FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yigitbas, E Uner, A Dorak, MT Ding, WZ Tatayoglu, G Balci, B Duzova, A Ozaltin, F Ozen, S Besbas, N Topaloglu, R Yilmaz, E Bakkaloglu, A Ozguc, M Kansu, E Fraser, PA AF Yigitbas, E Uner, A Dorak, MT Ding, WZ Tatayoglu, G Balci, B Duzova, A Ozaltin, F Ozen, S Besbas, N Topaloglu, R Yilmaz, E Bakkaloglu, A Ozguc, M Kansu, E Fraser, PA TI MICA exon 5 microsatellite alleles in Turkish patients with FMF 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 USA. Hacettepe Univ, Inst Oncol, Ankara, Turkey. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RI Uner, Aysegul /A-9028-2011 OI Uner, Aysegul /0000-0002-2522-1606 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 S105 EP S105 DI 10.1016/j.humimm.2004.07.200 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300203 ER PT J AU Makrigiorgos, GM AF Makrigiorgos, GM TI PCR-based detection of minority point mutations SO HUMAN MUTATION LA English DT Review DE mutation detection; mutation scanning; PCR; minority mutations; ligation-mediated PCR; hairpin-PCR; ATM; Ku80; XRCC5; TP53; SNP ID SINGLE NUCLEOTIDE POLYMORPHISMS; ENZYME MISMATCH CLEAVAGE; LIGATION-MEDIATED PCR; DNA POOLS; LINKAGE DISEQUILIBRIUM; QUANTITATIVE DETECTION; GENOTYPIC SELECTION; ESCHERICHIA-COLI; GENOMIC DNA; AMPLIFICATION AB The need for detection of minority mutations (i.e., a few mutants within a high excess of wild-type alleles) arises frequently in the field of cancer and molecular genetics. Current mutation detection technologies are limited by several technical factors when it comes to the detection of minority point mutations, including generation of misincorporations by the DNA polymerase during PCR amplification. Primer ligation-mediated PCR methodologies for detection Of mutations in an excess wild-type sequences are described, that can be applied for detection of both known and unknown minority point mutations. Furthermore, a new methodology is described, hairpin-PCR, which has the potential to completely eliminate PCR errors from amplified sequences, prior to minority mutation detection. Combination of these technologies can effectively tackle the problem of minority mutation detection, in order to pursue demanding applications such as identification of cancer cells at an early stage, detection of mutations in single cells, identification of minimal residual disease, or investigation of mechanisms of spontaneous mutagenesis. (C) 2004 Wiley Liss, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org NR 46 TC 13 Z9 15 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 23 IS 5 BP 406 EP 412 DI 10.1002/humu.20024 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 816OP UT WOS:000221119500001 ER PT S AU Solo, V Long, CJ Brown, EN Aminoff, E Bar, M Saha, S AF Solo, V Long, CJ Brown, EN Aminoff, E Bar, M Saha, S GP IEEE TI FMRI signal modeling using Laguerre polynomials SO ICIP: 2004 INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, VOLS 1- 5 SE IEEE International Conference on Image Processing (ICIP) LA English DT Proceedings Paper CT International Conference on Image Processing (ICIP 2004) CY OCT 24-27, 2004 CL Singapore, SINGAPORE SP 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 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. This is not the case in FIR modeling, because a low FIR order is unable to cover the whole length of the HR over its region of support while a high FIR order results in overestimation of signal and underestimation of noise leading to misleading interpretations. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Solo, V (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. OI Aminoff, Elissa/0000-0002-6455-8930 NR 8 TC 2 Z9 2 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-4880 BN 0-7803-8554-3 J9 IEEE IMAGE PROC PY 2004 BP 2431 EP 2434 PG 4 WC Computer Science, Software Engineering; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BBV71 UT WOS:000228043503075 ER PT J AU Yun, SH Boudoux, C Pierce, MC de Boer, JF Tearney, GJ Bouma, BE AF Yun, SH Boudoux, C Pierce, MC de Boer, JF Tearney, GJ Bouma, BE TI Extended-cavity semiconductor wavelength-swept laser for biomedical imaging SO IEEE PHOTONICS TECHNOLOGY LETTERS LA English DT Article DE optical coherence tomography (OCT) semiconductor lasers; tunable lasers ID OPTICAL COHERENCE TOMOGRAPHY; ACOUSTOOPTIC TUNABLE FILTER; FIBER LASER; REFLECTOMETRY AB We demonstrate a compact high-power rapidly swept wavelength tunable laser source based on a semiconductor optical amplifier and an extended-cavity grating filter. The laser produces excellent output characteristics for biomedical imaging, exhibiting >4-mW average output power, <0.06-nm instantaneous linewidth, and >80-dB noise extinction with its center wavelength swept over 100 nm at 1310 nm at variable repetition rates up to 500 Hz. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. MIT, Dept Nucl Engn, Wellman Labs Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM syun@bics.bwh.harvard.edu RI Boudoux, Caroline/A-6399-2012; de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769, R01 CA103769-02] NR 12 TC 50 Z9 53 U1 0 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1041-1135 J9 IEEE PHOTONIC TECH L JI IEEE Photonics Technol. Lett. PD JAN PY 2004 VL 16 IS 1 BP 293 EP 295 DI 10.1109/LPT.2003.820096 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 761DX UT WOS:000187885800098 PM 20640193 ER PT J AU Ancuta, P Moses, A Gabuzda, D AF Ancuta, P Moses, A Gabuzda, D TI Transendothelial migration of CD16(+) monocytes in response to fractalkine under constitutive and inflammatory conditions SO IMMUNOBIOLOGY LA English DT Article DE monocytes; dendritic cells; siglecs ID IMMUNODEFICIENCY-VIRUS-INFECTION; MICROVASCULAR ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; BLOOD MONOCYTES; TNF-ALPHA; HIV-INFECTION; IFN-GAMMA; TISSUE MACROPHAGES; ADHESION MOLECULE; IN-VITRO AB CD16(+) monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16(+) monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16(+) monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16(+) monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16(-) and CD16(+) monocyte subsets adhered to TNF/IFN-gamma-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16(-) monocytes across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16(+) monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16(+) monocytes in response to soluble FKN. Thus, pro-inflammatory CD16(-) monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules. (C) 2004 Elsevier GmbH. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 816, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI2869]; NIDA NIH HHS [DA0165495] NR 48 TC 59 Z9 63 U1 1 U2 6 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PY 2004 VL 209 IS 1-2 BP 11 EP 20 DI 10.1016/j.imbio.2004.04.001 PG 10 WC Immunology SC Immunology GA 857EB UT WOS:000224097900003 PM 15481136 ER PT J AU Re, F Strominger, JL AF Re, F Strominger, JL TI Heterogeneity of TLR-induced responses in dendritic cells: from innate to adaptive immunity SO IMMUNOBIOLOGY LA English DT Review DE dendritic cells; toll-like receptors ID TOLL-LIKE RECEPTOR-2; HUMAN MAST-CELLS; SIGNALING PATHWAY; CUTTING EDGE; IN-VITRO; GENE-EXPRESSION; IFN-BETA; T-CELLS; B-CELLS; INTERLEUKIN-12 AB Toll-like receptors (TLR) mediate recognition of several microbial products. Accumulating evidence indicates that TLR are capable of inducing distinct responses in dendritic cells and other antigen-presenting cells, and can direct T-helper cell differentiation in opposing directions. The generation of such varied responses is achieved through the selective utilization of adaptor molecules that link TLR to distinct signal transduction pathways. The ability of TLR to activate and guide innate and adaptive immunity has the potential to be exploited for practical application that may lead to the development of more successful immunotherapies and vaccination strategies. A review of recent literature, unpublished observations, and future challenges is presented here. (C) 2004 Elsevier GmbH. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Re, F (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. EM fre@utmem.edu FU NIAID NIH HHS [AI-05466501, AI-4952402] NR 50 TC 39 Z9 43 U1 1 U2 3 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PY 2004 VL 209 IS 1-2 BP 191 EP 198 DI 10.1016/j.imbio.2004.03.005 PG 8 WC Immunology SC Immunology GA 857EB UT WOS:000224097900020 PM 15481153 ER PT B AU Bellucci, R Wu, CJ Chiaretti, S Alyea, EP Munshi, NC Ritz, J AF Bellucci, R Wu, CJ Chiaretti, S Alyea, EP Munshi, NC Ritz, J GP MEDIMOND TI Antibody response to BCMA in patients with multiple myeloma SO IMMUNOLOGY 2004: AUTOIMMUNITY, GENETIC AND DEGENERATIVE DISORDERS, MALIGNANCIES, AND TRANSPLANTATION LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID DONOR LYMPHOCYTE INFUSION; STEM-CELL TRANSPLANTATION; SURVIVAL; BAFF AB To identify target antigens associated with tumor response after donor lymphocyte infusion (DLI) in patients with multiple myeloma (MM) we screened an MM cDNA expression library with serum from MM patients who had a complete response after DLI. One of the antigens identified in the screening was BCMA a membrane receptor of the TNF superfamily selectively expressed by plasma cells. Two of 9 MM DLI responders were found to have an antibody response against BCMA. In testing serial samples after DLI, the antibody response appeared to be associated with the time of the response after DLI Using flow cytometry, post-DLI serum was found to specifically react with cell surface BCMA. Post-DLI serum was also able to initiate complement mediated cytotoxicity and antibody dependant cellular cytotoxicity (ADCC) of cells expressing BCMA. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bellucci, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-074-8 PY 2004 BP 355 EP 359 PG 5 WC Genetics & Heredity; Immunology; Transplantation SC Genetics & Heredity; Immunology; Transplantation GA BBQ57 UT WOS:000227161200065 ER PT B AU Shi, L Takahashi, K Dundee, J Shahroor-Karni, S Thiel, S Jensenius, JC Gad, F Hamblin, MR Sastry, KN Ezekowitz, RAB AF Shi, L Takahashi, K Dundee, J Shahroor-Karni, S Thiel, S Jensenius, JC Gad, F Hamblin, MR Sastry, KN Ezekowitz, RAB GP MEDIMOND TI Mannose-binding lectin deficient mice are susceptible to infection with Staphylococcus aureus SO IMMUNOLOGY 2004: IMMUNODEFICIENCY, INFECTIOUS DISEASES, IMMUNOMODULATION, AND VACCINES LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc AB Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity and mortality worldwide. The mannose-binding lectin (MBL) recognizes a broad range of infectious agents including S. aureus. Circumstantial evidence suggests that MBL plays a key role in first line host defense. We tested this contention in vivo by generating mice that were devoid of all MBL activity. We found that 100% of MBL-null mice died 48 h after an intravenous inoculation of S. aureus compared with 45% mortality in wildtype mice. Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus. The phenotype was reversed by reconstitution with exogenous MBL. Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and may act as a disease susceptibility gene against staphylococci infections in humans. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. RP Shi, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-075-6 PY 2004 BP 241 EP 249 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BBQ60 UT WOS:000227165600043 ER PT J AU Peden-Adams, MM Dudley, AC EuDaly, JG Allen, CT Gilkeson, GS Keil, DE AF Peden-Adams, MM Dudley, AC EuDaly, JG Allen, CT Gilkeson, GS Keil, DE TI Pyridostigmine bromide (PYR) alters immune function in B6C3F1 mice SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article DE pyridostigmine bromide; IgM antibody responses; Gulf War illness; immunotoxicity ID CELL-MEDIATED-IMMUNITY; GULF-WAR VETERANS; CONCURRENT EXPOSURE; HOST-RESISTANCE; ETHYL CARBAMATE; PERSIAN-GULF; INHIBITION; TOXICITY; EXERCISE; DEET AB Pyridostigmine bromide (PYR) is an anti cholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4+/CD8+ (20 mg/kg/day) and CD4-/CD8- (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses. C1 Med Univ S Carolina, Dept Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29425 USA. Ralph Johnson VAMC, Med Res Serv, Charleston, SC USA. NIOSH, Morgantown, WV 26505 USA. RP Peden-Adams, MM (reprint author), MUSC MBES, 221 Fort Johnson Rd, Charleston, SC 29412 USA. EM pedenada@muse.edu NR 56 TC 11 Z9 11 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 2004 VL 26 IS 1 BP 1 EP 15 DI 10.1081/IPH-120029939 PG 15 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 811SK UT WOS:000220791400001 PM 15106728 ER PT J AU Keefe, B AF Keefe, B TI Getting on our nerves: A look at group therapy interventions in inflammatory bowel disease - Comment SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Keefe, B (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2004 VL 10 IS 1 BP 64 EP 65 DI 10.1097/00054725-200401000-00013 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 758JL UT WOS:000187630900013 PM 15058532 ER PT S AU Youn, CH Kim, B Nam, DS Lee, BH Shim, EB Clifford, G Healey, J AF Youn, CH Kim, B Nam, DS Lee, BH Shim, EB Clifford, G Healey, J BE Kahng, HK Goto, S TI Resource reconfiguration scheme based on temporal quorum status estimation in computational grids SO INFORMATION NETWORKING: NETWORKING TECHNOLOGIES FOR BROADBAND AND MOBILE NETWORKS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT International Conference on Information Networking (ICOIN 2004) CY FEB 18-20, 2004 CL Busan, SOUTH KOREA SP Korea Informat Sci Soc, Informat Proc Soc Japan AB Quality of Service (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 includes a system resource and network resource, both of which can satisfy the requirements of application QoS. We also propose the resource reconfiguration algorithm based on temporal execution time estimation method. Resource reconfiguration performs the reshuffling of the current available resource set for maintaining the quality level of the resources. We evaluate the effectiveness of resource reconfiguration mechanism in a Heart Hemodynamics analysis. Our approach increases the stability of execution environment as well as decreases the completion time compared to the method that does not adopt the proposed reconfiguration scheme. C1 Harvard Univ, MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. Informat & Commun Univ, Sch Engn, Taejon 305732, South Korea. Daejeon Univ, Dept Informat & Commun Engn, Taejon 300716, South Korea. Kangwon Natl Univ, Dept Mech Engn, Chunchon 200701, South Korea. Harvard Univ, Sch Med, Dept Translat Med, BIDMC, Boston, MA 02215 USA. RP Harvard Univ, MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. EM chyoun@mit.edu; bskim@icu.ac.kr; dsnam@icu.ac.kr; blee@dju.ac.kr; ebshim@kangwon.ac.kr; gari@mit.edu; jhealey@bidmc.harvard.edu RI Youn, Chan-Hyun/C-1729-2011 NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-23034-3 J9 LECT NOTES COMPUT SC PY 2004 VL 3090 BP 699 EP 707 PG 9 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Telecommunications SC Computer Science; Telecommunications GA BAW85 UT WOS:000223980100070 ER PT J AU Bauer, AM Boyce, WT AF Bauer, AM Boyce, WT TI Prophecies of childhood: How children's social environments and biological propensities affect the health of populations SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Review DE child development; social environment; stress response systems; public health ID PITUITARY-ADRENAL AXIS; POSTTRAUMATIC-STRESS-DISORDER; LONG-TERM OUTCOMES; ALZHEIMERS-DISEASE; SALIVARY CORTISOL; SOCIOECONOMIC-STATUS; HEART-RATE; CARDIOVASCULAR REACTIVITY; ADRENOCORTICAL RESPONSES; NEUROENDOCRINE ACTIVITY AB During the past decade, important steps have been taken globally to improve the status of children. Concurrently, significant advances have been made toward understanding how child development is shaped by transactions between biological and environmental influences. Despite such advances, ongoing adversities in the lives of children worldwide undermine the development of individuals and thus the health of nations. The primary tenets of this paper are that: children continue to suffer a disproportionate share of the world's adversities; exposure to early adversities is not only associated with increased morbidity during childhood, but also across the lifespan; and recent advances in understanding the operation and ontogeny of stress-response systems can help explain how adversity is translated into lifelong effects on health. Acknowledging the long-lasting sequelae of childhood adversity has important implications for public health and society. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Boston, MA 02114 USA. Univ Calif Berkeley, Inst Human Dev, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Bauer, AM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bulfinch 440, Boston, MA 02114 USA. EM ambauer@partners.org NR 130 TC 12 Z9 12 U1 2 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 2004 VL 11 IS 3 BP 164 EP 175 DI 10.1207/s15327558ijbm1103_5 PG 12 WC Psychology, Clinical SC Psychology GA 866PW UT WOS:000224786400005 PM 15496344 ER PT J AU Steinberg, M Tschanz, JT Corcoran, C Steffens, DC Norton, MC Lyketsos, CG Breitner, JCS AF Steinberg, M Tschanz, JT Corcoran, C Steffens, DC Norton, MC Lyketsos, CG Breitner, JCS TI The persistence of neuropsychiatric symptoms in dementia: the Cache County Study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE dementia; neuropsychiatric; persistence ID MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; BEHAVIORAL DISTURBANCES; PREVALENCE; HEALTH; AD AB Objective To estimate the 18-month persistence of neuropsychiatric symptoms in dementia in a population-based sample, and to compare the severity of neuropsychiatric symptoms at baseline to the severity at 18-month follow-up. Methods A population-based sample of 329 residents of Cache County, Utah, diagnosed with dementia was rated on the Neuropsychiatric Inventory (NPI). Of the 204 participants with neuropsychiatric symptoms at baseline (defined as total NPI score >0), NPI data were obtained approximately 18 months later on 117 who were alive and available for follow-up. Results Eighty-one percent of those with neuropsychiatric symptoms at baseline (defined as total NPI score >0) continued to have at least one symptom at follow-up. Sixty-seven percent of participants with a clinically significant total NPI score (defined as greater than or equal to4) at baseline continued to have a clinically significant total NPI score at follow-up. Among the ten neuropsychiatric domains assessed at baseline, delusions persisted in 65.5% of individuals, followed by depression (58.3%), and aberrant motor behavior (55.6%), while hallucinations and disinhibition persisted in only 25.0% and 11.1% respectively. In participants who were symptomatic at both baseline and follow-up, the mean severity scores at the two observation points were comparable in all ten neuropsychiatric domains. Conclusions Neuropsychiatric symptoms in dementia overall were highly persistent. Among those in whom symptoms did persist, symptom severity a year and a half later appeared to be comparable. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27706 USA. Utah State Univ, Dept Family & Human Dev, Logan, UT 84322 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Steinberg, M (reprint author), Johns Hopkins Univ Hosp, Osler 320,600 N Wolfe St, Baltimore, MD 21287 USA. EM martins@jhmi.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [AG-21136, AG-11380] NR 19 TC 73 Z9 75 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 2004 VL 19 IS 1 BP 19 EP 26 DI 10.1002/gps.1025 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 768KF UT WOS:000188541600003 PM 14716695 ER PT J AU Sherman, AC Mosier, J Leszcz, M Burlingame, GM Ulman, KH Cleary, T Simonton, S Latif, U Hazelton, L Strauss, B AF Sherman, AC Mosier, J Leszcz, M Burlingame, GM Ulman, KH Cleary, T Simonton, S Latif, U Hazelton, L Strauss, B TI Group interventions for patients with cancer and HIV disease: Part I: Effects on psychosocial and functional outcomes at different phases of illness SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Review ID BEHAVIORAL STRESS-MANAGEMENT; RANDOMIZED-CONTROLLED-TRIAL; RISK-REDUCTION INTERVENTION; METASTATIC BREAST-CANCER; AFRICAN-AMERICAN ADOLESCENTS; SUPPORT GROUP INTERVENTION; AIDS-PREVENTION PROGRAM; SEXUALLY-TRANSMITTED-DISEASE; CONTROLLED CLINICAL-TRIAL; FEMALE COLLEGE-STUDENTS AB Group interventions for individuals facing cancer or HI-V disease have drawn considerable attention among researchers and clinicians over the past 20 years. C1 Univ Arkansas Med Sci, Dept Otolaryngol, Program Dev Behav Med, Little Rock, AR 72205 USA. Univ Toronto, Dept Psychiat, Grp Psychotherapy, Toronto, ON, Canada. Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 3J5, Canada. Univ Klinikum Friederich Schiller, Inst Med Psychol, D-6900 Jena, Germany. RP Sherman, AC (reprint author), Univ Arkansas Med Sci, Dept Otolaryngol, Program Dev Behav Med, 4301 W Markham St,756, Little Rock, AR 72205 USA. EM ShermanAllenC@uams.edu RI Burlingame, Gary/L-2449-2014; Leszcz, Molyn/N-9043-2016 FU PHS HHS [01M00894601D] NR 192 TC 29 Z9 29 U1 10 U2 15 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 EI 1943-2836 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JAN PY 2004 VL 54 IS 1 BP 29 EP 82 DI 10.1521/ijgp.54.1.29.40376 PG 54 WC Psychology, Clinical SC Psychology GA 770FW UT WOS:000188713400004 PM 14986573 ER PT J AU Pitman, MB Triratanachat, S Young, RH Oliva, E AF Pitman, MB Triratanachat, S Young, RH Oliva, E TI Hepatocyte paraffin 1 antibody does not distinguish primary ovarian tumors with hepatoid differentiation from metastatic hepatocellular carcinoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE anti-hepatocyte antibody; HepPar-1; HP1; immunohistochemistry; ovarian hepatoid carcinoma; ovarian hepatoid yolk sac tumor; metastatic hepatocellular carcinoma ID HEP PAR-1; EXTRAHEPATIC TUMORS; MONOCLONAL-ANTIBODY; CELL CARCINOMA; IMMUNOREACTIVITY; DIAGNOSIS; ANTIGEN; MARKER; LIVER AB Anti-hepatocyte antibody, hepatocyte paraffin 1, is a monoclonal antibody that is highly specific for normal and neoplastic hepatocytes and that can differentiate hepatocytic from nonhepatocytic tumors. This marker has been rarely studied in extrahepatic tumors and to our knowledge has not been investigated in ovarian tumors with hepatoid differentiation. We studied hepatocyte paraffin I immunoreactivity in a series of ovarian hepatoid carcinomas, ovarian hepatoid yolk sac tumors (YSTs), and hepatocellular carcinomas metastatic to the ovary to assess the potential utility of hepatocyte paraffin I in differential diagnosis. Hepatocyte paraffin I positivity was seen in three of seven ovarian hepatoid carcinomas, five of eight hepatoid yolk sac tumors, and six of eight metastatic hepatocellular carcinomas. The extent of positivity ranged from <25% to >50% of the tumor cells. There was strong coarsely granular cytoplasmic staining in all three tumor types without a distinctive staining pattern in any group. The degree of hepatic differentiation correlated with hepatocyte paraffin I positivity in the three groups: 83% of the well differentiated tumors, 50% of the moderately differentiated tumors, and none of the poorly differentiated tumors were positive. All ovarian hepatoid carcinomas were either immunoreactive for alpha-fetoprotein or had an elevated serum alpha-fetoprotein level; more than half of these tumors were hepatocyte paraffin I negative. All but one hepatocyte paraffin I negative hepatoid yolk sac tumor and ovarian hepatocellular carcinoma were also negative for alpha-fetoprotein. In conclusion, hepatocyte paraffin I is positive in primary ovarian tumors with hepatoid differentiation, with the degree of hepatocyte paraffin I positivity correlating with the degree of hepatoid differentiation. Hepatocyte paraffin 1, however, is not useful in distinguishing metastatic hepatocellular carcinoma from primary ovarian hepatoid carcinoma or hepatoid yolk sac tumor. C1 Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Med Sch,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Med Sch,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 37 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2004 VL 23 IS 1 BP 58 EP 64 DI 10.1097/01.pgp.0000101141.31270.a0 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 755WP UT WOS:000187434700011 PM 14668552 ER PT J AU Berka, C Levendowski, DJ Cvetinovic, MM Petrovic, MM Davis, G Lumicao, MN Zivkovic, VT Popovic, MV Olmstead, R AF Berka, C Levendowski, DJ Cvetinovic, MM Petrovic, MM Davis, G Lumicao, MN Zivkovic, VT Popovic, MV Olmstead, R TI Real-time analysis of EEG indexes of alertness, cognition, and memory acquired with a wireless EEG headset SO INTERNATIONAL JOURNAL OF HUMAN-COMPUTER INTERACTION LA English DT Article ID ADAPTIVE TASK ALLOCATION; WORKING-MEMORY; SLEEP-DEPRIVATION; PERFORMANCE; ATTENTION; PSYCHOPHYSIOLOGY; QUANTIFICATION; SPECTRUM; DRIVERS; SYSTEM AB The integration of brain monitoring into the man-machine interface holds great promise for real-time assessment of operator status and intelligent allocation of tasks between machines and humans. This article presents an integrated hardware and software solution for acquisition and real-time analysis of the electroencephalogram (EEG) to monitor indexes of alertness, cognition, and memory. Three experimental paradigms were evaluated in a total of 45 participants to identify EEG indexes associated with changes in cognitive workload: the Warship Commander Task (WCT), a simulated navy command and control environment that allowed workload levels to be systematically manipulated; a cognitive task with three levels of difficulty and consistent sensory inputs and motor outputs; and a multisession. image learning and reccognition memory test. Across tasks and participants, specific changes in the EEG were identified that were reliably associated with levels of cognitive workload. The EEG indexes were also shown to change as a function of training on the WCT and the learning and memory task. Future applications of the system to augment cognition in military and industrial environments are discussed. C1 Adv Brain Monitoring Inc, Carlsbad, CA 92008 USA. Univ Belgrade, Fac Elect Engn, YU-11001 Belgrade, Serbia and Mont, Yugoslavia. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Berka, C (reprint author), Adv Brain Monitoring Inc, 2850 Pio Pico Dr,Suite A, Carlsbad, CA 92008 USA. EM chris@b-alert.com NR 55 TC 125 Z9 125 U1 9 U2 33 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1044-7318 J9 INT J HUM-COMPUT INT JI Int. J. Hum.-Comput. Interact. PY 2004 VL 17 IS 2 BP 151 EP 170 DI 10.1207/s15327590ijhc1702_3 PG 20 WC Computer Science, Cybernetics; Ergonomics SC Computer Science; Engineering GA 840UH UT WOS:000222884900003 ER PT J AU O'Rourke, N Wollman, L Camann, W AF O'Rourke, N Wollman, L Camann, W TI Bilateral spontaneous vertebral artery dissection: management during labor and vaginal delivery SO INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA LA English DT Article ID INTERNAL CAROTID-ARTERY; STROKE AB We report the successful management of labor and delivery of a parturient with a history of spontaneous bilateral vertebral artery dissection. We also outline the reasons why the obstetric anesthetist should be aware of this condition as well as other cranio-cervical dissections. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Camann, W (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. EM wcamann@partners.org NR 24 TC 4 Z9 4 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0959-289X J9 INT J OBSTET ANESTH JI Int. J. Obstet. Anesth. PD JAN PY 2004 VL 13 IS 1 BP 44 EP 46 DI 10.1016/S0959-289X(03)00069-4 PG 3 WC Anesthesiology; Obstetrics & Gynecology SC Anesthesiology; Obstetrics & Gynecology GA 764WG UT WOS:000188228500010 PM 15321440 ER PT J AU Williams, JW Stellato, CP Cornell, J Barrett, JE AF Williams, JW Stellato, CP Cornell, J Barrett, JE TI The 13-and 20-item Hopkins Symptom checklist depression scale: Psychometric properties in primary care patients with minor depression or dysthymia SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE depressive disorder; psychological tests; Outcome and Process Assessment (Health Care) ID RANDOMIZED CONTROLLED-TRIAL; RATING-SCALE; HEALTH-STATUS; RESPONSIVENESS; INSTRUMENTS; MANAGEMENT; DISABILITY; VALIDITY; SEVERITY; IMPROVE AB Objective: Depression scales that are responsive to changes in clinical symptoms are important for clinical monitoring and outcomes assessment in longitudinal studies. We evaluated the psychometric properties and responsiveness to clinical change of the 13- and 20-item versions of the Hopkins Symptom Checklist Depression Scale (HSCL-D). Methods: A secondary data analysis from a large 11-week, multicenter clinical trial, comparing three treatments was performed. Adult patients with minor depression or dysthymia and a score of greater than or equal to 10 on the Hamilton Depression Rating Scale (HDRS) were recruited from primary care clinics. Item-total correlations and Cronbach alphas were computed for HSCL-D-13 and HSCL-D-20. Clinical response at 11 weeks was defined by a Hamilton Depression Rating Scale (HDRS) < 10, clinical remission by a HDRS < 7, and criterion symptom remission by less than or equal to 1 DSM-III-R criterion symptoms. Standardized effect sizes and Guyatt's responsiveness statistic were determined for the 13- and 20-item HSCL-D. Results: Of the 656 subjects enrolled, 511 (77.9%) had complete data and were included in the analysis. Patients were 61.1 +/- 15.0 years old; minor depression was diagnosed in 238, dysthymia in 273. Both scales had good internal consistency; Cronbach's alpha = 0.835 and 0.859 for the 13- and 20-items questionnaires respectively. Standardized effect sizes for clinical response (0.62 for the HSCL-D-13; 0.66 for the HSCL-D-20), clinical remission (0.69 and 0.70), and criterion symptom remission (0.65 and 0.67) showed moderate to large effects and did not differ significantly for the two versions. Responsiveness was virtually identical for patients with minor depression and dysthymia but responsiveness was substantially lower for ethnic minorities. Conclusion: The HSCL-D-13 and 20-item versions have similar responsiveness to change. For use in European Americans, we recommend the HSCL-D-13 if response burden is the preeminent consideration. To more fully capture DSM criterion symptoms, we recommend the HSCL-D-20. C1 Duke Univ, DVAMC, Med Ctr, HSR&D,Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Univ Texas, Hlth Sci Ctr, Dept Vet Affairs Med Ctr, San Antonio VA Hlth Serv Res Ctr Excellence, San Antonio, TX USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Williams, JW (reprint author), Duke Univ, DVAMC, Med Ctr, HSR&D,Ctr Hlth Serv Res Primary Care, Bldg 6,508 Fulton St, Durham, NC 27705 USA. EM jw.williams@duke.edu RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 34 TC 18 Z9 19 U1 2 U2 8 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2004 VL 34 IS 1 BP 37 EP 50 PG 14 WC Psychiatry SC Psychiatry GA 832SQ UT WOS:000222287800003 PM 15242140 ER PT J AU Mendez, MF AF Mendez, MF TI The accuracy of clinical criteria for the diagnosis of frontotemporal dementia SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE frontotemporal dementia; dementia; organic personality changes; neuropsychiatry ID ALZHEIMERS-DISEASE; LOBAR DEGENERATION; CONSENSUS; CHROMOSOME-17; FEATURES; AD AB The clinical diagnosis of frontotemporal dementia (FTD) can be challenging even to experienced clinicians. In the absence of a definitive clinical test, this diagnosis relies on behavioral criteria. Difficulty applying these criteria arise for four main reasons. First, FTD patients present with social and personality changes that defy the neuropsychological model of dementia. Second, FTD is not a single disorder but a spectrum of clinical syndromes with asymmetric and motor variants. Third, there may be qualitatively different symptoms during stages of FTD. Finally, pathologic and genetic variability contributes to the clinical variability. Future research should refine the clinical criteria for FTD using clinicopathological correlation in addition to working on the development of neurobiological markers. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu NR 20 TC 6 Z9 6 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2004 VL 34 IS 2 BP 125 EP 130 DI 10.2190/8V1X-11UN-YDXR-A9KF PG 6 WC Psychiatry SC Psychiatry GA 850QB UT WOS:000223626400002 PM 15387396 ER PT J AU Aitken, CL Schultz, D Cote, K Lopes, L D'Amico, AV AF Aitken, CL Schultz, D Cote, K Lopes, L D'Amico, AV TI Ability of preoperative endorectal magnetic resonance imaging to identify extracapsular extension and seminal vesicle invasion in a prostate-specific antigen screened population SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Joint Ctr Radiat Oncol, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Millersville, PA 17551 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2220 BP S468 EP S468 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700563 ER PT J AU Celik, OK Adams, J Gierga, DP Delaney, TF Busse, PM AF Celik, OK Adams, J Gierga, DP Delaney, TF Busse, PM TI Optimized radiotherapy in a locally advanced oropharyngeal carcinoma: Comparison of IMRT and proton beam SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2311 BP S523 EP S523 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700654 ER PT J AU Chan, AW Pommier, P Deschler, DG Liebsch, NJ McIntyre, JF Adams, JA Lopes, VV Frankenthaler, RJ Fabian, RL Thornton, AF AF Chan, AW Pommier, P Deschler, DG Liebsch, NJ McIntyre, JF Adams, JA Lopes, VV Frankenthaler, RJ Fabian, RL Thornton, AF TI Change in patterns of relapse after combined proton and photon irradiation for locally advanced paranasal sinus cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1108 BP S320 EP S320 DI 10.1016/S0360-3016(04)01426-9 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700314 ER PT J AU Chen, Y Rietzel, ER Adams, JA Willett, CG Busse, PM Chen, GT AF Chen, Y Rietzel, ER Adams, JA Willett, CG Busse, PM Chen, GT TI Comparison of intrahepatic tumor coverage and liver dose volume histogram using light-breathing 3DCT and 4DCT planning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2137 BP S415 EP S416 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700480 ER PT J AU Constine, LS Tarbell, N Hudson, M Schwartz, C Fisher, S Basu, S Muhs, A Kun, L Mauch, P Mendenhall, N AF Constine, LS Tarbell, N Hudson, M Schwartz, C Fisher, S Basu, S Muhs, A Kun, L Mauch, P Mendenhall, N TI Second malignancies after pediatric Hodgkin lymphoma: Associations with radiation dose and volume SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Rochester, Med Ctr, Rochester, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Florida, Med Ctr, Gainesville, FL 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 148 BP S219 EP S220 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700148 ER PT J AU Floyd, SR Strom, EA Buchholz, TA Goldberg, S Raad, RFA Oswald, MJ Powell, SN Taghian, AG AF Floyd, SR Strom, EA Buchholz, TA Goldberg, S Raad, RFA Oswald, MJ Powell, SN Taghian, AG TI Low local recurrence rate among node negative breast cancer patients with tumor size 5cm and larger treated with surgery and chemotherapy without radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 11 BP S135 EP S136 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700012 ER PT J AU Gluck, C Petit, JH Karasiewicz, C Henry, DL Berg, S Talcott, J Kaplan, I AF Gluck, C Petit, JH Karasiewicz, C Henry, DL Berg, S Talcott, J Kaplan, I TI Bicalutamide monotherapy achieves comparable cytoreduction prior to interstitial brachytherapy and represents an effective, less expensive, less morbid alternative to luteinizing hormone-releasing hormone analogues SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol 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 ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2181 BP S444 EP S445 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700524 ER PT J AU Horwitz, EM Levy, LB Kuban, DA Thames, HD Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL AF Horwitz, EM Levy, LB Kuban, DA Thames, HD Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL TI The biochemical and clinical significance of the post-treatment PSA bounce for prostate cancer patients treated with external beam radiation therapy alone: A multi-institutional pooled analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. MD Anderson, Houston, TX USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 171 BP S235 EP S235 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700171 ER PT J AU Hurwitz, MD Schultz, DJ Richie, JP Wein, A Malkowicz, SB Whittington, R D'Amico, AV AF Hurwitz, MD Schultz, DJ Richie, JP Wein, A Malkowicz, SB Whittington, R D'Amico, AV TI Is there a role for local therapy alone in treatment of high grade prostate cancer?: Assessment of outcome with radical prostatectomy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Millersville, PA 17551 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2223 BP S470 EP S470 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700566 ER PT J AU Jiang, SB Sharp, GC Berbeco, RI Chen, GT Mostafavi, H Jeung, A AF Jiang, SB Sharp, GC Berbeco, RI Chen, GT Mostafavi, H Jeung, A TI Development of an integrated radiotherapy imaging system (IRIS) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Varian Med Syst Inc, Ginzton Technol Ctr, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2453 BP S611 EP S611 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700796 ER PT J AU Kuban, DA Thames, H Horwitz, E Levy, L Kupelian, P Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A AF Kuban, DA Thames, H Horwitz, E Levy, L Kupelian, P Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A TI Predicting outcome after PSA failure in prostate cancer patients treated by radiation. Who needs salvage therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Cleveland Clin, Cleveland, OH 44106 USA. William Beaumont Hosp, Detroit, MI USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 64 BP S167 EP S168 DI 10.1016/S0360-3016(04)01147-2 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700065 ER PT J AU Kupelian, PA Thames, H Levy, L Horwitz, E Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A Kuban, D AF Kupelian, PA Thames, H Levy, L Horwitz, E Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A Kuban, D TI Year of treatment as an independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 MD Anderson Canc Ctr, Orlando, FL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cleveland Clin Fdn, Cleveland, OH 44195 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 172 BP S236 EP S236 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700172 ER PT J AU Liebsch, NJ Deschler, DG McIntyre, JF Adams, JA Frankenthaler, RJ Fabian, RL Chan, AW AF Liebsch, NJ Deschler, DG McIntyre, JF Adams, JA Frankenthaler, RJ Fabian, RL Chan, AW TI Favorable outcome of combined proton radiotherapy and chemotherapy for T4 nasopharyngeal carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2299 BP S515 EP S515 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700642 ER PT J AU Loeffler, LS Shih, HA Betensky, RA Dorfman, MV Louis, DN Batchelor, TT AF Loeffler, LS Shih, HA Betensky, RA Dorfman, MV Louis, DN Batchelor, TT TI Genetic determinants of radiation response in glioblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1011 BP S263 EP S263 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700218 ER PT J AU Marucci, L Ancukiewicz, M Lane, AM Collier, JM Gragoudas, ES Munzenrider, JE AF Marucci, L Ancukiewicz, M Lane, AM Collier, JM Gragoudas, ES Munzenrider, JE TI Uveal melanoma recurrent after fractionated proton beam therapy: Comparison of survival in patients treated with re-irradiation or with enucleation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Regina Elena Res Inst, Rome, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S BP S310 EP S311 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700297 ER PT J AU Myers, C Niemierko, A AF Myers, C Niemierko, A TI Percolation-based cluster models of dose-volume effects SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 46 BP S157 EP S157 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700047 ER PT J AU Ng, AK Li, S Recklitis, C Neuberg, D Silver, B Diller, L Mauch, PM AF Ng, AK Li, S Recklitis, C Neuberg, D Silver, B Diller, L Mauch, PM TI Fatigue in long-term survivors of Hodgkin's disease is associated with underlying cardiac disease SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 146 BP S218 EP S218 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700146 ER PT J AU Petit, JH Coen, J Yock, T Swearingen, B Billers, B Chapman, P Loeffler, JS AF Petit, JH Coen, J Yock, T Swearingen, B Billers, B Chapman, P Loeffler, JS TI Proton radiosurgery in the management of functioning and non-functioning pituitary adenomas: A 10-year experience at the Massachusetts General Hospital SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1094 BP S312 EP S312 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700300 ER PT J AU Pieters, RS Fullerton, BF Niemierko, A Munzenrider, JE AF Pieters, RS Fullerton, BF Niemierko, A Munzenrider, JE TI Long term neurological sequelae of high dose 3D Conformal fractionated combined proton-photon therapy to the cauda equina SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 30 BP S146 EP S147 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700031 ER PT J AU Pisansky, TM Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA AF Pisansky, TM Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA TI Clinical outcomes and prognostic factors in 4839 patients treated with external radiotherapy for stage T1-T2 prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Mayo Clin, Coll Med, Rochester, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. MD Anderson Canc Ctr, Orlando, FL USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Washington Univ, St Louis, MO 63130 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 63 BP S167 EP S167 DI 10.1016/S0360-3016(04)01146-0 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700064 ER PT J AU Pommier, P Niemierko, A Adams, JA Thornton, AF Loeffler, JS Chan, AW AF Pommier, P Niemierko, A Adams, JA Thornton, AF Loeffler, JS Chan, AW TI Equivalent uniform dose predicts delayed hyperintensity on T1-weighted magnetic resonance imaging after combined proton and photon irradiation in paranasal sinus cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Ctr Leon Berard, F-69373 Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2276 BP S501 EP S502 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700619 ER PT J AU Powell, SN Doppke, KP Chen, GT Taghian, AG AF Powell, SN Doppke, KP Chen, GT Taghian, AG TI Set-up uncertainty in accelerated partial-breast irradiation using 3D-conformal external beam radiotherapy: A companion study to a prospective phase I ongoing trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2110 BP S400 EP S401 DI 10.1016/S0360-3016(04)01578-0 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700453 ER PT J AU Punglia, RS Hughes, M Edge, S Theriault, R Bookman, M Burak, W Ottensen, R Niland, J Weeks, J AF Punglia, RS Hughes, M Edge, S Theriault, R Bookman, M Burak, W Ottensen, R Niland, J Weeks, J TI Factors associated with the addition of radiation therapy after mastectomy in women with stage I-II breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Ohio State Univ, Columbus, OH 43210 USA. City Hope Natl Med Ctr, Duarte, CA 91010 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 24 BP S142 EP S143 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700025 ER PT J AU Ray, ME Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA AF Ray, ME Thames, HD Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA TI PSA nadir predicts biochemical and distant failures after external beam radiation therapy for prostate cancer: A multi-institutional analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63110 USA. Mayo Clin, Coll Med, Div Radiat Oncol, Rochester, MN USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 169 BP S234 EP S234 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700169 ER PT J AU Reed, DR Mueller, A Wallner, K Ford, E Merrick, G AF Reed, DR Mueller, A Wallner, K Ford, E Merrick, G TI RAPID Strand(TM) vs. loose (Iodine-125 seeds): A prospective randomized trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 VA Puget Sound, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Schiffler Canc Ctr, Wheeling, WV USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2208 BP S461 EP S461 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700551 ER PT J AU Rietzel, E Liu, AK Chen, GT Doppke, KP Choi, NC AF Rietzel, E Liu, AK Chen, GT Doppke, KP Choi, NC TI Clinical implementation: 4D computed tomography for thoracic tumor treatment planning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2451 BP S609 EP S610 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700794 ER PT J AU Roach, M DeSilvo, M Thomas, CR Valicenti, R Asbell, SO Lawton, C Shipley, WS AF Roach, M DeSilvo, M Thomas, CR Valicenti, R Asbell, SO Lawton, C Shipley, WS TI Progression free survival (PFS) after whole-pelvic (WP) vs. mini-pelvic (MP) or prostate only (PO) radiotherapy (RT): A subset analysis of RTOG 9413, a phase III prospective randomized trial using neoadjuvant and concurrent (N&CHT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. RTOG, Philadelphia, PA USA. Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX USA. Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA USA. Dept Radiat Oncol, Philadelphia, PA USA. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1014 BP S264 EP S265 DI 10.1016/S0360-3016(04)01314-8 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700221 ER PT J AU Roof, K Mazal, A Sarkar, S Zietman, A Chen, G Shipley, W AF Roof, K Mazal, A Sarkar, S Zietman, A Chen, G Shipley, W TI A three-dimensional CT based analysis of inter-fraction bladder motion during radiotherapeutic treatment of bladder cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2160 BP S430 EP S430 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700503 ER PT J AU Ruhl, U Albrecht, MR Lueders, H Marciniak, H Doerffel, W AF Ruhl, U Albrecht, MR Lueders, H Marciniak, H Doerffel, W TI The German multinational GPOH-HD 95 trial: Treatment results and analysis of failures in pediatric Hodgkins disease using combination chemotherapy with and without radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Loma Linda Univ, Ctr Med, Loma Linda, CA 92350 USA. Amer Coll Radiol, Philadelphia, PA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 3 BP S131 EP S132 DI 10.1016/S0360-3016(04)01086-7 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700005 ER PT J AU Shih, HA Harisinghani, M Zietman, AL Saksena, M Weissleder, R AF Shih, HA Harisinghani, M Zietman, AL Saksena, M Weissleder, R TI Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic node radiation based on vascular rather than bony anatomy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1013 BP S264 EP S264 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700220 ER PT J AU Smalley, SR Benedetti, J Williamson, S Robertson, J Fisher, B Martenson, J Benson, A Mayer, R Cripps, C Estes, N MacDonald, J AF Smalley, SR Benedetti, J Williamson, S Robertson, J Fisher, B Martenson, J Benson, A Mayer, R Cripps, C Estes, N MacDonald, J TI Intergroup 0144 a phase III rectal surgical adjuvant study of pelvic radiation (XRT) plus 5-FU based chemotherapy (bolus 5-FU before and after PVI plus XRT vs PVT before, during, and after XRT vs biochemically modulated bolus 5-FU and XRT): Mature outcome results and pelvic failure analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Olathe Radiat Oncol Ctr, Olathe, KS USA. SW Oncol Grp, Seattle, WA USA. Univ Kansas, Kansas City, KS 66103 USA. London Reg Canc Ctr, London, ON, Canada. Mayo Clin, Rochester, MN USA. Northwestern Univ, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. Univ Illinois, Coll Med, Peoria, IL 61656 USA. St Vincent Comprehens Canc Ctr, New York, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 14 BP S137 EP S138 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700015 ER PT J AU Strasser, JF Li, S Neuberg, D Silver, B Ng, AK Mauch, PM AF Strasser, JF Li, S Neuberg, D Silver, B Ng, AK Mauch, PM TI Late cardiac toxicity after mediastinal radiation therapy for Hodgkin's disease SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 145 BP S217 EP S218 DI 10.1016/S0360-3016(04)01227-1 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700145 ER PT J AU Taghian, AG Doppke, K Recht, A Katz, MS Malaquias, S Gadd, MA Hughes, K Smith, BL Chen, G Powell, SN AF Taghian, AG Doppke, K Recht, A Katz, MS Malaquias, S Gadd, MA Hughes, K Smith, BL Chen, G Powell, SN TI Accelerated partial-breast irradiation using 3D conformal external beam radiotherapy for patients with early-stage breast cancer: Preliminary results of an ongoing phase I trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA USA. Harvard Univ, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1029 BP S274 EP S275 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700236 ER PT J AU Thames, HD Kuban, DA Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL AF Thames, HD Kuban, DA Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL TI Prognostic risk group stratification for clinical and biochemical failure after external beam radiation of localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Cleveland Clin, Cleveland, OH 44106 USA. William Beaumont Hosp, Detroit, MI USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 166 BP S231 EP S232 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700166 ER PT J AU Thurman, SA Schnitt, SJ Connolly, JL Gelman, R Silver, B Harris, JR Recht, A AF Thurman, SA Schnitt, SJ Connolly, JL Gelman, R Silver, B Harris, JR Recht, A TI Impact of surgery-to-radiotherapy interval (SRI) on local control in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy (BCT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2078 BP S382 EP S383 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700421 ER PT J AU Tsai, HK Manola, J Abner, A Talcott, JA D'Amico, AV Beard, C AF Tsai, HK Manola, J Abner, A Talcott, JA D'Amico, AV Beard, C TI Patient-reported acute gastrointestinal and genitourinary toxicities during conventional dose 3-dimensional conformal radiation therapy for adenocarcinoma of the prostate planned following neoadjuvant hormonal therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Mt Auburn Hosp, Dept Radiat Oncol, Cambridge, MA 02238 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2388 BP S567 EP S568 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700731 ER PT J AU Viswanathan, AN Hanson, E Lee, H Berkowitz, R Crum, C AF Viswanathan, AN Hanson, E Lee, H Berkowitz, R Crum, C TI The influence of margin status after hysterectomy in stage IB cervical cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Brigham & Womens Hosp, Dana Farber Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Dana Farber Harvard Canc Care Ctr, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 1080 BP S304 EP S304 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700286 ER PT J AU Willers, H Powell, SN Dahm-Daphi, J AF Willers, H Powell, SN Dahm-Daphi, J TI Genetic analysis of chromosomal double-strand break repair by non-homologous end-joining SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hamburg, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2009 BP S345 EP S345 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700352 ER PT J AU Yock, TI Krailo, MD Grier, HE Miser, JS Donaldson, SS Fry, CJ Gebhardt, MC Tarbell, NJ AF Yock, TI Krailo, MD Grier, HE Miser, JS Donaldson, SS Fry, CJ Gebhardt, MC Tarbell, NJ TI A comparison of local control achieved by surgery and radiotherapy in patients with non-metastatic pelvic Ewing sarcoma enrolled on INT-0091 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. COG Stat & Data Ctr, Arcadia, CA USA. DFCI, Boston, MA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Stanford Med Ctr, Palo Alto, CA USA. King Khalid Natl Hosp, Jeddah, Saudi Arabia. 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 192 BP S247 EP S248 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700192 ER PT J AU Beard, CJ Chen, MH Cote, K Loffredo, M Renshaw, AA Hurwitz, M D'Amico, AV AF Beard, CJ Chen, MH Cote, K Loffredo, M Renshaw, AA Hurwitz, M D'Amico, AV TI Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Soc Therapeut Radiol & Oncol DE prostate cancer; perineural invasion; conformal radiotherapy ID NEEDLE-BIOPSY SPECIMENS; RADICAL PROSTATECTOMY; EXTRAPROSTATIC EXTENSION; PROGNOSTIC-SIGNIFICANCE; RADIATION-THERAPY; INCREASED FAILURE; ADENOCARCINOMA; PREDICTION; CARCINOMA; GLEASON AB Purpose: To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). Methods and Materials: The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Results: Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75 % (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level greater than or equal to20 ng/mL (p = 0.01) and Gleason score greater than or equal to8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0.033). Conclusion: A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients. (C) 2004 Elsevier Inc. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Beard, CJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 25 TC 63 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2004 VL 58 IS 1 BP 19 EP 24 DI 10.1016/S0360-3016(03)01433-0 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 758JP UT WOS:000187631300004 PM 14697416 ER PT J AU Olvera, RL Glahn, DC Caetano, SC Pliszka, SR Soares, JC AF Olvera, RL Glahn, DC Caetano, SC Pliszka, SR Soares, JC TI Neuroimaging studies in bipolar children and adolescents SO INTERNATIONAL REVIEW OF NEUROBIOLOGY, VOL 62 SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; WHITE-MATTER HYPERINTENSITIES; SUBGENUAL PREFRONTAL CORTEX; DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE FOLLOW-UP; REGIONAL CEREBRAL METABOLISM; CLINICALLY REFERRED CHILDREN; MAJOR DEPRESSIVE DISORDER; SUBCORTICAL BRAIN-REGIONS; TEMPORAL-LOBE STRUCTURES C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Psychiat, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. RP Olvera, RL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 154 TC 3 Z9 3 U1 5 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2004 VL 62 BP 121 EP 146 DI 10.1016/S0074-7742(04)62004-6 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BBI36 UT WOS:000225608200004 PM 15530570 ER PT J AU Stuart, K Levy, DE Anderson, T Axiotis, CA Dutcher, JP Eisenberg, A Erban, JK Benson, AB AF Stuart, K Levy, DE Anderson, T Axiotis, CA Dutcher, JP Eisenberg, A Erban, JK Benson, AB TI Phase II study of interferon gamma in malignant carcinoid tumors (E9292): A trial of the eastern cooperative oncology group SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE carcinoid; interferon ID METASTATIC NEUROENDOCRINE TUMORS; INDOLEAMINE 2,3-DIOXYGENASE; COMBINATION CHEMOTHERAPY; ALPHA-INTERFERON; STREPTOZOTOCIN; OCTREOTIDE; THERAPY; 5-FLUOROURACIL; FLUOROURACIL; TRYPTOPHAN AB Purpose: To determine the safety and efficacy of treatment with gamma interferon (IFN-gamma) in patients with metastatic carcinoid tumor. Patients and methods: 51 patients were enrolled on this Phase II Eastern Cooperative Oncology Group (ECOG) study. Seventy five percent of them had hormonally active tumors. Treatment consisted of IFN-gamma subcutaneously at a daily dose of 0.1 mg/m(2). Patents were evaluated for toxicity weekly for the first month and monthly thereafter; response was determined radiologically every 8 weeks. Results: Patients received treatment with IFNgamma for a median of 17.9 weeks (range 2-175). Toxicity was generally mild and expected: 61% experienced noninfected fever and 21% developed granulocytopenia. Three patients (6%) had a partial response; there were no complete responses. Median time to progression was 5.5 months (95% confidence interval 3.9-11.1). The 1-year progression free rate was 28% (13.4-43.4%). Median survival was 42 months, with a 1-year survival rate of 67% (53.3-80%). Discussion: This Phase II study demonstrated that therapy with IFNgamma in patients with metastatic carcinoid tumor was well-tolerated, but did not produce significant antitumor effects. The overall results were somewhat comparable to those previously seen with alpha interferons as well as cytotoxic drugs. C1 Beth Israel Deaconess Med Ctr, Hepatobiliary & Gastrointestinal Oncol Program, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Billings Oncol Associates, Billings, MT USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Our Lady Mercy Med Ctr MBCCOP, Bronx, NY USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Stuart, K (reprint author), Beth Israel Deaconess Med Ctr, Hepatobiliary & Gastrointestinal Oncol Program, 330 Brookline Ave,Shapiro 913D, Boston, MA 02215 USA. FU NCI NIH HHS [CA21115, CA80775, CA23318, CA13650, CA07190] NR 38 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JAN PY 2004 VL 22 IS 1 BP 75 EP 81 DI 10.1023/B:DRUG.0000006177.46798.1f PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 749AC UT WOS:000186895600008 PM 14707497 ER PT J AU Hong, DH Pawlyk, BS Adamian, M Li, TS AF Hong, DH Pawlyk, BS Adamian, M Li, TS TI Dominant, gain-of-function mutant produced by truncation of RPGR SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LINKED RETINITIS-PIGMENTOSA; REGULATOR (RPGR)-INTERACTING PROTEIN; EXON ORF15; TRANSGENIC MICE; MUTATIONS; GENE; IDENTIFICATION; DEGENERATION; MOUSE; DYSTROPHY AB PURPOSE. The retinitis pigmentosa GTPase regulator (RPGR) is essential in the maintenance of photoreceptor viability. Mutations in the X-linked RPGR gene have generally been assumed to be recessive. This study was undertaken to investigate whether certain mutant RPGR alleles may act dominantly. METHODS. An RPGR transgene representing the RPGR ORF15 variant was placed under a non-tissue-specific promoter and introduced into transgenic mice. The transgene was crossed into both a wild type (WT) and an RPGR null background. Its expression was analyzed by RT-PCR, immunoblot analysis, and immunofluorescence. Photoreceptor survival was assessed by electroretinography and histology. RESULTS. The RPGR transgene transcript underwent photoreceptor-specific, alternative splicing involving the purine-rich region of the ORF 15 exon, generating a shortened mRNA and a premature stop codon. This truncation mutant caused more rapid photoreceptor degeneration than that in the RPGR null (knockout) mutant. The disease course was similar, whether the transgene was coexpressed with WT RPGR or expressed alone in the RPGR null background. CONCLUSIONS. Certain truncated forms of RPGR can behave as a dominant, gain-of-function mutant. These data suggest that human PPGR mutations are not necessarily null and some may also act as dominant alleles, leading to a more severe phenotype than a null mutant. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Bermand Gund Lab Study Retinal Degenerat, Sch Med, Boston, MA 02114 USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Bermand Gund Lab Study Retinal Degenerat, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu FU NEI NIH HHS [EY10309] NR 26 TC 33 Z9 34 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2004 VL 45 IS 1 BP 36 EP 41 DI 10.1167/iovs.03-0787 PG 6 WC Ophthalmology SC Ophthalmology GA 761AF UT WOS:000187875600006 PM 14691151 ER PT B AU Foster, CS AF Foster, CS GP MEDIMOND TI Biologic therapy for ocular inflammatory diseases SO ISOPT: PROCEEDINGS OF THE 5TH INTERNATIONAL SYMPOSIUM ON OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Symposium on Ocular Pharmacology and Therapeutics CY MAR 11-14, 2004 CL Monte Carlo, MONACO C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-100-0 PY 2004 BP 53 EP 54 PG 2 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA BBR25 UT WOS:000227351700009 ER PT B AU Foster, CS AF Foster, CS GP MEDIMOND TI Non-steroidal immunomodulatory therapy for ocular inflammatory disease SO ISOPT: PROCEEDINGS OF THE 5TH INTERNATIONAL SYMPOSIUM ON OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Proceedings Paper CT 5th International Symposium on Ocular Pharmacology and Therapeutics CY MAR 11-14, 2004 CL Monte Carlo, MONACO C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-100-0 PY 2004 BP 55 EP 57 PG 3 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA BBR25 UT WOS:000227351700010 ER PT J AU Zohar, AH Shen, G Dycian, A Pauls, D Apter, A King, R Cohen, D Kron, S AF Zohar, AH Shen, G Dycian, A Pauls, D Apter, A King, R Cohen, D Kron, S TI The military life scale: A measure of perceived stress and support in the Israeli Defense Force SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article AB Goals: The purpose of this study was to construct a reliable and valid measure of perceived stress and support by adolescents in the Israeli military, and to explore its structure and psychometric properties. Method: A large stratified sample of soldiers, representing different types of units, different lengths of service in the Israel Defense Force, and different ranks, were administered the Military Life Scale. Principal component factor analysis with varimax rotation resulted in a 5-factor structure for the stress scale, and a 5-factor structure for the support scale. Results: All factor-derived scales showed satisfactory scale reliability and discriminant validity. Conclusions: The Military Life Scale is useful for measuring the stress experienced by individuals and groups within the Israel Defense Force. In addition, the Military Life Scale may be of use in other military environments, and with minor revision, in non-military environments in which the normative passage from late adolescence into adulthood occurs, such as a college setting. C1 Ruppin Acad Ctr, IL-40250 Emek Hefer, Israel. Geha Mental Hlth Ctr, Petah Tiqwa, Israel. IDF, Med Corps, Mental Hlth Branch, Haifa, Israel. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Unit Psychiat & Neurodev Genet, Boston, MA USA. Schneider Childrens Hosp, Feinberg Child Study Ctr, Petah Tiqwa, Israel. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Shalvata Mental Hlth Ctr, Hod Hasharon, Israel. RP Zohar, AH (reprint author), Ruppin Acad Ctr, IL-40250 Emek Hefer, Israel. EM adaz@ruppin.ac.il NR 11 TC 3 Z9 3 U1 1 U2 1 PU GEFEN PUBLISHING HOUSE LTD PI JERUSALEM PA PO BOX 36004, JERUSALEM 91360, ISRAEL SN 0333-7308 J9 ISRAEL J PSYCHIAT JI Isr. J. Psychiatr. Relat. Sci. PY 2004 VL 41 IS 1 BP 33 EP 44 PG 12 WC Psychiatry SC Psychiatry GA 828BA UT WOS:000221946300005 PM 15160654 ER PT J AU Arroyo, JG Bula, DV Grant, CA Murtha, T AF Arroyo, JG Bula, DV Grant, CA Murtha, T TI Bilateral Candida albicans endophthalmitis associated with an infected deep venous thrombus SO JAPANESE JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Candida albicans; deep venous thrombosis; endophthalmitis; fungus; retinal granuloma; vitrectomy AB Background: To describe the clinical and histopathologic findings in a patient with bilateral Candida albicans endophthalmitis due to an infected deep venous thrombus. Case: A 43-year-old patient with bilateral Candida albicans endophthalmitis due to an infected central venous thrombus. The patient's ophthalmology and hospital charts were reviewed. Histopathologic sections of the Candida albicans retinal granuloma were examined under light microscopy. Observations: Our patient had multiple blood cultures positive for Candida albicans owing to an infected subclavicular venous thrombosis. Bilateral Candida albicans endophthalmitis was diagnosed. Bilateral vitrectomy and membrane peeling for macular traction retinal detachments were performed. In the right eye, a large retinal granuloma was excised during surgery to adequately relieve traction on the macula. Vision improved in both eyes after surgery. Histopathologic findings revealed branching hyphae surrounded by giant cells, endothelial cell-lined vascular channels, and inflammatory cells. Conclusions: This is the first report of an infected deep venous thrombosis causing bilateral endogenous endophthalmitis. Appropriate management of these patients requires clear differentiation between endogenous chorioretinitis and endophthalmitis. Patients with documented fungemia should have a dilated fundus examination on a regular basis until complete clearance of the infection. Jpn J Ophthalmol 2004;48:30-33 (C) Japanese Ophthalmological Society 2004. C1 Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Beetham Eye Unit, Boston, MA 02215 USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 12th Floor, Boston, MA 02114 USA. EM jarroyo@caregroup.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-5155 J9 JPN J OPHTHALMOL JI Jpn. J. Ophthalmol. PD JAN-FEB PY 2004 VL 48 IS 1 BP 30 EP 33 DI 10.1007/s10384-003-0008-0 PG 4 WC Ophthalmology SC Ophthalmology GA 770ZG UT WOS:000188760800006 PM 14767647 ER PT J AU O'Toole, TP Freyder, PJ Gibbon, JL Hanusa, BJ Seltzer, D Fine, MJ AF O'Toole, TP Freyder, PJ Gibbon, JL Hanusa, BJ Seltzer, D Fine, MJ TI ASAM patient placement criteria treatment levels: Do they correspond to care actually received by homeless substance abusing adults? SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE homelessness; substance abuse; substance abuse treatment ID MATCHING CLIENTS; ALCOHOLISM; INPATIENT; SERVICES AB We report findings from a community-based two-city survey of homeless adults comparing the level of substance abuse treatment assigned to them using the ASAM Patient Placement Criteria with care actually received during the previous 12 months. Overall 531 adults were surveyed with 382 meeting DSM-IIIR criteria of being in need of treatment or having a demand for treatment. Of those with a treatment need, 1.5% met criteria for outpatient care, 40.3% intensive outpatient/partial hospitalization care, 29.8% medically monitored care and 28.8% managed care levels. In contrast, of those receiving treatment (50.5%, 162 persons), almost all care received by this cohort was either inpatient or residential based (83.6%). Unsheltered homeless persons and those without insurance were significantly more likely to report not receiving needed treatment. Lack of treatment availability or capacity, expense, and changing one's mind while on a wait Est were the most commonly cited reasons for no treatment. C1 Johns Hopkins Univ, Welch Ctr Epidemiol Prevent & Clin Res, Baltimore, MD 21205 USA. Maricopa Cty Dept Publ Hlth, Phoenix, AZ USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP O'Toole, TP (reprint author), Johns Hopkins Univ, Welch Ctr Epidemiol Prevent & Clin Res, 2024 E Monument St, Baltimore, MD 21205 USA. EM totoole@jhmi.edu NR 19 TC 12 Z9 12 U1 1 U2 7 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 1 BP 1 EP 15 DI 10.1300/J069v23n01_01 PG 15 WC Substance Abuse SC Substance Abuse GA 808BX UT WOS:000220545700001 PM 15077836 ER PT J AU Somoza, EC Winhusen, TM Bridge, TP Rotrosen, JP Vanderburg, DG Harrer, JM Mezinskis, JP Montgomery, MA Ciraulo, DA Wulsin, LR Barrett, JA AF Somoza, EC Winhusen, TM Bridge, TP Rotrosen, JP Vanderburg, DG Harrer, JM Mezinskis, JP Montgomery, MA Ciraulo, DA Wulsin, LR Barrett, JA TI An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE cocaine dependence; attention deficit disorder; ADHD; methylphenidate ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; ABUSERS; SYMPTOMS; PLACEBO AB A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted. C1 CinARC, Cincinnati, OH 45220 USA. Cincinnati VA UC NIDA MDRU, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 10010 USA. VHA New York Harbor Healthcare Syst, New York, NY 10010 USA. Boston Univ, Sch Med, Dept Psychiat, MDRU,VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Somoza, EC (reprint author), CinARC, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM somoza@uc.edu OI Ciraulo, Domenic/0000-0001-7706-8765; Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [Y01 DA 50038-00] NR 28 TC 39 Z9 39 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 1 BP 77 EP 92 DI 10.1300/J069v23n01_07 PG 16 WC Substance Abuse SC Substance Abuse GA 808BX UT WOS:000220545700007 PM 15077842 ER PT J AU Becker, AE Keel, P Anderson-Fye, EP Thomas, JJ AF Becker, AE Keel, P Anderson-Fye, EP Thomas, JJ TI Genes and/or jeans?: Genetic and socio-cultural contributions to risk for eating disorders SO JOURNAL OF ADDICTIVE DISEASES LA English DT Review DE genetic; socio-cultural; eating disorders ID BODY-IMAGE DISTURBANCE; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; PROMOTER POLYMORPHISM; PSYCHIATRIC-DISORDERS; ADOLESCENT GIRLS; ENVIRONMENTAL-INFLUENCES; PHYSICAL SIMILARITY; CONTROLLED FAMILY; MAJOR DEPRESSION AB Eating disorders are prevalent among young adult females and pose serious psychological and medical risks. Notwithstanding important advances, efforts to develop effective means of preventing and treating eating disorders have been limited by an incomplete understanding of their multifactorial etiology. Whereas epidemiologic data strongly suggest the influence of socio-cultural context in moderating risk, many hypotheses about how these effects are exerted have remained empirically unevaluated. Specifically, experimental and observational data suggest that social transition (e.g., transnational migration, urbanization, modernization), Western media exposure, and certain peer environments (involving social comparison and teasing) may all contribute to risk. With respect to genetic influences on etiology, family and twin studies have supported a genetic diathesis to eating disorders. Whereas, molecular genetic studies have generated interesting leads-with the most promising findings emerging for genes related to the function of serotonin-they have yet to identify well-replicated susceptibility loci. This paper reviews the data supporting both socio-cultural and genetic contributions for eating disorders and suggests productive future strategies for continuing to unravel their likely multiple and complex interactions. C1 Massachusetts Gen Hosp, Dept Psychiat, Adult Eating & Weight Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Culture & Hlth, Los Angeles, CA 90024 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Becker, AE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Adult Eating & Weight Disorders Program, WAC 816,15 Parkman St, Boston, MA 02114 USA. NR 105 TC 11 Z9 12 U1 10 U2 28 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 3 BP 81 EP 103 DI 10.1300/J069v23n03_07 PG 23 WC Substance Abuse SC Substance Abuse GA 842NY UT WOS:000223012300007 PM 15256346 ER PT J AU Jaffe, C Saxon, AJ Meredith, C Bush, KR Straits-Troster, KA Romwall, L AF Jaffe, C Saxon, AJ Meredith, C Bush, KR Straits-Troster, KA Romwall, L TI A pilot comparison of methamphetamine users with and without ADHD SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 UWSOM, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 2 MA 15A BP 139 EP 139 PG 1 WC Substance Abuse SC Substance Abuse GA 820NL UT WOS:000221396400024 ER PT J AU Oepen, G Baldessarini, RJ Salvatore, P AF Oepen, G Baldessarini, RJ Salvatore, P TI On the periodicity of manic-depressive insanity, by Eliot Slater (1938): translated excerpts and commentary SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; cycles; kindling; manic-depressive; periodicity; progressive course; Kraepelin; sensitization; slater; wellness intervals ID PROSPECTIVE FOLLOW-UP; AFFECTIVE-DISORDER; CASE REGISTER; BIPOLAR DISORDER; RECURRENCE; ILLNESS; SENSITIZATION; PSYCHOSIS; PROGNOSIS; EPISODES AB Since the classic descriptions of the course of bipolar and recurrent depressive forms of manic-depressive illness by Emil Kraepelin a century ago, it has been considered a truism that the rate of cycling increases, and wellness intervals shorten, with rising counts of recurrences, particularly early in the natural history of the illness. Less well known is that the analysis of this phenomenon is vulnerable to a computational artifact first described by Eliot Slater, based on his reanalysis of data from manic-depressive patients first evaluated by Kraepelin at the Munich Psychiatric Institute. Slater realized that there is an increasingly disproportionate representation of faster-cycling patients in sub-samples involving higher cycle-counts in pooled samples of subjects. More accurate results require analyzing illness-course either within individuals, or in groups matched for episode-counts. This artifact is pervasive in the older and modem research literature, but still not widely recognized. Since Slater's 1938 report in German is not well known, we provide an abbreviated English translation with commentary and additional reanalysis to highlight the phenomenon that might be termed 'Slater's Fallacy'. (C) 2002 Elsevier B.V. All rights reserved. C1 Univ Alabama, Sch Med, Dept Psychiat & Behav Neurobiol, Birmingham, AL USA. Harvard Univ, Sch Med, Dept Psychiat, Int Consortium Bipolar Disorder Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA 02478 USA. Univ Parma, Psychiat Clin, I-43100 Parma, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org NR 39 TC 24 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2004 VL 78 IS 1 BP 1 EP 9 DI 10.1016/S0165-0327(02)00359-2 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764LC UT WOS:000188207500001 PM 14672791 ER PT J AU Garrett, JK Jameson, SC Thomson, B Collins, MH Wagoner, LE Freese, DK Beck, LA Boyce, JA Filipovich, AH Villanueva, JM Sutton, SA Assa'ad, AH Rothenberg, ME AF Garrett, JK Jameson, SC Thomson, B Collins, MH Wagoner, LE Freese, DK Beck, LA Boyce, JA Filipovich, AH Villanueva, JM Sutton, SA Assa'ad, AH Rothenberg, ME TI Anti-interieukin-5 (mepolizumab) therapy for hypereosinophilic syndromes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE eosinophils; esophagitis; IL-5; cytokine; hypereosinophilic; humanized antibody ID EOSINOPHILIC ESOPHAGITIS; INTERLEUKIN-5; AIRWAY; ANTIBODY; IMATINIB; ASTHMA AB Background: IL-5 is a cytokine critically involved in regulating several aspects of eosinophils including their production, activation, and tissue recruitment. As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia. Objective: We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hypereosinophilic syndromes. Methods: We performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10 mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with hypereosinophilic syndromes (defined by peripheral blood and/or tissue eosinophilia). The effects of treatment on safety, eosinophil levels (in peripheral blood and/or diseased tissue), pulmonary function, and quality of life were measured over a 28-week period. Results: Anti-IL-5 was well tolerated in all patients and lowered peripheral blood eosinophil counts despite ongoing systemic glucocorticoid therapy. The decline in circulating eosinophil counts was sustained for at least 12 weeks after the last dose of anti-IL-5. In addition, anti-IL-5 improved clinical and quality of life measurements. In one patient with striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a 10-fold reduction in tissue eosinophil levels. Conclusions: These results suggest that anti-IL-5 is safe, effective in lowering eosinophil levels, and has potential glucocorticoid-sparing effects in patients with a variety of hypereosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic potential for hypereosinophilic syndromes. C1 Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Dept Med, Cincinnati, OH USA. Mayo Clin & Mayo Fdn, Dept Pediat, Rochester, MN 55905 USA. Johns Hopkins Sch Med, Johns Hopkins Asthma & Allergy Ctr, Dept Med, Sch Med, Baltimore, MD USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Rothenberg, ME (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, 3333 Burnet Ave,MLC 7028, Cincinnati, OH 45229 USA. FU NIAID NIH HHS [R01 AI045839] NR 16 TC 226 Z9 236 U1 1 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2004 VL 113 IS 1 BP 115 EP 119 DI 10.1016/j.jaci.2003.10.049 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 760MP UT WOS:000187837900015 PM 14699394 ER PT J AU Porter, D Polyak, K AF Porter, D. Polyak, K. TI Emerging genomic technologies for studying mammary development and mammary cancer SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE genornics; mammary; SAGE C1 [Porter, D.; Polyak, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Porter, D.; Polyak, K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PY 2004 VL 82 SU 1 BP 239 EP 239 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UM UT WOS:000203095201002 ER PT J AU Danaher, PJ Cao, MK Anstead, GM Dolan, MJ DeWitt, CC AF Danaher, PJ Cao, MK Anstead, GM Dolan, MJ DeWitt, CC TI Reversible dilated cardiomyopathy related to amphotericin B therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE posaconazole; coccidioidomycosis; Coccidioides immitis ID COCCIDIOIDOMYCOSIS; PERICARDITIS; MICE AB We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB. C1 David Grant USAF Med Ctr, Dept Infect Dis, Travis AFB, CA 94535 USA. David Grant USAF Med Ctr, Dept Cardiol, Travis AFB, CA 94535 USA. Dept Vet Affairs Med Ctr, Med Serv, S Texas Hlth Care Syst, San Antonio, TX 78229 USA. Wilford Hall USAF Med Ctr, Dept Infect Dis, Lackland AFB, TX 78236 USA. RP Danaher, PJ (reprint author), Infect Dis Serv, 60MDG-60MDOS-SGOMB,101 Bodin Circle, Travis AFB, CA 94535 USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2004 VL 53 IS 1 BP 115 EP 117 DI 10.1093/jac/dkg472 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 756JW UT WOS:000187462800020 PM 14657095 ER PT J AU Otto, MW Safren, SA Pollack, MH AF Otto, MW Safren, SA Pollack, MH TI Internal cue exposure and the treatment of substance use disorders: lessons from the treatment of panic disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE substance abuse; panic disorder; benzodiazepine discontinuation; interoceptive exposure; emotional avoidance; emotional acceptance ID COGNITIVE-BEHAVIORAL THERAPY; INFORMATION-PROCESSING ANALYSIS; DETOXIFIED OPIATE ADDICTS; 35-PERCENT CO2 CHALLENGE; ANXIETY SENSITIVITY; BENZODIAZEPINE TREATMENT; EXPERIENTIAL AVOIDANCE; ALPRAZOLAM DISCONTINUATION; BIOLOGICAL CHALLENGE; GENDER DIFFERENCES AB Despite early recognition of the importance of internal cues (craving sensations and emotional states) for relapse in substance use disorders, relatively little attention has been devoted to exposure-based treatments targeting these cues. Drawing upon research on the conceptualization and treatment of panic disorder, we discuss the application of internal (largely emotional) cue exposure for substance use disorders. Our model for this discussion was based on the role of exposure to feared sensations of anxiety in the treatment of panic disorder and benzodiazepine (BZ) discontinuation. Shared research strategies between panic disorder and substance use-studies of biological provocation and anxiety sensitivity-were discussed, as were gender differences in drug-use motives. In accordance with research on anxiety sensitivity, provocation effects, and the treatment of benzodiazepine withdrawal, we discussed the potential value of internal cue-exposure strategies for individuals who use substances as a way to cope with negative affect. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC-812,15 Parkman St, Boston, MA 02114 USA. EM motto@partners.org FU NIDA NIH HHS [R01 DA10040, R10 DA09692] NR 92 TC 46 Z9 46 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2004 VL 18 IS 1 BP 69 EP 87 DI 10.1016/j.janxdis.2003.07.007 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 766LE UT WOS:000188377200006 PM 14725869 ER PT J AU Devineni, T Blanchard, EB Hickling, EJ Buckley, TC AF Devineni, T Blanchard, EB Hickling, EJ Buckley, TC TI Effect of psychological treatment on cognitive bias in motor vehicle accident-related Posttraumatic Stress Disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; stroop; information processing; cognitive bias ID GENERALIZED ANXIETY DISORDER; ATTENTIONAL BIAS; INFORMATION; DEPRESSION; INVENTORY; PHOBIA; PTSD; TASK AB The modified or "emotional" Stroop paradigm has been frequently employed in previous evaluations of information processing models of Posttraumatic Stress Disorder (PTSD) and other anxiety disorders. These studies have frequently documented an attentional bias to trauma-specific threatening stimuli in PTSD patients. However, the response of the Stroop color-naming interference effect to psychological treatment has yet to be tested in a trauma population. The present study evaluated the effects of three treatment conditions on the Stroop interference effect in motor vehicle accident (MVA) survivors with PTSD. Following treatment, participants were classified as either treatment responders or nonresponders. Participants named the color of three types of stimuli: MVA trauma-specific words, neutral words, and nonwords. Results showed that change in selective color-naming interference for trauma cues was unrelated to treatment response or modality at either posttreatment or follow-up. Findings cast doubt on the clinical utility of the modified Stroop test as a measure of treatment outcome in this population. (C) 2002 Elsevier Inc. All rights reserved. C1 SUNY Albany, Albany, NY 12222 USA. Sage Colleges & Capital Psycholog Associates, Albany, NY 12222 USA. Boston Univ, Boston VA Med Ctr, Natl Ctr PTSD, Sch Med, Boston, MA USA. RP Devineni, T (reprint author), Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. EM headache@albany.edu FU NIMH NIH HHS [MH-48476] NR 31 TC 26 Z9 26 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2004 VL 18 IS 2 BP 211 EP 231 AR PII S0887-6185(02)00247-5 DI 10.1016/S0887-6185(02)00247-5 PG 21 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 807VC UT WOS:000220528000008 PM 15033217 ER PT J AU Li, J Helmerhorst, EJ Leone, CW Troxler, RF Yaskell, T Haffajee, AD Socransky, SS Oppenheim, FG AF Li, J Helmerhorst, EJ Leone, CW Troxler, RF Yaskell, T Haffajee, AD Socransky, SS Oppenheim, FG TI Identification of early microbial colonizers in human dental biofilm SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE acquired enamel pellicle; bacteria; biofilm; microbial; plaque; salivary ID SCANNING ELECTRON-MICROSCOPY; ACQUIRED ENAMEL PELLICLE; ROOT SURFACES INVIVO; ACTINOMYCES-VISCOSUS; SUBGINGIVAL PLAQUE; STREPTOCOCCUS-MUTANS; BACTERIAL ADHERENCE; EARLY COLONIZATION; GNOTOBIOTIC-RATS; TOOTH SURFACES AB Aims: To elucidate the first colonizers within in vivo dental biofilm and to establish potential population shifts that occur during the early phases of biofilm formation. Methods and Results: A 'checkerboard' DNA - DNA hybridization assay was employed to identify 40 different bacterial strains. Dental biofilm samples were collected from 15 healthy subjects, 0, 2, 4 and 6 h after tooth cleaning and the composition of these samples was compared with that of whole saliva collected from the same individuals. The bacterial distribution in biofilm samples was distinct from that in saliva, confirming the selectivity of the adhesion process. In the very early stages, the predominant tooth colonizers were found to be Actinomyces species. The relative proportion of streptococci, in particular Streptococcus mitis and S. oralis, increased at the expense of Actinomyces species between 2 and 6 h while the absolute level of Actinomyces remained unaltered. Periodontal pathogens such as Tannerella forsythensis ( Bacteroides forsythus), Porphyromonas gingivalis and Treponema denticola as well as Actinobacillus actinomycetemcomitans were present in extremely low levels at all the examined time intervals in this healthy group of subjects. Conclusion: The data provide a detailed insight into the bacterial population shifts occurring within the first few hours of biofilm formation and show that the early colonizers of the tooth surface predominantly consist of beneficial micro-organisms. Significance and Impact of the Study: The early colonizers of dental plaque are of great importance in the succession stages of biofilm formation and its overall effect on the oral health of the host. C1 Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Helmerhorst, EJ (reprint author), 700 Albany St,W201, Boston, MA 02118 USA. EM helmer@bu.edu OI Helmerhorst, Eva/0000-0002-4803-3018 FU NIDCR NIH HHS [DE 05672, DE 07652, DE 11691, DE 14368, DE 14950] NR 32 TC 167 Z9 181 U1 5 U2 35 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PY 2004 VL 97 IS 6 BP 1311 EP 1318 DI 10.1111/j.1365-2672.2004.02420.x PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 870MP UT WOS:000225061600022 PM 15546422 ER PT J AU McGibbon, CA Krebs, DE AF McGibbon, CA Krebs, DE TI Discriminating age and disability effects in locomotion: neuromuscular adaptations in musculoskeletal pathology SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE mechanical power; joint angles and moments; hip and ankle compensation; lower extremity arthritis ID COMPENSATORY GAIT MECHANICS; STRENGTH IMPAIRMENT; DISABLED ELDERS; WALKING; SPEED; REHABILITATION; PROGRESSION; ARTHRITIS; EXERCISE; SUPPORT AB We identified biomechanical variables indicative of lower extremity dysfunction, distinct from age-related gait adaptations, and examined interrelationships among these variables to better understand the neuromuscular adaptations in gait. Sagittal plane ankle, knee, and hip peak angles, moments, and powers and spatiotemporal parameters were acquired during preferred-speed gait in 120 subjects: 45 healthy young, 37 healthy elders, and 38 elders with functional limitations due to lower extremity musculoskeletal pathology, primarily arthritis. Multiple analysis of covariance with discriminate analysis, adjusted for gait speed, was used to identify the variables discriminating groups. Correlation analysis was used to explore interrelationships among these variables within each group. Healthy elders were discriminated ( sensitivity 76%, specificity 82%) from young adults via decreased late-stance ankle plantar flexion angle, increased late-stance knee power absorption, and early-stance hip extensor power generation. Disabled elders were discriminated ( sensitivity 74%, specificity 73%) from healthy elders via decreased late-stance ankle plantar flexor moment and power generation, increased early-stance ankle dorsiflexor moment, and late-stance hip flexor moment and power absorption. Relationships among variables showed a higher degree of coupling for the disabled elders compared with the healthy groups, suggesting a reduced ability to alter motor strategies. Our data suggest that, beyond age-related changes, elders with lower extremity dysfunction rely excessively on passive action of hip flexors to provide propulsion in late stance and contralateral ankle dorsiflexors to enhance stability. These findings support a growing body of evidence that gait changes with age and disablement have a neuromuscular basis, which may be informative in a motor control framework for physical therapy interventions. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG-12561]; NIAMS NIH HHS [R01-AR-45278] NR 33 TC 39 Z9 40 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2004 VL 96 IS 1 BP 149 EP 160 DI 10.1152/japplphysiol.00422.2003 PG 12 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 750HC UT WOS:000186984400022 PM 12949019 ER PT J AU Conhaim, RL Watson, KE Heisey, DM Leverson, GE Harms, BA AF Conhaim, RL Watson, KE Heisey, DM Leverson, GE Harms, BA TI Thromboxane receptor analog, U-46619, redistributes pulmonary microvascular perfusion in isolated rat lungs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE alveolar perfusion; fluorescent microspheres; vasoconstriction; dispersion index analysis; perfusion heterogeneity ID VASCULAR-RESISTANCE; CIRCULATION; HYPOXIA; VOLUME AB Effects of vasoconstriction on the distribution of perfusion among alveoli are not well understood. To address this, we used a new method we developed to determine how microvascular perfusion distribution was affected by a potent vasoconstrictor, the thromboxane receptor analog U- 46619. Our method was to infuse 4-mum- diameter fluorescent latex microspheres into the circulation of isolated rat lungs vasoconstricted with U- 46619. We used a confocal microscope to image trapping patterns of the particles in dried sections of the lungs and then used dispersion index analysis to quantify the particle patterns in the images, which encompassed similar to 2,000 alveoli. Dispersion indexes revealed significantly more particle clustering ( inhomogeneous distribution) in vasoconstricted lungs than in normal flow controls or in controls in which flow was reduced by either lowering pulmonary arterial pressure or raising left atrial pressure. These results suggest that vasoconstriction occurred in the microvessels themselves, which are much smaller vessels than those previously thought to be capable of vasoconstriction. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Conhaim, RL (reprint author), Univ Wisconsin, Sch Med, Dept Surg, H5-301-BX3236 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. NR 17 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2004 VL 96 IS 1 BP 245 EP 252 DI 10.1152/japplphysiol.00271.2003 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 750HC UT WOS:000186984400034 PM 12959963 ER PT J AU Muratoglu, OK Greenbaum, ES Bragdon, CR Jasty, M Freiberg, AA Harris, WH AF Muratoglu, OK Greenbaum, ES Bragdon, CR Jasty, M Freiberg, AA Harris, WH TI Surface analysis of early retrieved acetabular polyethylene liners - A comparison of conventional and highly crosslinked polyethylenes SO JOURNAL OF ARTHROPLASTY LA English DT Article DE ultra-high molecular weight polyethylene (UHMWPE); total hip arthroplasty; cross-linking; wear; retrieval study; melt-recovery ID MOLECULAR-WEIGHT POLYETHYLENE; WEAR; ARTHROPLASTY AB In vivo wear behavior of 16 highly cross-linked and 19 conventional polyethylene acetabular explants, at an average in vivo duration of 6 months were studied. Highly cross-linked groups showed machining marks from the original manufacturing process in some areas and extensive scratching and some polishing of the articulating surfaces. The conventional group showed greater loss of machining marks, scratching, and polishing. Representative samples were melted to allow recovery of plastic deformation and to show true removal of material caused by wear. Melt-recovery experiments consistently showed the disappearance of surface scratches and the restoration of the original machining marks in the highly crosslinked explants. In the conventional group, few of the scratches were eliminated and only limited restoration of the machining marks was apparent. These observations support the hypothesis that the early in vivo scratching of highly cross-linked polyethylene acetabular liners is primarily caused by plastic deformation. