS HHS [M64027] NR 75 TC 22 Z9 23 U1 8 U2 26 PU C I C-EDIZIONI INTERNAZIONALI SRL PI ROME PA CORSO TRIESTE, 42, 00198 ROME, ITALY SN 0393-5264 J9 FUNCT NEUROL JI Funct. Neurol. PD JAN-MAR PY 2004 VL 19 IS 1 BP 9 EP 17 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 828WK UT WOS:000222004200002 PM 15212111 ER PT J AU Gerbino, A Hofer, AM McKay, B Lau, BW Soybel, DI AF Gerbino, A Hofer, AM McKay, B Lau, BW Soybel, DI TI Divalent cations regulate acidity within the lumen and tubulovesicle compartment of gastric parietal cells SO GASTROENTEROLOGY LA English DT Article ID EPITHELIAL-CELLS; ALPHA-TOXIN; GLAND MODEL; SECRETION; PH; TRANSPORT; STIMULATION; CALCIUM; CA2+; DETERMINANTS AB Background & Aims: Until recently, it has not been possible to evaluate factors that regulate the acidity of the microenvironment within the tubulovesicles and luminal (TV/L) spaces of the gastric gland. The goal of this study was to develop a method for monitoring the mechanisms that regulate acidity in the TV/L compartment. Methods: Isolated rabbit gastric glands (intact or permeabilized with S. aureus alpha-toxin) were loaded with a recently characterized fluorescent dye, LysoSensor YellowBlue DND 160 (Molecular Probes, Eugene, OR), which localizes to highly acidic compartments and can be used to monitor acidity ratiometrically. Results: In resting glands, the pH of the TV/L compartment was similar to3.4. Moderate alkalizations (similar to0.5 to 1.0 pH unit alkalization) were observed during exposure to inhibitors of the apical H+/K+ ATPase (omeprazole and SCH28080), thereby unmasking a stable, low-level leak of H+ ions from the TV/L compartment. Similar changes were observed in alpha-toxin permeabilized glands following depletion of ATP in the cytoplasm. In intact and permeabilized glands, we used the cell-permeant, divalent cation chelator, tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) to probe the effects of lowering divalent cation content of the TV/L compartment. Exposure to relatively low concentrations (20 mumol/L, 50 mumol/L) of TPEN reversibly promoted H+ leakage. At these concentrations, simultaneous inhibition using SCH28080 led to marked enhancement of the rate of alkalization. Conclusions: The effects of low-dose TPEN suggests that acidity within the TV/L compartment of the gastric gland may be regulated, at least in part, by its content of divalent cations such as Zn2+, for which TPEN has high affinity. C1 Brigham & Womens Hosp, Dept Surg, VA Boston Hlth Care Syst, Boston, MA 02115 USA. Univ Bari, Dipartimento Fisiol & Ambientale, Bari, Italy. RP Soybel, DI (reprint author), Brigham & Womens Hosp, Dept Surg, VA Boston Hlth Care Syst, 75 Francis St, Boston, MA 02115 USA. OI Gerbino, Andrea/0000-0002-2839-0130 FU NIDDK NIH HHS [R01 DK44571, DK34854] NR 44 TC 15 Z9 15 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2004 VL 126 IS 1 BP 182 EP 195 DI 10.1053/j.gastro.2003.10.068 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 760GM UT WOS:000187803300024 PM 14699499 ER PT J AU Burgio, KL AF Burgio, KL TI Behavioral treatment options for urinary incontinence SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Conference on Advancing the Treatment of Fecal and Urinary Incontinence Through Rresearch: Trial Design Outcome Measures and Research Priorities CY NOV 03-05, 2002 CL MILWAUKEE, WISCONSIN ID RANDOMIZED CONTROLLED-TRIAL; PELVIC MUSCLE EXERCISE; GENUINE STRESS-INCONTINENCE; OLDER WOMEN; DETRUSOR INSTABILITY; URGE INCONTINENCE; BLADDER DRILL; ELECTRICAL-STIMULATION; DRUG-TREATMENT; ELDERLY WOMEN AB Behavioral treatments improve bladder control by changing the incontinent patient's behavior, especially his or her voiding habits, and by teaching skills for preventing urine loss. These treatments are effective for most outpatient men and women with stress, urge, or mixed incontinence. The average reduction in the frequency of incontinence ranges from 57% to 86%. In long-term care settings, treatment is generally more challenging and yields more modest results. The advantages of behavioral interventions include the absence of side-effects, patient comfort, and high levels of patient satisfaction. Although most patients who receive behavioral treatment achieve significant improvement, most are not completely dry. Thus, there is a need for research to explore ways to enhance the effectiveness of these conservative therapies. Combining behavioral treatment with other treatments may have additive effects. Research is also needed to understand better the mechanisms of therapeutic change, the best methods for teaching pelvic floor muscle control, the optimal exercise regimens, the predictors of outcome, and the efficacy of behavioral treatments in men. Although behavioral interventions aria more accepted today than 20 years ago, they are still not widely available or integrated into most clinical practices, and we know little of how effective they will be in these settings. Thus, it will be important to develop and evaluate creative modes of delivery, such as group intervention (especially by non-physician providers), in a variety of clinical settings. C1 Birmingham VA Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL 35233 USA. Univ Alabama, Birmingham, AL USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Ctr Geriatr Res Educ & Clin, 700 19th St S, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu NR 52 TC 18 Z9 19 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 JAN PY 2004 VL 126 IS 1 SU 1 BP S82 EP S89 DI 10.1053/j.gastro.2003.10.042 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 761CJ UT WOS:000187881900013 PM 14978643 ER PT J AU Naliboff, BD AF Naliboff, BD TI Choosing outcome variables: Global assessment and diaries SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Conference on Advancing the Treatment of Fecal and Urinary Incontinence Through Rresearch: Trial Design Outcome Measures and Research Priorities CY NOV 03-05, 2002 CL MILWAUKEE, WISCONSIN ID CHRONIC PAIN; CLINICAL-TRIALS AB This report reviews the advantages and disadvantages of 2 types of outcome assessment regularly used in the literature on incontinence: (1) global assessments of symptoms or relief and (2) ratings of specific symptoms of incontinence. Global assessments are usually used when the target condition involves multiple and variable symptoms, They are easy for patients to understand and yield data that seem to correspond closely to the target of the treatment (e.g., symptom severity). The 2 major scaling approaches used in clinical symptom assessment, categorical scaling and cross-modality matching of symptom intensity to line length (visual analogue scales), are reviewed for their reliability and validity. Numerical scales provide the advantage of a large number of possible ratings (usually 9-100) and are intuitively easy to use. All methods of symptom assessment using patient recall are subject