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. NR 13 TC 50 Z9 53 U1 1 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2004 VL 19 IS 1 BP 68 EP 77 DI 10.1016/j.arth.2003.08.003 PG 10 WC Orthopedics SC Orthopedics GA 765AL UT WOS:000188244400013 PM 14716654 ER PT J AU Kalayci, O Sonna, LA Woodruff, PG Camargo, CA Luster, AD Lilly, CM AF Kalayci, O Sonna, LA Woodruff, PG Camargo, CA Luster, AD Lilly, CM TI Monocyte chemotactic protein-4 (MCP-4; CCL-13): A biomarker of asthma SO JOURNAL OF ASTHMA LA English DT Article DE asthma; chemokine; biomarker; MCP-4; inflammation ID CC-CHEMOKINE; EMERGENCY-DEPARTMENT; EXPRESSION; EOTAXIN; CELLS; INFLAMMATION; EOSINOPHILS; CYTOKINES; ACTIVATION; POPULATION AB Airway expression of monocyte chemotactic protein-4 (MCP-4; CCL-13) is known to be increased in asthmatic airways where it is induced by proallergic cytokines, but the relationship of its systemic expression to asthma and naturally occurring exacerbations is unknown. We determined plasma levels of MCP-4 in 356 individuals with chronic-stable asthma and 240 normal subjects and compared plasma levels of MCP-4 in 30 patients who presented for emergent treatment of asthma with levels in 90 subjects with chronic-stable asthma matched for age, gender, and ethnicity. Median plasma MCP-4 levels were higher in patients with chronic-stable asthma than in normal subjects (399 vs. 307 pg/mL) (p < 0.001). In our entire cohort (n = 596), subjects with an MCP-4 greater than or equal to 218 pg/mL were at increased risk of asthma (p < 0.001 odds ratio, 3.26; 95% Cl, 2.22-4.79). Logistic regression identified MCP-4 as an independent predictor of asthma diagnosis. The MCP-4 levels are higher in individuals with an acute asthma exacerbation than in subjects with chronic-stable asthma (513 vs. 355 pg/mL) (p = 0.002). The MCP-4 is a systemically expressed biomarker that independently predicts susceptibility to asthma and is directly associated with exacerbations. Elevated MCP-4 levels identify a group of asthmatics with systemic evidence of allergic inflammation who may be at risk for exacerbations or may benefit from abrogation of MCP-4. C1 Harvard Univ, Div Pulm & Crit Care, Sch Med, Brigham & Womens Hosp,Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. USA, Environm Med Res Inst, Natick, MA 01760 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Boston, MA 02115 USA. RP Lilly, CM (reprint author), Harvard Univ, Div Pulm & Crit Care, Sch Med, Brigham & Womens Hosp,Channing Lab,Dept Med, 75 Francis St,Tower 4, Boston, MA 02115 USA. EM clilly@partners.org FU NHLBI NIH HHS [HL/AI-64104]; NIAID NIH HHS [AI 40618] NR 24 TC 23 Z9 25 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PY 2004 VL 41 IS 1 BP 27 EP 33 DI 10.1081/JAS-120024590 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 805CZ UT WOS:000220345700004 PM 15046375 ER PT J AU Cense, B Chen, HC Park, BH Pierce, MC de Boer, JF AF Cense, B Chen, HC Park, BH Pierce, MC de Boer, JF TI In vivo birefringence and thickness measurements of the human retinal nerve fiber layer using polarization-sensitive optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE birefringence; glaucoma; retinal nerve fiber layer; polarization-sensitive optical coherence tomography ID RESOLUTION AB Glaucoma causes damage of the nerve fiber layer, which may cause loss of retinal birefringence. Therefore, PS-OCT is a potentially useful technique for the early detection of glaucoma. We built a fiber-based PS-OCT setup that produces real-time images of the human retina in vivo, coregistered with retinal video images of the location of PS-OCT scans. Preliminary measurements of a healthy volunteer show that the double-pass phase retardation per unit of depth of the RNFL is not constant and varies with location, with values between 0.18 and 0.37 deg/mum. A trend in the preliminary measurements shows that the nerve fiber layer located inferior and superior to the optic nerve head is more birefringent than the thinner layer of nerve fiber tissue in the temporal and nasal regions. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Cense, B (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 50 Blossom St,BAR 714, Boston, MA 02114 USA. EM bcense@helix.mgh.harvard.edu; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [1R24 EY 12877] NR 17 TC 81 Z9 82 U1 0 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN-FEB PY 2004 VL 9 IS 1 BP 121 EP 125 DI 10.1117/1.1627774 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 765BR UT WOS:000188247700011 PM 14715063 ER PT J AU Bragdon, CR Jasty, M Greene, M Rubash, HE Harris, WH AF Bragdon, CR Jasty, M Greene, M Rubash, HE Harris, WH TI Biologic fixation of total hip implants - Insights gained from a series of canine studies SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY MAR, 2004 CL San Francisco, CA SP Amer Acad Orthopaed Surg ID BONE INGROWTH; COMPONENTS; COATINGS C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1206,55 Fruit St, Boston, MA 02114 USA. EM cbragdon@partners.org NR 11 TC 25 Z9 26 U1 1 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PY 2004 VL 86A SU 2 BP 105 EP 117 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 880FO UT WOS:000225774600015 PM 15691115 ER PT J AU Valverde, P Kawai, T Taubman, MA AF Valverde, P Kawai, T Taubman, MA TI Selective blockade of voltage-gated potassium channels reduces inflammatory bone resorption in experimental periodontal disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP Amer Soc Bone Mineral Res DE bone resorption; T-lymphocyte; potassium channel; RANKL; osteoprotegerin ID KAPPA-B-LIGAND; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; OSTEOCLASTOGENESIS-INHIBITORY FACTOR; ACTINOMYCETEMCOMITANS SEROTYPE-B; T-CELL ACTIVATION; RECEPTOR ACTIVATOR; K+ CHANNELS; OSTEOPROTEGERIN LIGAND; CYCLOSPORINE-A; ION CHANNELS AB The effects of the potassium channel (Kv1.3) blocker kaliotoxin on T-cell-mediated periodontal bone resorption were examined in rats. Systemic administration of kaliotoxin abrogated the bone resorption in conjunction with decreased RANKL mRNA expression by T-cells in gingival tissue. This study suggests a plausible therapeutic approach for inflammatory bone resorption by targeting Kv1.3. Introduction: Kv1.3 is a critical potassium channel to counterbalance calcium influx at T-cell receptor activation. It is not known if Kv1.3 also regulates RANKL expression by antigen-activated T-cells, and consequently affects in vivo bone resorption mediated by activated T-cells. Materials and Methods: Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein-specific Th1-clone cells were used to evaluate the expression of Kv1.3 (using reverse transcriptase-polymerase chain reaction [RT-PCR] and Western blot analyses) and the effects of the potassium channel blocker kaliotoxin (0-100 nM) on T-cell activation parameters ([H-3]thymidine incorporation assays and ELISA) and expression of RANKL and osteoprotegerin (OPG; flow cytometry, Western blot, and RT-PCR analyses). A rat periodontal disease model based on the adoptive transfer of activated 29-kDa outer membrane protein-specific Th1 clone cells was used to analyze the effects of kaliotoxin in T-cell-mediated alveolar bone resorption and RANKL and OPG mRNA expression by gingival T-cells. Stimulated 29-kDa outer membrane protein-specific Th1 clone cells were transferred intravenously on day 0 to all animals used in the study (n = 7 animals per group). Ten micrograms of kaliotoxin were injected subcutaneously twice per day on days 0, 1, 2, and 3, after adoptive transfer of the T-cells. The control group of rats was injected with saline as placebo on the same days as injections for the kaliotoxin-treated group. The MOCP-5 osteoclast precursor cell line was used in co-culture studies with fixed 29-kDa outer membrane protein-specific Th1-clone cells to measure T-cell-derived RANKL-mediated effects on osteoclastogenesis and resorption pit formation assays in vitro. Statistical significance was evaluated by Student's t-test. Results: Kaliotoxin decreased T-cell activation parameters of 29-kDa outer membrane protein-specific Th1 clone cells in vitro and in vivo. Most importantly, kaliotoxin administration resulted in an 84% decrease of the bone resorption induced in the saline-treated control group. T-cells recovered from the gingival tissue of kaliotoxin-treated rats displayed lower ratios of RANKL and OPG mRNA expression than those recovered from the control group. The ratio of RANKL and osteoprotegerin protein expression and induction of RANKL-dependent osteoclastogenesis by the activated T-cells were also markedly decreased after kaliotoxin treatments in vitro. Conclusion: The use of kaliotoxin or other means to block Kv1.3 may constitute a potential intervention therapy to prevent alveolar bone loss in periodontal disease. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Dept Oral & Dev Biol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA USA. RP Valverde, P (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St,Room 626, Boston, MA 02111 USA. RI Valverde, Paloma/A-9897-2008 FU NIDCR NIH HHS [DE-03420, DE-14551] NR 35 TC 65 Z9 71 U1 1 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2004 VL 19 IS 1 BP 155 EP 164 DI 10.1359/JBMR.0301213 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 757NF UT WOS:000187567800018 PM 14753747 ER PT J AU Ansari, M Araoz, PA Gerard, SK Watzinger, N Lund, GK Massie, BM Higgins, CB Saloner, DA AF Ansari, M Araoz, PA Gerard, SK Watzinger, N Lund, GK Massie, BM Higgins, CB Saloner, DA TI Comparison of late enhancement cardiovascular magnetic resonance and thallium SPECT in patients with coronary disease and left ventricular dysfunction SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE heart failure; magnetic resonance imaging; SPECT; myocardial infarction ID POSITRON-EMISSION-TOMOGRAPHY; MYOCARDIAL VIABILITY; ARTERY-DISEASE; HIBERNATING MYOCARDIUM; MOTION ARTIFACTS; TL-201; REST; RECOVERY; ATTENUATION; IMPROVEMENT AB Purpose: Late enhancement magnetic resonance imaging (MRI) was compared with thallium-201 rest-redistribution single photon emission computed tomography (SPECT) in patients with reduced left ventricular (LV) function and prior myocardial infarction (MI). Background: Hyperenhancement on contrast cardiac MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) has been reported to identify nonviable myocardium. Comparisons of MRI and thallium-201 SPECT have recently been reported. This study focuses on the comparison of these modalities specifically in patients with ischemic heart failure, where viability determination is most clinically relevant. Methods: Fifteen patients with LV dysfunction and prior MI [mean ejection fraction (EF) 35 +/- 11%] underwent thallium-201 rest-redistribution scintigraphy and contrast MRI on separate days. Each short axis slice was divided into six 60-degree segments, and correlations between MRI and scintigraphy were made on viability detection for each segment. For SPECT, the mean uptake score was calculated from the average of all percent relative activity values throughout each segment. Areas with <50% of maximal thallium uptake were considered nonviable. On MRI, regions with increased signal intensity after an injection of 0.1 mmol/kg Gd-DPTA were considered nonviable. Results: A total of 558 segments were analyzed. Overall, there was a strong inverse relationship between the area of hyperenhancement on MRI and diminished thallium-201 uptake on SPECT (r=-0.51, P<0.001). There was a significant correlation between the imaging methods for each individual segment, except for the inferior-septal segment (r=-0.38, P<0.08). Conclusions: In patients with LV dysfunction and prior MI, our data suggest MRI hyperenhancement significantly correlates with myocardial nonviability by thallium-201 SPECT. Correlations were weaker in the inferior-septal region, which may be due to SPECT attenuation artifact. C1 Univ Calif San Francisco, Dept Radiol 114D, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Serv Radiol, San Francisco, CA USA. EM saloner@itsa.ucsf.edu NR 23 TC 17 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 EI 1532-429X J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PY 2004 VL 6 IS 2 BP 549 EP 556 DI 10.1081/JCMR-120030582 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 819KE UT WOS:000221313000010 PM 15137339 ER PT J AU Baron, A Migita, T Tang, D Loda, M AF Baron, A Migita, T Tang, D Loda, M TI Fatty acid synthase: A metabolic oncogene in prostate cancer? SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE fatty acid synthase; prostate cancer; metabolism ID MOLECULAR MARKER; ANDROGEN INDEPENDENCE; MEDIATED APOPTOSIS; MASS-SPECTROMETRY; LIPID-METABOLISM; APOLIPOPROTEIN-E; GENE-EXPRESSION; ADVANCED-STAGE; COENZYME-A; IN-VIVO AB In 1920, Warburg suggested that tumors consistently rely on anaerobic pathways to convert glucose to ATP even in the presence of abundant oxygen [Warberg, 1956] despite the fact that it is less efficient for energy supply than aerobic glycolysis. The reasons for this remain obscure to date. More often than not, the microenvironment of solid tumors contains regions of poor oxygenation and high acidity. In this context hypoxia can act in an epigenetic fashion, inducing changes in gene expression and in metabolism for survival. It is reasonable to assume that only the tumor cells capable of developing an unusual tolerance to limiting oxygen availability and to the acidosis resulting from excessive lactate production, can survive. In addition to the striking changes that occur in glucose metabolism, studies in human cancer patients suggest that there is often also an increase in free fatty acid turnover, oxidation and clearance [Legaspi et al., 1987; Hyltander et al., 1991]. For instance, a lipid mobilizing factor produced by tumor cells appears to be responsible for the increase in whole body fatty acid oxidation [Russell and Tisdale, 2002]. Fatty acids synthesis in tumor tissues also occurs at very high rates, as first demonstrated more than half a century ago [Medes et al., 1953]. Importantly, C-14 glucose studies have shown that in tumor cells almost all fatty acids derive from de novo synthesis despite adequate nutritional supply [Sabine and Abraham, 1967; Ookhtens et al., 1984; Weiss et al., 1986]. In addition, tumors overexpressing fatty acid synthase (FAS), the enzyme responsible for de novo synthesis of fatty acids, display aggressive biologic behavior compared to those tumors with normal FAS levels, suggesting that FAS overexpression confers a selective growth advantage. Here, we will review the roles that FAS plays in important cellular processes such as apoptosis and proliferation. In addition, speculations on the putative role of FAS in the altered metabolic pathways of prostate cancer cells will be explored. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease. (C) 2003 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D-740B,44 Binney St, Boston, MA 02115 USA. NR 67 TC 154 Z9 162 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 2004 VL 91 IS 1 BP 47 EP 53 DI 10.1002/jcb.10708 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 759AG UT WOS:000187714700007 PM 14689581 ER PT J AU Wang, YH Pampou, S Fujikawa, K Varticovski, L AF Wang, YH Pampou, S Fujikawa, K Varticovski, L TI Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; GROWTH-FACTOR; VASCULAR-PERMEABILITY; IN-VITRO; MICROVASCULAR PERMEABILITY; INDUCED INCREASE; NITRIC-OXIDE; ANGIOGENESIS; CADHERIN; TIE2 AB Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) cooperate in migration and survival of endothelial cells by activation of phosphatidylinositol-3 (PI-3) kinase and mitogen activating protein (MAP) kinase pathways. However, Ang1 opposes the effect of VEGF on vascular permeability. We found that Ang1 also blocks VEGF-mediated diffusion of fluoresin isothiocyanate (FITC)-labeled albumin across an endothelial cell monolayer. VEGF-mediated vascular permeability has been attributed, in part, to activation of phospholipase A(2) and subsequent formation of platelet activating factor. However, Ang1 had no effect on VEGF-induced activation of phospholipase A(2) or the release of arachidonic acid. VEGF-mediated permeability was associated with disruption of endothelial cell junctional complexes, dissociation of beta-catenin from VE-cadherin, and accumulation of beta-catenin in the cytosol. In contrast, Ang1 enhanced the interaction of beta-catenin with VE-cadherin and impaired VEGF-mediated dissociation of this complex. Ang1 also blocked VEGF-induced translocation of protein kinase C (PKC) and beta(2) to the membrane, but had no effect on activation of PKCa. In addition, staurosporine and a PKCbeta inhibitor, LY3791 96, blocked VEGF-mediated dissociation of beta-catenin from VE-cadherin, diffusion of albumin across the endothelial cell monolayer, and translocation of PKCbeta isoforms. These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKCbeta isoforms and that this pathway is blocked by Ang1. (C) 2003 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Sapporo Med Univ, Dept Sci 4, Sapporo, Hokkaido, Japan. NCI, Off Director Lab Human Cancinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, YH (reprint author), Harvard Univ, Inst Med, BIDMC Genom Ctr, Room 208,4 Blackfan Circle, Boston, MA 02115 USA. FU NCI NIH HHS [CA53094] NR 52 TC 35 Z9 36 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2004 VL 198 IS 1 BP 53 EP 61 DI 10.1002/jcp.10386 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 745WF UT WOS:000186713200007 PM 14584044 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI GCMB - Another serendipitous gift from evolution to clinical investigators SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID PARATHYROID-GLANDS; THYMUS; MORPHOGENESIS; GENE C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 12 TC 4 Z9 4 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 6 EP 7 DI 10.1210/jc.2003-031943 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000002 PM 14715817 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, NE DePinho, RA TI Telomeres, stem cells, senescence, and cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; MAMMARY EPITHELIAL-CELLS; ARF TUMOR-SUPPRESSOR; IMMORTAL HUMAN-CELLS; CARCINOMA IN-SITU; HUMAN FIBROBLASTS; ATAXIA-TELANGIECTASIA; DEFICIENT MICE; COLORECTAL CARCINOGENESIS; P53-DEPENDENT APOPTOSIS AB Mammalian aging occurs in part because of a decline in the restorative capacity of tissue stem cells. These self-renewing cells are rendered malignant by a small number of oncogenic mutations, and overlapping tumor suppressor mechanisms (e.g., p16(INK4a)-Rb, ARF-p53, and the telomere) have evolved to ward against this possibility. These beneficial antitumor pathways, however, appear also to limit the stem cell life span, thereby contributing to aging. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Med & Genet, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst,Dept Med & Genet, Boston, MA USA. RP Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Med & Genet, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu NR 123 TC 287 Z9 315 U1 3 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2004 VL 113 IS 2 BP 160 EP 168 DI 10.1172/JCI200420761 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 764EZ UT WOS:000188195600003 PM 14722605 ER PT J AU Kitamura, T Kitamura, Y Nakae, J Giordano, A Cinti, S Kahn, CR Efstratiadis, A Accili, D AF Kitamura, T Kitamura, Y Nakae, J Giordano, A Cinti, S Kahn, CR Efstratiadis, A Accili, D TI Mosaic analysis of insulin receptor function SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; GROWTH-FACTOR-I; FACTOR-BINDING-PROTEINS; PANCREATIC BETA-CELLS; TYPE-1 IGF RECEPTOR; ADIPOSE-TISSUE; GLUCOSE-INTOLERANCE; GENE-TRANSCRIPTION; TRANSGENIC MOUSE; POSTNATAL-GROWTH AB Insulin promotes both metabolism and growth. However, it is unclear whether insulin-dependent growth is merely a result of its metabolic actions. Targeted ablation of insulin receptor (Insr) has not clarified this issue, because of early postnatal lethality. To examine this question, we generated mice with variable cellular mosaicism for null Insr alleles. Insr ablation in approximately 80% of cells caused extreme growth retardation, lipoatrophy, and hypoglycemia, a clinical constellation that resembles the human syndrome of leprechaunism. Insr ablation in 98% of cells, while resulting in similar growth retardation and lipoatrophy, caused diabetes without beta-cell hyperplasia. The growth retardation was associated with a greater than 60-fold increase in the expression of hepatic insulin-like growth factor binding protein-1. These findings indicate that insulin regulates growth independently of metabolism and that the number of insulin receptors is an important determinant of the specificity of insulin action. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Univ Marche, Dept Anat, Ancona, Italy. Harvard Univ, Joslin Diabet Ctr, Boston, MA USA. Columbia Univ, Coll Phys & Surg, Dept Genet, New York, NY USA. RP Accili, D (reprint author), Med Sci Res Pavil, 1150 St Nicholas Ave,Room 238A, New York, NY 10032 USA. EM da230@columbia.edu FU NIDDK NIH HHS [R01 DK058282, DK58282, R37 DK058282] NR 52 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2004 VL 113 IS 2 BP 209 EP 219 DI 10.1172/JCI200417810 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 764EZ UT WOS:000188195600011 PM 14722613 ER PT J AU Goldberg, RM Sargent, DJ Morton, RF Fuchs, CS Ramanathan, RK Williamson, SK Findlay, BP Pitot, HC Alberts, SR AF Goldberg, RM Sargent, DJ Morton, RF Fuchs, CS Ramanathan, RK Williamson, SK Findlay, BP Pitot, HC Alberts, SR TI A Randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer 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 CONTINUOUS-INFUSION; 1ST-LINE TREATMENT; MODULATION; FAILURE; BOLUS; DNA AB Purpose Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. Patients and Methods Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. Results A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6,5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. Conclusion The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer. C1 Univ N Carolina, Div Hematol Oncol, N Cent Canc Treatment Grp, Chapel Hill, NC 27599 USA. Univ N Carolina, Div Med Oncol, Chapel Hill, NC USA. Mayo Clin, Div Biostat, N Cent Canc Treatment Grp, Rochester, MN USA. Iowa Oncol Res Assoc, Community Clin Oncol Program, N Cent Canc Treatment Grp, Des Moines, IA USA. Dana Farber Canc Inst, Dept Oncol, Canc & Acute Leukemia Grp B, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Div Med Oncol, Eastern Cooperat Oncol Grp, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Div Hematol & Oncol, SW Oncol Grp, Kansas City, KS 66103 USA. Natl Canc Inst Canada, St Catharines, ON, Canada. RP Goldberg, RM (reprint author), Univ N Carolina, Div Hematol Oncol, N Cent Canc Treatment Grp, CB 7305,3009 Old Clin Bldg, Chapel Hill, NC 27599 USA. RI Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 FU NCI NIH HHS [CA 32102, CA 21115, CA 25224, CA 38926, CA 77202] NR 22 TC 1382 Z9 1443 U1 2 U2 23 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 1 PY 2004 VL 22 IS 1 BP 23 EP 30 DI 10.1200/JCO.2004.09.046 PG 8 WC Oncology SC Oncology GA 760DL UT WOS:000187796300006 PM 14665611 ER PT J AU Meyerhardt, JA Tepper, JE Niedzwiecki, D Hollis, DR Schrag, D Ayanian, JZ O'Connell, MJ Weeks, JC Mayer, RJ Willett, CG MacDonald, JS Benson, AB Fuchs, CS AF Meyerhardt, JA Tepper, JE Niedzwiecki, D Hollis, DR Schrag, D Ayanian, JZ O'Connell, MJ Weeks, JC Mayer, RJ Willett, CG MacDonald, JS Benson, AB Fuchs, CS TI Impact of hospital procedure volume on surgical operation and long-term outcomes in high-risk curatively resected rectal cancer: Findings from the Intergroup 0114 study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT THERAPY; RADIATION-THERAPY; COLORECTAL-CANCER; UNITED-STATES; MORTALITY; SURVIVAL; SURGERY; FLUOROURACIL; POPULATION; VARIABLES AB Purpose Prior studies have demonstrated superior outcomes after a curative surgical resection of rectal cancer at hospitals where the volume of such surgeries is high. However, because these studies often lack detailed information on tumor and treatment characteristics as well as cancer recurrence, the true nature of this relation remains uncertain. Patients and Methods We studied a nested cohort of 1,330 patients with stage II and stage III rectal cancer participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed differences in rates of sphincter-preserving operations, overall survival, and cancer recurrence by hospital surgical volume. Results We observed a significant difference in the rates of abdominoperineal resections across tertiles of hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after adjustment for tumor distance from the anal verge. However, this higher rate of sphincter-sparing operations at high-volume centers was not accompanied by any increase in recurrence rates. Hospital surgical volume did not predict overall, disease-free, recurrence-free, or local recurrence-free survival. However, among patients who did not complete the planned adjuvant chemoradiotherapy (270 patients), those who underwent surgery at low-volume hospitals had a significant increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% Cl, 1.01 to 3.72; P =.04 for the trend) and a nonsignificant trend toward increased overall mortality (P =.08) and local recurrence (P =.10). In contrast, no significant volume-outcome relation was noted among patients who did complete postoperative therapy. Conclusion Using prospectively recorded data, we found that hospital surgical volume had no significant effect on rectal cancer recurrence or survival when patients completed standard adjuvant therapy. Sphincter-preserving surgery was more commonly performed at high-volume centers. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Hlth Outcomes Res Grp, New York, NY 10021 USA. St Vincents Clin Canc Ctr, New York, NY USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1K07 CA 97992-01A1, CA 31946] NR 33 TC 81 Z9 87 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2004 VL 22 IS 1 BP 166 EP 174 DI 10.1200/JCO.2004.04.172 PG 9 WC Oncology SC Oncology GA 760DL UT WOS:000187796300025 PM 14701779 ER PT J AU Biederman, J AF Biederman, J TI Impact of comorbidity in adults with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Diagnosing and Treating Attention-Deficit/Hyperactivity Disorder in Adults CY JAN 17, 2003 CL Boston, MA ID DEFICIT HYPERACTIVITY DISORDER; AGE-DEPENDENT DECLINE; PSYCHIATRIC STATUS; GENDER DIFFERENCES; ECONOMIC BURDEN; DEPRESSION; CHILDREN; COST; BOYS; ADHD AB Persistence of attention-deficit/hyperactivity disorder (ADHD) into adulthood and male-to-female ratios of this disorder in childhood and adulthood have been controversial issues in the ADHD diagnosis in adults. Research has resolved these controversies and in turn provided support for the validity of the diagnosis in adults. Support for the diagnosis can also be found in data that show the lifetime prevalence rate for comorbid conditions such as antisocial disorders, mood and anxiety disorders, and substance abuse disorders to be consistent across pediatric and adult populations with ADHD. These coexisting conditions add not only to the impairment associated with ADHD in adults but also to the disorder's economic burden, the extent of which is currently unknown. However, adults with the disorder, like children, probably have higher health care use and costs than people without the disorder. Little, too, is known about the social cost of ADHD, but if left untreated, the impact may be substantial. Research to determine the occupational costs associated with ADHD is ongoing, but until that and other cost-of-illness data are available, studies on the economic costs of the comorbid conditions depression, anxiety, and substance abuse and dependence may be used to make suppositions about the economic impact of ADHD in adults. More studies are needed on the outcomes of adults with this disorder, especially cost-of-illness studies. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), 15 Parkman St,WACC 725, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu NR 22 TC 138 Z9 143 U1 1 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 3 BP 3 EP 7 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BU UT WOS:000222312200001 PM 15046528 ER PT J AU Rosenbaum, JF AF Rosenbaum, JF TI The development of Clonazepam as a psychotropic: The Massachusetts General Hospital experience SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Revisiting the Use of High-Potency Benzodiazepines CY JUL 11, 2003 CL Boston, MA ID PANIC-DISORDER; BIPOLAR DISORDER; SOCIAL PHOBIA; DOUBLE-BLIND; ALPRAZOLAM; AGORAPHOBIA; EFFICACY; THERAPY; TRIAL AB The pathophysiology of anxiety disorders is not clearly understood; therefore, clinical observation, case reports, and case reviews continue to enhance physicians' understanding of disease and treatment mechanisms. At Massachusetts General Hospital (MGH), physicians and researchers are guided by the recognition that available approved treatments are a small subset of what is sensible to try in anxiety disorders and have thus chosen to remain open minded and prepared to challenge assumptions about therapeutic agents and to explore new uses, including early work with high-potency benzodiazepines. Clinical trials established alprazolam as efficacious for panic disorder, and the agent was widely prescribed for patients at MGH after its approval. Soon, however, clinical observation suggested a short duration of benefit for a given dose in some patients. In some cases, patients who missed a dose reported rebound worsening. In response to the apparent problematic pharmacokinetics of alprazolam, members of the MGH psychiatry department pursued investigation that ultimately established the anti-panic efficacy of clonazepam as well as examined its effectiveness in the treatment of other disorders. such as bipolar disorder and social phobia. The process of exploring new uses of older agents remains a worthy effort while we await newer agents with innovative mechanisms of action. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM jrosenbaum@partner.org NR 21 TC 8 Z9 8 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 5 BP 3 EP 6 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BY UT WOS:000222312600001 PM 15078111 ER PT J AU Alexopoulos, GS Streim, J Carpenter, D Docherty, JP AF Alexopoulos, GS Streim, J Carpenter, D Docherty, JP TI Introduction: Methods, commentary, and summary SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; ELDERLY-PATIENTS; DOUBLE-BLIND; LONG-TERM; ATYPICAL ANTIPSYCHOTICS; PARKINSONS-DISEASE; BEHAVIORAL DISTURBANCES; PSYCHOTIC DISORDERS; TARDIVE-DYSKINESIA AB Antipsychotics are widely used in geriatric psychiatric disorders. A growing number of atypical antipsychotics are available, expanding clinical options but complicating decision-making. Many questions about use of antipsychotics in older patients remain unanswered by available clinical literature. We therefore surveyed expert opinion on antipsychotic use in older patients (65 years of age or older) for recommendations concerning indications for antipsychotics, choice of antipsychotics for different conditions (e.g., delirium, dementia, schizophrenia, delusional disorder, psychotic mood disorders) and for patients with comorbid conditions or history of side effects, dosing strategies, duration of treatment, and medication combinations. Method. Based on a literature review, a 47-question survey with 1,411 options was developed. Approximately three quarters of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, experts were asked to write in answers. The survey was sent to 52 American experts on treatment of older adults (38 geriatric psychiatrists, 14 geriatric internists/family physicians), 48 (92%) of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Guidelines indicating preferred treatment strategies were then developed for key clinical situations. Results. The expert panel reached consensus on 78% of options rated on the 9-point scale. The experts did not recommend using antipsychotics in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, neuropathic pain, severe nausea, motion sickness, or irritability, hostility, and sleep disturbance in the absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts' first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with nonpsychotic major depression fails to respond to antidepressants at adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer plus an antipsychotic (57% first line) or a mood stabilizer alone (48% first line) and would discontinue any antidepressant the patient is receiving. For psychotic mania, treatment of choice is a mood stabilizer plus an antipsychotic (98% first line). Risperidone (1.25-3.0 mg/day) and olanzapine (5-15 mg/day) were first-line options in combination with a mood stabilizer for mania with psychosis, with quetiapine (50-250 mg/day) high second line. If a patient has responded well, the experts recommended the following duration of treatment before attempting to taper and discontinue the antipsychotic: delirium, 1 week; agitated dementia, taper within 3-6 months to determine the lowest effective maintenance dose; schizophrenia, indefinite treatment at the lowest effective dose; delusional disorder, 6 months-indefinitely at the lowest effective dose; psychotic major depression, 6 months; and mania with psychosis, 3 months. For patients with diabetes, dyslipidemia, or obesity, the experts would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency). Quetiapine is first line for a patient with Parkinson's disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. More than a quarter of the experts considered these combinations contraindicated: clozapine + carbamazepine, ziprasidone + tricyclic antidepressant (TCA), and a low-potency conventional antipsychotic + fluoxetine. In combining antidepressants and antipsychotics, the experts would be much more cautious with selective serotonin reuptake inhibitors that are more potent inhibitors of the CYP 450 enzymes (i.e., fluoxetine, fluvoxamine, paroxetine) and with nefazodone, TCAs, and monoamine oxidase inhibitors. The experts recommended extra monitoring when combining any antipsychotic with lithium, carbamazepine, lamotrigine, or valproate (except aripiprazole, risperidone, or a high-potency conventional plus valproate) or with codeine, phenytoin, or tramadol. Conclusions. The experts reached a high level of consensus on many of the key treatment questions. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for common clinical dilemmas in the use of antipsychotics in elderly patients. Clinicians should keep in mind that no guidelines can address the complexities of an individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations. C1 Cornell Univ, Cornell Inst Geriatr Psychiat, Ithaca, NY 14853 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Alexopoulos, GS (reprint author), Cornell Univ, Cornell Inst Geriatr Psychiat, Ithaca, NY 14853 USA. NR 76 TC 200 Z9 208 U1 6 U2 31 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 2 BP 5 EP 99 PG 95 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BR UT WOS:000222311900001 PM 14994733 ER PT J AU Wirshing, DA AF Wirshing, DA TI Schizophrenia and obesity: Impact of antipsychotic medications SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID INDUCED WEIGHT-GAIN; PLACEBO-CONTROLLED TRIAL; BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIALS; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; ACUTE EXACERBATION; INSULIN-RESISTANCE; UNITED-STATES; OPEN-LABEL AB Obesity is an epidemic in this country and much of the rest of the developed world. It is a major contributor to a range of metabolic disorders responsible for much of the medical morbidity and mortality that burden our society. The combination of the costs to society of the chronic illness of schizophrenia with the costs of obesity and the chronic illnesses associated with it, e.g., metabolic disorders, diabetes, dyslipidemias, and cardiovascular disease, represents a major public health problem. Obesity in schizophrenia is accentuated even further largely through illness-related factors, like poor dietary conditions and more sedentary lifestyles, and particularly because many of the psychiatric medications (antipsychotics, mood stabilizers, and antidepressants) used to combat this devastating illness themselves result in weight gain that, if untreated, may result in the usual obesity-associated morbidity and mortality. This article is intended to review some of the physiology of obesity and obesity-related metabolic disorders, the risks to schizophrenia patients engendered by obesity, the evidence for weight gain associated with the antipsychotic drugs, and the possible mechanisms involved in antipsychotic medication-associated weight gain. C1 W Los Angeles Vet Affairs Med Ctr, Schizophrenia Treatment Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Wirshing, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Schizophrenia Treatment Unit, 11301 Wilshire Blvd,B151-H Mail Code 166747 Code, Los Angeles, CA 90073 USA. EM Donna.Wirshing@bmed.va.gov NR 163 TC 98 Z9 110 U1 5 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 18 BP 13 EP 26 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 884QW UT WOS:000226101900002 PM 15600381 ER PT J AU Spencer, TJ AF Spencer, TJ TI ADHD treatment across the life cycle SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Diagnosing and Treating Attention-Deficit/Hyperactivity Disorder in Adults CY JAN 17, 2003 CL Boston, MA ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; CLINICAL-TRIAL; CHILDREN; PLACEBO; ADULTS; ATOMOXETINE; BUPROPION; METHYLPHENIDATE AB Since attention-deficit/hyperactivity disorder (ADHD) is usually diagnosed in children, evidence from the studies of pharmacologic treatments for children with ADHD is used to inform pharmacologic treatment recommendations for adults. A large percentage of children diagnosed with ADHD have symptoms that persist into adolescence and adulthood. Evidence shows that pharmacologic treatments improve functional outcomes in children with ADHD, and studies using similar pharmacologic treatments show positive results in adults with ADHD. This article reviews the use of long-acting methylphenidate, mixed amphetamine salts, desipramine, monoamine oxidase inhibitors, bupropion, and atomoxetine in studies of children, adolescents, and adults with ADHD. C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, 15 Parkman St,WACC 725, Boston, MA 02114 USA. NR 17 TC 30 Z9 31 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 3 BP 22 EP 26 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BU UT WOS:000222312200005 PM 15046532 ER PT J AU Doyle, A Pollack, MH AF Doyle, A Pollack, MH TI Long-term management of panic disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Revisiting the Use of High-Potency Benzodiazepines CY JUL 11, 2003 CL Boston, MA ID NATURALISTIC FOLLOW-UP; BEHAVIORAL GROUP TREATMENT; AGORAPHOBIA; CLONAZEPAM; IMIPRAMINE; ALPRAZOLAM; THERAPY; STRATEGIES; SERTRALINE; PREDICTORS AB Panic disorder is a chronic, disabling condition that is often associated with a need for long-term clinical treatment. While a variety of pharmacotherapy options, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and benzodiazepines, are effective in reducing symptoms in the acute phase, a significant number of patients do not fully respond to initial treatment, and a large majority of patients experience relapse after medication discontinuation. Optimal long-term treatment of panic disorder involves attention to adequate medication dosing and adequate duration of treatment to achieve maximum improvement before discontinuing. Recent reports suggest the efficacy of adjunctive pharmacotherapies and combining pharmacotherapy with behavioral therapy to improve treatment response. Further research is necessary to determine the long-term effectiveness of these multifaceted treatment strategies among patients suffering from refractory panic disorder. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA USA. RP Pollack, MH (reprint author), Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM mpollack@partners.org NR 26 TC 10 Z9 10 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 5 BP 24 EP 28 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BY UT WOS:000222312600005 PM 15078115 ER PT J AU Fava, M AF Fava, M TI Daytime sleepiness and insomnia as correlates of depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Teleconference on Differential Diagnosis and Management of Daytime Sleepiness and Nighttime Wakefulness CY APR, 2004 CL ELECTR NETWORK ID SEROTONIN-REUPTAKE INHIBITORS; MAJOR DEPRESSION; RESIDUAL SYMPTOMS; ANTIDEPRESSANT TREATMENT; PSYCHIATRIC-DISORDERS; YOUNG-ADULTS; REM-SLEEP; FLUOXETINE; MODAFINIL; TRAZODONE AB Insomnia and daytime sleepiness are often associated with depression. The possible relationships between sleep difficulties and depression are numerous. Insomnia and other sleep disturbances can be precursors to the onset of major depressive disorder, so they may act as risk factors for or predictors of depression. The symptomatology of depression also prominently includes insomnia, and sleep disturbances may be residual symptoms after response to antidepressant treatment. Insomnia and the resultant daytime sleepiness may be short-term or long-term side effects of antidepressant treatment as well. Whether insomnia is a precursor, symptom, residual symptom, or side effect of depression or its treatment, clinicians must give serious attention to and attempt to resolve sleep disturbances because of the risk of depression onset, worsening of depressive symptoms, and relapse of depression after response to antidepressant treatment. Remission of depression cannot be fully achieved until the associated insomnia and daytime sleepiness are resolved. This article describes the relationships between insomnia and depression and discusses the effects of various antidepressants on sleep. Finally, several different treatment options, including antidepressant monotherapy and augmentation of antidepressants with other medications, are explored. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC-812, Boston, MA 02114 USA. EM mfava@partners.org NR 49 TC 130 Z9 138 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 16 BP 27 EP 32 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 880FQ UT WOS:000225774800006 PM 15575802 ER PT J AU Otto, MW Smits, JAJ Reese, HE AF Otto, MW Smits, JAJ Reese, HE TI Cognitive-behavioral therapy for the treatment of anxiety disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Revisiting the Use of High-Potency Benzodiazepines CY JUL 11, 2003 CL Boston, MA ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; EMPIRICALLY SUPPORTED TREATMENT; RANDOMIZED CONTROLLED-TRIAL; VEHICLE ACCIDENT SURVIVORS; 1-YEAR FOLLOW-UP; PANIC DISORDER; SOCIAL PHOBIA; PHARMACOLOGICAL-TREATMENT; BENZODIAZEPINE TREATMENT AB In this article, we consider the evidence supporting the range of applications of cognitive-behavioral therapy (CBT) for anxiety disorders, and we examine some of the complex issues encountered for the combination of pharmacologic and cognitive-behavioral treatment strategies. The available evidence supports CBT as an effective first-line treatment for anxiety disorders offering longer-term maintenance of treatment gains. There is also evidence that CBT is an effective strategy for pharmacotherapy non-responders, a replacement strategy for patients who wish to discontinue their medications, and a standard strategy for pharmacotherapy patients who need to boost their treatment response. Relative to combination therapy, we review some of the conditions that may influence the longevity of treatment gains from CBT. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC-812,15 Parkman St, Boston, MA 02114 USA. EM MOTTO@PARTNERS.ORG RI Smits, Jasper/A-4350-2008; OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 NR 95 TC 66 Z9 66 U1 1 U2 16 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 5 BP 34 EP 41 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BY UT WOS:000222312600007 PM 15078117 ER PT J AU Wilens, TE AF Wilens, TE TI Impact of ADHD and its treatment on substance abuse in adults SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on Diagnosing and Treating Attention-Deficit/Hyperactivity Disorder in Adults CY JAN 17, 2003 CL Boston, MA ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY; COCAINE DEPENDENCE; CONDUCT DISORDER; DOUBLE-BLIND; FOLLOW-UP; METHYLPHENIDATE; PREVALENCE; PHARMACOTHERAPY AB Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance abuse in adults. Additional psychiatric comorbidity increases this risk. ADHD is associated with different characteristics of substance abuse: substance abuse transitions more rapidly to dependence, and lasts longer in adults with ADHD than those without ADHD. Self-medication may be a factor in the high rate of substance abuse in adults with ADHD. While previous concerns arose whether stimulant therapy would increase the ultimate risk for substance abuse, recent studies have indicated that pharmacologic treatment appears to reduce the risk of substance abuse in individuals with ADHD. When treating adults with ADHD and substance abuse, clinicians should assess the relative severity of the substance abuse, the symptoms of ADHD, and any other comorbid disorders. Generally, stabilizing or addressing the substance abuse should be the first priority when treating an adult with substance abuse and ADHD. Treatment for adults with ADHD and substance abuse should include a combination of addiction treatment/psychotherapy and pharmacotherapy. The clinician should begin pharmacotherapy with medications that have little likelihood of diversion or low liability, such as bupropion and atomoxetine, and, if necessary, progress to the stimulants. Careful monitoring of patients during treatment is necessary to ensure compliance with the treatment plan. C1 Massachusetts Gen Hosp, Substance Abuse Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Substance Abuse Program Pediat Psychopharmacol, 15 Parkman St,WAC 725, Boston, MA 02114 USA. EM twilens@partners.org NR 48 TC 85 Z9 88 U1 3 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 3 BP 38 EP 45 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BU UT WOS:000222312200007 PM 15046534 ER PT J AU Alexopoulos, GS Streim, JE Carpenter, D AF Alexopoulos, GS Streim, JE Carpenter, D TI Expert consensus guidelines for using antipsychotic agents in older patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article C1 Cornell Univ, Cornell Inst Geriatr Psychiat, White Plains, NY USA. Cornell Univ, Weill Med Coll, White Plains, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Comprenhens NeuroSci, White Plains, NY 10605 USA. RP Carpenter, D (reprint author), Comprenhens NeuroSci, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM dcarpenter@cnsmail.com NR 0 TC 60 Z9 62 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2004 VL 65 SU 2 BP 100 EP 105 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 833BR UT WOS:000222311900002 ER PT J AU Li, HW Liu, H Balt, S Mann, S Corrales, CE Heller, S AF Li, HW Liu, H Balt, S Mann, S Corrales, CE Heller, S TI Correlation of expression of the actin filament-bundling protein espin with stereociliary bundle formation in the developing inner ear SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cochlea; vestibular; hair cell; cytoskeleton ID HAIR CELL STEREOCILIA; JERKER MOUSE; CUTICULAR PLATE; CHICK COCHLEA; BIRD COCHLEA; CROSS-LINKS; TIP LINKS; TRANSDUCTION; IDENTIFICATION; MORPHOLOGY AB The vertebrate hair cell is named for its stereociliary bundle or hair bundle that protrudes from the cell's apical surface. Hair bundles mediate mechanosensitivity, and their highly organized structure plays a critical role in mechanoelectrical transduction and amplification. The prototypical hair bundle is composed of individual stereocilia, 50-300 in number, depending on the animal species and on the type of hair cell. The assembly of stereocilia, in particular, the formation during development of individual rows of stereocilia with descending length, has been analyzed in great morphological detail. Electron microscopic studies have demonstrated that stereocilia are filled with actin filaments that are rigidly cross-linked. The growth of individual rows of stereocilia is associated with the addition of actin filaments and with progressively increasing numbers of cross-bridges between actin filaments. Recently, a mutation in the actin filament-bundling protein espin has been shown to underlie hair bundle degeneration in the deaf jerker mouse, subsequently leading to deafness. Our study was undertaken to investigate the appearance and developmental expression of espin in chicken inner ear sensory epithelia. We found that the onset of espin expression correlates with the initiation and growth of stereocilia bundles in vestibular and cochlear hair cells. Intense espin immunolabeling of stereocilia was colocalized with actin filament staining in all types of hair cells at all developmental stages and in adult animals. Our analysis of espin as a molecular marker for actin filament cross-links in stereocilia is in full accordance with previous morphological studies and implicates espin as an important structural component of hair bundles from initiation of bundle assembly to mature chicken hair cells. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Heller, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00241, DC006167, DC04563] NR 30 TC 31 Z9 33 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 1 PY 2004 VL 468 IS 1 BP 125 EP 134 DI 10.1002/cne.10944 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 750JV UT WOS:000186988300008 PM 14648695 ER PT J AU Ganchi, PA Movassaghi, K Yaremchuk, MJ AF Ganchi, PA Movassaghi, K Yaremchuk, MJ TI Treatment of bilateral symptomatic enophthalmos associated with weight loss SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE enophthalmos correction; intraorbital implants; orbital reconstruction; hydrocephalus; ventriculoperitoneal shunt ID VOLUME C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg,Dept Surg, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg,Dept Surg, 55 Fruit St,WACC 453, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JAN PY 2004 VL 15 IS 1 BP 84 EP 87 DI 10.1097/00001665-200401000-00024 PG 4 WC Surgery SC Surgery GA 881FJ UT WOS:000225848500023 PM 14704570 ER PT J AU Porter, D Polyak, K AF Porter, D. Polyak, K. TI Emerging genomic technologies for studying mammary development and mammary cancer SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE genomics; mammary; SAGE C1 [Porter, D.; Polyak, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Porter, D.; Polyak, K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2004 VL 87 SU 1 BP 239 EP 239 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA V45UN UT WOS:000203095301002 ER PT J AU Finberg, RW Re, F Popova, L Golenbock, DT Kurt-Jones, EA AF Finberg, RW Re, F Popova, L Golenbock, DT Kurt-Jones, EA TI Cell activation by Toll-like receptors: role of LBP and CD14 SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article DE cellular activation; lipopolysaccharide; inflammatory mediators ID BINDING PROTEIN; LPS; RESPONSES; DECTIN-1 AB Members of the Toll-like receptor (TLR) family have been shown to be important in the activation of cells by a variety of microbial ligands. TLRs are thought to mediate the 'recognition event' that follows an encounter between a mammalian cell and a microbial agent. In the case of the response to bacterial lipopolysaccharide (LPS), it is clear that the ability of these cell surface proteins to initiate the events necessary for activation of cells to produce cytokines is dependent upon 'accessory proteins' such as the pattern recognition protein CD14 and the lipopolysaccharide binding protein (LBP). While the role of these proteins in the LPS-specific response is defined, their role in other TLR responses has not been defined, but it is important in understanding these events and, potentially, in designing new therapeutic strategies. Here we report on the role of these proteins in the response to yeast zymosan. The requirements for this response (which unlike the response to LPS is a response to a particulate antigen) and the role of other serum proteins are defined. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. RP Finberg, RW (reprint author), Univ Massachusetts, Sch Med, Dept Med, 264 Plantat St, Worcester, MA 01605 USA. EM robert.finberg@umassmed.edu FU NIAID NIH HHS [R01AI38515, R01AI39576, R01AI31628]; NIDDK NIH HHS [DK 32520]; NIGMS NIH HHS [R01GM54060] NR 12 TC 27 Z9 29 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2004 VL 10 IS 6 BP 413 EP 418 DI 10.1179/096805104225006273 PG 6 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 875WB UT WOS:000225451700004 PM 15588424 ER PT J AU Duke-Cohan, JS Kim, JH Azouz, A AF Duke-Cohan, JS Kim, JH Azouz, A TI Attractin: Cautionary tales for therapeutic intervention in molecules with pleiotropic functionality SO JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY LA English DT Article DE attractin; agouti; neurodegeneration; membrane biogenesis; vesicle trafficking ID PEPTIDASE IV; VESICLE TRANSPORT; MUTANT MICE; CUB-FAMILY; DPPT-L; GENE; MAHOGANY; MUTATIONS; PROTEIN; MOUSE AB First discovered as a circulating secreted molecule expressed by activated T lymphocytes, attractin was examined as a potential marker of immune activity. The discovery that a transmembrane form not only controls neuropeptide regulation of hair pigmentation in animals but also affects basal metabolism led to proposals that attractin may also be an extracellular target amenable for the development of obesity-regulating drugs. Examination of several animal mutants used as models of juvenile-onset neurodegeneration revealed mutations at the attractin locus as the cause, and the reassessment of earlier attractin mutants demonstrated that neurodegeneration, alterations in pigmentation regulation, and basal metabolic rate were common to all the allelic variants. The presentation and severity of the symptoms differ depending upon the mutation, and some may be variably penetrant even within an allelic line. In this report, we review our rapidly altering perception of the functional activity of attractin with each further addition to its sphere of physiological involvement. We further reappraise our concepts of the subcellular location of attractin, leading to a new proposal that provides a unifying mechanism for attractin's pleiotropic activities. Progress in elucidating each new aspect of attractin function provides a case study in the evolution of possible therapeutic interventions as well as illuminating some of the pitfalls of studying molecular pathways isolated from the whole organism physiology. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Duke-Cohan, JS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Jonathan_Duke_Cohan@dfci.harvard.edu RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 37 TC 12 Z9 13 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-8898 J9 J ENVIRON PATHOL TOX JI J. Environ. Pathol. Toxicol. Oncol. PY 2004 VL 23 IS 1 BP 1 EP 11 DI 10.1615/JEnvPathToxOncol.v23.i1.10 PG 11 WC Toxicology SC Toxicology GA 866AJ UT WOS:000224745000001 PM 14994991 ER PT J AU Shioda, T AF Shioda, T TI Application of DNA microarray to toxicological research SO JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY LA English DT Article DE affymetrix; data mining; DNA microarray; gene expression; perl; toxicology; toxicogenomics; toxicogenetics; transcriptome ID GENE-EXPRESSION PATTERNS; ARTIFICIAL NEURAL NETWORKS; HUMAN BREAST-TUMORS; MOLECULAR CLASSIFICATION; CLUSTER-ANALYSIS; CELL-CYCLE; CANCER; TOXICOGENOMICS; PREDICTION; REVEALS AB DNA microarray technology is becoming increasingly popular in the field of toxicological research. Information on the global gene expression profile may provide clues to understanding biological actions of toxic substances at the molecular, cellular, tissue, and individual animal levels. This review focuses on the practical aspects of DNA microarray experiments and their applications to relatively small sizes of research projects in toxicology. First, different types of DNA microarrays and their characters are reviewed. Then, two fundamental concepts of DNA microarray data analysis-supervised and unsupervised methods-and their applications to toxicological research projects are discussed. Typical pitfalls of DNA microarray experiments are examined. Finally, strategies of experimental design and data analysis of minimum scale DNA microarray project are provided. C1 Massachusetts Gen Hosp, Ctr Canc, DNA Microarray Core Facil, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, DNA Microarray Core Facil, Bldg 149,7th Floor,13th St, Charlestown, MA 02129 USA. EM tshioda@partners.org NR 74 TC 16 Z9 20 U1 0 U2 2 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 0731-8898 J9 J ENVIRON PATHOL TOX JI J. Environ. Pathol. Toxicol. Oncol. PY 2004 VL 23 IS 1 BP 13 EP 31 DI 10.1615/JEnvPathToxOncol.v23.i1.20 PG 19 WC Toxicology SC Toxicology GA 866AJ UT WOS:000224745000002 PM 14994992 ER PT J AU Maulik, G Bharti, A Khan, E Broderick, RJ Kijima, T Salgia, R AF Maulik, G Bharti, A Khan, E Broderick, RJ Kijima, T Salgia, R TI Modulation of c-Kit/SCF pathway leads to alterations in topoisomerase-I activity in small cell lung cancer SO JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY LA English DT Article DE small cell lung cancer (SCLC); cancer treatment; chemotherapy; receptor tyrosine kinase; c-Kit; stem cell factor (SCF); topoisomerase-1 (topo-1); Gleevec (STI571); camptothecin (CPT); irinotecan (CPT-11); cisplatin; etoposide ID TYROSINE KINASE INHIBITOR; GASTROINTESTINAL STROMAL TUMOR; PHASE-II; GROWTH; KIT; STI571; LEUKEMIA; COEXPRESSION; IRINOTECAN; TOPOTECAN AB Small cell lung cancer (SCLC) is an aggressive type of lung cancer, for which cytotoxic chemotherapy appears to have reached its maximal efficacy. This neoplasm is characterized by the overexpression of several receptor tyrosine kinases (RTKs), especially c-Kit. The ligan for c-Kit is stem cell factor (SCF). In SCLC, SCF can influence c-Kit activation by autocrine or paracrine mechanisms. We have recently shown that the c-Kit/SCF pathway is operational in SCLC and can be inhibited by Glivec (STI571). Because the inhibition of topoisomerase-I (topo-I) is one approach used to treat SCLC, we determined the effects of c-Kit/SCF signaling on topo-I activity. A unique phosphorylation of c-Kit on amino acid 823 and amino acid 703 was identified with the SCF stimulation of H526 cells. We demonstrate that with SCF stimulation over 16 hours (dose response 0-100 ng/mL) in H526 SCLC cells (c-Kit positive, SCF responsive), a decrease in topo-I activity was observed, whereas in H82 SCLC cells (c-Kit negative, SCF unresponsive) there was no modulation of topo-I activity by SCF. Using STI571 (5 muM, 16 hours) to inhibit the c-Kit pathway following stimulation with SCF (100 ng/mL), an upregulation of topo-I activity was observed in H526 cells but not in H82 cells. Performing viability assays, we show that STI571 in combination with topo-I inhibition by camptothecin or SN38, the active metabolite of irinotecan, can cooperatively inhibit H526 cell viability (but not H82 cell viability) for 72 hours. We also show that STI571 does not directly inhibit topo-I activity in SCLC. The combination of STI571 with topo-I inhibition could provide a useful combination in the treatment of SCLC. C1 Univ Chicago, Pritzker Sch Med, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Pritzker Sch Med, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115,M255A, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu NR 35 TC 10 Z9 12 U1 1 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-8898 J9 J ENVIRON PATHOL TOX JI J. Environ. Pathol. Toxicol. Oncol. PY 2004 VL 23 IS 4 BP 237 EP 251 DI 10.1615/JEnvPathToxOncol.v23.i4.10 PG 15 WC Toxicology SC Toxicology GA 874WB UT WOS:000225380000001 PM 15511212 ER PT J AU Psarras, S Karagianni, N Kellendonk, C Tronche, F Cosset, FL Stocking, C Schirrmacher, V von Boehmer, H Khazaie, K AF Psarras, S Karagianni, N Kellendonk, C Tronche, F Cosset, FL Stocking, C Schirrmacher, V von Boehmer, H Khazaie, K TI Gene transfer and genetic modification of embryonic stem cells by Cre- and Cre-PR-expressing MESV-based retroviral vectors SO JOURNAL OF GENE MEDICINE LA English DT Article DE gene transfer; ES cells; MESV retroviral vectors; adenoviral vectors; Cre recombinase; Cre.PR fusion ID HEMATOPOIETIC PROGENITOR CELLS; HIGH-TITER; RECOMBINANT ADENOVIRUS; MAMMALIAN-CELLS; TRANSGENE EXPRESSION; SOMATIC MUTAGENESIS; CARCINOMA-CELLS; VIRAL VECTORS; PLASMID DNA; IN-VITRO AB Background Genetic modification of embryonic stem (ES) cells represents a powerful tool for transgenic and developmental experiments. We report that retroviral constructs based on murine embryonal stem cell virus (MESV) can efficiently deliver and express Cre recombinase or a post-translationally inducible Cre-Progesterone receptor (Cre.PR) fusion in mouse fibroblasts and ES cells. Methods To study the vectors a sensitive reporter cell line, 3TZ, was derived from the murine 3T6 fibroblast line that expresses beta-galactosidase only upon Cre-mediated recombination. This was used together with the ROSA26-R ES cell Cre-reporter system or unmodified mouse ES cells as targets of infection. Efficiency of gene transfer was evaluated immunohistochemically by the use of an anti-Cre polyclonal antibody, and by monitoring the expression of beta-galactosidase. Results Infection of the 3TZ cells with high titer 718C or 719CP virus revealed efficient gene transduction of constitutive or hormone-inducible recombinase activity, respectively. The vectors efficiently transduced murine ES cells with Cre, Cre-PR (fusion of Cre and progesterone receptor) or beta-galactosidase. Cre-mediated recombination in more than 60% of ROSA26-R ES cells was achieved when infected by a VSV-G-pseudotyped MESV retrovirus at MOI of 50. Conclusions The MESV-based retroviral systems, when combined with hormone inducible Cre, represent efficient tools for the transfer of Cre activity in ES cells. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, Div Cellular & Viral Genet, Hamburg, Germany. INSERM U412, Lab Retroviral Vectorol & Gene Therapy, Lyon, France. German Canc Res Ctr, D-6900 Heidelberg, Germany. German Canc Res Ctr, Div Cellular Immunol, Tumor Immunol Program, D-6900 Heidelberg, Germany. Inst Necker, INSERM U373, Paris, France. RP Khazaie, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, Smith Bldg,7th Floor,44 Binney St, Boston, MA 02115 USA. EM sha_Khazaie@dfci.harvard.edu NR 54 TC 6 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JAN PY 2004 VL 6 IS 1 BP 32 EP 42 DI 10.1002/jgm.442 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 769QU UT WOS:000188661900004 PM 14716675 ER PT J AU Huang, ES Gleason, S Gaudette, R Cagliero, E Murphy-Sheehy, P Nathan, DM Singer, DE Meigs, JB AF Huang, ES Gleason, S Gaudette, R Cagliero, E Murphy-Sheehy, P Nathan, DM Singer, DE Meigs, JB TI Health care resource utilization associated with a diabetes center and a general medicine clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes mellitus; endocrinology; health care costs; hospitalization; primary health care ID IMPROVED GLYCEMIC CONTROL; MANAGED CARE; QUALITY; MELLITUS; OUTCOMES; HYPERTENSION; SPECIALTY; INSULIN; COSTS AB OBJECTIVE: Studies have proposed that the features of diabetes clinics may decrease hospital utilization and costs by reducing complications and providing more efficient outpatient care. We compared the health care utilization associated with a diabetes center (DC) and a general medicine clinic (GMC). DESIGN: Retrospective cohort study. SETTING: An urban academic medical center. PATIENTS/PARTICIPANTS: Type 2 diabetes patients (N = 601) under care in a DC and GMC before March 1996. MEASUREMENTS AND MAIN RESULTS: We compared baseline patient characteristics and outpatient care for the period of March 1996 to August 1997. Using administrative data from March 1996 to October 2000, we compared the probability of a hospitalization, length of stay, costs of hospitalizations, the probability of an emergency room visit, and costs of emergency room visits. Diabetes center patients had a longer mean duration of diabetes (12 years vs 6 years, P < .01), more baseline microvascular disease (65% vs 44%, P < .01), and higher baseline glucose levels (hemoglobin A(1c) 8.6% vs 7.9%, P < .01) than GMC patients. Diabetes center patients received more intensive outpatient care directed toward glucose monitoring and control. In all crude and adjusted analyses of hospitalizations and emergency room visits, we found no statistically significant differences for inpatient utilization or cost outcomes comparing clinic populations. CONCLUSIONS: Diabetes center attendance did not have a definitive positive or negative impact on inpatient resource utilization over a 4-year period. However, DC patients had more severe diabetes but no greater hospital utilization compared with GMC patients. Clear demonstration of the clinical and financial benefits of features of diabetes centers will require long-term controlled trials of interventions that promote comprehensive diabetes care, including cardiovascular prevention. C1 Univ Chicago, Div Gen Med, Chicago, IL 60637 USA. Trinity Coll, Dept Econ, Hartford, CT 06106 USA. Harvard Univ, Sch Med, Dept Med, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Diabet Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Clin Res Program, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Huang, ES (reprint author), Univ Chicago, Div Gen Med, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. EM ehuang@medicine.bsd.uchicago.edu NR 25 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2004 VL 19 IS 1 BP 28 EP 35 DI 10.1111/j.1525-1497.2004.30402.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 766EP UT WOS:000188354000004 PM 14748857 ER PT J AU Rose, A Peters, N Shea, JA Armstrong, K AF Rose, A Peters, N Shea, JA Armstrong, K TI Development and testing of the health care system distrust scale SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE distrust; health care ID PATIENTS TRUST; AFRICAN-AMERICANS; MEDICAL-RESEARCH; PHYSICIAN SCALE; PATIENT TRUST; MANAGED CARE; PERFORMANCE; SATISFACTION; ATTITUDES; TUSKEGEE AB BACKGROUND: Distrust of the health care system may be a significant barrier to seeking medical care, adhering to preventive health care and treatment regimens, and participating in medical research. OBJECTIVE: To describe the development and psychometric testing of an instrument (the Health Care System Distrust Scale) to measure distrust of the health care system. METHODS: Scale development involved 2 phases. In Phase 1, a pilot instrument was developed based on a conceptual model of health care-related distrust. Draft items were created using focus group sessions with members of the general public, literature review, and expert opinion. Draft items were pilot tested with 55 individuals waiting to be assigned to jury duty at the Municipal Court of Philadelphia. A priori, candidate items for elimination or revision included those with >5% missing data, extremely low or high interitem or item-total correlations, or those having a negative effect on the scale's internal consistency. In Phase 2, we conducted a survey of 400 prospective jurors to assess the reliability and validity of the final scale scores. RESULTS: In Phase 1, a 10-item scale was constructed that included 4 items measuring honesty, 2 items measuring confidentiality, 2 items measuring competence, and 2 items measuring fidelity. The participants in Phase 2 had a mean age of 41 years. Forty-three percent were African-American, 45% white, and 4% Hispanic. Scores on the Health Care System Distrust scale ranged from 12 to 46 with a possible range from 10 to 50. The mean score was 29.4 with a standard deviation of 6.33. No item had over 5% missing data. Internal consistency (Cronbach's alpha) was 0.75. Item-total correlations ranged from 0.27 to 0.57. Principal components analysis revealed 1 general component accounting for 32% of the variance. Nine of the variables had loadings higher than 0.40. As predicted, distrust of the health care system was higher among African Americans than whites and was inversely correlated with trust in personal physicians. CONCLUSIONS: Initial testing suggests that we developed an instrument with valid and reliable scores in order to measure distrust of the health care system. Future research is needed to evaluate the validity and reliability of the Health Care System Distrust scale among diverse populations. This instrument can facilitate the investigation of the prevalence, causes, and effects of health care system distrust in the United States. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu NR 44 TC 76 Z9 78 U1 0 U2 10 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2004 VL 19 IS 1 BP 57 EP 63 DI 10.1111/j.1525-1497.2004.21146.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 766EP UT WOS:000188354000008 PM 14748861 ER PT J AU Ring, D McCarty, LP Campbell, D Jupiter, JB AF Ring, D McCarty, LP Campbell, D Jupiter, JB TI Condylar blade plate fixation of unstable fractures of the distal ulna associated with fracture of the distal radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE fracture; ulna; radius; internal fixation; blade plate ID COLLES FRACTURES; FOREARM; BONES; INJURIES; DEFORMITIES; SUPINATION; ADULTS AB Purpose: To review the results of condylar blade plate fixation of unstable fractures of the distal ulna associated with fracture of the distal radius. Methods: Twenty-four patients in whom a minicondylar blade plate was used to repair an unstable fracture of the distal ulna associated with a fracture of the distal radius were reviewed retrospectively an average of 26 months (range, 12-50 months) after injury. According to the Q modifier of the Comprehensive Classification of Fractures, there were I simple fracture of the ulnar neck (Q2), 20 comminuted fractures of the ulnar neck (Q3), and 3 fractures of the head and neck (Q5). Subsequent surgeries included repeat fixation and autogenous cancellous bone grafting in 2 patients with nonunion of the distal radius and I with nonunion of the distal ulna. Seven patients had a second operation to remove the ulnar plate secondary to discomfort from plate prominence. Results: The final average motion was as follows: 50degrees of flexion (range, 30degrees-80degrees), 52degrees of extension (range, 40degrees-90degrees), 76degrees of pronation (range, 45degrees-90degrees), and 70degrees of supination (range, 45degrees-90degrees). Grip strength averaged 64% of the contralateral, uninjured extremity (range, 35%-100%). Final radiographic measurements included an average palmar tilt of the distal articular surface of the radius of 8degrees (range, 0degrees-20degrees of palmar tilt), ulnar inclination of 21degrees (range, 15degrees-25degrees), and ulnar positive variance of 1 mm (range, 0-4 mm). There were no problems related to the distal radioulnar joint. According to the system of Gartland and Werley as modified by Sarmiento, there were 6 excellent, 15 good, and 4 fair results at final evaluation. Conclusions: For unstable fractures of the distal ulna associated with fracture of the distal radius, condylar blade plate fixation can achieve healing with good alignment, satisfactory function, and an acceptable rate of secondary surgery. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ambulatory Care Ctr 525, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Combined Orthopaed Residency, Boston, MA USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ambulatory Care Ctr 525, Hand & Upper Extrem Serv,Dept Orthopaed Surg, 15 Parkman St, Boston, MA 02114 USA. NR 21 TC 19 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2004 VL 29A IS 1 BP 103 EP 109 DI 10.1016/j.jhsa.2003.10.019 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 769AJ UT WOS:000188603700018 PM 14751112 ER PT J AU Ring, D Chin, K Jupiter, JB AF Ring, D Chin, K Jupiter, JB TI Radial nerve palsy associated with high-energy humeral shaft fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE radial nerve; nerve injury; fracture; humerus ID PARALYSIS AB Purpose: To determine whether the radial nerve should be explored when there is a complete sensory and motor deficit after a high-energy fracture of the humeral diaphysis. Methods: Twenty-four patients aged 16 years or older with a high-energy, diaphyseal fracture of the humerus and complete motor and sensory radial nerve palsy were reviewed retrospectively. Eleven fractures were open-6 of these were part of a very complex upper-extremity injury (multiple ipsilateral fractures in 3 patients and near amputation in 3). All 11 patients with open fractures and 3 of 13 patients with closed injuries had radial nerve exploration. Results: All 6 patients with a transected radial nerve had an open humerus fracture and were part of a complex upper-extremity injury. Five of 6 had primary repair of the radial nerve, and none recovered. All 8 intact explored nerves and 9 of 10 unexplored nerves recovered; the only nonrecovery occurred in a patient treated with closed intramedullary rod fixation who may have had iatrogenic nerve injury. The average time to initial signs of recovery was 7 weeks (range, 1-25 weeks). The average time to full recovery was 6 months (range, 1-21 months). Conclusions: Transection of the radial nerve is usually associated with open fractures of the humerus that are part of a very complex upper-extremity injury. The results of primary nerve repair in this circumstance are poor, likely related to an extensive zone of injury and the need for nerve grafting. Intact nerves and nerve palsies that are part of a closed fracture nearly always recover, even after high-energy injuries. Because the first signs of nerve recovery and complete recovery of the nerve can be quite delayed, patience is merited before considering tendon transfers. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA USA. Harvard Combined Orthopaed Residency, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Ambulatory Care Ctr 525, 15 Parkman St, Boston, MA 02114 USA. NR 22 TC 52 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2004 VL 29A IS 1 BP 144 EP 147 DI 10.1016/j.jhsa.2003.09.013 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 769AJ UT WOS:000188603700024 PM 14751118 ER PT J AU Weinstein, ND Atwood, K Puleo, E Fletcher, R Colditz, G Emmons, KM AF Weinstein, ND Atwood, K Puleo, E Fletcher, R Colditz, G Emmons, KM TI Colon cancer: Risk perceptions and risk communication SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID BREAST-CANCER; COLORECTAL-CANCER; RANDOMIZED-TRIAL; FAMILY-HISTORY; PERCEIVED RISK; MAMMOGRAPHY; WOMEN; SUSCEPTIBILITY; FREQUENCY; BIASES AB Members of a health maintenance organization (N=353) interacted with a computer program that provided personalized information about their risk of developing colon cancer in the next 20 years. Prior to computer feedback, most people greatly overestimated their numerical, absolute risk (chances per 1000) and also overestimated their relative risk compared to peers (e.g., "above average"). Their relative risk estimates were correlated with several risk factors, whereas their absolute risk estimates were not, suggesting that assessing individual risk perceptions with numerical, absolute risk scales may provide misleading information about what people believe. Computer feedback improved the accuracy of mean risk estimates, but about half of participants did not accept the personalized feedback as correct. In fact, correlations between actual and perceived risk were no greater among participants who received risk scores than among those who did not. Three possible explanations for resistance to lower-than-expected risk feedback are considered. C1 Rutgers State Univ, Dept Human Ecol, New Brunswick, NJ 08901 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Massachusetts, Amherst, MA 01003 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab,Ctr Canc Prevent, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cambridge, MA USA. RP Weinstein, ND (reprint author), Rutgers State Univ, Dept Human Ecol, Cook Off Bldg,55 Dudley Rd, New Brunswick, NJ 08901 USA. EM Neilw@aesop.rutgers.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 38 TC 54 Z9 54 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD JAN-FEB PY 2004 VL 9 IS 1 BP 53 EP 65 DI 10.1080/10810730490271647 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 770VJ UT WOS:000188751200004 PM 14761833 ER PT J AU Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC AF Houser, SL McMorrow, IM LeGuern, C Schwarze, ML Fuchimoto, Y Sachs, DH Madsen, JC TI Histomorphometric comparison of cardiac allograft vasculopathy in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL PROLIFERATION; GRAFT ARTERIOSCLEROSIS; HEART-TRANSPLANTATION; CHRONIC REJECTION; TIME-COURSE; ARTERIOPATHY; EXPRESSION; INTERLEUKIN-10; DISEASE AB Background: Whether the pathologic characteristics of vascular lesions manifested in recipients with cardiac allograft vasculopathy (CAV) differ with the severity of the histocompatibility barrier crossed at transplantation or with the type or amount of immunosuppression used to prolong graft survival is unclear. We used miniature swine to determine whether a wide variance in heart transplantation protocols, both in histoincompatibility and immunosuppression, affects the histomorphometry of CAV. Methods: We compared explanted hearts from major histocompatibility complex Class I-disparate recipients who were treated for 12 days with cyclosporine (Group 1) with minor-antigen-disparate hearts transplanted into mixed chimeric recipients previously engrafted with donor hematopoietic progenitor cells (Group 2). We analyzed coronary intimal lesions using computerized morphometry, immunohistochemistry, and TUNEL assay. Myocardial cytokine-gene expression was determined using RNAse protection, assays and reverse-transcriptase polymerase chain reaction. Results: The prevalence of CAV in Group 2 was significantly less than that observed in Group 1, but the severity of the lesions -in both groups was similar. The vascular lesions that developed in both groups demonstrated the presence of alpha-smooth-muscle-actin- positive spindle cells expanding the intima, with few inflammatory cells. We noted an absence of proliferating cell nuclear antigen activity and TUNEL-positive cells in both groups. We observed prominent myocardial interferon-gamma gene expression only in Group 1. Conclusion: Despite differences in myocardial interferon-gamma gene expression, the histology and severity. of the vascular lesions in CAV did not vary significantly with different histoincompatibilities or treatment protocols. These results suggest that the origin of CAV cannot be determined by histology alone. J Heart Lung Transplant 2004; 23:50-60. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646, R01 HL54211]; NIAID NIH HHS [P01 AI50157] NR 38 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2004 VL 23 IS 1 BP 50 EP 60 DI 10.1016/S1053-2498(03)00065-2 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 765PZ UT WOS:000188293800007 PM 14734127 ER PT J AU Markowitz, DH Systrom, DM AF Markowitz, DH Systrom, DM TI Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ANAEROBIC THRESHOLD; PROSTACYCLIN ANALOG; GAS-EXCHANGE; ARTERIAL-HYPERTENSION; LUNG TRANSPLANTATION; DOUBLE-BLIND; DISEASE; VENTILATION; ABNORMALITIES AB Background: Given the recent development of newer and less-invasive treatments for pulmonary hypertension, and the long wait for,lung transplantation, early and correct diagnosis of this condition is increasingly important. The purpose of this study was to determine and improve the accuracy of a non-invasive, cardiopulmonary exercise-testing algorithm for detecting a pulmonary vascular limit to exercise. Methods: We performed 130 consecutive, incremental cycling-exercise tests for exertional symptoms with pulmonary and radial artery catheters in place. Pulmonary vascular limit was defined as pulmonary vascular resistance at maximum exercise > 120 dynes (.) sec/cm(5) and a peak-exercise systemic oxygen delivery < 80% predicted, without a pulmonary mechanical limit or poor effort. We applied a previously reported non-invasive exercise-test-interpretation algorithm to each patient and sequentially manipulated branch point threshold values to maximize accuracy. Results: The sensitivity of the original non-invasive algorithm for pulmonary vascular limit was 79%, specificity was 75%, and accuracy was 76%. Sensitivity did not change with systematic alteration of branch-point threshold values, but specificity and accuracy improved to 88% and 85%, respectively. Accuracy improved most by modifying the threshold values for percent predicted maximum oxygen uptake and carbon dioxide output ventilatory equivalents at lactate threshold. Conclusion: Non-invasive cardiopulmonary exercise testing is a useful tool for detecting and excluding a pulmonary vascular limit and for determining whether abnormal pulmonary hemodynamics limit aerobic capacity. J Heart Lung Transplant 2004;23: 88-95. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Med Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Markowitz, DH (reprint author), Univ Massachusetts, Sch Med, Pulm Allergy & Crit Care Med Div, UMass Mem Hlth Care,55 Lake Ave N,Room S6-719, Worcester, MA 01655 USA. EM markowid@ummhc.org OI Systrom, David/0000-0002-9610-6330 FU NHLBI NIH HHS [1K24 HL04022-01] NR 40 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2004 VL 23 IS 1 BP 88 EP 95 DI 10.1016/S1053-2498(03)00064-0 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 765PZ UT WOS:000188293800012 PM 14734132 ER PT J AU Kamide, K Rakugi, H Nagai, M Takiuchi, S Matsukawa, N Higaki, J Kawano, Y Ogihara, T Tuck, ML AF Kamide, K Rakugi, H Nagai, M Takiuchi, S Matsukawa, N Higaki, J Kawano, Y Ogihara, T Tuck, ML TI Insulin-mediated regulation of the endothelial renin-angiotensin system and vascular cell growth SO JOURNAL OF HYPERTENSION LA English DT Article DE angiotensin-coverting enzyme; angiotensinogen; insulin; renin; vascular endothelial cells ID SMOOTH-MUSCLE-CELLS; ISCHEMIC-HEART-DISEASE; ESSENTIAL-HYPERTENSION; CONVERTING-ENZYME; IN-VIVO; RESISTANCE; EXPRESSION AB Objective Insulin has a growth-stimulating effect for vascular tissue. At the tissue level, the vascular renin-angiotensin system (RAS) may be involved in the progression of atherosclerosis or vascular hypertrophy. We previously reported that the vascular RAS activity is activated in vascular smooth muscle cells (SMC) by insulin stimulation. However, the effect of insulin on the RAS in endothelial cells (EC) is not fully understood. Methods Cultured human EC were incubated with or without insulin. After incubation for 48 h, cellular angiotensinogen and renin mRNA expression and levels in the cells were quantified by slot-blot hybridization and radioimmunoassay. Angiotensin I converting enzyme (ACE) activity in EC homogenates was measured by modified Cushman and Cheung method. EC growth and SMC with or without EC using co-culture were assessed by H-3-thymidine uptake for evaluation of their growth. Results All doses of insulin (110, 100, 1000 muU/ml) decreased angiotensinogen and renin mRNA expression (angiotensinogen: 19.3%, P < 0.05; 25.4%, P < 0.01; 26.2%, P < 0.01, renin: 12.9%, P < 0.05; 21.3%, P < 0.01; 14.3%, P < 0.05, respectively). Both cellular angiotensinogen and renin level were also reduced by high levels of insulin. Neither 10 nor 100 muU/ml insulin increased cellular angiotensin converting enzyme (ACE) activity (2.17 to 3.48-folds, P = 0.077, 0.125, respectively) significantly, but 1000 muU/ml insulin strongly up-regulated ACE activity by 16.67-folds (P = 0.001) in cultured EC. For the co-culture with EC and SMC, 100 muU/ml insulin was not able to induce SMC but 1000 muU/ml insulin accelerated SMC growth in the co-culture. In contrast insulin that was over 100 muU/mI induced SMC growth in the sole culture of SMC. Conclusion Either low or high levels of insulin suppressed angiotensinogen and renin expression, however, high doses of insulin stimulated ACE activity in cultured human aortic EC. This may indicate that insulin regulates vascular cell growth and endothelial function via bifunctional modification of the vascular angiotensin generation. (C) 2004 Lippincott Williams Wilkins. C1 Natl Cardiovasc Ctr, Div Nephrol & Hypertens, Suita, Osaka 5658565, Japan. Osaka Univ, Dept Geriatr Med, Grad Sch Med, Suita, Osaka, Japan. Ehime Univ, Sch Med, Shigenobu, Ehime, Japan. Univ Calif Los Angeles, Sch Med, Div Endocrinol, Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Kamide, K (reprint author), Natl Cardiovasc Ctr, Div Nephrol & Hypertens, 5-7-1 Fujishirodai, Suita, Osaka 5658565, Japan. EM kamide@hsp.ncvc.go.jp NR 21 TC 14 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2004 VL 22 IS 1 BP 121 EP 127 DI 10.1097/01.hjh.0000098157.70956.61 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 837WQ UT WOS:000222672400020 PM 15106803 ER PT J AU Yan, Y Phan, L Yang, F Talpaz, M Yang, Y Xiong, ZY Ng, B Timchenko, NA Wu, CJ Ritz, J Wang, H Yang, XF AF Yan, Y Phan, L Yang, F Talpaz, M Yang, Y Xiong, ZY Ng, B Timchenko, NA Wu, CJ Ritz, J Wang, H Yang, XF TI A novel mechanism of alternative promoter and splicing regulates the epitope generation of tumor antigen CML66-L SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; TISSUE-SPECIFIC PROMOTERS/; CANCER-TESTIS ANTIGENS; IMMUNE-RESPONSE; GENE-EXPRESSION; DENDRITIC CELLS; T-LYMPHOCYTES; NY-ESO-1; IDENTIFICATION; IMMUNOTHERAPY AB This report describes the difference in the epitope generation of two isoforms of self-tumor Ag CML66 and the regulation mechanism. We identified a new CML66 short isoform, termed CML66-S. The previously identified long CML66 is referred to as CML66-L. CML66-S shares the C terminus with CML66-L but has its unique N terminus. CML66-S is predominantly expressed in testis, but is also expressed in very low levels in tumor cells, whereas CML66-L is expressed in tumor cells and testis. Differential expression of CML66-L and CML66-S in tumor cells resulted from regulation at transcription, although alternative splicing also participated in the generation of the isoforms. In addition, Ab titers to a CML66-L peptide were significantly higher than that to CML66-S peptide in the sera from patients with tumors. Finally, the Abs to full-length CML66-L in the sera from patients with tumors were correlated with the Abs in the sera from these patients to CML66-L-38, which is a fusion protein with a CML66-L-specific N terminus. This suggests that the CML66-L isoform is mainly responsible for the epitope generation. Our studies have identified the alternative promoter in combination with alternative splicing as a novel mechanism for regulation of the epitope generation of a self-tumor Ag. C1 Baylor Coll Med, Biol Inflammat Ctr, Dept Med, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. RP Yan, Y (reprint author), Baylor Coll Med, Biol Inflammat Ctr, Dept Med, Sect Immunol Allergy & Rheumatol, 1 Baylor Pl,BCM 285,Suite 672E, Houston, TX 77030 USA. EM xyang1@bcm.tmc.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [P20 CA103698, P20 CA 103698, P50 CA 58204, P50 CA058204]; NIAID NIH HHS [K08 AI 054514, K08 AI054514]; NIDDK NIH HHS [P30 DK 56238, R01 DK056238] NR 53 TC 28 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2004 VL 172 IS 1 BP 651 EP 660 PG 10 WC Immunology SC Immunology GA 755TN UT WOS:000187427700080 PM 14688378 ER PT J AU Ferrantelli, F Kitabwalla, M Rasmussen, RA Cao, C Chou, TC Katinger, H Stiegler, G Cavacini, LA Bai, Y Cotropia, J Ugen, KE Ruprecht, RM AF Ferrantelli, F Kitabwalla, M Rasmussen, RA Cao, C Chou, TC Katinger, H Stiegler, G Cavacini, LA Bai, Y Cotropia, J Ugen, KE Ruprecht, RM TI Potent cross-group neutralization of primary human immunodeficiency virus isolates with monoclonal antibodies - Implications for acquired immunodeficiency syndrome vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CLADE NEUTRALIZATION; NEONATAL MACAQUES; TYPE-1; GP41; HIV-1; EPITOPE; COMBINATION; GLYCOPROTEIN; INFECTION; BINDING AB Human immunodeficiency virus type 1 (HIV-1) is phylogenetically classified into groups and clades ( or subtypes). Human neutralizing monoclonal antibodies (nMAbs), originally isolated from individuals infected with HIV-1 group M-clade B, neutralized not only primary HIV-1 clade B isolates in vitro but also primary isolates of other group M clades ( A, C, D, E, and F). This corrected the previously held notion that primary HIV-1 isolates are resistant to neutralizing antibodies. Here we show that anti-HIV-1 group M-clade B nMAbs potently neutralized primary isolates of the phylogenetically distant HIV-1 group O. We and others have previously shown that passive immunization with human nMAbs protected adult or neonatal primates against infection with simian-human immunodeficiency virus strains encoding HIV-1 group M-clade B envelope genes. The in vitro cross-group neutralization shown here underscores the broad potential of these nMAbs against divergent virus variants and the relevance of their epitopes in the design of acquired immunodeficiency syndrome vaccines. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Univ S Florida, Coll Med, Dept Med Microbiol & Immunol, Tampa, FL 33612 USA. Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10021 USA. BioClonetics, Philadelphia, PA USA. Agr Univ Vienna, Inst Appl Life Sci, A-1180 Vienna, Austria. Polymun Sci Immunobiol Forsch GmbH, Vienna, Austria. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF-809,44 Binney St, Boston, MA 02115 USA. RI Chou, Ting-Chao/B-4111-2009; Ugen, Kenneth/H-6544-2011; Ferrantelli, Flavia/J-7794-2016 OI Chou, Ting-Chao/0000-0002-3340-1594; Ferrantelli, Flavia/0000-0002-0768-1078 FU NCIRD CDC HHS [IP30 28691]; NIAID NIH HHS [P01 AI48240, R01 AI34266] NR 25 TC 36 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2004 VL 189 IS 1 BP 71 EP 74 DI 10.1086/380102 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 759DP UT WOS:000187723300010 PM 14702155 ER PT J AU Swartz, MN AF Swartz, MN TI Commentary: Rosenow EC. Studies in pneumonia and pneumococcus infection. J Infect Dis 1904; 1 : 280-312 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Swartz, MN (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Rm 127,Bulfinch Bldg,32 Fruit St, Boston, MA 02114 USA. NR 49 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2004 VL 189 IS 1 BP 128 EP 164 DI 10.1086/381788 PG 37 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 759DP UT WOS:000187723300018 PM 14986334 ER PT J AU Stoler, JM Sabry, MA Hanley, C Hoppel, CL Shih, VE AF Stoler, JM Sabry, MA Hanley, C Hoppel, CL Shih, VE TI Successful long-term treatment of hepatic carnitine palmitoyltransferase I deficiency and a novel mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID DEHYDROGENASE-DEFICIENCY; UNCOOKED CORNSTARCH; HUMAN LIVER; HYPOGLYCEMIA; THERAPY; CPT1A AB Individuals with carnitine palmitoyltransferase I (CPT-I) deficiency cannot metabolize long-chain fatty acids and can develop life-threatening hypoglycaemia. We present a boy with CPT-I deficiency maintained on a very low-fat diet with nighttime uncooked cornstarch feedings for 51/2 years with good success. He has had normal growth and no episodes of hypoglycaemia or adverse side-effects. We found that he was homozygous for a previously undescribed mutation, T314I, in the CPT1A protein. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Serv,Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Amino Acid Disorders Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nutr & Food Serv, Boston, MA 02114 USA. Rainbow Babies & Childrens Hosp, Dept Pediat, Ctr Inherited Disorders Energy Metab, Cleveland, OH 44106 USA. RP Stoler, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Serv,Genet & Teratol Unit, 55 Fruit St Warren 801, Boston, MA 02114 USA. EM jstoler@partners.org NR 20 TC 8 Z9 10 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2004 VL 27 IS 5 BP 679 EP 684 DI 10.1023/B:BOLI.0000042979.42120.55 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 857EX UT WOS:000224100100015 PM 15669684 ER PT J AU Detmar, M AF Detmar, M TI Evidence for vascular endothelial growth factor (VEGF) as a modifier gene in psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID SKIN; IDENTIFICATION; ANGIOGENESIS; MICE C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 15 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2004 VL 122 IS 1 BP XIV EP XV DI 10.1046/j.0022-202X.2003.22140.x PG 2 WC Dermatology SC Dermatology GA 761FT UT WOS:000187891300003 PM 14962120 ER PT J AU Tschachler, E Reinisch, CM Mayer, C Paiha, K Lassmann, H Weninger, W AF Tschachler, E Reinisch, CM Mayer, C Paiha, K Lassmann, H Weninger, W TI Sheet preparations expose the dermal nerve plexus of human skin and render the dermal nerve end organ accessible to extensive analysis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE skin nerves; Schwann cell; sensory end organ; nerve endings ID CUTANEOUS INNERVATION; HUMAN EPIDERMIS; IMMUNOHISTOCHEMISTRY; MICROSCOPY; FIBERS; CELL; LESIONS; DENSITY AB Since vertical tissue sections used for the study of the human cutaneous nervous system inherently allow visualization of only a small part of the mainly horizontally oriented cutaneous nerves, we searched for possibilities to extend this view. We now propose a method based on the immuno-staining of dermal sheet preparations for subsequent analysis by electron-, light- or laser scanning microscopy. Dermal sheet preparations for the first time allowed the imaging of the complex structure of the nerve end organ over several cm(2), and facilitated viewing of its topological relationship to other tissue components. We could visualize that the bulk of free ending nerve fibers ramified within 25mum of the dermo-epidermal junction, whereas below that only larger nerve bundles were present. This method further allowed the detection and quantification of NCAM/CD56(+) non-myelinating Schwann cells which envelope terminal axons within the dermis. Depending on the body region, we detected between 140 to over 300 individual terminal Schwann cells per mm(2) skin surface. Our method should allow the acquisition of new insights into the highly organized architecture of the skin nerve end organ. Its further application will give new impetus in the investigation of alterations of this skin compartment under pathological conditions. C1 Univ Vienna, Sch Med, Dept Dermatol, A-1090 Vienna, Austria. Univ Vienna, Sch Med, Div Neuroimmunol, Brain Res Inst, A-1090 Vienna, Austria. Inst Mol Pathol, A-1030 Vienna, Austria. Ctr Rech & Invest Epiderm & Sensorielles, Neuilly, France. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Tschachler, E (reprint author), Univ Vienna, Sch Med, Dept Dermatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM Erwin.Tschachler@akh-wien.ac.at OI Tschachler, Erwin/0000-0002-0248-1798 NR 29 TC 41 Z9 42 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2004 VL 122 IS 1 BP 177 EP 182 DI 10.1046/j.0022-202X.2003.22102.x PG 6 WC Dermatology SC Dermatology GA 761FT UT WOS:000187891300028 PM 14962106 ER PT J AU Yano, K Kajiya, K Ishiwata, M Hong, YK Miyakawa, T Detmar, M AF Yano, K Kajiya, K Ishiwata, M Hong, YK Miyakawa, T Detmar, M TI Ultraviolet B-induced skin angiogenesis is associated with a switch in the balance of vascular endothelial growth factor and thrombospondin-1 expression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; vascular regression; thrombospondin (TSP-1); acute UVB irradiation ID TRANSGENIC MICE; MOUSE SKIN; OVEREXPRESSION; UVB; KERATINOCYTES; IRRADIATION; RADIATION; VEGF; CARCINOGENESIS; EPIDERMIS AB We have previously shown that targeted overexpression of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in the epidermis prevented chronic ultraviolet B (UVB)-induced angiogenesis and cutaneous photodamage in mice, suggesting that angiogenesis plays a critical role in the mediation of UVB effects on the skin. Nevertheless, the molecular regulation of angiogenesis factors and inhibitors by acute UVB irradiation still remains to be elucidated. We performed quantitative analyses of cutaneous vascularity and of vascular endothelial growth factor (VEGF) and TSP-1 expression after acute UVB irradiation of mouse skin. Skin vascularity in the upper dermis was greatly increased until day 8 after a single dose of UVB irradiation (200 mJ per cm(2)) and associated with upregulation of VEGF mRNA expression, with downregulation of TSP-1 mRNA, and with protein expression in the hyperplastic epidermis. After 13 days, skin vascularity was normalized with downregulation of VEGF mRNA expression and upregulation of TSP-1 mRNA expression to the levels observed in non-UVB-irradiated skin. In contrast, the angiogenic UVB response was prolonged in TSP-1-deficient mice. We found a pronounced induction of the TSP-1 receptor CD36 in CD31-positive vessels on day 8 after UVB irradiation, associated with vascular endothelial cell apoptosis. These results demonstrate that acute UVB irradiation leads to a shift toward a proangiogenic environment and they suggest that the balance between VEGF and TSP-1 plays a critical role in the control of angiogenesis and vascular regression induced by acute UVB irradiation. C1 Shiseido Life Sci Res Ctr, Tsuzuki Ku, Yokohama, Kanagawa 2248558, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Hiroshima Univ, Dept Mol Biotechnol, Grad Sch Adv Sci Matter, Higashihiroshima 724, Japan. RP Yano, K (reprint author), Shiseido Life Sci Res Ctr, Tsuzuki Ku, 2-2-1 Hayabuchi, Yokohama, Kanagawa 2248558, Japan. EM kiichiro.yano@to.shiseido.co.jp FU NCI NIH HHS [CA91861, CA69184, CA92644] NR 37 TC 50 Z9 51 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2004 VL 122 IS 1 BP 201 EP 208 DI 10.1046/j.0022-202X.2003.22101.x PG 8 WC Dermatology SC Dermatology GA 761FT UT WOS:000187891300031 PM 14962109 ER PT J AU Nath, SK Namjou, B Kilpatrick, J Garriott, CP Bruner, GR Scofield, RH Harley, JB AF Nath, SK Namjou, B Kilpatrick, J Garriott, CP Bruner, GR Scofield, RH Harley, JB TI A candidate region on 11p13 for systemic lupus erythematosus: A linkage identified in African-American families SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 51st Annual Montagna Symposium on the Biology of Skin CY AUG 16-20, 2002 CL SNOWMASS, COLORADO ID GENOME-WIDE SEARCH; SIB-PAIR FAMILIES; SUSCEPTIBILITY GENES; SLE FAMILIES; GENETICS; LOCUS; SCAN AB Systemic Lupus Erythematosus (SLE), a chronic, complex disease, is the prototype for systemic human autoimmune diseases. Although environmental factors are crucial in triggering the condition, twin and family studies, as well as genetic linkage and association studies, have established its strong genetic predisposition. During the past few years, there has been considerable interest in identifying genomic segments linked to SLE through either a whole genome scan or a candidate gene approach. The discoid lupus erythematosus (DLE) skin lesion is one of the major, and discriminating, manifestations in SLE, especially in African American patients. In this study we have identified 58 multiplex families-27 African American, 26 European American, and 5 others-where at least one SLE patient is also reported to be afflicted with DLE. These families were chosen from the collection of families that are part of our ongoing linkage study for SLE. A genome-wide parametric and nonparametric linkage analysis was conducted with 320 markers. Significant evidence of linkage was identified in only one chromosomal location, 11p13, in the African American families. The maximum 2-point linkage was 5.6 in these pedigrees, obtained at a marker located 47 cm away from the p-terminal end of chromosome 11. The peak multipoint LOD score of 4.6 was obtained very nearby. The segregation of this gene suggests dominant inheritance. These results reveal an important genetic effect related to discoid rash at 11p13 in African Americans with SLE, and demonstrate, through increasing genetic homogeneity, the power of pedigree stratification to detect linkage in complex diseases. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Univ Oklahoma, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM swapan-nath@omrf.ouhsc.edu FU NCRR NIH HHS [RR15577]; NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR42460, AR45231, AR-12253, AR048940, AR049084, AR048928] NR 28 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD JAN PY 2004 VL 9 IS 1 BP 64 EP 67 DI 10.1111/j.1087-0024.2004.00830.x PG 4 WC Dermatology SC Dermatology GA 764FB UT WOS:000188195800012 PM 14870988 ER PT J AU Oates, JC Gilkeson, GS AF Oates, JC Gilkeson, GS TI Nitric oxide induces apoptosis in spleen lymphocytes from MRL/lpr mice SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE apoptosis; lupus; nitric oxide ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROGRAMMED CELL-DEATH; IN-VITRO APOPTOSIS; MRL-LPR/LPR MICE; FLOW-CYTOMETRIC DETECTION; PROTEIN-KINASE; DEPENDENT APOPTOSIS; AUTOIMMUNE-DISEASE; MURINE LUPUS; PHOSPHATIDYLSERINE EXPRESSION AB Background: MRL/MpJ-Tnfrsf6(lpr)(MRL/lpr) mice, a murine model of systemic lupus erythematosus (SLE), have defective expression of Fas, substantially reducing signaling for apoptosis via this mechanism. However, it is known that MRL/lpr mice have increased spontaneous apoptosis of leukocytes. These conflicting observations have stimulated interest in apoptosis in this SLE model. MRL/lpr mice overproduce nitric oxide (NO) as autoimmune disease progresses. In vitro administration of NO may induce or decrease apoptosis depending on the cell type. Therefore, we hypothesized that NO induces MRL/lpr spleen lymphocyte apoptosis independent of Fas receptor engagement. Methods: Percentages of apoptotic spleen lymphocytes from MRL/lpr and BALB/cJ mice were determined ex vivo after in vivo treatment with N-G-monomethyl-L-arginine (NMMA), a nitric oxide synthase (NOS) inhibitor. After culture in varying concentrations of a slow-acting NO donor, the following were determined in spleen lymphocytes: (1) levels of apoptosis, (2) the effect of phorbol myristate acid (PMA) on levels of NO-induced apoptosis, and (3) protein kinase C (PKC) activity. Results: Spleen. lymphocytes from MRL/lpr mice with active disease had increased levels of ex vivo apoptosis when compared with BALB/cJ controls. This increase was reduced by pharmacologic inhibition of NOS in MRL/lpr but not in BALB/cJ mice. Exogenous administration of NO in vitro reduced PKC activity and induced apoptosis in MRL/lpr spleen lymphocytes, an effect that could be reduced via coadministration of PMA in vitro. Conclusion: These results suggest that NO plays a role in spleen lymphocyte apoptosis in MRL/lpr mice, possibly via inhibition of PKC, despite a Fas defect. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250637, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU NIAMS NIH HHS [AR002193, AR45476] NR 65 TC 11 Z9 13 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP 62 EP 71 DI 10.2310/6650.2004.12395 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600019 PM 14989372 ER PT J AU Chen, X Akis, N Choudhury, GG Madaio, M Kasinath, BS AF Chen, X Akis, N Choudhury, GG Madaio, M Kasinath, BS TI Dual signaling pathways regulate vascular endothelial growth factor (VEGF) induction of eNOS in glomerular endothelial (G Endo) cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S320 EP S320 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600927 ER PT J AU Chi, R Jackson, LA Neuzil, KM AF Chi, R Jackson, LA Neuzil, KM TI Characteristics and outcomes of older adults with community-acquired pneumococcal bacteremia. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S95 EP S95 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600115 ER PT J AU Feliers, D Choudhury, GG Barnes, J Kasinath, BS AF Feliers, D Choudhury, GG Barnes, J Kasinath, BS TI Angiotensin II (AII) regulation of vascular endothelial growth factor (VEGF) synthesis in proximal tubular cells (MCT) by protein translation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S301 EP S301 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600825 ER PT J AU Gorin, Y Ricono, JM Wagner, B Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Wagner, B Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Nox4 mediates angiotensin II-induced mesangial cell hypertrophy via activation of Akt/protein kinase B. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S321 EP S321 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600932 ER PT J AU Grippa, J Watson, PA Reusch, JEB AF Grippa, J Watson, PA Reusch, JEB TI Insulin resistance accelerates age related loss of vascular CREB content. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Denver VAMC, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S153 EP S153 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600443 ER PT J AU Huang, JV Casebeer, AW Plomondon, ME Shroyer, AL McDonald, GO Bell, MR Fullerton, D Grover, F Cunningham, F AF Huang, JV Casebeer, AW Plomondon, ME Shroyer, AL McDonald, GO Bell, MR Fullerton, D Grover, F Cunningham, F TI Department of Veterans Affairs post-coronary artery bypass graft patient six-month filling rates for key ischemic heart disease medication compared with non-Veterans Affairs facilities. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S124 EP S124 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600277 ER PT J AU Mahimainathan, L Choudhury, GG AF Mahimainathan, L Choudhury, GG TI Tumor suppressor PTEN regulates TGF beta and high glucose-induced mesangial hypertrophy: Involvement of AKR kinase via PI 3 kinase signaling. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S301 EP S301 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600822 ER PT J AU Mariappan, MM Choudhury, GG Kasinath, BS AF Mariappan, MM Choudhury, GG Kasinath, BS TI Novel role for PLC in regulation of VEGF-induced Erk activation in proximal tubular epithelial cells and its role in protein synthesis. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S320 EP S321 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600928 ER PT J AU Page, ST Herbst, KL Amory, JK Coviello, AD Anawalt, BD Matsumoto, AM Bremner, WJ AF Page, ST Herbst, KL Amory, JK Coviello, AD Anawalt, BD Matsumoto, AM Bremner, WJ TI Short term effects of androgen manipulation on adiponectin in normal men SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Washington, Dept Med, Sch Med, Seattle, WA USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, Seattle, WA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Charles Drew Univ, Dept Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S97 EP S98 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600129 ER PT J AU Phan, J Reue, K AF Phan, J Reue, K TI The role of lipin in diabetes and insulin resistance. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S152 EP S152 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600437 ER PT J AU Phan, J Peterfy, M Reue, K AF Phan, J Peterfy, M Reue, K TI Lipin: A novel modulator of adiposity. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S137 EP S137 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600348 ER PT J AU Tong, J Fujimoto, WY Kahn, SE Weigle, DS McNeely, MJ Leonetti, DL Shofer, JB Boyko, EJ AF Tong, J Fujimoto, WY Kahn, SE Weigle, DS McNeely, MJ Leonetti, DL Shofer, JB Boyko, EJ TI Predictors for increased visceral adiposity at 10-year follow-up in non-diabetic Japanese-Americans. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S130 EP S130 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600311 ER PT J AU Tylee, T Overduin, J Frayo, RS Cummings, DE AF Tylee, T Overduin, J Frayo, RS Cummings, DE TI Intestinal infusions of lactulose suppress ghrelin in a dose-dependent manner: Role of intestinal osmolarity in prandial ghrelin regulation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S131 EP S131 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600315 ER PT J AU Tylee, T Overduin, J Frayo, RS Cummings, DE AF Tylee, T Overduin, J Frayo, RS Cummings, DE TI Intestinal infusions of lactulose suppress ghrelin in a dose-dependent manner: Role of intestinal osmolarity in prandial ghrelin regulation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S92 EP S92 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600096 ER PT J AU Wagner, B Gorin, Y Ghosh-Choudhury, G Ricono, JM Simon, M Chen, Y Abboud, HE AF Wagner, B Gorin, Y Ghosh-Choudhury, G Ricono, JM Simon, M Chen, Y Abboud, HE TI NADPH oxidase signaling in platelet-derived growth factor-BB stimulated metanephric mesenchymal cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. UTHSCSA, Div Nephrol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S320 EP S320 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600926 ER PT J AU Epperson, TK Valente, AJ Gamez, MD Sumimoto, H Banfi, B Krause, KH Clark, RA AF Epperson, TK Valente, AJ Gamez, MD Sumimoto, H Banfi, B Krause, KH Clark, RA TI Specific requirement of the NADPH binding domain of NOX1 for superoxide generation with the NOXA1 and NOXO1 co-factors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland. Kyushu Univ, Med Inst Bioregulat, Fukuoka 812, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 35 EP 35 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100064 ER PT J AU Valente, AJ El Jamali, A Epperson, TK Gamez, M Clark, RA AF Valente, AJ El Jamali, A Epperson, TK Gamez, M Clark, RA TI Regulation of NOX1 NADPH oxidase activity by the SH3 domain of NOXA1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 35 EP 36 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100065 ER PT J AU Mundhekar, AN Bullard, DC Kucik, DF AF Mundhekar, AN Bullard, DC Kucik, DF TI Intra-cellular variability in adhesive properties of endothelial cells affects early steps in leukocyte recruitment SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Genom & Pathobiol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Res Serv, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 37 EP 37 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100070 ER PT J AU Li, SL He, WJ Qiang, M Wang, W Xiao, QF Valente, AJ Quinones, M Ahuja, S Clark, RA Freeman, GL AF Li, SL He, WJ Qiang, M Wang, W Xiao, QF Valente, AJ Quinones, M Ahuja, S Clark, RA Freeman, GL TI A synthetic promoter drives macrophage expression of ApoE and ameliorates atherosclerosis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 55 EP 56 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100138 ER PT J AU Wu, JY Zhang, YJ Edwards, RA Finegold, MJ Jin, YZ Wu, MX AF Wu, JY Zhang, YJ Edwards, RA Finegold, MJ Jin, YZ Wu, MX TI Impairment of TGF-beta signaling in T cells of G alpha i2-/- mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Synta Pharmaceut, Lexington, MA 02421 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Univ Calif Irvine, Irvine, CA 92697 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 62 EP 62 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100162 ER PT J AU Sena, DF Finzi, S Rodgers, K Del Bono, E Haines, JL Wiggs, JL AF Sena, DF Finzi, S Rodgers, K Del Bono, E Haines, JL Wiggs, JL TI Founder mutations of CYP1B1 gene in patients with congenital glaucoma from the United States and Brazil SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CYTOCHROME P4501B1 CYP1B1; JAPANESE PATIENTS; FAMILIES; IDENTIFICATION; POPULATION; SUGGEST; LOCUS; 2P21 C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Johns Hopkins Ctr Hereditary Eye Dis, Baltimore, MD 21205 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [R01 EY09847] NR 24 TC 26 Z9 26 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD JAN 1 PY 2004 VL 41 IS 1 AR e6 DI 10.1136/jmg.2003.010777 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 764QM UT WOS:000188217600023 PM 14729846 ER PT J AU Bates, SH Myers, MG AF Bates, SH Myers, MG TI The role of leptin -> STAT3 signaling in neuroendocrine function: an integrative perspective SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE leptin; obesity; cell signaling; neuroendocrine ID LEPTIN RECEPTOR GENE; MESSENGER-RIBONUCLEIC-ACID; BODY-WEIGHT; FOOD-INTAKE; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; MELANOCORTIN RECEPTORS; INDUCED ANOREXIA; OBESITY SYNDROME; ARCUATE NUCLEUS AB The hormone leptin is secreted by adipose tissue in proportion to fat mass to signal the repletion of body energy stores to the neuroendocrine system. Leptin acts on neurons in the hypothalamus and elsewhere in the brain to decrease appetite and regulate the activity of the thyroid, adrenal, growth, gonadal, and lactational axes. Conversely, absence of leptin signaling initiates the neuroendocrine starvation response. Leptin mediates these effects by activating the long form (LRb) of its receptor. One LRb signal, STAT3, has recently been shown to play a critical role in the regulation of body weight and some elements of neuroendocrine function (thyroid, adrenal, lactation), although the participation of STAT3 in the gonadal and growth axes is negligible. We discuss these findings in the context of the hypothalamic neuroendocrine system as it is presently understood. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. RP Myers, MG (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM martin.myers@joslin.harvard.edu FU NIDDK NIH HHS [DK 56731, DK 57768] NR 75 TC 48 Z9 54 U1 2 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JAN PY 2004 VL 82 IS 1 BP 12 EP 20 DI 10.1007/s00109-003-0494-z PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 769XN UT WOS:000188690300003 PM 14557860 ER PT J AU Puglielli, L Ellis, BC Ingano, LAM Kovacs, DM AF Puglielli, L Ellis, BC Ingano, LAM Kovacs, DM TI Role of acyl-coenzyme A - Cholesterol acyltransferase activity in the processing of the amyloid precursor protein SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; amyloid; cholesterol; lipid; secretion ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; GENERATION; PATHOLOGY AB Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory deficit, cognitive impairment, and personality changes accompanied by specific structural abnormalities in the brain. Deposition of amyloid-beta (Abeta) peptide into senile plaques is a consistent feature of the brains of patients affected by AD. Studies with both animal and cellular models of AD have shown that cholesterol homeostasis and distribution regulate Abeta generation. We have provided genetic, biochemical, and metabolic evidence that implicates intracellular cholesterol distribution, rather than total cholesterol levels, in the regulation of Abeta generation. This minireview focuses on the role of acyl-coenzyme A: cholesterol acyltransferase activity (ACAT) in Abeta generation. In genetically mutant cell lines that overproduce cholesterol but cannot synthesize cholesteryl esters (CEs) because of deficient ACAT activity, Abeta production is almost completely inhibited. Acyl-coenzyme A: cholesterol acyltransferase activity (ACAT) inhibitors, currently being developed for the treatment and prevention of atherosclerosis, reduce CE levels and Abeta generation by up to 50% in cell culture models of AD. Future mechanistic and transgenic animal studies are needed to evaluate the potential use of ACAT inhibitors in the therapeutic treatment or prevention of AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,NIND, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,NIND, Charlestown, MA 02129 USA. EM kovacs@helix.mgh.harvard.edu NR 14 TC 26 Z9 26 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 24 IS 1 BP 93 EP 96 DI 10.1385/JMN:24:1:093 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 849EO UT WOS:000223521700014 PM 15314256 ER PT J AU Morse, LJ Payton, SM Cuny, GD Rogers, JT AF Morse, LJ Payton, SM Cuny, GD Rogers, JT TI FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE RNA-therapeutics; anti-amyloid; amyloid precursor protein (APP); 5 '-untranslated region; translation block; paroxetine; Dimercaptopropanol; iron chelation; FDA drugs; Alzheimer's disease ID MESSENGER-RNA; ALZHEIMERS-DISEASE; TRANSGENIC MICE; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; MOUSE MODEL; INTERLEUKIN-1; METABOLISM; PATHOLOGY; APP AB The 5' untranslated region (5'UTR) of the transcript encoding the Alzheimer's amyloid precursor protein (APP) is a key regulatory sequence that determines the amount of intracellular APP holoprotein present in brain derived cells. Using neuroblastoma cells (SY5Y) we developed a transfection based screen of a library of FDA drugs to identify compounds that limited APP luciferase reporter expression translated from the APP 5'UTR. Paroxetine (Paxil(TM)), dimercaptopropanol, phenserine, desferrioxamine, tetrathiolmobdylate, and azithromycin were six leads that were subsequently found to also suppress APP holoprotein levels or to alter APP cleavage (azithromycin). Since APP holoprotein levels are proportionate to Abeta peptide output in many systems we tested the efficacy of paroxetine and dimercaptopropanol to limit Abeta secretion as measured by ELISA assays. Paroxetine and dimercaptopropanol limited Abeta peptide secretion from lens epithelial cells (B3 cells). Interestingly, paroxetine changed the steady-state levels of transferrin receptor mRNAs. These data suggested that this serotonin reuptake inhibitor (SSRI) provided extra pharmacological action to chelate interacellular iron or change the intracellular iron distribution. An altered iron distribution would be predicted to indirectly limit APP holoprotein expression and Abeta peptide secretion. C1 Harvard Univ, Sch Med, Lab Funct Genom, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Drug Design Discovery & Neurodegenerat Dis, Cambridge, MA 02138 USA. RP Rogers, JT (reprint author), Harvard Univ, Sch Med, Lab Funct Genom, Brigham & Womens Hosp, Cambridge, MA 02138 USA. EM jrogers@partners.org FU NIA NIH HHS [R01 AG21081-01A1] NR 20 TC 29 Z9 30 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 24 IS 1 BP 129 EP 136 DI 10.1385/JMN:24:1:129 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 849EO UT WOS:000223521700019 PM 15314261 ER PT J AU Parekh-Olmedo, H Wang, J Gusella, JF Kmiec, EB AF Parekh-Olmedo, H Wang, J Gusella, JF Kmiec, EB TI Modified single-stranded oligonucleotides inhibit aggregate formation and toxicity induced by expanded polyglutamine SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE HD; aggregation inhibition; Htt; modified single-stranded oligonucleotides ID HUMAN DENDRITIC CELLS; HUNTINGTONS-DISEASE; PROTEIN AGGREGATION; MAMMALIAN-CELLS; NEURODEGENERATIVE DISORDERS; MESSENGER-RNA; POLYAMINES; DROSOPHILA; PEPTIDES; KINETICS AB Huntington's disease (HD) is caused by an increase in the length of the poly(Q) tract in the huntingtin (Htt) protein, which changes its solubility and induces aggregation. Aggregation occurs in two general phases, nucleation and elongation, and agents designed to block either phase are being considered as potential therapeutics. We demonstrate that inclusion formation can be retarded by introducing modified, single-stranded oligonucleotides into a model neuronal cell line. This cell-based assay is used in conjunction with a standardized biochemical assay to identify molecules that can disrupt the process of aggregate formation. Active oligonucleotides include a 6-mer containing a single phosphorothioate linkage on each terminus, a 53-mer and a 9-mer containing three phosphorothioate linkages at each end, and a 25-mer consisting of all modified RNA residues. The disruption process directed by the active oligonucleotides appears to be independent of sequence specificity and complementarity. In contrast, the activity is more dependent on the type of chemical modifications contained within the oligonucleotide. Some oligonucleotides that demonstrated inhibition activity were also found to extend the life span of PC12 cells after the toxic Htt aggregation process was induced. Our data provide the first evidence that short synthetic oligonucleotides inhibit a fundamental pathological pathway of HD and may provide the basis for a novel therapeutic approach. C1 Univ Delaware, Dept Biol Sci, Delaware Biotechnol Inst, Newark, DE 19711 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Kmiec, EB (reprint author), Univ Delaware, Dept Biol Sci, Delaware Biotechnol Inst, Newark, DE 19711 USA. EM ekmiec@udel.edu FU NINDS NIH HHS [NS16367] NR 36 TC 8 Z9 9 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 24 IS 2 BP 257 EP 267 DI 10.1385/JMN:24:2:257 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 864IX UT WOS:000224628300012 PM 15456939 ER PT J AU Bubber, P Tang, JC Haroutunian, V Xu, H Davis, KL Blass, JP Gibson, GE AF Bubber, P Tang, JC Haroutunian, V Xu, H Davis, KL Blass, JP Gibson, GE TI Mitochondrial enzymes in schizophrenia SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE schizophrenia; mitochondria; tricarboxylic acid cycle; neurodegenerative diseases; energy metabolism ID CEREBRAL GLUCOSE-METABOLISM; DEHYDROGENASE COMPLEX; BRAIN; POSTMORTEM; DISEASE; GENES AB The responses of brain metabolism and blood flow to stimulation are diminished in the dorsolateral prefrontal cortexes (DLPFCs) of schizophrenic patients. Reductions in mitochondrial enzymes underlie diminished metabolism in several neurodegenerative diseases. Thus, we tested whether reductions in selected mitochondrial enzymes could underlie the changes in schizophrenia. The activities of the pyruvate dehydrogenase complex (PDHC), aconitase, isocitrate dehydrogenase (ICDH), and the alpha-ketoglutarate dehydrogenase complex (KGDHC) were determined on DLPFCs from patients with schizophrenia (n = 26) and normal nonpsychiatric disease controls (n = 13). The enzyme activities (mU/mg protein; mean +/- SEM) were similar (values for controls and schizophrenic patients, respectively) for PDHC (11.36 +/- 1.5, 10.33 +/- 0.8), aconitase (1.06 +/- 0.1, 1.35 +/- 0.2), ICDH (31.70 +/- 2.7, 32.00 +/- 2.6), and KGDHC (2.62 +/- 0.4, 3.09 +/- 0.3). Separate analyses of the patients matched for age or postmortem interval gave similar conclusions. Cognitive dementia rating scores correlated poorly with activities of PDHC, aconitase, ICDH, and KGDHC. In one schizophrenic patient, activity of aconitase was undetectable, and in two others KGDHC activity was very low. Both had low activities of ICDH. A reduced activity of these enzymes in a subgroup is consistent with other data, suggesting that some patients with schizophrenia have abnormalities in brain mitochondria. However, in schizophrenia, unlike a number of neurodegenerative diseases, reductions in the activities of the key mitochondrial enzymes KGDHC and PDHC are not frequent. C1 Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA. Cornell Univ, Dept Psychiat, New York Presbyterian Hosp, Weill Med Coll, White Plains, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10021 USA. Bronx Vet Affairs Med Ctr, MIRECC, Bronx, NY 10468 USA. RP Gibson, GE (reprint author), Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA. EM ggibson@med.cornell.edu FU NIA NIH HHS [AG14930, AG19589]; NIMH NIH HHS [MH45212] NR 31 TC 24 Z9 25 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 24 IS 2 BP 315 EP 321 DI 10.1385/JMN:24:2:315 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 864IX UT WOS:000224628300018 PM 15456945 ER PT J AU Germano, PM Le, SV Oh, DS Fan, R Lieu, S Siu, A Pisegna, JR AF Germano, PM Le, SV Oh, DS Fan, R Lieu, S Siu, A Pisegna, JR TI Differential coupling of the PAC1 SV1 splice variant on human colonic tumors to the activation of intracellular cAMP but not intracellular Ca2+ does not activate tumor proliferation SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 13th Annual Summer Neuropeptides Conference CY 2003 CL MONTAUK, NY DE pituitary adenylate cyclase-activating polypeptide; pituitary adenylate cyclase-activating polypeptide type 1 receptor; adenylyl cyclase ID LUNG-CANCER CELLS; ADENYLATE-CYCLASE; SIGNAL-TRANSDUCTION; I RECEPTOR; POLYPEPTIDE; PEPTIDE; INTERNALIZATION; PHARMACOLOGY; EXPRESSION; GROWTH AB PAC1 is a recently cloned and characterized heptahelical, G protein-coupled receptor with high affinity to PACAP-27 and PACAP-38 and is differentially coupled to activate intracellular Call and cAMP. PAC1 is expressed as four major splice variants, each possessing differential coupling to inositol phosphates and intracellular Ca2+. PAC1 has been shown previously to be expressed and regulate the growth and proliferation of nonsquamous cell lung cancer cells, as well as breast cancer cell lines. PAC1 is expressed on the HCT8 human colon cancer cell line and is coupled to the activation of both intracellular cAMP and Ca2+ with consequent stimulation of growth. In the current study, we contrast the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the HCT8 colon cancer cell lines to the HCT116 and FET cell lines wherein PAC1 is expressed as the SV1 or HIP splice variant and is coupled to the activation only of cAMP but not of intracellular Ca2+. These data indicate that human colon tumor cells express PAC1 and are differentially coupled to intracellular signal transduction molecules. The ability to activate both cAMP and Ca2+ appears to be a prerequisite for activation of tumor proliferation, indicating a potentially important factor in how PACAP potentiates the growth of certain tumors. C1 Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM pgermano@ucla.edu; jpisegna@ucla.edu NR 17 TC 9 Z9 10 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 22 IS 1-2 BP 83 EP 91 DI 10.1385/JMN:22:1-2:83 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 773LG UT WOS:000188924800010 PM 14742913 ER PT J AU Gan, L Falzone, TL Zhang, KH Rubinstein, M Baldessarini, RJ Tarazi, FI AF Gan, L Falzone, TL Zhang, KH Rubinstein, M Baldessarini, RJ Tarazi, FI TI Enhanced expression of dopamine D-1 and glutamate NMDA receptors in dopamine D-4 receptor knockout mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE autoradiography; caudate putamen; dopamine receptors; D-4-receptor; genetic knockout; glutamate receptors; mutant mice ID NEONATAL 6-HYDROXYDOPAMINE LESIONS; ANTIPSYCHOTIC-DRUG-TREATMENT; RAT-BRAIN; ATYPICAL ANTIPSYCHOTICS; SELECTIVE ANTAGONISTS; MOTOR HYPERACTIVITY; NOVELTY SEEKING; DRD4 GENE; FOREBRAIN; SUBTYPES AB Expression of dopamine ([DA] D-1 and D-2) and glutamate ([Glu], (N-methyl-D-aspartic acid [NMDA] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kanaic acid [KA]) receptor types were analyzed autoradiographically in forebrain regions of D-4 receptor knockout mice and their wild-type controls. Selective radioligand binding to D-4 receptors was virtually absent in D-4 receptor knockout mouse brain in contrast to significant specific D-4 binding in forebrain tissue of wild-type controls. Labeling of D-1 receptors was significantly increased in nucleus accumbens (NAc; 39%) and caudate putamen (CPu; 42%) of D-4-knockout mice vs wild-type controls. In addition, NMDA receptor labeling was significantly increased in NAc (31%), CPu (40%), and hippocampal CA(1) (21%) and CA(3) (25%) regions of D-4 knockouts vs wild-type controls. No changes in D-2, AMPA or KA receptors were found. The findings suggest that D-1, D-4, and NMDA receptors might interact functionally and that developmental absence of D-4 receptors might trigger compensatory mechanisms that enhance expression of D-1 receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Univ Buenos Aires, CONICET, Inst Invest Ingn Genet & Biol Mol, Buenos Aires, DF, Argentina. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. EM ftarazi@hms.harvard.edu NR 43 TC 33 Z9 33 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 22 IS 3 BP 167 EP 177 DI 10.1385/JMN:22:3:167 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 804QD UT WOS:000220312300002 PM 14997010 ER PT J AU Takahashi, T Kinsman, S Makris, N Grant, E Haselgrove, C McInerney, S Kennedy, DN Takahashi, T Fredrickson, K Mori, S Caviness, VS AF Takahashi, T Kinsman, S Makris, N Grant, E Haselgrove, C McInerney, S Kennedy, DN Takahashi, T Fredrickson, K Mori, S Caviness, VS TI Holoprosencephaly - Topologic variations in a Liveborn series: A general model based upon MRI analysis SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID BRAIN-DEVELOPMENT; DORSAL CYST; PERSPECTIVES; MALFORMATIONS; MUTATIONS; GENETICS; SPECIFICATION; DEFINITION; FOREBRAIN; SHH AB We present an MRI-based anatomic analysis of a series of 9 human brains, representing lobar, semilobar and alobar forms of holoprosencephaly. The analysis of these variable forms of the malformation is based upon a topologic systematics established in a prior analysis of a homogeneous set of semilobar malformations. This systematics has the dual advantage that it serves both as a uniform reference for qualitative description and as a quantitative descriptive base for mathematical correlations between parameters of topology and of growth and development. Within this systematics, the prosencephalic midline is divided from caudal to rostral into diencephalic (DD-right and left, subthalamus through suprachiasmatic junction with telencephalon), telencephalic (TT-right and left, suprachiasmatic border of telencephalon midline to hippocampal commissure) and diencephalic-telencephalic (DT-right and left-hippocampal commissure through temporal limb of choroid fissure) segments. The topologic abnormality of the initial semilobar series was expressed in an orderly rostral to caudal gradient along the TT segment. In each malformation, normal midline topology began with a small posterior corpus callosum. Although the topologic anomaly in the present series invariably also involved the TT segment, this involvement was not continuous and was variably associated with anomalies of the DD in 6 and unilaterally of the DT in 1 brain. In the present as well as with the earlier series of HPE malformations but not in "normative brains,'' total telencephalic growth is strongly correlated with the length of the midline telencephalic segment. We propose that this system of analysis will be sensitive to the developmental stage and locus of expression of genetic and non-genetic determinants of the formal origin of HPE. For all of the present series, karyotype anlyses were normal. Mutations in the Shh and Zic2 genes were excluded in 2 cases. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. RP Caviness, VS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [NS12005, NS34189] NR 44 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD JAN PY 2004 VL 33 IS 1 BP 23 EP 35 DI 10.1023/B:NEUR.0000029646.75645.9c PG 13 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 825GX UT WOS:000221745300002 PM 15173630 ER PT J AU Kunjathoor, VV Tseng, AA Medeiros, LA Khan, T Moore, KJ AF Kunjathoor, Vidya V. Tseng, Anita A. Medeiros, Lea A. Khan, Tayeba Moore, Kathryn J. TI beta-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins SO JOURNAL OF NEUROINFLAMMATION LA English DT Article AB Background: Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar beta-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether beta-amyloid altered oxidized lipoprotein clearance via CD36. Methods: The availability of mice genetically deficient in class A (SRAI & II) and class B (CD36) scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of A beta on: (a) cholesterol ester accumulation by GC-MS and neutral lipid staining, (b) binding, uptake and degradation of I-125-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c) expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether A beta-CD36 signaling altered metabolism of oxidized lipoproteins. Results: In primary microglia and macrophages, A beta inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL) in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with A beta were devoid of cholesterol ester. Pretreatment of cells with A beta did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of A beta did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that A beta inhibited oxidized lipoprotein binding and its subsequent degradation via CD36, but not SRA, and this was independent of A beta-CD36-signaling. Furthermore, A beta treatment decreased CD36, but not SRA, mRNA and protein, thereby reducing cell surface expression of this oxLDL receptor. Conclusions: Together, these data demonstrate that in the presence of beta-amyloid, CD36-mediated clearance of oxidized lipoproteins is abrogated, which would promote the extracellular accumulation of these pro-inflammatory lipids and perpetuate lipid peroxidation. C1 [Kunjathoor, Vidya V.; Tseng, Anita A.; Medeiros, Lea A.; Khan, Tayeba; Moore, Kathryn J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit,Dept Med, Boston, MA 02114 USA. RP Moore, KJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit,Dept Med, Boston, MA 02114 USA. EM kunjathoor@molbio.mgh.harvard.edu; tseng@molbio.mgh.harvard.edu; medeiros@molbio.mgh.harvard.edu; Khan@molbio.mgh.harvard.edu; kmoore@molbio.mgh.harvard.edu OI Moore, kathryn/0000-0003-2505-2547 FU NIH [AG20255]; Ellison Foundation FX This work was supported by NIH AG20255 and an award from the Ellison Foundation (KJM). NR 47 TC 24 Z9 24 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PY 2004 VL 1 AR 23 DI 10.1186/1742-2094-1-23 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA V29PB UT WOS:000208759200023 PM 15546489 ER PT J AU Sanchez-Pernaute, R Ferree, A Cooper, O Yu, MX Brownell, AL Isacson, O AF Sanchez-Pernaute, Rosario Ferree, Andrew Cooper, Oliver Yu, Meixiang Brownell, Anna-Liisa Isacson, Ole TI Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease SO JOURNAL OF NEUROINFLAMMATION LA English DT Article AB Several lines of evidence point to a significant role of neuroinflammation in Parkinson's disease (PD) and other neurodegenerative disorders. In the present study we examined the protective effect of celecoxib, a selective inhibitor of the inducible form of cyclooxygenase (COX-2), on dopamine (DA) cell loss in a rat model of PD. We used the intrastriatal administration of 6-hydroxydopamine (6-OHDA) that induces a retrograde neuronal damage and death, which progresses over weeks. Animals were randomized to receive celecoxib (20 mg/kg/day) or vehicle starting 1 hour before the intrastriatal administration of 6-OHDA. Evaluation was performed in vivo using micro PET and selective radiotracers for DA terminals and microglia. Post mortem analysis included stereological quantification of tyrosine hydroxylase, astrocytes and microglia. 12 days after the 6-OHDA lesion there were no differences in DA cell or fiber loss between groups, although the microglial cell density and activation was markedly reduced in animals receiving celecoxib (p < 0.01). COX-2 inhibition did not reduce the typical astroglial response in the striatum at any stage. Between 12 and 21 days, there was a significant progression of DA cell loss in the vehicle group (from 40 to 65%) that was prevented by celecoxib. Therefore, inhibition of COX-2 by celecoxib appears to be able, either directly or through inhibition of microglia activation to prevent or slow down DA cell degeneration. C1 [Sanchez-Pernaute, Rosario; Ferree, Andrew; Cooper, Oliver; Yu, Meixiang; Brownell, Anna-Liisa; Isacson, Ole] Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. [Sanchez-Pernaute, Rosario; Ferree, Andrew; Cooper, Oliver; Isacson, Ole] McLean Hosp, Neuroregenerat Labs, Belmont, MA 02178 USA. [Yu, Meixiang; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. EM rosario_pernaute@hms.harvard.edu; aferree@mclean.harvard.edu; ocooper@mclean.harvard.edu; ymeixiang@partners.org; abrownell@partners.org; isacson@hms.harvard.edu FU NIH [R01NS41263]; Udall Parkinson's Disease Research Center [P50NS39793]; Kinetics Foundation; Parkinson Foundation National Capital Area; Consolidated Anti-Aging Foundation FX This work was supported by the NIH grants, R01NS41263 and Udall Parkinson's Disease Research Center P50NS39793 (OI). The support of the Kinetics Foundation, the Parkinson Foundation National Capital Area and the Consolidated Anti-Aging Foundation is also gratefully acknowledged. NR 68 TC 104 Z9 109 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PY 2004 VL 1 AR 6 DI 10.1186/1742-2094-1-6 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA V29PB UT WOS:000208759200006 PM 15285796 ER PT J AU Goral, M AF Goral, M TI First-language decline in healthy aging: implications for attrition in bilingualism SO JOURNAL OF NEUROLINGUISTICS LA English DT Review DE aging; bilingualism; language attrition; lexical retrieval; word production ID BOSTON NAMING TEST; ADULT AGE-DIFFERENCES; OLDER ADULTS; WORKING-MEMORY; NORMATIVE DATA; INDIVIDUAL-DIFFERENCES; PROCESSING-SPEED; VERBAL FLUENCY; FRONTAL-LOBE; TERM-MEMORY AB Studies of language attrition have focused on the decline observed in individuals' first-language (L1) or second language (L2) in the context of bilingualism. L1 decline has also been extensively studied in monolingual adults in the context of healthy aging. One language domain that has been found to decline with age is lexical retrieval. This paper focuses on longitudinal and cross-sectional studies of healthy aging, which show that older adults, as compared to younger adults, demonstrate greater difficulty in performing naming tasks as well as accelerated decline in performance over time. Relevant findings of age-related decline in word retrieval and theories that have been proposed to account for it are summarized and their relations to the patterns and theories of lexical attrition reported for bilingual speakers are discussed. It is concluded that despite fundamental differences between these two circumstances of attrition, applying methods and theories from one study area to the other can be beneficial for understanding processes of language attrition. (C) 2003 Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Boston VA Healthcare Syst, Language Aging Brain Lab,Dept Neurol, Boston, MA 02130 USA. RP Goral, M (reprint author), Boston Univ, Sch Med, Boston VA Healthcare Syst, Language Aging Brain Lab,Dept Neurol, 150 S Huntington Ave, Boston, MA 02130 USA. EM mgoral@bu.edu NR 137 TC 18 Z9 19 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD JAN PY 2004 VL 17 IS 1 BP 31 EP 52 DI 10.1016/S0911-6044(03)00052-6 PG 22 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 801VK UT WOS:000220123200002 ER PT J AU Filley, CM Halliday, W Kleinschmidt-DeMasters, BK AF Filley, CM Halliday, W Kleinschmidt-DeMasters, BK TI The effects of toluene on the central nervous system SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE dementia; magnetic resonance imaging; neurotoxin; solvent vapor abuse; toluene; leukoencephalopathy; white matter ID FETAL ALCOHOL SYNDROME; SOLVENT VAPOR ABUSE; WHITE-MATTER; MAGNETIZATION-TRANSFER; MRI ABNORMALITIES; PRENATAL EXPOSURE; EMBRYOPATHY; BRAIN; INHALATION; ENCEPHALOPATHY AB In recent decades the organic solvent toluene (methylbenzene) has emerged as one of the best-studied neurotoxins. Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. RP Kleinschmidt-DeMasters, BK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. NR 67 TC 74 Z9 84 U1 1 U2 13 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2004 VL 63 IS 1 BP 1 EP 12 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 757HL UT WOS:000187556900001 PM 14748556 ER PT J AU Becerra, L Iadarola, M Borsook, D AF Becerra, L Iadarola, M Borsook, D TI CNS activation by noxious heat to the hand or foot: Site-dependent delay in sensory but not emotion circuitry SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID A-DELTA FIBERS; CHRONIC PAIN; HUMAN BRAIN; CONDUCTION-VELOCITY; 1ST PAIN; THERMAL THRESHOLDS; NEURAL RESPONSES; NERVE-FIBERS; EVOKED PAIN; REWARD AB Recently, functional magnetic resonance imaging has been used as a novel method of evaluating the CNS response to noxious stimuli. In a previous study, a prolonged noxious thermal stimulus applied to the dorsum of the hand produced more than one hemodynamic response that was temporally segregated. The two major responses displayed activation in primary sensory regions (classic pain circuitry) and regions involved in emotion (reward/aversion circuitry), respectively. In the current study, we applied the same thermal stimulus separately to the dorsum of the left foot and the dorsum of the left hand in the same subjects and compared the hemodynamic responses to evaluate the effects of conduction distance on CNS activation within these two segregated systems. After stimulus delivery to the foot, the hemodynamic response in primary sensory networks occurs after a delay of 3.6+/-1.3 s as compared with the response after hand stimulation. The relative delay of the hemodynamic response in reward/aversion regions is not significantly different between hand and foot stimulation (0.6+/-2.1 s). These results within the primary sensory system are consistent with the greater conduction distance of the peripheral nerves from the hand versus the foot. The observation that the response within the reward/aversion pathways occurs with the same rapid temporal characteristics after either hand or foot stimulation supports the notion that the circuitry involved in the evaluation of aversive stimuli is rapid in onset and probably represents a major protective mechanism for survival. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Ctr Funct Pain Neuroimaging & Therapy Res, Charlestown, MA 02129 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosci Mech Branch, NIH, Bethesda, MD 20892 USA. RP Borsook, D (reprint author), Descartes Therapeut Inc, 790 Mem Dr,Suite 104, Cambridge, MA 02139 USA. EM dborsook@dtrx.com FU PHS HHS [012581, 12650] NR 69 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2004 VL 91 IS 1 BP 533 EP 541 DI 10.1152/jn.00326.2003 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 762GW UT WOS:000187964500045 PM 14715722 ER PT J AU Ramsey, MJ McKenna, MJ Barker, FG AF Ramsey, MJ McKenna, MJ Barker, FG TI Superior semicircular canal dehiscence syndrome SO JOURNAL OF NEUROSURGERY LA English DT Article DE superior semicircular canal; dehiscence; dysequilibrium; vertigo; middle cranial fossa AB The authors present the case of a man who had superior semicircular canal dehiscence syndrome in addition to chronic otitis media. This case is atypical because the patient coincidentally had middle ear and mastoid disease, which previously had been treated surgically. The prior ear surgery delayed the diagnosis of superior semicircular canal dehiscence syndrome and increased the complexity of the repair of the superior semicircular canal dehiscence. Superior semicircular canal dehiscence syndrome is a recently recognized syndrome resulting in acute or chronic vestibular symptoms. The diagnosis is made using history, vestibular examination, and computerized tomography studies. Neurosurgeons should be aware that patients with superior semicircular canal dehiscence syndrome who experience disabling chronic or acute vestibular symptoms can be treated using a joint neurosurgical-otological procedure through the middle cranial fossa. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol, Boston, MA USA. Harvard Univ, Sch Med, Dept Laryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM mjm@epl.meei.harvard.edu NR 3 TC 5 Z9 7 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2004 VL 100 IS 1 BP 123 EP 124 DI 10.3171/jns.2004.100.1.0123 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 761YQ UT WOS:000187943400020 PM 14743923 ER PT J AU Valero-Cabre, A Tsironis, K Skouras, E Navarro, X Neiss, WF AF Valero-Cabre, A Tsironis, K Skouras, E Navarro, X Neiss, WF TI Peripheral and spinal motor reorganization after nerve injury and repair SO JOURNAL OF NEUROTRAUMA LA English DT Article DE electromyography; misdirected reinnervation; regeneration; retrograde tracers; sciatic nerve; spinal cord reorganization; tubulization ID HYPOGLOSSAL-FACIAL ANASTOMOSIS; RAT SCIATIC-NERVE; MUSCLE REINNERVATION; REGENERATING AXONS; TARGET MUSCLES; ADULT-RATS; DYNAMIC ORGANIZATION; SENSORY NEURONS; CORTEX OUTPUT; DISTAL STUMP AB Functional recovery after peripheral nerve injury depends on the amount as well as on the accuracy of reinnervation by regenerative axons. In this study, the rat sciatic nerve was subjected to crush injury or complete transection repaired by either (1) straight nerve suture, (2) crossed nerve suture of tibial and peroneal fascicles, or (3) silicone tubulization leaving a gap of 4 mm. The compound muscle action potentials (CMAP) of gastrocnemius, tibialis anterior and plantar muscles were recorded 90 days post operation to assess functional reinnervation and Fast Blue, Fluoro Gold and DiI were applied to the nerve branches projecting into these muscles to quantify morphological reinnervation. The CMAP amplitude achieved in gastrocnemius, tibialis anterior and plantar muscles was higher after nerve crush (86%, 82%, 65% of control) than after any surgical nerve repair (straight suture: 49%, 53%, 32%; crossed suture: 56%, 50%, 31%; silicone tube: 42%, 44%, 25%). The total number of labeled motoneurons, however, did not significantly differ between groups (control: 1238 +/- 82, crush: 1048 +/- 49, straight suture: 1175 +/- 106, crossed suture: 1085 +/- 84, silicone tube: 1250 +/- 182). The volume occupied by labeled motoneurons within the spinal cord was larger after surgical nerve repair than in crush or normal control animals, and fewer neurons showed abnormal multiple projections after crush (2.5%) or straight suture (2.2%) than following crossed suture (5%) or silicone tube (6%). In conclusion, nerve repair with a silicone tube leaving a short gap does not increase accuracy of reinnervation. C1 Univ Cologne, Inst Anat 1, D-50931 Cologne, Germany. Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, E-08193 Barcelona, Spain. Klinikum Univ Cologne, Klin Unfall Hand & Wiederherstellungschirurg, Cologne, Germany. Harvard Univ, Sch Med, BIDMC, Dept Neurol, Boston, MA 02115 USA. RP Neiss, WF (reprint author), Univ Cologne, Inst Anat 1, Bldg 35,Joseph Stelzmann Str 9, D-50931 Cologne, Germany. EM neiss.anatomie@uni-koeln.de RI Navarro, Xavier/C-9577-2011 OI Navarro, Xavier/0000-0001-9849-902X NR 78 TC 66 Z9 68 U1 0 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN PY 2004 VL 21 IS 1 BP 95 EP 108 DI 10.1089/089771504772695986 PG 14 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 766GU UT WOS:000188368700010 PM 14987469 ER PT J AU Erickson, JI Duffy, ME Gibbons, MP Fitzmaurice, J Ditomassi, M Jones, D AF Erickson, JI Duffy, ME Gibbons, MP Fitzmaurice, J Ditomassi, M Jones, D TI Development and psychometric evaluation of the professional practice environment (PPE) scale SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE professional practice environment; acute care settings; measurement ID INTENSIVE-CARE UNITS; NURSING WORK INDEX; MAGNET HOSPITALS; OUTCOMES; ORGANIZATION; EXCELLENCE; SERVICES AB Purpose: To describe the Professional Practice Environment (PPE) scale, its conceptual development and psychometric evaluation, and its uses in measuring eight characteristics of the professional practice environment in an acute care setting. Design and Methods: The 38-item PPE Scale was validated on a sample of 849 professional practice staff at the Massachusetts General Hospital in Boston. Psychometric analysis included: item analysis, principal components analysis (PCA) with varimax rotation and Kaiser normalization, and internal consistency reliability using Cronbach's alpha coefficient. Findings: Eight components were shown, confirming the original conceptually derived model's structure and accounting for 61% of explained variance. Cronbach's alpha coefficients for the eight PPE subscales ranged from .78 to .88. Conclusions: Findings showed the 38-item PPE Scale was reliable and valid for use in health outcomes research to examine the professional practice environment of staff working in acute care settings. C1 Massachusetts Gen Hosp, Boston Coll, Ctr Nursing Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin & Profess Dev, Boston, MA 02114 USA. Massachusetts Gen Hosp, Off Qual & Safety, Boston, MA 02114 USA. Massachusetts Gen Hosp, Patient Care Serv Operat, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, Boston Coll, Ctr Nursing Res, 55 Fruit St, Boston, MA 02114 USA. EM jiveserickson@partners.org RI Benneyworth, Brian/A-4667-2009 OI Benneyworth, Brian/0000-0002-4692-5303 NR 37 TC 35 Z9 35 U1 0 U2 4 PU SIGMA THETA TAU INT PI INDIANAPOLIS PA 550 W NORTH STREET, INDIANAPOLIS, IN 46202 USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2004 VL 36 IS 3 BP 279 EP U2 DI 10.1111/j.1547-5069.2004.04050.x PG 7 WC Nursing SC Nursing GA 852RP UT WOS:000223774400023 PM 15495499 ER PT J AU Dodson, TB Guralnick, WC Donoff, RB Kaban, LB AF Dodson, TB Guralnick, WC Donoff, RB Kaban, LB TI Massachusetts General Hospital/Harvard Medical School MD Oral and Maxillofacial Surgery program: A 30-year review SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: The first resident enrolled in the Massachusetts General Hospital/Harvard MID Oral and Maxillofacial Surgery (MD/OMFS) program graduated from Harvard Medical School (HMS) in 1972. The purpose of this report is to provide a summary of the first 30 years of the program and to outline plans for its future. Materials and Methods: This was a retrospective cohort study and the sample was composed of the residents enrolled in the MD/OMFS program between 1971 and 2000. Study variables included the dental school from which the resident graduated, successful completion of the MD/OMFS program, performance on parts I and 11 of the United States Medical Licensing Examination/National Board of Medical Examinations (USMLE/NBME), HMS grades, and career trajectories (full- or part-time academic or private practice). Appropriate descriptive and bivariate statistics were computed for all study variables. Results: During the study interval, 56 residents entered the MD/OMFS program and graduated from HMS. All members of the cohort, regardless of the dental school from which they graduated, performed well as evidenced by USMLE/NBME scores and medical school grades. Ninety-four percent of eligible graduates have completed the American Board of Oral and Maxillofacial Surgery examination. The pass rate was 100%. Thirty-four graduates are involved in full- or part-time academic practice. Four trainees completed medical school but did not complete the OMFS program. Conclusion: The overwhelming majority of trainees completed the program, became board certified, and currently practice OMFS or a related specialty. A disproportionate number entered academic careers. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org NR 3 TC 23 Z9 24 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2004 VL 62 IS 1 BP 62 EP 65 DI 10.1016/j.joms.2002.12.002 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 761DN UT WOS:000187884900013 PM 14699551 ER PT J AU Li, G Zayontz, S DeFrate, LE Most, E Suggs, JF Rubash, HE AF Li, G Zayontz, S DeFrate, LE Most, E Suggs, JF Rubash, HE TI Kinematics of the knee at high flexion angles: an in vitro investigation SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE high flexion; knee; kinematics; muscle loading; soft tissue constraints ID ANTERIOR CRUCIATE LIGAMENT; MUSCLE FORCES; SITU FORCES; QUADRICEPS; ARTHROPLASTY; POSTERIOR; VIVO; RECONSTRUCTION; HAMSTRINGS; STRAIN AB Restoration of knee function after total knee, meniscus, or cruciate ligament surgery requires an understanding of knee behavior throughout the entire range of knee motion. However, little data are available regarding knee kinematics and kinetics at flexion angles greater than 120degrees (high flexion). In this study, 13 cadaveric human knee specimens were tested using an in vitro robotic experimental setup. Tibial anteroposterior translation and internal-external rotation were measured along the passive path and under simulated muscle loading from full extension to 150degrees of flexion. Anterior tibial translation was observed in the unloaded passive path throughout, with a peak of 31.2 +/- 13.2 mm at 150degrees. Internal tibial rotation increased with flexion to 150degrees on the passive path to a maximum of 11.1 +/- 6.7degrees. The simulated muscle loads affected tibial translation and rotation between full extension and 120degrees of knee flexion. Interestingly, at high flexion, the application of muscle loads had little effect on tibial translation and rotation when compared to values at 120degrees. The kinematic behavior of the knee at 150degrees was markedly different from that measured at other flexion angles. Muscle loads appear to play a minimal role in influencing tibial translation and rotation at maximal flexion. The results imply that the knee is highly constrained at high flexion, which could be due in part to compression of the posterior soft tissues (posterior capsule, menisci, muscle, fat, and skin) between the tibia and the femur. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Med Sch,Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. RP Li, G (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 30 TC 56 Z9 62 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD JAN PY 2004 VL 22 IS 1 BP 90 EP 95 DI 10.1016/S0736-0266(03)00118-9 PG 6 WC Orthopedics SC Orthopedics GA 761DG UT WOS:000187884300014 PM 14656665 ER PT J AU Merriam, GR Carney, C Smith, LC Kletke, M AF Merriam, GR Carney, C Smith, LC Kletke, M TI Adult growth hormone deficiency: Current trends in diagnosis and dosing SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 17th Annual National Cooperative Growth Study (NCGS)/4th Annual National Cooperative Somatropin Surveillance Investigator Meeting (NCSS) CY SEP 17-21, 2003 CL Baltimore, MD DE growth hormone; growth hormone deficiency; adults; diagnosis; growth hormone dosing ID GH-RELEASING-HORMONE; BODY-COMPOSITION; DOSE-RESPONSE; YOUNG-ADULTS; REPLACEMENT; SECRETION; THERAPY; AGE; ARGININE AB Only similar to 20 % of adults with GH deficiency (GHD) have a history of childhood-onset GHD; the remainder acquire GHD in adult life, usually through acquired damage to the pituitary-hypothalamic region. Diagnosis of GHD in adults is more difficult than in children and is made first from the clinical context, reinforced by signs and symptoms, and then confirmed by biochemical testing. The signs and symptoms, however, including altered body composition, reduced energy, and mild depression, are too common to have diagnostic value without a suggestive clinical context. Furthermore, biochemical tests for GH or IGF-I levels are imperfect, characterized by significant false-positive and-negative rates. GH dosing in adults has shifted to an individualized dose-titration approach, in which treatment is begun at a fixed dose and then titrated upward until IGF-I levels normalize, significant side effects develop, or beneficial effects plateau. Generally, women require higher GH doses than do men. Reflecting age-related differences in normal GH secretion, GH doses may be higher in young adults and lower in older patients. C1 VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Tacoma, WA USA. Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Merriam, GR (reprint author), VA Puget Sound Hlth Care Syst, Bldg 18C,Room 127 9600 Vet Dr SW, Tacoma, WA 98493 USA. EM merriam@u.washington.edu NR 34 TC 6 Z9 6 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PY 2004 VL 17 SU 4 BP 1307 EP 1320 PG 14 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 951XV UT WOS:000230966600008 PM 15506077 ER PT J AU Ho, CL Walton, DS AF Ho, CL Walton, DS TI Primary megalocornea: Clinical features for differentiation from infantile glaucoma SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article; Proceedings Paper CT 73rd Meeting of the Association-of-Vision-Research-in-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Vision Res Ophthalmol ID AUTOSOMAL-DOMINANT MEGALOCORNEA; SYNDROME CEREBRAL GIGANTISM; X-LINKED MEGALOCORNEA; CONGENITAL GLAUCOMA AB Purpose: To describe the ocular findings in megalocornea to assist in its differentiation from infantile glaucoma in the evaluation of children with abnormally enlarged corneas. Methods: The clinical findings of 4 boys found to have megalocornea following referral for evaluation of large corneas and suspected glaucoma were reviewed. Results: Three of the 4 patients had photophobia. Clear and enlarged corneas were observed associated with deep anterior chambers, posterior bowing of the irides, and normal intraocular pressures (IOPs) in all eyes. Transillumination of the irides was found in 6 of 8 eyes and pigment dispersion was seen in 4 of 8 eyes. Pigment dispersion appeared to be acquired over time, and the youngest patient in this series who had pigment dispersion detected on slit-lamp examination was 15 years; the youngest patient with the condition detected on gonioscopy was. 8 years. No breaks in Descemet's membrane were present. Family history obtained from 3 of the 4 patients revealed evidence of sex-linked recessive inheritance. These findings are distinct from the clinical features of infantile glaucoma characterized by elevated IOP, breaks in Descemet's membrane, corneal edema, a generally flat iris profile, less pronounced enlargement of the anterior segment, the absence of iris transillumination and pigment dispersion, and autosomal recessive inheritance. Three patients had corneal size asymmetry, a finding that has not been previously reported. Conclusion: Hereditary megalocornea has defining clinical findings that help to identify and differentiate it from other causes of enlarged corneas. Asymmetry in corneal size does not preclude its diagnosis. C1 Singapore Natl Eye Ctr, Singapore, Singapore. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. NR 25 TC 9 Z9 9 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD JAN-FEB PY 2004 VL 41 IS 1 BP 11 EP 17 PG 7 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 765AV UT WOS:000188245500003 PM 14974829 ER PT J AU Lin, A Harding, C Silberbach, M AF Lin, A Harding, C Silberbach, M TI Hand it to the skin in Costello syndrome SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Div Metab, Dept Pediat, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Metab, Dept Mol & Med Genet, Portland, OR 97239 USA. Doernbecher Mem Hosp Children, Div Pediat Cardiol, Portland, OR 97201 USA. RP Lin, A (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2004 VL 144 IS 1 BP 135 EP 135 DI 10.1016/S0022-3476(03)00346-9 PG 1 WC Pediatrics SC Pediatrics GA 763MZ UT WOS:000188091100026 PM 14722534 ER PT J AU Shikama, Y Shichishima, T Matsuoka, I Colin, S Paul, J Maruyama, Y AF Shikama, Y Shichishima, T Matsuoka, I Colin, S Paul, J Maruyama, Y TI Accumulation of premature mRNA of GM-CSF receptor common beta subunit in myelodysplastic syndromes SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 77th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2004 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 Fukushima Med Univ, Sch Med, Dept Pharmacol, Fukushima 9601295, Japan. Fukushima Med Univ, Dept Internal Med 1, Fukushima 9601295, Japan. Dana Farber Canc Inst, Dept Pediat Oncol & Hematol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2004 VL 94 SU 1 BP 148P EP 148P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 802CT UT WOS:000220142300547 ER PT J AU Wu, MF John, J Boehmer, LN Yau, D Nguyen, GB Siegel, JM AF Wu, MF John, J Boehmer, LN Yau, D Nguyen, GB Siegel, JM TI Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy in narcoleptic dogs SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID FREELY MOVING CATS; LOCUS-COERULEUS NEURONS; SINGLE-UNIT RESPONSES; IN-VIVO MICRODIALYSIS; BEHAVIORAL ORGANIZATION; RETICULAR-FORMATION; HYPOCRETIN NEURONS; CANINE NARCOLEPSY; UNRESTRAINED CAT; REM-SLEEP AB Cataplexy, a symptom associated with narcolepsy, represents a unique dissociation of behavioural states. During cataplectic attacks, awareness of the environment is maintained, as in waking, but muscle tone is lost, as in REM sleep. We have previously reported that, in the narcoleptic dog, noradrenergic cells of the locus coeruleus cease discharge during catapilexy. In the current study, we report on the activity of serotonergic cells of the dorsal raphe nucleus. The discharge patterns of serotonergic dorsal raphe cells across sleep-waking states did not differ from those of dorsal raphe and locus coeruleus cells recorded in normal rats, cats and monkeys, with tonic discharge in waking, reduced activity in non-REM sleep and cessation of activity in REM sleep. However, in contrast with locus coeruleus cells, dorsal raphe REM sleep-off neurones did not cease discharge during cateplexy. Instead, discharge continued at a level significantly higher than that seen in REM sleep and comparable to that seen in non-REM sleep. We also identified several cells in the dorsal raphe whose pattern of activity was the opposite of that of the presumed serotonergic cells. These cells were maximally active in REM sleep and minimally active in waking and increased activity during cataplexy. The difference between noradrenergic and serotonergic cell discharge profiles in cataplexy suggests different roles for these cell groups in the normal regulation of environmental awareness and muscle tone and in the pathophysiology of narcolepsy. C1 Vet Adm GLAHS Sepulveda, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wu, MF (reprint author), Vet Adm GLAHS Sepulveda, Neurobiol Res 151A3,16111 Plummer St, Sepulveda, CA 91343 USA. EM mfwu@ucla.edu FU NHLBI NIH HHS [HL41370, R01 HL041370, R37 HL041370]; NIMH NIH HHS [MH64109, R01 MH064109]; NINDS NIH HHS [NS14610, R01 NS014610, R37 NS014610] NR 50 TC 61 Z9 62 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2004 VL 554 IS 1 BP 202 EP 215 DI 10.1113/jphysiol.2003.052134 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 770XN UT WOS:000188756800020 PM 14678502 ER PT J AU Tsuang, MT Taylor, L Faraone, SV AF Tsuang, MT Taylor, L Faraone, SV TI An overview of the genetics of psychotic mood disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT Conference on Non Schizophrenic Psychoses CY JAN, 2002 CL Stanford Univ, Stanford, CA HO Stanford Univ DE mood disorder; psychosis; bipolar gene; depression; review ID BIPOLAR AFFECTIVE-DISORDER; SEROTONIN TRANSPORTER GENE; D2 RECEPTOR GENE; EUROPEAN MULTICENTER ASSOCIATION; POSSIBLE SUSCEPTIBILITY LOCUS; UNIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; MAJOR AFFECTIVE-DISORDER; POSTMORTEM BRAIN-TISSUE; CARDIO-FACIAL SYNDROME AB This article presents a conceptual review of the genetic underpinnings of psychotic mood disorders. Both unipolar and bipolar forms of mood disorder sometimes feature psychotic symptoms. Some evidence from epidemiological research suggests that psychotic forms of mood disorder specifically might be heritable. Linkage studies of mood disorders in general have also provided some support for that notion, as have associated studies involving serotonin and dopamine genes and psychotic mood disorder. Some research suggests there might be a genetic connection between schizophrenia and bipolar disorder, undermining the Kraepelinian dichotomous classification of the psychoses. Future research should continue to examine psychotic forms of mood disorder using both epidemiological and molecular approaches. (C) 2003 Published by Elsevier Ltd. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. EM ming_tsuang@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R37MH43518-01, 5 U01 MH46318-02, 1 R01MH41879-01] NR 126 TC 36 Z9 39 U1 4 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN PY 2004 VL 38 IS 1 BP 3 EP 15 DI 10.1016/S0022-3956(03)00096-7 PG 13 WC Psychiatry SC Psychiatry GA 802VJ UT WOS:000220190700002 PM 14690766 ER PT J AU Radulovic, M Spungen, AM Wecht, JM Korsten, MA Schilero, GJ Bauman, WA Lesser, M AF Radulovic, M Spungen, AM Wecht, JM Korsten, MA Schilero, GJ Bauman, WA Lesser, M TI Effects of neostigmine and glycopyrrolate on pulmonary resistance in spinal cord injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE glycopyrrolate; impulse oscillation; neostigmine; spinal cord injury ID AIRWAY HYPERRESPONSIVENESS; ATROPINE; INHALATION; MECHANICS; DISEASE; ASTHMA AB Preliminary findings in subjects with spinal cord injury (SCI) suggest that neostigmine administered intravenously increases colonic tone, increases colonic contractions, and facilitates bowel evacuation. Of concern are potential pulmonary side effects, including an increase in airway secretions and bronchospasm. The objectives of the study were to determine the effects of intravenously administered neostigmine or neostigmine combined with glycopyrrolate on forced oscillation indices in persons with SCI. Pulmonary resistances at 5 Hz (R5) and 20 Hz (R20) were measured with the use of an impulse oscillation system (IOS) in 11 subjects with SCI. Values were obtained before and after the intravenous administration of 2 mg of neostigmine alone and, on a separate day, before and after the administration of 2 mg of neostigmine combined with 0.4 mg of glycopyrrolate. Baseline R5 and R20 values before neostigmine correlated significantly with baseline values before neostigmine combined with glycopyrrolate. Following neostigmine, mean R5 values increased 25% and mean R20 values increased 18%. Following neostigmine combined with glycopyrrolate, mean R5 values fell 9% and mean R20 values fell 7%. In summary, baseline IOS values obtained on 2 different days were highly reproducible in this population. Neostigmine alone induced significant bronchoconstriction, whereas neostigmine combined with glycopyrrolate caused bronchodilation. C1 Bronx Vet Adm Med Ctr, Med Serv, Bronx, NY 10468 USA. Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. RP Lesser, M (reprint author), Bronx Vet Adm Med Ctr, Med Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Drmlesser@aol.com NR 17 TC 4 Z9 4 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2004 VL 41 IS 1 BP 53 EP 57 DI 10.1682/JRRD.2004.01.0053 PG 5 WC Rehabilitation SC Rehabilitation GA 805XM UT WOS:000220399000008 PM 15273897 ER PT J AU Schilero, GJ Grimm, D Spungen, AM Lenner, R Lesser, M AF Schilero, GJ Grimm, D Spungen, AM Lenner, R Lesser, M TI Bronchodilator responses to metaproterenol sulfate among subjects with spinal cord injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE adrenergic beta-agonists; airway resistance; bronchodilator agents; paraplegia; spinal cord diseases; spirometry; tetraplegia; whole-body plethysmography ID HYPERREACTIVITY; OBSTRUCTION; THERAPY; LESIONS AB A previous study using spirometric methods demonstrated that 42% of subjects with tetraplegia experienced significant bronchodilation following inhalation of metaproterenol sulfate (MS). Comparative studies involving subjects with paraplegia were not performed and none has been performed in this population using body plethysmography, a more sensitive method used to assess airway responsiveness. Stable subjects with tetraplegia (n = 5) or paraplegia (n = 5) underwent spirometry and determination of specific airway conductance (sGaw) by body plethysmography at baseline and 30 minutes after nebulization of MS (0.3 mL of a 5% solution). Among subjects with tetraplegia, inhaled MS resulted in significant increases in spirometric indices and sGaw. Among subjects with paraplegia, only sGaw increased significantly, although this increase was considerably less than that seen in subjects with tetraplegia. Our findings indicate that subjects with tetraplegia exhibit greater bronchodilation in response to inhaled MS than do subjects with paraplegia and that sGaw measurements may confer greater sensitivity for assessing bronchodilator responsiveness in tetraplegia. C1 Bronx Dept Vet Affairs Med Ctr, Pulm Crit Care Med Sect, Bronx, NY USA. New York Chiropract Coll, Basic Sci Dept, Seneca Falls, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Schilero, GJ (reprint author), Bronx Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM greg.schilero@med.va.gov NR 20 TC 10 Z9 11 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2004 VL 41 IS 1 BP 59 EP 64 DI 10.1682/JRRD.2004.01.0059 PG 6 WC Rehabilitation SC Rehabilitation GA 805XM UT WOS:000220399000009 PM 15273898 ER PT J AU Korsten, MA Fajardo, NR Rosman, AS Creasey, GH Spungen, AM Bauman, WA AF Korsten, MA Fajardo, NR Rosman, AS Creasey, GH Spungen, AM Bauman, WA TI Difficulty with evacuation after spinal cord injury: Colonic motility during sleep and effects of abdominal wall stimulation SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bowel care; colon; constipation; difficulty with evacuation; motility; neuromuscular stimulation; spinal cord injury ID TRANSIT AB Difficulty with evacuation (DWE) is common in individuals with spinal cord injury (SCI). Numerous studies have concluded that constipation, impaction, and incontinence cause significant morbidity and, collectively, constitute an important quality-of-life issue in individuals with SCI. Colonic motor activity was assessed using a solid-state manometry probe. We report here that colonic pressure activity is depressed during sleep compared to that observed in able-bodied controls. In addition, pressure activity was decreased during sleep compared to pre-sleep and post-sleep. We suspect that this may contribute to delayed colon transit time after SCI. In addition, since contraction of the abdominal wall musculature plays a role in normal defecation, we assessed whether an abdominal belt with implanted electrodes would improve DWE. In this respect, we demonstrated that neuromuscular stimulation of the abdominal wall improves a number of indices of defecatory function, including time to first stool and total bowel care time. C1 Bronx Vet Adm Med Ctr, Dept VA Rehabil Res, Spinal Cord Injury Serv & Med Serv, Bronx, NY 10468 USA. VA Med Ctr, Dev Ctr Excellence, Spinal Cord Injury Serv & Med Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. Mt Sinai Sch Med, Spinal Cord Damage Res Ctr, New York, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. MetroHlth Med Ctr, Cleveland, OH 44109 USA. RP Korsten, MA (reprint author), Bronx Vet Adm Med Ctr, Dept VA Rehabil Res, Spinal Cord Injury Serv & Med Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM mark.korsten@med.va.gov NR 12 TC 10 Z9 12 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN-FEB PY 2004 VL 41 IS 1 BP 95 EP 99 DI 10.1682/JRRD.2004.01.0095 PG 5 WC Rehabilitation SC Rehabilitation GA 805XM UT WOS:000220399000013 PM 15273902 ER PT J AU Cooper, GS Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Taylor, JA AF Cooper, GS Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Taylor, JA TI N-acetyl transferase genotypes in relation to risk of developing systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; N-acetyl transferase metabolism; tobacco; arylamines ID NAT1; POLYMORPHISMS; PHENOTYPE; CYP1A1 AB Objective. To examine the association between N-acetyl transferase (NAT) genotype (NAT1 and NAT2) and risk of developing systemic lupus erythematosus (SLE). Methods. DNA samples were collected from 243 recently diagnosed cases and 298 controls enrolled in a population based case-control study conducted in 60 counties in North Carolina and South Carolina, USA. Results. There was no association between SLE and NAT1 genotype (OR 0.96, 95% CI 0.65, 1.4 for the presence of a *10 allele) or NAT2 genotype (OR 1.1, 95 % CI 0.73, 1.6 for the slow- compared with fast-acetylation genotype). We saw some evidence of interaction between NAT genotypes and use of hair dyes (a source of arylamines), with higher risk seen among hair dye users who had both the *10 NAT1 allele and the NAT2 slow-acetylation genotype (OR 2.9, 95% CI 1.2, 6.9 in this subgroup compared with all others). Conclusion. Our results suggest that although there is little overall association between NAT genotypes and risk of developing SLE, the interaction between NAT1 and NAT2 and specific exposures such as hair dyes may be important. This finding highlights the need to consider exposure when assessing genetic susceptibility. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC 27515 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC 27858 USA. Duke Univ, Med Ctr, Div Rheumatol, Durham, NC 27706 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM cooper1@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 15 TC 8 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2004 VL 31 IS 1 BP 76 EP 80 PG 5 WC Rheumatology SC Rheumatology GA 763GG UT WOS:000188066100015 PM 14705222 ER PT J AU Garrison, A Clifford, K Gleason, SF Tun, CG Brown, R Garshick, E AF Garrison, A Clifford, K Gleason, SF Tun, CG Brown, R Garshick, E TI Alcohol use associated with cervical spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article; Proceedings Paper CT 30th Annual Scientific Meeting of the American-Spinal-Injury-Association CY MAY 14-16, 2004 CL Denver, CO SP Amer Spinal Injury Assoc DE cervical spine; substance abuse; alcohol; traumatic spinal cord injuries ID MOTORCYCLE DRIVERS; EPIDEMIOLOGY AB Objectives: To determine whether alcohol use at time of spinal cord injury (SCI) is more common with cervical injury than with lower levels of spinal injury. Methods: Veterans and nonveterans with SCI were assessed at a Veteran's Affairs Medical Center from 1994 through 2002 and completed a health questionnaire that included information on alcohol use at time of traumatic injury. Results: Of 362 men, 45% had neurologically complete or incomplete cervical injuries. Participants with cervical injury were more likely to have used alcohol when injured (62/162, 38%) compared with participants without cervical injury (45/200, 23%). Adjusting for age at injury and accident type, participants with cervical SCI had an increased relative odds of having used alcohol at injury compared with participants without cervical SCI (2.06, 95% confidence interval = 1.24-3.43). Conclusion: Alcohol use at time of SCI is a risk factor for cervical injury. This finding is of public health concern and should be included in alcohol educational programs. C1 VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. VA Boston Healthcare Syst, Rehabil Med Serv, Boston, MA USA. Massachusetts Gen Hosp, Pulm & Crit Care Med Sect, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM eric.garshick@med.va.gov FU NICHD NIH HHS [R01 HD 42141, R01 HD042141] NR 19 TC 8 Z9 9 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2004 VL 27 IS 2 BP 111 EP 115 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 823HY UT WOS:000221602600006 PM 15162880 ER PT J AU Schilero, GJ Grimm, D Lesser, M AF Schilero, GJ Grimm, D Lesser, M TI Comparison of lung volume measurements in individuals with spinal cord injury by two different methods SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE lung volume measurements; paraplegia; plethysmography; whole body; nitrogen washout; spinal cord injuries; tetraplegia ID THORACIC GAS VOLUME; HEALTHY NONSMOKING ADULTS; MECHANICS; QUADRIPLEGIA; OBSTRUCTION; FREQUENCY AB Background/Objective: Few detailed studies have been performed among subjects with spinal cord injury (SCI) using whole body plethysmography for measurement of static lung volumes. Because abdominal gas volumes and respiratory patterns among subjects with varying levels of SCI may differ significantly from able-bodied individuals, methodological concerns related to this technique could conceivably lead to inaccuracies in lung volume measurements. The purpose of this study was to compare lung volume parameters obtained by whole body plethysmography with those determined by the commonly used nitrogen washout technique among individuals with SCI. Participants: Twenty-nine clinically stable men, 14 with chronic tetraplegia (injury C4-C7) and 15 with paraplegia (injury below T5) participated in the study. Methods: Lung volumes were obtained using whole body plethysmography and the open-circuit nitrogen washout technique. Within both study groups, data were evaluated by the paired Student's t test and by determination of correlation coefficients. Results: No statistically significant differences for any lung volume parameter were found within either group. In subjects with tetraplegia on paraplegia, respectively, strong correlation coefficients were found for measurements of total lung capacity (.86 and .97), functional residual capacity (.87 and .96), and residual volume (.77 and .85). Conclusion: These findings indicate that body plethysmography is a valid technique for determining lung volumes among subjects with SCI. Because airway resistance measurements can also be obtained during same study sessions for assessment of airway caliber and bronchial responsiveness, body plethysmography is a useful tool for examining multiple aspects of pulmonary physiology in this population. C1 Bronx Vet Affairs Med Ctr, Spinal Cord Damage Res Ctr, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Pulm Crit Care Med Sect, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. New York Chiropract Coll, Dept Basic Sci, Seneca Falls, NY USA. RP Schilero, GJ (reprint author), Bronx Vet Affairs Med Ctr, Spinal Cord Damage Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM greg.schilero@med.va.gov NR 26 TC 1 Z9 1 U1 0 U2 1 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2004 VL 27 IS 5 BP 443 EP 447 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 884GJ UT WOS:000226072500005 PM 15648798 ER PT J AU Fitzgerald, SG Cooper, RA Thorman, T Cooper, R Guo, SF Boninger, ML AF Fitzgerald, SG Cooper, RA Thorman, T Cooper, R Guo, SF Boninger, ML TI The GAME(Cycle) exercise system: Comparison with standard ergometry SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE spinal cord injuries; wheelchair; exercise; computer games; cardiovascular fitness; ergometry ID SPINAL-CORD-INJURY; DENSITY-LIPOPROTEIN CHOLESTEROL; WHEELCHAIR ERGOMETRY; PHYSICAL-ACTIVITY; COMPUTER GAMES; HEART-DISEASE; ARM EXERCISE; RISK-FACTORS; VIDEO-GAME; INDIVIDUALS AB Background: It is well established that physical activity is beneficial to health. For the individual in a wheelchair, a regular exercise program might not be available or may be too difficult to participate in physically and/or psychologically. Many exercise devices and regimes are boring. The goal, therefore, is to develop a device that makes exercise more exciting and, thus, motivates a person to exercise more or for a longer period of time, yielding increased energy expenditure. Our laboratory developed an interface between an arm ergometer and a computer game that allows the user to control game play on the screen as if using a joystick. The purpose of this study was to determine (a) whether the GAME(Cycle) system would elicit an exercise effect similar to arm ergometry, (b) whether perceived exertion would be different between the 2 devices, and (c) individuals' impressions regarding the GAME(Cycle) system. Methods: Thirteen individuals who used wheelchairs participated in the study. Participants were asked to exercise for 2 separate, 19-minute sessions. For 1 session, a GAME(Cycle) system was used and for the other session, the same arm ergometer was used, but without the computer game being played. Physiologic data and perceived exertion were collected for each session. Results: There were significant differences between playing the game and not playing the game for VO2 (P = 0.03) and VCO2 (P = 0.02), with higher values being found when the game was played. Perceived exertion was not significantly different between the 2 trials. Conclusion: GAME(Cycle) appears to be similar in nature with respect to energy expenditure to arm ergometry. Because this study was conducted on athletes, further research is needed with sedentary individuals to determine exercise effects and perceived exertion. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Forum Hlth Hillside Rehab Hosp, Warren, OH USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr,Bldg 4,2nd Floor E,151R-1, Pittsburgh, PA 15213 USA. EM sgf9@pitt.edu RI Loureiro, Nuno/I-6400-2012; OI Loureiro, Nuno/0000-0002-1166-3219; Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [1R41HD39535-01] NR 39 TC 16 Z9 16 U1 1 U2 5 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2004 VL 27 IS 5 BP 453 EP 459 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 884GJ UT WOS:000226072500007 PM 15648800 ER PT J AU Cooper, RA Wolf, E Fitzgerald, SG Kellerher, A Ammer, W Boninger, ML Cooper, R AF Cooper, RA Wolf, E Fitzgerald, SG Kellerher, A Ammer, W Boninger, ML Cooper, R TI Evaluation of selected sidewalk pavement surfaces for vibration experienced by users of manual and power wheelchairs SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE wheelchairs; vibration; injury; pavement surfaces ID WHOLE-BODY VIBRATION; LOW-BACK-PAIN; SEAT VIBRATION; SUSPENSION; DRIVERS AB Background: Obstacles such as bumps, curb descents, and uneven driving surfaces cause vibrations that affect the wheelchair, and in turn, the wheelchair user. Chronic exposure can cause low-back pain, disk degeneration, and other harmful effects. Little research has been conducted to assess the vibrations experienced by wheelchair users. Objective: The purpose of this study was to conduct an evaluation of the vibration exposure during electric-powered wheelchair driving and mechanical energy requirements for manual wheelchair propulsion over selected sidewalk surfaces. The goal was to determine the criteria for a wheelchair-pedestrian access route that does not require excessive propulsive work or expose wheelchair users to potentially harmful vibrations. Methods: Ten unimpaired individuals participated in this study. Six sidewalk surfaces were tested. Measured variables included power of the acceleration per octave, mechanical work to propel over surfaces, peak acceleration, and frequency at which peak acceleration occurs. Results: For both the manual and electric-powered wheelchair, at 1 m/s, significant differences were found in peak accelerations between the seat and footrest (P < 0.0001) and between the sidewalk surfaces (P = 0.004). The greatest risk for injury caused by shock and vibration exposure occurs at frequencies near the natural frequency of seated humans (4-15 Hz). The values for work required to propel over the surfaces tested were not statistically significantly different. Besides appearance and construction, the only distinguishing characteristic was surface roughness caused by the joints. Conclusion: When treating the poured concrete sidewalk as the standard, surfaces 2, 3, 5, and 6 compared most favorably in terms of vibration exposure, whereas surface 4 produced mixed results. Surfaces 2, 3, 5, and 6 yielded results that were similar to the poured concrete sidewalk and could be considered acceptable for wheelchair users. In conclusion, surfaces other than the traditional poured concrete can be used for pedestrian access routes without adding vibration exposure or reducing propulsion efficiency. C1 VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Cooper, R (reprint author), VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, 151-R1,71080 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper+9@pitt.edu NR 26 TC 12 Z9 12 U1 0 U2 3 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2004 VL 27 IS 5 BP 468 EP 475 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 884GJ UT WOS:000226072500009 PM 15648802 ER PT J AU Tolbert, G Tuck, ML AF Tolbert, G Tuck, ML TI Ambulatory blood pressure monitoring in persons with chronic spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE blood pressure; sympathetic nervous activities; spinal cord injuries; ambulatory blood pressure measurements ID AUTONOMIC HYPERREFLEXIA; ORTHOSTATIC HYPOTENSION; HYPERTENSION; VARIABILITY; DYSREFLEXIA; MANAGEMENT AB Background: Hypertension alone or in the presence of autonomic dysreflexia (AD) may be underdiagnosed and consequently mismanaged in people with chronic spinal cord injury (SCI). Blood pressure (BP) derangements caused by AD are characterized by labile BP, in addition to episodic hypertension. Consequently, random BP readings often prove insufficient, which makes traditional outpatient evaluation and management suboptimal. Because elevated BP is common to essential hypertension (EH) and AD, distinction between the 2 entities proves challenging. The distinction is imperative because the treatments differ. Conventional BP monitoring in the office may miss labile BP patterns and episodic BP elevations. Ambulatory BP monitoring (ABPM) is used in the general population to improve the diagnosis and management of hypertension. ABPM provides the average BP level, circadian rhythm, and short-term BP variability. There is a paucity of ABPM studies in persons with SCI. Objective: To explore the role of ABPM in individuals with SCI. Methods: This study is a case description and detailed analysis of the use of ambulatory blood pressure monitoring (ABPM) in 3 persons with chronic SCI. Results: Three cases were identified in which the diagnosis of autonomic dysreflexia, exaggerated blood pressure variability and disruption of circadian blood pressure pattern was delayed using conventional blood pressure evaluation. ABPM aided in diagnosis by providing the average blood pressure level, circadian rhythm and short-term BP variability. Conclusion: Because conventional office BP monitoring may miss labile BP patterns and episodic BP elevations, it is limited in the SCI population. ABPM may improve the outpatient management of blood pressure abnormalities in individuals with chronic SCI by clarifying mechanisms and patterns of BP in this patient population. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Tolbert, G (reprint author), Ctr Rehabil & Wellness, 17609 Ventura Blvd,114, Encino, CA 91316 USA. EM gtolbert1@yahoo.com NR 21 TC 3 Z9 5 U1 0 U2 2 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PY 2004 VL 27 IS 5 BP 476 EP 480 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 884GJ UT WOS:000226072500010 PM 15648803 ER PT J AU Peng, L Zhou, XH AF Peng, L Zhou, XH TI Local linear smoothing of receiver operating characteristic (ROC) curves SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE empirical distribution; empirical quantile; ROC curve; smoothing ID STATISTICS AB For measuring the accuracy of a continuous diagnostic test, the receiver operating characteristic (ROC) curve is often used. The empirical ROC curve is the most commonly used non-parametric estimator for the ROC curve. Recently, Lloyd (J. Amer. Statist. Assoc. 93(1998) 1356) proposed a kernel smoothing estimator for the ROC curve and showed his estimator has better mean square error than the empirical ROC curve estimator. However, Lloyd's estimator involves two bandwidths and has a boundary problem. In addition, his choice of bandwidths is ad hoc. In this paper. we propose another kernel smoothing estimator which involves only one bandwidth and does not have the boundary problem. Furthermore, our choice of the bandwidth is asymptotically optimal. (C) 2002 Elsevier B.V.. All rights reserved. C1 Georgia Inst Technol, Sch Math, Atlanta, GA 30332 USA. Indiana Univ, Sch Med, Div Biostat, Indianapolis, IN 46202 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. RP Peng, L (reprint author), Georgia Inst Technol, Sch Math, Atlanta, GA 30332 USA. NR 12 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN 1 PY 2004 VL 118 IS 1-2 BP 129 EP 143 AR PII S0378-3758(02)00394-4 DI 10.1016/S0378-3758(02)00394-4 PG 15 WC Statistics & Probability SC Mathematics GA 739ZM UT WOS:000186376500009 ER PT J AU Regimbeau, JM Abdalla, EK Vauthey, JN Lauwers, GY Durand, FO Nagorney, DM Ikai, I Yamaoka, Y Belghiti, J AF Regimbeau, JM Abdalla, EK Vauthey, JN Lauwers, GY Durand, FO Nagorney, DM Ikai, I Yamaoka, Y Belghiti, J TI Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: Results of a multicenter study SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE hepatocellular carcinoma; liver resection; Child-Pugh class; hepatitis; fibrosis; cirrhosis ID CELL NUCLEAR ANTIGEN; LONG-TERM-SURVIVAL; HEPATIC RESECTION; INTRAHEPATIC RECURRENCE; MULTIVARIATE ANALYSES; CIRRHOTIC-PATIENTS; RANDOMIZED-TRIAL; HEPATECTOMY; PROGNOSIS; MARGIN AB Background and Objectives: Recurrence after partial liver resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. To identify risk factors for early death from recurrence after liver resection for HCC. Methods: All 547 patients in this study had greater than 1 year of follow-up after complete resection of HCC (1980-1999) at one of the four hepatobiliary centers in Japan, France, and the United States. Patients who died of recurrence less than or equal to1 year post-resection and all of those alive at least 1 year were compared. Survival and clinicopathological factors associated with death from recurrence within 1 year of resection were analyzed. Results: Overall postoperative mortality rate was 5%. In the first postoperative year, 123 (22%) patients died. Of these, 53 (43%) died of recurrence, 30 (24%) of postoperative complications, and 40 (33%) of liver failure/hemorrhage. On multivariate analysis, tumor size greater than 5 cm (P < 0.02; odds ratio, 3.0), multiple tumors (P < 0.01; odds ratio, 3.3), and greater than 5 mitoses per 10 high-power fields (P < 0.03; odds ratio, 3) were associated with increased risk of early death due to recurrence. Conclusions: These findings enable identification of patients with HCC who are at high risk for early death due to recurrence following potentially curative resection who might be candidates for adjuvant therapy trials. (C) 2003 Wiley-Liss, Inc. C1 Hop Beaujon, Paris, France. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Belghiti, J (reprint author), Hop Beaujon, Serv Chirurg, 100 Blvd Gen Leclerc, F-92118 Clichy, France. EM j.bel@bjn.ap-hop-paris.fr NR 40 TC 87 Z9 93 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JAN PY 2004 VL 85 IS 1 BP 36 EP 41 DI 10.1002/jso.10284 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 760DQ UT WOS:000187796700006 PM 14696085 ER PT J AU Bonheur, JA Albadawi, H Patton, GM Watkins, MT AF Bonheur, JA Albadawi, H Patton, GM Watkins, MT TI A noninvasive murine model of hind limb ischemia-reperfusion injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE ischemia; reperfusion; laser Doppler imager; myeloperoxidase; controlled tension tourniquet ID LOWER-TORSO ISCHEMIA; TUMOR-NECROSIS-FACTOR; SKELETAL-MUSCLE; GENE-TRANSFER; GROWTH-FACTOR; SELECTIN; ANGIOGENESIS; PROTEIN; HR AB Background. This study describes a novel murine method of the Controlled Tension Tourniquet (CTT). The CTT applies a measured circumferential tension to hind limbs using a tourniquet attached to digital strain gauges, and is useful for investigating hind limb ischemia reperfusion (IR). Materials and methods. Mice were subjected to 1, 3, or 6 h of unilateral hind limb ischemia followed by either 4 or 24 h of reperfusion. Blood flow in the ischemic, reperfused, and contralateral limbs was monitored using a Laser Doppler Imager. Edema in the IR limbs was documented by changes in the wet weight to dry weight ratio. Myeloperoxidase and tetrazolium based mitochondrial activity assays indicated neutrophil infiltration and tissue viability, respectively. Results. During reperfusion following 1, 4, or 6 h, flow stabilized at 100%, 53%, and 23% of baseline levels, respectively. Edema was present all in IR limbs after 4 h of reperfusion, but increased with the duration of ischemia. After 24 h of reperfusion neutrophil infiltration was equivalent in all IR limbs after all intervals of ischemia. After 24 h of reperfusion, tissue viability after 1 h of ischemia was equivalent to sham or contralateral limbs. At 3 or 6 h of ischemia and 24 h reperfusion decreased tissue viability to 40% of sham and contralateral limbs. Conclusions. The CTT provides a reproducible, non-invasive model of acute limb ischemia, which reflects the biochemical indices of microvascular injury, inflammation and flow characteristic of reperfusion injury. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. VA Boston Healthcare Syst, Dept Surg, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Watkins, MT (reprint author), Div Vasc Surg, Dept Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 28 TC 36 Z9 41 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2004 VL 116 IS 1 BP 55 EP 63 DI 10.1016/S0022-4804(03)00232-4 PG 9 WC Surgery SC Surgery GA 766GV UT WOS:000188368900008 PM 14732349 ER PT J AU Baer, CA Williams, CM Vickers, L Kvedar, JC AF Baer, CA Williams, CM Vickers, L Kvedar, JC TI A pilot study of specialized nursing care for home health patients SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article AB We conducted a pilot study to assess the feasibility of remote (Web-based) consultations for leg wounds. The wounds were photographed by a home care nurse using a digital camera and the images were transmitted to a server from the nurses' office, together with patient details. The home care nurse graded the wounds and suggested a treatment plan. Subsequently, a specialist wound-care nurse also graded them and suggested a treatment plan, using the data stored on the Web server. Thirty-four patients were studied. The Web system proved simple to use and staff responses were positive. The agreement between the home care nurses and the specialist nurse in assessing wounds was good (kappa coefficients 0.41 to 0.71). Agreement over the treatment of wounds was more variable (kappa coefficients -0.75 to 0.81). The results of the pilot study are encouraging and suggest that Web-based communication can improve the quality of care for patients with leg wounds and reduce costs. C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners Healthcare Inc, Ctr Telemed, Boston, MA USA. Partners Healthcare Inc, Partners Home Care, Boston, MA USA. RP Kvedar, JC (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, 2 Longfellow Pl,Suite 216, Boston, MA 02114 USA. EM jkvedar@partners.org NR 15 TC 6 Z9 7 U1 1 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2004 VL 10 IS 6 BP 342 EP 345 DI 10.1258/1357633042602099 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 880JQ UT WOS:000225786500006 PM 15603632 ER PT J AU Goldschmidt, L Goodrich, GL AF Goldschmidt, L Goodrich, GL TI Development and evaluation of a point-of-care interactive patient education kiosk SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article; Proceedings Paper CT 4th International Conference on Successes and Failurew in Telehealth CY JUL 22-23, 2004 CL Brisbane, AUSTRALIA ID COMPLICATIONS; INFORMATION; RISK AB We have developed an interactive patient education kiosk. The kiosk provides access to stored health information and to selected Websites via a high-speed Internet connection. The output is bilingual (English or Spanish) and an enclosed printer allows information to be printed and taken home for later reading. Each kiosk records patient usage, as well as the results of a brief, voluntary, online evaluation questionnaire. Three kiosks were placed in the patient waiting area of busy multi-specialty clinics. Two kiosks were active for 2.5 years and one was active for 1.5 years. There were 38,868 user sessions recorded and 2878 users participated in the online survey questionnaire (7% of all user sessions). Patient satisfaction was high; for example, 68% of respondents found some or all of the information they were looking for on the kiosk. In the year following the introduction of the first kiosk (the 2001/02 flu season), there was a 24% increase in the number of patients receiving flu vaccinations within the Palo Alto health-care system, compared with the previous year. Experience to date suggests that the kiosks may increase patient compliance with selected clinical guidelines and instructions. C1 VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. US Dept Vet Affairs, Psychol Serv, Palo Alto, CA USA. RP Goldschmidt, L (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM Leonard.Goldschmidt2@med.va.gov NR 11 TC 2 Z9 2 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2004 VL 10 SU 1 BP S30 EP S32 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 882NW UT WOS:000225946600010 ER PT J AU Rauch, PK Muriel, AC AF Rauch, PK Muriel, AC TI The Yale child study guide to understanding your child. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat, Cambridge, MA 02138 USA. RP Rauch, PK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2004 VL 43 IS 1 BP 114 EP 115 DI 10.1097/01.chi.0000096623.64367.61 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 759EB UT WOS:000187724400022 ER PT J AU Middelkamp-Hup, MA Pathak, MA Parrado, C Garcia-Caballero, T Rius-Diaz, F Fitzpatrick, TB Gonzalez, S AF Middelkamp-Hup, MA Pathak, MA Parrado, C Garcia-Caballero, T Rius-Diaz, F Fitzpatrick, TB Gonzalez, S TI Orally ministered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 20th World Congress of Dermatology CY JUL 03-05, 2002 CL PARIS, FRANCE ID CUTANEOUS MALIGNANT-MELANOMA; B-INDUCED APOPTOSIS; LANGERHANS CELLS; METHOXSALEN PHOTOCHEMOTHERAPY; ULTRAVIOLET-RADIATION; PUVA TREATMENT; LIPID-PEROXIDATION; MYCOSIS-FUNGOIDES; FINNISH PATIENTS; FOLLOW-UP AB Background. The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. Objective. We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level. Methods: A total of 10 healthy patients with skin phototypes II to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to PUVA with 7.5 mg/kg of oral PL. Results. Clinically, phototoxicity was always lower in PL-treated skin after 48 to 72 hours (P < .005), and pigmentation was also reduced 4 months later. Histologically, PL-treated skin showed a significant numeric reduction of sunburn cells (P = .05), preservation of Langerhans cells (P less than or equal to .01), decrease of tryptase-positive mast cell infiltration (P < .05), and decrease of vasodilation (P < .01). No differences were found in Ki-67(+) proliferating cells. Conclusions. PL is an effective chemophotoprotector against PUVA-induced skin phototoxicity and leads to substantial benefits of skin protection against damaging effects of PUVA as evidenced by histology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Malaga, Fac Med, Dept Morphol Sci, E-29071 Malaga, Spain. Univ Santiago de Compostela, Fac Med, Dept Morphol Sci, Santiago De Compostela, Spain. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, BHX 630, Boston, MA 02114 USA. EM sgonzalez3@partners.org RI Parrado, Concepcion/K-9270-2014; Garcia-Caballero, Tomas/H-7213-2015 OI Parrado, Concepcion/0000-0002-7627-4310; NR 61 TC 54 Z9 56 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2004 VL 50 IS 1 BP 41 EP 49 DI 10.1016/S0190-9622(03)02732-4 PG 9 WC Dermatology SC Dermatology GA 763MC UT WOS:000188088900007 PM 14699363 ER PT J AU Kohn, WG Harte, JA Malvitz, DM Cleveland, JL Eklund, KJ AF Kohn, WG Harte, JA Malvitz, DM Cleveland, JL Eklund, KJ TI Guidelines for infection control in dental health care settings-2003 SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS AB Background. The Centers for Disease Control and Prevention, or CDC, is the lead federal agency for disease prevention in the United States. It has been 10 years since CDC infection control guidelines for dental health care settings were last published. During those 10 years, new technologies and issues have emerged, and other CDC infection control guidelines for health care settings have been updated. Results. In light of these developments, CDC collaborated with experts in infection control to revise its infection control recommendations for dental health care settings. Existing guidelines and published research pertinent to dental infection control principles and practices were reviewed. This article provides background information, describes the process used to create these guidelines, and lists the new recommendations. Clinical Implications. CDC believes that dental offices that follow these new recommendations will strengthen an already admirable record of safe dental practice. Patients and providers alike can be assured that oral health care can be delivered and received in a safe manner. C1 Ctr Dis Control & Prevent, Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. USAF, Dent Invest Serv, Great Lakes, IL USA. Forsyth Inst, Boston, MA USA. RP Kohn, WG (reprint author), Ctr Dis Control & Prevent, Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway,MS F-10, Atlanta, GA 30341 USA. EM wak8@cdc.gov NR 10 TC 46 Z9 47 U1 1 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2004 VL 135 IS 1 BP 33 EP 45 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 767WH UT WOS:000188496500014 PM 14959873 ER PT J AU Hazzard, WR AF Hazzard, WR TI I am a geriatrician SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Hazzard, WR (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2004 VL 52 IS 1 BP 161 EP 161 DI 10.1111/j.1532-5415.2004.52041.x PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 756DR UT WOS:000187451000028 PM 14687334 ER PT J AU Hardy, DJ Castellon, SA Hinkin, CH AF Hardy, DJ Castellon, SA Hinkin, CH TI Perceptual span deficits in adults with HIV SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article; Proceedings Paper CT 81st Annual Convention of the Western-Psychological-Association CY MAY, 2001 CL MAUI, HAWAII SP W Psycholog Assoc DE perceptual span; HIV infection; attention ID DEMENTIA COMPLEX; PERFORMANCE; INFECTION; TIME; SCHIZOPHRENICS; TASK AB Studies have found that infection with the Human Immunodeficiency Virus (HIV) leads to cognitive dysfunction. In fact, attention problems have been reported to be the most frequent cognitive symptom in HIV-infected adults. One question is how early in the course of information processing can attention impairment be detected? To address this issue, performance on a perceptual span task was examined in 54 HIV-infected adults and 19 seronegative controls. In this task a target had to be identified in a briefly presented (50 Pus) array of 1, 4, or 12 letter-characters. Response accuracy was differentially worse in the HIV+ group relative to seronegative controls in the most difficult condition, the 12-item array, but not in the easier conditions. There was no evidence of a group difference in response strategy due to disinhibition or in psychomotor speed. These data suggest that HIV infection leads to a reduction in early visual processing capacity (or span of apprehension). The present results illustrate a new type of attentional deficit in HIV and show the impact of HIV on cognition at an earlier point in information processing than has been previously reported. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hardy, DJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. FU NIA NIH HHS [R03 AG-18549]; NIMH NIH HHS [R01 MH058552, R01 MH-58552] NR 29 TC 6 Z9 7 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 2004 VL 10 IS 1 BP 135 EP 140 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 758ZQ UT WOS:000187713000014 PM 14751015 ER PT J AU Webber, AP Benjamin, C AF Webber, AP Benjamin, C TI Wandering hemiparesis SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Article ID HYPOGLYCEMIA C1 Univ Calif Los Angeles, Sch Med, Sepulveda, LA USA. GRECC, VA Greater Los Angeles, Sepulveda, LA USA. RP Webber, AP (reprint author), 10982 Roebling Ave,Unit 341, Los Angeles, CA 90024 USA. EM drawebber@hotmail.com NR 6 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD JAN PY 2004 VL 97 IS 1 BP 26 EP 27 DI 10.1258/jrsm.97.1.26 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 767DW UT WOS:000188425800009 PM 14702361 ER PT J AU Ashiku, SK Kuzucu, A Grillo, HC Wright, CD Wain, JC Lo, B Mathisen, DJ AF Ashiku, SK Kuzucu, A Grillo, HC Wright, CD Wain, JC Lo, B Mathisen, DJ TI Idiopathic laryngotracheal stenosis: Effective definitive treatment with laryngotracheal resection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 05-09, 2002 CL WASHINGTON, D.C. SP Amer Assoc Thorac Surg ID SUBGLOTTIC STENOSIS; GASTROESOPHAGEAL REFLUX; WEGENERS-GRANULOMATOSIS; MANAGEMENT; AUTOANTIBODIES; RECONSTRUCTION; ANASTOMOSIS; DIAGNOSIS; LARYNGEAL AB Objective: Little was known about idiopathic laryngotracheal stenosis when it was first described. We have operated on 73 patients with idiopathic laryngotracheal stenosis, have confirmed its mode of presentation and response to surgical therapy, and have established long-term follow-up. Methods: Charts of 73 patients treated surgically for idiopathic laryngotracheal stenosis. between 1971 and 2002 were retrospectively reviewed. Results: All patients were treated with a single-staged laryngotracheal resection, with (36/73) and without (37/73) a posterior membranous tracheal wall flap. Nearly all were women (71/73), with a mean age of 46 years (range, 13-74 years). Twenty-eight (38%) of 73 had undergone a previous procedure with laser, dilation, tracheostomy, T-tube, or laryngotracheal operations. After laryngotracheal resection, the majority of patients (67/73) were extubated in the operating room, and 7 required temporary tracheostomies, only I of whom was among the last 30 patients. All were successfully decannulated. There was no perioperative mortality. Principal morbidity was alteration of voice quality, which was mild and tended to improve with time. Sixty-seven (91%) of 73 patients had good to excellent long-term results with voice and breathing quality and do not require further intervention for their idiopathic laryngotracheal stenosis. Conclusion: Idiopathic laryngotracheal stenosis is an entity that occurs almost exclusively in women and is without a known cause. It is not a progressive process, but the timing of the operation is crucial. Single-staged laryngotracheal resection is successful in restoring the airway while preserving voice quality in more than 90% of patients. Protective tracheostomy is now rarely required (1/30). Long-term follow-up shows a stable airway and improvement in voice quality. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02214 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02214 USA. NR 15 TC 45 Z9 51 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2004 VL 127 IS 1 BP 99 EP 107 DI 10.1016/j.jtcvs.2002.11.001 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 770EG UT WOS:000188709800017 PM 14752419 ER PT J AU Maher, MM Kalra, MK Toth, TL Wittram, C Saini, S Shepard, J AF Maher, MM Kalra, MK Toth, TL Wittram, C Saini, S Shepard, J TI Application of rational practice and technical advances for optimizing radiation dose for chest CT SO JOURNAL OF THORACIC IMAGING LA English DT Article DE CT; radiation; chest; risks ID HIGH-RESOLUTION CT; COMPUTED-TOMOGRAPHY; TUBE CURRENT; SPIRAL CT; PULMONARY NODULES; IMAGE QUALITY; HELICAL CT; REDUCTION; MRI; MULTISLICE AB Though clinical benefits of CT exceed the adverse effects of radiation, the increasing use of CT has raised a compelling case for reducing radiation exposure. This controversy has been compounded by the sheer magnitude of CT examinations being performed annually, alleged overuse; and inappropriate selection of optimum scanning parameters, all of which expose the patient population to increased radiation exposure. Recommended clinical strategies for radiation dose optimization include optimization of scanning parameters and creating awareness and adopting guidelines for legitimate indications for CT scanning to avoid overuse and hence, the associated over-exposure. Whereas technological advances have increased the applications of the modality, it is also assisting in development of promising techniques to reduce associated radiation exposure, while maintaining "optimum image quality" needed to make a confident diagnosis. The present pictorial essay describes the fundamentals of CT radiation exposure and need for CT radiation dose reduction on the basis of documented scanning practices and technological advances. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Gen Elect Med Syst, Waukesha, WI USA. RP Maher, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Founders House,55 Fruit St, Boston, MA 02114 USA. EM mmaher@partners.org NR 36 TC 30 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JAN PY 2004 VL 19 IS 1 BP 16 EP 23 DI 10.1097/00005382-200401000-00003 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 765BU UT WOS:000188247900003 PM 14712126 ER PT J AU Resendiz, JC Feng, S Ji, G Kroll, MH AF Resendiz, JC Feng, S Ji, G Kroll, MH TI von Willebrand factor binding to platelet glycoprotein Ib-IX-V stimulates the assembly of an alpha-actinin-based signaling complex SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE actinin; polyphosphoinositides; shear stress; von Willebrand factor ID PATHOLOGICAL SHEAR-STRESS; PHOSPHOINOSITIDE 3-KINASE; INTEGRIN ALPHA(IIB)BETA(3); ACTIVATION; AGGREGATION; LOCALIZATION; CYTOSKELETON; 14-3-3-ZETA; ADHESION; GELSOLIN AB Background: Pathological shear stress induces platelet aggregation that is dependent on von Willebrand factor (VWF) binding to glycoprotein (Gp)Ib-IX-V and phosphatidylinositol 3-kinase activation. We tested the hypothesis that pathological shear stress stimulates phosphatidylinositol 3,4,5-trisphosphate (PIP3) synthesis by directing the assembly of a molecular signaling complex that includes class IA phosphatidylinositol 3-kinase (PI 3-KIA). Methods: Platelets were subjected to 120 dynes cm(-2) shear stress in a cone-plate viscometer. Resting and sheared platelets were lyzed, immunoprecipitations of PI 3-KIA performed, or lipids extracted for PIP3 measurements. alpha-Actinin was incubated with phosphatidylinositol 4,5-bisphosphate (PIP2), immunoprecipitated, and used as a substrate for in vitro PI 3-KIA activity. Results: Pathological shear stress induces biphasic PIP3 production. In resting platelets, PI 3-KIA associates with alpha-actinin and PIP2. After exposure to shear stress, alpha-actinin and PIP2 rapidly disassociate from PI 3-KIA. PI 3-KIA then gradually reassociates with PIP2 and alpha-actinin, and this complex becomes linked to GpIbalpha through the cytoskeleton. PIP3 production and the observed changes in the association between alpha-actinin, PIP2, and PI 3-KIA are inhibited when VWF binding to GpIbalpha is blocked. In a cell-free system, alpha-actinin binds PIP2 and when the alpha-actinin-PIP2 complex is added to platelet PI 3-KIA, PIP3 production is stimulated. Conclusions: These results suggest that pathological shear-induced VWF binding to GpIb-IX-V stimulates PIP3 production through the assembly of an alpha-actinin-based complex that colocalizes PI 3-KIA with substrate PIP2. C1 Wihuri Res Inst, SF-00140 Helsinki, Finland. Rice Univ, Baylor Coll Med, VA Med Ctr, Houston, TX 77251 USA. RP Resendiz, JC (reprint author), Wihuri Res Inst, Kalliolinnantie 4, SF-00140 Helsinki, Finland. EM julio.resendiz@wri.fi NR 33 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2004 VL 2 IS 1 BP 161 EP 169 DI 10.1111/j.1538-7836.2003.00497.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 767VT UT WOS:000188495100025 PM 14717980 ER PT J AU Zietman, AL Chung, CS Coen, JJ Shipley, WU AF Zietman, AL Chung, CS Coen, JJ Shipley, WU TI 10-year outcome for men with localized prostate cancer treated with external radiation therapy: Results of a cohort study SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; radiotherapy; outcome assessment (healthcare) ID DOSE-ESCALATION; FOLLOW-UP; RADIOTHERAPY; IRRADIATION; DISEASE AB Purpose: We determine the efficacy of conventional dose, external beam radiation for localized prostate cancer using cohort analysis with maximized followup. Materials and Methods: A total of 205 men with T1-2 prostate cancer were treated with conventional external beam radiation to a median and modal dose of 68.4 Gy during a 16-month period from 1991 to 1993. Followup was maximized in these patients, and median followup for those alive with or without disease was 114 months. Results: Median patient age at treatment was 72 years, and overall survival at 5 and 10 years was 78% and 53%, respectively. The actuarial risk of local failure was 18% at 10 years as was the risk of metastatic disease. The actuarial risk of being free of biochemical failure at 10 years (American Society for Therapeutic Radiology and Oncology definition) was 49%. That risk was 42% if the definition was used without backdating failure to a time between last low value and first increase. When a crude analysis of 10-year outcome was performed 127 of the 205 treated patients (62%) were still alive, including 59% with no evidence of biochemical failure and a median prostate specific antigen of 1.0 ng/ml. Of the 78 men (38% of total) who died during the 10 years 32 died either of or with recurrent cancer. Conclusions: Mature followup minimizes many of the biases seen in previously published radiation series. This study provides a yardstick against which newer radiation modalities may be measured. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM azietman@partners.org NR 17 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JAN PY 2004 VL 171 IS 1 BP 210 EP 214 DI 10.1097/01.ju.0000100980.13364.a6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 755EM UT WOS:000187390800048 PM 14665878 ER PT J AU McGibbon, CA Krebs, DE Wolf, SL Wayne, PM Scarborough, DM Parker, SW AF McGibbon, CA Krebs, DE Wolf, SL Wayne, PM Scarborough, DM Parker, SW TI Tai Chi and vestibular rehabilitation effects on gaze and whole-body stability SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibulopathy; gaze stability; whole body stability; Tai Chi; vestibular rehabilitation ID TRAJECTORY ANALYSIS; REDUCING FRAILTY; CONTROLLED-TRIAL; OLDER PERSONS; BALANCE; CHUAN; ADULTS; FALLS; EXERCISE; POSTURE AB Tai Chi (TC) is a comparatively new intervention for peripheral vestibular hypofunction, which is often treated with vestibular rehabilitation (VR). We compared gaze stability (GZS), whole-body stability (WBS) and footfall stability (FFS) during locomotion among 26 people with vestibulopathy (VSP), randomized into two treatment arms (13 TC and 13 VR). Each intervention program was offered for 10 weeks. GZS improved more for VR than for TC, but WBS (and FFS) improved more for TC than for VR. There was a significant relationship between changes in GZS and WBS for the VR subjects (r = 0.60, p = 0.01), but not for TC subjects. There was a significant relationship between changes in WBS and FFS for both VR (r = 0.65, p < 0.01) and TC (r = 0.58, p = 0.02) groups; the relationship disappeared in the VR but not the TC group when controlling for GZS. These findings suggest that VR and TC both benefit patients with VSP but via differing mechanisms. Moreover, these data are the first to test the assumption that improving gaze control among patients with VSP perforce improves postural stability: it does not. We conclude that GZS is most improved in those who receive VR, but that TC improves WBS and FFS without improving GZS, suggesting patients with VSP can rely on non-gaze related, mechanisms to improve postural control. C1 Univ New Brunswick, Inst Biomed Engn, Fredericton, NB E3B 5A3, Canada. Univ New Brunswick, Fac Kinesiol, Fredericton, NB E3B 5A3, Canada. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. New England Sch Acupuncture, Watertown, MA 02472 USA. Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA. RP McGibbon, CA (reprint author), Univ New Brunswick, Inst Biomed Engn, 25 Dineen Dr, Fredericton, NB E3B 5A3, Canada. EM cmcgibb@unb.ca RI Wolf, Steven/F-6588-2010 OI Wolf, Steven/0000-0002-9446-8995 FU NCCIH NIH HHS [R21 AT00553-01] NR 59 TC 32 Z9 33 U1 2 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PY 2004 VL 14 IS 6 BP 467 EP 478 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 903ZK UT WOS:000227464100005 PM 15735329 ER PT J AU Quinn, G Wood, J Suling, K Arn, S Sachs, DH Schuurman, HJ Patience, C AF Quinn, G Wood, J Suling, K Arn, S Sachs, DH Schuurman, HJ Patience, C TI Genotyping of porcine endogenous retroviruses from a family of miniature swine SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE LEUKEMIA-VIRUS; LONG TERMINAL REPEATS; HUMAN-CELLS; NO EVIDENCE; NUCLEOTIDE-SEQUENCE; INFECTION; PIG; TRANSMISSION; IDENTIFICATION; GENOMES AB The identification of animals in an inbred miniature swine herd that consistently fail to produce replication-competent humantropic porcine endogenous retrovirus (PERV) has prompted studies on the biology of PERV in transmitter and nontransmitter animals. We analyzed PERV RNA transcript profiles in a family of inbred miniature swine (SLA(d/d) haplotype) in which individual members differed in their capacity to generate humantropic and ecotropic (i.e., pigtropic) virus. We identified unique HaeIII and HpaII gag restriction fragment length polymorphism (RFLP) profiles resulting from single nucleotide polymorphisms in blood cells; these were found only in animals that produced humantropic PERV. These HaeIII and HpaII gag RFLP profiles proved to be components of humantropic PERV as they were transmitted to 293 human target cells in vitro. The humantropic HaeIII and HpaII gag RFLP genotypes in the family of study were not present in other miniature swine in the herd that produced humantropic PERV, indicating that these RFLP profiles relate specifically to this family's lineage. C1 Immerge BioTherapeut Inc, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. RP Quinn, G (reprint author), Immerge BioTherapeut Inc, 300 Technol Sq, Cambridge, MA 02139 USA. NR 27 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 1 BP 314 EP 319 DI 10.1128/JVI.78.1.314-319.2004 PG 6 WC Virology SC Virology GA 756DZ UT WOS:000187451700032 PM 14671113 ER PT J AU Rosendorff, A Illanes, D David, G Lin, J Kieff, E Johannsen, E AF Rosendorff, A Illanes, D David, G Lin, J Kieff, E Johannsen, E TI EBNA3C coactivation with EBNA2 requires a SUMO homology domain SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; NUCLEAR ANTIGEN 3C; ACUTE PROMYELOCYTIC LEUKEMIA; UBIQUITIN-ACTIVATING ENZYME; LATENT MEMBRANE-PROTEIN; BINDING-PROTEIN; J-KAPPA; CONJUGATING ENZYME; TRANSCRIPTIONAL ACTIVATION; SUBNUCLEAR LOCALIZATION AB Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is critical for EBV immortalization of infected B lymphocytes and can coactivate the EBV LMP1 promoter with EBNA2. EBNA3C amino acids 365 to 545 are necessary and sufficient for coactivation and are required for SUMO-1 and SUMO-3 interaction. We found that EBNA3C but not EBNA3CDelta343-545 colocalized with SUMO-1 in nuclear bodies and was modified by SUMO-2, SUMO-3, and SUMO-1. EBNA3C amino acids 545 to 628 and amino acids 30 to 365 were also required for EBNA3C sumolation and nuclear body localization but were dispensable for coactivation, indicating that EBNA3C sumolation is not required for coactivation. Furthermore, EBNA3C amino acids 476 to 992 potently coactivated with EBNA2 but EBNA3C amino acids 516 to 922 lacked activity, indicating that amino acids 476 to 515 are critical for coactivation. EBNA3C amino acids 476 to 515 include DDDVIEV507-513, which are similar to SUMO-1 EEDVIEV84-90. EBNA3C m1 and m2 point mutations, DDD507-509 mutated to AAA and DVIEVID509-513 mutated to AVIAVIA, respectively, diminished SUMO-1 and SUMO-3 interaction in directed yeast two-hybrid and glutathione S-transferase pulldown assays. Furthermore, EBNA3C m1 and m2 did not coactivate the LMP1 promoter with EBNA2. Overexpression of wild-type SUMO-1, SUMO-3, and the SUMO-conjugating enzyme UBC9 coactivated the LMP1 promoter with EBNA2. Since EBNA2 activation is dependent on p300/CBP, the possible effect of EBNA3C on p300-mediated transcription was assayed. EBNA3C potentiated transcription of p300 fused to a heterologous DNA binding domain, whereas EBNA3C m1 and m2 did not. All of these data are consistent with a model in which EBNA3C upregulates EBNA2-mediated gene activation by binding to a sumolated repressor and inhibiting repressive effects on p300/CBP and other transcription factor(s) at EBNA2-regulated promoters. C1 Brigham & Womens Hosp, Virol Program, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Microbiol, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Mol Genet, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kieff, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA47006, R01 CA047006, R35 CA047006]; NIAID NIH HHS [1K-08 AI49943-02] NR 58 TC 41 Z9 43 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 1 BP 367 EP 377 DI 10.1128/JVI.78.1.367-377.2004 PG 11 WC Virology SC Virology GA 756DZ UT WOS:000187451700037 PM 14671118 ER PT J AU Draenert, R Verrill, CL Tang, Y Allen, TM Wurcel, AG Boczanowski, M Lechner, A Kim, AY Suscovich, T Brown, NV Addo, MM Walker, BD AF Draenert, R Verrill, CL Tang, Y Allen, TM Wurcel, AG Boczanowski, M Lechner, A Kim, AY Suscovich, T Brown, NV Addo, MM Walker, BD TI Persistent recognition of autologous virus by high-avidity CD8 T cells in chronic, progressive human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; CYTOTOXIC LYMPHOCYTES-T; CHRONIC HIV-INFECTION; VIRAL LOAD; DNA VACCINATION; ESCAPE VARIANTS; RHESUS-MONKEYS; CTL RESPONSES; ANTIVIRAL CD8; NEF PROTEIN AB CD8 T-cell responses are thought to be crucial for control of viremia in human immunodeficiency virus (HIV) infection but ultimately fail to control viremia in most infected persons. Studies in acute infection have demonstrated strong CD8-mediated selection pressure and evolution of mutations conferring escape from recognition, but the ability of CD8 T-cell responses that persist in late-stage infection to recognize viruses present in vivo has not been determined. Therefore, we studied 24 subjects with advanced HIV disease (median viral load = 142,000 copies/ml; median CD4 count = 71/mul) and determined HIV-1-specific CD8 T-cell responses to all expressed viral proteins using overlapping peptides by gamma interferon Elispot assay. Chronic-stage virus was sequenced to evaluate autologous sequences within Gag epitopes, and functional avidity of detected responses was determined. In these subjects, the median number of epitopic regions targeted was 13 (range, 2 to 39) and the median cumulative magnitude of CD8 T-cell responses was 5,760 spot-forming cells/10(6) peripheral blood mononuclear cells (range, 185 to 24,700). On average six (range, one to 8) proteins were targeted. For 89% of evaluated CD8 T-cell responses, the autologous viral sequence was predicted to be well recognized by these responses and the majority of analyzed optimal epitopes were recognized with medium to high functional avidity by the contemporary CD8 T cells. Withdrawal of antigen by highly active antiretroviral therapy led to a significant decline both in breadth (P = 0.032) and magnitude (P = 0.0098) of these CD8 T-cell responses, providing further evidence that these responses had been driven by recognition of autologous virus. These results indicate that strong, broadly directed, and high-avidity gamma-interferon-positive CD8 T-cells directed at autologous virus persist in late disease stages, and the absence of mutations within viral epitopes indicates a lack of strong selection pressure mediated by these responses. These data imply functional impairment of CD8 T-cell responses in late-stage infection that may not be reflected by gamma interferon-based screening techniques. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Cambridge, MA 02138 USA. Lemuel Shattuck Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. RP Walker, BD (reprint author), Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM bwalker@helix.mgh.harvard.edu RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R56 AI054178, AI054178-01, R01 AI028568, R01 AI054178, R01 AI28568]; PHS HHS [N01-A1-15442] NR 58 TC 112 Z9 120 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 630 EP 641 DI 10.1128/JVI.78.2.630-641.2004 PG 12 WC Virology SC Virology GA 762EG UT WOS:000187957700009 PM 14694094 ER PT J AU Lu, R Nakajima, N Hofmann, W Benkirane, M Teh-Jeang, K Sodroski, J Engelman, A AF Lu, R Nakajima, N Hofmann, W Benkirane, M Teh-Jeang, K Sodroski, J Engelman, A TI Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID SV40 LARGE-T; DNA-BINDING DOMAIN; GENE-THERAPY; MEDIATED TRANSFORMATION; NUCLEAR-LOCALIZATION; VIRAL REPLICATION; HIV DNA; INFECTION; ANTIGEN; MUTATIONS AB Integrase function is required for retroviral replication in most instances. Although certain permissive T-cell lines support human immunodeficiency virus type 1 (HIV-1) replication in the absence of functional integrase, most cell lines and primary human cells are nonpermissive for integrase mutant growth. Since unintegrated retroviral DNA is lost from cells following cell division, we investigated whether incorporating a functional origin of DNA replication into integrase mutant HIV-1 might overcome the block to efficient gene expression and replication in nonpermissive T-cell lines and primary cells. Whereas the Epstein-Barr virus (EBV) origin (oriP) did little to augment expression from an integrase mutant reporter virus in EBV nuclear antigen 1-expressing cells, simian virus 40 (SV40) oriT dramatically enhanced integrase mutant infectivity in T-antigen (Tag)-expressing cells. Incorporating oriT into the nef position of a full-length, integrase-defective virus strain yielded efficient replication in Tag-expressing nonpermissive Jurkat T cells without reversion to an integration-competent genotype. Adding Tag to integrase mutant-oriT viruses yielded 11.3-kb SV40-HIV chimeras that replicated in Jurkat cells and primary monocyte-derived macrophages. Real-time quantitative PCR analyses of Jurkat cell infections revealed that amplified copies of unintegrated DNA likely contributed to SV40-HIV integrase mutant replication. SV40-based HIV-1 integrase mutant replication in otherwise nonpermissive cells suggests alternative approaches to standard integrase-mediated retroviral gene transfer strategies. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. Natl Inst Allergy & Infect Dis, Lab Mol Microbiol, Bethesda, MD 20892 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI45313, AI28691, P30 AI028691] NR 56 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 658 EP 668 DI 10.1128/JVI.78.2.658-668.2004 PG 11 WC Virology SC Virology GA 762EG UT WOS:000187957700012 PM 14694097 ER PT J AU Horowitz, TS Holcombe, AO Wolfe, JM Arsenio, HC DiMase, JS AF Horowitz, TS Holcombe, AO Wolfe, JM Arsenio, HC DiMase, JS TI Attentional pursuit is faster than attentional saccade SO JOURNAL OF VISION LA English DT Article DE attention; attentive tracking; apparent motion ID FEATURE-INTEGRATION-THEORY; VISUAL-SEARCH; SPATIAL ATTENTION; TEMPORAL DYNAMICS; EYE-MOVEMENT; OBJECT; MOTION; PERCEPTION; TRACKING; SHIFTS AB How quickly can we shift the focus of visual attention? We compared the rates of two types of attentional shifts: attentional saccades (shifts between objects) and attentional pursuit (shifts along with a moving object). Instead of measuring the time required for a single shift, which confounds shift time with cue interpretation time, we measured the pace at which observers could make multiple successive shifts in a predictable order. We find that successive attentional saccades between objects are quite slow (300-500 ms). The object-based theory of attention predicts that attention should shift between locations more quickly when in pursuit of a moving object. Our results support this theory. Attentional pursuit is substantially faster-taking only 200-250 ms to cover the same distance. "Indexing" a moving object (keeping track of one object) can be done at even faster rates, supporting a distinction between attending to and indexing objects. C1 Brigham & Womens Hosp, Visual Attent Lab, Cambridge, MA 02319 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales. Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Horowitz, TS (reprint author), Brigham & Womens Hosp, Visual Attent Lab, 64 Sidney St,Suite 170, Cambridge, MA 02319 USA. EM toddh@search.bwh.harvard.edu RI Holcombe, Alex/A-2344-2012; Wolfe, Jeremy/C-1621-2012; Horowitz, Todd/J-3376-2013; Wolfe, Jeremy/A-9248-2016 OI Wolfe, Jeremy/0000-0002-6475-1984; Wolfe, Jeremy/0000-0002-6475-1984 FU NEI NIH HHS [EY01711] NR 69 TC 32 Z9 34 U1 3 U2 9 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2004 VL 4 IS 7 BP 585 EP 603 DI 10.1167/4.7.6 PG 19 WC Ophthalmology SC Ophthalmology GA 848XK UT WOS:000223501200006 PM 15330704 ER PT J AU Elliott, MK Jarmi, T Ruiz, P Xu, YY Holers, VM Gilkeson, GS AF Elliott, MK Jarmi, T Ruiz, P Xu, YY Holers, VM Gilkeson, GS TI Effects of complement factor D deficiency on the renal disease of MRL/lpr mice SO KIDNEY INTERNATIONAL LA English DT Article DE lupus nephritis; animal models; complement alternative pathway ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ISCHEMIA-REPERFUSION INJURY; FACTOR-B; ALTERNATIVE PATHWAY; MONOCLONAL-ANTIBODY; AUTOIMMUNE-DISEASE; COMPONENT C3; FACTOR-H; EXPRESSION; ACTIVATION AB Background. The alternative complement pathway (AP) is activated in individuals with lupus nephritis and in murine models of systemic lupus erythematosus, including MRL/lpr mice. A previous study from our laboratory evaluated the development of renal disease in MRL/lpr mice genetically deficient in factor B (Bf-/-), a protein necessary for AP activation. MRL/lpr Bf-/- mice developed less renal disease and had improved survival; however, these mice were also a different major histocompatibility complex (MHC) haplotype (H-2(b)) than their wild-type littermates (H-2(k)) due to the gene for Bf being located in the MHC gene complex. We undertook the current study to determine if the decreased renal disease in MRL/lpr Bf-/- mice was due to the lack of AP activation or the H-2(b) haplotype by studying the effects of factor D(Df) deficiency, a critical protein for AP activation, on disease development in MRL/lpr mice. Methods. Df-deficient mice were backcrossed with MRL/lpr mice for four to nine generations. MRL/lpr H-2(k) Df-/-,Df+/-, and Df +/+ littermates were evaluated for disease development. Lack of AP activation in MRL/lpr Df-/- mice was determined by the zymosan assay. Serum creatinine levels were measured using a creatinine kit. Proteinuria and autoantibody levels were determined by enzyme-linked immunosorbent assay (ELISA). Sections from one kidney were stained with fluorescein isothiocyanate (FITC) alpha-murine C3 or alpha-murine IgG to detect C3 and IgG deposition. The remaining kidney was cut in half with one half fixed, sectioned, and stained with hematoxylin and eosin and periodic acid-Schiff (PAS) to evaluate pathology and another half fixed in glutaraldehyde and examined via electron microscopy. Results. MRL/lpr Df-/- mice had similar glomerular IgG deposition, proteinuria and autoantibody levels, as Df+/+ and Df+/- littermates. However, glomerular C3 deposition, serum creatinine levels, and pathologic renal disease were significantly reduced in Df-/- mice. Despite the lack of renal disease in Df-/- mice, life span was not impacted by factor D deficiency. Conclusion. The absence of Df and AP activation is protective against the development of proliferative renal disease in MRL/lpr mice suggesting the similar effect of Bf deficiency in MRL/lpr mice was also due to the lack of AP activation. C1 Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. Med Univ S Carolina, Dept Med, Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29425 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Colorado, Dept Med, Denver, CO USA. Univ Colorado, Dept Immunol, Denver, CO USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Div Rheumatol Immunol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. FU NIAID NIH HHS [AI47469]; NIAMS NIH HHS [AR39162, AR45476, P60AR20614] NR 46 TC 60 Z9 61 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2004 VL 65 IS 1 BP 129 EP 138 DI 10.1111/j.1523-1755.2004.00371.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 753YP UT WOS:000187276200013 PM 14675043 ER PT J AU Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO AF Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO TI Parathyroidectomy rates among United States dialysis patients: 1990-1999 SO KIDNEY INTERNATIONAL LA English DT Article DE parathyroidectomy; rates; incidence; dialysis; diabetes ID CHRONIC-RENAL-FAILURE; ADYNAMIC BONE-DISEASE; HEMODIALYSIS-PATIENTS; SECONDARY HYPERPARATHYROIDISM; DIABETIC-PATIENTS; REGULAR DIALYSIS; MORTALITY RISK; OSTEODYSTROPHY; HORMONE; TRANSPLANTATION AB Background. Medical therapy for secondary hyperparathyroidism (SHPTH) has evolved considerably during the past decade. It is not known how changes in medical therapy might impact the parathyroidectomy (PTX) rate among dialysis patients. Relatively low parathyroid hormone (PTH) levels have been found among elderly dialysis patients and those with diabetes. Clinical factors associated with differing PTX rates among United States dialysis patients have not been reported. We report PTX rates in the United States from 1990 to 1999 among persons with end- stage renal disease, accounting for changes in patient characteristics. Methods. Data from the United States Renal Database were utilized. Patients insured by Medicare or Medicaid and receiving renal replacement therapy between January 1, 1990, and December 31, 1999 were considered for analysis. PTX was determined by ICD- 9 procedure codes. Multivariate Poisson models were used to estimate adjusted PTX rates. Results. The overall observed PTX rate in the study sample was 7.16 per 1000 person- years at risk. After a slight rise during the early 1990s, adjusted PTX rates declined by approximately 30% between 1995 and 1999. Adjusted PTX rates were higher among patients who were younger, female, nondiabetic, receiving peritoneal dialysis, and those with a longer cumulative duration of dialysis. Conclusion. PTX rates have recently decreased in the United States, independent of changes in patient characteristics. The effectiveness of medical therapy in targeting secondary hyperparathyroidism may be improving. Younger, nondiabetic patients with a longer cumulative dialysis burden are at particularly high risk for PTX. C1 Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98195 USA. RP Kestenbaum, B (reprint author), Univ Washington, Dept Med, Div Nephrol, Box 3565221 BB 1265,Hlth Sci Bldg,1959 NE Pacific, Seattle, WA 98195 USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 NR 34 TC 46 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2004 VL 65 IS 1 BP 282 EP 288 DI 10.1111/j.1523-1755.2004.00368.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 753YP UT WOS:000187276200031 PM 14675061 ER PT J AU Maher, MM Kalra, MK Rizzo, S Mueller, PR Saini, S AF Maher, MM Kalra, MK Rizzo, S Mueller, PR Saini, S TI Multidetector CT urography in imaging of the urinary tract in patients with hematuria SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE multidetector CT; urography ID UNENHANCED HELICAL CT; ASYMPTOMATIC MICROSCOPIC HEMATURIA; AMERICAN-UROLOGICAL-ASSOCIATION; URETERAL CALCULI; INITIAL-EXPERIENCE; PRACTICE POLICY; RENAL MASSES; FLANK PAIN; URETEROLITHIASIS; COMPRESSION AB This review article comprehensively discusses multidetector CT urography protocols and their role in imaging of the urinary tract in patients with hematuria. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 40 TC 31 Z9 33 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-MAR PY 2004 VL 5 IS 1 BP 1 EP 10 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 811TH UT WOS:000220793700001 PM 15064553 ER PT J AU Maher, MM Kalra, MK Sahani, DV Perumpillichira, JJ Rizzo, S Saini, S Mueller, PR AF Maher, MM Kalra, MK Sahani, DV Perumpillichira, JJ Rizzo, S Saini, S Mueller, PR TI Techniques, clinical applications and limitations of 3D reconstruction in CT of the abdomen SO KOREAN JOURNAL OF RADIOLOGY LA English DT Editorial Material DE computed tomography; abdomen; multidetector, 3D ID HELICAL CT; COMPUTED-TOMOGRAPHY; BLADDER AB Enhanced z-axis coverage with thin overlapping slices in breath-hold acquisitions with multidetector CT (MDCT) has considerably enhanced the quality of multiplanar 3D reconstruction. This pictorial essay describes the improvements in 3D reconstruction and technical aspects of 3D reconstruction and rendering techniques available for abdominal imaging. Clinical applications of 3D imaging in, abdomen including liver, pancreaticobiliary system, urinary and gastrointestinal tracts and imaging before and after transplantation are discussed. In addition, this article briefly discusses the disadvantages of thin-slice acquisitions including increasing numbers of transverse images, which must be reviewed by the radiologist. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02184 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Maher, MM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02184 USA. EM mmaher@partners.org NR 15 TC 18 Z9 18 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-MAR PY 2004 VL 5 IS 1 BP 55 EP 67 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 811TH UT WOS:000220793700008 PM 15064560 ER PT J AU Pritt, S Nostrant, F AF Pritt, S Nostrant, F TI IACUC in a bind thanks to lack of information SO LAB ANIMAL LA English DT Editorial Material C1 Joslin Diabet Ctr, Anim Resources Facil, Boston, MA 02215 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. RP Pritt, S (reprint author), Joslin Diabet Ctr, Anim Resources Facil, Boston, MA 02215 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2004 VL 33 IS 1 BP 17 EP + DI 10.1038/laban0104-17b PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 761JQ UT WOS:000187867100004 PM 14752527 ER PT J AU Finch, RG Metlay, JP Davey, PG Baker, LJ AF Finch, RG Metlay, JP Davey, PG Baker, LJ CA Int Forum Antibiotic Resistance co TI Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002 SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID RESPIRATORY-TRACT INFECTIONS; HEALTH-BEHAVIOR-CHANGE; STREPTOCOCCUS-PNEUMONIAE; PENICILLIN RESISTANCE; FAMILY-PRACTICE; ERYTHROMYCIN; CONSUMPTION; IMPACT; CARE; EXPECTATIONS AB National and international strategies for the control of antibiotic resistance recommend education for health-care professionals and the public to promote prudent antibiotic use. This paper, based on discussions at the 2002 colloquium of the International Forum on Antibiotic Resistance (IFAR), provides an international discourse between theoretical approaches to behaviour change and practical experience gained in large-scale antibiotic use educational campaigns. Interventions are more likely to be effective if their aim is to change behaviour, rather than provide information. They should target all relevant groups, especially parents, children, day-care staff, and health-care professionals. They should use clear and consistent messages concerning bacterial versus viral infection, prudent antibiotic use, symptomatic treatment, and infection-control measures (eg, handwashing). Campaigns should use a range of communications using pilot-testing, strong branding, and sociocultural adaptation. Prime-time television is likely to be the most effective public medium, while academic detailing is especially useful for health-care professionals. Multifaceted interventions can improve antibiotic prescribing to some degree. However, there are few data on their effects on resistance patterns and patient outcomes, and on their cost-effectiveness. Current research aims include the application of behaviour-change models, the development and validation of prudent antibiotic prescribing standards, and the refinement of tools to assess educational interventions. C1 City Hosp Nottingham, Nottingham NG5 1PB, England. Univ Nottingham, Nottingham NG7 2RD, England. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Dundee, Ninewells Hosp & Med Sch, Med Monitoring Unit, Dundee DD1 9SY, Scotland. RP Finch, RG (reprint author), City Hosp Nottingham, Clin Sci Bldg,Hucknall Rd, Nottingham NG5 1PB, England. NR 60 TC 93 Z9 97 U1 1 U2 16 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2004 VL 4 IS 1 BP 44 EP 53 DI 10.1016/S1473-3099(03)00860-0 PG 12 WC Infectious Diseases SC Infectious Diseases GA 760HR UT WOS:000187806000023 PM 14720568 ER PT J AU McKeith, I Mintzer, J Aarsland, D Burn, D Chiu, H Cohen-Mansfield, J Dickson, D Dubois, B Duda, JE Feldman, H Gauthier, S Halliday, G Lawlor, B Lippa, C Lopez, OL Machado, JC O'Brien, J Playfer, J Reid, W AF McKeith, I Mintzer, J Aarsland, D Burn, D Chiu, H Cohen-Mansfield, J Dickson, D Dubois, B Duda, JE Feldman, H Gauthier, S Halliday, G Lawlor, B Lippa, C Lopez, OL Machado, JC O'Brien, J Playfer, J Reid, W CA Int Psychogeriatric Assoc Expert M TI Dementia with Lewy bodies SO LANCET NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting of the International-Psychogeriatric-Association (IPA) CY NOV, 2002 CL BUDAPEST, HUNGARY SP Int Psychogeriatric Assoc ID SLEEP BEHAVIOR DISORDER; CLINICAL DIAGNOSTIC-CRITERIA; CSF AMYLOID BETA-42; NORMAL TAU LEVELS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; BODY DEMENTIA; NEUROLEPTIC SENSITIVITY; VASCULAR DEMENTIA AB Dementia with Lewy bodies (DLB) is the second commonest cause of neurodegenerative dementia in older people. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. DLB has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's disease. Here we review the current state of scientific knowledge on DLB. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other common types of dementia. Severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality. Treatment with cholinesterase inhibitors is well tolerated by most patients and substantially improves cognitive and neuropsychiatric symptoms. Clear guidance on the management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life. C1 Royal Liverpool Hosp, Liverpool L7 8XP, Merseyside, England. Inst Res & Educ Aging, Aurus IEPE, Belo Horizonte, MG, Brazil. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. St James Hosp, Dublin 8, Ireland. Prince Wales Med Res Inst, Sydney, NSW, Australia. McGill Ctr Studies Aging, Quebec City, PQ, Canada. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Vet Affairs Med Ctr, Philadelphia, PA USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Mayo Clin, Jacksonville, FL 32224 USA. George Washington Univ, Washington, DC USA. Res Inst Aging Hebrew Home Greater Washington, Washington, DC USA. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Rogaland Psychiat Hosp, Stavanger, Norway. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Newcastle Upon Tyne, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP McKeith, I (reprint author), Newcastle Gen Hosp, Inst Ageing & Hlth, Westgate Rd, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. RI Halliday, Glenda/E-8555-2011; OI Halliday, Glenda/0000-0003-0422-8398; Dickson, Dennis W/0000-0001-7189-7917; Feldman, Howard/0000-0002-9258-4538; Aarsland, Dag/0000-0001-6314-216X NR 110 TC 387 Z9 403 U1 8 U2 42 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2004 VL 3 IS 1 BP 19 EP 28 DI 10.1016/S1474-4422(03)00619-7 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 756BZ UT WOS:000187447100022 PM 14693108 ER PT J AU Gass, A Ay, H Szabo, K Koroshetz, WJ AF Gass, A Ay, H Szabo, K Koroshetz, WJ TI Diffusion-weighted MRI for the "small stuff": the details of acute cerebral ischaemia SO LANCET NEUROLOGY LA English DT Review ID CAPSULAR WARNING SYNDROME; MAGNETIC-RESONANCE; ACUTE STROKE; CLINICAL CHARACTERISTICS; SUBARACHNOID HEMORRHAGE; LACUNAR INFARCTION; WATER DIFFUSION; TIME-COURSE; TRANSIENT; ATTACKS AB Diffusion-weighted MRI (DWI) has already had a substantial effect on the diagnosis of patients with ischaemic stroke. It provides in vivo pathological information and allows the differentiation of acute stroke from chronic stroke and from non-specific white-matter lesions. The high contrast of the acute DWI lesion against the dark background facilitates the detection of lesions even when they are 1 mm or less in diameter. Small lesions, which are undetectable by other means, include small lacunar infarcts, punctate cortical infarcts, and DWI bright dots in patients with transient ischaemic attacks (TIA). The latter constitute remnants or "footprints" of recent ischaemia and confirm the clinical TIA syndrome as ischaemic. Because of these attributes, DWI not only confirms the clinical diagnosis, but also facilitates the recognition of certain patterns of ischaemia, thereby providing clues to the underlying aetiology. DWI is becoming an important technique for optimum management of patients. C1 Univ Klinikum Mannheim, Dept Neurol, NMR Res Neurol, D-38137 Mannheim, Germany. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gass, A (reprint author), Univ Klinikum Mannheim, Dept Neurol, NMR Res Neurol, Theodor Kutzer Ufer 1-3, D-38137 Mannheim, Germany. NR 53 TC 61 Z9 64 U1 0 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2004 VL 3 IS 1 BP 39 EP 45 DI 10.1016/S1474-4422(03)00621-5 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 756BZ UT WOS:000187447100024 PM 14693110 ER PT J AU Zeitels, SM Dailey, SH Burns, JA AF Zeitels, SM Dailey, SH Burns, JA TI Technique of en block laser endoscopic frontolateral laryngectomy for glottic cancer SO LARYNGOSCOPE LA English DT Article DE vocal fold; vocal cord; glottic; glottis; cancer; laryngectomy; microlaryngoscopy; CO2 laser ID VOCAL FOLD; CLINICAL EXPERIENCE; SURGERY; COMMISSURE; CO2-LASER; CARCINOMAS; EXPOSURE; LARYNX; MICROSURGERY; MANAGEMENT AB During the last 30 years, there has been expansion of the role of endoscopic partial laryngectomy procedures since Jako, Strong, and Vaughan explored the possibilities of CO2 laser microlaryngeal procedures. Despite the fact that a number of investigators have verified the validity of endolaryngeal laser resection of mid-sized glottic cancer, there are many who are unfamiliar with the technique and others who are uncomfortable with sectioning the tumor to facilitate its resection. In the past 3 years, 15 patients underwent successful en block resection of mid-sized glottic cancer (T1b 2, T2b 11, T3 2). Because en block resection is more consistent with open oncologic approaches, this method should widen the acceptance of this approach in selected lesions. The nuances of en block endoscopic frontolateral laryngectomy are presented with the hope that more surgeons will adopt this philosophy as an aspect of their armamentarium. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 49 TC 12 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2004 VL 114 IS 1 BP 175 EP 180 DI 10.1097/00005537-200401000-00033 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 882CM UT WOS:000225916200030 PM 14710017 ER PT S AU Hasan, T Solban, N AF Hasan, T Solban, N BE Jacques, SL Roach, WP TI Photochemical effects in laser-tissue interactions: photodynamic therapy, an overview. SO LASER INTERACTION WITH TISSUE AND CELLS XV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Laser Interaction with Tissue and Cells XV CY JAN 26-28, 2004 CL San Jose, CA SP SPIE, USAF Off Sci Res DE photodynamic therapy; history; cancer; porphyrins ID FLUENCE RATE; IN-VIVO; HEMATOPORPHYRIN; TUMOR; APOPTOSIS; HISTORY; PHOTOCHEMOTHERAPY; PHTHALOCYANINE; PHOTODAMAGE; CHLORIN AB Photodynamic Therapy (PDT) is the best-known biomedical application of photochemical approaches to therapeutics. Although regulatory approvals for this modality have been obtained only over the last decade, the concept and indeed clinical studies of PDT are over a century old. During the first part of the last quarter century the focus of PDT applications had been on the treatment of cancer. However in recent years this has been broadened to a variety of non-cancer and diagnostic applications. This may be considered a return to the "roots" of PDT where one of the initial observations that form the basis of this approach was the inactivation of paramecium when exposed to acridine orange and light and the fluorescence of tumors when treated with porphyrins and light. Currently the most successful application of PDT is non-oncologic in the treatment of age-related macular degeneration (AMD) with Visudyne; so far this is the only first line use of PDT. At the present time, other diseases are being explored as targets for PDT in laboratories worldwide with a variety of strategies and PDT may now be considered a platform technology where photochemistry may be directed to specific anatomical sites and molecular targets with potentially a large number of applications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 38 TC 0 Z9 0 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 0-8194-5227-0 J9 P SOC PHOTO-OPT INS PY 2004 VL 5319 BP 41 EP 49 DI 10.1117/12.537251 PG 9 WC Biophysics; Engineering, Biomedical; Optics SC Biophysics; Engineering; Optics GA BAO13 UT WOS:000223056000006 ER PT S AU Castano, AP Liu, QD Hamblin, MR AF Castano, AP Liu, QD Hamblin, MR BE Jacques, SL Roach, WP TI Photodynamic therapy cures green fluorescent protein expressing RIF1 tumors in mice SO LASER INTERACTION WITH TISSUE AND CELLS XV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Laser Interaction with Tissue and Cells XV CY JAN 26-28, 2004 CL San Jose, CA SP SPIE, USAF Off Sci Res DE photodynamic therapy; photosensitizer; fluorescence imaging; green fluorescent protein; anti-tumor immunity ID HEAT-SHOCK PROTEINS; MODEL SYSTEM; CELL-DEATH; CANCER; METASTASIS; IMMUNOTHERAPY; IMMUNITY; VACCINES AB Cancer is a leading cause of death among modem people, largely due to metastatic disease. The ideal cancer treatment should destroy both the primary tumor and distant metastases with minimal toxicity to normal tissue. This is best accomplished by educating the body's immune system to recognize the tumor as foreign so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens are likely to emerge in the future to even further enhance immunity. Green fluorescent protein is used as an optical reporter to non-invasively image the progression of mouse tumors, and in addition, may act as a foreign (jellyfish) antigen. We asked whether the response of tumor bearing mice to PDT differed when a non-immunogenic tumor cell line was transfected with GFP? We injected RIF-1 or RIF1-EGFP cells in the leg of C3H/HeN mice and both the cells and tumors grew equally well. We used two PDT protocols (benzoporphyrin derivative (BPD) with 15-minute interval or Photofrin with 24-hour interval). The results showed significant differences between the responses of RIF1 or RIF1-EGFP tumors after BPD or Photofrin PDT and complete cures and mouse survival when RIF-1 EGFP tumors were treated with BPD. This increased tumor response may be due to antibody-mediated cytotoxicity and the presence of an artificial tumor antigen (GFP) that can produce a CD8 T-cell response against the whole tumor. The presence of antibodies against EGFP in mouse serum correlates with the hypothesis. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Castano, AP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 30 TC 4 Z9 4 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5227-0 J9 P SOC PHOTO-OPT INS PY 2004 VL 5319 BP 50 EP 59 DI 10.1117/12.528381 PG 10 WC Biophysics; Engineering, Biomedical; Optics SC Biophysics; Engineering; Optics GA BAO13 UT WOS:000223056000007 ER PT S AU Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF AF Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF BE Bartels, KE Bass, LS DeRiese, WTW Gregory, KW Hirschberg, H Katzir, A Kollias, N Madsen, SJ Malek, RS McNallyHeintzelman, KM Paulsen, KD Robinson, DS Tate, LP Trowers, EA Wong, BJ TI Birefringence measurements in human skin using polarization-sensitive optical coherence tomography SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutics and Systems XIV CY JAN 24-27, 2004 CL San Jose, CA SP SPIE DE medical imaging; polarization; birefringence; collagen; dermatology ID RESOLVED MUELLER MATRIX; BIOLOGICAL TISSUE; FIBER; INTERFEROMETER AB Optical coherence tomography enables cross-sectional imaging of tissue structure to depths of around 1.5 mm, at high-resolution and in real-time. Incorporation of polarization-sensitivity enables the birefringent properties of tissues to be visualized and quantified. We present polarization-sensitive optical coherence tomography images and quantitative birefringence analysis of in vivo human skin. From measurements on a sample of 5 human volunteers, mean double-pass phase retardation rates of 0.340 +/- 0.143, 0.250 +/- 0.076 and 0.592 +/- 0.142degrees/mum were obtained for normal skin at the dorsal hand, temple and lower back regions respectively. Compared to these values measured in normal skin, a reduction in birefringence was observed and quantified in human skin following thermal injury. Conversely, increased birefringence was consistently measured at skin sites following wound healing and repair. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, Boston, MA 02114 USA. OI strasswimmer, john/0000-0002-5790-2633 NR 30 TC 0 Z9 0 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 0-8194-5220-3 J9 P SOC PHOTO-OPT INS PY 2004 VL 5312 BP 35 EP 40 DI 10.1117/12.529627 PG 6 WC Medicine, Research & Experimental; Optics; Physics, Applied; Surgery SC Research & Experimental Medicine; Optics; Physics; Surgery GA BAR78 UT WOS:000223294600005 ER PT J AU Khadem, J Martino, M Anatelli, F Dana, MR Hamblin, MR AF Khadem, J Martino, M Anatelli, F Dana, MR Hamblin, MR TI Healing of perforating rat corneal incisions closed with photodynamic laser-activated tissue glue SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; tissue glue; laser activation; rat corneal incision; Janus Green ID PROTEIN SOLDER; JANUS GREEN; ADHESIVE; ANASTOMOSES; STRENGTH; REPAIR; LIGHT AB Background and Objectives: Laser-activated photodynamic biologic tissue glues may be useful for closing incisions in ophthalmology. We report on the use of two such preparations to close perforating corneal incisions in living rats. Study Design/Materials and Methods: A previously described preparation containing a covalent albumin-chlorin e6 (ce6) conjugate (bovine serum albumin (BSA)ce6), and a novel mixture of albumin and Janus Green (BSA/JG), both activated with a 665-nm diode laser were used to glue mouse skin ex vivo. The optimized glues were then used to seal incisions in rat corneas and results were compared to control incisions. Rats were sacrificed at day 1, 7, and 14 and eyes tested for leaking pressure and examined histopathologically. Results: One day after treatment eyes closed with BSA-ce6 had a leaking pressure (in mmHg) of 357 compared to 193 for control incisions (P<0.01); closure with BSA/JG gave a leaking pressure of 430 (P<0.05 compared to BSA-ce6, and P<0.001 compared to control). Histological examination showed eyes sealed with BSA/JG have less inflammation present than untreated eyes at 7 days. Conclusions: These data demonstrate that photodynamic laser activated tissue glues can be used to effectively seal corneal incisions in living animals without thermal damage or undue inflammation. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR314B,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA/AI 83880 1]; NIAID NIH HHS [R01 AI050875-01A2, R01 AI050875] NR 25 TC 9 Z9 9 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 VL 35 IS 4 BP 304 EP 311 DI 10.1002/lsm.20099 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 867MP UT WOS:000224847000009 PM 15493025 ER PT J AU Taylor, CR Racette, AL AF Taylor, CR Racette, AL TI A 308-nm Excimer laser for the treatment of scalp psoriasis SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE narrowband phototherapy; ultraviolet B ID UV-B PHOTOTHERAPY; 311-NM UVB; PHOTOCHEMOTHERAPY; LIGHT AB Background and Objectives: Scalp psoriasis is a frustrating disorder whose treatments can all too often be cumbersome and ineffective. Our objective was to test a combination device involving the 308-nm excimer laser in tandem with a hair blower for treating scalp psoriasis. Study Design/Materials and Methods: Adult subjects with scalp psoriasis unresponsive to class I topical steroids used in conjunction with medicated shampoos were treated with 308-nm excimer laser pulses in conjunction with a hair blower that parted the obstructing hair twice a week for up to 15 weeks. Half of the scalp served as a control. Starting doses were based on standard minimal erythema. dose (MED)'s with subsequent increments of up to 20%. Results: Thirteen subjects completed the study without adverse events. Two were dropped due to lack of compliance. At the end of the investigation, the difference in the mean modified PASI scores between the control and treated sites was 4.0 (<0.0001). Conclusions: The air blower device in conjunction with the 308-nm excimer laser can safely and effectively treat otherwise refractory scalp psoriasis. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,32 Fruit St, Boston, MA 02114 USA. EM crtaylor@partners.org NR 20 TC 20 Z9 21 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 VL 34 IS 2 BP 136 EP 140 DI 10.1002/lsm.10218 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 800GA UT WOS:000220015700012 PM 15004825 ER PT J AU Poureshagh, M AF Poureshagh, M TI Selective photothermal effects by low fluence diode laser on hair follicles ex vivo SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 43 BP 15 EP 15 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700044 ER PT J AU Manstein, D Bowes, LE Rius, F Poureshagh, M Anderson, RR AF Manstein, D Bowes, LE Rius, F Poureshagh, M Anderson, RR TI Hair growth management with a low-dose, continuous-wave diode laser used in scanning mode SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 69 BP 23 EP 23 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700068 ER PT J AU Herron, GS Tanner, H Sink, RK Hauser, B Frangineas, G Chan, K Anderson, RR Manstein, D AF Herron, GS Tanner, H Sink, RK Hauser, B Frangineas, G Chan, K Anderson, RR Manstein, D TI Fractional resurfacing treatment of periorbital wrinkles SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Telang LLC, Palo Alto, CA USA. Reliant Technol Inc, Palo Alto, CA USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 72 BP 24 EP 24 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700071 ER PT J AU Laughlin, S Yaroslavsky, I Manstein, D Altshuler, G Anderson, RR AF Laughlin, S Yaroslavsky, I Manstein, D Altshuler, G Anderson, RR TI Photothermal therapy of cellulite with a continuous wave (CW) infrared source SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Univ Ottawa, Ottawa, ON, Canada. Palomar Med Technol Inc, Burlington, MA USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 97 BP 32 EP 32 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700096 ER PT J AU Akita, H Farinelli, WA Flotte, T Anderson, RR AF Akita, H Farinelli, WA Flotte, T Anderson, RR TI Can ocular melanosis be safely treated with laser therapy? SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatopathol Unit, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 99 BP 33 EP 33 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700098 ER PT J AU Manstein, D Yaroslavsky, I Altshuler, G Anderson, RR AF Manstein, D Yaroslavsky, I Altshuler, G Anderson, RR TI Photothermal excitation of subcutaneous fat and deep dermis, by CW filtered infrared radiation and contact cooling SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Palomar Med Technol Inc, Burlington, MA USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 98 BP 33 EP 33 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700097 ER PT J AU Manstein, D Rius, F Anderson, RR AF Manstein, D Rius, F Anderson, RR TI Epidermal safety of a scanned, continuous-wave diode laser SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 220 BP 67 EP 67 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700204 ER PT J AU Manstein, D Khan, MH Sink, RK Anderson, RR AF Manstein, D Khan, MH Sink, RK Anderson, RR TI Fractional resurfacing - A new treatment concept for skin rejuvenation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Reliant Technol Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 221 BP 67 EP 67 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700205 ER PT J AU Manstein, D Khan, MH Sink, RK Anderson, RR AF Manstein, D Khan, MH Sink, RK Anderson, RR TI Fractional resurfacing - A new treatment concept for skin rejuvenation SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Laser-Medicine-and-Syrgery CY MAR 31-APR 04, 2004 CL Dallas, TX SP Amer Soc Laser Med & Surg C1 Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Reliant Technol Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 SU S16 MA 261 BP 76 EP 76 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 808UJ UT WOS:000220593700233 ER PT J AU Oken, MM Lee, S Kay, NE Knospe, W Cassileth, PA AF Oken, MM Lee, S Kay, NE Knospe, W Cassileth, PA TI Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia: A phase I/II study by the eastern cooperative oncology group study E1488 SO LEUKEMIA & LYMPHOMA LA English DT Article DE B-CLL; pentostatin; alkylators; combination therapy ID FLUDARABINE PLUS CYCLOPHOSPHAMIDE; TERM-FOLLOW-UP; LYMPHOPROLIFERATIVE DISORDERS; II TRIAL; CANCER; DEOXYCOFORMYCIN; MALIGNANCIES; REGIMEN AB Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. The purpose of this study was to determine the dose of pentostatin (dCF) that could be combined with chlorambucil and prednisone to treat chronic lymphocytic leukemia (CLL), evaluate the toxicity of the resulting regimen and to estimate its efficacy. This was a multi-institutional Eastern Cooperative Oncology Group (ECOG) phase I - II study. Individuals with active B-CLL were eligible if they had no prior treatment or were in sensitive first relapse, provided they had normal renal and hepatic function. Pentostatin was evaluated in combination with orally administered chlorambucil 30 mg/m(2) and prednisone 80 mg/day, 1 - 5 of each 14-day cycle. The pentostatin dose was 2 mg/m(2) IV, day 1 for the first 6 patients; 3 mg/m(2) IV, day 1 for the next 6 patients; and 4 mg/m(2) IV, day 1 for the last set of 6 patients. Fifty-five patients were entered. Because of increasing toxicity with no apparent improvement in clinical efficacy on escalation of the pentostatin dose, 2 mg/m(2) was chosen as the phase II dose, and 43 patients were treated at this level. Thirty-nine of these patients were eligible, of which 38 were evaluable for response, 36 of these 38 had no prior treatment. Complete response (CR) manifested by normal bone marrow morphology, peripheral blood counts and resolution of any lymphadenopathy or hepatosplenomegaly occurred in 17 patients (45%). The overall objective response rate was 87%. The median response duration was 33 months and the median survival 5 years. The median time to treatment failure is 32 months. Severe (Grade 3 + ) infections were seen in 31% of patients and included bacterial pneumonia (n = 4), Pneumocystis pneumonia (n = 1), fungal pneumonia (n = 2), urinary tract infection with sepsis (n = 1) and Herpes Zoster (n = 5). Overall, 11 patients had H. Zoster while on study. Due to toxicity, 33% of patients stopped therapy. Pentostatin, chlorambucil and prednisone is a highly active regimen in CLL but cannot be recommended in present form because of an unacceptable incidence of opportunistic infections. These findings add to other recent reports which suggest combination therapy with pentostatin and alkylators are active in B-CLL. However, these combination chemotherapies will need to be combined with appropriate addition of anti-bacterial and anti-viral prophylaxis to reduce infection risk for B-CLL patients. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Minnesota, Minneapolis, MN USA. Hubert H Humphrey Canc Ctr, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Miami, Miami, FL 33152 USA. RP Kay, NE (reprint author), Mayo Clin & Mayo Fdn, Stabile 628,200 1st St SW, Rochester, MN 55905 USA. NR 29 TC 21 Z9 23 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2004 VL 45 IS 1 BP 79 EP 84 DI 10.1080/1042819031000151897 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 739JZ UT WOS:000186342500011 PM 15061201 ER PT J AU Friedberg, JW Fischman, A Neuberg, D Kim, H Takvorian, T Ng, AK Mauch, PM Canellos, GP Van den Abbeele, AD AF Friedberg, JW Fischman, A Neuberg, D Kim, H Takvorian, T Ng, AK Mauch, PM Canellos, GP Van den Abbeele, AD TI FDG-PET is superior to gallium scintigraphy in staging and more sensitive in the follow-up of patients with de novo hodgkin lymphoma: A blinded comparison SO LEUKEMIA & LYMPHOMA LA English DT Article DE PET; gallium scintigraphy; Hodgkin lymphoma; spleen; staging; relapse ID POSITRON-EMISSION-TOMOGRAPHY; MALIGNANT-LYMPHOMA; GA-67 SCINTIGRAPHY; IMAGE-RECONSTRUCTION; PROGNOSTIC VALUE; BONE-MARROW; DISEASE; MANAGEMENT; FLUORODEOXYGLUCOSE; CHEMOTHERAPY AB Accurate staging of Hodgkin lymphoma (HD) allows for minimization of therapy and reduction of long-term toxicities. The present study prospectively compares FDG-PET with gallium/SPECT scintigraphy at time of diagnosis and in follow-up of 36 patients with HD. Prior to therapy, whole body FDG-PET and gallium/SPECT were performed. Follow-up scans were obtained after 3 cycles of chemotherapy (n = 22), and at the end of chemotherapy (n = 32). Two nuclear medicine physicians independently interpreted scans in blinded and random order and a consensus was obtained. Baseline scans revealed a greater number of supradiaphragmatic disease sites detected by PET, and 5 patients had splenic involvement on PET not noted by gallium (P = 0.05); 3 patients were upstaged on PET. Midway through therapy, 5 patients had positive PET (4 of whom relapsed), and 3 had positive gallium (1 relapsed). At conclusion of chemotherapy, 8 patients had a positive PET (4 relapsed) and 3 had a positive gallium (2 relapsed). In conclusion, diagnostic PET and gallium are largely concordant, with the exception of unique detection of splenic disease by PET. However, more patients have persistently positive PET at the end of chemotherapy compared with gallium (P = 0.04), although only half of these patients have relapsed. C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol Nucl Med, Boston, MA 02115 USA. RP Friedberg, JW (reprint author), Univ Rochester, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. FU NCI NIH HHS [CA 78936] NR 39 TC 74 Z9 82 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2004 VL 45 IS 1 BP 85 EP 92 DI 10.1080/1042819031000149430 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 739JZ UT WOS:000186342500012 PM 15061202 ER PT J AU Cheng, JH Zhang, DS Zhou, CH Marasco, WA AF Cheng, JH Zhang, DS Zhou, CH Marasco, WA TI Down-regulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4(+) T-cells SO LEUKEMIA RESEARCH LA English DT Article DE signal transductiom; adult T-cell leukemia; retrovirus; cancer; IL-2 receptor ID TYROSINE-PHOSPHATASE SHP-1; LEUKEMIA LYMPHOMA VIRUS; JAK-STAT PATHWAY; GENE-EXPRESSION; CONSTITUTIVE ACTIVATION; SH2-CONTAINING PROTEIN; TRANSCRIPTION FACTORS; HISTONE DEACETYLASE; MESSENGER-RNA; DNA AB Adult T-cell leukemia (ATL) is an aggressive malignancy that is associated with human T-cell lymphotropic virus 1 (HTLV-1) infection. HTLV-1 transformed T-cell lines and fresh ATL cells are characterized by constitutive activation of the interleukin-2 receptor (IL-2R) signaling pathway however, the mechanism(s) responsible for constitutive IL-2R activation are unknown. To further examine the cause of this signaling pathway deregulation, we measured mRNA and protein expression levels by real-time PCR and Western blots, respectively, of four negative regulators of the IL-2R signaling pathway including src homology 2 (SH2)-containing phosphatase (SHP]), cytokine-inducible (CIS) SH2-containing protein, suppressor of cytokine signaling-1 (SOCS1) and protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) in six HTLV-1 negative and seven HTLV-1 positive T-cell leukemia lines. The activation status of the JAK/STAT pathway was also examined. SHP1 mRNA and protein expression levels were selectively down regulated in all HTLV-1-infected transformed cell lines, while CIS, SOCS 1, and PIAS3 protein expression were markedly but variably upregulated and the cells showed evidence of constitutive STAT3 activation. In acutely HTLV-1 infected primary CD4(+) T-cells there was a gradual loss of SHP1 expression over 10 weeks in culture which correlated with progression from immortalization to transformation and loss of IL-2 dependence for growth. Two transformed cell lines that were established following HTLV-1 infection showed loss of SHP1 expression and overexpression of CIS, SOCS1, PIAS3. However, this overexpression was not adequate to block constitutive activation of the JAK/STAT pathway. Thus, multiple levels of IL-2 receptor signal deregulation are found in HTLV-1 transformed cells, which may be a result of early loss of SHP1 expression. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. 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, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu NR 68 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2004 VL 28 IS 1 BP 71 EP 82 DI 10.1016/S0145-2126(03)00158-9 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 761EQ UT WOS:000187888000010 PM 14630083 ER PT J AU Stone, ME AF Stone, ME TI The 30-day natural hormone plan: Look and feel young again-without synthetic HRT. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JAN PY 2004 VL 129 IS 1 BP 148 EP 148 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 761NR UT WOS:000187915300299 ER PT J AU Novak, J Schleman, S Scott, J Balderman, VL Krech, L Kane, MA AF Novak, J Schleman, S Scott, J Balderman, VL Krech, L Kane, MA TI Dexamethasone regulation of gastrin-releasing peptide receptor in human lung cells SO LUNG CANCER LA English DT Article DE bombesin; gastrin-releasing peptide; receptors; gtucocorticoid; lung cancer; human; regulation ID CARCINOMA NCI-H345 CELLS; BOMBESIN-LIKE PEPTIDES; MESSENGER-RNA LEVELS; CANCER CELLS; BICINCHONINIC ACID; GENE-EXPRESSION; DOWN-REGULATION; IN-VITRO; GROWTH; GLUCOCORTICOIDS AB We investigated the effects of the glucocorticoid, dexamethasone (Dex), on expression of the gastrin-releasing peptide (GRP) receptor by human small cell lung carcinoma (SCLC) SHP77 cells. After 12 h of 10 nM Dex exposure, a six-fold increase in the peak of GRP receptor mRNA compared with untreated controls (10.5 +/- 4 versus 1.65 +/- 0.15 attomols/mug total RNA, respectively, P < 0.05) occurred. GRP receptor mRNA levels fell to less than 0.5 attomots/mug total RNA after 24h; in Dex-treated cells, these levels rose to 1.2 compared with 0.12 attomots/mug total RNA in the absence of Dex after 7 days. A significant increase (P < 0.05) in the GRP receptor-specific binding was also found. Stimulation of SHP77 cell proliferation (25-35% in the presence of 10-100nM Dex; P < 0.0001) was observed after 4-8 days of exposure; this stimulation was inhibited by GRP receptor antagonists. SHP77 cell content and concentration of bombesin-Like peptides (BLP) in conditioned medium (approximately 4nM) was unchanged by Dex. Stimulation of human SCLC SHP77 cell proliferation by Dex may, in part, occur via effects on the GRP autocrine system in these cells. Published by Elsevier Ireland Ltd. C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Sect Med Oncol, Denver, CO 80220 USA. Univ Colorado, Ctr Canc, Denver, CO 80220 USA. RP Kane, MA (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Sect Med Oncol, 1055 Clermont St, Denver, CO 80220 USA. EM madeteine.kane@uchsc.edu NR 44 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JAN PY 2004 VL 43 IS 1 BP 17 EP 28 DI 10.1016/j.lungan.2003.07.002 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 766MT UT WOS:000188380700003 PM 14698533 ER PT J AU Person, SD Allison, JJ Kiefe, CI Weaver, MT Williams, OD Centor, RM Weissman, NW AF Person, SD Allison, JJ Kiefe, CI Weaver, MT Williams, OD Centor, RM Weissman, NW TI Nurse staffing and mortality for Medicare patients with acute myocardial infarction SO MEDICAL CARE LA English DT Article DE acute myocardial infarction; mortality; nurse staffing; Medicare ID QUALITY-OF-CARE; COOPERATIVE CARDIOVASCULAR PROJECT; LICENSED PRACTICAL NURSES; HOSPITAL MORTALITY; INTENSIVE-CARE; PARTNERSHIP MODEL; RISK ADJUSTMENT; ADVERSE EVENTS; US HOSPITALS; DRUG-THERAPY AB Context: Recent hospital reductions in registered nurses (RNs) for hospital care raise concerns about patient outcomes. Objective: Assess the association of nurse staffing with in-hospital mortality for patients with acute myocardial infarction (AMI). Design, Setting, and Patients. Medical record review data from the 1994-1995 Cooperative Cardiovascular Project were linked with American Hospital Association data for 118,940 fee-for-service Medicare patients hospitalized with AMI. Staffing levels were represented as nurse to patient ratios categorized into quartiles for RNs and for licensed practical nurses (LPNs). Main Outcome Measures. In-hospital mortality. Results: From highest to lowest quartile of RN staffing, in-hospital mortality was 17.8%, 17.4%, 18.5%, and 20.1%, respectively (P < 0.001 for trend). However, from highest to lowest quartile of LPN staffing, mortality was 20.1%, 18.7%, 17.9%, and 17.2%, respectively P < 0.001. After adjustment for patient demographic and clinical characteristics, treatment, and for hospital volume, technology index, and teaching and urban status, patients treated in environments with higher RN staffing were less likely to die in-hospital; odds ratios (95% confidence intervals) of quartiles 4, 3, and 2 versus quartile 1 were 0.91 (0.86-0.97), 0.94 (0.88-1.00), and 0.96 (0.90-1.02), respectively. Conversely, after adjustment, patients treated in environments with higher LPN staffing were more likely to die in-hospital; odds ratios (95% confidence intervals) of quartiles 4, 3, and 2 versus quartile 1 were 1.07 (1.00-1.15), 1.02 (0.96-1.09), and 1.00 (0.94-1.07), respectively. Conclusions: Even after extensive adjustment, higher RN staffing levels were associated with lower mortality. Our findings suggest an important effect of nurse staffing on in-hospital mortality. C1 Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Nursing, Birmingham, AL 35294 USA. Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Person, SD (reprint author), Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, MT 612,1530 3rd Ave S, Birmingham, AL 35294 USA. OI Allison, Jeroan/0000-0003-4472-2112 FU AHRQ HHS [HS08843, HS09446] NR 87 TC 64 Z9 64 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2004 VL 42 IS 1 BP 4 EP 12 DI 10.1097/01.mlr.0000102369.67404.b0 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 758DP UT WOS:000187617900002 PM 14713734 ER PT J AU O'Brien, MM Shroyer, ALW Moritz, TE London, MJ Grunwald, GK Villanueva, CB Thottapurathu, LG MaWhinney, S Marshall, G McCarthy, M Henderson, WG Sethi, GK Grover, FL Hammermeister, KE AF O'Brien, MM Shroyer, ALW Moritz, TE London, MJ Grunwald, GK Villanueva, CB Thottapurathu, LG MaWhinney, S Marshall, G McCarthy, M Henderson, WG Sethi, GK Grover, FL Hammermeister, KE CA Participants VA Cooperative Study TI Relationship between processes of care and coronary bypass operative mortality and morbidity SO MEDICAL CARE LA English DT Article DE coronary bypass surgery; processes of care; perioperative mortality and morbidity; operative duration; inotropic agents; transesophageal echocardiography; hemoconcentration/ultrafiltration ID INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INDUCED MYOCARDIAL NECROSIS; CONGESTIVE-HEART-FAILURE; CONTRACTION BAND LESIONS; CARDIAC-SURGERY; ARTERY-BYPASS; RISK-FACTORS; CARDIOPULMONARY BYPASS; OUTCOMES; DYSFUNCTION AB Background: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac, Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. Methods: Data on 734 risk, process, and structure variables were collected prospectively on 3988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment., We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. Results: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting the se processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). Conclusions: Our results viewed in the context of past studies suggest the possibility that, inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Denver VA Med Ctr, Med Res Serv, Denver, CO 80220 USA. Denver VA Med Ctr, Surg Serv, Denver, CO 80220 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. San Francisco VA Med Ctr, Anesthesiol Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Anesthesiol, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Boulder, CO 80309 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Arizona, Hlth Sci Ctr, Dept Surg, Tucson, AZ 85721 USA. Pontificia Univ Catolica Chile, Dept Salud Publ, Santiago, Chile. RP Hammermeister, KE (reprint author), Denver VA Med Ctr, Cardiol Sect, 111B,1055 Clermont, Denver, CO 80220 USA. RI Marshall, Guillermo/F-2302-2011; Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 62 TC 15 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JAN PY 2004 VL 42 IS 1 BP 59 EP 70 DI 10.1097/01.mlr.0000102295.08379.57 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 758DP UT WOS:000187617900008 PM 14713740 ER PT J AU Blum, RH Raemer, DB Carroll, JS Sunder, N Felstein, DM Cooper, JB AF Blum, RH Raemer, DB Carroll, JS Sunder, N Felstein, DM Cooper, JB TI Crisis resource management training for an anaesthesia faculty: a new approach to continuing education SO MEDICAL EDUCATION LA English DT Article DE education; medical; undergraduate, methods, standards; anesthesia, standards; patient care, standards; safety; curriculum; clinical competence, standardst anaesthesia crisis resource management; anaesthesia faculty; behavioural skills; critical events; non-technical skills; patient safety; performance; teamwork ID OPERATING-ROOM AB Background Human error and system failures continue to play a substantial role in adverse outcomes in health care. Anaesthesia crisis resource management addresses many patient safety issues by teaching behavioural skills for critical events but it has not been systematically utilized to teach experienced faculty. Methods An anaesthesia crisis resource management course was created for the faculty of our medical school's anaesthesia teaching programmes. The course objectives were to understand and improve participants' proficiency in crisis resource management (CRM) skills and to learn skills for debriefing residents after critical events. Through surveys, measurement objectives assessed acceptance, utility and need for recurrent training immediately post-course. These were measured again approximately 1 year later along with self-perceived changes in the management of difficult or critical events. Results The highly rated course was well received in terms of overall course quality, realism, debriefings and didactic presentation. Course usefulness, CRM principles, debriefing skills and communication were highly rated immediately post-course and 1 year later. Approximately half of the faculty staff reported a difficult or critical event following the course; of nine self-reported CRM performance criteria surveyed all claimed improvement in their CRM non-technical skills. Conclusions A unique and highly rated anaesthesia faculty course was created; participation made the faculty staff eligible for malpractice premium reductions. Self-reported CRM behaviours in participants' most significant difficult or critical events indicated an improvement in performance. These data provide indirect evidence supporting the contention that this type of training should be more widely promoted, although more definitive measures of improved outcomes are needed. C1 Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. RP Blum, RH (reprint author), Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, 300 Longwood Ave,Bader 3, Boston, MA 02115 USA. NR 20 TC 83 Z9 84 U1 3 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD JAN PY 2004 VL 38 IS 1 BP 45 EP 55 DI 10.1046/j.1365-2923.2004.01696.x PG 11 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 761FP UT WOS:000187890900012 PM 14962026 ER PT J AU Mendez, MF AF Mendez, MF TI Dementia as a window to the neurology of art SO MEDICAL HYPOTHESES LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; CLINICAL CHARACTERISTICS; ARTISTIC CREATIVITY; SEMANTIC DEMENTIA; PREFRONTAL CORTEX; TEMPORAL VARIANT; PICKS-DISEASE AB Art is an expression of neurological function and how it organizes and interprets perception. Recent reports of changes in art performance among patients with frontotemporal dementia have provided an unexpected window to the neurology of art. They confirm that visual art is predominantly in the right hemisphere and suggest a neuroanatomical schema for artistic creativity. The right parietal region is critical for the visuospatial prerequisites of art, and the right temporal lobe integrates and interprets these percepts. The right temporal lobe appears necessary for extracting and exaggerating the essential features of an artistic composition. In contrast, the left parietal region and the left temporal lobe have inhibitory effects on artistic expression through attention to visuospatial detail and semantic labeling, respectively. Frontal-executive functions are also required for artistic expression, particularly right dorsolateral frontal initiation of a network for novelty-seeking behavior. Further study of art in dementia can profitably evaluate this proposed schema for the mechanisms of art in the brain. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Focal Type Dementias Clin, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater LA Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu NR 65 TC 29 Z9 31 U1 3 U2 15 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2004 VL 63 IS 1 BP 1 EP 7 DI 10.1016/j.mehy.2004.03.002 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 832VA UT WOS:000222294200001 PM 15193339 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI We only see what we already know - a modified Bayes' formula to explain inherent limitations of diagnostic tests SO MEDICAL HYPOTHESES LA English DT Article ID ULTRASOUND AB In medical tests involving human judgment, human testers are inclined to diagnose only symptoms and signs that they already know. The present analysis delineates the relationship between prior knowledge and test characteristics. The relationship between test outcome and a given diagnosis is generally described in terms of sensitivity and specificity. In the present analysis, this relationship is broken down into two separate contributions: First, the association between the test measure and the presence of disease and second, the association between the actual test outcome and the presence of the test measure. The second relationship describes the performance of a human tester in assessing the presence of a test measure irrespective of the disease status. Bayes' formula can be adjusted to include contributions by both relationships. The ability to increase a diagnostic probability through testing depends on a tester's familiarity with the test measure and reliability in eliciting its presence. Testing yields the most reliable results if the test measure falls well within a tester's own level of competence. Test measures outside the tester's competence level lead to tests with worse outcome than no testing at all. Published by Elsevier Ltd. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 13 TC 5 Z9 5 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2004 VL 63 IS 4 BP 759 EP 763 DI 10.1016/j.mehy.2004.03.027 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 855BD UT WOS:000223947000034 PM 15325029 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Process and accomplishment in academic medicine SO MEDICAL HYPOTHESES LA English DT Article AB Medical academic systems are characterized by interplay between accomplishment and process. The term accomplishment refers to fulfillment of the system's original goats, such as education, research and medical care, whereas the term process refers to the culture and structure, which are developed to pursue these goals. A mathematical model is developed to simulate the mechanisms that govern growth of medical systems over time. Because system performance is easier to measure by process than accomplishment, in the long run investments in growth are shifted away from accomplishment towards process. In all aging medical systems alike, the proportion of process tends to increase at the expense of accomplishment. Published by Elsevier Ltd. C1 Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 9 TC 3 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2004 VL 62 IS 6 BP 1006 EP 1011 DI 10.1016/j.mehy.2004.01.005 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 825FI UT WOS:000221741000032 PM 15142665 ER PT S AU Tsai, A Wells, W Warfield, SK Willsky, A AF Tsai, A Wells, W Warfield, SK Willsky, A BE Barillot, C Haynor, DR Hellier, P TI Level set methods in an EM framework for shape classification and estimation SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 1, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes AB In this paper, we propose an Expectation-Maximization (EM) approach to separate a shape database into different shape classes, while simultaneously estimating the shape contours that best exemplify each of the different shape classes. We begin our formulation by employing the level set function as the shape descriptor. Next, for each shape class we assume that there exists an unknown underlying level set function whose zero level set describes the contour that best represents the shapes within that shape class. The level set function for each example shape is modeled as a noisy measurement of the appropriate shape class's unknown underlying level set function. Based on this measurement model and the judicious introduction of the class labels as hidden data, our EM formulation calculates the labels for shape classification and estimates the shape contours that best typify the different shape classes. This resulting iterative algorithm is computationally efficient, simple, and accurate. We demonstrate the utility and performance of this algorithm by applying it to two medical applications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Tsai, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RI Warfield, Simon/B-3352-2009; OI Warfield, Simon/0000-0002-7659-3880 NR 11 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22976-0 J9 LECT NOTES COMPUT SC PY 2004 VL 3216 BP 1 EP 9 PN 1 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ60 UT WOS:000224321100001 ER PT S AU Tan, KH Kobler, J Dietz, P Raskar, R Feris, RS AF Tan, KH Kobler, J Dietz, P Raskar, R Feris, RS BE Barillot, C Haynor, DR Hellier, P TI Shape-enhanced surgical visualizations and medical illustrations with multi-flash imaging SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes AB We present a novel approach for enhancing images and video used in endoscopic surgery so that they are better able to convey shape. Our method is based on multi-flash imaging, in which multiple light sources are strategically positioned to cast shadows along depth discontinuities. We describe designs for achieving multi-flash imaging using multiple endoscopes as well as in single endoscopes. Multi-flash photography can also be used for creating medical illustrations. By highlighting the detected edges, suppressing unnecessary details, or combining features from multiple images, the resulting images convey more clearly the 3D structure of the subject. The method is easy to implement both in software and hardware, and can operate in realtime. C1 Univ Illinois, Champaign, IL 61820 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Mitsubishi Elect Res Labs, Cambridge, MA USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Tan, KH (reprint author), Univ Illinois, Champaign, IL 61820 USA. EM tankh@vision.ai.uiuc.edu; james_kobler@meei.harvard.edu; dietz@merl.com; raskar@merl.com; rferis@cs.ucsb.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 438 EP 445 PN 2 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400054 ER PT S AU Brewer, J Betke, M Gierga, DP Chen, GTY AF Brewer, J Betke, M Gierga, DP Chen, GTY BE Barillot, C Haynor, DR Hellier, P TI Real-time 4D tumor tracking and modeling from internal and external fiducials in fluoroscopy SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes ID RADIOTHERAPY; MOTION; LUNG; HEARTBEAT; THERAPY; CANCER AB Fluoroscopy is currently used in treatment planning for patients undergoing radiation therapy. Radiation oncologists would like to maximize the amount of dose the tumor receives and minimize the amount delivered to the surrounding tissues. During treatment, patients breathe freely and so the tumor location will not be fixed. This makes calculating the amount of dose delivered to the tumor, and verifying that the tumor actually receives that dose, difficult. We describe a correlation-based method of tracking the two-dimensional (2D) motion of internal markers (surgical clips) placed around the tumor. We established ground truth and evaluated the accuracy of the tracker for 10 data sets of 5 patients. The root mean squared error in estimating 2D marker position was 0.47 mm on average. We also developed a method to model the average and maximum three-dimensional (3D) motion of the clips given two orthogonal fluoroscopy videos of the same patients that were taken sequentially. On average, the error was 3.0 mm for four pairs of trajectories. If imaging is possible during treatment, such motion models may be used for beam guided radiation; otherwise, they may be correlated to a set of external markers for use in respiratory gating. C1 Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brewer, J (reprint author), Boston Univ, Dept Comp Sci, Boston, MA 02215 USA. EM johannab@cs.bu.edu NR 15 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 594 EP 601 PN 2 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400073 ER PT S AU Cardenas, VA Studholme, C AF Cardenas, VA Studholme, C BE Barillot, C Haynor, DR Hellier, P TI Co-analysis of maps of atrophy rate and atrophy state in neurodegeneration SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes ID VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; ANATOMICAL MRI; BRAIN ATROPHY; DEFORMATION; VALIDATION; VOLUMETRY; DEMENTIA; AD AB The variability in atrophy rate in patients with neurodegenerative disease can be partially explained by disease stage. Since atrophy state (baseline scan tissue volume) correlates with cognitive impairment and disease stage, we use local atrophy state as a covariate in the analysis of local atrophy rate. A general linear model with a spatially varying dependent variable was employed to study the effects of disease over the brain. An efficient method of solving this spatially varying model was developed, implemented, and applied to maps of atrophy state and rate derived from serial MRI data of 13 Semantic Dementia (SD) and 13 control subjects. Our results demonstrate that group differences in atrophy rate are affected by the inclusion of atrophy state in the model. Specifically, estimated contrasts in atrophy rate between controls and SD in the left temporal lobe white matter increased when the local rate was covaried for atrophy state. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Cardenas, VA (reprint author), Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 680 EP 687 PN 2 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400083 ER PT S AU Zou, KH Greve, DN Wang, M Pieper, SD Warfield, SK White, NS Vangel, MG Kikinis, R Wells, WM Birn, F AF Zou, KH Greve, DN Wang, M Pieper, SD Warfield, SK White, NS Vangel, MG Kikinis, R Wells, WM Birn, F BE Barillot, C Haynor, DR Hellier, P TI A prospective multi-institutional study of the reproducibility of fMRI: A preliminary report from the Biomedical Informatics Research Network SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes ID CHARACTERISTIC ROC CURVES; TEST-RETEST RELIABILITY; STATISTICAL VALIDATION; FUNCTIONAL MRI; WORKING-MEMORY; SEGMENTATION AB Functional magnetic resonance imaging (fMRI) has significantly contributed to understanding both normal and diseased human brains. Variability often exists in the magnitude, spatial distribution, and statistical significance of the resulting fMRI maps due to differences in equipment and other site-specific differences. In addition, because of costly imaging, demanding tasks, and analytical burden, understanding the effect of these differences may help develop an efficient pooling and comparison mechanism. Prospective multi-institutional repeated fMRI data were acquired recently in the first phase of the extensive Functional Imaging Research of Schizophrenia Testbed study, sponsored by the Biomedical Informatics Research Network (BIRN) in the US. Five "human phantoms," who were right-handed healthy males, were included in the study. These subjects repeatedly performed the same sensory-motor task over 10 of the 11 study sites on 2 separate visits per site. The effects of factors such as subject, study site, field strength, vendor, K-space, visit, and repeated run on the fMRI reproducibility were evaluated. Over 4 repeated runs per visit at each site, at a given binarizing activation threshold, we first calculated a three-dimensional (3D) brain activation map via an intial expectation and maximization (EM) algorithm. Site-to-site differences were then assessed based on a second-level hiearchical EM. Against the estimated gold standard of the 3D activation map, activation percentage, sensitivity, specificity, and receiver operating characteristic curves were then estimated using voxel counts. A statistical regression model was used to. assess the significance of accuracy predictors with p-values generated in order to explain those factors contributing towards the variability in repeated brain activation maps. C1 Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Computat Radiol Lab, Boston, MA 02115 USA. RP Zou, KH (reprint author), Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. EM zou@bwh.harvard.edu; greve@nmr.mgh.harvard.edu; mwang@bwh.harvard.edu; pieper@bwh.harvard.edu; warfield@bwh.harvard.edu; nwhite@nmr.mgh.harvard.edu; vangel@nmr.mgh.harvard.edu; kikinis@bwh.harvard.edu; sw@nmr.mgh.harvard.edu RI Warfield, Simon/B-3352-2009; OI Warfield, Simon/0000-0002-7659-3880 NR 17 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 769 EP 776 PN 2 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400094 ER PT S AU Bouix, S Ungar, L Dickey, CC McCarley, RW Shenton, ME AF Bouix, S Ungar, L Dickey, CC McCarley, RW Shenton, ME BE Barillot, C Haynor, DR Hellier, P TI Evaluating automatic brain tissue classifiers SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes AB We present a quantitative evaluation of MR brain images segmentation. Five classifiers were tested. The task was to classify an MR image into four different classes: background, cortical spinal fluid, gray matter and white matter. The performance was rated by first estimating a ground truth (EGT) using STAPLE and then analyzing the volume differences as well as the Dice similarity measure between each of the 5 classifiers. C1 Harvard Univ, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. Boston VA Healthcare Syst, Dept Psychiat, Boston, MA USA. RP Harvard Univ, Sch Med, Surg Planning Lab, Boston, MA 02115 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 1038 EP 1039 PN 2 PG 2 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400127 ER PT S AU Wu, T Zhang, JM Moore, R Rafferty, E Kopans, D Meleis, W Kaeli, D AF Wu, T Zhang, JM Moore, R Rafferty, E Kopans, D Meleis, W Kaeli, D BE Yaffe, MJ Flynn, MJ TI Digital tomosynthesis mammography using a parallel maximum likelihood reconstruction method SO MEDICAL IMAGING 2004: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2004 Conference CY FEB 17-19, 2004 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE tomosynthesis; breast imaging; 3-D reconstruction; parallel computation; iterative reconstruction ID FILTERED BACKPROJECTION AB A parallel reconstruction method, based on an iterative maximum likelihood (ML) algorithm, is developed to provide fast reconstruction for digital tomosynthesis mammography. Tomosynthesis mammography acquires 11 low-dose projections of a breast by moving an x-ray tube over a 50degrees angular range. In parallel reconstruction, each projection is divided into multiple segments along the chest-to-nipple direction. Using the 11 projections, segments located at the same distance from the chest wall are combined to compute a partial reconstruction of the total breast volume. The shape of the partial reconstruction forms a thin slab, angled toward the x-ray source at a projection angle 0degrees. The reconstruction of the total breast volume is obtained by merging the partial reconstructions. The overlap region between neighboring partial reconstructions and neighboring projection segments is utilized to compensate for the incomplete data at the boundary locations present in the partial reconstructions. A serial execution of the reconstruction is compared to a parallel implementation, using clinical data. The serial code was run on a PC with a single PentiumIV 2.2GHz CPU. The parallel implementation was developed using MPI and run on a 64-node Linux cluster using 800MHz Itanium CPUs. The serial reconstruction for a medium-sized breast (5cm thickness, 11 cm chest-to-nipple distance) takes 115 minutes, while a parallel implementation takes only 3.5 minutes. The reconstruction time for a larger breast using a serial implementation takes 187 minutes, while a parallel implementation takes 6.5 minutes. No significant differences were observed between the reconstructions produced by the serial and parallel implementations. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wu, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 15 TC 29 Z9 29 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5281-5 J9 P SOC PHOTO-OPT INS PY 2004 VL 5368 BP 1 EP 11 DI 10.1117/12.53446 PN 1&2 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BAF46 UT WOS:000222012700002 ER PT S AU Ottensmeyer, MP Kerdok, AE Howe, RD Dawson, SL AF Ottensmeyer, MP Kerdok, AE Howe, RD Dawson, SL BE Cotin, S Metaxas, D TI The effects of testing environment on the viscoelastic properties of soft tissues SO MEDICAL SIMULATION, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT International Symposium on Medical Simulation CY JUN 17-18, 2004 CL Cambridge, MA SP USA Telemed & Adv Technol Res Ctr ID LIVER-TRANSPLANTATION; PIG AB Mechanical properties of biological tissues are needed for accurate surgical simulation and diagnostic purposes. These properties change postmortem due to alterations in both the environmental and physical conditions of the tissue. Despite these known changes, the majority of existing data have been acquired ex vivo due to ease of testing. This study seeks to quantify the effects of testing conditions on the measurements obtained when testing the same tissue in the same locations with two different instruments over time. We will discuss measurements made with indentation probes on whole porcine livers in vivo, ex vivo with a perfusion system that maintains temperature, hydration, and physiologic pressure, ex vivo unperfused, and untreated excised lobes. The data show >50% differences in steady state stiffness between tissues in vivo and unperfused, but only 17% differences between in vivo and perfused tests. Variations also exist in the time-domain and frequency domain responses between all test conditions. C1 CIMIT, Simulat Grp, Cambridge, MA 02139 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ottensmeyer, MP (reprint author), CIMIT, Simulat Grp, 65 Landsdowne St,Ste 142, Cambridge, MA 02139 USA. EM ottensmeyer.mark@mgh.harvard.edu; kerdok@fas.harvard.edu; howe@deas.harvard.edu; sdawson@partners.org NR 19 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22186-7 J9 LECT NOTES COMPUT SC PY 2004 VL 3078 BP 9 EP 18 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BAI81 UT WOS:000222468800002 ER PT J AU Zhao, M Weissleder, R AF Zhao, M Weissleder, R TI Intracellular cargo delivery using tat peptide and derivatives SO MEDICINAL RESEARCH REVIEWS LA English DT Article DE tat peptide; transduction; cell permeable peptides ID VON-HIPPEL-LINDAU; CELL-PENETRATING PEPTIDES; ARGININE-RICH PEPTIDES; HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN BASIC DOMAIN; MOLECULAR TRANSPORTERS; DENDRITIC CELLS; FUSION PROTEIN; DRUG-DELIVERY; MEMBRANE TRANSLOCATION AB Efficient delivery of therapeutic and diagnostic agents across the plasma membrane is crucial in developing novel therapies. Membrane permeating peptides, in particular HIV-1 tat peptide and its derivatives, have enabled the intracellular delivery of cargos of various sizes and physicochemical properties. This review summarizes the current knowledge of tat-derived cell permeating peptides in the transduction of exogenous molecules/complexes. (C) 2003 Wiley Periodicals, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Rm 5404,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P50 CA86355, T32 CA79443] NR 83 TC 127 Z9 127 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD JAN PY 2004 VL 24 IS 1 BP 1 EP 12 DI 10.1002/med.10056 PG 12 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758DN UT WOS:000187617700001 PM 14595670 ER PT S AU Lester, WT Grant, R Barnett, GO Chueh, H AF Lester, WT Grant, R Barnett, GO Chueh, H BE Fieschi, M Coiera, E Li, YCJ TI Facilitated lipid management using interactive e-mail: Preliminary results of a randomized controlled trial SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE clinical guidelines; decision support; disease management; hyperlipidemia ID CARE; PHYSICIANS; GUIDELINES; SYSTEMS AB We describe the design and implementation of a clinical decision support system for ambulatory hyperlipidemia management. Despite readily available and evidence-based guidelines, cholesterol control remains persistently sub-optimal in clinical practice. "FastTrack" is an integrated, multi-faceted informatics tool to reduce barriers to effective cholesterol management by proactively integrating pertinent clinical information, evidence-based decision support and a simple means to act via a single FastTrack e-mail. We tested the intervention in a randomized, controlled trial involving 15 physicians and 256 patients. In an interim analysis, we found that physicians on average were able to review and act upon 9 patient e-mails in less than 15 minutes. Significantly more intervention patients were initiated on a statin therapy or had their dose increased (15.3% vs. 2.3%, p < 0.001). Impact of the intervention on LDL levels will be assessed at trial completion. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Lester, WT (reprint author), Comp Sci Lab, 5th Floor,50 Staniford St, Boston, MA 02114 USA. OI Lester, William/0000-0003-4086-9280; Grant, Richard/0000-0002-6164-8025 FU NLM NIH HHS [2T15 LM 07092-11] NR 12 TC 9 Z9 9 U1 1 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 232 EP 236 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300047 PM 15360809 ER PT S AU Barnett, GO Barry, MJ Robb-Nicholson, C Morgan, M AF Barnett, GO Barry, MJ Robb-Nicholson, C Morgan, M BE Fieschi, M Coiera, E Li, YCJ TI Overcoming information overload: an information system for the primary care physician SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE database management systems; evidence-based medicine; decision making; computer assisted ID CLINICAL INFORMATION; NEEDS; MET AB Primary Care Office InSite (PCOI) is a Web-based intranet application that provides ready access to a collection of information useful in primary care. The PCOI Web site was developed by, and is widely used within, the Massachusetts General Hospital (MGH) and its affiliated community practices. Over 1600 users logged 60,000 separate sessions in the past year. The site contains clinical practice guidelines, patient educational material, drug prescription and cost information and referral information, all designed for use during routine patient care activity. A continuing and dynamic collaboration between the users and developers of the system, just-in-time access and a 'one-stop portal' to a variety of resources have resulted in a very high approval rating by the users. This paper discusses the important characteristics of the Web site, specific functions that improve the work flow of the practicing clinician, and limitations of the present implementation. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA USA. RP Barnett, GO (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. NR 9 TC 5 Z9 5 U1 1 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 273 EP 276 PG 4 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300055 PM 15360817 ER PT S AU Brown, SH Elkin, PL Rosenbloom, ST Husser, C Bauer, BA Lincoln, MJ Carter, J Erlbaum, M Tuttle, MS AF Brown, SH Elkin, PL Rosenbloom, ST Husser, C Bauer, BA Lincoln, MJ Carter, J Erlbaum, M Tuttle, MS BE Fieschi, M Coiera, E Li, YCJ TI VA National Drug File Reference Terminology: A cross-institutional content coverage study SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE vocabulary; controlled; information storage and retrieval; information theory ID VOCABULARIES AB Background: Content coverage studies provide valuable information to potential users of terminologies. We detail the VA National Drug File Reference Terminology's (NDF-RT) ability to represent dictated medication list phrases from the Mayo Clinic. NDF-RT is a description logic-based resource created to support clinical operations at one of the largest healthcare providers in the US. Methods: Medication list phrases were extracted from dictated patient notes from the Mayo Clinic. Algorithmic mappings to NDF-RT using the SmartAccess Vocabulary Server (SAVS) were presented to two non-VA physicians. The physicians used a terminology browser to determine the accuracy of the algorithmic mapping and the content coverage of NDF-RT Results: The 509 extracted documents on 300 patients contained 847 medication concepts in medication lists. NDF-RT covered 97.8% of concepts. Of the 18 phrases that NDF-RT did not represent, 10 were for OTCs and food supplements, 5 were for prescription medications, and 3 were missing synonyms. The SA VS engine properly mapped 773 of 810 phrases with an overall sensitivity (precision) was 95.4% and positive predictive value (recall) of 99.9%. Conclusions: This study demonstrates that NDF-RT has more general utility than its initial design parameters dictated. C1 US Dept Vet Affairs, Nashville, TN USA. RP Brown, SH (reprint author), 1310 24th Ave S, Nashville, TN 37212 USA. NR 20 TC 21 Z9 21 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 477 EP 481 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300096 PM 15360858 ER PT S AU Ollendieck, M Chueh, H AF Ollendieck, M Chueh, H BE Fieschi, M Coiera, E Li, YCJ TI Transforming clinical dictation into structured notes in an ambulatory care practice SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE structured data; electronic medical record; dictation; transcription AB Structured clinical encounter notes offer many advantages compared to free text notes. However, cost and other issues limit their widespread use. At our institution, the electronic medical record (EMR) used by an Internal Medicine practice was designed years ago to utilize structured data. This paper describes a technique to improve the process by which structured notes are dictated and transcribed. We outsourced transcription services and then passed the files through parsing software to structure the data to the granularity required for our database. Software was built to handle all aspects of the process including file validation, parsing, and review. During our pilot project, more than 10, 000 notes were parsed, reviewed and uploaded into the EMR. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Ollendieck, M (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. FU NLM NIH HHS [2T15 LM 07092-11] NR 7 TC 0 Z9 0 U1 0 U2 1 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 668 EP 672 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300135 PM 15360897 ER PT S AU Namini, AH Berkowicz, DA Kohane, IS Chueh, H AF Namini, AH Berkowicz, DA Kohane, IS Chueh, H BE Fieschi, M Coiera, E Li, YCJ TI A submission model for use in the indexing, searching, and retrieval of distributed pathology case and tissue specimens SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE pathology; distributed systems; HIPAA AB This paper describes the Shared Pathology Informatics Network (SPIN) submission model for uploading de-identifted XML annotations of pathology case and specimen information to a distributed peer-to-peer network architecture. SPIN use cases, architecture, and technologies, as well as pathology information design is described. With the architecture currently in use by six member institutions, SPIN appears to be a viable, secure methodology to submit pathology information for query and specimen retrieval by investigators. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. RP Namini, AH (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. FU NCI NIH HHS [U01 CA91429] NR 5 TC 4 Z9 4 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 1264 EP 1267 PG 4 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300256 PM 15361017 ER PT J AU Desindes, S AF Desindes, S TI Treatment of vasomotor symptoms during perimenopause SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; MENOPAUSAL HOT FLASHES; QUALITY-OF-LIFE; MEDROXYPROGESTERONE ACETATE; BREAST-CANCER; WOMEN; TRANSITION; ESTRADIOL; BONE C1 Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. RP Desindes, S (reprint author), Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2004 VL 11 IS 1 BP 2 EP 4 DI 10.1097/01.GME.0000104155.19923.A0 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 765FD UT WOS:000188255700002 PM 14716175 ER PT J AU Eckler, K AF Eckler, K TI Are all estrogens created equal? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; ESTRIOL; RISK; INCONTINENCE; ESTRADIOL; MENOPAUSE; THERAPY; CANCER C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Eckler, K (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2004 VL 11 IS 1 BP 7 EP 8 DI 10.1097/01.GME.0000103023.32049.FD PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 765FD UT WOS:000188255700004 PM 14716177 ER PT J AU Shouse, MN Scordato, JC Farber, PR AF Shouse, MN Scordato, JC Farber, PR TI Sleep and arousal mechanisms in expeirjmental epilepsy: Epileptic components of NREM and antiepileptic components of REM sleep SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE sleep; epilepsy; animal models; cats; amygdala kindling; penicillin epilepsy ID AMYGDALA-KINDLED KITTENS; SEIZURES; AUTISM AB Neural generators related to different sleep components have different effects on seizure discharge. These sleep-related systems can provoke seizure discharge propagation during nonrapid eye movement (NREM) sleep and can suppress propagation during REM sleep. Experimental manipulations of discrete physiological components were conducted in feline epilepsy models, mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy. The sleep-wake state distribution of seizures was quantified before and after discrete lesions, Systemic and localized drug administration, and/or photic stimulation, as well as in relation to microdialysis of norepinephrine. We found that (1) neural generators of synchronous EEG oscillations-including tonic background slow waves and phasic "arousal" events (sleep EEG transients such as sleep spindles and k-complexes)-combine to promote electrographic seizure propagation during NREM and drowsiness, and antigravity muscle tone permits seizure-related movement; (2) neural generators of asynchronous neuronal discharge patterns reduce electrographic seizures during alert waking and REM sleep, and skeletal motor paralysis blocks seizure-related movement during REM; (3) there are a number of similarities between amygdala-kindled kittens and children with Landau-Kleffner Syndrome (LKS) that suggest a link among seizures, sleep disorders, and behavioral abnormalities/regression. Published 2004 Wiley-Liss, Inc. C1 VA Greater Los Angeles Hlth Care Syst, Sleep Disturbance Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA USA. RP Shouse, MN (reprint author), 2242 S Bentley Ave, Los Angeles, CA 90064 USA. EM wshouse@ucla.edu NR 23 TC 16 Z9 16 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2004 VL 10 IS 2 BP 117 EP 121 DI 10.1002/mrdd.20022 PG 5 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 857KL UT WOS:000224115100008 PM 15362167 ER PT J AU Wade, BK Burrus, JK Balkovetz, DF AF Wade, BK Burrus, JK Balkovetz, DF TI Hepatocyte growth factor inhibits intrinsic antibacterial activity of Madin-Darby canine kidney cells SO MICROBES AND INFECTION LA English DT Article DE Escherichia coli; uropathogenic; renal epithelia; defensins; hepatocyte growth factor ID ACUTE-RENAL-FAILURE; FACTOR ALTERS; MONOLAYERS; SUSCEPTIBILITY; EXPRESSION; COMPLEXES; POLARITY; TISSUES AB We investigated whether or not polarized renal epithelial cells produce antibacterial factors, which aid in host defense at the cell surface of renal epithelium. A model of polarized Madin-Darby canine kidney (MDCK) epithelial cells grown on filters was used to test for the presence of apically or basolaterally secreted factors on the growth of non-virulent (XLI-Blue) and uropathogenic (J96) strains of Escherichia coli (E. coli). Growth of both XLI-Blue and J96 strains of E. coli in medium on the apical and basolateral surface of MDCK cells was inhibited as compared to bacterial growth in medium not exposed to MDCK cells. The inhibition of bacterial growth was similar in both apical and basolateral surface medium. Pretreatment of MDCK cells with hepatocyte growth factor (HGF) blunted the inhibition of XLI-Blue and J96 growth in apical and basolateral surface medium as compared to growth in medium on the surfaces of untreated MDCK cells. Immunofluorescent analysis demonstrated the presence of P-defensin isoforms 1-3 in MDCK cells, with isoform I being the most prevalent form observed. HGF treatment reduced the amount of immunoreactive beta-defensin-1 in MDCK cells. These data demonstrate that polarized renal epithelium produce antibacterial factors. The renotropic growth factor HGF inhibits these antibacterial factors. beta-defensins may contribute to this antibacterial activity and play an important role in renal epithelial resistance to bacterial infections. (C) 2003 Elsevier SAS. All rights reserved. C1 Univ Alabama, Dept Surg, Birmingham, AL USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Balkovetz, DF (reprint author), 668 LHRB,1530 3rd Ave, Birmingham, AL 35294 USA. EM balkovet@uab.edu NR 21 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2004 VL 6 IS 1 BP 51 EP 57 DI 10.1016/j.micinf.2003.10.008 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 770HR UT WOS:000188717600007 PM 14738893 ER PT J AU Nazzal, JA Johnson, TS Gordon, CR Randolph, MA Lee, WPA AF Nazzal, JA Johnson, TS Gordon, CR Randolph, MA Lee, WPA TI Heterotopic limb allotransplantation model to study skin rejection in the rat SO MICROSURGERY LA English DT Article ID COMPOSITE TISSUE ALLOTRANSPLANTATION; OF-THE-LITERATURE; ALLOGRAFT TOLERANCE; CATTLE TWINS; INDUCTION; TRANSPLANTATION; FAILURE; CELLS; SWINE AB Current rodent models for investigation of limb allotransplantation typically utilize orthotopic whole-limb transplantation, a morbid and time-consuming procedure. Our objective was to design a less morbid rat model to explore the immunological obstacles of limb transplantation, and particularly skin. Twenty lower hindlimbs from 10 donors were transplanted into a heterotopic subcutaneous position into 20 animals (10 isogeneic and 10 allogeneic). Each group was further subdivided to include animals with (n = 5) and without (n = 5) a skin paddle for observation of cutaneous signs of rejection. All grafts in the isogeneic group survived for 100 days, i.e., the endpoint of the study. Allogeneic transplants rejected their allografts at a mean of 12.8 days (with skin) and 20.6 days (without). Our heterotopic limb transplantation model takes less time and is less stressful to the animals, while allowing for early observation of graft skin rejection, when compared to orthotopic whole-limb transplantation. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, ACC 4,Suite 453,25 Fruit St, Boston, MA 02114 USA. EM Randolph.mark@mgh.harvard.edu NR 26 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2004 VL 24 IS 6 BP 448 EP 453 DI 10.1002/micr.20062 PG 6 WC Surgery SC Surgery GA 877RZ UT WOS:000225589100007 PM 15499552 ER PT J AU Kilbourne, AM Schulberg, HC Post, EP Rollman, BL Belnap, BH Pincus, HA AF Kilbourne, AM Schulberg, HC Post, EP Rollman, BL Belnap, BH Pincus, HA TI Translating evidence-based depression management services to community-based primary care practices SO MILBANK QUARTERLY LA English DT Article DE patient care management; delivery of health care; integrated quality of care; depressive disorder; depression ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; QUALITY IMPROVEMENT; MAJOR DEPRESSION; DISEASE MANAGEMENT; COLLABORATIVE CARE; COST-EFFECTIVENESS; CHRONIC ILLNESS; HEALTH; INTERVENTION AB Randomized controlled trials have demonstrated the efficacy and cost-effectiveness of using treatment models for major depression in primary care settings. Nonetheless, translating these models into enduring changes in routine primary care has proved difficult. Various health system and organizational barriers prevent the integration of these models into primary care settings. This article discusses barriers to introducing and sustaining evidence-based depression management services in community-based primary care practices and suggests organizational and financial solutions based on the Robert Wood Johnson Foundation Depression in Primary Care Program. It focuses on strategies to improve depression care in medical settings based on adaptations of the chronic care model and discusses the challenges of implementing evidence-based depression care given the structural, financial, and cultural separation between mental health and general medical care. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Ctr Hlth Equ Res & Promot, 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM Amy.Kilbourne@med.va.gov FU NIMH NIH HHS [K23-MH01879, K23 MH001879] NR 48 TC 66 Z9 67 U1 2 U2 6 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0887-378X J9 MILBANK Q JI Milbank Q. PY 2004 VL 82 IS 4 BP 631 EP 659 DI 10.1111/j.0887-378X.2004.00326.x PG 29 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 880MQ UT WOS:000225794300002 PM 15595945 ER PT J AU Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Chan, HH Brugge, WR Shimizu, M AF Lauwers, GY Ban, S Mino, M Ota, S Matsumoto, T Arai, S Chan, HH Brugge, WR Shimizu, M TI Endoscopic mucosal resection for gastric epithelial neoplasms: a study of 39 cases with emphasis on the evaluation of specimens and recommendations for optimal pathologic analysis SO MODERN PATHOLOGY LA English DT Article DE endoscopic mucosal resection; stomach; dysplasia; early gastric cancer; therapy ID PROGNOSTIC-FACTORS; CANCER; ULTRASONOGRAPHY; DYSPLASIA; CARCINOMA AB Endoscopic mucosal resection of gastric neoplasms is a curative technique that avoids surgery and its potential complications. Infrequently performed in the West, the limitations, pitfalls and challenges provided by this new therapeutic modality are not well known by general surgical pathologists. We evaluated a series of 39 endoscopic mucosal resections and assessed the correlation between original biopsies and final diagnoses, depth of excision, status of deep and lateral margins, artifactual changes and recurrence rate. The tumors consisted of 24 intramucosal carcinomas, six high-grade dysplasias, eight low-grade dysplasias and one submucosal invasive carcinoma. The preresection diagnoses corresponded to the final evaluation in 63% of the cases with previous biopsies. In 37% of the cases, the biopsies under-diagnosed the neoplasia. The rate of positive margins was 38%. Iatrogenic changes, that is, intramucosal hemorrhage and electrodiathermic burn, were noted in 44% of the cases but hindered the pathologic evaluation in only 10% of the cases. Persistence or recurrence was observed in only seven cases and there was no progression to advanced adenocarcinoma. Based on our experience, we offer some recommendations in order to provide optimal pathologic analysis of endoscopic mucosal resection specimens. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Saitama Med Sch, Dept Internal Med 5, Moroyama, Saitama, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan. Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Saitama Med Sch, Dept Pathol, Moroyama, Saitama, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, WRN 2,55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 29 TC 22 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2004 VL 17 IS 1 BP 2 EP 8 DI 10.1038/modpathol.3800012 PG 7 WC Pathology SC Pathology GA 773KE UT WOS:000188922300002 PM 14631370 ER PT J AU Rodriguez, TA Sparrow, DB Scott, AN Withington, SL Preis, JI Michalicek, J Clements, M Tsang, TE Shioda, T Beddington, RSP Dunwoodie, SL AF Rodriguez, TA Sparrow, DB Scott, AN Withington, SL Preis, JI Michalicek, J Clements, M Tsang, TE Shioda, T Beddington, RSP Dunwoodie, SL TI Cited1 is required in trophoblasts for placental development and for embryo growth and survival SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PRIMORDIAL GERM-CELLS; X-CHROMOSOME INACTIVATION; MOUSE INTERSPECIFIC HYBRIDS; TARGETED DISRUPTION; GENE-EXPRESSION; FEMALE MOUSE; MICE LACKING; ADULT LIFE; CARDIOVASCULAR-DISEASE; NUCLEAR-PROTEIN AB Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors alpha and beta, TFAP2, and CBP/p300. It is expressed in a restricted manner in the embryo as well as in extraembryonic tissues during embryonic development. In this study we report the engineering of a loss-of-function Cited1 mutation in the mouse. Cited1 null mutants show growth restriction at 18.5 days postcoitum, and most of them die shortly after birth. Half the heterozygous females, i.e., those that carry a paternally inherited wild-type Cited1 allele, are similarly affected. Cited1 is normally expressed in trophectoderm-derived cells of the placenta; however, in these heterozygous females, Cited1 is not expressed in these cells. This occurs because Cited1 is located on the X chromosome, and thus the wild-type Cited1 allele is not expressed because the paternal X chromosome is preferentially inactivated. Loss of Cited1 resulted in abnormal placental development. In mutants, the spongiotrophoblast layer is irregular in shape and enlarged while the labyrinthine layer is reduced in size. In addition, the blood spaces within the labyrinthine layer are disrupted; the maternal sinusoids are considerably larger in mutants, leading to a reduction in the surface area available for nutrient exchange. We conclude that Cited1 is required in trophoblasts for normal placental development and subsequently for embryo viability. C1 Victor Chang Cardiac Res Inst, Dev Biol Program, Darlinghurst, NSW 2010, Australia. Victor Chang Cardiac Res Inst, Mol Cardiol Program, Darlinghurst, NSW 2010, Australia. Natl Inst Med Res, Mammalian Dev Div, London NW7 1AA, England. Univ New S Wales, Dept Biotechnol & Biomol Sci, Sydney, NSW, Australia. Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA USA. RP Dunwoodie, SL (reprint author), Victor Chang Cardiac Res Inst, Dev Biol Program, 384 Victoria St, Darlinghurst, NSW 2010, Australia. RI Sparrow, Duncan/B-3994-2008; OI Sparrow, Duncan/0000-0002-1141-6613; Dunwoodie, Sally/0000-0002-2069-7349 FU NCI NIH HHS [R01 CA082230, R01-CA82230] NR 79 TC 51 Z9 52 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 1 BP 228 EP 244 DI 10.1128/MCB.24.1.228-244.2004 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757CL UT WOS:000187531200021 PM 14673158 ER PT J AU Chen, D Mauvais-Jarvis, F Bluher, M Fisher, SJ Jozsi, A Goodyear, LJ Ueki, K Kahn, CR AF Chen, D Mauvais-Jarvis, F Bluher, M Fisher, SJ Jozsi, A Goodyear, LJ Ueki, K Kahn, CR TI P50 alpha/p55 alpha phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID P85 ALPHA-GENE; REGULATORY SUBUNIT; PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-TRANSPORT; PI 3-KINASE; P85-ALPHA; LACKING; MUSCLE; OVEREXPRESSION; HYPOGLYCEMIA AB Class la phosphoinositide (PI) 3-kinases are heterodimers composed of a regulatory and a catalytic subunit and are essential for the metabolic actions of insulin. In addition to p85alpha and p85beta, insulin-sensitive tissues such as fat, muscle, and liver express the splice variants of the pik3r1 gene, p50alpha and p55alpha. To define the role of these variants, we have created mice with a deletion of p50alpha and p55a by using homologous recombination. These mice are viable, grow normally, and maintain normal blood glucose levels but have lower fasting insulin levels. Results of an insulin tolerance test indicate that p50alpha/p55alpha knockout mice have enhanced insulin sensitivity in vivo, and there is an increase in insulin-stimulated glucose transport in isolated extensor digitorum longus muscle tissues and adipocytes. In muscle, loss of p50alpha/p55alpha results in reduced levels of insulin-stimulated insulin receptor substrate 1 (IRS-1) and phosphotyrosine-associated PI 3-kinase but enhanced levels of IRS-2-associated PI 3-kinase and Akt activation, whereas in adipocytes levels of both insulin-stimulated PI 3-kinase and Akt are unchanged. Despite this, adipocytes of the knockout mice are smaller and have increased glucose uptake with altered glucose metabolic pathways. When treated with gold thioglucose, p50alpha/p55alpha knockout mice become hyperphagic like their wild-type littermates. However, they accumulate less fat and become mildly less hyperglycemic and markedly less hyperinsulinemic. Taken together, these data indicate that p50alpha and p55alpha play an important role in insulin signaling and action, especially in lipid and glucose metabolism. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK055545, DK55545-04] NR 24 TC 58 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 1 BP 320 EP 329 DI 10.1128/MCB.24.1.320-329.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757CL UT WOS:000187531200028 PM 14673165 ER PT J AU Lu, J Pazin, MJ Ravid, K AF Lu, J Pazin, MJ Ravid, K TI Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MEGAKARYOCYTE-SPECIFIC EXPRESSION; HISTONE TAIL DOMAINS; TRANSCRIPTION FACTORS; REMODELING FACTOR; NUCLEOSOMAL DNA; IN-VIVO; HIV-1 ENHANCER; MPL LIGAND; PROMOTER; COMPLEX AB Ets-1 is important for transcriptional regulation in several hematopoietic lineages, including megakaryocytes. Some transcription factors bind to naked DNA and chromatin with different affinities, while others do not. In the present study we used the megakaryocyte-specific promoters platelet factor 4 (PF4), and glycoprotein IIb (GPIIb) as model systems to explore the properties of Ets-1 binding to chromatin. Chromatin immunoprecipitation assays indicated that Ets-1 binds to proximal regions in the PF4 and GPIIb promoters in vivo. In vitro and in vivo experiments showed that Ets-1 binding to chromatin on lineage-specific promoters does not require lineage-specific factors. Moreover, this binding shows the same order of affinity as the binding to naked DNA and does not require ATP-dependent or Sarkosyl-sensitive factors. The effect of Ets-1 binding on promoter activity was examined using the PF4 promoter as a model. We identified a novel Ets-1 site (at -50), and a novel Sarkosyl-sensitive DNase 1-hypersensitive site generated by Ets-1 binding to chromatin, which significantly affect PF4 promoter activity. Taken together, our results suggest a model by which Ets-1 binds to chromatin without the need for lineage-specific accessory factors, and Ets-1 binding induces changes in chromatin and affects transactivation, which are essential for PF4 promoter activation. C1 Boston Univ, Sch Med, Ctr Canc, Dept Biochem, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Ravid, K (reprint author), Boston Univ, Sch Med, Ctr Canc, Dept Biochem, K225,715 Albany St, Boston, MA 02118 USA. OI Ravid, Katya/0000-0002-9918-3024; Pazin, Michael/0000-0002-7561-3640 FU NIGMS NIH HHS [GM61011, R01 GM061011] NR 60 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 1 BP 428 EP 441 DI 10.1128/MCB.24.1.428-441.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757CL UT WOS:000187531200038 PM 14673175 ER PT J AU Barbie, DA Kudlow, BA Frock, R Zhao, JY Johnson, BR Dyson, N Harlow, E Kennedy, BK AF Barbie, DA Kudlow, BA Frock, R Zhao, JY Johnson, BR Dyson, N Harlow, E Kennedy, BK TI Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE GENE-TRANSCRIPTION; ASSEMBLY FACTOR-I; REPLICATION FACTORIES; SACCHAROMYCES-CEREVISIAE; LYSINE 9; CHROMATIN; ORGANIZATION; POLYMERASE; CLUSTERS; YEAST AB In primary mammalian cells, DNA replication initiates in a small number of perinucleolar, lamin A/C-associated foci. During S-phase progression in proliferating cells, replication foci distribute to hundreds of sites throughout the nucleus. In contrast, we find that the limited perinucleolar replication sites persist throughout S phase as cells prepare to exit the cell cycle in response to contact inhibition, serum starvation, or replicative senescence. Proteins known to be involved in DNA synthesis, such as PCNA and DNA polymerase delta, are concentrated in perinucleolar foci throughout S phase under these conditions. Moreover, chromosomal loci are redirected toward the nucleolus and overlap with the perinucleolar replication foci in cells poised to undergo cell cycle exit. These same loci remain in the periphery of the nucleus during replication under highly proliferative conditions. These results suggest that mammalian cells undergo a large-scale reorganization of chromatin during the rounds of DNA replication that precede cell cycle exit. C1 Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Rochester, Dept Biomed Genet, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kennedy, BK (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM bkenn@u.washington.edu OI Frock, Richard/0000-0001-6963-4931 FU NIGMS NIH HHS [GM 07270, T32 GM007270] NR 43 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 2 BP 595 EP 607 DI 10.1128/MCB.24.2.595-607.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MT UT WOS:000188211200010 PM 14701733 ER PT J AU Zhang, JR Willers, H Feng, ZH Ghosh, JC Kim, S Weaver, DT Chung, JH Powell, SN Xia, F AF Zhang, JR Willers, H Feng, ZH Ghosh, JC Kim, S Weaver, DT Chung, JH Powell, SN Xia, F TI Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-FREE-EXTRACTS; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; CANCER SUSCEPTIBILITY; CHROMOSOME STABILITY; IONIZING IRRADIATION; V(D)J RECOMBINATION; KINASE-ACTIVITY; MEIOTIC CELLS; MRE11 COMPLEX AB The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body of evidence suggests that promotion of DNA double-strand break repair by homologous recombination (HR) may be the means by which BRCA1 maintains genomic stability, while a role of BRCA1 in error-prone nonhomologous recombination (NHR) processes has just begun to be elucidated. The BRCA1 protein becomes phosphorylated in response to DNA damage, but the effects of phosphorylation on recombinational repair are unknown. In this study, we tested the hypothesis that the BRCA1-mediated regulation of recombination requires the Chk2- and ATM-dependent phosphorylation sites. We studied Rad51-dependent HR and random chromosomal integration of linearized plasmid DNA, a subtype of NHR, which we demonstrate to be dependent on the Mre11-Rad50-Nbs1 complex. Prevention of Chk2-mediated phosphorylation via mutation of the serine 988 residue of BRCA1 disrupted both the BRCA1-dependent promotion of HR and the suppression of NHR. Similar results were obtained when endogenous Chk2 kinase activity was inhibited by expression of a dominant-negative Chk2 mutant. Surprisingly, the opposing regulation of HR and NHR did not require the ATM phosphorylation sites on serines 1423 and 1524. Together, these data suggest a functional link between recombination control and breast cancer predisposition in carriers of Chk2 and BRCA1 germ line mutations. We propose a dual regulatory role for BRCA1 in maintaining genome integrity, whereby BRCA1 phosphorylation status controls the selectivity of repair events dictated by HR and error-prone NHR. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Ctr Blood Res, Boston, MA 02115 USA. Natl Heart Lung & Blood Inst, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 149 13th St, Charlestown, MA 02129 USA. EM snpowell@partners.org; fen.xia@vanderbilt.edu RI Xia, Fen/G-3708-2013 NR 76 TC 209 Z9 214 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 2 BP 708 EP 718 DI 10.1128/MCB.24.2.708-718.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MT UT WOS:000188211200020 PM 14701743 ER PT J AU Li, W Fan, JH Chen, M Guan, SX Sawcer, D Bokoch, GM Woodley, DT AF Li, W Fan, JH Chen, M Guan, SX Sawcer, D Bokoch, GM Woodley, DT TI Mechanism of human dermal fibroblast migration driven by type I collagen and platelet-derived growth factor-BB SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; CELL-MIGRATION; CHEMOTACTIC MIGRATION; GENE-EXPRESSION; MESSENGER-RNA; FACTOR-BETA; P38 MAPK; INTEGRIN; STIMULATION; INDUCTION AB Migration of human dermal fibroblasts (HDFs) is critical for skin wound healing. The mechanism remains unclear. We report here that platelet-derived growth factor-BB (PDGF-BB) is the major promotility factor in human serum for HDF motility on type I collagen. PDGF-BB recapitulates the full promotility activity of human serum and anti-PDGF neutralizing antibodies completely block it. Although collagen matrix initiates HDF migration without growth factors, PDGF-BB-stimulated migration depends upon attachment of the cells to a collagen matrix. The PDGF-BB's role is to provide directionality and further enhancement for the collagen-initiated HDF motility. To study the collagen and PDGF-BB "dual signaling" in primary HDF, we establish "gene cassettes" plus lentiviral gene delivery approach, in which groups of genes are studied individually or in combination for their roles in HDF migration. Focal adhesion kinase, p21(Rac,CDC42)-activated kinase and Akt are grouped into an upstream kinase gene cassette, and the four major mitogenactivated protein kinases (extracellular signal-regulated kinase 1/2, p38, c-Jun NH2-teriminal kinase, and extracellular signal-regulated kinase 5) are grouped into a downstream kinase gene cassette. The experiments demonstrate 1) the genes' individual roles and specificities, 2) their combined effects and sufficiency, and 3) the mechanisms of their intermolecular connections in HDF migration driven by collagen and PDGF-BB. C1 Univ So Calif, Keck Sch Med, Div Dermatol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Norris Canc Ctr, Los Angeles, CA 90033 USA. Greater Los Angles Vet Adm Hlth Syst, Los Angeles, CA 90073 USA. Scripps Res Inst, Dept Immunol & Cell Biol, La Jolla, CA 92037 USA. RP Li, W (reprint author), Univ So Calif, Keck Sch Med, Div Dermatol, Los Angeles, CA 90033 USA. FU NIAMS NIH HHS [R01 AR046538, AR46538]; NIGMS NIH HHS [GM/AR67100-01] NR 55 TC 85 Z9 88 U1 4 U2 14 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2004 VL 15 IS 1 BP 294 EP 309 PG 16 WC Cell Biology SC Cell Biology GA 760JT UT WOS:000187808400029 PM 14595114 ER PT J AU Larsen, JE Massol, RH Nieland, TJF Kirchhausen, T AF Larsen, JE Massol, RH Nieland, TJF Kirchhausen, T TI HIVNEF-mediated major histocompatibility complex class I down-modulation is independent of Arf6 activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HIV-1 NEF PROTEIN; SH3 DOMAIN; PLASMA-MEMBRANE; PHOSPHOLIPASE-D; ENDOCYTIC PATHWAY; CRYSTAL-STRUCTURE; BINDING SURFACE; DILEUCINE MOTIF; COATED PITS; INDUCED CD4 AB HIV Nef has a number of important biological effects, including the down-modulation of several immunological important molecules (CD4, major histocompatibility complex [MHC] class I). Down-modulation of CD4 seems to be via clathrin-dependent endocytosis, whereas down-modulation of MHC class I remains unexplained. Several mutant proteins, including mutations in the small GTPase Arf6, have been used to probe membrane traffic pathways. One such mutant has recently been used to propose that Nef acts through Arf6 to activate the endocytosis of MHC class I. Here, we show that MHC class I down-modulation is unaffected by other Arf6 mutants that provide more specific perturbations in the GDP-GTP cycling of Arf6. Inhibition of phosphatidylinositol-3-phosphate kinase, an upstream activator of Arf6, also had no effect on the internalization step, but its activity is required to direct MHC class I to the trans-Golgi network. We conclude that the apparent Arf6 dependency of Nef-mediated MHC class I down-modulation is due to nonspecific perturbations in membrane traffic. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM-60357] NR 44 TC 34 Z9 36 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2004 VL 15 IS 1 BP 323 EP 331 DI 10.1091/mbc.E03-08-0578 PG 9 WC Cell Biology SC Cell Biology GA 760JT UT WOS:000187808400031 PM 14617802 ER PT J AU Qi, H Gervais, ML Li, W DeCaprio, JA Challis, JRG Ohh, M AF Qi, H Gervais, ML Li, W DeCaprio, JA Challis, JRG Ohh, M TI Molecular cloning and characterization of the von Hippel-Lindau-like protein SO MOLECULAR CANCER RESEARCH LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; TUMOR-SUPPRESSOR PROTEIN; PAS DOMAIN PROTEIN; PROLYL HYDROXYLATION/; CELL CARCINOMAS; GENE-EXPRESSION; REGULATE HIF; ELONGIN-B; VHL; ALPHA AB von Hippel-Lindau (VHL) tumor suppressor protein-inactivated in VHL disease and sporadic kidney cancer- is a component of an E3 ubiquitin ligase complex that selectively ubiquitinates the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor for subsequent destruction by the 26S proteasome. Here, we report the identification and characterization of the first VHL homologue, VHL-like protein (VLP), located on chromosome 1q21.2. A 676-bp partial cDNA encoding a 139-amino acid protein that is 78% similar to VHL was isolated by reverse transcription-PCR from human brain cerebellum and several cancer cell lines. The expression of VLP transcript is most abundant in the placenta. Like VHL, VLP contains a beta domain capable of binding HIFalpha. However, unlike VHL, it does not contain a recognizable alpha domain, which is required for nucleating the multiprotein E3 ubiquitin ligase complex. The increased expression of VLP in the presence of VHL attenuated the ubiquitination of HIFalpha and led to the accumulation of downstream HIF target genes. These results taken together indicate that VLP functions as a dominant-negative VHL to serve as a protector of HIFalpha. C1 Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 1A8, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Mol Oncol, Boston, MA 02115 USA. RP Ohh, M (reprint author), Univ Toronto, Dept Lab Med & Pathobiol, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM michael.ohh@utoronto.ca RI Challis, John/E-7419-2014 NR 40 TC 5 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2004 VL 2 IS 1 BP 43 EP 52 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 770HU UT WOS:000188717800006 PM 14757845 ER PT J AU Ikeda, T Nakata, Y Kimura, F Sato, K Anderson, K Motoyoshi, K Sporn, M Kufe, D AF Ikeda, T Nakata, Y Kimura, F Sato, K Anderson, K Motoyoshi, K Sporn, M Kufe, D TI Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3, 12-dioxoolean-1,9-dien-28-oic acid SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CDDO INDUCES APOPTOSIS; CYTOCHROME-C; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; FLOW-CYTOMETRY; LEUKEMIA-CELLS; B-CELLS; DEATH; MITOCHONDRIA; PROTEIN; ACTIVATION AB The synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and its chemical derivatives induce differentiation and apoptosis of human leukemia cells. The precise mechanisms responsible for the effects of CDDO, however, remain unclear. In the present study, we examined the effects of CDDO and its C-28 imidazolide ester (CDDO-Im) on apoptosis of multiple myeloma (MM) cells. The results show that both CDDO and CDDO-Im are potent inducers of MM cell apoptosis and that CDDO-Inn is more active than CDDO. CDDO-Inn treatment was associated with (a) depletion of glutathione, (b) increases in reactive oxygen species, (c) a reduction of the Fas-associated death domain (FADD)-like interleukin-1-converting enzyme (FLICE) inhibitory protein, (d) activation of caspase-8, and (e) a decrease of the mitochondrial transmembrane potential. The reducing agents, N-acetyl-L-cysteine, DTT, and catalase inhibited each of these CDDO-Im-induced proapoptotic signals. Inhibition of caspase-8 with z-IETD-fmk also abrogated CDDO-im-induced decreases of the mitochondrial transmembrane potential and inhibited apoptosis. These results demonstrate that CDDO-Im disrupts intracellular redox balance and thereby activates the extrinsic caspase-8-dependent apoptotic pathway. We further show that CDDO-Im induces apoptosis of primary MM cells at submicromolar concentrations and that MM cells are more sensitive to this agent than normal bone marrow mononuclear cells. These results suggest that CDDO compounds have potential as new agents for the treatment of MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Coll, Dept Pharmacol, Hanover, NH 03755 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 830,44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu NR 43 TC 65 Z9 65 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2004 VL 3 IS 1 BP 39 EP 45 DI 10.2463/mrms.3.39 PG 7 WC Oncology SC Oncology GA 767RK UT WOS:000188466300005 PM 14749474 ER PT J AU Keutmann, HT Schneyer, AL Sidis, Y AF Keutmann, HT Schneyer, AL Sidis, Y TI The role of follistatin domains in follistatin biological action SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; EPIDERMAL-GROWTH-FACTOR; CELL-LINE PA-1; ACTIVIN-BINDING; STRUCTURAL CONSEQUENCES; TRANSMEMBRANE PROTEIN; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; II RECEPTORS; GENE FAMILY AB Follistatin (FS) is an important regulator of pituitary FSH secretion through its potent ability to bind and bioneutralize activin. It also represents a prototype for binding proteins that control bioavailability of other TGFbeta-related growth factors such as the bone morphogenetic proteins. The 288-residue FS molecule has a distinctive structure comprised principally of three 10-cysteine FS domains. These are preceded by an N-terminal segment shown by us previously to contain hydrophobic residues essential for activin binding. To establish the contribution of the FS domains themselves to FS's bioactivity, we prepared mutants with deleted or exchanged domains and intradomain point mutations. Mutants were expressed from mammalian ( Chinese hamster ovary) cells and evaluated for activin binding and for biological activity in assays measuring differing aspects of FS bioactivity: activin-mediated transcriptional activity and suppression of FSH secretion in primary pituitary cell cultures. The N-terminal domain ( residues 1 - 63) alone could not bind activin or suppress activin-mediated transcription, either alone or combined in solution with the FS domain region ( residues 64 - 288). Deletion of FS domains 1 or 2 abolished activin binding and biological activity in both assays, whereas deletion of domain 3 was tolerated. Bioactivity was also reduced or eliminated after exchange of domains ( FS 2/1/3 and FS 3/1/2) or doubling of domain 1 ( FS 1/1/3) or domain 2 ( FS 2/2/3). Several hydrophobic residues clustered within the C-terminal region of FS domains 1 and 2 are highly conserved among all FS domains. Mutation of any of these to Asp or Ala either reduced or eliminated FS bioactivity and disrupted distant epitopes for heparin binding ( FS domain 1) or antibody recognition ( FS domain 2), suggesting their role in maintaining the conformational integrity of the domain and possibly the FS molecule as a whole. These results are consistent with the importance of domain conformation as well as the overall order of the domains in FS function. A continuous sequence comprising the N-terminal domain and followed by FS domains 1 and 2 fulfills the minimum structural requirement for activin binding and FS bioactivity. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Keutmann, HT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. NR 60 TC 38 Z9 42 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN 1 PY 2004 VL 18 IS 1 BP 228 EP 240 DI 10.1210/me.2003-0112 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758GB UT WOS:000187624600020 PM 14563935 ER PT J AU Guinn, KM Hickey, MJ Mathur, SK Zakel, KL Grotzke, JE Lewinsohn, DM Smith, S Sherman, DR AF Guinn, KM Hickey, MJ Mathur, SK Zakel, KL Grotzke, JE Lewinsohn, DM Smith, S Sherman, DR TI Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis SO MOLECULAR MICROBIOLOGY LA English DT Article ID BACILLUS-CALMETTE-GUERIN; NECROSIS-FACTOR-ALPHA; T-CELL ANTIGENS; BOVIS BCG; COMPARATIVE GENOMICS; PROTEIN SECRETION; ESAT-6; IDENTIFICATION; RD1; MONOCYTES AB The RD1 genomic region is present in virulent strains of Mycobacterium tuberculosis (MTB), missing from the vaccine strain M. bovis BCG, and its importance to virulence has been established experimentally. Based on in silico analysis, it has been suggested that RD1 may encode a novel secretion system, but the mechanism by which this region affects virulence is unknown. Here we examined mutants disrupted in five individual RD1 genes. Both in vitro and in vivo, each mutant displayed an attenuated phenotype very similar to a mutant missing the entire RD1 region. Genetic complementation of individual genes restored virulence. Attenuated mutants could multiply within THP-1 cells, but they were unable to spread to uninfected macrophages. We also examined export of two immunodominant RD1 proteins, CFP-10 and ESAT-6. Export of these proteins was greatly reduced or abolished in each attenuated mutant. Again, genetic complementation restored a wild-type phenotype. Our results indicate that RD1 genes work together to form a single virulence determinant, and argue that RD1 encodes a novel specialized secretion system that is required for pathogenesis of MTB. C1 Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr, Portland, OR 97239 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. RP Sherman, DR (reprint author), Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NHLBI NIH HHS [HL68533, HL64550, R01 HL064550, R01 HL068533]; NIAID NIH HHS [N01 AI-75320] NR 53 TC 299 Z9 325 U1 0 U2 13 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2004 VL 51 IS 2 BP 359 EP 370 DI 10.1046/j.1365-2958.2003.03844.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 761FN UT WOS:000187890800006 PM 14756778 ER PT J AU Dunah, AW Sirianni, AC Fienberg, AA Bastia, E Schwarzschild, MA Standaert, DG AF Dunah, AW Sirianni, AC Fienberg, AA Bastia, E Schwarzschild, MA Standaert, DG TI Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requires Fyn protein tyrosine kinase but not DARPP-32 SO MOLECULAR PHARMACOLOGY LA English DT Article ID LONG-TERM POTENTIATION; NMDA-RECEPTOR; RAT-BRAIN; POSTSYNAPTIC MEMBRANE; SYNAPTIC TRANSMISSION; PARKINSONS-DISEASE; PHOSPHATASE STEP; BASAL GANGLIA; SRC-FAMILY; 2B SUBUNIT AB Interactions between dopaminergic and glutamatergic systems in the striatum are thought to underlie both the symptoms and adverse effects of treatment of Parkinson's disease. We have previously reported that activation of the dopamine D1 receptor triggers a rapid redistribution of striatal N-methyl-D-aspartate (NMDA) receptors between intracellular and postsynaptic subcellular compartments. To unravel the signaling pathways underlying this trafficking, we studied mice with targeted disruptions of either the gene that encodes the dopamine- and cAMP-regulated phosphoprotein (DARPP-32), a potent and selective inhibitor of protein phosphatase-1, or the protein tyrosine kinase Fyn. In striatal tissue from DARPP-32-depleted mice, basal tyrosine and serine phosphorylation of striatal NMDA receptor subunits NR1, NR2A, and NR2B was normal, and activation of dopamine D1 receptors with the agonist SKF-82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine] produced redistribution of NMDA receptors from vesicular compartments (P3 and LP2) to synaptosomal membranes (LP1). In the Fyn knockout mice, basal tyrosine phosphorylation of NR2A and NR2B was drastically reduced, whereas serine phosphorylation of these NMDA subunits was unchanged. In the Fyn knockout mice, the dopamine D1 receptor agonist failed to induce subcellular redistribution of NMDA receptors. In addition, Fyn-depleted mice lesioned with 6-hydroxydopamine also failed to exhibit L-DOPA-induced behavioral sensitization, but this may be caused, at least in part, by resistance of these mice to the neurotoxic lesion. These findings suggest a novel mechanism for the trafficking of striatal NMDA receptors by signaling pathways that are independent of DARPP-32 but require Fyn protein tyrosine kinase. Strategies that prevent NMDA receptor subcellular redistribution through inhibition of Fyn kinase may prove useful in the treatment of Parkinson's disease. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Aging Genet & Neurodgenerat, Charlestown, MA 02129 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, 114 16th St,CNY114-2004, Charlestown, MA 02129 USA. EM standaert@helix.mgh.harvard.edu OI Standaert, David/0000-0003-2921-8348 FU NIDA NIH HHS [DA13508]; NINDS NIH HHS [NS34361] NR 63 TC 109 Z9 114 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN 1 PY 2004 VL 65 IS 1 BP 121 EP 129 DI 10.1124/mol.65.1.121 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 762XQ UT WOS:000188010000015 PM 14722243 ER PT J AU Samuels, SC Brickman, AM Burd, JA Purohit, DP Qureshi, PQ Serby, M AF Samuels, SC Brickman, AM Burd, JA Purohit, DP Qureshi, PQ Serby, M TI Depression in autopsy-confirmed dementia with Lewy bodies and Alzheimer's disease SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY FEB 23-26, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Geriatr Psychiat DE dementia; depression; Lewy bodies; Alzheimer's disease; autopsy ID MAJOR DEPRESSION; BODY DISEASE; DISTINGUISH PATIENTS; PARKINSONS-DISEASE; CLINICAL-CRITERIA; MINOR DEPRESSION; PREVALENCE AB Depression has frequently been cited as a manifestation of dementia with Lewy bodies (DLB). Previous studies have suggested an increase of depression in patients with DLB, compared to those with Alzheimer's disease (AD). The purpose of this study was to examine depressive symptomatology in nursing home residents, from a consecutive series of DLB (n=16) and AD (n=39) autopsy-confirmed cases. Subjects received standard neuropathological analysis and postmortem chart review for clinical assessment of depression. Depressive symptomatology did not differ between the AD and DLB groups, and there was no significant relationship between depression and cortical or subcortical Lewy body (LB) count in the locus ceruleus or substantia nigra. This study suggests that the presence or absence of depression cannot be used to distinguish between AD and DLB. Furthermore, depressive symptomatology in DLB does not appear to be related to severity of cortical or subcortical LB pathology. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. CUNY, Queens Coll, Dept Psychol, New York, NY 10021 USA. CUNY, Grad Ctr, New York, NY 10021 USA. Beth Israel Med Ctr, Dept Psychiat, New York, NY 10003 USA. RP Samuels, SC (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1230,1 E 100th St, New York, NY 10029 USA. EM Steven.Samuels@med.va.gov FU NIA NIH HHS [P01-AG02219, P50-AG05138] NR 39 TC 13 Z9 14 U1 0 U2 2 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD JAN PY 2004 VL 71 IS 1 BP 55 EP 62 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 766QF UT WOS:000188386500009 PM 14770251 ER PT S AU Bacskai, BJ Skoch, J Hickey, GA Berezovska, O Hyman, BT AF Bacskai, BJ Skoch, J Hickey, GA Berezovska, O Hyman, BT BE Periasamy, A TI Multiphoton imaging in mouse models of Alzheimer's disease SO MULTIPHOTON MICROSCOPY IN THE BIOMEDICAL SCIENCES IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Multiphoton Microscopy in the Biomedical Sciences IV CY JAN 25-27, 2004 CL San Jose, CA SP SPIE, Bio-Rad Lab Inc, Carl Zeiss Inc, Chroma Technol Corp, Coherent Inc, Nikon Inc, Omega Opt Inc, Spectra-Phys Inc DE multiphoton; Alzheimer; transgenic mouse; in vivo imaging; plaques; amyloid; FLIM ID TRANSGENIC MICE; IN-VIVO; AMYLOID PLAQUES; BETA PLAQUES; MICROSCOPY; CLEARANCE; BRAIN AB Alzheimer's disease is characterized by the presence of neurofibrillary tangles and senile plaques in the brain. Clinical techniques are just becoming available for detecting plaques, allowing a definitive diagnosis of the disease. Using multiphoton microscopy and transgenic mouse models that develop senile plaques as they age, we have demonstrated chronic, in vivo imaging of these neuropathological lesions. We have used these tools to evaluate contrast agents with high affinity and specificity for senile plaques that would be suitable for non-invasive imaging with PET scanning if appropriately radiolabeled. These imaging tools should translate into early diagnostic procedures, as well as end-points for clinical trials aimed at clearing senile plaques from the brain. We have also developed FLIM for FRET determinations in vitro and in vivo between appropriate donor and acceptor fluorophores to examine the proximity of domains within a single protein. These results indicate that FRET measurements using FLIM can determine interactions of proteins on the nanometer scale, facilitating an understanding of both static and dynamic protein assemblies in neuropathological diseases. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Unit, MassGen Inst Nuerodegenerat Dis, Charlestown, MA USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Unit, MassGen Inst Nuerodegenerat Dis, 114 16th St, Charlestown, MA USA. NR 18 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 0-8194-5231-9 J9 P SOC PHOTO-OPT INS PY 2004 VL 5323 BP 71 EP 76 DI 10.1117/12.537940 PG 6 WC Engineering, Biomedical; Microscopy; Optics; Spectroscopy SC Engineering; Microscopy; Optics; Spectroscopy GA BAN20 UT WOS:000222940200008 ER PT J AU Gruenewald, DA Higginson, IJ Vivat, B Edmonds, P Burman, RE AF Gruenewald, DA Higginson, IJ Vivat, B Edmonds, P Burman, RE TI Quality of life measures for the palliative care of people severely affected by multiple sclerosis: a systematic review SO MULTIPLE SCLEROSIS LA English DT Review DE multiple sclerosis; quality of life; palliative care; outcome; audit; caregiver; review ID CHRONIC DISABLING CONDITIONS; INFLAMMATORY-BOWEL-DISEASE; SECONDARY PROGRESSIVE MS; ILLNESS INTRUSIVENESS; IMPACT PROFILE; HEALTH-STATUS; RHEUMATOID-ARTHRITIS; OUTCOME MEASURE; DISABILITY; QUESTIONNAIRE AB Although there is increasing interest in measuring the quality of life (QoL) of people with multiple sclerosis (MS), relatively little is known about the issues of importance to people severely affected by MS. In the first of two systematic reviews, we searched the literature to identify measures that have been used to assess health-related QoL in people with MS, and described their measurement properties in terms of validity, reliability, responsiveness to change, and appropriateness for QoL assessment in people severely affected by MS. In the second review, we identified care domains important to people with MS, by reviewing survey, focus group and interview studies involving people with MS and/or their caregivers. Forty-six studies evaluating 12 disease-specific and ten generic QoL measures for patients, and one disease-specific measure for caregivers, satisfied all inclusion criteria. Sixteen focus group or interview studies and 51 questionnaire-based studies evaluated domains of care important to people with MS, and seven qualitative and 11 questionnaire-based studies assessed domains of care important to their caregivers. From these studies, we identified 15 domains of care important to people with MS and 12 domains important to caregivers. QoL measures differed markedly in their coverage of these care domains. Moreover, each measure fulfilled some but not all criteria of validity, reliability, responsiveness, and appropriateness. Further work is needed to clarify the domains of care relevant to people with severe MS, and to measure health-related QoL in this population. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Kings Coll London, Sch Med, Dept Palliat Care & Policy, London SE5 9RJ, England. RP Gruenewald, DA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM dgruen@u.washington.edu OI Vivat, Bella/0000-0002-0587-5688 FU Multiple Sclerosis Society [676] NR 129 TC 44 Z9 45 U1 6 U2 9 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PY 2004 VL 10 IS 6 BP 690 EP 725 DI 10.1191/1352458504ms1116rr PG 36 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 871AQ UT WOS:000225101700016 PM 15584496 ER PT J AU Nishiguchi, KM Sandberg, MA Kooijman, AC Martemyanov, KA Pott, JWR Hagstrom, SA Arshavsky, VY Berson, EL Dryja, TP AF Nishiguchi, KM Sandberg, MA Kooijman, AC Martemyanov, KA Pott, JWR Hagstrom, SA Arshavsky, VY Berson, EL Dryja, TP TI Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation SO NATURE LA English DT Article ID GTPASE-ACCELERATING PROTEIN; RETINITIS-PIGMENTOSA; MEMBRANE ANCHOR; EXPRESSION; ACTIVATION; ROD; ELECTRORETINOGRAPHY; PHOTOTRANSDUCTION; STANDARD; RECOVERY AB The RGS proteins are GTPase activating proteins that accelerate the deactivation of G proteins in a variety of signalling pathways in eukaryotes(1-6). RGS9 deactivates the G proteins (transducins) in the rod and cone phototransduction cascades(7,8). It is anchored to photoreceptor membranes by the transmembrane protein R9AP (RGS9 anchor protein), which enhances RGS9 activity up to 70-fold(9-11). If RGS9 is absent or unable to interact with R9AP, there is a substantial delay in the recovery from light responses in mice(4,12,13). We identified five unrelated patients with recessive mutations in the genes encoding either RGS9 or R9AP who reported difficulty adapting to sudden changes in luminance levels mediated by cones. Standard visual acuity was normal to moderately subnormal, but the ability to see moving objects, especially with low-contrast, was severely reduced despite full visual fields; we have termed this condition bradyopsia. To our knowledge, these patients represent the first identified humans with a phenotype associated with reduced RGS activity in any organ. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. Univ Groningen Hosp, Dept Ophthalmol, NL-9700 RB Groningen, Netherlands. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. EM Thaddeus_Dryja@meei.harvard.edu NR 27 TC 101 Z9 106 U1 1 U2 6 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 1 PY 2004 VL 427 IS 6969 BP 75 EP 78 DI 10.1038/nature02170 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 758YP UT WOS:000187710000037 PM 14702087 ER PT J AU Attardi, LD DePinho, RA AF Attardi, LD DePinho, RA TI Conquering the complexity of p53 SO NATURE GENETICS LA English DT Editorial Material ID IN-VIVO; APOPTOSIS; DEFICIENCY; MICE AB New evidence from a Trp53 'knock-in' mouse model suggests that p53-dependent cell cycle checkpoint control accompanied by maintenance of genome stability is important for keeping tumor growth in check. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Harvard Univ, Sch 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 Genet, Boston, MA 02115 USA. RP Attardi, LD (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. NR 15 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2004 VL 36 IS 1 BP 7 EP 8 DI 10.1038/ng0104-7 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 758TT UT WOS:000187666800004 PM 14702030 ER PT J AU Sheen, VL Ganesh, VS Topcu, M Sebire, G Bodell, A Hill, RS Grant, PE Shugart, YY Imitola, J Khoury, SJ Guerrini, R Walsh, CA AF Sheen, VL Ganesh, VS Topcu, M Sebire, G Bodell, A Hill, RS Grant, PE Shugart, YY Imitola, J Khoury, SJ Guerrini, R Walsh, CA TI Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex SO NATURE GENETICS LA English DT Article ID NUCLEOTIDE-EXCHANGE PROTEINS; ADP-RIBOSYLATION FACTORS; TRANS-GOLGI NETWORK; BREFELDIN-A; PERIVENTRICULAR HETEROTOPIA; NEURONAL MIGRATION; CORTICAL SIZE; CELL-ADHESION; GROWTH; BIG2 AB Disruption of human neural precursor proliferation can give rise to a small brain ( microcephaly), and failure of neurons to migrate properly can lead to an abnormal arrest of cerebral cortical neurons in proliferative zones near the lateral ventricles (periventricular heterotopia). Here we show that an autosomal recessive condition characterized by microcephaly and periventricular heterotopia 1 maps to chromosome 20 and is caused by mutations in the gene ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2). By northern-blot analysis, we found that mouse Arfgef2 mRNA levels are highest during embryonic periods of ongoing neuronal proliferation and migration, and by in situ hybridization, we found that the mRNA is widely distributed throughout the embryonic central nervous system (CNS). ARFGEF2 encodes the large (>200 kDa) brefeldin A (BFA)-inhibited GEF2 protein (BIG2), which is required for vesicle and membrane trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA, or by a dominant negative ARFGEF2 cDNA, decreases cell proliferation in vitro, suggesting a cell-autonomous regulation of neural expansion. Inhibition of BIG2 also disturbed the intracellular localization of such molecules as E-cadherin and beta-catenin by preventing their transport from the Golgi apparatus to the cell surface. Our findings show that vesicle trafficking is an important regulator of proliferation and migration during human cerebral cortical development. C1 Harvard Univ, Sch Med, Div Neurogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurol,Beth Israel Diaconess Med Ctr, Boston, MA 02115 USA. Hacettepe Univ, Fac Med, Ihsan Dogramaci Childrens Hosp, Dept Pediat Neurol, TR-06100 Ankara, Turkey. Univ Sherbrooke, CHU Fleurimont, Dept Pediat Neurol, Sherbrooke, PQ J1H 5N4, Canada. Harvard Univ, Sch Med, Athinoula A Marinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Pediat Neuroradiol, Boston, MA 02114 USA. Johns Hopkins Med Sch, Dept Pediat Epidemiol, Baltimore, MD 21205 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. Univ Pisa, Div Child Neurol & Psychiat, Epilepsy Neurophysiol & Neurogenet Unit, I-56018 Pisa, Italy. IRCCS Fdn Stella Maris, I-56018 Pisa, Italy. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. RP Walsh, CA (reprint author), Harvard Univ, Sch Med, Div Neurogenet, Boston, MA 02115 USA. OI khoury, samia/0000-0003-3198-6063 FU NIMH NIH HHS [K08 MH063886] NR 30 TC 185 Z9 191 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2004 VL 36 IS 1 BP 69 EP 76 DI 10.1038/ng1276 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 758TT UT WOS:000187666800016 PM 14647276 ER PT J AU Auchincloss, H AF Auchincloss, H TI No tolerance for depletion SO NATURE MEDICINE LA English DT Editorial Material ID DONOR BONE-MARROW; ALLOGRAFT TOLERANCE; T-CELLS; CHIMERISM; TRANSPLANTATION; MONKEYS AB T-cell depletion is commonly used in strategies that attempt to coax the immune system into tolerating foreign tissue after transplantation. Studies in mice now indicate that this depletion may be at odds with the goal of inducing tolerance (pages 87-92). C1 Massachusetts Gen Hosp, Transplant Unit, Surg Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Transplant Unit, Surg Serv, WAC 478,15 Parkman St, Boston, MA 02114 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2004 VL 10 IS 1 BP 21 EP 23 DI 10.1038/nm0104-21 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759NK UT WOS:000187743600024 PM 14702625 ER PT J AU Dranoff, G AF Dranoff, G TI Cytokines in cancer pathogenesis and cancer therapy SO NATURE REVIEWS CANCER LA English DT Review ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; RENAL-CELL CARCINOMA; PROSPECTIVE RANDOMIZED TRIAL; APOPTOSIS-INDUCING LIGAND; CYTOTOXIC T-LYMPHOCYTES; BINDING-PROTEIN ICSBP; NATURAL-KILLER-CELLS; RESPONSES IN-VIVO AB The mixture of cytokines that is produced in the tumour microenvironment has an important role in cancer pathogenesis. Cytokines that are released in response to infection, inflammation and immunity can function to inhibit tumour development and progression. Alternatively, cancer cells can respond to host-derived cytokines that promote growth, attenuate apoptosis and facilitate invasion and metastasis. A more detailed understanding of cytokine-tumour-cell interactions provides new opportunities for improving cancer immunotherapy. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Bell, Tiffany/F-4403-2010 NR 137 TC 536 Z9 556 U1 10 U2 80 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2004 VL 4 IS 1 BP 11 EP 22 DI 10.1038/nrc1252 PG 12 WC Oncology SC Oncology GA 759NB UT WOS:000187742800011 PM 14708024 ER PT J AU Storchova, Z Pellman, D AF Storchova, Z Pellman, D TI From polyploidy to aneuploidy, genome instability and cancer SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID YEAST SCHIZOSACCHAROMYCES-POMBE; INDUCED CHROMOSOME LOSS; CELL-SIZE HOMEOSTASIS; SACCHAROMYCES-CEREVISIAE; CENTROSOME AMPLIFICATION; DROSOPHILA EMBRYOGENESIS; TETRAPLOIDY CHECKPOINT; BARRETTS-ESOPHAGUS; PARASEXUAL CYCLE; MAMMALIAN-CELLS AB Polyploidy is a frequent phenomenon in the eukaryotic world, but the biological properties of polyploid cells are not well understood. During evolution, polyploidy is thought to be an important mechanism that contributes to speciation. Polyploid, usually non-dividing, cells are formed during development in otherwise diploid organisms. A growing amount of evidence indicates that polyploid cells also arise during a variety of pathological conditions. Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Room M621A,44 Binney St, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu NR 125 TC 425 Z9 445 U1 6 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2004 VL 5 IS 1 BP 45 EP 54 DI 10.1038/nrm1276 PG 10 WC Cell Biology SC Cell Biology GA 762QK UT WOS:000187993500014 PM 14708009 ER PT J AU Wilkinson, D Halligan, P AF Wilkinson, D Halligan, P TI Opinion - The relevance of behavioural measures for functional-imaging studies of cognition SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID LINE BISECTION JUDGMENTS; EVENT-RELATED FMRI; NEURAL BASIS; FAR SPACE; FACE RECOGNITION; VISUAL-SEARCH; PREFRONTAL CORTEX; MENTAL PROCESSES; BRAIN; ATTENTION AB The psychological structure of cognition is often inferred from conjoint measures of behaviour (such as reaction time) and brain activation (such as cerebral blood flow). In many experiments these measures produce divergent results. One example is where a significant pattern of brain activation occurs without a corresponding change in overt behaviour. In such circumstances, can cognitive theory be informed from brain-activation data alone? Or, given the more established link between behaviour and cognition, is behavioural corroboration necessary? C1 VA Boston Healthcare Syst, GRECC JP 182, Neuropsychol Lab, Boston, MA 02130 USA. Cardiff Univ, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. RP Wilkinson, D (reprint author), VA Boston Healthcare Syst, GRECC JP 182, Neuropsychol Lab, 150 S Huntington Ave, Boston, MA 02130 USA. NR 68 TC 145 Z9 146 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JAN PY 2004 VL 5 IS 1 BP 67 EP 73 DI 10.1038/nrn1302 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 760FW UT WOS:000187801800021 PM 14708005 ER PT J AU Weisbord, SD Bruns, FJ Saul, MI Palevsky, PM AF Weisbord, SD Bruns, FJ Saul, MI Palevsky, PM TI Provider use of preventive strategies for radiocontrast nephropathy in high-risk patients SO NEPHRON CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Nephrology CY NOV 01-06, 2002 CL PHILADELPHIA, PA SP Amer Soc Nephrol DE intravenous fluids; nonsteroidal anti-inflammatories; cyclo-oxygenase inhibitors; radiocontrast nephropathy ID ACUTE-RENAL-FAILURE; RADIOGRAPHIC-CONTRAST-AGENT; CARDIAC-CATHETERIZATION; PROSPECTIVE TRIAL; HYDRATION; NEPHROTOXICITY; INSUFFICIENCY; DYSFUNCTION; ANGIOGRAPHY; FUROSEMIDE AB Background/Aims: Radiocontrast nephropathy (RCN) is a common and costly form of acute renal failure. Current preventative strategies include the use of intravenous (IV) fluids and the discontinuation of nephrotoxic medications at the time of radiocontrast administration. We sought to determine whether providers employ these strategies in high-risk patients to limit the development of RCN. Methods: High-risk patients undergoing procedures using radiocontrast media over a 12-month period were identified. Medical records were reviewed for all subjects who developed RCN and a randomly selected 25% of patients without RCN. Patients with a contraindication to IV volume expansion were excluded. Medical records of the remaining patients were reviewed to determine whether IV fluids were administered and whether NSAIDs or COX-2 inhibitors were prescribed at the time of contrast administration. Results: RCN developed in 8% of patients overall. Of 144 patients eligible for IV volume expansion, 16% failed to receive any IV fluids. When IV fluids were employed, their dose and timing of administration varied significantly by treating specialty and procedure. NSAIDs and COX-2 inhibitors were prescribed to 8% of patients. Conclusions: Commonly accepted strategies for the prevention of RCN are underutilized. Quality improvement efforts are needed to increase the use of these two simple prophylactic measures. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Pittsburgh, Med Ctr, Renal Electrolyte Div, Sch Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Biomed Informat, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), Univ Pittsburgh, Med Ctr, Renal Electrolyte Div, Sch Med, A919 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM weisbordsd@msx.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU NHLBI NIH HHS [T32HL07820-05] NR 41 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2004 VL 96 IS 2 BP C56 EP C62 DI 10.1159/000076400 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 778KL UT WOS:000189240700006 PM 14988599 ER PT J AU Laterra, JJ Grossman, SA Carson, KA Lesser, GJ Hochberg, FH Gilbert, MR AF Laterra, JJ Grossman, SA Carson, KA Lesser, GJ Hochberg, FH Gilbert, MR TI Suramin and radiotherapy in newly diagnosed glioblastoma: Phase 2 NABTT CNS Consortium study SO NEURO-ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; LEWIS-LUNG-CARCINOMA; ONCOLOGY-GROUP TRIAL; PROSTATE-CANCER; RADIATION-THERAPY; IN-VITRO; CELLS; MULTIFORME; TRANSFORMATION; EFFICACY AB Suramin is a polysulfonated naphthylurea that inhibits the function of growth factors and growth factor receptors implicated in glioma progression, angiogenesis, and radioresistance. The safety and benefits of combining inhibitors of angiogenesis and growth factors with cytotoxic therapies in patients with neoplasms of the central nervous system remain unclear. The objectives of this phase 2 study were to determine the safety of administering suramin with standard cranial radiotherapy (RT) and to estimate survival using this approach in patients with newly diagnosed glioblastoma multiforme (GBM). Fifty-five patients with newly diagnosed GBM (Karnofsky performance status greater than or equal to60) were enrolled in this multicenter phase 2 study. Patients received suramin by a conventional intermittent fixed-dosing regimen for 1 week prior to and during cranial RT (60 Gy in 30 fractions, weeks 2-7). Patients with stable or responsive disease at week 18 received an additional 4 weeks of suramin (weeks 19-22). The median survival for suramin-treated patients was 11.6 months, with 1-year and 18-month survival rates of 49% (95% confidence interval [CI], 36%-62%) and 18% (95% CI, 8%-28%), respectively. Overall, 55% of the patients (30/55) had greater than grade 2 toxicity at least possibly related to suramin therapy. Two patients died of possibly related neurologic events (i.e., stroke, elevated intracranial pressure). Otherwise, toxicities were generally transient and self-limited. Administration of suramin using an intermittent fixed-dosing regimen during cranial RT was generally well tolerated. However, overall survival is not significantly improved when compared with the New Approaches to Brain Tumor Therapy GBM database or other comparable patient populations. C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Wake Forest Univ, Baptist Med Ctr, Dept Hematol & Oncol, Winston Salem, NC 27157 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Laterra, JJ (reprint author), NABTT CNS Consortium, G87 Canc Res Bldg,1650 Orleans St, Baltimore, MD 21231 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NCI NIH HHS [CA62475, U01 CA062475] NR 31 TC 25 Z9 26 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 15 EP 20 DI 10.1215/S1152.8517.03.00012.7 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800003 PM 14769135 ER PT J AU Batchelor, TT Gilbert, MR Supko, JG Carson, KA Nabors, LB Grossman, SA Lesser, GJ Mikkelsen, T Phuphanich, S AF Batchelor, TT Gilbert, MR Supko, JG Carson, KA Nabors, LB Grossman, SA Lesser, GJ Mikkelsen, T Phuphanich, S CA NABTT CNS Consortium TI Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: Final report of NABTT 97-11 SO NEURO-ONCOLOGY LA English DT Article ID CPT-11; CHEMOTHERAPY; PHARMACOLOGY; GLIOBLASTOMA; SCHEDULE; EFFICACY; THERAPY AB The primary objective of this study was to determine the proportion of patients exhibiting a radiographic response in a cohort of patients with recurrent malignant glioma who were treated with irinotecan. Secondary objectives were to determine progression-free survival, overall survival, and toxicity. The trial was terminated after the first 18 patients were enrolled in this multicenter, 2-stage, phase 2 study. Twelve patients received concurrent enzyme-inducing antiepileptic drugs, and 6 did not. Each cycle consisted of a 90-min i.v. infusion of irinotecan every week for 4 consecutive weeks, followed by 2 weeks off. One patient had a complete response, 5 patients had stable disease, 5 patients had radiographic progression, 6 patients were removed from the study because of toxicity, and 1 patient refused further therapy and was removed from the study. The response rate in this study was 6% (1/18), and 28% (5/18) of these patients progressed while receiving irinotecan. Dose-limiting toxicities consisted of diarrhea in 5 patients, neutropenia in 1 patient, infection in 1 patient, and respiratory failure in 1 patient. Irinotecan had minimal efficacy in this cohort of 18 patients with recurrent malignant glioma. Toxicity was significant but similar to that reported in other patient populations. C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Med Oncol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Wake Forest Univ, Med Ctr, Dept Hematol & Oncol, Winston Salem, NC 27157 USA. Univ S Florida, Div Neurooncol, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Henry Ford Hosp, Detroit, MI 48202 USA. RP Grossman, SA (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, G87 Bunting Blaustein Res Bldg,1650 Orleans St, Baltimore, MD 21231 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NCI NIH HHS [U01 CA062475, U01 CA62475] NR 29 TC 73 Z9 73 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 21 EP 27 DI 10.1215/S1152.8517.03.00021.8 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800004 PM 14769136 ER PT J AU Prados, MD Yung, WKA Jaeckle, KA Robins, HI Mehta, MP Fine, HA Wen, PY Cloughesy, TF Chang, SM Nicholas, MK Schiff, D Greenberg, HS Junck, L Fink, KL Hess, KR Kuhn, J AF Prados, MD Yung, WKA Jaeckle, KA Robins, HI Mehta, MP Fine, HA Wen, PY Cloughesy, TF Chang, SM Nicholas, MK Schiff, D Greenberg, HS Junck, L Fink, KL Hess, KR Kuhn, J TI Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study SO NEURO-ONCOLOGY LA English DT Article ID HUMAN LIVER; ACTIVE METABOLITE; GLUCURONIDATION; SN-38; CARBOXYLESTERASE; TRANSPORTERS; MICROSOMES; EXPRESSION; RESISTANCE; HUMANS AB This study was conducted to determine the maximum tolerated dose and dose-limiting toxicity of irinotecan (CPT-11) administered every 3 weeks to adults with progressive malignant glioma who were treated with enzyme-inducing antiepileptic drug (EIAED) therapy, and to compare the pharmacokinetics with those in patients not on EIAED therapy treated at the recommended phase 2 dose for other cancers. The CPT-11 dose was 350 mg/m(2) i.v. every 3 weeks and remained fixed in patients not on EIAED therapy, but the dose was escalated by 50-mg/m(2) increments in patients on EIAED therapy. CPT-11 and its metabolites SN-38, SN-38 glucuronide (SN-38G), and APC (7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin) were characterized in both groups. Patients on EIAEDs received 350 to 800 mg/m(2) of CPT-11. Dose-limiting toxicity was due to grade 3 diarrhea despite maximal doses of loperamide. The systemic levels of CPT-11, APC, SN-38G, and SN-38 were all lower in the EIAED group. There was a moderate-to-fair relationship between CPT-11 dose and the area under the curve (AUC) for CPT-11 and APC over the dosage range of 350 to 800 mg/m(2), but no relationship between CPT-11 dose and the AUC for SN-38 or SN-38G. At the 750-mg/m(2) dose, the AUC for CPT-11 (21.6 mug x h/ml) matched the AUC (21.6 mug x h/ml) in the non-EIAED group treated with 350 mg/m(2) of CPT-11. We conclude that the recommended phase 2 dose of CPT-11 for patients on EIAEDs is 750 mg/m(2) when given every 3 weeks. A phase 2 study of patients with recurrent malignant glioma is ongoing to assess the efficacy of CPT-11 when the dose is stratified according to the use of EIAEDs. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurooncol, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Hematol Oncol, Jacksonville, FL 32224 USA. Univ Wisconsin, Dept Med, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiotherapy, Madison, WI 53792 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Univ Calif Los Angeles, Neurooncol Program, Los Angeles, CA 90095 USA. Univ Virginia, Hlth Sci Ctr, Div Neurooncol, Charlottesville, VA 22908 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Univ Texas, Hlth Sci Ctr, Coll Pharm, San Antonio, TX 78229 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. OI mehta, minesh/0000-0002-4812-5713 FU NCRR NIH HHS [M01 RR003186-15S30327, M01 RR003186] NR 23 TC 49 Z9 49 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 44 EP 54 DI 10.1215/S1152.8517.03.00029.2 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800008 PM 14769140 ER PT J AU Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM AF Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM TI Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium SO NEURO-ONCOLOGY LA English DT Review ID ANGIOGENESIS INHIBITOR TNP-470; IN-VIVO MICRODIALYSIS; HEAD-INJURED PATIENTS; CEREBRAL BLOOD-FLOW; INTRACEREBRAL MICRODIALYSIS; MALIGNANT GLIOMA; EXTRACELLULAR GLUTAMATE; CEREBROSPINAL-FLUID; DRUG TRANSPORT; GRADE GLIOMAS AB In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. CMA Microdialysis, N Chelmsford, MA 01863 USA. E Carolina Univ, Human Performance Lab, Greenville, NC 27858 USA. Yale Univ, Dept Psychiat, New Haven, CT 06519 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Neurooncol, Baltimore, MD 21231 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Benjamin, RK (reprint author), Carolina Neurosurg & Spine Associates, Neurooncol Ctr, 1628 E Morehead Rd,Suite 200, Charlotte, NC 28207 USA. EM Ramsis.benjamin@cnsa.co NR 66 TC 25 Z9 27 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 65 EP 74 DI 10.1215/S1152.8517.03.00010.3 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800011 PM 14769143 ER PT J AU Bartzokis, G AF Bartzokis, G TI Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Review DE aging; Alzheimer; myelin; degeneration; development; white matter; oligodendrocytes; amyloid; tau; neurons ID WHITE-MATTER CHANGES; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PROTEIN; GROWTH-FACTOR-I; SYNAPTIC PLASMA-MEMBRANES; NORMAL ADULT BRAIN; TOTAL GRAY-MATTER; A-BETA; OXIDATIVE STRESS; PRECURSOR PROTEIN AB A hypothetical model of Alzheimer's disease (AD) as a uniquely human brain disorder rooted in its exceptional process of myelination is presented. Cortical regions with the most protracted development are most vulnerable to AD pathology, and this protracted development is driven by oligodendrocytes, which continue to differentiate into myelin producing cells late into the fifth decade of life. The unique metabolic demands of producing and maintaining their vast myelin sheaths and synthesizing the brain's cholesterol supply make oligodendrocytes especially susceptible to a variety of insults. Their vulnerability increases with increasing age at differentiation as later-differentiating cells myelinate increasing numbers of axonal segments. These vulnerable late-differentiating cells drive the protracted process of intracortical myelination and by increasing local cholesterol and iron levels, progressively increase the toxicity of the intracortical environment forming the basis for the age risk factor for AD. At older ages, the roughly bilaterally symmetrical continuum of oligodendrocyte vulnerability manifests as a progressive pattern of myelin breakdown that recapitulates the developmental process of myelination in reverse. The ensuing homeostatic responses to myelin breakdown further increase intracortical toxicity and results in the relentless progression and non-random anatomical distribution of AD lesions that eventually cause neuronal dysfunction and degeneration. This process causes a slowly progressive disruption of neural impulse transmission that degrades the temporal synchrony of widely distributed neural networks underlying normal brain function. The resulting network "disconnections" first impact functions that are most dependent on large-scale synchronization including higher cognitive functions and formation of new memories. Multiple genetic and environmental risk factors (e.g. amyloid beta-peptide and free radical toxicity, head trauma, anoxia, cholesterol levels, etc.) can contribute to the cognitive deficits observed in aging and AD through their impact on the life-long trajectory of myelin development and breakdown. This development-to-degeneration model is testable through imaging and post mortem methods and highlights the vital role of myelin in impulse transmission and synchronous brain function. The model offers a framework that explains the anatomical distribution and progressive course of AD pathology, some of the failures of promising therapeutic. interventions, and suggests further testable hypotheses as well as novel approaches for intervention efforts. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurol, Alzheimers Dis Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lab Neuroimaging, Dept Neurol, Div Brain Mapping, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Dept Neurol, Alzheimers Dis Ctr, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG 16570]; NIMH NIH HHS [MH 635701A1] NR 272 TC 449 Z9 457 U1 5 U2 54 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2004 VL 25 IS 1 BP 5 EP 18 DI 10.1016/j.neurobiolaging.2003.03.001 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 759HT UT WOS:000187732800003 PM 14675724 ER PT J AU Bartzokis, G AF Bartzokis, G TI Quadratic trajectories of brain myelin content: unifying construct for neuropsychiatric disorders SO NEUROBIOLOGY OF AGING LA English DT Editorial Material DE brain development; aging; dementia; myelin; white matter; oligodendrocytes; Alzheimer; Parkinson; degeneration; amyloid; tau; alpha; synuclein; iron; cholesterol; free radicals; gender; head trauma; Lewy body; frontotemporal; FTD; ADHD; autism; learning disability; schizophrenia; addiction; impulse control; language; oscillations; processing speed; memory; medication; butyrylcholinesterase; evolution; brain; behavior; tauopathy; synucleinopathy; proteinopathy ID CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER CHANGES; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BUTYRYLCHOLINESTERASE K-VARIANT; CHILDHOOD-ONSET SCHIZOPHRENIA; AMYLOID PRECURSOR PROTEIN; MILD COGNITIVE IMPAIRMENT; PRIMARY VISUAL-CORTEX; NORMAL ADULT BRAIN; TOTAL GRAY-MATTER AB Myelin plays an essential but largely underappreciated role in human brain structure and function. The central challenge raised by the six commentaries is whether the developmental model of age-related cognitive decline and Alzheimer's disease (AD) (Bartzokis, 2003, this issue) is applicable to a wider range of neurodegenerative and neuropsychiatric disorders. The model's premise that the trajectory of myelin development and breakdown is essential to our very uniqueness as a species, directly addresses this issue. In its widest perspective, the model primarily delineates a myelin hypothesis of human brain evolution and normal development and is "secondarily" useful in conceptualizing a wide range of age-related neuropsychiatric diseases. The unique vulnerabilities of oligodendrocytes and the highly protracted and extensive developmental process of human brain myelination delineated in the model are directly pertinent to many uniquely human brain functions and neuropsychiatric diseases including late-life neurodegenerative disorders. This lifelong perspective classifies AD as a disorder likely to arise in old age after a normal trajectory of myelin development. Genetic and environmental factors causing deviations in the myelination trajectory at any point in the lifespan will contribute to differences in the manifestations of later-life degenerative diseases and/or be detected in epidemiologic studies as risk factors or risk mitigators (age, cholesterol, iron, gender, education, brain, trauma, etc.). Ultimately, these perturbations of the myelination process could result in divergent-appearing disorders, such as frontotemporal dementia, dementia pugilistica, AD, dementia with Lewy bodies, and Parkinson's disease, that nonetheless have overlapping neuropathologic and/or clinical manifestations. Furthermore, the model's developmental perspective suggests that dysregulation in the uniquely vulnerable myelination process also contributes to highly prevalent early-life psychiatric disorders such as autism, attention deficit, schizophrenia, addiction, as well as their striking male predominance. Eventually, the dysregulated myelination associated with such disorders may have a direct and predictable impact on the appearance and manifestations of the later-life dementias. By increasing the scientific focus on the process of myelination, this model may facilitate our understanding of the pathophysiology of multiple disorders and pathophysiologic, processes that cut across our current classification of diseases. Ultimately, the model provides a rational framework for the development of novel, myelin-centered treatments that may have widespread efficacy across multiple disease states and could potentially be used in delaying or even preventing some of the most devastating of human disorders. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lab Neuroimaging, Dept Neurol, Div Brain Mapping, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 NR 162 TC 81 Z9 81 U1 6 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2004 VL 25 IS 1 BP 49 EP 62 DI 10.1016/j.neurobiolaging.2003.08.001 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 759HT UT WOS:000187732800010 ER PT J AU Mercado, A Mount, DB Gamba, G AF Mercado, A Mount, DB Gamba, G TI Electroneutral cation-chloride cotransporters in the central nervous system SO NEUROCHEMICAL RESEARCH LA English DT Article DE KCC; potassium-chloride cotransporter; GABA; neural excitation ID K-CL COTRANSPORTER; GABA(A) RECEPTOR ACTIVATION; NEURONAL-SPECIFIC ISOFORM; POSTNATAL RAT BRAINS; NA+-K+-2CL(-) COTRANSPORTER; MOLECULAR-CLONING; NA-K-2CL COTRANSPORTER; FUNCTIONAL EXPRESSION; SYNAPTIC INHIBITION; EXCITATORY ACTIONS AB Several members of the cation-chloride cotransporter ( solute carrier family 12, SLC12) gene family are expressed within the central nervous system, with one family member, the K+-Cl- cotransporter KCC2, exclusive to neurons. These transporters are best known for their roles in cell volume regulation and epithelial salt transport, but are increasingly receiving attention in neuroscience. In particular, intracellular chloride activity and hence the neuronal response to GABA and glycine appears to be determined by a balance between chloride efflux and influx through KCC2 and the Na+-K+-2Cl(-) cotransporter NKCC1, respectively. This relationship has important implications for neuronal development, sensory perception, neuronal excitability, and the response to neuronal injury. Finally, the association between loss of function in the K+-Cl- cotransporter KCC3, with a severe peripheral neuropathy associated with agenesis of the corpus callosum, has revealed an unexpected role for K+-Cl- cotransport in the development and/or maintenance of both the central and peripheral nervous systems. C1 Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 14000, DF, Mexico. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Gamba, G (reprint author), Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Vasco Quiroga 15, Mexico City 14000, DF, Mexico. FU NIDDK NIH HHS [R01 DK36803, R01 DK57708] NR 67 TC 53 Z9 55 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JAN PY 2004 VL 29 IS 1 BP 17 EP 25 DI 10.1023/B:NERE.0000010432.44566.21 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 758PM UT WOS:000187659400004 PM 14992262 ER PT J AU Flibotte, JJ Lee, KE Koroshetz, WJ Rosand, J McDonald, CT AF Flibotte, JJ Lee, KE Koroshetz, WJ Rosand, J McDonald, CT TI Continuous antibiotic prophylaxis and cerebral spinal fluid infection in patients with intracranial pressure monitors SO NEUROCRITICAL CARE LA English DT Article DE antibiotic; infection; intracranial pressure; ventriculostomy; prophylaxis; cerebrospinal fluid ID VENTRICULOSTOMY-RELATED INFECTIONS; RISK-FACTORS; NOSOCOMIAL INFECTIONS; COMPLICATIONS; DURATION; DRAINAGE; COST AB Introduction: Inconsistencies in the recommendation of prophylactic antibiotics for patients with intracranial pressure monitors compelled us to assess the effect of our standard regimen of continuous antibiotic prophylaxis on cerebrospinal fluid infection. We examined the rate, possible risk factors, causative organisms, and characteristics of infection. Methods: Three hundred eleven patients admitted between September 1998 and February 2001 with an intracranial pressure monitoring device in place were included. Two hundred eleven patients received a ventriculostomy, 95 an intraparenchymal fiber optic intracranial pressure monitor (ICPM), and 5 both an ICPM and a ventriculostomy. Results: The overall infection rate was 5.5% (17/311). No patient with an ICPM developed CSF infection. The infection rate among ventriculostomy patients was 8.1% (17/211). The majority of infections (82%) were caused by Gram-positive species. Younger age (OR = 1.04 for each year, 95% CI = 1.01-1.08, p = 0.03) and increasing duration of ventriculostomy insertion (OR = 1.2 for each day of catheter insertion, 95% Cl = 1.1-1.3, p < 0.001) were risk factors for CSF infection in multivariate analysis. Infected patients experienced longer lengths of stay in the NICU (p < 0.001) and hospital (p < 0.001); however, infection did not impact clinical outcome, as measured by mortality and discharge GCS. Conclusion: ICP monitors have a low overall infection rate. When infection occurs, gram positive organisms predominate. For patients with ventriculostomy, duration of catheter insertion strongly predicts infection, but did not alter in-hospital mortality. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP McDonald, CT (reprint author), S Shore Hosp, Stroke Program, S Weymouth, MA 02190 USA. EM ctmcd@massmed.org NR 27 TC 14 Z9 14 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 1 BP 61 EP 68 DI 10.1385/NCC:1:1:61 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FL UT WOS:000230488300007 PM 16174899 ER PT J AU Badjatia, N O'Donnell, J Baker, JR Huang, D Ayata, C Greer, DM Carter, BS Ogilvy, CS McDonald, CT AF Badjatia, N O'Donnell, J Baker, JR Huang, D Ayata, C Greer, DM Carter, BS Ogilvy, CS McDonald, CT TI Achieving normothermia in patients with febrile subarachnoid hemorrhage - Feasibility and safety of a novel intravascular cooling catheter SO NEUROCRITICAL CARE LA English DT Article DE subarachnoid hemorrhage; fever; normothermia; induced hypothermia ID BRAIN-INJURY; GLUTAMATE RELEASE; BODY-TEMPERATURE; CEREBRAL VASOSPASM; CLINICAL-TRIAL; OXYGEN-UPTAKE; ACUTE STROKE; PHASE-II; FEVER; HYPOTHERMIA AB Introduction: Fever is common and difficult to control in patients with subarachnoid hemorrhage (SAH). We have previously shown an inverse relationship between fever and outcome in patients with SAH. Materials/Methods: This was a prospective, single-arm, feasibility trial in which nine patients with SAH underwent temperature management using an intravascular cooling catheter (ICC) to restore and maintain 24 hours of normothermia (36.5 degrees +/- 0.2C). Enrollment occurred after development of a fever of at least 38.3 degrees C within 7 days of SAH that was refractory to acetaminophen treatment. The ICC was placed at the bedside through an introducer sheath via the femoral vein into the inferior vena cava (IVC). Portable X-ray confirmed placement. Results: Normothermia was achieved in seven of the nine patients treated (78%); it was achieved in 100% of the patients with a 14F catheter (n=4) and in 60% of the patients with a 9F catheter (n=5). The two patients not reaching normothermia were not adequately treated for shivering. All other patients reached normothermia irrespective of intubation status. Overall, normothermia was well tolerated and not discontinued because of discomfort or adverse events. Two incidences of deep vein thrombosis were diagnosis by ultrasound that were not associated with clinical sequelae, and IVC filters were placed. No unanticipated adverse events occurred. Discussion: We have demonstrated that fever can be safely and effectively controlled in patients with SAH for at least 24 hours using an ICC. Future studies are needed to assess the effect of such sustained therapy on outcome in patients with SAH. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Badjatia, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Blake 1291,55 Fruit St, Boston, MA 02114 USA. EM nbadjatia@partners.org NR 39 TC 24 Z9 25 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 2 BP 145 EP 156 DI 10.1385/NCC:1:2:145 PG 12 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FN UT WOS:000230488500003 PM 16174910 ER PT J AU Badjatia, N AF Badjatia, N TI Celsius Control (TM) system SO NEUROCRITICAL CARE LA English DT Article C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Badjatia, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Blake 1291,55 Fruit St, Boston, MA 02114 USA. EM nbadjatia@partners.org NR 3 TC 5 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 2 BP 201 EP 203 DI 10.1385/NCC:1:2:201 PG 3 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FN UT WOS:000230488500008 PM 16174915 ER PT J AU Greer, DM AF Greer, DM TI MRI in anoxic brain injury SO NEUROCRITICAL CARE LA English DT Article C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 3 TC 18 Z9 18 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 2 BP 213 EP 215 DI 10.1385/NCC:1:2:213 PG 3 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FN UT WOS:000230488500011 PM 16174918 ER PT J AU Xie, ZC Moir, RD Romano, DM Tesco, G Kovacs, DM Tanzi, RE AF Xie, Zhongcong Moir, Robert D. Romano, Donna M. Tesco, Giuseppina Kovacs, Dora M. Tanzi, Rudolph E. TI Hypocapnia Induces Caspase-3 Activation and Increases A beta Production SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; Amyloid beta-protein; Apoptosis; Caspase-3; Presenilin 1 mutation; Hypoxia; Hypocapnia; Extracellular alkalosis AB Background: At least half of all cases of early onset (<60) familial Alzheimer's disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death. Objective: We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid beta-protein (A beta) production, and assessed the influence of the PS1 Delta 9 FAD mutation on these effects. Method: For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO2 < 40 mm Hg) and hypocapnia plus hypoxia (PO2 <21%). Results: Hypocapnia (20 mm Hg CO2 for 6 h) induced caspase-3 activation and apoptosis; the PS1 Delta 9 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO2) and hypoxia (5%O-2) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased A beta production. Conclusion: The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis. Copyright (C) 2004 S. Karger AG, Basel C1 [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU US Public Health Service, AG/NS, MH [60009-02]; NIH from Harvard Medical School [GMO7592]; Massachusetts Alzheimer's Disease Research Center [P50 AG05134]; NIH [AG00294-17] FX This research was supported by the US Public Health Service, AG/NS, MH 60009-02; T32 NIH training grant from Harvard Medical School Anesthesia Program (GMO7592); Massachusetts Alzheimer's Disease Research Center pilot grant (P50 AG05134), and K12 NIH Mentored Clinical Scientist Development Program in Aging at Harvard Medical School (AG00294-17). NR 40 TC 21 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2004 VL 1 IS 1 BP 29 EP 37 DI 10.1159/000076667 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21RY UT WOS:000208225900005 PM 16908971 ER PT J AU Growdon, JH Adlkofer, FX AF Growdon, John H. Adlkofer, Franz X. TI Preface SO NEURODEGENERATIVE DISEASES LA English DT Editorial Material C1 [Growdon, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Adlkofer, Franz X.] Verum Fdn, Munich, Germany. RP Growdon, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM growdon@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2004 VL 1 IS 4-5 BP 157 EP 159 DI 10.1159/000080980 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21SA UT WOS:000208226100001 ER PT J AU Szekely, CA Thorne, JE Zandi, PP Ek, M Messias, E Breitner, JCS Goodman, SN AF Szekely, CA Thorne, JE Zandi, PP Ek, M Messias, E Breitner, JCS Goodman, SN TI Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review SO NEUROEPIDEMIOLOGY LA English DT Review DE Alzheimer's disease; nonsteroidal anti-inflammatory agents; meta-analysis; systematic review; prevention; observational studies ID ESTROGEN REPLACEMENT THERAPY; RHEUMATOID-ARTHRITIS; CACHE COUNTY; NSAID USE; NEUROPATHOLOGICAL FINDINGS; CONTROLLED-TRIAL; SENILE DEMENTIA; RISK-FACTORS; PREVALENCE; COMMUNITY AB Objective: Alzheimer's disease, the most prevalent dementia, is a prominent source of chronic illness in the elderly. Laboratory evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the onset of Alzheimer's disease. Since the early 1990s, numerous observational epidemiological studies have also investigated this possibility. The purpose of this meta-analysis is to summarize and evaluate available evidence regarding exposure to nonaspirin NSAIDs and risk of Alzheimer's disease using meta-analyses of published studies. Methods: A systematic search was conducted using Medline, Biological Abstracts, and the Cochrane Library for publications from 1960 onwards. All cross-sectional, retrospective, or prospective observational studies of Alzheimer's disease in relation to NSAID exposure were included in the analysis. At least 2 of 4 independent reviewers characterized each study by source of data and design, including method of classifying exposure and outcome, and evaluated the studies for eligibility. Discrepancies were resolved by consensus of all 4 reviewers. Results: Of 38 publications, 11 met the qualitative criteria for inclusion in the meta-analysis. For the 3 case-control and 4 cross-sectional studies, the combined risk estimate for development of Alzheimer's disease was 0.51 (95% CI = 0.40-0.66) for NSAID exposure. In the prospective studies, the estimate was 0.74 (95% CI = 0.62-0.89) for the 4 studies reporting lifetime NSAID exposure and it was 0.42 (95% CI = 0.26-0.66) for the 3 studies reporting a duration of use of 2 or more years. Conclusions: Based on analysis of prospective and nonprospective studies, NSAID exposure was associated with decreased risk of Alzheimer's disease. An issue that requires further exploration in future trials or observational studies is the temporal relationship between NSAID exposure and protection against Alzheimer's disease. Copyright (C) 2004 S. Karger AG, Basel. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Szekely, CA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Room 5010,615 N Wolfe St, Baltimore, MD 21205 USA. EM cszekely@jhsph.edu NR 70 TC 230 Z9 251 U1 2 U2 20 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2004 VL 23 IS 4 BP 159 EP 169 DI 10.1159/000078501 PG 11 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 848TT UT WOS:000223490800001 PM 15279021 ER PT J AU Boas, DA Dale, AM Franceschini, MA AF Boas, DA Dale, AM Franceschini, MA TI Diffuse optical imaging of brain activation: approaches to optimizing image sensitivity, resolution, and accuracy SO NEUROIMAGE LA English DT Article; Proceedings Paper CT Conference on Mathermatics in Brain Imaging CY JUL 12-23, 2004 CL Univ Calif Los Angeles, Inst Pure & Appl Math, Los Angeles, CA HO Univ Calif Los Angeles, Inst Pure & Appl Math DE near-infrared spectroscopy; diffuse optical imaging; HbR; HbT ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; TIME-RESOLVED REFLECTANCE; MONTE-CARLO SIMULATIONS; ADULT HUMAN HEAD; OXYGENATION CHANGES; PHOTON MIGRATION; HEMOGLOBIN OXYGENATION; SENSORY STIMULATION; VISUAL-STIMULATION AB Near-infrared spectroscopy (NIRS) and diffuse optical imaging (DOI) are finding widespread application in the study of human brain activation, motivating further application-specific development of the technology. NIRS and DOI offer the potential to quantify changes in deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration, thus enabling distinction of oxygen consumption and blood flow changes during brain activation. While the techniques implemented presently provide important results for cognition and the neurosciences through their relative measures of HbR and HbT concentrations, there is much to be done to improve sensitivity, accuracy, and resolution. In this paper, we review the advances currently being made and issues to consider for improving optical image quality. These include the optimal selection of wavelengths to minimize random and systematic error propagation in the calculation of the hemoglobin concentrations, the filtering of systemic physiological signal clutter to improve sensitivity to the hemodynamic response to brain activation, the implementation of overlapping measurements to improve image spatial resolution and uniformity, and the utilization of spatial prior information from structural and functional MRI to reduce DOI partial volume error and improve image quantitative accuracy. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anthinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anthinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01-EB002482, R01-EB00790] NR 131 TC 276 Z9 283 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 23 SU 1 BP S275 EP S288 DI 10.1016/j.neuroimage.2004.07.011 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874UA UT WOS:000225374100025 PM 15501097 ER PT J AU Fischl, B Salat, DH van der Kouwe, AJW Makris, N Segonne, F Quinn, BT Dale, AM AF Fischl, B Salat, DH van der Kouwe, AJW Makris, N Segonne, F Quinn, BT Dale, AM TI Sequence-independent segmentation of magnetic resonance images SO NEUROIMAGE LA English DT Article; Proceedings Paper CT Conference on Mathermatics in Brain Imaging CY JUL 12-23, 2004 CL Univ Calif Los Angeles, Inst Pure & Appl Math, Los Angeles, CA HO Univ Calif Los Angeles, Inst Pure & Appl Math DE morphometry; MRI; Alzheimer's disease ID AGE-RELATED-CHANGES; BRAIN IMAGES; CORTICAL SURFACE; HIGH-RESOLUTION; ANATOMICAL LOCALIZATION; STEREOTACTIC METHOD; COORDINATE SYSTEM; PULSE SEQUENCES; OPTIMIZATION; REGISTRATION AB We present a set of techniques for embedding the physics of the imaging process that generates a class of magnetic resonance images (MRIs) into a segmentation or registration algorithm. This results in substantial invariance to acquisition parameters, as the effect of these parameters on the contrast properties of various brain structures is explicitly modeled in the segmentation. In addition, the integration of image acquisition with tissue classification allows the derivation of sequences that are optimal for segmentation purposes. Another benefit of these procedures is the generation of probabilistic models of the intrinsic tissue parameters that cause MR contrast (e.g., T1, proton density, T2*), allowing access to these physiologically relevant parameters that may change with disease or demographic, resulting in nonmorphometric alterations in MR images that are otherwise difficult to detect. Finally, we also present a high band width multiecho FLASH pulse sequence that results in high signal-to-noise ratio with minimal image distortion due to B0 effects. This sequence has the added benefit of allowing the explicit estimation of T2* and of reducing test-retest intensity variability. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Radiol, MGH,Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. MIT, AI Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Neurol, Ctr Morphometr Anal,MGH, Boston, MA 02129 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Fischl, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fischl@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR14075, R01 RR16594-01A1] NR 46 TC 743 Z9 745 U1 3 U2 31 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 23 SU 1 BP S69 EP S84 DI 10.1016/j.neuroimage.2004.07.016 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874UA UT WOS:000225374100007 PM 15501102 ER PT J AU Alpert, NM Reilhac, A Chio, TT Selesnick, I AF Alpert, NM Reilhac, A Chio, TT Selesnick, I TI Wavelet denoising of dynamic PET measurements: Lead into gold? SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 Massachusetts Gen Hosp, PET Imaging Lab, Div Nucl Med, Boston, MA 02114 USA. McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. Polytech Univ, Dept Elect & Comp Engn, Brooklyn, NY 11201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T61 EP T62 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800032 ER PT J AU Franceschini, MA Boas, DA AF Franceschini, MA Boas, DA TI Noninvasive measurement of neuronal activity with near-infrared optical imaging SO NEUROIMAGE LA English DT Article DE neuronal activity; optical imaging; electro-encephalography; magneto-encephalography ID CEREBRAL HEMOGLOBIN OXYGENATION; ADULT HUMAN HEAD; HUMAN BRAIN; VISUAL-STIMULATION; LIGHT-SCATTERING; SPECTROSCOPY NIRS; PHOTON MIGRATION; MOTOR-CORTEX; SIGNAL; ACTIVATION AB Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and noninvasively measuring neuronal and vascular signals in the brain with temporal resolution of up to 1 ms. However, while optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the so-called fast signal) is just emerging and requires further optimization and validation. In this work, we present preliminary studies in which we measured the fast signal in 10 healthy volunteers during finger-tapping, tactile stimulation, and electrical median nerve stimulation. We used an instrument (CW4) with 8 source (690 and 830 nm) and 16 detector positions-more optodes than the instruments in previously reported studies. This allowed us to record the ipsilateral and contralateral sensorimotor cortex simultaneously, while at the same time measuring the evoked hemodynamic response. We used an acquisition time of 25 ms per image; after averaging approximately 1000 events, the signal-to-noise ratio was approximately 10(4). Since the expected relative intensity changes due to the fast signal (approximately 10(-3)) are smaller than the relative intensity changes due to physiological effects (approximately 10(-1)), we enhanced the suppression of competing signals such as the heartbeat-associated intensity changes, and established five criteria with which to assess the robustness of the fast signal. We detected the fast signal in 43% of the measurements during finger-tapping, 60% of those during tactile stimulation, and 23% of those during electrical median nerve stimulation. The relative changes in intensity associated with the fast signal were approximately 0.07% and the latency of the signal was approximately 100 ms. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Franceschini, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, 13th St Bldg 149, Charlestown, MA 02129 USA. EM mari@nmr.mgh.harvard.edu FU NCRR NIH HHS [5P41-RR14075, P41 RR014075]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-04A2, R01 EB001954-05]; NICHD NIH HHS [R01 HD042908, R01-HD42908]; NIMH NIH HHS [R01-MH62854] NR 51 TC 146 Z9 149 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2004 VL 21 IS 1 BP 372 EP 386 DI 10.1016/j.neuroimage.2003.09.040 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 768XY UT WOS:000188597500039 PM 14741675 ER PT J AU Richardson, RD Engel, CC AF Richardson, RD Engel, CC TI Evaluation and management of medically unexplained physical symptoms SO NEUROLOGIST LA English DT Article DE review; somatization; fibrorryalgia; chronic fatigue syndrome ID CHRONIC-FATIGUE-SYNDROME; CHILDHOOD SEXUAL ABUSE; PRIMARY-CARE; SOMATIZATION DISORDER; PSYCHIATRIC-ILLNESS; LIFE EVENTS; NEUROLOGY OUTPATIENT; CHRONIC PAIN; BACK-PAIN; PATIENT AB Background: Medically unexplained physical symptoms (MUPS) and related syndromes are common in medical care and the general population, are associated with extensive morbidity, and have a large impact on functioning. Much of medical practice emphasizes specific pharmacological and surgical intervention for discrete disease states. Medical science, with its emphasis on identifying etiologically meaningful diseases comprised of homogeneous groups of patients, has split MUPS into a number of diagnostic entities or syndromes, each with its own hypothesized pathogenesis. However, research suggests these syndromes may be more similar than different, sharing extensive phenomenological overlap and similar risk factors, treatments, associated morbidities, and prognoses. Examples of syndromes consisting of MUPS include chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivities, somatoform disorders, and 'Gulf War Syndrome.' Review Summary: This paper is a narrative review of the increasing body of evidence suggesting that MUPS and related syndromes are common, disabling, and costly. It emphasizes that MUPS occur along a continuum of symptom count, severity, and duration and may be divided into acute, subacute (or recurrent), and chronic types. Predisposing, precipitating, and perpetuating factors influence the natural history of MUPS. Conclusion: Effective symptom management involves collaborative doctor-patient approaches for identification of problems based on a combination of medical importance and patient readiness to initiate behavioral change, negotiated treatment goals and outcomes, gradual physical activation and exercise prescription. Additionally, efforts should be made to teach and support active rather than passive coping with the symptoms. C1 Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Engel, CC (reprint author), Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. EM cengel@usuhs.mil NR 76 TC 48 Z9 51 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD JAN PY 2004 VL 10 IS 1 BP 18 EP 30 DI 10.1097/01.nrl.0000106921.76055.24 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 768GE UT WOS:000188534600003 PM 14720312 ER PT J AU Garcia-Alloza, M Bacskai, BJ AF Garcia-Alloza, M Bacskai, BJ TI Techniques for brain imaging in vivo SO NEUROMOLECULAR MEDICINE LA English DT Review DE imaging; multiphoton; MRI; PET; SPECT; neurology; Alzheimer's disease ID POSITRON-EMISSION-TOMOGRAPHY; SMALL ANIMAL PET; UNIPOLAR MAJOR DEPRESSION; BETA-AMYLOID PLAQUES; CEREBRAL-BLOOD-FLOW; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MULTIPHOTON MICROSCOPY; HIPPOCAMPAL VOLUME AB Brain imaging technologies provide an unparalleled tool to assess the physiological and pathological changes in the central nervous system. The aim of this work is to review the technical characteristics of widely used imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography (PET), or single photon emission computed tomography (SPECT), as well as their utility in clinical diagnosis and follow-up of different neurological disorders. High-resolution developments of MRI and PET, as well as the more recent imaging technology, multiphoton microscopy, for small animal imaging are also analyzed, as rodent models offer an enormous opportunity to study not only the underlying mechanisms of Alzheimer's disease, Parkinson's disease, depression, and schizophrenia among others, but also potential new treatments for all these diseases. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG21084, AG020570]; NIBIB NIH HHS [EB00768] NR 101 TC 13 Z9 14 U1 3 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2004 VL 6 IS 1 BP 65 EP 78 DI 10.1385/NMM:6:1:065 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 953XX UT WOS:000231119800005 PM 15781977 ER PT J AU Stevens, B Ishibashi, T Chen, JF Fields, RD AF Stevens, Beth Ishibashi, Tomoko Chen, Jiang-Fan Fields, R. Douglas TI Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells SO NEURON GLIA BIOLOGY LA English DT Article DE Purinergic receptor; Schwann-cell development; cell proliferation; ERK/MAPK; adenosine; ATP; neuron-glia interactions; myelination AB Nonsynaptic release of ATP from electrically stimulated dorsal root gangion (DRG) axons inhibits Schwann cell (SC) proliferation and arrests SC development at the premyelinating stage, but the specific types of purinergic receptor(s) and intracellular signaling pathways involved in this form of neuron-glia communication are not known. Recent research shows that adenosine is a neuron-glial transmitter between axons and myelinating glia of the CNS. The present study investigates the Possibility that adenosine might have a similar function in communicating between axons and premyelinating SCs. Using a combination of pharmacological and molecular approaches, we found that mouse SCs in culture express functional adenosine receptors and ATP receptors, a far more complex array of purinergic receptors than thought previously. Adenosine, but not ATP, activates ERK/MAPK through stimulation of cAMP-linked A2(A) adenosine receptors. Both ATP and adenosine inhibit proliferation of SCs induced by platelet-derived growth factor (PDGF), via mechanisms that are partly independent. In contrast to ATP, adenosine failed to inhibit the differentiation of SCs to the O(4)+ stage. This indicates that, in addition to ATP, adenosine is an activity-dependent signaling molecule between axons and premyelinating Schwann cells, but that electrical activity, acting through adenosine, has opposite effects on the differentiation of myelinating glia in the PNS and CNS. C1 [Stevens, Beth; Ishibashi, Tomoko; Fields, R. Douglas] NICHD, Nervous Syst Dev & Plast Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Stevens, Beth] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Chen, Jiang-Fan] Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02114 USA. [Chen, Jiang-Fan] Harvard Univ, Sch Med, Boston, MA USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, Natl Inst Hlth, Bldg 49,Room 5A78,MSC 4495, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z01 HD000713-11] NR 49 TC 47 Z9 49 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 23 EP 34 DI 10.1017/s1740925x04000055 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V04OU UT WOS:000207068500004 PM 16429616 ER PT J AU Kensinger, EA Anderson, A Growdon, JH Corkin, S AF Kensinger, EA Anderson, A Growdon, JH Corkin, S TI Effects of Alzheimer disease on memory for verbal emotional information SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer disease (AD); emotional memory ID UNILATERAL AMYGDALA DAMAGE; DECLARATIVE MEMORY; SEMANTIC KNOWLEDGE; RECOGNITION MEMORY; ENHANCEMENT; ACTIVATION; ATROPHY; EVENTS; VOLUME; WORDS AB In healthy young and older adults, emotional information is often better remembered than neutral information. It is an open question, however, whether emotional memory enhancement is blunted or preserved in Alzheimer disease (AD). Prior studies of emotional memory in AD have included small samples of patients. In addition, studies that failed to find an enhancement effect in AD used stimuli lacking semantic coherence (e.g. lists of unrelated words, some that were emotional and others that were neutral). To circumvent these limitations, the present study examined a large number of AD patients (N = 80) and investigated whether AD patients would show better memory for a verbal description of an emotional event as compared to a neutral one. AD patients were equivalent to young and older control participants in rating the emotional descriptions for valence and arousal. Unlike the control groups, however, memory in AD patients did not benefit from the emotional narratives. We conclude that AD disrupts memory enhancement for at least some types of verbal emotional information. (C) 2003 Elsevier Ltd. All rights reserved. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kensinger, EA (reprint author), MIT, Dept Brain & Cognit Sci, Bldg NE20-392,77 Massachusetts Ave, Cambridge, MA 02138 USA. EM ekensing@alum.mit.edu FU NIA NIH HHS [AG 05134, AG 021525] NR 63 TC 55 Z9 56 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 6 BP 791 EP 800 DI 10.1016/j.neuropsychologia.2003.11.011 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 802FT UT WOS:000220150100008 PM 15037057 ER PT J AU Schnyer, DM Verfaellie, M Alexander, MP LaFleche, G Nicholls, L Kaszniak, AW AF Schnyer, DM Verfaellie, M Alexander, MP LaFleche, G Nicholls, L Kaszniak, AW TI A role for right medial prefrontal cortex in accurate feeling-of-knowing judgments: evidence from patients with lesions to frontal cortex SO NEUROPSYCHOLOGIA LA English DT Article DE metamemory; memory monitoring; frontal injury; feeling-of-knowing ID EPISODIC MEMORY; RECOGNITION MEMORY; CUE-FAMILIARITY; LOBE LESIONS; RETRIEVAL; AMNESIA; MODEL; ACCESSIBILITY; CONFIDENCE; METACOGNITION AB The hypothesis that prefrontal cortex plays a critical role in accurate predictions of episodic memory performance was tested using the feeling-of-knowing (FOK) paradigm. Fourteen patients with a broad spectrum of damaged to the frontal cortex and matched controls read sentences and later were tested for recall memory, confidence judgments, and FOK accuracy using as cues the sentences with the final word missing. While frontal patients were impaired at recall and recognition memory, they were able to make accurate confidence judgments about their recall attempts. By contrast, as a group, the patients were markedly impaired in the accuracy of their prospective FOK judgments. Lesion analysis of frontal patients with clear FOK impairment revealed an overlapping region of damage in right medial prefrontal: cortex. These findings provide functional and anatomical evidence for a dissociation between recall confidence and prospective memory monitoring and are discussed in terms of familiarity and access theories of FOK predictions. (C) 2004 Elsevier Ltd. All rights reserved. C1 Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med 151A, Boston, MA 02130 USA. MIT, MGH, HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Schnyer, DM (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM dschnyer@bu.edu FU NIMH NIH HHS [K23 MH064004-01, K23 MH64004]; NINDS NIH HHS [NS26985] NR 43 TC 92 Z9 100 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 7 BP 957 EP 966 DI 10.1016/j.neuropsychologia.2003.11.020 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 804TZ UT WOS:000220322300011 PM 14998710 ER PT J AU Johnson, SC Baxter, LC Susskind-Wilder, L Connor, DJ Sabbagh, MN Caselli, RJ AF Johnson, SC Baxter, LC Susskind-Wilder, L Connor, DJ Sabbagh, MN Caselli, RJ TI Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment SO NEUROPSYCHOLOGIA LA English DT Article DE fMRI; hippocampus; memory; aging; mild cognitive impairment ID EARLY ALZHEIMERS-DISEASE; ENDURING MEMORY IMPAIRMENT; INFERIOR TEMPORAL CORTEX; RECOGNITION MEMORY; ENTORHINAL CORTEX; NOVELTY DETECTION; BRAIN ACTIVATION; FUNCTIONAL MRI; LOBE EPILEPSY; VERBAL MEMORY AB We examined the dynamic process of encoding novel repeating faces using functional MRI (fMRI) in non-demented elderly volunteers with and without diagnosed memory problems. We hypothesized that adaptation (repetition dependent reduction in activity) would occur in the mesial temporal lobe (MTL), and that this would be associated with cognitive status. Twenty-three right-handed volunteers were studied with an experimental encoding paradigm during fMRI scanning. Twelve participants had the diagnosis of mild cognitive impairment-amnestic type (MCI). The remaining 11 were cognitively healthy. All were diagnosed with a comprehensive neuropsychological battery and neurological evaluation prior to the study; they also received a brief cognitive battery the day of the scan. During the event-related fMRI task, participants viewed unfamiliar faces that repeated on average every 25 s with seven repetitions. The reduction in activation response as a function of repetition of unfamiliar faces was modeled in SPM99. Statistical parametric maps of adaptation slopes reflecting the decrease in activation with stimulus repetition were calculated for each participant, followed by a random-effects group analysis in which slope images were tested for significant group differences. Significant differences in adaptation slopes, with more negative slopes in the controls, were found in the medial temporal search region in the hippocampus and parahippocampal gyrus bilaterally, right more than left. Gray matter density analyses suggest the adaptation difference is not due to atrophy. Results suggest that the medial temporal response over repeated presentation is related to clinical status. Probes of incremental encoding processes over trials may be useful markers of medial temporal lobe integrity. (C) 2003 Elsevier Ltd. All rights reserved. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Sun Hlth Res Inst, Cleo Roberts Ctr Clin Res, Sun City, AZ USA. Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace,11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Johnson, Sterling/0000-0002-8501-545X FU NIA NIH HHS [P30 AG019610, AG18540]; NIMH NIH HHS [MH65723] NR 68 TC 63 Z9 67 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 7 BP 980 EP 989 DI 10.1016/j.neuropsychologia.2003.11.015 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 804TZ UT WOS:000220322300013 PM 14998712 ER PT J AU Reger, MA Welsh, RK Watson, GS Cholerton, B Baker, LD Craft, S AF Reger, MA Welsh, RK Watson, GS Cholerton, B Baker, LD Craft, S TI The relationship between neuropsychological functioning and driving ability in dementia: A meta-analysis SO NEUROPSYCHOLOGY LA English DT Article ID MOTOR-VEHICLE CRASHES; SIMULATED CAR CRASHES; ALZHEIMERS-DISEASE; OLDER DRIVERS; PERFORMANCE; ATTENTION; RELIABILITY; IMPAIRMENT; FITNESS; SAFETY AB A meta-analysis of 27 primary studies was conducted to examine the relationship between neuropsychological functioning and driving ability for adults with dementia. When studies using a control group were included, the relationship between cognitive measures and on-road or non-road driving measures was significant for all reported domains; mean correlations ranged from .35 to .65. Caregiver reports of driving ability and cognitive variables were correlated significantly only on measures of mental status and visuospatial skills. When studies using a control group were excluded, moderate mean correlations were observed for visuospatial skills and on-road or non-road measures, and for mental status with non-road tests. Other effects were small or nonsignificant. Implications for basing driving recommendations on neuropsychological testing are, discussed. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC A182, Tacoma, WA 98493 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Reger, MA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC A182, 9600 Vet Dr, Tacoma, WA 98493 USA. EM mreger@u.washington.edu FU NIA NIH HHS [T32 AG00258] NR 55 TC 107 Z9 109 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2004 VL 18 IS 1 BP 85 EP 93 DI 10.1037/0894-4105.18.1.85 PG 9 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 766WJ UT WOS:000188398100009 PM 14744191 ER PT J AU Caruso, PA Poussaint, TY Tzika, AA Zurakowski, D Astrakas, LG Elias, ER Bay, C Irons, MB AF Caruso, PA Poussaint, TY Tzika, AA Zurakowski, D Astrakas, LG Elias, ER Bay, C Irons, MB TI MRI and H-1 MRS findings in Smith-Lemli-Opitz syndrome SO NEURORADIOLOGY LA English DT Article DE Smith-Lemli-Opitz; magnetic resonance imaging; magnetic resonance spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; ABNORMAL CHOLESTEROL-METABOLISM; SONIC-HEDGEHOG; CALIFORNIA POPULATION; PROTON SPECTROSCOPY; FACIAL ANOMALIES; HUMAN BRAIN; IN-VIVO; GENE; BIOSYNTHESIS AB Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clinical and biochemical findings with the results of MRI and H-1 MRS. Eighteen patients were studied; all underwent MRI of the brain, and 16 had H-1 MRS of the cerebral white matter. The ratios choline:NAA, lipid:NAA, and lipid:choline metabolite were found to be correlated with the clinical degree of disease severity, serum total sterol ratios (cholesterol/cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol) and in two cases with the effect of cholesterol therapy. Abnormal CNS findings were noted in five patients, including callosal abnormalities (n=4), Dandy-Walker variant (n=1), and arachnoid cyst (n=1). Holoprosencephaly was noted in one patient with a prevalence of 6%. Choline:NAA was elevated in seven patients. There was a statistically significant positive correlation between the lipid:choline ratio and the serum cholesterol precursor, 8-dehydrocholesterol. In two patients H-1 MRS demonstrated abnormally elevated lipids prior to cholesterol therapy, which improved on therapy. The use of MRI and H-1 MRS is an effective way to demonstrate brain structural abnormalities in patients with SLOS and may prove to be an effective method for the assessment of the effects of cholesterol replacement therapy in the brain. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat & Genet, Denver, CO 80218 USA. Childrens Hosp Pittsburgh, Dept Med Genet, Pittsburgh, PA 15213 USA. Childrens Hosp, Div Clin Genet & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Colorado, Sch Med, Denver, CO USA. RP Poussaint, TY (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Tina.Poussaint@tch.harvard.edu RI Astrakas, Loukas/F-5918-2011 FU NCRR NIH HHS [M01 RR02172] NR 64 TC 25 Z9 26 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JAN PY 2004 VL 46 IS 1 BP 3 EP 14 DI 10.1007/s00234-003-1110-1 PG 12 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 769DJ UT WOS:000188610900003 PM 14605787 ER PT J AU Cooper, RA Boninger, ML Cooper, R Fitzgerald, SG Kellerher, A AF Cooper, RA Boninger, ML Cooper, R Fitzgerald, SG Kellerher, A TI Preliminary assessment of a prototype advanced mobility device in the work environment of veterans with spinal cord injury SO NEUROREHABILITATION LA English DT Article ID WHEELCHAIRS AB The INDEPENDENCE(TM) 3000 IBOT(TM) Transporter (IBOT(TM) is an electronically stabilizing device for people with disabilities. The purpose of this study was to collect qualitative data on the potential for the IBOT(TM) to improve employment satisfaction of veterans who use wheelchairs to work. This study was based upon observations by trained clinicians, and responses to a survey completed by four men with traumatic spinal cord injury, who worked in an office environment. The mean age of the subjects was 52 +/- 8.8 years. The subjects used the devices to hold eye-level discussions with colleagues, climb stairs, ascend steep ramps, and negotiate curbs. When subjects were asked to rate the ease of getting around in the IBOT(TM) compared to their personal wheelchairs, they responded with a mean of 6.7 +/- 1.8 on a 10-point visual analog scale. The response to rating the overall function of the IBOT(TM) within their working environment yielded a rating of 6.0 +/- 2.8. Half of the users felt that the IBOT(TM) would help them at work and all thought it should be made available to veterans who use wheelchairs. A larger study should be conducted to determine if the IBOT(TM) affects work performance and the ability to return to work. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper+@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 20 TC 11 Z9 12 U1 2 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2004 VL 19 IS 2 BP 161 EP 170 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 836YW UT WOS:000222593500010 PM 15201475 ER PT J AU Yang, H Wang, L Wu, SV Tay, J Goulet, M Boismenu, R Czimmer, J Wang, Y Wu, S Ao, Y Tache, Y AF Yang, H Wang, L Wu, SV Tay, J Goulet, M Boismenu, R Czimmer, J Wang, Y Wu, S Ao, Y Tache, Y TI Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent SO NEUROSCIENCE LA English DT Article DE capsaicin; secretin receptor; nodose ganglia; vagus; nucleus tractus solitarii; central nucleus of the amygdala ID PHASEOLUS-VULGARIS LEUKOAGGLUTININ; CORTICOTROPIN-RELEASING-FACTOR; NUCLEUS-TRACTUS-SOLITARIUS; CCK-A RECEPTORS; AREA POSTREMA; EFFERENT PROJECTIONS; C-FOS; PARABRACHIAL NUCLEUS; GENE-EXPRESSION; SUBREGIONAL TOPOGRAPHY AB I.v. injection of secretin activates neurons in brain areas controlling autonomic function and emotion. Peripheral administration of secretin inhibits gastric functions through a central mechanism that is mediated by vagal dependent pathways. We investigated whether the vagus nerve is involved in i.p. injection of secretin-induced brain neuronal activation in conscious rats as monitored by Fos immunohistochemistry. Secretin (40 or 100 mug/kg, i.p., 90 min) induced a dose-related increase in the number of Fos positive neurons in the central nucleus of the amygdala (CeA), and a plateau Fos response in the area postrema (AP), nucleus tractus solitarii (NTS), locus coeruleus (LC), Barrington's nucleus (Bar), external lateral subnucleus of parabrachial nucleus (PBel) and arcuate nucleus, and at 100 mug/kg, in the dorsal motor nucleus of the vagus (DMV) compared with i.p. injection of vehicle. Double immunohistochemistry showed that secretin (40 mug/kg, i.p.) activates tyrosine hydroxylase neurons in the NTS. Subdiaphragmatic vagotomy (7 days) abolished Fos expression-induced by i.p. secretin (40 mug/kg) in the NTS, DMV, LC, Bar, PBel and CeA, while a significant rise in the AP was maintained. In contrast, s.c. capsaicin (10 days) did not influence the Fos induction in the above nuclei. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR showed that secretin receptor mRNA is expressed in the nodose ganglia and levels were higher in the right compared with the left ganglion. These results indicate that peripheral secretin activates catecholaminergic NTS neurons as well as neurons in medullary, pontine and limbic nuclei regulating autonomic functions and emotion through vagal-dependent capsaicin-resistant pathways. Secretin injected i.p. may signal to the brain by interacting with secretin receptors on vagal afferent as well as on AP neurons outside the blood-brain barrier. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Ctr Neruovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-41301] NR 75 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 128 IS 1 BP 131 EP 141 DI 10.1016/j.neuroscience.2004.06.027 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 855EE UT WOS:000223955100013 PM 15450360 ER PT J AU Sosa, MAG Wen, PH De Gasperi, R Perez, GM Senturk, E Friedrich, VL Elder, GA AF Sosa, MAG Wen, PH De Gasperi, R Perez, GM Senturk, E Friedrich, VL Elder, GA TI Entorhinal cortex lesioning promotes neurogenesis in the hippocampus of adult mice SO NEUROSCIENCE LA English DT Article DE ibotenic acid; 5'-bromo-2'-deoxyuridine; beta-III tubulin; calbindin; entorhinal cortex ID RAT DENTATE GYRUS; NMDA RECEPTOR ACTIVATION; REACTIVE SYNAPTOGENESIS; IBOTENIC ACID; GENETIC INFLUENCE; GRANULE NEURONS; FASCIA-DENTATA; PROLIFERATION; EXPRESSION; CELLS AB Hippocampal neurogenesis in adult mammals is influenced by many factors. Lesioning of the entorhinal cortex is a standard model used to study injury and repair in the hippocampus. Here we use bromodeoxyuridine (BrdU) labeling combined with immunohistochemical identification using cell type specific markers to follow the fate of neural progenitors in the hippocampus following entorhinal cortex lesioning in mice. We show that unilateral entorhinal cortex. lesioning does not alter the rate of neural progenitor proliferation in the ipsilateral dentate gyrus during the first 3 days after lesioning. However it enhances cell survival at 42 days post-lesioning leading to an increased number of beta-III tubulin and calbindin-immunoreactive neurons being produced. By contrast, when BrdU was administered 21 days post-lesioning, the number of surviving cells 21 days later was similar on the lesioned and non-lesioned sides. Thus, acutely entorhinal cortex lesioning promotes neurogenesis by enhancing survival of either neural progenitors or their progeny. However, this stimulus to neurogenesis is not sustained into the recovery period. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Bronx Vet Adm Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. RP Elder, GA (reprint author), Bronx Vet Adm Med Ctr, Psychiat Serv, 3F22,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu NR 71 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 4 BP 881 EP 891 DI 10.1016/j.neuroscience.2004.05.058 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 851NS UT WOS:000223692400009 ER PT J AU Szot, P Wilkinson, CW White, SS Leverenz, JB Greenup, JL Colasurdo, EA Peskind, ER Raskind, MA AF Szot, P Wilkinson, CW White, SS Leverenz, JB Greenup, JL Colasurdo, EA Peskind, ER Raskind, MA TI Chronic cortisol suppresses pituitary and hypothalamic peptide message expression in pigtailed macaques SO NEUROSCIENCE LA English DT Article DE hypercortisolemia; anterior pituitary; paraventricular nucleus (PVN); corticotropin-releasing factor (CRF); adrenocorticotropic hormone (ACTH); monkey ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RIBONUCLEIC-ACID; PARAVENTRICULAR NUCLEUS; GLUCOCORTICOID REGULATION; DIFFERENTIAL REGULATION; ARGININE VASOPRESSIN; RECEPTOR EXPRESSION; ANTERIOR-PITUITARY; RNA LEVELS; RAT-BRAIN AB The effects of chronic elevations in circulating glucocorticoids on the expression of peptides and peptide receptors of the hypothalamic-pituitary-adrenal (HPA) axis have been studied extensively in rodents, but they have not been examined in primates. To determine the responses of the HPA axis in primates to elevated cortisol, hypothalamic and pituitary tissue from normal older pigtailed macaques (Macaca nemestrina) that had received daily oral administration of cortisol or placebo for 1 year were studied. Proopiomelanocortin in the anterior pituitary and corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN) were significantly reduced in cortisol-treated monkeys in comparison with controls. CRF receptor 1 (CRF-R1) expression in the anterior pituitary and arginine vasopressin mRNA expression in the PVN were unchanged by chronic cortisol administration. Sustained elevation of circulating glucocorticoids results in suppression of HPA peptide and peptide receptor expression in the PVN and anterior pituitary similar to those found in rodents. Chronic therapeutic administration of glucocorticoids in humans may have unintended consequences for hypothalamic and pituitary function. Published by Elsevier Ltd on behalf of IBRO. C1 Vet Affairs Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriat Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Szot, P (reprint author), Vet Affairs Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM szot@u.washington.edu NR 36 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 126 IS 1 BP 241 EP 246 DI 10.1016/j.neuroscience.2004.03.030 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 824SP UT WOS:000221707100022 PM 15145089 ER PT J AU Sternini, C Anselmi, L Guerrini, S Cervio, E Pham, T Balestra, B Vicini, R Baiardi, P D'Agostino, GL Tonini, M AF Sternini, C Anselmi, L Guerrini, S Cervio, E Pham, T Balestra, B Vicini, R Baiardi, P D'Agostino, GL Tonini, M TI Role of galanin receptor 1 in peristaltic activity in the guinea pig ileum SO NEUROSCIENCE LA English DT Article DE cholinergic transmission; descending myenteric neurons; ascending myenteric neurons; longitudinal muscle-myenteric plexus preparations; noncholinergic; nonadrenergic inhibitory pathways ID MU-OPIOID RECEPTORS; SMALL-INTESTINE; MYENTERIC NEURONS; CHOLINERGIC NEUROTRANSMISSION; IMMUNOREACTIVITY; TRANSMISSION; SUBTYPES; GUT; INTERNALIZATION; ENDOMORPHIN-1 AB Galanin effects are mediated by distinct receptors, galanin receptor 1 (GAL-R1), GAL-R2 and GAL-R3. Here, we analyzed 1) the role of GAL-R1 in cholinergic transmission and peristalsis in the guinea-pig ileum using longitudinal muscle-myenteric plexus preparations and intact segments of the ileum in organ bath, and 2) the distribution of GAL-R1 immunoreactivity in the myenteric plexus with immunohistochemistry and confocal microscopy. Galanin inhibited electrically stimulated contractions of longitudinal muscle-myenteric plexus preparations with a biphasic curve. Desensitization with 1 muM galanin suppressed the high potency phase of the curve, whereas the GAL-R1 antagonist, RWJ-57408 (1 muM), inhibited the low potency phase. Galanin (3 muM) reduced the longitudinal muscle contraction and the peak pressure, and decreased the compliance of the circular muscle. All these effects were antagonized by RWJ-57408 (1 or 10 muM). RWJ-57408 (10 muM) per se did not affect peristalsis parameters in normal conditions, nor when peristalsis efficiency was reduced by partial nicotinic transmission blockade with hexamethonium. In the myenteric plexus, GAL-RI immunoreactivity was localized to neurons and to fibers projecting within the plexus and to the muscle. GAL-R1 was expressed mostly by cholinergic neurons and by some neurons containing vasoactive intestinal polypeptide or nitric oxide synthase. This study indicates that galanin inhibits cholinergic transmission to the longitudinal muscle via two separate receptors; GAL-R1 mediates the low potency phase. The reduced peristalsis efficiency could be explained by inhibition of the cholinergic drive, whereas the decreased compliance is probably due to inhibition of descending neurons and/or to the activation of an excitatory muscular receptor. Endogenous galanin does not appear to affect neuronal pathways subserving peristalsis in physiologic conditions via GAL-R1. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Vet Adm Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Pavia, Dept Physiol & Pharmacol Sci, I-27100 Pavia, Italy. Univ Pavia, S Maugeri Fdn, I-27100 Pavia, Italy. Univ Pavia, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy. RP Sternini, C (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Bldg 115,Room 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM csternin@ucla.edu OI Cervio, Elisabetta/0000-0002-9922-077X FU NIDDK NIH HHS [DK35740, DK41301, DK57037] NR 44 TC 15 Z9 15 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 1 BP 103 EP 112 DI 10.1016/j.neuroscience.2003.12.043 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 812SA UT WOS:000220858000011 PM 15051149 ER PT J AU Husson, I Mesples, B Medja, F Leroux, P Kosofsky, B Gressens, P AF Husson, I Mesples, B Medja, F Leroux, P Kosofsky, B Gressens, P TI Methylphenidate and MK-801, an N-methyl-D-aspartate receptor antagonist: shared biological properties SO NEUROSCIENCE LA English DT Article DE methylphenidate; MK-801; GBR-12783; apoptosis; ibotenate; NMDA receptor ID INDUCED APOPTOTIC NEURODEGENERATION; DEFICIT-HYPERACTIVITY DISORDER; PERIVENTRICULAR WHITE-MATTER; DEVELOPING RAT-BRAIN; CELL-DEATH; SYNAPTIC PLASTICITY; NUCLEUS-ACCUMBENS; DOPAMINE; STRIATUM; COCAINE AB Methylphenidate (MPH), a dopamine reuptake inhibitor, is used increasingly to treat attention deficit and hyperactivity disorders in children. Given that dopaminergic mechanisms, contribute to the structural and functional maturation of brain circuitry, consideration of the potential influence of MPH in disrupting such processes seems warranted. Following a similar logic regarding the relevance of glutamate neurotransmission in mediating aspects of brain maturation, we and others have previously utilized in vivo and in vitro studies of the developing rodent brain to establish that MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist has both neuroprotective and pro-apoptotic actions. In this study we used a neonatal murine model of excitotoxin-induced cortical injury to compare such actions between MPH and MK-801, and found that MPH shared some biological properties with MK-801. Specifically, both drugs were neuroprotective against excitotoxic challenge resulting in neonatal brain lesions and in vitro neuronal death, but both drugs also exacerbated programmed neural cell death. However, this profile of action was not shared by the dopamine reuptake blocker GBR-12783, a molecule which like MPH binds to and blocks the dopamine transporter, but which is structurally dissimilar to MPH, suggesting that inhibition of dopamine reuptake alone cannot explain the results from our MPH studies. The implications of our findings are that when studied in our developmental mouse model both drugs demonstrate similar capacities to be either neuroprotective or pro-apoptotic, depending on the specific biologic setting in which they act. Additional studies to identify some potential positive as well as negative consequences of exposure to these drugs during brain development in clinical settings are warranted. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Hop Robert Debre, INSERM E 9935, F-75019 Paris, France. Hop Robert Debre, Serv Neurol Pediat, F-75019 Paris, France. Fac Med & Pharm, Lab MERCI UPRESA 2122, F-76000 Rouen, France. Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, E Charlestown, MA 02129 USA. RP Gressens, P (reprint author), Hop Robert Debre, INSERM E 9935, 48 Bd Serurier, F-75019 Paris, France. EM gressens@rdebre.inserm.fr NR 45 TC 21 Z9 22 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 1 BP 163 EP 170 DI 10.1016/j.neuroscience.2004.01.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 812SA UT WOS:000220858000017 PM 15051155 ER PT J AU D'Angelo, I Brecha, NC AF D'Angelo, I Brecha, NC TI Y2 receptor expression and inhibition of voltage-dependent Ca2+ influx into rod bipolar cell terminals SO NEUROSCIENCE LA English DT Article DE retina; calcium imaging; fura-2 AM; Ca2+ channels; neuropeptides ID TIGER SALAMANDER RETINA; GAMMA-AMINOBUTYRIC-ACID; ROOT GANGLION NEURONS; NEUROPEPTIDE-Y; RAT RETINA; MAMMALIAN RETINA; NEUROTRANSMITTER RELEASE; IMMUNOREACTIVE NEURONS; SYNAPTIC TRANSMISSION; CALCIUM CURRENT AB Neuropeptide Y (NPY) is a potent inhibitory neuropeptide expressed by amacrine cells in the rat retina. NPY modulates the release of multiple neurotransmitters in mammalian retina, yet the mechanisms mediating this regulation are not well defined. To further understand the action of NPY in the retina, Y receptor coupling to voltage-dependent Ca2+ channels was investigated using Ca2+ imaging with fura-2 AM to measure [Ca2+](i) increases in rod bipolar cell terminals. Y receptor expression was studied in rat retinal tissue with reverse transcription-polymerase chain reaction (RT-PCR). NPY inhibited the depolarization-evoked Ca2+ influx into rod bipolar cell axon terminals and caused a dose-dependent reduction and an average maximal inhibition of 72% at 1 muM, which was reversed upon washout. K+-evoked Ca2+ increases were also inhibited by the selective Y2 receptor agonists, C2-NPY and NPY(13-36), at concentrations of 1 muM, but not by the selective Y1 receptor agonist, [Leu(31)Pro(34)]NPY, selective Y4 receptor agonist, rPP, or the selective Y5 receptor agonist, [D-Trp32]-NPY. Y receptor expression was determined using RT-PCR for all known Y receptor subtypes. Y2 receptor mRNA, as well as Y1, Y4, and Y5 receptor mRNAs, are present in the rat retina. Like the rod bipolar cell, other studies in central neurons have shown that the Y2 receptor is expressed predominantly as a presynaptic receptor and that it modulates transmitter release. Together, these findings suggest that NPY activates presynaptic Y2 receptors to inhibit voltage-dependent Ca2+ influx into rod bipolar cell terminals, and establishes one mechanism by which NPY may reduce L-glutamate release from the rod bipolar cell synapse. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP D'Angelo, I (reprint author), Univ Calif Los Angeles, Dept Neurobiol, Box 951763, Los Angeles, CA 90095 USA. EM impact@ucla.edu FU NEI NIH HHS [EY07026, EY04067]; NINDS NIH HHS [NS07101] NR 69 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 4 BP 1039 EP 1049 DI 10.1016/j.neuroscience.2003.10.041 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 824IF UT WOS:000221679300021 PM 15120863 ER PT J AU Broom, DC Samad, TA Kohno, T Tegeder, I Geisslinger, G Woolf, CJ AF Broom, DC Samad, TA Kohno, T Tegeder, I Geisslinger, G Woolf, CJ TI Cyclooxygenase 2 expression in the spared nerve injury model of neuropathic pain SO NEUROSCIENCE LA English DT Article DE partial nerve injury; allodynia; hyperalgesia; spinal dorsal horn; rofecoxib ID RAT SPINAL-CORD; PROSTAGLANDIN E-2 RELEASE; SUPERFICIAL DORSAL HORN; PERIPHERAL INFLAMMATION; SUBSTANTIA-GELATINOSA; ION CHANNELS; AMINO-ACIDS; INHIBITION; HYPERALGESIA; NEURONS AB Cyclooxygenase-2 (COX-2) after induction peripherally, and within the CNS, plays an important role in producing inflammatory pain. However, its role in neuropathic pain models is controversial. Recently a robust and persistent model of partial nerve injury pain, the spared nerve injury (SNI) model, has been developed. The aim of the present study was to examine the regulation of COX-2 in the rat SNI model and to evaluate the effectiveness of the selective COX-2 inhibitor rofecoxib in preventing neuropathic allodynia and hyperalgesia. RNase protection assays revealed only a very small and transient increase in COX-2 mRNA in the dorsal horn of the spinal cord in the SNI model with a maximum change at 24 h. Immunohistochemical analysis showed a small increase in COX-2 protein in the deep layers of the dorsal horn 10 h following SNI surgery. Rofecoxib (100 muM) did not affect spontaneous excitatory postsynaptic currents or ei-amino-3-hydroxy-5-methyl-4-isoxazole propanoic acid (AMPA) and N-methyl-D-aspartate (NMDA) responses in lamina 11 neurons from spinal cords of animals with SNI indicating no detectable action on transmitter release or postsynaptic activity. Furthermore, rofecoxib treatment (1 and 3.2 mg/kg for 5 and 3 days respectively starting on the day of surgery) failed to modify the development of allodynia and hyperalgesia in the SNI model. However, rofecoxib significantly reduced inflammatory hypersensitivity evoked by injection of complete Freund's adjuvant into one hindpaw, indicating that the doses used were pharmacologically active. The pain hypersensitivity produced by the SNI model is not COX-2-dependent. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM woolf.clifford@mgh.harvard.edu FU NINDS NIH HHS [NS38253] NR 40 TC 67 Z9 69 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 124 IS 4 BP 891 EP 900 DI 10.1016/j.neuoscience.2004.01.003 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 807VQ UT WOS:000220529400018 PM 15026129 ER PT J AU Patierno, S Raybould, HE Sternini, C AF Patierno, S Raybould, HE Sternini, C TI Abdominal surgery induces mu opioid receptor endocytosis in enteric neurons of the guinea-pig ileum SO NEUROSCIENCE LA English DT Article DE gastrointestinal transit; endogenous opioids; opiates; ascending pathway; descending pathway ID RAT GASTROINTESTINAL-TRACT; POSTOPERATIVE ILEUS; MYENTERIC NEURONS; CIRCULAR MUSCLE; INTESTINAL MOTILITY; ENDOGENOUS OPIOIDS; EXOGENOUS OPIOIDS; BOWEL DYSFUNCTION; NERVOUS-SYSTEM; PORCINE ILEUM AB Immunohistochemistry and confocal microscopy were used to investigate mu opioid receptor (muOR) internalization in enteric neurons of the guinea-pig ileum following abdominal surgery. The following surgical procedures were performed under halothane or isofluorane anesthesia: a) midline abdominal skin incision, b) laparotomy or c) laparotomy with intestinal manipulation. Gastrointestinal transit was evaluated by using a non-absorbable marker and measuring fecal pellet output. In neurons from normal and control (anesthesia alone) animals, muOR was predominantly at the cell surface. muOR endocytosis following skin incision was not significantly different from controls (21.2+/-3.5% vs. 13.7+/-2.1%, mean+/-S.E.M.), whereas it was significantly increased by laparotomy (46.5+/-6.1%; P<0.01 vs. controls) or laparotomy plus intestinal manipulation (40.5+/-6.1%; P<0.01 vs. controls) 30 min following surgery compared with controls. muOR endocytosis remained elevated at 4 h (38.6+/-1.2%; P<0.01 vs. controls), whereas it was similar to controls at 6 and 12 h (17.5+/-5.8% and 11.2+/-3.0%). muOR endocytosis occurred in cholinergic and nitrergic neurons. Gastrointestinal transit was significantly delayed by laparotomy or laparotomy plus intestinal manipulation (12.8+/-1.2 and 13.8+/-0.6 h vs. 7.0+/-0.5 in controls; P<0.01), but was not significantly changed by skin incision (8.2+/-0.6 h). The findings of the present study support the concept that the noxious stimulation caused by abdominal surgery induces release of endogenous opioids thus resulting in muOR endocytosis in neurochemically distinct enteric neurons. muOR internalization can serve as indirect evidence of opioid release and as a means to visualize neuronal pathways activated by opioids. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 CURE Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. RP CURE Digest Dis Res Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Div Digest Dis, Bldg 115,Room 224 VAGLAHS,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM kira@ucla.edu FU NIDA NIH HHS [P50 DA005010, DA 05010]; NIDDK NIH HHS [DK 41301, DK41004, DK54155] NR 76 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 123 IS 1 BP 101 EP 109 DI 10.1016/j.neuroscience.2003.08.052 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 757WK UT WOS:000187584300011 PM 14667445 ER PT J AU Karadsheh, MF Byun, N Mount, DB Delpire, E AF Karadsheh, MF Byun, N Mount, DB Delpire, E TI Localization of the KCC4 potassium-chloride cotransporter in the nervous system SO NEUROSCIENCE LA English DT Article DE spinal cord; nerve; choroid plexus; brain; cation-chloride; transport ID K-CL COTRANSPORTER; CATION-CHLORIDE COTRANSPORTERS; NEURONAL-SPECIFIC ISOFORM; POSTNATAL RAT BRAINS; CHOROID-PLEXUS; NA-K-2CL COTRANSPORTER; EXPRESSION; POTASSIUM; CELLS; INHIBITION AB Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the function and development of both the peripheral and central nervous systems. KCC4 is perhaps the least abundant KCC in the adult mammalian brain, where its localization is unknown. In the embryonic brain, KCC4 mRNA is found in the periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002) 2358]. To investigate the distribution of KCC4 protein in the nervous system we developed a rabbit polyclonal antibody directed against a short N-terminal peptide. Western blot analysis of brain microsomal protein using purified antibody revealed the presence of a band at approximately 145 kDa, consistent with the size of a glycosylated K-Cl cotransporter. Western blot analysis of brain, spinal cord and peripheral nerves revealed high expression levels in peripheral nerves and spinal cord, with low levels in whole brain. Within the brain, the cerebral cortex, hippocampus, and cerebellum revealed minimal KCC4 expression, whereas midbrain and brainstem demonstrated higher levels. In the adult mouse brain, KCC4 staining was observed on the apical membrane of choroid plexus epithelial cells as well as in cranial nerves. All other brain structures, e.g. cortex, hippocampus, cerebellum showed no KCC4 immunoreactivity, suggesting very low or absent expression of the cotransporter in these regions. Co-staining of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid plexus, where it likely participates to K+ reabsorption. KCC4 is also expressed in peripheral neurons, where its function remains to be determined. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Vanderbilt Univ Sch Med, Dept Anesthesiol, Anesthesiol Res Div, Nashville, TN 37232 USA. Vanderbilt Univ Sch Med, Dept Pediat, Nashville, TN 37232 USA. VA Boston Healthcare Syst, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Delpire, E (reprint author), Vanderbilt Univ Sch Med, Dept Anesthesiol, Anesthesiol Res Div, T-4202 Med Ctr N, Nashville, TN 37232 USA. EM eric.delpire@vanderbilt.edu FU NIDDK NIH HHS [DK57708]; NINDS NIH HHS [NS36758] NR 43 TC 47 Z9 48 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 123 IS 2 BP 381 EP 391 DI 10.1016/j.neuroscience.2003.10.004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 761BX UT WOS:000187880500007 PM 14698746 ER PT J AU Mueller, JL Ellenberger, EA Vaughn, LK Belknap, JK Quock, RM AF Mueller, JL Ellenberger, EA Vaughn, LK Belknap, JK Quock, RM TI Detection and mapping of quantitative trait loci that determine responsive-ness of mice to nitrous oxide antinociception SO NEUROSCIENCE LA English DT Article DE nitrous oxide; antinociception; quantitative trait loci; mice ID INBRED MOUSE STRAINS; ANALGESIA; LINKAGE; ANTAGONISM; TOLERANCE; RATS; MAP AB Exposure to 70% N2O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N2O. Offspring from the F-2 generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N2O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, 24 spleens were collected from each of the following four groups: male and female F-2 mice responding to 70% N2O in oxygen with 100% response (high-responders); and male and female F-2 mice responding with 0% response (low-responders). Genomic DNA was extracted from the spleens and genotyped with simple sequence length polymorphism MapPairs markers. Findings were combined with findings from the earlier QTL analysis from BXD recombinant inbred mice [Brain Res 725 (1996) 23]. Combined results revealed two significant QTL that influence responsiveness to nitrous oxide on proximal chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18. The chromosome 2 QTL was evident only in males. A significant interaction was found between a locus on chromosome 6 and another on chromosome 13 with a substantial effect on N2O antinociception. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Pullman, WA 99164 USA. Oregon Hlth Sci Univ, Res Serv, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Marquette Univ, Dept Biomed Sci, Milwaukee, WI 53201 USA. Univ Illinois, Coll Med, Dept Biomed Sci, Rockford, IL 61107 USA. RP Quock, RM (reprint author), Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, POB 646534, Pullman, WA 99164 USA. EM quockr@wsu.edu FU NIAAA NIH HHS [P60 AA010760]; NIDA NIH HHS [DA10913, DA05228]; NIDCR NIH HHS [DE 10047] NR 27 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 123 IS 3 BP 743 EP 749 DI 10.1016/j.neuroscience.2003.10.020 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 761YF UT WOS:000187942500018 PM 14706786 ER PT J AU Barker, FG Amin-Hanjani, S Butler, WE Hoh, BL Rabinov, JD Pryor, JC Ogilvy, CS Carter, BS AF Barker, FG Amin-Hanjani, S Butler, WE Hoh, BL Rabinov, JD Pryor, JC Ogilvy, CS Carter, BS TI Age-dependent differences in short-term outcome after surgical or endovascular treatment of unruptured intracranial aneurysms in the United States, 1996-2000 SO NEUROSURGERY LA English DT Article DE mortality; outcome; unruptured intracerebral aneurysm ID GUGLIELMI DETACHABLE COIL; CEREBRAL-ARTERY ANEURYSMS; IN-HOSPITAL MORTALITY; PROPENSITY SCORE; ADMINISTRATIVE DATA; CONSECUTIVE SERIES; CONTROLLED-TRIALS; COMPLICATIONS; EMBOLIZATION; EXPERIENCE AB INTRODUCTION: Unruptured intracranial aneurysm patients are frequently eligible for both open surgery ("clipping") and endovascular repair ("coiling"). We compared short-term end points (mortality, discharge disposition, complications, length of stay, and charges) for clipping and coiling in a nationally representative discharge database. METHODS: We conducted a retrospective cohort study using Nationwide Inpatient Sample data from 1996 to 2000. Multivariate logistic regression analyses adjusted for age, sex, race, payer status; geographic region, presenting signs and symptoms, admission type and source, procedure timing, hospital caseload, and possible clustering of outcomes within hospitals. The results were confirmed by performing propensity score analysis. RESULTS: A total of 3498 patients had clipping, and 421 underwent coiling. Clipped patients were slightly younger (P < 0.001). Medical comorbidity was similar between the groups. More clipped patients had urgent or emergency admissions (P = 0.02). More coiling procedures were performed on hospital Day 1 (P = 0.007). When only death and discharge to long-term care were counted as adverse outcomes, there was no significant difference between clipping and coiling. On the basis of a four-level discharge status outcome scale (dead, long-term care, short-term rehabilitation, or discharge to home), coiled patients had a significantly better discharge disposition (odds ratio, 2.1; P < 0.001). With regard to patient age, most of the difference in discharge disposition was in patients older than 65 years of age. The degree of difference between treatments increased from 1996 to 2000. Neurological complications were coded twice as frequently in clipped patients as in coiled patients (P = 0.002). Length of stay was longer (5 d versus 2 d, P < 0.001) and charges were higher ($21,800 versus $13,200, P = 0.007) for clipped patients than for coiled patients. CONCLUSION: There was no significant difference in mortality rates or discharge to long-term facilities after clipping or coiling of unruptured aneurysms. When discharge to short-term rehabilitation was counted as an adverse event, coiled patients had significantly better outcomes than clipped patients at the time of hospital discharge, but most of the coiling advantage was concentrated in patients older than 65 years of age. Even in older patients, long-term end points-including long-term functional status in patients discharged to rehabilitation and efficacy in preventing hemorrhage-will be critical in determining the best treatment option for patients with unruptured aneurysms. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 48 TC 85 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2004 VL 54 IS 1 BP 18 EP 28 DI 10.1227/01.NEU.0000097195.48840.C4 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 761ZA UT WOS:000187944300005 PM 14683537 ER PT J AU Mijailovich, SM Sullivan, MP Yalla, SV Venegas, JG AF Mijailovich, SM Sullivan, MP Yalla, SV Venegas, JG TI Theoretical analysis of the effects of viscous losses and abdominal straining on urinary outlet function SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE abdominal straining; pressure-flow relationship; tube law ID RESTING FEMALE URETHRA; PRESSURE-FLOW RELATION; COLLAPSIBLE TUBES; MALE MICTURITION; STEADY FLOW; ELASTICITY; RESISTANCE; HYDRODYNAMICS; MEN AB Aims: The aim of this study was to theoretically explore the relationship between the tube law (TL) of the urethra and the pressure-flow (p-Q) relationship during micturition. The understanding of this relation is important for the evaluation of outlet obstruction by urodynamic interpretation of p-Q plots. Methods: We simulated the outlet function by a lumped theoretical model, and suggested how the TL can be used to quantitatively predict the p-Q relationship of the system. Our analysis considered the relation between the TL and the steady state p-Q plot for various TLs including the hysteresis of the pressure-area relationship. Results and Conclusions: The inclusion of pressure losses distal to the flow controlling zone and experimentally measured p-A relations of the urethra in the model lead to the predictions that flow in the flow controlling zone is not always critical but is often in the sub-critical range, that an increase in abdominal pressure can increase the flow under certain conditions, and that hysteresis in the pressure-area relation is correlated to the hysteresis in the p-Q plot. Published 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. Vet Affairs Boston Healthcare Syst, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mijailovich, SM (reprint author), Harvard Univ, Sch Publ Hlth, Physiol Program, BLDG 1,Room 1306B,665 Huntington Ave, Boston, MA 02115 USA. OI Mijailovich, Srboljub/0000-0003-1498-308X FU NHLBI NIH HHS [P01 HL 33009]; NIAMS NIH HHS [R01 AR 048776-01A1] NR 38 TC 5 Z9 5 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 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2004 VL 23 IS 1 BP 76 EP 85 DI 10.1002/nau.10146 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 759HQ UT WOS:000187732600016 PM 14694462 ER PT J AU Azadzoi, KM Heim, VK Tarcan, T Siroky, MB AF Azadzoi, KM Heim, VK Tarcan, T Siroky, MB TI Alteration of urothelial-mediated tone in the ischemic bladder: Role of eicosanoids SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE bladder ischemia; hypoxia; leukotrienes; prostaglandins; urothelium ID GUINEA-PIG BLADDER; IN-VITRO CHANGES; URINARY-BLADDER; BLOOD-FLOW; SMOOTH-MUSCLE; OUTLET OBSTRUCTION; CONTRACTION; RELEASE; RABBIT; PROSTAGLANDINS AB Aims: Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role Of Urothelium and eicosanoid-release in ischemic bladder smooth muscle instability. Materials and Methods: Male New Zealand white rabbits were divided into treated (n = 12) and age-matched control (n = 10) groups. The treated group underwent balloon enclothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium,vas removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs). Results: A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro-) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro- tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF(2-alpha) and thromboxane A, release from the ischemic suburothelial tissue. Ischemia increased the release of LTB4, LTC4, and LTE4 from both urothelium and suburothelial tissue. Conclusions: Our studies Suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder. Published 2004 Wiley-Liss, Inc(dagger). C1 Boston Univ, Sch Med, Dept Urol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Marmara Univ, Sch Med, Istanbul, Turkey. RP Azadzoi, KM (reprint author), Boston VA Med Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM kazadzoi@bu.edu FU NIA NIH HHS [N IA/AG 17165] NR 22 TC 31 Z9 34 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2004 VL 23 IS 3 BP 258 EP 264 DI 10.1002/nau.20029 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 818YR UT WOS:000221280900014 PM 15098224 ER PT J AU Lewis, J Sullivan, M Nabha, K Bartolome, V Siroky, M Yalla, S AF Lewis, J Sullivan, M Nabha, K Bartolome, V Siroky, M Yalla, S TI Relationships between bladder outlet obstruction, bladder compliance and renal function in adult men with LUTS SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Joint Meeting of the International-Continence-Society/International-UroGynecological-Associat ion CY AUG 25-27, 2004 CL Paris, FRANCE SP Int Continence Soc, Int UroGynecolog Assoc C1 VA Boston Healthcare Syst, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2004 VL 23 IS 5-6 MA 61 BP 486 EP 487 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 843CB UT WOS:000223051900062 ER PT J AU MacGillivray, TE Vlahakes, GJ AF MacGillivray, TE Vlahakes, GJ TI Patency and the pump - The risks and benefits of off-pump CABG SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 11 Z9 11 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 1 PY 2004 VL 350 IS 1 BP 3 EP 4 DI 10.1056/NEJMp038185 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 758PT UT WOS:000187659900001 PM 14702419 ER PT J AU Talukder, SR Dudley, DD Alt, FW Takahama, Y Akamatsu, Y AF Talukder, SR Dudley, DD Alt, FW Takahama, Y Akamatsu, Y TI Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND BREAK REPAIR; CODING END SEQUENCE; C-TERMINAL REGION; SIGNAL SEQUENCES; SYNAPTIC COMPLEX; MEDIATED TRANSPOSITION; STRUCTURE REQUIREMENTS; MAMMALIAN-CELLS; JOINT FORMATION; DNA-SEQUENCE AB RAG1 and RAG2 play a central role in V(D)J recombination, a process for antigen receptor gene assembly. The truncated 'core' regions of RAGs are sufficient to catalyze the recombination reaction, although with lower joining efficiency than full-length proteins. To investigate the role of the non-core regions of RAGs in the end-joining phase of antigen receptor rearrangement, we analyzed recombination products isolated from core RAG1 and core RAG2 knock-in mice. Here, we report that the truncation of RAGs increases the frequency of aberrant recombination in vivo. Signal joints (SJs) associated with V-to-D recombination of core RAG1 knock-in mice were normal, whereas those of core RAG2 knock-in mice were highly imprecise, containing large deletions and additions, and in some cases coding sequences. In contrast, we found an elevated level of imprecise D-to-J associated SJs for both core RAG1- and RAG2-expressing mice. Likewise, sequences of coding joints (CJs) were also affected by the expression of core RAGs. Finally, sequences found at the junctions of rearranged T-cell receptor loci were highly influenced by differences in rearranging recombination signal sequence pairs. We provide the first evidence that the non-core regions of RAGs have critical functions in the proper assembly and resolution of recombination intermediates in endogenous antigen receptor loci. C1 Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,CBR Inst Biomed Res, Boston, MA 02115 USA. RP Akamatsu, Y (reprint author), Prot Design Labs Inc, 34801 Campus Dr, Fremont, CA 94555 USA. EM yakamatsu@pdl.com RI Takahama, Yousuke/A-5863-2010 NR 69 TC 41 Z9 41 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2004 VL 32 IS 15 BP 4539 EP 4549 DI 10.1093/nar/gkh778 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 855BE UT WOS:000223947100013 PM 15328366 ER PT J AU Tengs, T LaFramboise, T Den, RB Hayes, DN Zhang, JH DebRoy, S Gentleman, RC O'Neill, K Birren, B Meyerson, M AF Tengs, T LaFramboise, T Den, RB Hayes, DN Zhang, JH DebRoy, S Gentleman, RC O'Neill, K Birren, B Meyerson, M TI Genomic representations using concatenates of Type IIB restriction endonuclease digestion fragments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; COPY NUMBER; SERIAL ANALYSIS; DNA; IDENTIFICATION; SEQUENCE; SEARCH; TAGS; GENERATION; ALGORITHM AB We have developed a method for genomic representation using Type IIB restriction endonucleases. Representation by concatenation of restriction digests, or RECORD, is an approach to sample the fragments generated by cleavage with these enzymes. Here, we show that the RECORD libraries may be used for digital karyotyping and for pathogen identification by computational subtraction. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [1R01CA098185-01A1, R01 CA098185]; NIAID NIH HHS [T32 AI007358, T32-AI-07358] NR 28 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2004 VL 32 IS 15 AR e121 DI 10.1093/nar/gnh120 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 855BE UT WOS:000223947100031 PM 15329383 ER PT S AU Kang, JX AF Kang, Jing X. BE Simopoulos, AP Ordovas, JM TI Achieving Balance in the Omega-6/Omega-3 Ratio through Nutrigenomics Fat-1Transgenic Mice Convert Omega-6 to Omega-3 Fatty Acids SO NUTRIGENETICS AND NUTRIGENOMICS SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID EXPRESSION; CELLS C1 [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 11 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-7782-3 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2004 VL 93 BP 92 EP 98 PG 7 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA BKL89 UT WOS:000268458900005 PM 15496803 ER PT J AU Allison, DB Barnes, S Garvey, WT AF Allison, DB Barnes, S Garvey, WT TI Nutrigenomics special issue - Foreword SO NUTRITION LA English DT Editorial Material C1 Univ Alabama, Dept Biostat, Sect Stat Genet, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Purdue UAB Bot Ctr Age Related Dis, Dept Biochem & Mol Genet, Dept Pharmacol & Toxicol,UAB Ctr Nutrient Gene In, Birmingham, AL 35294 USA. Univ Alabama, Dept Nutr Sci, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Allison, DB (reprint author), Univ Alabama, Dept Biostat, Sect Stat Genet, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. OI Allison, David/0000-0003-3566-9399 NR 2 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 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2004 VL 20 IS 1 BP 1 EP 1 DI 10.1016/j.nut.2003.10.018 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 763KD UT WOS:000188083300001 PM 14698005 ER PT J AU Nagy, TR Blaylock, ML Garvey, WT AF Nagy, TR Blaylock, ML Garvey, WT TI Role of UCP2 and UCP3 in nutrition and obesity SO NUTRITION LA English DT Article ID UNCOUPLING PROTEIN-3 GENE; BROWN-ADIPOSE-TISSUE; MESSENGER-RNA EXPRESSION; SKELETAL-MUSCLE MITOCHONDRIA; HUMAN ENERGY HOMEOSTASIS; FATTY-ACID METABOLISM; BODY-MASS INDEX; THYROID-HORMONE; TRANSGENIC MICE; PIMA-INDIANS C1 Univ Alabama, Dept Nutr Sci, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Nagy, TR (reprint author), Univ Alabama, Dept Nutr Sci, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. EM tnagy@uab.edu FU NCI NIH HHS [CA47888]; NIDDK NIH HHS [DK54918, DK56336, DK38765, DK47461] NR 81 TC 24 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2004 VL 20 IS 1 BP 139 EP 144 DI 10.1016/j.nut.2003.09.024 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 763KD UT WOS:000188083300025 PM 14698029 ER PT J AU Campos, SM AF Campos, SM TI Aromatase inhibitors for breast cancer in postmenopausal women SO ONCOLOGIST LA English DT Article DE breast cancer; aromatase inhibitor; metastatic disease ID FIRST-LINE THERAPY; PHASE-III TRIAL; MEGESTROL-ACETATE; RANDOMIZED-TRIAL; DOUBLE-BLIND; ANASTROZOLE ARIMIDEX; OVARIECTOMIZED RAT; HORMONAL-THERAPY; TAMOXIFEN; EXEMESTANE AB Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naive postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease. Data from postmenopausal women with advanced disease suggest that steroidal and nonsteroidal aromatase inhibitors have similar tolerability profiles; however, emerging data suggest that there may be differences in their effects on end organs, which may become evident with longer term use, such as in the adjuvant or prevention settings. Steroidal agents appear to have beneficial effects on lipid and bone metabolism, whereas nonsteroidal agents may have neutral or unfavorable effects. These differences may be attributed to the androgenic effects of steroidal agents; clinical trials are currently under way to confirm these suspicions. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Campos, SM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Susana_Campos@dfci.harvard.edu NR 56 TC 49 Z9 54 U1 2 U2 3 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 2 BP 126 EP 136 DI 10.1634/theoncologist.9-2-126 PG 11 WC Oncology SC Oncology GA 809YM UT WOS:000220672000002 PM 15047917 ER PT J AU Kuter, DJ AF Kuter, DJ TI Thrombotic complications of central venous catheters in cancer patients SO ONCOLOGIST LA English DT Article DE thrombosis; warfarin; heparin; catheter; DVT; low molecular weight heparin ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; ACCESS DEVICES; DOUBLE-BLIND; RISK-FACTORS; ANTITHROMBOTIC AGENTS; ONCOLOGY PATIENTS; PREVENTION; THROMBOEMBOLISM; FONDAPARINUX AB Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic. Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%-30% of cases and pulmonary embolism in 11% (only half of which are symptomatic). Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit. Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, 100 Blossom St, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu NR 81 TC 100 Z9 116 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 2 BP 207 EP 216 DI 10.1634/theoncologist.9-2-207 PG 10 WC Oncology SC Oncology GA 809YM UT WOS:000220672000010 PM 15047925 ER PT J AU Penson, RT Talsania, SHG Chabner, BA Lynch, TJ AF Penson, RT Talsania, SHG Chabner, BA Lynch, TJ TI Help me help you: Support groups in cancer therapy SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; communication; care; connection ID ADJUVANT PSYCHOLOGICAL THERAPY; BREAST-CANCER; PSYCHOSOCIAL INTERVENTIONS; SURVIVAL; TRIAL; EDUCATION; IMPACT; PEER AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Three invited patients attended rounds and told their compelling stories; these each effectively demonstrated their fight as cancer survivors. Much of the strength that they displayed came from the different types of support they each received, and the invaluable role of the medical team. Each shared a very positive experience with 'The Wellness Community,' in Boston. The article discusses issues of support and the role of formal support groups. Types of support intervention, the impact they have on quality of life and survival are reviewed. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 30 TC 8 Z9 10 U1 2 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 2 BP 217 EP 225 DI 10.1634/theoncologist.9-2-217 PG 9 WC Oncology SC Oncology GA 809YM UT WOS:000220672000011 PM 15047926 ER PT J AU Chabner, BA AF Chabner, BA TI CME: The "third phase" of a doctor's education SO ONCOLOGIST LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Chabner, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 3 BP 241 EP 241 DI 10.1634/theoncologist.9-3-241 PG 1 WC Oncology SC Oncology GA 828KP UT WOS:000221972500001 PM 15169977 ER PT J AU Chabner, BA AF Chabner, BA TI The miracle of Iressa((R)) SO ONCOLOGIST LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Chabner, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. NR 3 TC 7 Z9 10 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 3 BP 245 EP 246 DI 10.1634/theoncologist.9-3-245 PG 2 WC Oncology SC Oncology GA 828KP UT WOS:000221972500003 PM 15169979 ER PT J AU Stone, RM AF Stone, RM TI Optimizing treatment of chronic myeloid leukemia: A rational approach SO ONCOLOGIST LA English DT Article DE leukemia, myeloid, chronic; stem cell transplantation; antineoplastic agents; imatinib; interferon-alfa ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; LOW-DOSE CYTARABINE; ABL TYROSINE KINASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; TERM HYDROXYUREA THERAPY; INTERFERON-ALPHA THERAPY; TOTAL-BODY IRRADIATION; CHRONIC-PHASE AB Imatinib mesylate, a novel, molecularly targeted agent for the treatment of chronic myeloid leukemia (CML), has expanded the management options for this disease and provided a paradigm for the treatment of other cancers. Imatinib is a potent, specific inhibitor of BCR-ABL, the constitutively active protein tyrosine kinase critical to the pathogenesis of CML. A randomized, phase III comparison of imatinib with interferon-alfa plus cytarabine as initial treatment for newly diagnosed chronic-phase CML, which demonstrated significantly higher rates of disease response with less toxicity, better quality of life, and a significantly longer progression-free survival time, provided the most persuasive data supporting a major role for imatinib. Currently, allogeneic stem cell transplantation is the only treatment modality with long-term data demonstrating curative potential in CML. An option for less than half of CML patients and associated with substantial morbidity and mortality, transplantation may still be appropriate initial therapy for certain patients. Busulfan and hydroxyurea have no demonstrable effect on disease natural history. The interferon-plus-cytarabine combination can induce durable cytogenetic remissions and was previously the CML pharmacotherapy standard of care, but it is often poorly tolerated. Imatinib is now indicated as first-line therapy for CML in all phases. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St,Room D-840, Boston, MA 02115 USA. EM rstone@partners.org NR 88 TC 26 Z9 28 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 3 BP 259 EP 270 DI 10.1634/theoncologist.9-3-259 PG 12 WC Oncology SC Oncology GA 828KP UT WOS:000221972500005 PM 15169981 ER PT J AU Penson, RT Daniels, KJ Lynch, TJ AF Penson, RT Daniels, KJ Lynch, TJ TI Too old to care? SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; communication; chemotherapy; connection; elderly; age ID COMPREHENSIVE GERIATRIC ASSESSMENT; LIFE-SUSTAINING TREATMENT; BREAST-CANCER; ADJUVANT-CHEMOTHERAPY; ADVANCE DIRECTIVES; DECISION-MAKING; LUNG-CANCER; NEGATIVE STEREOTYPES; COLORECTAL-CANCER; ELIGIBLE PATIENTS AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (NIGH), founded The Kenneth B. Schwartz Center at NIGH (http://www.theschwarzcenter.org/rounds.asp). The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers, and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multi-disciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Ageism is a pervasive problem throughout society. It is rooted in language, attitudes, beliefs, behaviors, and policies. Aging profoundly influences physiology, challenging the medical community to accommodate but not discriminate. The elderly are at an increased risk of disease and disability. Sixty percent of cancer occurs in people aged 65 and older, and the population is aging. The treatment of cancer in the elderly is complicated by comorbidities and other physiological factors, particularly renal, bone marrow, and metabolic reserve. Caregivers have to treat patients in a manner that optimizes treatment and avoids anticipated harm. However, the caregiver is often faced with situations where they must balance their personal beliefs, professional values, and knowledge of medicine with their patients' preferences and needs. Discussion in the Rounds focused on age bias, drug toxicity, life prolongation, and symptom relief, with the role of the caregiver, and the relationship to the patient, being pivotal. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 87 TC 31 Z9 35 U1 3 U2 16 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 3 BP 343 EP 352 DI 10.1634/theoncologist.9-3-343 PG 10 WC Oncology SC Oncology GA 828KP UT WOS:000221972500014 PM 15169990 ER PT J AU Sahani, DV Kalva, SP AF Sahani, DV Kalva, SP TI Imaging the liver SO ONCOLOGIST LA English DT Article DE CT; MRI; PET; liver tumors ID POSITRON-EMISSION-TOMOGRAPHY; FOCAL NODULAR HYPERPLASIA; PHASE HELICAL CT; HEPATOCELLULAR-CARCINOMA; HEPATIC METASTASES; ENHANCED MRI; SPIRAL CT; COMPUTED-TOMOGRAPHY; CIRRHOTIC LIVER; CANCER-PATIENTS AB Imaging of the liver is undertaken for the detection and characterization of suspected primary or secondary neoplasms, prior to planning a surgery or chemotherapy pump placement, for assessing treatment response, for evaluating biliary pathology, and for screening for liver neoplasms in high-risk groups. In this article, we review the advantages and disadvantages of various imaging modalities in the evaluation of the liver and formulate guidelines for the imaging of common clinical indications. A brief review of imaging findings in focal and diffuse liver disease is also presented. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 59 TC 38 Z9 42 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 4 BP 385 EP 397 DI 10.1634/theoncologist.9-4-385 PG 13 WC Oncology SC Oncology GA 843GT UT WOS:000223067300004 PM 15266092 ER PT J AU Brown, JR Skarin, AT AF Brown, JR Skarin, AT TI Clinical mimics of lymphoma SO ONCOLOGIST LA English DT Review DE lymphadenopathy; lymphoma; Castleman's disease; lymphomatoid granulomatosis; Kikuchi's disease ID T-CELL LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; ROSAI-DORFMAN-DISEASE; EPSTEIN-BARR-VIRUS; HISTIOCYTIC NECROTIZING LYMPHADENITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; KIKUCHI-FUJIMOTO-DISEASE AB Lymphadenopathy is a common clinical finding and is frequently benign. Warning signs suggestive of a malignant etiology include lymph nodes >2 cm in size, supraclavicular location, and generalized lymphadenopathy associated with hepatosplenomegaly or systemic symptoms. A metastatic solid tumor is always in the differential diagnosis of localized lymphadenopathy, particularly in older individuals. In the case of more generalized lymphadenopathy, in addition to the more common lymphomas, benign etiologies as well as benign and atypical lymphoproliferative disorders need to be considered. Benign etiologies of lymphadenopathy can include infections, autoimmune disorders, drug hypersensitivity reactions, sarcoidosis, and amyloidosis. Rare but benign lymphoproliferative disorders include Kikuchi's disease, Rosai-Dorfman disease, and progressive transformation of germinal centers. Atypical lymphoproliferative disorders that bear close surveillance for evolution to a more aggressive malignancy include Castleman's disease, lymphomatoid granulomatosis, and lymphomatoid papulosis. Previously considered in this category but now classified as a true lymphoma is angioimmunoblastic lymphadenopathy with dysproteinemia. Physicians need to be aware of all of these disorders when evaluating suspicious lymphadenopathy, while also considering the more common lymphomas and leukemias. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Skarin, AT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM arthur_skarin@dfci.harvard.edu NR 108 TC 39 Z9 41 U1 1 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 4 BP 406 EP 416 DI 10.1634/theoncologist.9-4-406 PG 11 WC Oncology SC Oncology GA 843GT UT WOS:000223067300006 PM 15266094 ER PT J AU Kirsch, DG Tarbell, NJ AF Kirsch, DG Tarbell, NJ TI Conformal radiation therapy for childhood CNS tumors SO ONCOLOGIST LA English DT Article DE pediatrics; radiation therapy; central nervous system neoplasms; protons; IMRT; side effects ID GERM-CELL TUMORS; LOW-GRADE ASTROCYTOMA; INDUCED 2ND CANCERS; PHASE-II TRIAL; BRAIN-TUMORS; NERVOUS-SYSTEM; STEREOTAXIC RADIOTHERAPY; CHILDREN; MEDULLOBLASTOMA; CHEMOTHERAPY AB Radiation therapy plays a central role in the management of many childhood brain tumors. By combining advances in brain tumor imaging with technology to plan and deliver radiation therapy, pediatric brain tumors can be treated with conformal radiation therapy. Through conformal radiation therapy, the radiation dose is targeted to the tumor, which can minimize the dose to normal brain structures. Therefore, by limiting the radiation dose to normal brain tissues, conformal radiation therapy offers the possibility of limiting the long-term side effects of brain irradiation. In this review, we describe different approaches to conformal radiation therapy for pediatric central nervous system tumors including: A) three-dimensional conformal radiation therapy; B) stereotactic radiation therapy with are photons; C) intensity-modulated radiation therapy; and D) proton beam radiation therapy. We discuss the merits and limitations of these techniques and describe clinical scenarios in which conformal radiation therapy offers advantages over conventional radiation therapy for treating pediatric brain tumors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Bulfinch 360, Boston, MA 02114 USA. EM ntarbell@partners.org NR 37 TC 21 Z9 22 U1 0 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 4 BP 442 EP 450 DI 10.1634/theoncologist.9-4-442 PG 9 WC Oncology SC Oncology GA 843GT UT WOS:000223067300009 PM 15266097 ER PT J AU Covarrubias, DJ Rosen, BR Lev, MH AF Covarrubias, DJ Rosen, BR Lev, MH TI Dynamic magnetic resonance perfusion imaging of brain tumors SO ONCOLOGIST LA English DT Article DE brain neoplasms; magnetic resonance imaging; perfusion; diagnostic techniques ID CEREBRAL BLOOD-VOLUME; CONTRAST-ENHANCED MR; DEXAMETHASONE TREATMENT; CLINICAL-APPLICATIONS; GRADIENT-ECHO; GLIOMAS; GRADE; PERMEABILITY; MAPS; FLOW AB In this paper, we review the technique of contrast-enhanced magnetic resonance (MR) perfusion imaging of brain neoplasms, with an emphasis on its clinical applications and utility. We start with a discussion of MR perfusion techniques available today and their relative merits and shortcomings. Next, the ability of MR perfusion to provide a preoperative assessment of tumor histology is examined. We also discuss the role of MR perfusion in helping guide tumor biopsy, and its advantages over more conventional methods. We will scrutinize the use of MR perfusion for assessing true lesion extent, in contrast to conventional MR imaging and other MR techniques. We will discuss the role of MR perfusion in differentiating treatment effects, such as radiation necrosis, from tumor recurrence. Finally, the future potential applications of this technology in the setting of novel antiangiogenic therapies for brain tumors will be addressed. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02144 USA. Massachusetts Gen Hosp, MGH, NMR Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Covarrubias, DJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, 55 Fruit St, Boston, MA 02144 USA. EM djcovarrubias@comcast.net NR 29 TC 118 Z9 126 U1 0 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 5 BP 528 EP 537 DI 10.1634/theoncologist.9-5-528 PG 10 WC Oncology SC Oncology GA 860NH UT WOS:000224349800006 PM 15477637 ER PT J AU Penson, RT Schapira, L Daniels, KJ Chabner, BA Lynch, TJ AF Penson, RT Schapira, L Daniels, KJ Chabner, BA Lynch, TJ TI Cancer as metaphor SO ONCOLOGIST LA English DT Article DE oncology; support; illness; military; psychosocial; communication; chemotherapy; connection ID EVERYDAY LANGUAGE; MEDICINE; WAR AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Metaphors illuminate complex issues and can paint a thousand words. However, fundamental to individual and collective expression, they are also capable of creating or perpetuating stereotypes, and stigma. In oncology, the military metaphor is perhaps the most pronunent, with the high profile of the "War on Cancer," and the imperative for patients to have a fighting spirit. Balancing the instinct to fight with words of healing and acceptance remains a challenge. The history of the military metaphor and how the humanities have illuminated cancer as a metaphor are reviewed. The advantages and disadvantages of the use of this metaphor are discussed, as well as the use of other metaphors in the psychosocial dynamic of care. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 39 TC 27 Z9 28 U1 2 U2 7 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2004 VL 9 IS 6 BP 708 EP 716 DI 10.1634/theoncologist.9-6-708 PG 9 WC Oncology SC Oncology GA 873XG UT WOS:000225314200011 PM 15561814 ER PT J AU Panagiotou, I Beer, TM Hsieh, YC Mori, M Peters, L Klein, T Garzotto, M AF Panagiotou, I Beer, TM Hsieh, YC Mori, M Peters, L Klein, T Garzotto, M TI Predictors of delayed therapy after expectant management for localized prostate cancer in the era of prostate-specific antigen SO ONCOLOGY LA English DT Article DE androgen deprivation; expectant management; prostate cancer; treatment ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; NATURAL-HISTORY; CONSERVATIVE MANAGEMENT; DOUBLING TIME; CARCINOMA; PROGRESSION; DISEASE; MEN; RECURRENCE AB Objective: To identify risk factors for delayed cancer-directed intervention in modern era prostate cancer patients who initially elect expectant management. Materials and Methods: An observational, cohort study of expectantly managed patients, diagnosed with clinical T1-4NxM0 prostate cancer between 1993 and 2000 was carried out. Data including TNM stage, age, serum prostate-specific antigen (PSA), prostate gland volume by transrectal ultrasound, Gleason score, percent biopsies positive for cancer, imaging results, initial treatment selection, and outcome data were collected on all patients. Results: 192 of 561 patients (34.3%) elected expectant management, and follow-up data were available for 187 (97.4%) patients. With a median follow-up of 3.6 years, 90 (48.1%) patients had a cancer-directed intervention. Gleason score (p=0.0097) and percent of positive biopsy cores (p=0.03) were independent predictors of time to intervention. As expected, PSA doubling time became the most significant predictor of intervention (p=0.0057) when added to the model. These independent covariates are able to characterize low-, intermediate- and high-risk groups for cancer-directed intervention. Conclusions: Cancer-directed intervention is common in patients who choose expectant management in the PSA era. Gleason score and percent of positive biopsy cores predict cancer-directed interventions, thus, these patients may be least suitable for expectant management. Copyright (C) 2004 S. Karger AG, Basel. C1 Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR USA. Portland VA Med Ctr, Div Urol, Portland, OR USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR USA. RP Garzotto, M (reprint author), Portland VA Med Ctr, Div Urol, 3710 SW US Vet Hosp Rd,Mailcode P3GU, Portland, OR 97201 USA. EM garzotto@ohsu.edu FU NCI NIH HHS [5P30 CA69533-04]; NCRR NIH HHS [5 M01 RR00334-33S2] NR 24 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2004 VL 67 IS 3-4 BP 194 EP 202 DI 10.1159/000081317 PG 9 WC Oncology SC Oncology GA 873DG UT WOS:000225258900003 PM 15557778 ER PT J AU Pandya, KJ Lefkopoulou, M Petrelli, NJ Vaughn, DJ Smith, TJ Harris, JE Haller, DG AF Pandya, KJ Lefkopoulou, M Petrelli, NJ Vaughn, DJ Smith, TJ Harris, JE Haller, DG TI Phase II study of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil (MVPF) in patients with metastatic large bowel cancer: An eastern cooperative oncology group study (EST 1285) SO ONCOLOGY LA English DT Article DE colorectal cancer; metastasis; chemotherapy; large bowel cancer ID ADVANCED COLORECTAL-CANCER; CONTINUOUS-INFUSION 5-FLUOROURACIL; PROSPECTIVE RANDOMIZED TRIAL; FLUOROURACIL PLUS CISPLATIN; COLON CARCINOMA-CELLS; COMBINATION CHEMOTHERAPY; CIS-DIAMMINEDICHLOROPLATINUM; CIS-DICHLORODIAMMINEPLATINUM(II); ADENOCARCINOMA; RESISTANCE AB Purpose: To compare the efficacy and the toxicity of cisplatin and 5-fluorouracil (PF) and mitomycin C, vincristine, cisplatin and 5-fluorouracil ( MVPF) in patients with metastatic large bowel cancer. Patients and Methods: A total of 94 patients with no prior chemotherapy and measurable metastatic large bowel cancer were randomly assigned to one of the two treatment regimens. Eastern Cooperative Oncology Group (ECOG) criteria were used to evaluate response and toxicity. Results: Fifty patients were randomized to PF and 44 to MVPF. Toxicity was evaluable in all patients except one; response was evaluable in 40 and 31, with response rate of 13 and 42%, respectively. Intent-to-treat analysis showed a response rate of 12 and 32%, respectively (p = 0.076), where it was assumed that none of the ineligible or unevaluable patients responded. Median survival for all patients was 9 months, with no difference between PF and MVPF. ECOG Performance Status (0 vs. 1), weight loss (less than or equal to 10 vs. >10%) and site of metastatic lesion had statistically significant impact on survival. MVPF was definitely more toxic than PF (p < 0.000005). Conclusion: Both treatment regimens showed clinical activity. The MVPF regimen resulted in more responses than PF, no improvement in survival, and more toxicity. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Rochester, Ctr Canc, Rochester, NY 14642 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Mem Inst, Buffalo, NY USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Morristown Mem Hosp, Morristown, NJ USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Pandya, KJ (reprint author), Univ Rochester, Ctr Canc, 601 Elmwood Ave,Box 704, Rochester, NY 14642 USA. EM Kishan_Pandya@urmc.rochester.edu FU NCI NIH HHS [CA21115, CA12296, CA15488, CA22318, CA25988, CA07190, CA11083, CA66636] NR 36 TC 2 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2004 VL 66 IS 2 BP 118 EP 125 DI 10.1159/000077437 PG 8 WC Oncology SC Oncology GA 819XP UT WOS:000221349900005 PM 15138363 ER PT J AU Sutton, KM Wright, M Fondren, G Towle, CA Mankin, HJ AF Sutton, KM Wright, M Fondren, G Towle, CA Mankin, HJ TI Cyclooxygenase-2 expression in chondrosarcoma SO ONCOLOGY LA English DT Article DE chondrosarcoma; cyclooxygenase; enchondroma ID SELECTIVE COX-2 INHIBITION; COLON-CANCER CELLS; CARCINOMA; APOPTOSIS; CELECOXIB; MODEL; ADENOCARCINOMA; ENHANCEMENT; REDUCTION; SYSTEM AB Objective: In recent years it has become evident that tissue cyclooxygenase-2 (COX-2) may play a role in carcinogenesis and tumor malignancy. There is now a mounting body of information that strongly implies that COX-2 inhibitors may be of some value in the management of patients with carcinomas, and most recently several similar reports have appeared relating to sarcomas. Methods: The authors studied 32 samples of cartilage tumors from our tumor tissue bank for the presence of COX-2 by a Western blot technique. There were 29 patients from whom the samples were obtained, including 8 with enchondromas and 21 with chondrosarcomas. Results: Thirteen of the 24 chondrosarcoma samples and none of the 8 enchondromas were positive for COX-2. An attempt was made to correlate these results with clinical data including age, gender, staging according to the Musculoskeletal Tumor Society, anatomical site, ploidic pattern, presence of metastases and death rate but no statistically valid correlation could be found. Conclusion: It is evident that COX-2 may play some role in chondrosarcoma but not in the benign enchondroma and that further studies with COX-2 inhibitors are warranted. Copyright (C) 2004 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Biol Res Labs, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Biol Res Labs, Boston, MA 02114 USA. EM hmankin@partners.org NR 33 TC 27 Z9 30 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2004 VL 66 IS 4 BP 275 EP 280 DI 10.1159/000078327 PG 6 WC Oncology SC Oncology GA 832AG UT WOS:000222238500004 PM 15218294 ER PT J AU Shepard, RC Levy, DE Berlin, JD Stuart, K Harris, JE Aviles, V Thomas, JP Benson, AB AF Shepard, RC Levy, DE Berlin, JD Stuart, K Harris, JE Aviles, V Thomas, JP Benson, AB TI Phase II study of gemcitabine in combination with docetaxel in patients with advanced pancreatic carcinoma (E1298) - A trial of the Eastern Cooperative Oncology Group SO ONCOLOGY LA English DT Article DE pancreas cancer; gemcitabine; docetaxel; phase II trial ID CANCER; ADENOCARCINOMA; CHEMOTHERAPY; THERAPY AB Background: Responses have been observed in several studies of docetaxel as treatment for advanced pancreatic carcinoma. This trial was designed to determine if the addition of docetaxel to gemcitabine therapy produced responses in greater than or equal to25% of patients with chemonaive advanced pancreatic cancer. Patients and Methods: This trial involved patients with biopsy-proven, advanced carcinoma of the pancreas not amenable to surgical resection. Patients received docetaxel 75 mg/m(2) i. v. over 1 h followed by gemcitabine 2,000 mg/m(2) biweekly until progression or intolerable toxicity. The primary endpoint of the trial was to determine the objective response rate with secondary endpoints of progression-free survival and overall survival. Results: Out of the 32 eligible patients, 2 patients had a complete response and 2 patients had a partial response for an observed objective response rate of 12.5% (90% CI: 4.4, 26.4%). Median survival was 4.7 months. Most toxicities were hematologic, with 48% of patients experiencing grade 4 toxicity. Conclusions: The confirmed complete response rate of 6% and partial response rate of 6% is encouraging, but the toxicity of this regimen appears significant. Based upon these results, this combination of gemcitabine and docetaxel is not worthy of further study. Different schedules and dosages may be more promising. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Virginia, Charlottesville, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Lehigh Valley Hosp, Allentown, PA USA. Univ Wisconsin, Madison, WI USA. Northwestern Univ, Chicago, IL 60611 USA. RP Berlin, JD (reprint author), 777 Preston Res Bldg, Nashville, TN 37232 USA. EM Jordan.berlin@vanderbilt.edu FU NCI NIH HHS [CA17145, CA21076, CA21115, CA23318, CA49957, CA66636, CA80775] NR 14 TC 28 Z9 29 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2004 VL 66 IS 4 BP 303 EP 309 DI 10.1159/000078331 PG 7 WC Oncology SC Oncology GA 832AG UT WOS:000222238500008 PM 15218298 ER PT J AU Garber, J AF Garber, J TI Advising women at high risk of breast cancer - The Wood article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Adult Oncol, Canc Risk & Prevent Clin, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Garber, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Canc Risk & Prevent Clin, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2004 VL 18 IS 1 BP 32 EP + PG 2 WC Oncology SC Oncology GA 052CZ UT WOS:000238210000005 ER PT J AU Penson, RT Amrein, PC AF Penson, RT Amrein, PC TI Faith and freedom: Leukemia in Jehovah Witness minors SO ONKOLOGIE LA English DT Editorial Material ID BLOOD-PRODUCTS C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 17 TC 1 Z9 1 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2004 VL 27 IS 2 BP 126 EP 128 DI 10.1159/000076900 PG 3 GA 819XM UT WOS:000221349600001 PM 15138343 ER PT J AU Ponce, BA Millett, PJ Warner, JJP AF Ponce, BA Millett, PJ Warner, JJP TI Acromioclavicular joint instability - Reconstruction indications and techniques SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE acromioclavicular (AC) joint instability; modified Weaver-Dunn ID SURGICAL-TREATMENT; STEINMANN PIN; DISLOCATION; MIGRATION; SEPARATIONS; INJURIES; CLAVICLE; REPAIR; PAIN AB Injuries to the acromioclavicular joint are common and may lead to instability or degenerative changes requiring surgical intervention. The spectrum of injury ranges from sprain to disruption of the acromioclavicular and coracoclavicular ligaments, which provide horizontal and vertical stability to the distal clavicle. Most injuries are the result of direct trauma to the acromioclavicular joint. The majority of injuries can be nonoperatively managed. However, with significant disruption to the surrounding supportive structures, painful instability may result. Multiple stabilization procedures for the acromioclavicular joint have been described. Many of these techniques have fallen out of favor due to high complication rates. Common reconstruction techniques include either coracoclavicular ligament reconstruction with or without clavicle resection (ie, modified Weaver-Dunn) or coracoclavicular stabilization (ie, with Bosworth screw) with repair or reconstruction of the coracoclavicular ligaments. The purpose of this paper is to review the basic anatomy, biomechanics, and treatment of acromioclavicular joint instability. C1 Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Shoulder Serv,Sch Med, Boston, MA USA. RP Millett, PJ (reprint author), Brigham & Womens Hosp, Harvard Shoulder Serv Sports Med, 75 Francis St, Boston, MA 02115 USA. NR 42 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 1060-1872 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD JAN PY 2004 VL 12 IS 1 BP 35 EP 42 DI 10.1053/j.otsm.2004.04.004 PG 8 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA 848AA UT WOS:000223438100008 ER PT J AU Vavvas, D Fay, A Watkins, L AF Vavvas, D Fay, A Watkins, L TI Two cases of orbital lymphangioma associated with vascular abnormalities of the retina and iris SO OPHTHALMOLOGY LA English DT Article ID CARBON-DIOXIDE LASER; VENOUS ANOMALIES; MANAGEMENT; MALFORMATIONS AB Purpose: To report 2 patients with combined intraocular and orbital vascular abnormalities. Design: Two interventional case reports. Main Outcome Measures: Clinical and pathologic findings. Intervention/Testing. Orbitotomy, fluorescein angiography, magnetic resonance imaging, and radiation therapy. Results: Two patients presented with vision loss, intermittent proptosis, and cosmetic deformity. These patients had orbital lymphangioma, ipsilateral retinal and iris vascular malformations, and smaller corneal diameter on the affected side. Conclusions: The coexistence of these diverse vascular anomalies supports the established hypothesis of pluripotential orbital vascular anlagen. Disruptive influences of various types during embryogenesis or development may produce a variety of congenital orbital and intraocular vascular malformations. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ophthalm Plast Orbital Reconstruct & Cosmet Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hemangioma & Vasc Malformat Clin, Boston, MA 02114 USA. RP Vavvas, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ophthalm Plast Orbital Reconstruct & Cosmet Surg, 243 Charles St, Boston, MA 02114 USA. OI Vavvas, Demetrios/0000-0002-8622-6478 NR 17 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2004 VL 111 IS 1 BP 189 EP 192 DI 10.1016/S0161-6420(03)00864-9 PG 4 WC Ophthalmology SC Ophthalmology GA 760JA UT WOS:000187806800030 PM 14711734 ER PT S AU Yaroslavsky, AN Neel, V Anderson, RR AF Yaroslavsky, AN Neel, V Anderson, RR BE Alfano, RR Katz, A TI Optical mapping of non-melanoma skin cancer SO OPTICAL BIOPSY V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Biopsy V CY JAN 27-28, 2004 CL San Jose, CA SP SPIE ID METHYLENE-BLUE; POLARIZED-LIGHT; STAINING TEST; TUMORS; CELLS AB More than two million cases of nonmelanoma skin cancers are diagnosed every year. Therefore, there is a strong need for practical, reliable, rapid, and precise methods for tumor delineation, to guide surgery and other treatments of skin cancer. Once developed, such methods may be useful for squamous cell carcinomas of other organs. Noninvasive optical imaging techniques including polarization sensitive reflectance and fluorescence imaging were evaluated for the demarcation of nonmelanoma skin tumors. Thick freshly excised tumor specimens obtained from Mohs surgery were used for the experiments. Imaging was performed using linearly polarized incident light in the visible and near infrared spectral range from 577 nm to 750 nm. Non-toxic absorbing and fluorescent dyes (Toluidine Blue O, Methylene Blue) were employed to enhance tumor contrast in the images. The images were acquired using the remitted light polarized in the directions parallel and perpendicular to the polarization of incident light. Reflectance and fluorescence polarization images were evaluated. The data were processed and analyzed for dependence of the remitted light polarization on the tissue type (cancerous/normal). The data obtained so far from fresh tumor specimens in vitro using dye-enhanced polarized light reflectance, and exogenous fluorescence polarization imaging suggest that optical mapping can become a valuable guidance tool in nonmelanoma cancer surgery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Yaroslavsky, AN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, MGH BHX630,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5234-3 J9 P SOC PHOTO-OPT INS PY 2004 VL 5326 BP 60 EP 63 DI 10.1117/12.532843 PG 4 WC Engineering, Biomedical; Optics; Spectroscopy SC Engineering; Optics; Spectroscopy GA BAS05 UT WOS:000223341600009 ER PT S AU Solban, N Georgakoudi, I Rice, WL Lin, C Hasan, T AF Solban, N Georgakoudi, I Rice, WL Lin, C Hasan, T BE Kessel, D TI Role of cell type and animal species in tumor metastasis. SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XIII CY JAN 24-25, 2004 CL San Jose, CA SP SPIE DE photodynamic therapy; adhesion; integrin; in vivo flow cytometry; prostate cancer cells ID PHOTODYNAMIC THERAPY; IN-VIVO; INTEGRIN EXPRESSION; FLUENCE RATE; ADHESION; CANCER; PHOTOIMMUNOTHERAPY AB Photodynamic therapy (PDT) is now a reasonably well-known therapeutic option and is approved as a first line treatment of age-related macular degeneration (AMD), a non-oncologic condition. For most cancer applications PDT is approved mainly as a palliative or adjunctive treatment often when all other options have failed. As the modality evolves toward becoming a first-line or curative option, long-term effects of processes involved will need to be studied. Cellular and tissue responses to PDT are more complex than responses to the more conventional therapies, perhaps because PDT is inherently a binary (or ternary) therapy. In addition to the nature and localization of the photosensitizer (PS), the timing of illumination after administration, the mode of administration and the PS and light doses, the efficacy and selectivity of responses are also determined by the physiology and geometry of tumors, the inherent survivability of tumor cells (in circulation and other anatomic sites) and cellular and molecular responses to PDT. The overall outcome of photodynamic treatment in the long term is determined by a combination, in varying degrees, of all of the above factors. In order to enhance and broaden the application of PDT to complex anatomical sites, an understanding of these factors would be useful. In the laboratory, the outcome is also dependent on the specific animal models being studied. This manuscript discusses preliminary studies along these lines using a variety of tools and implications, if any, of the results obtained. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Solban, N (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5223-8 J9 P SOC PHOTO-OPT INS PY 2004 VL 5315 BP 41 EP 48 DI 10.1117/12.533550 PG 8 WC Oncology; Engineering, Biomedical; Optics SC Oncology; Engineering; Optics GA BAM97 UT WOS:000222894800006 ER PT S AU Gad, F Zahra, T Hasan, T Hamblin, MR AF Gad, F Zahra, T Hasan, T Hamblin, MR BE Kessel, D TI Targeted photodynamic therapy of established soft-tissue infections in mice. SO OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XIII CY JAN 24-25, 2004 CL San Jose, CA SP SPIE DE photosensitizer; bioluminescence; Staphylococcus aureus; abscess; polylysine chlorin(e6) conjugate; cyclophosphamide ID RESISTANT STAPHYLOCOCCUS-AUREUS; IN-VIVO; WOUND INFECTIONS; BACTERIA; VIRULENCE; MODEL AB The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a low-light imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a light-dose dependent loss of bioluminescence (to < 5% of that seen in control infections) not seen in untreated or light alone treated infections, but in some cases the infection recurred. Conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin(e6) responded less and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have applications in drug-resistant soft-tissue infections. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Gad, F (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 23 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5223-8 J9 P SOC PHOTO-OPT INS PY 2004 VL 5315 BP 65 EP 75 DI 10.1117/12.528390 PG 11 WC Oncology; Engineering, Biomedical; Optics SC Oncology; Engineering; Optics GA BAM97 UT WOS:000222894800009 ER PT J AU Novak, J Georgakoudi, I Wei, X Prossin, A Lin, CP AF Novak, J Georgakoudi, I Wei, X Prossin, A Lin, CP TI In vivo flow cytometer for real-time detection and quantification of circulating cells SO OPTICS LETTERS LA English DT Article AB An in vivo flow cytometer is developed that allows the real-time detection and quantification of circulating fluorescently labeled cells in live animals. A signal from a cell population of interest is recorded as the cells pass through a slit of light focused across a blood vessel. Confocal detection of the excited fluorescence allows continuous monitoring of labeled cells in the upper layers of scattering tissue, such as the skin. The device is used to characterize the in vivo kinetics of red and white blood cells circulating in the vasculature of the mouse ear. Potential applications in biology and medicine are discussed. (C) 2004 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Novak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. FU NEI NIH HHS [EY14106, R01 EY014106, R01 EY014106-01]; NIBIB NIH HHS [EB0000664, R01 EB000664] NR 6 TC 105 Z9 107 U1 1 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JAN 1 PY 2004 VL 29 IS 1 BP 77 EP 79 DI 10.1364/OL.29.000077 PG 3 WC Optics SC Optics GA 757GB UT WOS:000187552800025 PM 14719666 ER PT J AU Friedlander, AH Friedlander, IK Marder, SR AF Friedlander, AH Friedlander, IK Marder, SR TI Posttraumatic stress disorder: Psychopathology, medical management, and dental implications SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; CHILDHOOD SEXUAL ABUSE; BURNING MOUTH SYNDROME; SCRIPT-DRIVEN IMAGERY; DYSFUNCTION SYNDROME; PSYCHOSOCIAL FACTORS; TEMPOROMANDIBULAR PAIN; HIPPOCAMPAL VOLUME; INDUCED BRUXISM; RISK-FACTORS AB PTSD is a chronic mental illness that may arise after an individual experiences or witnesses a life-threatening event. Symptoms consist of persistent reexperiencing of the event, avoidance of reminders of the event, a numbing of positive emotions, and social withdrawal. A depressed mood and excessive use of alcohol and tobacco may accompany the disorder. PTSD afflicts approximately 5% of men and 11% of women. Dental disease may be extensive because of neglect of oral hygiene compounded by cigarette smoking. Dental treatment includes preventive education, oral cancer screening, and prescribing saliva substitutes or stimulants and anticaries agents to combat medication-induced xerostomia. Precautions must be taken when prescribing or administering certain analgesics, antibiotics, or sedative agents that may adversely interact with the psychiatric medications or when performing surgery because of the long-term effects of alcohol abuse. C1 VA Greater Los Angeles Healthcare Syst, Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. W Valley Los Angeles Cty Dept Hlth, Van Nuys, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 105 TC 8 Z9 8 U1 9 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2004 VL 97 IS 1 BP 5 EP 11 DI 10.1016/j.tripleo.2003.09.004 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 763TD UT WOS:000188115800005 PM 14716250 ER PT J AU Redding, SW Dahiya, MC Kirkpatrick, WR Coco, BJ Patterson, TF Fothergill, AW Rinaldi, MG Thomas, CR AF Redding, SW Dahiya, MC Kirkpatrick, WR Coco, BJ Patterson, TF Fothergill, AW Rinaldi, MG Thomas, CR TI Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID COLONIZATION; ALBICANS; EPIDEMIOLOGY; STRAINS; INFECTION AB Oropharyngeal candidiasis (OPC) is relatively common in patients receiving radiation for head and neck cancer occurring in approximately 25% of patients. Candida albicans has been described as the primary infecting organism. Recently, other organisms, particularly Candida glabrata, have emerged as causative agents of OPC among immunocompromised patients. This study describes the characteristics of 6 patients with head and neck cancer treated with radiotherapy at our institution, who were found to have Candida glabrata-associated OPC and their responses to oral fluconazole. All 6 patients were successfully treated with oral fluconazole. However, most did not respond to the usual dose of 100 mg/day necessitating doses ranging from 200 to 800 mg/day to achieve clinical cure. All 3 patients receiving radiation only,were successfully treated with up to 200 mg/day; 2 of 3 patients receiving concomitant chemoradiation required doses ranging from 400 to 800 mg/day. As with systemic infection, previous fluconazole use appears to be a risk factor for this infection, but not with all patients. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Radiat Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Pathol, San Antonio, TX 78229 USA. RP Redding, SW (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM redding@uthscsa.edu NR 16 TC 32 Z9 36 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2004 VL 97 IS 1 BP 47 EP 52 DI 10.1016/j.tripleo.2003.09.008 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 763TD UT WOS:000188115800010 PM 14716255 ER PT J AU Devaney, KO Rinaldo, A Zeitels, SM Bradley, PJ Ferlito, A AF Devaney, KO Rinaldo, A Zeitels, SM Bradley, PJ Ferlito, A TI Laryngeal dysplasia and other epithelial changes on endoscopic biopsy: What does it all mean to the individual patient? SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Editorial Material ID UPPER AERODIGESTIVE TRACT; INTRAEPITHELIAL NEOPLASIA; INVASIVE-CARCINOMA; KERATOSIS; CANCER; INSITU; TRANSFORMATION; LESIONS; GLOTTIS C1 Univ Udine, ENT Clin, Dept Surg Sci, Policlin Univ, IT-33100 Udine, Italy. Foote Hosp, Dept Pathol, Jackson, MI USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Queens Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Nottingham NG7 2UH, England. RP Ferlito, A (reprint author), Univ Udine, ENT Clin, Dept Surg Sci, Policlin Univ, Piazzale S Maria Misericordia, IT-33100 Udine, Italy. EM a.ferlito@uniud.it NR 31 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2004 VL 66 IS 1 BP 1 EP 4 DI 10.1159/000077225 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 814KL UT WOS:000220973500001 PM 15103193 ER PT J AU Kujawski, OB Poe, TS AF Kujawski, OB Poe, TS TI Laser eustachian tuboplasty SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 135th Annual Meeting of the American-Otological-Society CY MAY 10-13, 2002 CL BOCA RATON, FL SP Amer Otol Soc DE eustachian tube dysfunction; laser eustachian tuboplasty ID VIDEO ENDOSCOPY; TUBE AB Objectives: Surgery on the eustachian tube for chronic eustachian tube dysfunction has been previously directed toward the bony isthmus and failed to produce lasting results. Dynamic video analysis demonstrates pathophysiology in the tubal cartilaginous portion. This study investigated a new endo-luminal procedure that focused on the cartilaginous eustachian tube. Study Design: Prospective surgical trial. Setting: Tertiary care private practice and outpatient surgical center. Patients: One hundred eight eustachian tubes with intractable eustachian tube dysfunction (middle ear atelectasis or effusion) in 56 patients underwent laser eustachian tuboplasty by the first author (O. B. K.) since 1997. Intervention: Dynamic video analyses of eustachian tube function were performed perioperatively. Laser eustachian tuboplasties were performed unilaterally or bilaterally under General anesthesia through a combined endoscopic nasal and transoral approach to the eustachian tube nasopharyngeal orifice. Carbon dioxide or 980-nm diode laser vaporization of mucosa and cartilage from the luminal posterior wall was accomplished until adequately dilation was achieved and the tube was packed. A laser myringotomy for temporary middle ear aeration while the eustachian tube was packed was also performed during surgery. Main Outcome Measures: There were two outcome measures: 1) the presence or absence of middle ear effusion or tympanic membrane atelectasis and 2) impedance tympanometry. In addition, dynamic videos were examined to rate the degree of visible opening of the tubal valve and effects on mucosal edema and muscular movements. Results: Seventy-four (68.51%) ears achieved normal middle ear aeration at 1 year, 70 (71.42%) at 2 years, and 60 (65.21%) at greater than or equal to 3 years. There were no intraoperative complications. Postoperative complications were limited to minimal peritubal synechia in nine (8.33%) tubes and epistaxis in one (0.9%) tubes. Seven (6.48%) ears failed treatment and required tympanostomy tubes. Conclusion: Laser eustachian tuboplasty is a new procedure that has demonstrated early promise in correcting intractable eustachian tube dysfunction with few complications. Further studies will be necessary to reproduce the results and establish the role of laser eustachian tuboplasty in the management of chronic intractable eustachian tube dysfunction. C1 Int ENT Ctr, Clin Grangettes, Eustacian Tube Disorder Ctr, Geneva, Switzerland. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kujawski, OB (reprint author), Int ENT Ctr, Clin Grangettes, Eustacian Tube Disorder Ctr, 110 Route Chene,1224 Chene Bougeries, Geneva, Switzerland. EM kujawski@eustachian-tube.com NR 23 TC 39 Z9 43 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2004 VL 25 IS 1 BP 1 EP 8 DI 10.1097/00129492-200401000-00001 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 780JZ UT WOS:000189378700001 PM 14724483 ER PT J AU Yang, HF Ivan, M Min, JH Kim, WY Kaelin, WG AF Yang, HF Ivan, M Min, JH Kim, WY Kaelin, WG TI Analysis of von Hippel-Lindau hereditary cancer syndrome: Implications of oxygen sensing SO OXYGEN SENSING SE METHODS IN ENZYMOLOGY LA English DT Review ID HYPOXIA-INDUCIBLE FACTOR; UBIQUITIN-PROTEASOME PATHWAY; FACTOR 1-ALPHA; PROTEIN; ACTIVATION; DISEASE; COMPLEX; DOMAIN C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Yang, HF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ivan, Mircea/A-8109-2012 NR 13 TC 7 Z9 7 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 381 BP 320 EP 335 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAC00 UT WOS:000221513700023 PM 15063684 ER PT J AU Reddy, VY Houghtaling, C Fallon, J Fischer, G Farr, N Clarke, J McIntyre, J Sinofsky, E Ruskin, JN Keane, D AF Reddy, VY Houghtaling, C Fallon, J Fischer, G Farr, N Clarke, J McIntyre, J Sinofsky, E Ruskin, JN Keane, D TI Use of a diode laser balloon ablation catheter to generate circumferential pulmonary venous lesions in an open-thoracotomy caprine model SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Scientific Sessions of the North-American-Society-of-Pacing-and-Electrophysiology CY MAY 08-11, 2002 CL SAN DIEGO, CALIFORNIA SP N Amer Soc Pacing Electrophysiol DE atrial fibrillation; catheter ablation; laser; arrhythmia; reflectance spectroscopy; goat ID PAROXYSMAL ATRIAL-FIBRILLATION; RADIOFREQUENCY ABLATION; VEINS; INITIATION AB Electrical isolation of the pulmonary veins (PVs) can be curative in certain patients with atrial fibrillation. The ability of a diode laser balloon ablation catheter to isolate PVs was assessed in an open-thoracotomy caprine model system. After a median sternotomy, the left atrial appendage was cannulated in 19 goats. A laser balloon catheter was placed at the PV ostia and used to deliver photonic energy to the periostial tissue. The applications were delivered at 3.71 4.5, or 5.4 W/cm for 90-150 seconds. Electrical continuity of the PV with the left atrium was assessed using a multielectrode mapping catheter. After a single application of photonic energy, electrical isolation of the PVs was achieved in (70%) 19/27 PVs. However, the success of electrical PV isolation did not correlate with the dose or duration of the applications. When reflectance spectroscopy was utilized to ensure adequate orientation and contact of the laser balloon catheter with the left atrial myocardium, complete PV isolation was achieved in 5/5 veins at 3.5 W/cm for 120 seconds. Pathological examination revealed no PV stenosis, no pericardial damage, minor lung lesions without pleural perforation, minimal endothelial disruption, and, in the presence of adequate heparinization, no endocardial charring or overlying thrombus. Effective isolation of the PVs can be achieved by delivery of a continuous circular beam of photonic energy to ablate the left atrial - pulmonary venous junction. The use of reflectance spectroscopy to provide real-time monitoring of the blanching effect of balloon-tissue contact optimizes lesion delivery. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. CardioFocus Inc, Norton, MA USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Dept Med, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org FU NHLBI NIH HHS [K23 HL68064-01A1] NR 14 TC 37 Z9 39 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2004 VL 27 IS 1 BP 52 EP 57 DI 10.1111/j.1540-8159.2004.00385.x PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 769MD UT WOS:000188653100009 PM 14720155 ER PT J AU Miller, LL Harvath, TA Ganzini, L Goy, ER Delorit, MA Jackson, A AF Miller, LL Harvath, TA Ganzini, L Goy, ER Delorit, MA Jackson, A TI Attitudes and experiences of Oregon hospice nurses and social workers regarding assisted suicide SO PALLIATIVE MEDICINE LA English DT Article DE attitudes; euthanasia; hospice; nurses; physician-assisted suicide; social workers ID EUTHANASIA; CARE; PHYSICIANS AB Background: When the Oregon Death with Dignity Act ( ODDA) legalizing physician-assisted suicide was enacted into law in 1997, Oregon hospice clinicians were uncertain how involved they would be with patients who wanted this option. However, 86% of the 171 persons in Oregon who have died by lethal prescription were enrolled in hospice programmes. Method: A mailed questionnaire was sent to all hospice nurses and social workers in Oregon in 2001 (n = 573) to assess their attitudes about legalized assisted suicide and interactions with patients concerning this issue. Responses from 306 nurses and 85 social workers are included in this report. Findings: Almost two-thirds of respondents reported that at least one patient had discussed assisted suicide as a potential option in the past year. Social workers were generally more supportive of both the ODDA and of patients choosing assisted suicide compared to nurses. Twenty-two per cent of all respondents were not comfortable discussing assisted suicide with patients. Ninety-five per cent of both groups, however, favoured hospice policies that would allow a patient to choose assisted suicide while enrolled in hospice and allow hospice clinicians to continue to provide care. Interpretations: Nurses and social workers in hospices and other settings can expect to encounter patient questions about physician-assisted suicide, whether legalized or not, and must be prepared to have these discussions. Most hospice professionals in Oregon do not believe that assisted suicide and hospice enrolment are mutually exclusive alternatives. C1 Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hospice Assoc, Portland, OR USA. RP Miller, LL (reprint author), Oregon Hlth Sci Univ, Sch Nursing, SN-5N,3455 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM millerlo@ohsu.edu NR 25 TC 14 Z9 14 U1 1 U2 9 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PY 2004 VL 18 IS 8 BP 685 EP 691 DI 10.1191/0269216304pm961oa PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 881KB UT WOS:000225865300003 PM 15623164 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 Transforming growth factor-beta(1), interleukin-10 and interferon-gamma cytokine polymorphisms in patients with hereditary, familial and sporadic chronic pancreatitis SO PANCREATOLOGY LA English DT Article DE chronic pancreatitis; gene polymorhisms; cytokines; hereditary pancreatitis ID TUMOR-NECROSIS-FACTOR; IDIOPATHIC CHRONIC-PANCREATITIS; FACTOR-ALPHA; GROWTH-FACTOR-BETA-1 GENE; TNF-ALPHA; ASSOCIATION; PROMOTER; DISEASE; SUSCEPTIBILITY; EXPRESSION AB Background: The genetic influence is undefined in about 40% of patients with hereditary and familial pancreatitis and in the majority of patients with sporadic chronic pancreatitis. The pathophysiological mechanisms underlying the progression from acute to chronic pancreatitis have not been clarified. Cytokines participate in the immunological progression of pancreatic inflammation and may play an important role in the development of pancreatic fibrosis. Aims: We determined whether functional polymorphisms in the transforming growth factor-beta(1) gene at positions -509, +869 (codon 10) and +915 (codon 25), in the interleukin-10 gene at position -1082, and in the intron 1 of the interferon-gamma gene at position +874 are associated with hereditary, familial or sporadic pancreatitis. Methods: We investigated 78 patients with hereditary and familial pancreatitis and 62 patients with sporadic pancreatitis that were tested negative for cationic trypsinogen gene mutations, and 73 controls. Mutational analysis was performed by direct DNA sequencing or by amplification refractory mutational system polymerase chain reaction. We used the age at onset as marker of disease severity. Results: The genotype frequencies were similar between patients and controls for all investigated cytokine polymorphisms (p > 0.05). We did not find an association between the different genotypes and the age at onset of the disease, and we did not detect different genotype distributions in patients with morphological alterations on pancreatic imaging after a disease duration of up to 5 years. Conclusion: These genetic variants do not play a dominant role in hereditary, familial or sporadic chronic pancreatitis. Copyright (C) 2004 S. Karger AG, Basel and IAP. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15101 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15101 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15101 USA. Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15101 USA. Univ Pittsburgh, Ctr Genom Sci, Pittsburgh, PA 15101 USA. Univ Heidelberg Hosp, Dept Med 2, D-68135 Mannheim, Germany. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15101 USA. EM whitcomb@pitt.edu OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 28 TC 9 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2004 VL 4 IS 6 BP 490 EP 494 DI 10.1159/000080245 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883XH UT WOS:000226048500002 PM 15316224 ER PT J AU Gukovskaya, AS Pandol, SJ AF Gukovskaya, AS Pandol, SJ TI Cell death pathways in pancreatitis and pancreatic cancer SO PANCREATOLOGY LA English DT Review DE apoptosis; necrosis; caspases; mitochondrial dysfunction ID NF-KAPPA-B; EXTRACELLULAR-MATRIX PROTEINS; PERMEABILITY TRANSITION PORE; TUMOR-NECROSIS-FACTOR; CYTOCHROME-C RELEASE; INTRACELLULAR TRYPSINOGEN ACTIVATION; CERULEIN-INDUCED PANCREATITIS; HUMAN DUCTAL ADENOCARCINOMAS; BLOOD MONONUCLEAR-CELLS; HEAT-SHOCK PROTEINS AB The understanding of the regulation of apoptosis and necrosis, the two principal cell death pathways, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis and pancreatic cancer. For example, in acute pancreatitis significant amounts of pancreatic necrosis are associated with increased morbidity and mortality. Thus, determining the key steps regulating necrosis should provide insights into potential therapeutic strategies for improving outcome in these patients. On the other hand, in pancreatic cancer various survival mechanisms act to prevent cell death, resulting in promotion of tumor growth and metastasis. Resistance of pancreatic cancer to apoptosis is the key factor preventing responses to therapies. Investigations of the regulation of cell death mechanisms specific to pancreatic cancer should lead to improvements in our current therapies for this disease. The present review is designed to provide information about cell death pathways in pancreatitis and pancreatic cancer with reference to areas that need further investigation, as well as to provide measurement techniques adapted to pancreatic tissue and cells. Copyright (C) 2004 S. Karger AG, Basel and IAP. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIDDK NIH HHS [DK59508, DK59936] NR 204 TC 105 Z9 109 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2004 VL 4 IS 6 BP 567 EP 586 DI 10.1159/000082182 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883XH UT WOS:000226048500015 PM 15550766 ER PT J AU Tran, AN Haidet, P Street, RL O'Malley, KJ Martin, F Ashton, CM AF Tran, AN Haidet, P Street, RL O'Malley, KJ Martin, F Ashton, CM TI Empowering communication: a community-based intervention for patients SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE physician-patient relations; persuasive communication; patient-centered care patient activation; cross-cultural comparison; community networks ID PARTICIPATORY DECISION-MAKING; MEDICAL-CARE; IMPROVE COMMUNICATION; BREAST-CANCER; SATISFACTION; CONSULTATIONS; PHYSICIANS; PROVIDER; SKILLS; OUTCOMES AB The "How to Talk to Your Doctor" community education forums operate under the assumption that information exchange and consumer involvement in healthcare can empower communities in need. We report on the development and preliminary evaluation of this community-based intervention designed to activate and enhance patients' communicative abilities in the medical encounter. We review evidence supporting the feasibility of and benefits that can be expected from improving patients' communication competency. Our intervention is simple and flexible so, therefore, can be portable to a large number of communities. Our preliminary evaluation suggests that the intervention is well-received and produces improved self-perceptions of communication competence across diverse settings and participants. We describe our intervention and its development and dissemination as a model for improving patients' communicative abilities through a community-based, active learner approach. By sharing our experiences, the barriers we encountered, and our ongoing efforts to improve patient communication in the medical encounter, we hope to empower patients to communicate better with their physicians. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Texas A&M Univ, Dept Commun, College Stn, TX 77843 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Res Ctr Excellence, US Dept Vet Affairs,Hlth Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Tran, AN (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, CB 7440, Chapel Hill, NC 27599 USA. EM anhtran@email.unc.edu FU AHRQ HHS [P01 HS10876] NR 48 TC 40 Z9 41 U1 0 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2004 VL 52 IS 1 BP 113 EP 121 DI 10.1016/S0738-3991(03)00002-8 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 768WG UT WOS:000188592700015 PM 14729298 ER PT J AU Bonner-Weir, S Toschi, E Inada, A Reitz, P Fonseca, SY Aye, T Sharma, A AF Bonner-Weir, S Toschi, E Inada, A Reitz, P Fonseca, SY Aye, T Sharma, A TI The pancreatic ductal epithelium serves as a potential pool of progenitor cells SO PEDIATRIC DIABETES LA English DT Article DE beta-cell growth; endocrine pancreas; pancreatic; progenitors ID HOMEODOMAIN PROTEIN IDX-1; GROWTH-FACTOR ALPHA; BETA-CELLS; ISLET NEOGENESIS; ENDOCRINE PANCREAS; PRECURSOR CELLS; TRANSGENIC MICE; RAT PANCREAS; REGENERATION; ADULT AB With the increasing success of islet transplantation, beta-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM weir@joslin.harvard.edu FU NIDDK NIH HHS [DK-36836, DK-61251, DK-44523] NR 48 TC 165 Z9 179 U1 1 U2 9 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PY 2004 VL 5 SU 2 BP 16 EP 22 DI 10.1111/j.1399-543X.2004.00075.x PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 888PH UT WOS:000226386200004 PM 15601370 ER PT J AU Habener, JF AF Habener, JF TI A perspective on pancreatic stem/progenitor cells SO PEDIATRIC DIABETES LA English DT Review DE diabetes, pancreas, stem cells ID INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; EPITHELIAL-MESENCHYMAL TRANSITIONS; NESTIN-POSITIVE PRECURSORS; DEVELOPING MOUSE PANCREAS; GLUCAGON-LIKE PEPTIDES; HUMAN FETAL PANCREAS; PROGENITOR CELLS; BONE-MARROW; BETA-CELLS AB The prevalence of both type 1 and type 2 diabetes mellitus is increasing throughout the world along with the ensuant morbidity and early mortality because of premature microvascular and macrovascular disease. Current insulin and drug therapies control diabetes, but do not cure it. Cell-based therapies offer the possibilities of a permanent cure for diabetes. Recently, success in the transplantation of pancreatic islets in the livers of type 1 diabetics has afforded the opportunity for a potential cure. However, the severe shortage of donor islets for transplantation limits the usefulness of this therapy. One approach is to exploit the use of stem cells, either embryo-derived or adult tissue-derived, as substrates to create islet tissue suitable for transplantation. Cells isolated from embryo blastocysts and from adult pancreas, liver, and bone marrow can be expanded extensively in vitro and differentiated into islet-like clusters that produce insulin, and, in some instances, can achieve glycemic control when transplanted into streptozotocin-induced diabetic mice. It is, now, also possible to envision the direct systemic administration of stem cells that would home in on and regenerate injured islets, or to administer stem cell stimulators that would enhance endogenous pancreatic stem cells to expand and differentiate into functional, insulin-producing beta-cells. This perspective discusses the potential applications of cellular medicines, in the new discipline of regenerative medicine, to achieve a cure for diabetes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Endocrinol, 55 Fruit St,WEL 320, Boston, MA 02114 USA. EM jhabener@partners.org NR 119 TC 11 Z9 11 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PY 2004 VL 5 SU 2 BP 29 EP 37 DI 10.1111/j.1399-543X.2004.00077.x PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 888PH UT WOS:000226386200006 PM 15601372 ER PT J AU Kodama, S Faustman, DL AF Kodama, S Faustman, DL TI Routes to regenerating islet cells: stem cells and other biological therapies for type 1 diabetes SO PEDIATRIC DIABETES LA English DT Article DE diabetes; islets of Langerhans; regeneration; spleen; stem cells ID BONE-MARROW; PANCREATIC-ISLETS; DISTAL PANCREATECTOMY; PROGENITOR CELLS; RAT PANCREAS; ADULT; DIFFERENTIATION; ENDOCRINE; MUSCLE; IDENTIFICATION AB New biological therapies for type 1 diabetes are emerging from the forefront of stem cell and islet cell biology. Basic research in animal models has uncovered a variety of mechanisms by which natural regeneration of pancreatic islet cells occurs, despite the underlying autoimmune defect. Two mechanisms - in particular, beta-islet cell proliferation and stem cell differentiation - can be harnessed in innovative ways in order to regenerate islets lost to disease. This review provides a background on stem cells and describes a range of potential. biological therapies for type 1 diabetes, including the use of adult stem cells from the spleen, an organ not previously considered a source of pancreatic stem cells. Stem cells of the spleen have been demonstrated to home to the pancreas, where they mature into fully functional islet cells responsible for restoring normoglycemia. If the underlying autoimmune defect can be eradicated, stem cells of the spleen, as well as related strategies, can be used in order to regrow islets destroyed by type I diabetes. C1 Harvard Univ, Sch Med, Boston, MA 02192 USA. E Massachusetts Gen Hosp, Boston, MA USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Bldg 149,13th St,Room 3602, Boston, MA 02192 USA. EM faustman@helix.mgh.harvard.edu NR 47 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PY 2004 VL 5 SU 2 BP 38 EP 44 DI 10.1111/j.1399-543X.2004.00078.x PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 888PH UT WOS:000226386200007 PM 15601373 ER PT B AU Newburg, D Morrow, A Jiang, X Ruiz-Palacios, G AF Newburg, D Morrow, A Jiang, X Ruiz-Palacios, G GP MEDIMOND TI Beyond FOS and GOS for infant formulas SO PEDIATRIC GASTROENTEROLOGY 2004 LA English DT Proceedings Paper CT 2nd World Congress of Pediatric Gastroenterology, Hepatology and Nutrition CY JUL 03-07, 2004 CL Paris, FRANCE ID HUMAN-MILK; OLIGOSACCHARIDES AB Breastfeeding increases colonization by bifidobacteria and enterobacteria, which is thought to protect infants from enteric disease. Fructooligosac-charides (FOS) and galactooligosaccharides (GOS) in the diet also increase the content of bifidobacteria and other commensals in intestinal microflora and, therefore, are being considered as dietary supplements for infants.(1) Human milk oligosaccharides (HOS) are chemically different from FOS and GOS and prevent binding by pathogens to the intestinal mucosa in vitro and in vivo. The expression of these oligosaccharides in milk varies by maternal genotype. Infants consuming milk high in 2-linked fucosyloligosaccharides have significantly lower risk of diarrhea due to ST-Escherichia coli (STEC), Campylobacter jejuni, human caliciviruses, and diarrhea of all causes, suggesting their utility as dietary supplements. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Newburg, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 9 TC 0 Z9 0 U1 0 U2 2 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-106-X PY 2004 BP 1 EP 7 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics SC Gastroenterology & Hepatology; Nutrition & Dietetics GA BBR35 UT WOS:000227354700001 ER PT J AU Rai, S Engelberts, D Laffey, JG Frevert, C Kajikawa, O Martin, TR Post, M Kavanagh, BP AF Rai, S Engelberts, D Laffey, JG Frevert, C Kajikawa, O Martin, TR Post, M Kavanagh, BP TI Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung SO PEDIATRIC RESEARCH LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; NECROSIS-FACTOR-ALPHA; FREQUENCY OSCILLATORY VENTILATION; ARTERIAL BLOOD OXYGENATION; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; PULMONARY-EDEMA; RAT LUNGS; INJURY; MODEL AB Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia- deliberate elevation of arterial P-CO2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 ML/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O-2 difference, arterial P-O2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O-2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-a was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable. C1 Hosp Sick Children, Lung Biol Program, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Crit Care Med & Anaesthesia, Toronto, ON M5G 1X8, Canada. Univ Toronto, Interdepartmental Div Crit Care Med, Toronto, ON M5G 1X8, Canada. Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Kavanagh, BP (reprint author), Hosp Sick Children, Dept Crit Care Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. OI Laffey, John/0000-0002-1246-9573 NR 47 TC 26 Z9 26 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2004 VL 55 IS 1 BP 42 EP 49 DI 10.1203/01.PDR.0000098502.72182.55 PG 8 WC Pediatrics SC Pediatrics GA 756UN UT WOS:000187502400006 PM 14561781 ER PT J AU Beal, AC Co, JPT Dougherty, D Jorsling, T Kam, J Perrin, J Palmer, RH AF Beal, AC Co, JPT Dougherty, D Jorsling, T Kam, J Perrin, J Palmer, RH TI Quality measures for children's health care SO PEDIATRICS LA English DT Article DE quality of care; child health; health care quality; Institute of Medicine; quality framework ID MEDICAID MANAGED CARE; OF-CARE; CHALLENGES; IMPROVEMENT; SERVICES; CULTURE; IMPACT; STATES; HOME AB Background. The ability to measure and improve the quality of children's health care is of national importance. Despite the existence of numerous health care quality measures, the collective ability of measures to assess children's health care quality is unclear. A review of existing health care quality measures for children is timely for both assessing the current state of quality measures for children and identifying areas requiring additional research and development. Objectives. To identify and collect current health care quality measures for child health and then to systematically categorize and classify measures and identify gaps in child health care quality measures requiring additional development. Design/Methods. We first identified child health care quality instruments with assistance from staff at the Agency for Healthcare Research and Quality, experts in the field, the Computerized Needs-oriented Quality Measurement Evaluation System, the Child and Adolescent Health Measurement Initiative, and a medical literature review. From these instruments, we then selected clinical performance measures applicable to children ( aged 0-18 years). We categorized the individual measures into the Institute of Medicine's framework for the National Health Care Quality Report. The framework includes health care quality domains ( patient safety, effectiveness, patient-centeredness, and timeliness) and patient-perspective domains ( staying healthy, getting better, living with illness, and end-of-life care). We then determined the balance of the measures ( how well they assess care for all children versus children with special health care needs) and their comprehensiveness ( how well the measures apply to the developmental range of children). Finally, we analyzed the ability of the measures to assess equity in care. Results. We identified 19 measure sets, and 396 individual measures were used to assess children's health care quality. The distribution of measures in the health care quality domains was: safety, 14.4%; effectiveness, 59.1%; patient-centeredness, 32.1%; and timeliness, 33.3%. The distribution of measures in the patient-perspective domains was: staying healthy, 24%; getting better, 40.2%; living with illness, 17.4%; end of life, 0%; and multidimensional, 23.5% ( measures were multidimensional if they applied to > 1 domain). Most of the measures were meant for use in the general pediatric population (81.1%), with a significant proportion designed for children with special health care needs (18.9%). The majority (greater than or equal to79%) of the measures could be applied to children across all age groups. However, there were relatively few measures designed specifically for each developmental stage. Regarding the use of measures to study equity in health care, 6 of the measure sets have been used in previous studies of equity. All the survey measure sets contain items that identify patients at risk for poor outcomes, and 4 are available in languages other than English. However, only 1 survey ( Consumer Assessment of Health Plans) has undergone studies of cross-cultural validation. Among the measure sets based on administrative data, 3 included infant mortality, a well-known measure of health disparity. Conclusions. There are several instruments designed to measure health care quality for children. Despite this, we found relatively few measures for assessing patient safety and living with illness and none for end-of-life care. Few measures are designed for specific age categories among children. Although equity is an overarching concern in health care quality, the application of current measures to assess disparities has been limited. These areas need additional research and development for a more complete assessment of health care quality for children. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Agcy Healthcare Res & Qual, Off Prior Populat Res, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Ctr Qual Care Res & Educ, Boston, MA 02115 USA. RP Beal, AC (reprint author), Commonwealth Fund, Qual Care Underdeserved Populat, 1 E 75th St, New York, NY 10021 USA. EM acb@cmwf.org NR 38 TC 69 Z9 69 U1 4 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2004 VL 113 IS 1 SU S BP 199 EP 209 PG 11 WC Pediatrics SC Pediatrics GA 762XY UT WOS:000188010700002 PM 14702502 ER PT J AU Kuhlthau, K Ferris, TGG Iezzoni, LI AF Kuhlthau, K Ferris, TGG Iezzoni, LI TI Risk adjustment for pediatric quality indicators SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting on Quality Measures for Childrens Health Care: Assessing the State of the Science and Practice CY FEB 05-06, 2002 CL ROCKVILLE, MARYLAND DE risk adjustment; pediatric quality indicators; child ID MEDICAID-ENROLLED CHILDREN; CONGENITAL HEART-DISEASE; NEONATAL INTENSIVE-CARE; AUTOMATED PHARMACY DATA; IN-HOSPITAL MORTALITY; MANAGED CARE; CASE-MIX; CARDIAC-SURGERY; BIRTH-WEIGHT; HEALTH-CARE AB The movement to measure medical care quality has been accelerating, spurred on by evidence of poor quality of care and trials of interventions to improve care. Appropriate measurement of quality of care is an essential aspect of improving the quality of care, yet some quality measures may be influenced by patients' attributes unrelated to quality of care. Risk adjustment is the term commonly applied to those methods that account for patient-related attributes, making measurement of health care quality as comparable as possible across providers or organizations seeing different mixes of patients. The measurement of quality of care for children poses specific challenges. In addition to these measurement challenges, analysts must ensure that quality comparisons among doctors, groups of doctors, hospitals, or health plans are not adversely affected by the likelihood that different types of patients seek care in different places. Although some techniques designed to adjust performance measures for case mix were developed for both adults and children, other systems are specific to childhood circumstances. The theoretical issues involved in risk-adjusting childhood outcomes measures for newborns in the neonatal intensive care unit were reviewed recently. Here, we go beyond the neonatal intensive care unit setting to consider risk adjustment for pediatric quality measures more broadly. In particular, we 1) review the conceptual background for risk-adjusting quality measures, 2) present policy issues related to adjusting pediatric quality measures, and 3) catalog existing risk-adjustment methodologies for pediatric quality measures. We conclude with an overall assessment of the status of risk adjustment for pediatric quality measures and recommendations for additional research and application. C1 Harvard Univ, Sch Med, MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy,Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy,Dept Med,Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Gen Med & Primary Care, Boston, MA USA. Charles A Dana Res Inst, Boston, MA 02215 USA. Harvard Thorndike Lab, Boston, MA USA. RP Kuhlthau, K (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy,Dept Pediat, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM kkuhlthau@partners.org NR 54 TC 17 Z9 17 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2004 VL 113 IS 1 SU S BP 210 EP 216 PG 7 WC Pediatrics SC Pediatrics GA 762XY UT WOS:000188010700003 PM 14702503 ER PT B AU Ho, NH Weissleder, R Tung, CH AF Ho, Nan-Hui Weissleder, Ralph Tung, Ching-Husan BE Chorev, M Sawyer, TK TI New approach for peptide ligation SO Peptide Revolution: Genomics, Proteomics & Therapeutics LA English DT Proceedings Paper CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Ho, NH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA BN 0-9715560-1-6 PY 2004 BP 121 EP 122 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BEQ46 UT WOS:000238911100053 ER PT B AU Tung, CH Ho, NH Zeng, Q Weissleder, R AF Tung, Ching-Hsuan Ho, Nan-Hui Zeng, Qing Weissleder, Ralph BE Chorev, M Sawyer, TK TI In vivo imaging of thrombosis-associated enzyme using fluorescence peptide probes SO Peptide Revolution: Genomics, Proteomics & Therapeutics LA English DT Proceedings Paper CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MA ID FACTOR-XIII; ACTIVATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA BN 0-9715560-1-6 PY 2004 BP 325 EP 326 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BEQ46 UT WOS:000238911100134 ER PT B AU Pham, W Weissleder, R Tung, CH AF Pham, Wellington Weissleder, Ralph Tung, Ching-Husan BE Chorev, M Sawyer, TK TI Peptide-based near infrared optical probes specific for matrix metalloproteinases activity detection SO Peptide Revolution: Genomics, Proteomics & Therapeutics LA English DT Proceedings Paper CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Pham, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St, Boston, MA 02129 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA BN 0-9715560-1-6 PY 2004 BP 367 EP 368 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BEQ46 UT WOS:000238911100154 ER PT B AU Khatri, A Huang, XC Shimizu, N Gardella, TJ AF Khatri, Ashok Huang, Xiang-Chen Shimizu, Naoto Gardella, Thomas J. BE Chorev, M Sawyer, TK TI Synthesis of conformation ally constrained PTH(1-14) analogs SO Peptide Revolution: Genomics, Proteomics & Therapeutics LA English DT Proceedings Paper CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MA ID PARATHYROID-HORMONE; RECEPTOR; POTENCY C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Khatri, A (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA BN 0-9715560-1-6 PY 2004 BP 677 EP 678 PG 2 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BEQ46 UT WOS:000238911100285 ER PT J AU Vanduffel, W AF Vanduffel, W TI Virtual lesions: Examining cortical function with reversible deactivation SO PERCEPTION LA English DT Book Review C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Katholieke Univ Leuven, Lab Neuro & Psychophysiol, B-3000 Louvain, Belgium. RP Vanduffel, W (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM wim@nmr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2004 VL 33 IS 7 BP 891 EP 893 PG 3 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 856QD UT WOS:000224058800010 ER PT J AU Quinn, J Kaye, J Montine, T Stackman, R AF Quinn, J Kaye, J Montine, T Stackman, R TI Phytochemicals in Alzheimer disease: The development of clinical trials SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Alzheimer disease; antioxidants; oxidative stress; polyphenolics ID BETA-AMYLOID NEUROTOXICITY; MILD COGNITIVE IMPAIRMENT; APP(SW) TRANSGENIC MICE; GINKGO-BILOBA; CEREBROSPINAL-FLUID; LIPID-PEROXIDATION; A-BETA; NEUROFIBRILLARY TANGLES; HIPPOCAMPAL VOLUME; UNCARIA-TOMENTOSA AB Polyphenolics and other phytochemicals may have a role in the prevention or treatment of Alzheimer disease. Targets of therapy in Alzheimer disease include neurotransmitter deficits, beta amyloid neurotoxicity, oxidative damage, and inflammation, to name a few. Challenges to the development of phytochemical and other neuroprotectant therapy in Alzheimer disease include the inability to measure pathology in living patients and the challenge of detecting modification of an indolent disease course. These challenges are partially surmounted by the use of animal models and of biomarkers of disease. This review describes currently available animal models and biomarkers and surveys clinical trials of phytochemical therapies that. are recently completed or currently under way. Both animal studies and clinical trials of Ginkgo biloba are described, as well as a trial of Uncaria tomentosa that has not been previously reported. C1 Portland Vet Affairs Med Ctr, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. RP Quinn, J (reprint author), Portland Vet Affairs Med Ctr, Dept Neurol, P3 R&D,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM quinnj@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478; Stackman Jr, Robert/0000-0002-5950-046X NR 64 TC 3 Z9 3 U1 3 U2 11 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2004 VL 42 SU S BP 64 EP 73 DI 10.1080/138802090893531 PG 10 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 890QU UT WOS:000226526700006 ER PT J AU Neeser, K Lubben, G Siebert, U Schramm, W AF Neeser, K Lubben, G Siebert, U Schramm, W TI Cost effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a German statutory healthcare perspective SO PHARMACOECONOMICS LA English DT Article ID BLOOD-GLUCOSE CONTROL; LONG-TERM INCIDENCE; GLYCEMIC CONTROL; ECONOMIC-EVALUATION; RISK-FACTORS; MANAGEMENT STRATEGIES; METFORMIN THERAPY; PROSIT-PROJECT; LIPID PROFILE; TASK-FORCE AB Background: Pioglitazone has been approved in Europe for oral combination therapy for type 2 diabetes mellitus. Along with other agents of the thiazolidinedione class, it has a novel intracellular mechanism of action. Clinical trials with pioglitazone have confirmed a strong product profile in terms of control of blood glucose and lipids. However, the drug acquisition cost for pioglitazone is greater than standard medications for type 2 diabetes. Long-term data regarding the cost effectiveness of pioglitazone-based combination therapy are not available. Objective: To evaluate, using a decision analysis model, the cost effectiveness of pioglitazone-based combination therapy compared with relevant alternative medications for the treatment of type 2 diabetes in Germany. Methods: This study compared the clinical effects and costs of pioglitazone 30mg added to metformin in patients who failed metformin monotherapy and pioglitazone added to a sulphonylurea in patients who failed sulphonylurea monotherapy, with the most relevant treatment alternatives. A published and validated Markov model was adapted to reflect the management of type 2 diabetes. This simulated the number of severe complications occurring and the mean life expectancy of a diabetic cohort, which was based on the overweight group of the UK Prospective Diabetes Study at year 6 of follow-up. Drug treatment costs, other costs for general management of type 2 diabetes and the costs of complications were combined to compute overall lifetime treatment costs from the perspective of the German statutory healthcare system in 2002. Results: Combination therapy with pioglitazone/metformin was associated with a higher life expectancy (15.2 years) relative to sulphonylurea/metformin (14.9 years) or acarbose/metformin (14.7 years). Likewise, pioglitazone/sulphonylurea (15.5 years) was superior to metformin/sulphonylurea (14.9 years) and acarbose/sulphonylurea (14.8 years). Undiscounted incremental cost-effectiveness ratios in comparison to the next best strategy were euro20 002 per life-year gained (LYG) for pioglitazone/metformin versus sulphorylurea/metformin, and euro8707 per LYG for pioglitazone/sulphorylurea versus metformin/sulphonylurea. After discounting costs and life expectancy at 5% per year, the incremental cost-effectiveness ratio was euro47 636 per LYG for pioglitazone/metformin versus sulphonylurea/metfor-min, and euro19 745 per LYG for pioglitazone/sulphonylurea versus metformin/ sulphonylurea. Conclusions: In this model, with its underlying assumptions and data, combination therapy with pioglitazone increased life expectancy in overweight type 2 diabetes patients at acceptable cost compared with other well established medications in Germany. These findings should be re-evaluated as soon as additional evidence becomes available from the currently ongoing long-term clinical and economic studies. C1 IMIB, CH-4058 Basel, Switzerland. Takeda Pharma, Aachen, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. RP Neeser, K (reprint author), IMIB, Clarastr 15, CH-4058 Basel, Switzerland. EM neeser@imib.ch NR 95 TC 15 Z9 15 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 EI 1179-2027 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2004 VL 22 IS 5 BP 321 EP 341 DI 10.2165/00019053-200422050-00006 PG 21 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 815YJ UT WOS:000221077300006 PM 15061682 ER PT J AU Zhu, QB Qi, LJ Shi, AG Abou-Samra, A Deth, RC AF Zhu, QB Qi, LJ Shi, AG Abou-Samra, A Deth, RC TI Protein kinase C regulates alpha(2A/D)-adrenoceptor constitutive activity SO PHARMACOLOGY LA English DT Article DE adrenoceptors; protein kinase C; epinephrine; rauwolscine; G-protein-coupled receptors ID ALPHA-2-ADRENERGIC RECEPTOR; ALPHA(2A)-ADRENERGIC RECEPTOR; ALPHA(2)-ADRENERGIC RECEPTOR; PHOSPHOLIPID METHYLATION; SIGNALING SPECIFICITY; ADRENERGIC-RECEPTORS; INTRACELLULAR LOOP; COUPLED RECEPTORS; ACTIVATION; IDENTIFICATION AB We investigated a possible role for protein kinases in the constitutive activity of alpha(2A/D) adrenoceptors in membranes from transfected PC12 cells, using a [S-35]GTPgammaS binding assay. After treatment of intact cells with various protein kinase inhibitors, constitutive activity was assessed by the reduction in basal GTP binding caused by the inverse agonist rauwolscine (RAU). Inhibitors of protein kinase C (PKC) caused the loss of RAU-sensitive GTP binding, while inhibitors of other protein kinases were ineffective. Anti-G(alpha) antibody treatments showed that constitutive alpha(2A/D)-receptor activity is directed toward different G proteins than agonist-stimulated activity. T373A mutant receptors exhibited increased constitutive activity, including a component that was insensitive to PKC inhibition. Since T373 is located within a putative G(i/o) activator sequence, these results suggest that PKC-dependent phosphorylation of T373 increases alpha(2A/D)-adrenergic receptor constitutive activity and causes a switch in G protein preference. Copyright (C) 2004 S. Karger AG, Basel. C1 Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Deth, RC (reprint author), Northeastern Univ, Dept Pharmaceut Sci, 312 Mugar Hall,360 Huntington Ave, Boston, MA 02115 USA. EM r.deth@neu.edu NR 39 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PY 2004 VL 71 IS 2 BP 80 EP 90 DI 10.1159/000076944 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 816LR UT WOS:000221111900004 PM 15118347 ER PT J AU Kossodo, S Wong, WR Simon, G Kochevar, IE AF Kossodo, S Wong, WR Simon, G Kochevar, IE TI Effects of UVR and UVR-induced cytokines on production of extracellular matrix proteins and proteases by dermal fibroblasts cultured in collagen gels SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; HUMAN-SKIN; GENE-EXPRESSION; ULTRAVIOLET-RADIATION; ELASTIC FIBERS; 3-DIMENSIONAL CULTURE; HUMAN KERATINOCYTES; PHOTOAGED SKIN; A IRRADIATION AB Synthesis of extracellular matrix (ECM) proteins and their degradation by matrix metalloproteinases (MMP) are part of the dermal remodeling resulting from chronic exposure of skin to ultraviolet radiation (UVR). We have compared two alternative mechanisms for these responses, namely, a direct mechanism in which UV-B or UV-A is absorbed by fibroblasts and an indirect mechanism in which cytokines, produced in skin in response to UVR, stimulate production of the ECM proteins and MMP. These studies were carried out on human dermal fibroblasts grown in contracted, free-floating 9 day old collagen gels as a dermal equivalent. Synthesis of tropoelastin, collagen, fibrillin, MMP-1, -2, -3 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were measured. Tropoelastin, collagen and fibrillin levels were stable between days 4 and 10, and MMP and TIMP decreased by day 10. Neither UV-B (2.5-50 mJ/cm(2)) nor UV-A (2-12 J/cm(2)) altered synthesis of ECM proteins, but UV-A increased MMP-1 and -3 production. Tropoelastin synthesis increased in response to transforming growth factor-beta1 (5 ng/mL) treatment. Both interleukin-ID and tumor necrosis factor-alpha (10 ng/mL) decreased fibrillin messenger RNA levels but increased MMP-1, -3 and -9 synthesis markedly. Collagen synthesis was not modulated by UV-B, UV-A or cytokine treatment. These results indicate that certain cytokines may have greater effects on production of ECM proteins and MMP than absorption of UV-B and UV-A by fibroblasts grown in dermal equivalents and suggest that the former pathway may play a role in the dermal remodeling in photoaged skin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, WEL-224, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR43895] NR 50 TC 14 Z9 16 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN PY 2004 VL 79 IS 1 BP 86 EP 93 DI 10.1111/j.1751-1097.2004.tb09861.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 765GZ UT WOS:000188259900012 PM 14974720 ER PT J AU Mansury, Y Deisboeck, TS AF Mansury, Y Deisboeck, TS TI Simulating 'structure-function' patterns of malignant brain tumors SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MATRIX METALLOPROTEINASES; CELLULAR-AUTOMATON; GROWTH DYNAMICS; GLIOMA INVASION; RAT-BRAIN; IN-VITRO; MODEL; CANCER; CELLS AB Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called 'beaten-path advantage' intensifies, i.e., rising 'mechanical rewards' for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed. (C) 2003 Elsevier B.V. All rights reserved. C1 MIT, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, HST Biomed Engn Ctr, Complex Biosyst Modeling Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. RP Deisboeck, TS (reprint author), MIT, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, HST Biomed Engn Ctr, Complex Biosyst Modeling Lab, Bldg 16-352,77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 34 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JAN 1 PY 2004 VL 331 IS 1-2 BP 219 EP 232 DI 10.1016/j.physa.2003.09.013 PG 14 WC Physics, Multidisciplinary SC Physics GA 753AP UT WOS:000187209300018 ER PT J AU Bastille, JV Gill-Body, KM AF Bastille, JV Gill-Body, KM TI A yoga-based exercise program for people with chronic poststroke hemiparesis SO PHYSICAL THERAPY LA English DT Article DE balance; exercise; hemiparesis; mobility; stroke; yoga ID CHRONIC STROKE PATIENTS; INDUCED MOVEMENT THERAPY; CORONARY-HEART-DISEASE; LIFE-STYLE CHANGES; COPENHAGEN STROKE; BALANCE SCALE; TIME-COURSE; PERFORMANCE; RELIABILITY; STRENGTH AB Background and Purpose. This was a preliminary investigation of the effects of a yoga-based exercise program on people with chronic (greater than 9 months) poststroke hemiparesis. Many people who have had a stroke report an impaired health status because of a reduced level of activity. Proponents of yoga contend that it offers a gentle alternative exercise program that can be easily adapted for people who have had a stroke. Subjects and Methods. Four subjects with chronic poststroke hemiparesis participated in this single-case study. The primary outcome measures were the Berg Balance Scale (BBS) and the Timed Movement Battery (TMB). A secondary outcome measure,was the Stroke Impact Scale (SIS). The baseline testing phase varied for each subject and ranged from 4 to 7 weeks. The 8-week intervention phase consisted of 1.5-hour yoga sessions, 2 times per week, in the subject's home. The primary outcome data were collected each week, and the secondary outcome data were collected before the baseline testing phase and before and after the intervention phase. Results. Subjects 1, 2, and 4 had improved TMB scores, and subjects 3 and 4 had improved BBS scores. Discussion and Conclusion. The results suggest that yoga may be beneficial to people who have had a stroke. Further investigation is warranted to further examine the effects of yoga in this population. [Bastille JV, Gill-Body KM. A yoga-based exercise program for people with chronic poststroke hemiparesis]. C1 Boudreau Phys Therapy Associates, Keene, NH USA. MGH Inst Hlth Prof, Grad Program Phys Therapy, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bastille, JV (reprint author), 12 Dearborn Circle, Walpole, NH 03608 USA. EM jvbastille@msn.com NR 67 TC 27 Z9 27 U1 2 U2 8 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JAN PY 2004 VL 84 IS 1 BP 33 EP 48 PG 16 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 805XW UT WOS:000220400000004 PM 14992675 ER PT J AU Yanagisawa, S Yoo, SD Sheen, J AF Yanagisawa, S Yoo, SD Sheen, J TI Plant immunity influenced by environmental stresses and nutrient signaling: Molecular mechanism of antagonistic interaction between ethylene and glucose SO PLANT AND CELL PHYSIOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the Japanese-Society-for-Plant-Physiologists CY MAR 27-29, 2004 CL Tokyo Metropolitan Univ, Hachioji, JAPAN SP Japanese Soc Plant Physiol HO Tokyo Metropolitan Univ C1 Okayama Univ, Res Inst Bioresources, Okayama 7008530, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0032-0781 J9 PLANT CELL PHYSIOL JI Plant Cell Physiol. PY 2004 VL 45 SU S BP S2 EP S2 PG 1 WC Plant Sciences; Cell Biology SC Plant Sciences; Cell Biology GA 808TZ UT WOS:000220592700009 ER PT J AU Walker, TS Bais, HP Deziel, E Schweizer, HP Rahme, LG Fall, R Vivanco, JM AF Walker, TS Bais, HP Deziel, E Schweizer, HP Rahme, LG Fall, R Vivanco, JM TI Pseudomonas aeruginosa-plant root interactions. Pathogenicity, biofilm formation, and root exudation SO PLANT PHYSIOLOGY LA English DT Article ID CYSTIC-FIBROSIS; BACTERIAL BIOFILMS; ANTIBIOTIC-RESISTANCE; ANTIMICROBIAL AGENTS; MICROBIAL BIOFILMS; TWITCHING MOTILITY; VIRULENCE FACTORS; PATHOGENESIS; PENETRATION; INITIATION AB Pseudomonas aeruginosa is an opportunistic human pathogen capable of forming a biofilm under physiological conditions that contributes to its persistence despite long-term treatment with antibiotics. Here, we report that pathogenic P. aeruginosa strains PAO1 and PA14 are capable of infecting the roots of Arabidopsis and sweet basil (Ocimum basilicum), in vitro and in the soil, and are capable of causing plant mortality 7 d postinoculation. Before plant mortality, PAO1 and PA14 colonize the roots of Arabidopsis and sweet basil and form a biofilm as observed by scanning electron microscopy, phase contrast microscopy, and confocal scanning laser microscopy. Upon P. aeruginosa infection, sweet basil roots secrete rosmarinic acid (RA), a multifunctional caffeic acid ester that exhibits in vitro antibacterial activity against planktonic cells of both P. aeruginosa strains with a minimum inhibitory concentration of 3mug mL(-1). However, in our studies RA did not attain minimum inhibitory concentration levels in sweet basil's root exudates before P. aeruginosa formed a biofilm that resisted the microbicidal effects of RA and ultimately caused plant mortality. We further demonstrated that P. aeruginosa biofilms were resistant to RA treatment under in vivo and in vitro conditions. In contrast, induction of RA secretion by sweet basil roots and exogenous supplementation of Arabidopsis root exudates with RA before infection conferred resistance to P. aeruginosa. Under the latter conditions, confocal scanning laser microscopy revealed large clusters of dead P. aeruginosa on the root surface of Arabidopsis and sweet basil, and biofilm formation was not observed. Studies with quorum-sensing mutants PAO210 (DeltarhlI), PAO214 (DeltalasI), and PAO216 (DeltalasI DeltarhlI) demonstrated that all of the strains were pathogenic to Arabidopsis, which does not naturally secrete RA as a root exudate. However, PAO214 was the only pathogenic strain toward sweet basil, and PAO214 biofilm appeared comparable with biofilms formed by wild-type strains of P. aeruginosa. Our results collectively suggest that upon root colonization, P. aeruginosa forms a biofilm that confers resistance against root-secreted antibiotics. C1 Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. Colorado State Univ, Cell & Mol Biol Program, Ft Collins, CO 80523 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Shriners Inst, Boston, MA 02114 USA. Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA. RP Vivanco, JM (reprint author), Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. EM jvivanco@lamar.colostate.edu RI Rechsteiner, Cynthia/C-5894-2011; Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 FU NIGMS NIH HHS [GM56685] NR 39 TC 113 Z9 128 U1 4 U2 32 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JAN PY 2004 VL 134 IS 1 BP 320 EP 331 DI 10.1104/pp.103.027888 PG 12 WC Plant Sciences SC Plant Sciences GA 767EL UT WOS:000188427200033 PM 14701912 ER PT J AU Petit, F Minns, AB Nazzal, JA Hettiaratchy, SP Lantieri, LA Randolph, MA Lee, WPA AF Petit, F Minns, AB Nazzal, JA Hettiaratchy, SP Lantieri, LA Randolph, MA Lee, WPA TI Prolongation of skin allograft survival after neonatal injection of donor bone marrow and epidermal cells SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Plastic-Surgery-Research-Council CY APR 17-20, 2002 CL Boston, MA SP Past Surg Res Council ID HAND TRANSPLANTATION; RADIATION CHIMAERAS; CATTLE TWINS; TOLERANCE; REJECTION; INDUCTION; GRAFTS; SWINE AB Composite-tissue (e.g., hand allograft) allotransplantation is currently limited by the need for immunosuppression to prevent graft rejection. Inducing a state of tolerance in the recipient could potentially eliminate the need for immunosuppression but requires reprogramming of the immunological repertoire of the recipient. Skin is the most antigenic tissue in the body and is consistently refractory to tolerance induction regimens using bone marrow transplantation alone. It was hypothesized that tolerance to skin allografts could be induced in rats by injecting epidermal cells with bone marrow cells during the first 24 hours of life of the recipients. Brown Norway rats (RT1(n)) served as donors for the epidermal cells, bone marrow cells, and skin grafts. Epidermal cells were injected intraperitoneally and bone marrow cells were injected intravenously into Lewis (RT1(1)) newborn recipient rats. In control groups, recipients received saline solution with no cells (group I, n = 12), bone marrow cells only (group II, n = 15), or epidermal cells only (group III, n. = 15). In the experimental group (group IV, n = 18) recipients received epidermal and bone marrow cells simultaneously. Skin grafts were transplanted from Brown Norway (RT1(n)) rats to the Lewis (RT1(1)) rats 8 weeks after cell injections. Skin grafts survived an average of 8.5 days in group I (10 grafts), 9.2 days in group II (12 grafts), and 12 days in group III (14 grafts). Grafts survived 15.5 days (8 to 26 days) in group IV (15 grafts). The difference was statistically significant (p < 0.05). Hair growth was observed in some accepted grafts in group IV but never in the control groups. This is the first report of prolonged survival of skin allografts in a rat model after epidermal and bone marrow cell injections. Survival prolongation was achieved across a major immunological barrier, without irradiation, myeloablation, or immunosuppression. It is concluded that the presentation of skin-specific antigens generated a temporary state of tolerance to the skin in the recipients that could have delayed the rejection of skin allografts. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab,Div Plast Surg, Boston, MA 02114 USA. Univ Paris 12, Hop Henri Mondor, Dept Plast Reconstruct & Aesthet Surg, Paris, France. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab,Div Plast Surg, WAC-453,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org NR 29 TC 15 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2004 VL 113 IS 1 BP 270 EP 276 DI 10.1097/01.PRS.0000095952.38251.4C PG 7 WC Surgery SC Surgery GA 800YI UT WOS:000220063200038 PM 14707646 ER PT J AU Porter, D Polyak, K AF Porter, D. Polyak, K. TI Emerging genomic technologies for studying mammary development and mammary cancer SO POULTRY SCIENCE LA English DT Meeting Abstract DE genomics; mammary; SAGE C1 [Porter, D.; Polyak, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Porter, D.; Polyak, K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2004 VL 83 SU 1 BP 239 EP 239 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V45UO UT WOS:000203095401002 ER PT J AU Monnier, J Grubaugh, AL Knapp, RG Magruder, KM Frueh, BC AF Monnier, J Grubaugh, AL Knapp, RG Magruder, KM Frueh, BC TI US female veterans in VA primary care: post traumatic stress disorder symptoms and functional status SO PRIMARY CARE PSYCHIATRY LA English DT Article DE female veterans; PTSD symptoms ID VIETNAM VETERANS; PTSD CHECKLIST; SCREENING INSTRUMENT; HEALTH-STATUS; PREVALENCE; DIAGNOSIS; COMORBIDITY; PREDICTORS; SERVICES; CANCER AB We sought to examine the relationship between post traumatic stress disorder (PTSD) symptomatology, demographic variables, and functional status in US female veterans. One hundred ninety-one female veterans were identified from primary care clinics in four VA Medical Centers for participation in this study. The relationship between demographic variables, physical and mental health functional status on the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and PTSD severity on the PTSD Checklist (PCL) was examined using ANOVAs and simple and multiple linear regression modeling. After adjusting for other demographic covariates, PTSD severity was related to age (older patients reported less symptoms), and employment status (veterans who were not working due to disability reported significantly more PTSD symptoms than those who were working). Additionally, after adjusting for relevant demographic covariates, greater PTSD symptomatology was related to worse functioning across both physical and mental health domains on the SF-36. PTSD symptom severity was easily assessed in this primary care sample of female veterans using the PCL. Screening female veterans through primary care clinics is likely to identify women with PTSD who are not functioning as well as their peers and who are in need of specialized services. These findings are similar to those using men identified through VA primary care clinics. C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Monnier, J (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250681, Charleston, SC 29425 USA. EM monnierj@musc.edu NR 31 TC 5 Z9 5 U1 8 U2 8 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, 26-32 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 1355-2570 J9 PRIMARY CARE PSYCHIA JI Prim. Care Psychiatry PY 2004 VL 9 IS 4 BP 145 EP 150 DI 10.1185/135525704X20394 PG 6 WC Medicine, General & Internal; Psychiatry SC General & Internal Medicine; Psychiatry GA 912WB UT WOS:000228109500006 ER PT B AU Carey, JL Gupta, V Kawakubo, H Maheswaran, S AF Carey, JL Gupta, V Kawakubo, H Maheswaran, S GP MEDIMOND TI Regulation of prostate cancer cell growth by activin SO PROCEEDINGS OF THE 12TH INTERNATIONAL CONGRESS OF ENDOCRINOLOGY LA English DT Proceedings Paper CT 12th International Congress of Endocrinology CY AUG 31-SEP 04, 2004 CL Lisbon, PORTUGAL ID INHIBINS; ANDROGEN; LNCAP; PROLIFERATION; FOLLISTATINS; LOCALIZATION; EXPRESSION; APOPTOSIS; PROTEINS; LINES AB The effects of activin and androgen on regulation of prostate cancer cell growth are mutually antagonistic. In the absence of androgen, activin induced apoptosis in the androgen-dependent human prostate cancer cell line LNCaP, an effect suppressed by androgen. Although activin by itself did not alter the cell cycle, it suppressed androgen-induced cell cycle progression and thus inhibited androgen-stimulated growth. The inhibitory effect of activin on growth was independent of Smad3 phosphorylation. Despite their antagonistic effect on growth, activin and androgen co-stimulated PSA mRNA through distinct mechanisms, and dominant negative Smad3 expression mitigated both androgen and activin-induced PSA expression. Thus activin and androgen regulate gene expression and growth in the prostate through a complex molecular crosstalk. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carey, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-071-3 PY 2004 BP 65 EP 71 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BBR36 UT WOS:000227355300010 ER PT S AU Reisner, A McCombie, D Asada, H AF Reisner, A McCombie, D Asada, H GP ieee TI Estimation of cardiac output from peripheral pressure waveforms using Laguerre model blind system identification SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS DE system identification; signal processing; cardiovascular monitoring ID GENERALIZED ORTHONORMAL BASIS; ALGORITHM AB We have developed a new technique, which may enable a more accurate, complete characterization of the circulatory system, including local or global hydrodynamic phenomena, using multiple measurements from several anatomic locations and/or multiple modalities. This technique, Laguerre Model Blind System Identification (LMBSI), uses a Laguerre function series expansion to provide a compact but complete quantitative description of the distinct behavior of two or more circulatory waveforms. LMBSI identifies a set of five parameters per channel plus one common parameter that can be treated as a feature vector and used to predict cardiovascular parameters of interest. Standard statistical techniques can be used to extract information from that compact feature vector. In this paper, multi-parameter regression is used to predict cardiac output, using two separate arterial pressure waveforms and the LMBSI algorithm. This serves as a proof-of-principle that two distinct circulatory waveforms, with LMBSI, can be used to characterize the circulatory system. In the future, this technique might be applied to non-invasive circulatory. measurements. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reisner, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 913 EP 916 PN 1-7 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461800234 ER PT S AU Reisner, A Shaltis, P McCombie, D Asada, H AF Reisner, A Shaltis, P McCombie, D Asada, H GP ieee TI A critical appraisal of opportunities for wearable medical sensors SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS DE wearable sensor opportunities; field-monitoring criteria; use-model ID ACUTE MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; CARDIOGENIC-SHOCK; TRAUMA; HYPERTENSION; TRIAGE; RISK; CARE; EXPERIENCE; DISEASE AB This paper provides an appraisal of the sensor requirements and prospects available for the growing field of wearable medical sensors. The results of a literature survey for various sensor use-models indicate that the design goals for each intended sensor application must focus on task specific criteria for ultimate sensor acceptance. Provided use-models include the examination of the relevant medical problems, the diagnostic utility of the available physiologic signals, and the impact of false alarms on the specific implementation area. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reisner, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 2149 EP 2152 PN 1-7 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461800555 ER PT S AU Barbieri, R Brown, EN AF Barbieri, R Brown, EN GP ieee TI A point process adaptive filter for time-variant analysis of heart rate variability SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS DE heart rate; heart rate variability; time-variant; adaptive filters; stochastic processes; inverse Gaussian ID SPECTRAL-ANALYSIS; MYOCARDIAL-INFARCTION; NEUROPATHY AB Estimating time-variant heart variability indices from R-R interval beat series has been widely investigated by current research involving cardiovascular control. Most of the currently accepted approaches in time-variant heart rate analysis ignore the underlying discrete structure of human heart beats, and usually require minutes of data. We derive an adaptive point process Bayes' filter based on a statistical model which considers the stochastic structure of heart beat intervals as a point process. From the explicit inverse Gaussian probability density describing heart rate and heart rate variability we are able to extract and recursively update, at any time resolution, a set of indices related to the first and second moments of this probability density. We apply our algorithm in an analysis of human heart beat intervals from a tilt-table experiment. Our results describe real instantaneous estimates of heart rate variability and may have important implications for research studies of cardiovascular and autonomic regulation. Our algorithm is easy to implement for on-line analysis of heart rate variability in the intensive care unit, operating room or labor and delivery suits. C1 Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp,Div Hlth Sci & Technol, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barbieri, R (reprint author), Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp,Div Hlth Sci & Technol, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. OI Barbieri, Riccardo/0000-0001-9381-3833 NR 21 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 3941 EP 3944 PN 1-7 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461801027 ER PT S AU Barbieri, R Frank, LM Nguyen, DP Quirk, MC Solo, V Wilson, MA Brown, EN AF Barbieri, R Frank, LM Nguyen, DP Quirk, MC Solo, V Wilson, MA Brown, EN GP ieee TI Bayesian decoding algorithm for analysis of information encoding in neural ensembles SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS DE point process; Bayesian algorithms; decoding algorithms; CA1 place cells ID HIPPOCAMPAL PLACE CELLS; POPULATION; RECONSTRUCTION; PREDICTION; SPACE; CODE; RAT AB Developing optimal strategies for constructing and testing decoding algorithms is an important question in computational neuroscience. In this field, decoding algorithms are mathematical methods that model ensemble neural spiking activity as they dynamically represent a biological signal. We present a recursive decoding algorithm based on a Bayesian point process model of individual neuron spiking activity and a linear stochastic state-space model of the biological signal. We assess the accuracy of the algorithm by computing, along with the decoding error, the true coverage probability of the approximate 0.95 confidence regions for the individual signal estimates. We illustrate the new algorithm by analyzing the position and ensemble neural spiking activity of CA1 hippocampal neurons from a rat foraging in an open circular environment. The median decoding error during 10 minutes of open foraging was 5.5 cm, and the true coverage probability for 0.95 confidence regions was 0.75 using 32 neurons. These findings improve significantly on our previous results and suggest an approach to reading dynamically information represented in ensemble neural spiking activity. C1 Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp,Div Hlth Sci & Technol, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barbieri, R (reprint author), Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp,Div Hlth Sci & Technol, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 4483 EP 4486 PN 1-7 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461801172 ER PT S AU Zupan, LH Park, S Merfeld, DM AF Zupan, LH Park, S Merfeld, DM GP ieee TI The nervous system uses internal models to achieve sensory integration SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS ID GRAVITO-INERTIAL CUES; SQUIRREL-MONKEY; VESTIBULOOCULAR REFLEX; LINEAR ACCELERATION; SEMICIRCULAR CANALS; ECCENTRIC ROTATION; OCULOGRAVIC ILLUSION; SPATIAL ORIENTATION; ROLL TILT; HUMANS AB All linear accelerometers measure gravito-inertial force, which is the sum of gravitational force (tilt) and inertial force due to linear acceleration (translation). Neural strategies must exist to elicit tilt and translation responses from this ambiguous cue. To investigate these neural processes, we developed a model of human responses and simulated a number of motion paradigms used to investigate this tilt/translation ambiguity. In this model, the separation of GIF into neural estimates of gravity and linear acceleration is accomplished via an internal model made up of 3 principal components: 1) the influence of rotational cues (e.g., semicircular canals) on the neural representation of gravity, 2) the resolution of gravito-inertial force into neural representations of gravity and linear acceleration, and 3) the neural representation of the dynamics of the semicircular canals. By combining these simple hypotheses within the internal model framework, the model mimics human translation and tilt responses for preliminary data from one human subject. These modeled response characteristics are consistent with preliminary data and with the hypothesis that the nervous system uses internal models to estimate tilt and translation in the presence of ambiguous sensory cues. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Zupan, LH (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 4487 EP 4490 PN 1-7 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461801173 ER PT S AU Ryan, CM AF Ryan, CM GP ieee TI Neurological manifestations of electrical trauma SO PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 01-05, 2004 CL San Francisco, CA SP IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS DE electrical injury; neurological injury; paralysis ID INJURY; SHOCK; BURN; PARAPLEGIA; MEMBRANE AB Some degree of neurological impairment is often found in patients following electrical injury. A wide range of neurological impairments can occur including peripheral neuropathies, chronic pain syndromes, brain injury and rarely severe paralytic syndromes. Outcome is difficult to accurately predict. The symptoms can present immediately or be delayed in onset. They can also be temporary, permanent or get progressively worse with time. The neurological impairment resulting from the current often comprises a substantial proportion of the morbidity associated with such injuries. It is known that electrical current can cause nerve injury, however, the primary etiology of such damage is yet to be elucidated. An unusual case of transient paralysis after high voltage burn associated with severe hypokalemia provides unique insight into a potential mechanism for nerve injury following electrical trauma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burns Hosp,Surg Serv, Boston, MA 02115 USA. RP Ryan, CM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burns Hosp,Surg Serv, Boston, MA 02115 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-8439-3 J9 P ANN INT IEEE EMBS PY 2004 VL 26 BP 5437 EP 5439 PN 1-7 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical; Medicine, Research & Experimental; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Research & Experimental Medicine; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BBG76 UT WOS:000225461801445 ER PT B AU Peake, WT Peake, HC AF Peake, WT Peake, HC BE Guo, K Wada, H Hato, N Koike, T TI Interspecies variation in cat-family middle ears SO PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY LA English DT Proceedings Paper CT 3rd Symposium on Middle Ear Mechanics in Research and Otology CY JUL 09-12, 2003 CL Matsuyama, JAPAN ID FELIS-MARGARITA AB The middle ears of all mammals have the same components, which vary in size and configuration among species. It is generally presumed that some of these structural variations benefit hearing behavior and survival in a species' niche, but testing specific hypotheses for evolutionary mechanisms is difficult because of multidimensional differences among species. To narrow the variation we have focused on the cat family, Felidae, in which the 36 species are similar in their structure and predatory life style, but vary in size, habitat, and lineage. Our measurements of ear and skull dimensions from 400 museum specimens allow searches for structural relations to ethological variables. Correlations of ear structure with skull "shape" show that species with relatively wide anterior skulls are most likely to have an unusual location of the bony septum that divides the felid middle-ear airspace into two sub-cavities; the 8 species with this ear-skull structural combination all live in relatively open habitiats. The assignment of these 8 species to several different lineages by recent taxomomic studies suggests that this set of features evolved more than once. Speculation about the adaptive value of this arrangement of the septum could suggest testable hypotheses. Habitats with few trees allow a hunting cat to cover a large territory. Open habitats also permit low-frequency sounds to propagate with small attenuation, which allows detection of inter- and intraspecies sounds over large distances. Percepts from the received signal that are important to survival include the direction of the sound source, the nature of the source (e.g. intraspecies or predator) and the signal's meaning (e.g. kitten alarm call). A general hypothesis is that the unusual septum location provides high sensitivity for low frequency sounds along with preservation of spectral features that provide cues for the percepts. The wide facial skull of these species could be adaptive in improving olfactory sensitivity in detection and identification of conspecifics, e.g. invaders of one's territory. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Peake, WT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wtp@epl.meei.harvard.edu NR 23 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-603-3 PY 2004 BP 11 EP 18 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BCL41 UT WOS:000229835200002 ER PT B AU Ravicz, ME Peake, WT Nakajima, HH Merchant, SN Rosowski, JJ AF Ravicz, ME Peake, WT Nakajima, HH Merchant, SN Rosowski, JJ BE Guo, K Wada, H Hato, N Koike, T TI Modeling flexibility in the human ossicular chain: comparison to ossicular fixation data SO PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY LA English DT Proceedings Paper CT 3rd Symposium on Middle Ear Mechanics in Research and Otology CY JUL 09-12, 2003 CL Matsuyama, JAPAN ID MIDDLE-EAR AB Evidence exists for flexibility in the ossicular chain. This evidence includes the observation that patients with otosclerotic lesions sufficient to cause a substantial reduction in stapes mobility and conductive hearing loss show only small reductions in low-frequency umbo velocity. In models of the middle ear, ossicular flexibility has often been assigned to the incudostapedial (I-S) joint - the incudomalleal (I-M) joint is assumed rigid - and this presumed flexibility is generally not well described. We introduce flexibility in the I-M joint in a simple middle-ear model to explain the discrepancy in reductions in umbo and stapes velocity at low frequencies observed in human temporal bones with simulated stapes fixation by Nakajima et al. (2003ab). We determine the magnitude of I-M joint flexibility from measurements of low-frequency relative rotational velocity (Willi et al., 2002) and assume the I-S joint is rigid. The relationship between umbo and stapes velocities predicted by the model for normal ears and the reduction in umbo velocity predicted for various degrees of stapes fixation (modeled by reductions in annular ligament compliance) are a good match to experimental data in temporal bones and to clinical data in patients with stapes fixation. Reductions in umbo velocity due to stapes fixation are successfully predicted by varying a single model parameter, the annular ligament compliance, at the site of fixation. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Audiol Physiol, Boston, MA 02114 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Audiol Physiol, 243 Charles St, Boston, MA 02114 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-603-3 PY 2004 BP 91 EP 98 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BCL41 UT WOS:000229835200013 ER PT B AU Songer, JE Brinsko, KM Rosowski, JJ AF Songer, JE Brinsko, KM Rosowski, JJ BE Guo, K Wada, H Hato, N Koike, T TI Superior semicircular canal dehiscence and bone conduction in Chinchilla SO PROCEEDINGS OF THE 3RD SYMPOSIUM ON MIDDLE EAR MECHANICS IN RESEARCH AND OTOLOGY LA English DT Proceedings Paper CT 3rd Symposium on Middle Ear Mechanics in Research and Otology CY JUL 09-12, 2003 CL Matsuyama, JAPAN AB Superior semicircular canal dehiscence (SSCD) syndrome is primarily associated with vertigo and disequilibrium induced by loud sounds (Tullio's phenomenon) and middle-ear pressure changes. SSCD syndrome may also cause increased bone-conduction sensitivity and decreased air-conduction sensitivity leading to an air-bone gap. The abnormalities in both air and bone sensitivities are typically greatest at frequencies below 2 kHz. Understanding the mechanisms that cause this air-bone gap may aid in the diagnosis of SSCD syndrome and in understanding the pathology that causes the symptoms. We examined the effects of SSCD on responses to bone-conduction stimuli in a chinchilla model by measuring the motion of the fluid within the dehiscence and the cochlear potential. In surgically induced dchiscences we found differential motion between the inner-ear fluid and the adjacent bone in response to bone-conduction stimuli for frequencies from 569 Hz - 2440 Hz. An increase in sensitivity to bone-conducted stimuli (as measured by cochlear potential) near 500 Hz of 8 dB was also found. The sensitivity to bone-conducted stimuli is dependent on the size of the dehiscence. Increased CP in chinchillas with surgically induced SSCD is consistent with lower bone-conduction thresholds in SSCD syndrome patients suggesting that bone-conduction hypersensitivity is an indicator of a SSCD. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Songer, JE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 5 Z9 5 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-603-3 PY 2004 BP 234 EP 241 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BCL41 UT WOS:000229835200035 ER PT S AU Walker, WA AF Walker, WA BE Pickering, LK Morrow, AL RuizPalacios, GM Schanler, RJ TI The dynamic effects of breastfeeding on intestinal development and host defense SO PROTECTING INFANTS THROUGH HUMAN MILK: ADVANCING THE SCIENTIFIC EVIDENCE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 11th International Conference of the International-Society-for-Research-in-Human-Milk-and-Lactation CY OCT 04-08, 2002 CL Mexico City, MEXICO SP Int Soc Res Human Milk & Lactat ID NEONATAL NECROTIZING ENTEROCOLITIS; HUMAN-MILK; PRETERM INFANTS; ATOPIC DISEASE; CHOLERA-TOXIN; ZINC-BINDING; FOLLOW-UP; ALLERGY; COLONIZATION; MODULATION AB In this review, evidence is provided to support the hypothesis that human milk provides a link between the mother and her newborn infant in the extrauterine environment in a manner similar to the placental link between mother and fetus in utero. In addition, breastfeeding helps prevent age-related diseases affecting the gastrointestinal tract during the newborn period. To provide evidence to support this hypothesis, anecdotal clinical studies are sited to suggest that human milk contains factors that may be missing in inherited diseases of inborn errors in metabolism and provide passive protective factors that lessen the expression of neonatal allergic and infectious diseases. In some instances, by providing the missing factor in an inherited disease, the newborn may be protected from serious damage to its developing brain. A second line of evidence to support this hypothesis is the observation that the composition of human milk varies with the infant's needs. To illustrate this principal, the composition of milk from mothers delivering prematurely and milk of mothers of full-term infants were compared, and the differences in trophic and protective factors in colostrum versus mature milk from mothers delivering full-term are cited. Finally, using observations from-the laboratory that define the immaturities in neonatal and premature human intestinal defenses as the neonate's host defense deficiency, the specific effect that anti-inflammatory and maturational factors in human milk has on these immaturities is discussed. The active stimulus of maternal milk on the rapid development of host defenses is underscored. These cited examples of human milk effects in the newborn help support the stated hypothesis. Additional studies of human immature gut function along with translational and clinical studies are necessary to provide further objective evidence in support of breastfeeding for all neonates, particularly premature neonates. C1 Harvard Univ, Sch Med, Dept Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pediat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dev Gastroenterol Lab, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Dept Nutr, 114 16th St,114-3503, Charlestown, MA 02129 USA. EM allan_walker@hms.harvard.edu NR 51 TC 32 Z9 35 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-48588-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2004 VL 554 BP 155 EP 170 PG 16 WC Medicine, Research & Experimental; Nutrition & Dietetics; Obstetrics & Gynecology; Pediatrics SC Research & Experimental Medicine; Nutrition & Dietetics; Obstetrics & Gynecology; Pediatrics GA BAU75 UT WOS:000223641000012 PM 15384575 ER PT S AU Cole, GM Morihara, T Lim, GP Yang, FS Begum, A Frautschy, SA AF Cole, GM Morihara, T Lim, GP Yang, FS Begum, A Frautschy, SA BE Lahiri, DK TI NSAID and antioxidant prevention of Alzheimer's disease lessons from in vitro and animal models SO PROTECTIVE STRATEGIES FOR NEURODEGENERATIVE DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Protective Strategies for Neurodegenerative Diseases CY AUG 14-18, 2004 CL Univ British Columbia, Vancouver, CANADA SP NIH, Vancouver BioMed Hlth Res Fdn HO Univ British Columbia DE interleukin-1 beta; a-1-antichymotrypsin; docosahexaenoic acid; ibuprofen ID AMYLOID-BETA-PROTEIN; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PRESENILIN-1 TRANSGENIC MICE; NEURONAL OXIDATIVE DAMAGE; PRECURSOR PROTEIN; SYNAPTIC PLASTICITY; LIPID-PEROXIDATION; MOUSE MODEL AB Both oxidative damage and inflammation are elevated in brains of Alzheimer's disease (AD) patients, but their pathogenic significance remains unclear. The reduced AD risk associated with high intake of both nonsteroidal anti-inflammatory drugs (NSAIDs) and antioxidants; suggests causal roles, but clinical trials in AD patients have yielded only limited or negative results. To test the potential efficacy and mechanisms of candidate approaches, we have explored conventional and unconventional MAIDS, antioxidants, and combined NSAID/antioxidants in cell culture and animal models for AD (including aging APPsw transgenic mice and soluble A beta rodent infusion models). The conventional NSAID ibuprofen has the strongest epidemiological support. At sustainable doses designed to mimic protective consumption in the epidemiology, ibuprofen reduces amyloid accumulation but suppresses a surprisingly limited subset of inflammatory markers in APPsw transgenic mice. Both A beta production (APP, beta- and gamma-secretases) and post-production pathways (those affecting A beta aggregation or clearance: e.g., IL-1 or alpha 1ACT) are potentially involved in ibuprofen and other NSAID anti-AD activities. The post-production pathways are predictably shared with other seemingly protective NSAIDs, including naproxen that do not lower A beta 42 in vitro. Using clinically feasible dosing, brain levels of NSAIDs appear too low to implicate a number of pharmacological dose targets that have been demonstrated in vitro. Ibuprofen did not suppress microglial markers related to phagocytosis. The putative anti-inflammatory omega-3 fatty acid DHA had a profound impact on pathogenesis but did not lower inflammation, while vitamin E was surprisingly ineffective in reducing oxidative damage or amyloid in the aged APPsw mouse. In contrast, the unconventional NSAID/antioxidant curcumin was effective, lowering oxidative damage, cognitive deficits, synaptic marker loss, and amyloid deposition. Curcumin proved to be immunomodulatory, simultaneously inhibiting cytokine and microglial activation indices related to neurotoxicity, but increasing an index of phagocytosis. Curcumin directly targeted A beta and was also effective in other models, warranting further preclinical and clinical exploration. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA 91343 USA. Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. RP Cole, GM (reprint author), Vet Adm Med Ctr, Greater Los Angeles Healthcare Syst, 16111 Plummer St,Bldg 7,Room A102, North Hills, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [R01 AT003008]; NIA NIH HHS [AG13471, R01 AG013741, P50 AG016570, R01 AG010685, U01 AG028583, R01 AG016793]; NINDS NIH HHS [NS43946] NR 92 TC 82 Z9 89 U1 1 U2 11 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-529-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1035 BP 68 EP 84 DI 10.1196/annals.1332.005 PG 17 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BBW48 UT WOS:000228130300005 PM 15681801 ER PT S AU Greig, NH Mattson, MP Perry, T Chan, SL Giordano, T Sambamurti, K Rogers, JT Ovadia, H Lahiri, DK AF Greig, NH Mattson, MP Perry, T Chan, SL Giordano, T Sambamurti, K Rogers, JT Ovadia, H Lahiri, DK BE Lahiri, DK TI New therapeutic strategies and drug candidates for neurodegenerative diseases p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists SO PROTECTIVE STRATEGIES FOR NEURODEGENERATIVE DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Protective Strategies for Neurodegenerative Diseases CY AUG 14-18, 2004 CL Univ British Columbia, Vancouver, CANADA SP NIH, Vancouver BioMed Hlth Res Fdn HO Univ British Columbia DE TNF-alpha; p53; GLP-1 receptor (GLP-1R) ID GLUCAGON-LIKE PEPTIDE-1; NECROSIS-FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; PROGRAMMED CELL-DEATH; PROTEIN MESSENGER-RNA; UA-RICH SEQUENCES; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; PRECURSOR PROTEIN AB Owing to improving preventative, diagnostic, and therapeutic measures for cardiovascular disease and a variety of cancers, the average ages of North Americans and Europeans continue to rise. Regrettably, accompanying this increase in life span, there has been an increase in the number of individuals afflicted with age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and stroke. Although different cell types and brain areas are vulnerable among these, each disorder likely develops from activation of a common final cascade of biochemical and cellular events that eventually lead to neuronal dysfunction and death. In this regard, different triggers, including oxidative damage to DNA, the overactivation of glutamate receptors, and disruption of cellular calcium homeostasis, albeit initiated by different genetic and/or environmental factors, can instigate a cascade of intracellular events that induce apoptosis. To forestall the neurodegenerative process, we have chosen specific targets to inhibit that are at pivotal rate-limiting steps within the pathological cascade. Such targets include TNF-alpha, p53, and GLP-1 receptor. The cytokine TNF-alpha is elevated in Alzheimer's disease, Parkinson's disease, stroke, and amyotrophic lateral sclerosis. Its synthesis can be reduced via posttranscriptional mechanisms with novel analogues of the classic drug, thalidomide. The intracellular protein and transcription factor, p53, is activated by the Alzheimer's disease toxic peptide, A beta, as well as by excess glutamate and hypoxia to trigger neural cell death. It is inactivated by novel tetrahydrobenzo-thiazole and -oxazole analogues to rescue cells from lethal insults. Stimulation of the glucagon-like peptide-1 receptor (GLP-1R) in brain is associated with neurotrophic functions that, additionally, can protect cells against excess glutamate and other toxic insults. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Gerontol Res Ctr,Intramural Res Program,NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Dept Mol Biol & Biochem, Shreveport, LA 71130 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. Hadassah Hebrew Univ Hosp, Agnes Ginges Ctr Human Neurogenet, Dept Neurol, Jerusalem, Israel. Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Gerontol Res Ctr,Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM greign@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 119 TC 67 Z9 71 U1 1 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-529-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1035 BP 290 EP 315 DI 10.1196/annals.1332.018 PG 26 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BBW48 UT WOS:000228130300018 PM 15681814 ER PT J AU Bauer-Wu, S Healey, M Rosenbaum, E Blood, E Xu, R Ott, MJ Sullivan, A McLoughlin, M Kubicek, L Fonteyn, M Lovett, B AF Bauer-Wu, S Healey, M Rosenbaum, E Blood, E Xu, R Ott, MJ Sullivan, A McLoughlin, M Kubicek, L Fonteyn, M Lovett, B TI Facing the challenges of stem cell/bone marrow transplantation with mindfulness meditation: A pilot study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2004 VL 13 IS 1 SU S BP S10 EP S11 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 767DM UT WOS:000188425000019 ER PT J AU O'Leary, TE Recklitis, CJ AF O'Leary, TE Recklitis, CJ TI The effects of response bias on self-reported quality of life among childhood cancer survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2004 VL 13 IS 1 SU S BP S23 EP S24 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 767DM UT WOS:000188425000043 ER PT J AU Pirl, WF Goode, MJ Smith, MR AF Pirl, WF Goode, MJ Smith, MR TI Prospective study of depression and androgen blockade therapy for prostate cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2004 VL 13 IS 1 SU S BP S17 EP S18 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 767DM UT WOS:000188425000032 ER PT J AU Recklitis, CJ Hudson, MM Zebrack, BJ Mertens, AC Mitby, PA Nagarajan, R Robison, LL Zeltzer, L AF Recklitis, CJ Hudson, MM Zebrack, BJ Mertens, AC Mitby, PA Nagarajan, R Robison, LL Zeltzer, L TI Psychosocial functioning in a large scale cohort of childhood cancer survivors: A report from the Childhood Cancer Survivor Study SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2004 VL 13 IS 1 SU S BP S22 EP S23 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 767DM UT WOS:000188425000041 ER PT J AU Recklitis, CJ Comeau, P Diller, L AF Recklitis, CJ Comeau, P Diller, L TI Psychological screening for adult survivors of childhood cancer: Development of the Computer Assisted Survivor Screening (CASS) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2004 VL 13 IS 1 SU S BP S16 EP S17 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 767DM UT WOS:000188425000031 ER PT J AU Thompson, R Gupta, S Miller, K Mills, S Orr, S AF Thompson, R Gupta, S Miller, K Mills, S Orr, S TI The effects of vasopressin on human facial responses related to social communication SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE vasopressin; human emotion; behavior; aggression; facial ID BLOOD-BRAIN-BARRIER; VASOACTIVE INTESTINAL POLYPEPTIDE; ARGININE VASOTOCIN; MONOGAMOUS VOLE; GOLDEN-HAMSTERS; V-1A RECEPTOR; CRICKET FROGS; RAT-BRAIN; BEHAVIOR; AGGRESSION AB Arginine vasopressin (AVP) and arginine vasotocin (AVT) influence social behaviors in a number of species from diverse taxonomic groups, therefore suggesting a conservation of social functions for these homologous neuropeptides during vertebrate evolution. However, whether or not AVP has the ability to directly influence social behavior in humans has not yet been determined. Because influences of AVT/AVP on behaviors related to social communication, particularly in aggressive contexts, are among the most consistently observed across species from diverse vertebrate groups, the present study was designed to determine if AVP administration would influence cognitive, autonomic and/or somatic responses to species-specific social stimuli important for agonistic communication in humans. Specifically, we tested the effects of intranasal AVP administration on attention towards emotionally expressive facial expressions, as well as on heart rate (HR), skin conductance (SC) and corrugator supercilii electromyograms (corrugator EMG) in response to these social stimuli. AVP did not affect attention toward, nor autonomic arousal in response to, emotionally neutral, happy or angry facial expressions, but it did selectively enhance the corrugator EMG responses evoked by emotionally neutral facial expressions, making them similar in magnitude to responses evoked by angry facial expressions in control subjects. Because this muscle group is involved in agonistic communication, these results suggest that AVP may influence aggression in human males by biasing individuals to respond to emotionally ambiguous social stimuli as if they were threatening/aggressive. (C) 2003 Elsevier Ltd. All rights reserved. C1 Bowdoin Coll, Dept Psychol, Brunswick, ME 04011 USA. MidCoast Hosp, Brunswick, ME USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Med Ctr, Dept Vet Affairs, Manchester, NH USA. RP Thompson, R (reprint author), Bowdoin Coll, Dept Psychol, Banister Hall, Brunswick, ME 04011 USA. RI chen, xuanlan/H-4158-2011 NR 47 TC 96 Z9 98 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2004 VL 29 IS 1 BP 35 EP 48 DI 10.1016/S0306-4530(02)00133-6 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 740JQ UT WOS:000186399600004 PM 14575728 ER PT J AU Frazier, TW Strauss, ME Steinhauer, SR AF Frazier, TW Strauss, ME Steinhauer, SR TI Respiratory sinus arrhythmia as an index of emotional response in young adults SO PSYCHOPHYSIOLOGY LA English DT Article DE respiratory sinus arrhythmia; emotion; heart period; skin conductance; valence; arousal ID HEART-RATE-VARIABILITY; AUTONOMIC NERVOUS-SYSTEM; VAGAL TONE; INFANT TEMPERAMENT; REACTIVITY; BEHAVIOR; CHILDREN; IMAGERY; EXPRESSION; PHYSIOLOGY AB The relationship between respiratory sinus arrhythmia (RSA) and valence and arousal remains unclear. In the present study, the associations between emotion responses and tonic or task-related changes in RSA were assessed. Specifically; the sensitivities of changes in interbeat interval, RSA, and skin conductance to the valence and arousal values of emotional stimuli were examined. This study also explored the association between tonic RSA and subjective, expressive, and physiological emotional responses. Response measures were collected from 56 adults during baseline and film-viewing periods. Tonic RSA was not significantly related to any of the response measures. Increased skin conductance and decreased RSA were associated with arousal independent of valence. Interbeat interval was related to affective valence and not arousal. These findings suggest that RSA may be a useful adjunct to skin conductance measures in assessing emotional arousal. C1 Case Western Reserve Univ, Dept Psychol, Cleveland, OH 44106 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Frazier, TW (reprint author), Case Western Reserve Univ, Dept Psychol, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM twf3@po.cwru.edu FU NIA NIH HHS [AG08012-12A1]; NIMH NIH HHS [MH55762] NR 58 TC 75 Z9 76 U1 4 U2 15 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2004 VL 41 IS 1 BP 75 EP 83 DI 10.1046/j.1469-8986.2003.00131.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 768WJ UT WOS:000188592900008 PM 14693002 ER PT J AU Griffin, MG Resick, PA AF Griffin, MG Resick, PA TI Auditory startle modification following treatment for posttraumatic stress disorder SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res C1 Univ Missouri, St Louis, MO 63121 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S8 EP S8 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200021 ER PT J AU Miller, MW Gronfier, C AF Miller, MW Gronfier, C TI Circadian effects on the human startle reflex SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. INSERM, Ctr Chronobiol, F-75654 Paris 13, France. RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S21 EP S22 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200075 ER PT J AU Putnam, KM Pizzagalli, DA Gooding, DC Kalin, NH Davidson, RJ AF Putnam, KM Pizzagalli, DA Gooding, DC Kalin, NH Davidson, RJ TI Orbital frontal cortex, the regulation of emotion, and diurnal variation in cortisol: Evidence from brain electrical tomography analysis SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res DE anhedonia; cortisol; orbital frontal cortex C1 Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S87 EP S87 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200336 ER PT J AU Siegle, GJ Silk, JS Forbes, EE Steinhauer, SR Dahl, RE Carter, CS Thase, ME AF Siegle, GJ Silk, JS Forbes, EE Steinhauer, SR Dahl, RE Carter, CS Thase, ME TI Sustained pupil dilation to emotional information in depression: Developmental and mechanistic considerations SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S9 EP S9 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200026 ER PT J AU Spencer, KM Nestor, PG Perlmutter, R Niznikiewicz, MA Klump, M Frumin, M Shenton, ME McCarley, RW AF Spencer, KM Nestor, PG Perlmutter, R Niznikiewicz, MA Klump, M Frumin, M Shenton, ME McCarley, RW TI Gamma-band synchrony indexes disordered perception and cognition in schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res DE schizophrenia; gamma band EEG; synchrony C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S90 EP S90 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200347 ER PT J AU Woodward, SH Kaloupek, DG AF Woodward, SH Kaloupek, DG TI Baseline heart rate in posttraumatic stress disorder: What is it telling us? SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res C1 VA Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S7 EP S7 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200019 ER PT J AU Yang, YL Raine, A Loeber, R Steinhauer, SR Lacasse, L AF Yang, YL Raine, A Loeber, R Steinhauer, SR Lacasse, L TI Abnormal EEG responses to an emotional stressor in antisocial adolescents SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 20-24, 2004 CL Santa Fe, NM SP Soc Pychophysiol Res DE antisocial C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2004 VL 41 SU 1 BP S50 EP S50 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 849RL UT WOS:000223558200187 ER PT J AU DuHamel, KN Manne, S Nereo, N Ostroff, J Martini, R Parsons, S Williams, S Mee, L Sexson, S Wu, L Winkel, G Boulad, F Redd, WH AF DuHamel, KN Manne, S Nereo, N Ostroff, J Martini, R Parsons, S Williams, S Mee, L Sexson, S Wu, L Winkel, G Boulad, F Redd, WH TI Cognitive processing among mothers of children undergoing bone marrow/stem cell transplantation SO PSYCHOSOMATIC MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PEDIATRIC CANCER SURVIVORS; PSYCHOMETRIC PROPERTIES; BREAST-CANCER; SOCIAL CONSTRAINTS; INTRUSIVE THOUGHTS; BECK DEPRESSION; EVENT SCALE; MODEL; DISTRESS AB Objective: This study investigated the role of cognitive processing in maternal adjustment to a life-threatening pediatric medical procedure (bone marrow/stem cell transplantation: BMT/SCT). Methods: Ninety-one mothers participated in structured interviews about their fears, intrusions, avoidance, and distress regarding their child's BMT/SCT at two time points: during their child's hospitalization and during his/her recovery. Structural equation modeling was used to determine the role of fears, intrusions, and avoidance in mothers' distress. Results: Mothers' fears played a primary role in their adjustment to their child's transplantation. Intrusions mediated the relations of fears with distress at both time points. Mothers' avoidance of thoughts, feelings, and reminders of their child's illness during the child's transplantation was associated with their distress three months later. The child's risk for an unsuccessful transplantation outcome was not associated with mothers' fears or distress during the child's hospitalization, but was associated with mothers' distress during the child's posthospital course of recovery. Conclusions: The results of this study indicate the critical role of mothers' fears, intrusions, avoidance, and the child's transplant risk in maternal distress and have treatment implications for reducing maternal distress during pediatric transplantation. C1 CUNY Mt Sinai Sch Med, Ruttenberg Canc Ctr, Program Canc Prevent & Control, New York, NY 10029 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Northwestern Univ, Med Ctr, Childrens Mem Hosp, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Packard Childrens Hosp, Palo Alto, CA USA. Emory Univ, Ctr Med, Atlanta, GA USA. RP DuHamel, KN (reprint author), CUNY Mt Sinai Sch Med, Ruttenberg Canc Ctr, Program Canc Prevent & Control, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM katherine.duhamel@mssm.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU NIMH NIH HHS [MH 57738] NR 53 TC 18 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2004 VL 66 IS 1 BP 92 EP 103 DI 10.1097/01.PSY.0000108104.23738.04 PG 12 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 768VL UT WOS:000188555700014 PM 14747643 ER PT J AU Nierenberg, AA Sonino, N AF Nierenberg, AA Sonino, N TI From clinical observations to clinimetrics: A tribute to Alvan R. Feinstein, MD SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Padua, Dept Stat Sci, Padua, Italy. Univ Padua, Dept Mental Hlth, Padua, Italy. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM anierenberg@partners.org NR 0 TC 15 Z9 16 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2004 VL 73 IS 3 BP 131 EP 133 DI 10.1159/000076447 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 804LY UT WOS:000220301400001 PM 15352272 ER PT J AU Cohen, LS Altshuler, LL Stowe, ZN Faraone, SV AF Cohen, LS Altshuler, LL Stowe, ZN Faraone, SV TI Reintroduction of antidepressant therapy across pregnancy in women who previously discontinued treatment - A preliminary retrospective study SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE antidepressants; depression; pregnancy; relapse; treatment discontinuation ID MAJOR DEPRESSIVE DISORDER; MOOD AB Background: Pregnancy has frequently been described as a time of emotional well-being conferring 'protection' against psychiatric disorders. However, data to support this impression are sparse. Methods: A retrospective review was undertaken in order to examine rates of reintroduction of antidepressants across pregnancy among a cohort of 54 euthymic pregnant women who had discontinued these medications around the time of conception. Reintroduction of antidepressants was used as a marker suggesting relapse of depression. Results: Forty-two percent (n = 23) of these women reintroduced antidepressant therapy during pregnancy, with nearly half of these ( n = 11) doing so in the first trimester. A greater time spent in episodes since depressive onset and a prior history of suicide attempts was associated with antidepressant reintroduction. Conclusions: Nearly half of the women who discontinued antidepressants during pregnancy to avoid fetal exposure appeared to experience symptoms severe enough to prompt reintroduction of treatment with these medications. The implications of these findings are discussed with respect to treatment planning for women who are maintained on antidepressants and who plan to conceive. Copyright (C) 2004 S. Karger AG, Basel. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Med, Mood Disorders Res Program, Los Angeles, CA USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Pregnancy & Postpartum Mood Disorders Program, Atlanta, GA USA. RP Cohen, LS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. EM lcohen2@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH 19445, MH-51761, R01-MH56420] NR 8 TC 15 Z9 16 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2004 VL 73 IS 4 BP 255 EP 258 DI 10.1159/000077745 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 827ES UT WOS:000221882500008 PM 15184721 ER PT J AU Waters, GS Caplan, D AF Waters, GS Caplan, D TI Verbal working memory and on-line syntactic processing: Evidence from self-paced listening SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY LA English DT Article ID ADULT AGE-DIFFERENCES; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; ALZHEIMERS-DISEASE; LANGUAGE COMPREHENSION; COMPUTATIONAL APPROACH; AMBIGUITY RESOLUTION; CAPACITY THEORY; CARPENTER 1992; COMPLEXITY AB Two experiments investigated the relationship between performance on standard tests of verbal working-memory and the on-line construction of syntactic form. In Experiment 1, working-memory was measured in 100 college students on a version of the Daneman and Carpenter (1980) reading-span task, and online syntactic processing was assessed using a self-paced listening task with four sentence types. In Experiment 2, working-memory was measured in 48 college students on two versions of the reading-span task and two other tests of verbal working-memory, and on-line syntactic processing was assessed using the self-paced listening task with an additional sentence type. In both experiments, there was no relationship between working-memory capacity and the increase in processing time seen for the on-line construction of syntactic form for either syntactically more complex or syntactically simpler sentences. The results indicate that the capacity of the working-memory system that is measured by standard working-memory tests does not determine the efficiency of on-line syntactic processing. They are consistent with the view that the working-memory system used for parsing is at least partially separate from that measured by traditional measures of working-memory capacity. C1 Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Waters, GS (reprint author), Boston Univ, Dept Hlth Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. FU NIA NIH HHS [AG09661] NR 73 TC 29 Z9 30 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0272-4987 J9 Q J EXP PSYCHOL-A JI Q. J. Exp. Psychol. Sect A-Hum. Exp. Psychol. PD JAN PY 2004 VL 57 IS 1 BP 129 EP 163 DI 10.1080/02724980343000170 PG 35 WC Psychology; Psychology, Experimental SC Psychology GA 755AA UT WOS:000187364600006 PM 14681007 ER PT J AU Yanch, JC Folkert, MF Ledoux, RJ Dart, A Albritton, JR Boisseau, RP O'Meara, JM Nett, WP Johnson, ED Held, KD AF Yanch, JC Folkert, MF Ledoux, RJ Dart, A Albritton, JR Boisseau, RP O'Meara, JM Nett, WP Johnson, ED Held, KD TI Development of a charged-particle microbeam for single-particle subcellular irradiations at the MIT laboratory for accelerator beam applications SO RADIATION RESEARCH LA English DT Meeting Abstract CT 6th International Workshop/12th L H Gray Workshop on Microbeam Probes of Cellular Radiation Response CY MAR 29-31, 2003 CL ST CATHERINE COLL, OXFORD, ENGLAND HO ST CATHERINE COLL C1 MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. MIT, Whitaker Coll Hlth Sci & Technol, Cambridge, MA 02139 USA. Pyramid Tech Consultants, Waltham, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 6 Z9 7 U1 1 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2004 VL 161 IS 1 BP 96 EP 97 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 758HB UT WOS:000187627300020 ER PT J AU Folkert, MR Albritton, JR Dart, A Ledoux, RJ Luo, CM Held, KD Yanch, JC AF Folkert, MR Albritton, JR Dart, A Ledoux, RJ Luo, CM Held, KD Yanch, JC TI Design, characterization and application of a charged-particle microslit for subnuclear irradiation SO RADIATION RESEARCH LA English DT Meeting Abstract CT 6th International Workshop/12th L H Gray Workshop on Microbeam Probes of Cellular Radiation Response CY MAR 29-31, 2003 CL ST CATHERINE COLL, OXFORD, ENGLAND HO ST CATHERINE COLL ID BREAKS C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Radiol Sci Joint Program, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Pyramid Tech Consulting, Waltham, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2004 VL 161 IS 1 BP 100 EP 101 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 758HB UT WOS:000187627300025 ER PT J AU Buchmann, RF Jaramillo, D AF Buchmann, RF Jaramillo, D TI Imaging of articular disorders in children SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; POWER DOPPLER SONOGRAPHY; TRANSIENT SYNOVITIS; MAGNETIC-RESONANCE; SEPTIC ARTHRITIS; IDIOPATHIC ARTHRITIS; LYME ARTHRITIS; KNEE-JOINT; HIP; MRI AB This article reviews aspects of arthritis imaging that are specific to children. The pediatric skeleton is unique and responds in characteristic ways to articular inflammation. Epiphyseal and physeal cartilage are affected by joint diseases, and disturbances of growth and maturation are sometimes the cardinal manifestations of arthritis. The target joints of pediatric articular diseases differ considerably from those of diseases in adults. Imaging techniques should be tailored to the children being studied. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jaramillo, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM djaramillo@partners.org NR 48 TC 30 Z9 32 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2004 VL 42 IS 1 BP 151 EP + DI 10.1016/S0033-8389(03)00159-3 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 804JM UT WOS:000220295000010 PM 15049529 ER PT J AU Kopans, DB AF Kopans, DB TI Mammography screening is saving thousands of lives, but will it survive medical malpractice? SO RADIOLOGY LA English DT Editorial Material DE breast neoplasms; radiography; 08.111; breast radiography; quality assurance; editorials; medicolegal problems ID BREAST-CARCINOMA MORTALITY; RADIOLOGY; TRIALS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ambulatory Care Bldg,Suite 219,15 Parkman St, Boston, MA 02114 USA. NR 18 TC 19 Z9 19 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2004 VL 230 IS 1 BP 20 EP 24 DI 10.1148/radiol.2301030619 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 758BR UT WOS:000187613100004 PM 14695383 ER PT J AU Beinfeld, MT Bosch, JL Isaacson, KB Gazelle, GS AF Beinfeld, MT Bosch, JL Isaacson, KB Gazelle, GS TI Cost-effectiveness of uterine artery embolization and hysterectomy for uterine fibroids SO RADIOLOGY LA English DT Article DE arteries, therapeutic embolization; cost-effectiveness; uterine neoplasms; uterine neoplasms, therapy ID DECISION-MAKING; UNITED-STATES; HEALTH; MENORRHAGIA; LEIOMYOMATA; OUTCOMES; WOMEN AB PURPOSE: To compare the cost-effectiveness of uterine artery embolization (UAE) with that of hysterectomy for women with symptomatic uterine fibroids. MATERIALS AND METHODS: The authors developed a decision model to compare the costs and effectiveness of UAE and hysterectomy. In the model, a cohort of women aged 40 years with a diagnosis of uterine fibroids and no desire for future pregnancy was followed up until menopause. The analysis was performed from a societal perspective, including all costs and effects, regardless of who incurs them. Transition probability and quality-of-life estimates were obtained from the literature and a gynecologist, whereas costs (in 1999 U.S. dollars) were estimated by using rates of Medicare reimbursement for hospital costs and physician fees. Sensitivity analyses of key estimates were performed. Results were expressed in costs per quality-adjusted life-year (QALY). RESULTS: UAE was more effective (8.29 vs 8.18 QALYs) and less expensive ($6,916 vs $7,847) than hysterectomy. Cost-effectiveness results, with the exception of quality-of-life data, were robust to changes in most model assumptions. When the quality-of-life adjustment was eliminated, the two procedures were equally effective. CONCLUSION: UAE is a cost-effective alternative to hysterectomy across a wide range of assumptions about the costs and effectiveness of the two procedures. However, the study results were sensitive to changes in quality-of-life values. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Gynecol Serv, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Newton Wellesley Hosp, Dept Med, Newton, MA USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. NR 28 TC 30 Z9 31 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2004 VL 230 IS 1 BP 207 EP 213 DI 10.1148/radiol.2301021482 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 758BR UT WOS:000187613100029 PM 14695395 ER PT J AU Myers, MG AF Myers, MG TI Leptin receptor signaling and the regulation of mammalian physiology SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 59 SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review ID BODY-WEIGHT; MESSENGER-RNA; FOOD-INTAKE; OBESITY SYNDROME; OB/OB MICE; BRAIN-STEM; IN-VIVO; OB-R; ACTIVATION; GENE AB While the hormone leptin and its receptor were discovered relatively recently, a great deal is already known about the molecular details of leptin receptor (LR) signaling and physiologic regulation. While multiple alternatively spliced LR isoforms exist, only the long (LRb) form associates with the Janus kinase 2 (Jak2) tyrosine kinase to mediate intracellular signaling. LRb initiates signaling via three major mechanisms: 1) Tyr(985) of LRb recruits SH2-containing tyrosine phosphatase (SHP-2); 2) Tyr(1138) of LRb recruits signal transducer and activator of transcription 3 (STAT3); and 3) tyrosine phosphorylation sites on the receptor-associated Jak2 likely recruit numerous undefined signaling proteins. The Tyr(985) --> SHP-2 pathway is a major regulator of extracellular signal-regulated kinase (ERK) activation during leptin signaling in cultured cells, while the Tyr(1138) --> STAT3 pathway induces the feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), as well as important positive effectors of leptin action. The Jak2-dependent activation of the insulin receptor substrate (IRS) protein --> phosphatidylinositol 3-kinase (PI3'-K) pathway appears to regulate membrane potential in LRb-expressing neurons and contributes to the regulation of feeding. The Tyr(1138) --> STAT3 pathway mediates transcriptional regulation of the hypothalamic melanocortin pathway in vivo. This pathway is required for the regulation of appetite and energy expenditure by leptin. Interestingly, the Tyr(1138) --> STAT3 pathway does not strongly regulate neuropeptide Y (NPY) and thus is not required for the control of reproduction and growth. Thus, other as-yet-undefined leptin receptor signals are central to these and perhaps other aspects of leptin action. C1 Joslin Diabet Ctr, Div Res, Sect Obes, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, Sect Obes, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK56731, DK57768] NR 63 TC 252 Z9 264 U1 3 U2 11 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 J9 RECENT PROG HORM RES PY 2004 VL 59 BP 287 EP 304 DI 10.1210/rp.59.1.287 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BY89X UT WOS:000189490300014 PM 14749507 ER PT J AU Huang, XD Moir, RD Tanzi, RE Bush, AI Rogers, JT AF Huang, XD Moir, RD Tanzi, RE Bush, AI Rogers, JT TI Redox-active metals, oxidative stress, and Alzheimer's disease pathology SO REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE metals; oxidative stress; Alzheimer's disease; amyloid precursor protein; A beta amyloidosis; metal chelator; antioxidant ID AMYLOID-BETA-PROTEIN; IRON-RESPONSIVE ELEMENT; A-BETA; CEREBROSPINAL-FLUID; PRECURSOR PROTEIN; TRANSGENIC MICE; HYDROGEN-PEROXIDE; FREE-RADICALS; MUTANT PRESENILINS; PARKINSONS-DISEASE AB Considerable evidence is mounting that dyshomeostasis of the redox-active biometals, Cu and Fe, and oxidative stress contribute to the neuropathology of Alzheimer's disease (AD). Present data suggest that metals can interact directly with Abeta peptide, the principal component of beta-amyloid that is one of the primary lesions in AD. The binding of metals to Abeta modulates several physiochemical properties of Abeta that are thought to be central to the pathogenicity of the peptide. First, We and others have shown that metals can promote the in vitro aggregation into tinctorial Abeta amyloid. Studies have confirmed that insoluble amyloid plaques in postmortem AD brain are abnormally enriched in Cu, Fe, and Zn. Conversely, metal chelators dissolve these proteinaceous deposits from postmortem AD brain tissue and attenuate cerebral Abeta amyloid burden in APP transgenic mouse models of AD. Second, we have demonstrated that redox-active Cu(II) and, to a lesser extent, Fe(III) are reduced in the presence of Abeta with concomitant production of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). These Abeta/metal redox reactions, which are silenced by redox-inert Zn(II), but exacerbated by biological reducing agents, may lead directly to the widespread oxidation damages observed in AD brains. Moreover, studies have also shown that H2O2 mediates Abeta cellular toxicity and increases the production of both Abeta and amyloid precursor protein (APP). Third, the 5' untranslated region (5'UTR) of APP mRNA has a functional iron-response element (IRE), which is consistent with biochemical evidence that APP is a redox-active metalloprotein. Hence, the redox interactions between Abeta, APP, and metals may be at the heart of a pathological positive feedback system wherein Abeta amyloidosis and oxidative stress promote each other. The emergence of redox-active metals as key players in AD pathogenesis strongly argues that amyloid-specific metal-complexing agents and antioxidants be investigated as possible disease-modifying agents for treating this horrible disease. C1 Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Huang, XD (reprint author), Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA 02129 USA. EM huangx@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIMH NIH HHS [5-K01-MH02001] NR 95 TC 234 Z9 245 U1 4 U2 34 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1012 BP 153 EP 163 DI 10.1196/annals.1306.012 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA BAB76 UT WOS:000221503700012 PM 15105262 ER PT S AU Bartzokis, G Tishler, TA Shin, IS Lu, PH Cummings, JL AF Bartzokis, G Tishler, TA Shin, IS Lu, PH Cummings, JL BE LeVine, SM Connor, JR Schipper, HM TI Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases SO REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS SE Annals of the New York Academy of Sciences LA English DT Article DE iron; ferritin; risk factor; age at onset; aging; Alzheimer's disease; Parkinson's disease; dementia; sex; gender; brain development; myelin; oligodendrocytes; degeneration; amyloid; tau; alpha-synuclein; free radicals; Lewy body; neuritic plaques; synucleinopathy; proteinopathy; tauopathy; chelation; treatment; hemochromatosis ID IN-VIVO EVALUATION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; HEMOCHROMATOSIS GENE; ALPHA-SYNUCLEIN; HEREDITARY HEMOCHROMATOSIS; RESPONSE FLUCTUATIONS; OXIDATIVE STRESS; PRECURSOR CELLS; MRI EVALUATION AB Tissue iron can promote oxidative damage. Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Higher iron levels in males may contribute to higher risk for younger-onset PD and recent studies have linked the presence of the hemo-chromatosis gene with a younger age at onset of AD. We examined whether age at onset of PD and AD was associated with increased brain ferritin iron. Ferritin iron can be measured with specificity in vivo with MRI utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in three basal ganglia regions (caudate, putamen, and globus pallidus) and frontal lobe white matter for younger- and older-onset male PD and AD patients and healthy controls. Significant increases in basal ganglia FDRI levels were observed in the younger-onset groups of both diseases compared to their respective control groups, but were absent in the older-onset patients. The results support the suggestion that elevated ferritin iron and its associated toxicity is a risk factor for age at onset of neurodegenerative diseases such as AD and PD. Clinical phenomena such as gender-associated risk of developing neurodegenerative diseases and the age at onset of such diseases may be associated with brain iron levels. In vivo MRI can measure and track brain ferritin iron levels and provides an opportunity to design therapeutic interventions that target high-risk populations early in the course of illness, possibly even before symptoms appear. C1 Univ Calif Los Angeles, Dept Neurol, Lab Neuroimaging, Div Brain Mapping, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Neurosci Interdept Grad Program, Los Angeles, CA USA. Chonnam Natl Univ, Sch Med, Dept Psychiat, Kwangju, South Korea. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 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 FU NIA NIH HHS [AG 16570] NR 76 TC 108 Z9 117 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-502-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1012 BP 224 EP 236 DI 10.1196/annals.1306.019 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA BAB76 UT WOS:000221503700019 PM 15105269 ER PT J AU Martemyanov, KA Arshavsky, VY AF Martemyanov, KA Arshavsky, VY TI Kinetic approaches to study the function of RGS9 isoforms SO REGULATORS OF G-PROTEIN SIGNALING, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID GTPASE-ACCELERATING PROTEIN; TRANSITION-STATE; MEMBRANE ANCHOR; MICE LACKING; IN-VITRO; TRANSDUCIN; PHOTOTRANSDUCTION; PHOTORECEPTORS; ACTIVATION; AFFINITY AB The experimental strategies developed in kinetic studies of interactions between RGS9 isoforms with G proteins of the G(i) subfamily provide a useful framework for conducting similar studies with essentially any regulator of G-protein signaling (RGS) protein - G-protein pair. This article describes two major kinetic approaches used in the studies of RGS9 isoforms: single turnover and multiple turnover GTPase assays. We also describe pull-down assays as a method complementary to the kinetic assays. The discussion of the strengths and limitations of each individual assay emphasizes the importance of combining multiple experimental approaches in order to obtain comprehensive and internally consistent information regarding the mechanisms of RGS protein action. C1 Harvard Univ, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