to potential reporting bias. Measures of current symptoms, although less biased, may not reflect ongoing symptom levels, and current symptom levels tend to influence patients' recall of both symptom severity and medication counts. However, patient-initiated ratings are relevant to assessing real-time" symptoms in incontinence trials, and even single retrospective ratings of "usual" symptom intensity may actually be an adequate reflection of the average symptom severity (at least for chronic pain). Applying subjective, predetermined criteria for success, such as the provision of "adequate relief," allows researchers to closely mimic clinical situations and use a cutoff point ("threshold") specifically associated with the condition and treatment being investigated. Devices such as personal digital assistants that can cue subjects for information at set or random intervals, record multiple types of responses, and accurately assess compliance with data recording should help facilitate future research. C1 Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Rm 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu NR 13 TC 12 Z9 13 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 JAN PY 2004 VL 126 IS 1 SU 1 BP S129 EP S134 DI 10.1053/j.gastro.2003.10.011 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 761CJ UT WOS:000187881900019 PM 14978649 ER PT J AU Schnelle, JF Leung, FW AF Schnelle, JF Leung, FW TI Urinary and fecal incontinence in nursing homes SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Conference on Advancing the Treatment of Fecal and Urinary Incontinence Through Rresearch: Trial Design Outcome Measures and Research Priorities CY NOV 03-05, 2002 CL MILWAUKEE, WISCONSIN ID LONG-TERM-CARE; ELDERLY-PATIENTS; RISK-FACTORS; CONTROLLED TRIAL; RESIDENTS; INTERVENTION; QUALITY; CONSTIPATION; MANAGEMENT; CONTINENCE AB Urinary and fecal incontinence affect 50% or more of nursing home residents and frequently occur together because immobility and dementia are primary risk factors for both conditions. Many residents (40%-60%) show immediate improvement when provided with consistent toileting assistance, which compensates for the immobility and dementia risk factors that prevent them from toileting independently. Residents who are responsive to assistance can be identified with a 2-day run-in trial during which prompts are provided every 2 hours to encourage toileting. This run-in trial also provides an opportunity to use protocols to identify and treat other reversible causes of incontinence (e.g., urinary tract infection, fecal impaction) and to diagnose problems with bladder or anorectal functioning. The effects of toileting assistance on the frequency of fecal incontinence, while significant, are less dramatic than those reported for urinary incontinence, primarily because of constipation. Fortunately, noninvasive interventions have been identified that address most of the risk factors common to both constipation and fecal incontinence. Trials are needed to evaluate treatments that integrate noninvasive interventions directed toward the use of laxatives or constipating agents, low toileting frequency, low food and fluid intake, and physical activity to improve constipation and fecal incontinence in nursing home residents. The scientific documentation of the efficacy of such a noninvasive intervention and the labor costs of implementing these measures can lead to major changes in how nursing home care is funded and provided. C1 Univ Calif Los Angeles, David Geffen Sch Med, Borun Ctr Gerontol Res, Div Geriatr, Reseda, CA 91335 USA. VA Greater Los Angeles Healthcare Syst, Jewish Home Aging, Reseda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Schnelle, JF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Borun Ctr Gerontol Res, Div Geriatr, 7150 Tampa Ave, Reseda, CA 91335 USA. EM jschnell@ucla.edu NR 44 TC 23 Z9 23 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2004 VL 126 IS 1 SU 1 BP S41 EP S47 DI 10.1053/j.gastro.2003.10.017 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 761CJ UT WOS:000187881900007 PM 14978637 ER PT S AU Chung, DC AF Chung, DC BE Wiedenmann, B Christofori, GM Hocker, M Reubi, JC TI Cyclin D1 in human neuroendocrine tumorigenesis SO GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR DISEASE: MOLECULAR AND CELL BIOLOGICAL ASPECTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Conference on Molecular and Cell Biological Aspects of Gastroenteropancreatic Neuroendocrine Tumor Disease CY JUN 19-21, 2003 CL Berlin, GERMANY SP Novartis DE neuroendocrine tumors; MEN1 tumor suppressor gene; cyclin D1 ID TUMOR-SUPPRESSOR GENE; PANCREATIC ENDOCRINE TUMORS; PARATHYROID ADENOMAS; TRANSGENIC MICE; ESTROGEN-RECEPTOR; MEN1 GENE; BETA-CATENIN; ONCOGENE; EXPRESSION; MUTATIONS AB Human neuroendocrine tumors exhibit unique biological properties, and defining the molecular genetic alterations that underlie these distinctive features remains an important challenge. In addition to the MEN1 tumor suppressor gene, the cyclin D1 oncogene has demonstrated a role in the pathogenesis of parathyroid and gastroenteropancreatic neuroendocrine tumors. Up-regulation of cyclin D1 is observed early in tumor formation, implying a possible role in tumor initiation. Overexpression of cyclin D1 in the parathyroid glands of mice resulted in the tandem regulation of cellular proliferation and hormonal secretion, a feature intrinsic to neuroendocrine tumors. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu NR 46 TC 20 Z9 21 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-492-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1014 BP 209 EP 217 DI 10.1196/annals.1294.022 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Endocrinology & Metabolism; Gastroenterology & Hepatology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Endocrinology & Metabolism; Gastroenterology & Hepatology; Science & Technology - Other Topics GA BAE71 UT WOS:000221898100022 PM 15153436 ER PT J AU Chan, HH Nishioka, NS Mino, M Lauwers, GY Puricelli, WP Collier, KN Brugge, WR AF Chan, HH Nishioka, NS Mino, M Lauwers, GY Puricelli, WP Collier, KN Brugge, WR TI EUS-guided photodynamic therapy of the pancreas: a pilot study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SYRIAN GOLDEN-HAMSTER; 5-AMINOLEVULINIC ACID; ESOPHAGEAL CANCER; ADJACENT TISSUES; PHOTOFRIN-II; ABLATION; TUMORS; PHTHALOCYANINE; SENSITIZATION; IRRADIATION AB Background: Photodynamic therapy of pancreatic cancer by using percutaneously placed light catheters has been reported. The feasibility and safety of EUS-guided photodynamic therapy of the pancreas was studied in a porcine model. Methods: After injection of porfimer sodium, a 19-gauge needle was inserted into the pancreas, the liver, the spleen, and the kidney under EUS guidance. A small diameter quartz optical fiber was passed through the EUS needle and used to illuminate the tissue with laser light. The tissue response to photodynamic therapy was examined. Results: Localized tissue necrosis was achieved in all organs, without significant complication. There was no significant difference in inflammation induced by photodynamic therapy within the various organs. Conclusions: EUS-guided photodynamic therapy is a safe and simple technique that can induce small areas of focal tissue ablation within the liver, the pancreas, the kidney, and the spleen, and potentially could be used to treat a variety of benign and malignant conditions. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chan, HH (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 59 Z9 63 U1 0 U2 4 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 JAN PY 2004 VL 59 IS 1 BP 95 EP 99 AR PII S0016-5107(03)02361-7 DI 10.1016/S0016-5107(03)02361-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 763AQ UT WOS:000188046500022 PM 14722560 ER PT J AU Wakimoto, H Fulci, G Tyminski, E Chiocca, EA AF Wakimoto, H Fulci, G Tyminski, E Chiocca, EA TI Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's enhancement of viral oncolysis SO GENE THERAPY LA English DT Article DE brain tumors; oncolytic virus; replication-competent virus; immune responses ID HERPES-SIMPLEX-VIRUS; ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; BRAIN-TUMORS; RIBONUCLEOTIDE REDUCTASE; TYPE-1 REPLICATION; MALIGNANT GLIOMA; IMMUNE-RESPONSE; DNA-SYNTHESIS AB Oncolytic viruses (OVs) are being used as anticancer agents in preclinical and clinical trials. Propagation of OVs inside infected tumors is critical to their efficacy and is mediated by the productive generation of progeny OVs within infected tumor cells. In turn, this progeny can spread the infection to other tumor cells in successive rounds of oncolysis. Previously, we had found that, in rats, cyclophosphamide (CPA) pretreatment increased infection of brain tumors by an intra-arterially administered herpes simplex virus type 1 OV, because it inhibited activation of complement responses, mediated by innate IgM. We also have previously shown that other pharmacologic inhibitors of complement, such as cobra venom factor (CVF), allowed for increased infection. However, in these studies, further inhibition of complement responses by CVF did not result in additional infection of brain tumor cells or in propagation of OV to surrounding tumor cells. In this study, we sought to determine if CPA did lead to increased infection/propagation from initially infected tumor cells. Unlike our results with CVF, we find that CPA administration does result in a time-dependent increase in infection of tumor cells, suggestive of increased propagation, in both syngeneic and athymic models of brain tumors. This increase was due to increased survival of OV within infected tumors and brain surrounding tumors. CPA's effect was not due to a direct enhancement of viral replication in tumor cells, rather was associated with its immunosuppressive effects. RT-PCR analysis revealed that CPA administration resulted in impaired mRNA production by peripheral blood mononuclear cells (PBMCs) of several cytokines (interferons alpha/beta, interferon gamma, TNFalpha, IL-15, and IL-18) with anti-HSV function. These findings suggest that the CPA-mediated facilitation of OV intraneoplastic propagation is associated with a general decrease of antiviral cytokines mRNAs in PBMCs. These findings not only suggest a potential benefit for the addition of transient immunosuppression in clinical applications of oncolytic HSV therapy, but also suggest that innate immunomodulatory pathways may be amenable to manipulation, in order to increase OV propagation and survival within infected tumors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv,Mol Neurooncol Labs, Charlestown, MA USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp East, Mol Neurooncol Lab, CNY6,Bldg 149, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01 CA069246-04, CA 69246, P01 CA069246] NR 40 TC 66 Z9 68 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2004 VL 11 IS 2 BP 214 EP 223 DI 10.1038/sj.gt.3302143 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 761KZ UT WOS:000187909100012 PM 14712306 ER PT J AU Papakostas, GI Petersen, T Mahal, Y Mischoulon, D Nierenberg, AA Fava, M AF Papakostas, GI Petersen, T Mahal, Y Mischoulon, D Nierenberg, AA Fava, M TI Quality of life assessments in Major Depressive Disorder: a review of the literature SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE quality of life; major depression ID NATIONAL-COMORBIDITY-SURVEY; EPIDEMIOLOGIC CATCHMENT-AREA; PRIMARY-CARE PATIENTS; PSYCHIATRIC-DISORDERS; DOUBLE-BLIND; SOCIAL-CONSEQUENCES; DYSTHYMIC PATIENTS; MEDICAL OUTCOMES; GLOBAL BURDEN; HEALTH-CARE AB According to the DSM-IV classification, a diagnosis of Major Depressive Disorder (MDD) is possible only when there is evidence of significant inference with functioning. However, despite the high prevalence of MDD in the general population [1], it is uncommon for clinicians to assess overall functioning in a systematic way before making such diagnosis. An important correlate of functioning is quality of life, which is typically defined as "patients' own assessments of how they feel about what they have, how they are functioning, and their ability to derive pleasure from their life activities" [2]. In the present article, we review studies focusing on the relationship between depression and quality of life, particularly focusing on the impact of the treatment of depression on quality of life. Studies focusing on the quality of life in MDD are reviewed. Candidate studies published between 1970 and recently were initially identified by Pubmed and Ovid search cross-referencing the terms "quality of life," "psychosocial functioning" with "major depression" and "treatment." A number of studies report poorer quality of life in MDD patients compared to controls. Several studies also report an improvement in quality of life measures during various phases of treatment with antidepressants and/or psychotherapy. However, trials comparing the role of newer psychopharmacologic agents in the acute phase of treatment, and the role of newer psychotherapies in the continuation and maintenance phases of treatment in restoring psychosocial functioning and improving the quality of life in MDD are lacking. Exploring the impact of these modalities on psychosocial function and quality of life in MDD are necessary to help translate clinical response into restoration of psychosocial function and to thus further improve the standard of care. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 63 TC 113 Z9 122 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2004 VL 26 IS 1 BP 13 EP 17 DI 10.1016/j.genhosppsych.2003.07.004 PG 5 WC Psychiatry SC Psychiatry GA 772AW UT WOS:000188819000004 PM 14757297 ER PT J AU Yeung, A Chan, R Mischoulon, D Sonawalla, S Wong, E Nierenberg, AA Fava, M AF Yeung, A Chan, R Mischoulon, D Sonawalla, S Wong, E Nierenberg, AA Fava, M TI Prevalence of major depressive disorder among Chinese-Americans in primary care SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE prevalence; major depressive disorder; Chinese-Americans; primary care ID PSYCHIATRIC-DISORDERS; 12-MONTH PREVALENCE; LOS-ANGELES; HEALTH-CARE; COMMUNITY; INVENTORY; LIFETIME; VERSION; TAIWAN AB An epidemiological study in Los Angeles showed that Chinese Americans had lower rates of depression compared to the U.S. national estimates. This study surveys the prevalence of major depressive disorder (MDD) among Asian-Americans in the primary care setting. A two-phase epidemiological survey was performed in the primary care clinic of a community health center in Boston, MA, which provides treatment to under-served Asian-Americans. Participants were Chinese Americans in the waiting area of the primary care clinic, 18 years of age or older, who spoke any one the four commonly used Chinese dialects. The Chinese version of the Beck Depression Inventory (CBDI) was used for initial screening. All consenting patients who screened positive (CBDI greater than or equal to 16) and a fraction of those who screened negative (CBDI < 16) were inter-viewed by a bilingual and bicultural psychiatrist with the Structured Clinical Interview for DSM-III-R, patient version, for confirmation of the diagnosis of MDD. There were 815 in the primary care clinic that were approached, of which 503 patients (62% female, mean age 50 +/- 17 years) filled out the CBDI in the initial phase of depression screening. Extrapolating the results from the SCID-P interviews, the prevalence of MDD among Asian-Americans in the primary care setting was estimated to be 19.6% +/- 0.06. MDD is common among Asian-Americans in primary care settings. The prevalence of MDD is comparable to or higher than those found in the U.S. nonminority populations. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. S Cover Community Hlth Ctr, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. EM ayeung@partners.org FU NIMH NIH HHS [5T32MH19126-10] NR 32 TC 28 Z9 29 U1 5 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2004 VL 26 IS 1 BP 24 EP 30 DI 10.1016/j.genhosppsych.2003.08.006 PG 7 WC Psychiatry SC Psychiatry GA 772AW UT WOS:000188819000006 PM 14757299 ER PT S AU Solban, N Georgakoudi, I Ortel, B Lin, C Hasan, T AF Solban, N Georgakoudi, I Ortel, B Lin, C Hasan, T BE Brovko, AP Bornhop, DJ Raghavachari, R Achilefu, SI TI Optical imaging in photodynamic therapy: mechanisms and applications SO GENETICALLY ENGINEERED AND OPTICAL PROBES FOR BIOMEDICAL APPLICATIONS II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Genetically Engineered and Optical Probes for Biomedical Applications II CY JAN 24-27, 2004 CL San Jose, CA SP SPIE DE photodynamic therapy; optical imaging; photo-immunotargeted therapies; treatment monitoring ID GROWTH-FACTOR RECEPTOR; 5-AMINOLEVULINIC ACID; SELECTIVE PHOTOSENSITIZATION; FLUORESCENCE DETECTION; MURINE SARCOMAS; CHLORIN E(6); IN-VIVO; CANCER; CELLS; BENZOPHENOTHIAZINE AB Molecular excitation of photosensitizing agents provides reactive excited states, which can initiate chemical reactions, but it can also lead to molecular relaxation via radiative photophysical processes, providing the basis for fluorescence diagnostics. The best-known example of the former is Photodynamic Therapy (PDT), which is now approved for the treatment of a number of neoplastic and non-neoplastic pathologies. Although the concept of the use of photodynamic agents in diagnostics is as old as their use in therapy, the focused development of this aspect has been relatively recent. Typically, photodynamic agents have high triplet yields and relatively long triplet lifetimes (microsecond range), which allows them to interact and destroy molecular targets near them either directly or indirectly by producing other toxic molecular species. Associated with a high triplet yield is the fortunate attribute of most PDT agents in having low but finite fluorescence quantum yields. Fluorescence from these molecules may be used not only for diagnostics of disease de novo but also for guided surgery, PDT dosimetry and therapeutic monitoring. Other uses of fluorescence in PDT (not necessarily from the PDT agents) include the development of technologies that allow tracking of cells during treatment in vivo, studies of sub-cellular localization of molecules for mechanistic studies and photosensitizer tracking for specific targeting. An overview of studies on these aspects from different laboratories will be presented. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Solban, N (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5237-8 J9 P SOC PHOTO-OPT INS PY 2004 VL 5329 BP 192 EP 200 DI 10.1117/12.533177 PG 9 WC Biochemical Research Methods; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BAL96 UT WOS:000222771800023 ER PT J AU Cai, L Huang, HY Blackshaw, S Liu, JS Cepko, C Wong, WH AF Cai, L Huang, HY Blackshaw, S Liu, JS Cepko, C Wong, WH TI Clustering analysis of SAGE data using a Poisson approach SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; SERIAL ANALYSIS; PATTERNS; CANCER; ARRAYS AB Serial analysis of gene expression ( SAGE) data have been poorly exploited by clustering analysis owing to the lack of appropriate statistical methods that consider their specific properties. We modeled SAGE data by Poisson statistics and developed two Poisson-based distances. Their application to simulated and experimental mouse retina data show that the Poisson-based distances are more appropriate and reliable for analyzing SAGE data compared to other commonly used distances or similarity measures such as Pearson correlation or Euclidean distance. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Res Comp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Ctr Sci, Dept Stat, Cambridge, MA 02138 USA. RP Wong, WH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM wwong@stat.harvard.edu FU NCI NIH HHS [P20 CA96470, P20 CA096470]; NEI NIH HHS [EY08064, R01 EY008064]; NHGRI NIH HHS [R01 HG002518, R01 HG02518-01] NR 26 TC 48 Z9 51 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 7 AR R51 DI 10.1186/gb-2004-5-7-r51 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 834RX UT WOS:000222429500016 PM 15239836 ER PT J AU Gentleman, RC Carey, VJ Bates, DM Bolstad, B Dettling, M Dudoit, S Ellis, B Gautier, L Ge, YC Gentry, J Hornik, K Hothorn, T Huber, W Iacus, S Irizarry, R Leisch, F Li, C Maechler, M Rossini, AJ Sawitzki, G Smith, C Smyth, G Tierney, L Yang, JYH Zhang, JH AF Gentleman, RC Carey, VJ Bates, DM Bolstad, B Dettling, M Dudoit, S Ellis, B Gautier, L Ge, YC Gentry, J Hornik, K Hothorn, T Huber, W Iacus, S Irizarry, R Leisch, F Li, C Maechler, M Rossini, AJ Sawitzki, G Smith, C Smyth, G Tierney, L Yang, JYH Zhang, JH TI Bioconductor: open software development for computational biology and bioinformatics SO GENOME BIOLOGY LA English DT Article AB The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. Univ Calif Berkeley, Div Biostat, Berkeley, CA 94720 USA. ETH Zentrum, Seminar Stat LEO C16, CH-8092 Zurich, Switzerland. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA. Vienna Tech Univ, Inst Stat & Wahrscheinlichkeitstheorie, A-1040 Vienna, Austria. Univ Erlangen Nurnberg, Inst Med Informat Biometrie & Epidemiol, D-91054 Erlangen, Germany. Deutsch Krebsforschungszentrum, Div Mol Genome Anal, D-69120 Heidelberg, Germany. Univ Milan, Dept Econ, I-20123 Milan, Italy. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Univ Washington, Dept Med Educ & Biomed Informat, Seattle, WA 98195 USA. Inst Angew Math, Stat Lab, D-69120 Heidelberg, Germany. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Genet & Bioinformat, Parkville, Vic 3050, Australia. Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA. Univ Calif San Francisco, Ctr Bioinformat & Mol Biostat, San Francisco, CA 94143 USA. RP Gentleman, RC (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. EM rgentlem@jimmy.harvard.edu RI iacus, stefano maria/F-1150-2011; Hothorn, Torsten/A-3639-2010; Smith, Colin/E-5713-2012; Gautier, Laurent/F-9849-2012; Leisch, Friedrich/A-6977-2013; Smyth, Gordon/B-5276-2008; Yang, Jean /D-2920-2015 OI Hothorn, Torsten/0000-0001-8301-0471; Smith, Colin/0000-0002-4651-167X; Leisch, Friedrich/0000-0001-7278-1983; Smyth, Gordon/0000-0001-9221-2892; Yang, Jean /0000-0002-5271-2603 NR 26 TC 6154 Z9 6217 U1 21 U2 240 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 10 AR R80 DI 10.1186/gb-2004-5-10-r80 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 859DS UT WOS:000224243400013 PM 15461798 ER PT J AU Nairz, K Zipperlen, P Dearolf, C Basler, K Hafen, E AF Nairz, K Zipperlen, P Dearolf, C Basler, K Hafen, E TI A reverse genetic screen in Drosophila using a deletion-inducing mutagen SO GENOME BIOLOGY LA English DT Article ID DISRUPTION PROJECT; INDUCED MUTATIONS; RNA-INTERFERENCE; MELANOGASTER; HEXAMETHYLPHOSPHORAMIDE; CELLS; ZEBRAFISH; RESOURCE; PIGGYBAC AB We report the use of the cross-linking drug hexamethylphosphoramide ( HMPA), which introduces small deletions, as a mutagen suitable for reverse genetics in the model organism Drosophila melanogaster. A compatible mutation-detection method based on resolution of PCR fragment-length polymorphisms on standard DNA sequencers is implemented. As the spectrum of HMPA-induced mutations is similar in a variety of organisms, it should be possible to transfer this mutagenesis and detection procedure to other model systems. C1 Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nairz, K (reprint author), Univ Zurich, Inst Zool, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM nairz@zool.unizh.ch NR 32 TC 4 Z9 4 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 10 AR R83 DI 10.1186/gb-2004-5-10-r83 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 859DS UT WOS:000224243400016 PM 15461801 ER PT J AU Lafayette, JM Stern, TA AF Lafayette, JM Stern, TA TI The impact of a patient's suicide on psychiatric trainees: A case study and review of the literature SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE psychiatry; resident; suicide; training ID COMMITS SUICIDE; TRAINING-CENTER; INPATIENT UNIT; THERAPISTS; RESIDENCY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lafayette, JM (reprint author), Massachusetts Gen Hosp, Warren 605,33 Fruit St, Boston, MA 02114 USA. EM jlafayette@partners.org NR 27 TC 9 Z9 10 U1 4 U2 5 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 2004 VL 12 IS 1 BP 49 EP 55 DI 10.1080/10673220490279152 PG 7 WC Psychiatry SC Psychiatry GA 801GT UT WOS:000220085100004 PM 14965854 ER PT J AU Scully, C Epstein, J Sonis, S AF Scully, C Epstein, J Sonis, S TI Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: Diagnosis and management of mucositis SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE cancer; chemotherapy; mucositis; oral; radiotherapy ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; REMISSION-INDUCTION THERAPY; NECK-CANCER PATIENTS; DOUBLE-BLIND TRIAL; QUALITY-OF-LIFE; SUCRALFATE SUSPENSION; RADIATION-THERAPY; IMMUNOCOMPROMISED PATIENTS; HEMATOLOGIC MALIGNANCIES AB Background. Oral mucositis is a common sequel of radiotherapy, chemotherapy, and radiochemotherapy in patients with cancer or patients requiring hemopoietic stem cell transplants. Mucositis has a direct and significant impact on the duration of disease remission and cure rates, because it is a treatment-limiting toxicity. Mucositis also affects survival because of the risk of infection and has a significant impact on quality of life and cost of care. Methods. This article reviews publications on the diagnosis and management of oral mucositis accessible from a MEDLINE search using as key words mucositis, radiotherapy, chemotherapy, hemopoietic stem, cell transplant, and oral. Conclusions. Conventional care of patients with mucositis is currently essentially palliative, with good oral hygiene, narcotic analgesics, and topical palliative mouth rinses. (C) 2004 Wiley Periodicals, Inc. C1 UCL, Int Ctr Excellence Dent, World Hlth Org Collaborating Ctr Oral Hlth Disabi, London WC1X 8LD, England. UCL, Eastman Dent Inst Oral Hlth Care Sci, World Hlth Org Collaborating Ctr Oral Hlth Disabi, London WC1X 8LD, England. Univ Illinois, Dept Oral Med & Diagnost Sci, Coll Dent, Coll Med,Chicago Canc Ctr, Chicago, IL USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Brigham & Womens Hosp,Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Brigham & Womens Hosp,Div Oral & Maxillofacial Su, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Brigham & Womens Hosp,Div Dent, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Scully, C (reprint author), UCL, Int Ctr Excellence Dent, World Hlth Org Collaborating Ctr Oral Hlth Disabi, 256 Grays Inn Rd, London WC1X 8LD, England. EM c.scully@eastman.ucl.ac.uk NR 89 TC 65 Z9 72 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JAN PY 2004 VL 26 IS 1 BP 77 EP 84 DI 10.1002/hed.10326 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 758AP UT WOS:000187610600012 PM 14724910 ER PT J AU Landon, BE Reschovsky, JD Blumenthal, D AF Landon, BE Reschovsky, JD Blumenthal, D TI Physicians' views of formularies: Implications for Medicare drug benefit design SO HEALTH AFFAIRS LA English DT Article AB As Congress considers introducing a drug benefit for Medicare, it will more than likely adopt a program that uses a formulary. We examined data from the Community Tracking Study Physicians Survey, a large, nationally representative study of physicians, to learn about physicians' views of formularies. Our results suggest that several aspects of formularies are associated with physicians' positive views about them. Policymakers should consider imposing limits on the number of competing Medicare formularies operating in a particular area, promoting the adoption and use of information technology, and incorporating financial incentives for physicians to adhere to formularies. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Washington, DC USA. Ctr Studying Hlth Syst Change, Washington, DC USA. Inst Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Partners HealthCare Syst, Boston, MA 02114 USA. RP Landon, BE (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. FU AHRQ HHS [P01-1-HS-10803] NR 16 TC 10 Z9 10 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN-FEB PY 2004 VL 23 IS 1 BP 218 EP 226 DI 10.1377/hlthaff.23.1.218 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 761KH UT WOS:000187907600028 PM 15002646 ER PT J AU Furst, M Bresloff, I Levine, RA Merlob, PL Attias, JJ AF Furst, M Bresloff, I Levine, RA Merlob, PL Attias, JJ TI Interaural time coincidence detectors are present at birth: evidence from binaural interaction SO HEARING RESEARCH LA English DT Article DE binaural interaction; interaural time delay; neonate; binaural difference ID AUDITORY BRAIN-STEM; EVOKED-POTENTIALS; INTERACTION COMPONENT; CLICK LATERALIZATION; SOUND LOCALIZATION; HEARING-LOSS; INFANTS; FREQUENCY; LATENCY; CAT AB Binaural processing of sounds in mammals is presumably initiated within the auditory nuclei of the caudal pons. The binaural difference waveform (BD) can be derived from the sum of the waveforms evoked by right monaural clicks plus left monaural clicks minus the waveform evoked by binaural clicks. In adults, the BD's first positive peak (beta) is large only for stimuli with interaural time differences (ITDs) that produce a fused acoustic percept. Humans at birth can localize and discriminate sound sources, but their head circumference is about two-thirds of an adult head. In order to test whether beta is related to head circumference, we recorded beta in human neonates as a function of ITD. Binaural clicks with ITDs ranging between 0 and 1000 mus were used to derive BD waveforms in 34 neonates. For ITD=0, beta was detectable in 56% of newborns. The incidence of beta detection then decreased as ITD increased. Only 9% of the babies had detectable beta for all ITDs. No correlation was found between the existence of beta and other properties of the monaural or binaural auditory brainstem response. The finding that for some infants beta was present for all ITDs up to 1.0 ms suggests that there is no recalibration of brainstem delay lines with head growth. Our data suggest that the brainstem auditory pathway for detecting interaural time differences in the adult is probably present at birth. Maturational factors such as increased myelination and greater firing synchrony probably improve the detectability of beta with age. The second peak in the BD waveform. (delta) was highly correlated with the existence of wave VI in the binaural and monaural waveforms. (C) 2003 Elsevier B.V. All rights reserved. C1 Tel Aviv Univ, Fac Engn, Dept Elect Engn Syst, IL-69978 Tel Aviv, Israel. Schneider Childrens Hosp, Rabin Med Ctr, Petah Tiqwa, Israel. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Haifa, Dept Commun Disorders, IL-31999 Haifa, Israel. RP Furst, M (reprint author), Tel Aviv Univ, Fac Engn, Dept Elect Engn Syst, IL-69978 Tel Aviv, Israel. EM mira@eng.tau.ac.il NR 42 TC 14 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JAN PY 2004 VL 187 IS 1-2 BP 63 EP 72 DI 10.1016/S0378-5955(03)00331-9 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 762KR UT WOS:000187971300007 PM 14698088 ER PT J AU Whittemore, KR Merchant, SN Poon, BB Rosowski, JJ AF Whittemore, KR Merchant, SN Poon, BB Rosowski, JJ TI A normative study of tympanic membrane motion in humans using a laser Doppler vibrometer (LDV) SO HEARING RESEARCH LA English DT Article DE middle-ear function; Tympanic membrane velocity; clinical evaluation of hearing function ID HUMAN MIDDLE-EAR; TIME-AVERAGED HOLOGRAPHY; CONDUCTIVE HEARING-LOSS; MONGOLIAN GERBIL; STATIC PRESSURE; VIBRATIONS; MECHANICS; TYMPANOPLASTY; TRANSMISSION; TYMPANOMETRY AB Laser Doppler vibrometry was used to measure the sound-induced tympanic membrane (TM) velocity, assessed near the umbo, in 56 normal hearing human subjects at nine sound frequencies. A second series of measurements was made in 47 subjects with sensorineural hearing loss (SNHL). Each set of measurements has features in common with previously published results. The measured velocity magnitude (normalized by the stimulus sound pressure) at any one frequency ranged among subjects by factors of 3-0.3 (+/-10 dB) from the mean and the phase angle of the normalized velocity ranged from 15degrees around the mean at low frequencies to more than +/-200degrees around the mean at 6 kHz. Measurements repeated after intervals of minutes to months were generally within 40% in magnitude (+/-3 dB) and 20degrees in phase. Sources of variability included the effect of small differences in the location of the measurement on the TM and small static middle-ear pressures. No effects of stimulus level, ear sidedness (right or left), gender, age or the presence or absence of SNHL were found. These results provide a baseline normal response for studies of TM velocity with conductive hearing losses of different etiologies. (C) 2003 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM jjr@epl.meei.harvard.edu FU NIDCD NIH HHS [T32DC00038, R01DC04798] NR 55 TC 66 Z9 68 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JAN PY 2004 VL 187 IS 1-2 BP 85 EP 104 DI 10.1016/S0378-5955(03)00332-0 PG 20 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 762KR UT WOS:000187971300009 PM 14698090 ER PT J AU Catley, L Anderson, K AF Catley, L Anderson, K TI Strategies to improve the outcome of stem cell transplantation in multiple myeloma SO HEMATOLOGY JOURNAL LA English DT Review DE multiple; myeloma; transplantation ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE THERAPY; COLONY-STIMULATING FACTOR; BLOOD PROGENITOR CELLS; OVERCOMES DRUG-RESISTANCE; DONOR LEUKOCYTE INFUSIONS; VERSUS-HOST DISEASE; TERM-FOLLOW-UP; PROSPECTIVE RANDOMIZED TRIAL; NEWLY-DIAGNOSED MYELOMA AB Multiple myeloma (MM) is an incurable hematological malignancy with an average survival of 3 years with conventional therapy. Allogeneic hematopoietic cell transplantation (allo-HCT) may cure some patients, but has been associated with a very high transplantation-related mortality (TRM) of over 40%.(1) In contrast to allo-HCT, autologous hematopoietic cell transplantation (AHCT) has been much safer, with a TRM <3% in the 1990s. Therefore, in the last 15 years AHCT has become a common procedure for MM patients. The widespread use of AHCT has been associated with a median survival of 55-72 months,(2-6) and two large randomized trials have shown that AHCT is superior to conventional chemotherapy for the treatment of MM.(1,7) Approaches to improve the outcome of stem cell transplantation for MM patients include consideration of patient status, efficacy and toxicity of induction therapy, source of hematopoietic rescue, conditioning regimens, and maintenance therapy. Recent attempts to improve outcome include tandem AHCT, AHCT followed by RIC (reduced intensity conditioning) allo-HCT, and allo-HCT with T-cell depletion and subsequent donor-lymphocyte infusions (DLI), while novel therapies and improved supportive care may improve the overall survival (OS) of all MM patients with or without transplantation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 NR 190 TC 10 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4860 J9 HEMATOL J JI Hematol. J. PY 2004 VL 5 IS 1 BP 9 EP 23 DI 10.1038/sj.thj.6200322 PG 15 WC Hematology SC Hematology GA 902LH UT WOS:000227358100002 PM 14745425 ER PT J AU Griffin, JD AF Griffin, JD TI FLT3 tyrosine kinase as a target in acute leukemias SO HEMATOLOGY JOURNAL LA English DT Article; Proceedings Paper CT 9th Annual Congress of the European-Hematology-Association CY JUN 10-13, 2004 CL Geneva, SWITZERLAND SP European Hematol Assoc ID ACUTE MYELOID-LEUKEMIA; RELAPSE; MUTATIONS; SAMPLES; GENE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4860 J9 HEMATOL J JI Hematol. J. PY 2004 VL 5 SU 3 BP S188 EP S190 DI 10.1038/sj.thj.6200450 PG 3 WC Hematology SC Hematology GA 903ND UT WOS:000227431800040 PM 15190306 ER PT J AU Giovanello, KS Schnyer, DM Verfaellie, M AF Giovanello, KS Schnyer, DM Verfaellie, M TI A critical role for the anterior hippocampus in relational memory: Evidence from an fMRI study comparing associative and item recognition SO HIPPOCAMPUS LA English DT Article DE hippocampus; relational memory; fMRI ID MEDIAL TEMPORAL-LOBE; PERIRHINAL CORTEX; RETRIEVAL AB Neuroscientific research has established that the hippocampal formation, a structure within the medial temporal lobe (MTL), plays a critical role in memory for facts and events (declarative memory) (Milner et al., 1998). However, its precise role remains unclear. According to one view, the hippocampus has a special role in relating or binding together previously unrelated pieces of information, while another view proposes that the hippocampus is equally involved in all forms of declarative memory, regardless of their demands on relational processing. Using functional magnetic resonance imaging (fMRI), we show that hippocampal activation is modulated by the extent to which a retrieval task depends on relational processing. (C) 2003 Wiley-Liss, Inc. C1 Boston VA Healthcare Syst 151A, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Massachusetts Inst Technol, Boston, MA 02115 USA. RP Giovanello, KS (reprint author), Boston VA Healthcare Syst 151A, Memory Disorders Res Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM ksull@bu.edu FU NIMH NIH HHS [MH57681, MH64004]; NINDS NIH HHS [NS26985] NR 16 TC 157 Z9 160 U1 1 U2 20 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 1 BP 5 EP 8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 780EZ UT WOS:000189360500003 PM 15058477 ER PT J AU Heckers, S Zalesak, M Weiss, AP Ditman, T Titone, D AF Heckers, S Zalesak, M Weiss, AP Ditman, T Titone, D TI Hippocampal activation during transitive inference in humans SO HIPPOCAMPUS LA English DT Article DE neuroimaging; fMRI; relational memory; parahippocampal gyrus ID MEDIAL TEMPORAL-LOBE; RECOGNITION MEMORY; PERIRHINAL CORTEX; SYSTEM; ASSOCIATIONS; REGION; RATS; SEQUENCES; ROLES AB Studies in rodents have demonstrated that the integration and flexible expression of memories, necessary for transitive inference, depend on an intact hippocampus. To test this hypothesis in humans, we studied brain activation during the discrimination of a series of overlapping and non-overlapping arbitrary visual stimulus pairs. We report that transitive inference about overlapping pairs is associated with right anterior hippocampal activation, whereas recognition of non-overlapping stimulus pairs is associated with bilateral medial temporal lobe activation centered in the anterior parahippocampal gyrus. We conclude that immediate access to simple stimulus-stimulus relationships is mediated via the parahippocampal gyrus, whereas the flexible representation of memory requires the recruitment of the hippocampus. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. McGill Univ, Dept Psychol, Montreal, PQ, Canada. RP Heckers, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, East CNY-9112,Bldg 149,13th St, Charlestown, MA 02129 USA. EM heckers@psych.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [MH01763-01, MH60272] NR 46 TC 145 Z9 148 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 2 BP 153 EP 162 DI 10.1002/hipo.10189 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 805TF UT WOS:000220387900004 PM 15098721 ER PT J AU Shin, LM Shin, PS Heckers, S Krangel, TS Macklin, ML Orr, SP Lasko, N Segal, E Makris, N Richert, K Levering, J Schacter, DL Alpert, NM Fischman, AJ Pitman, RK Rauch, SL AF Shin, LM Shin, PS Heckers, S Krangel, TS Macklin, ML Orr, SP Lasko, N Segal, E Makris, N Richert, K Levering, J Schacter, DL Alpert, NM Fischman, AJ Pitman, RK Rauch, SL TI Hippocampal function in posttraumatic stress disorder SO HIPPOCAMPUS LA English DT Article DE hippocampus; PET; memory; limbic; PTSD ID CHILDHOOD SEXUAL-ABUSE; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; MAJOR DEPRESSION; COMBAT VETERANS; WHITE-MATTER; CONSCIOUS RECOLLECTION; GERIATRIC DEPRESSION; PYRAMIDAL NEURONS; VOLUME REDUCTION AB Recent studies have reported memory deficits and reduced hippocampal volumes in posttraumatic stress disorder (PTSD). The goal of the current research was to use functional neuroimaging and a validated explicit memory paradigm to examine hippocampal function in PTSD. We used positron emission tomography (PET) and a word-stem completion task to study regional cerebral blood flow (rCBF) in the hippocampus in 16 firefighters: 8 with PTSD (PTSD group) and 8 without PTSD (Control group). During PET scanning, participants viewed three-letter word stems on a computer screen and completed each stem with a word they had previously encoded either deeply (High Recall condition) or shallowly (Low Recall condition). Relative to the Control group, the PTSD group exhibited significantly smaller rCBF increases in the left hippocampus in the High vs Low Recall comparison. However, this finding reflected relatively elevated rCBF in the Low Recall condition in the PTSD group. Collapsing across High and Low Recall conditions, (1) the PTSD group had higher rCBF in bilateral hippocampus and left amygdala than the Control group, and (2) within the PTSD group, symptom severity was positively associated with rCBF in hippocampus and parahippocampal gyrus. The groups did not significantly differ with regard to accuracy scores on the word-stem completion task. The PTSD group had significantly smaller right (and a trend for smaller left) hippocampal volumes than the Control group. The results suggest an abnormal rCBF response in the hippocampus during explicit recollection of nonemotional material in firefighters with PTSD, and that this abnormal response appears to be driven by relatively elevated hippocampal rCBF in the comparison condition. Published 2004 Wiley-Liss, Inc. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Harvard Univ, Dept Philosophy, Cambridge, MA 02138 USA. VA Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM lisa.shin@tufts.edu RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH60219, MH57915, MH60941] NR 86 TC 151 Z9 158 U1 6 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 3 BP 292 EP 300 DI 10.1002/hipo.10183 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 813EE UT WOS:000220889600003 PM 15132428 ER PT J AU Purcell, S Sham, P AF Purcell, S Sham, P TI Properties of structured association approaches to detecting population stratification SO HUMAN HEREDITY LA English DT Article DE population stratification; lateral class analysis; structured association; genomic control; linkage disequilibrium ID GENETIC ASSOCIATION; GENOMIC CONTROL; MODEL AB Objective: To examine the properties of the structured association approach for the detection and correction of population stratification. Method: A method is developed, within a latent class analysis framework, similar to the methods proposed by Satten et al. (2001) and Pritchard et al. (2000). A series of simulations illustrate the relative impact of number and type of loci, sample size and population structure. Results: The ability to detect stratification and assign individuals to population strata is determined for a number of different scenarios. Conclusion: The results underline the importance of careful marker selection. Copyright (C) 2004 S. Karger AG, Basel. C1 Whitehead Inst, Cambridge, MA 02142 USA. Univ London Kings Coll, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London WC2R 2LS, England. Univ Hong Kong, Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Fac Med, Genome Res Ctr, Hong Kong, Hong Kong, Peoples R China. RP Purcell, S (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 149 13th St,Floor 10, Charlestown, MA 02129 USA. EM spurcell@pngu.mgh.harvard.edu NR 22 TC 33 Z9 35 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2004 VL 58 IS 2 BP 93 EP 107 DI 10.1159/000083030 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 897BR UT WOS:000226979500005 PM 15711089 ER PT J AU Faraone, SV Su, J Taylor, L Wilcox, M AF Faraone, SV Su, J Taylor, L Wilcox, M TI A novel permutation testing method implicates sixteen nicotinic acetylcholine receptor genes as risk factors for smoking in schizophrenia families SO HUMAN HEREDITY LA English DT Article DE acetylcholine; linkage; nicotinic receptor; linkage; genetics; permutation testing; candidate genes ID GENOME-WIDE SEARCH; ALPHA-BUNGAROTOXIN RECEPTORS; LINKAGE ANALYSIS; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; CHROMOSOME 15Q13-14; SUGGESTIVE EVIDENCE; MILLENNIUM CONSORTIUM; DIAGNOSTIC INTERVIEW; THYMIC POLYPEPTIDE AB Smoking is a common correlate of schizophrenia, which leads to medical morbidity. Although twin and adoption studies have consistently implicated genes in the etiology of both smoking and schizophrenia, finding genes has been difficult. Several authors have suggested that clinical or neurobiological features associated with schizophrenia, such as smoking, might improve the ability to detect schizophrenia susceptibility genes by identifying genes related to the etiology of that feature. The objective of this study is to assess evidence for linkage of sixteen nicotinic acetylcholine receptor genes and smoking in schizophrenia families, using data from the NIMH Genetics Initiative for schizophrenia. Sixteen nicotinic acetylcholine receptor genes were selected prior to analysis. We used a multipoint sibling pair linkage analysis program, SIBPAL2, with a smoking trait in schizophrenia families. The significance of the group of candidate genes, in addition to each individual candidate gene, was assessed using permutation testing, which adjusted for multiple comparisons. The group of genes showed significant linkage to the smoking trait after adjusting for multiple comparisons through permutation testing (p = 0.039). In addition, two of the individual candidate genes were significant (CHRNA2, p = 0.044) and (CHRNB2, p = 0.015) and two genes were marginally significant (CHRNA7, p = 0.095; CHRNA1, p = 0.076). The significance of the complex hypothesis, involving sixteen genes, implicates the nicotinic system in smoking for schizophrenic families. Individual gene analysis suggests that CHRNA2 and CHRNB2 may play a particular role in this involvement. Such findings help prioritize genes for future case control studies. In addition, we provide a novel permutation method that is useful in future analyses involving a single hypothesis, with multiple candidate genes. Copyright (C) 2004 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Genom Therapeut Corp, Waltham, MA USA. RP Faraone, SV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 37 Shields Ave, Brockton, MA 02301 USA. EM sfaraone@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [U01 MH 46289, 1R37 MH 43518, 5U01 MH 46318, R01 MH 41874-01, R01 MH 44292, R01 MH 59624, R01 MH 60485, R01 MH43518, R25 MH 60485, U01 MH 46276] NR 88 TC 39 Z9 40 U1 3 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2004 VL 57 IS 2 BP 59 EP 68 DI 10.1159/000077543 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 827ZA UT WOS:000221941000001 PM 15192278 ER PT J AU Chen, DF Dong, LS Howard, A Rabson, A Fraser, P AF Chen, DF Dong, LS Howard, A Rabson, A Fraser, P TI Novel HLA-B alleles revealed by SSOP and identified by single-allele sequencing SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Natl Marrow Donor Program, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S85 EP S85 DI 10.1016/j.humimm.2004.07.160 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300163 ER PT J AU Frahm, N Yusim, K Hraber, P Adams, S Marincola, F Korber, B Brander, C AF Frahm, N Yusim, K Hraber, P Adams, S Marincola, F Korber, B Brander, C TI Extensive HLA class I binding promiscuity among EBV- and HIV-derived cytotoxic T lymphocyte epitopes SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S2 EP S2 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300004 ER PT J AU Tocco, G Yoshinobu, A Tanaka, T Patel, R Iwamoto, Y Benichou, G AF Tocco, G Yoshinobu, A Tanaka, T Patel, R Iwamoto, Y Benichou, G TI Reactive oxygen species synthetic catalytic scavengers for prevention of allograft rejection SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S56 EP S56 DI 10.1016/j.humimm.2004.07.104 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300107 ER EF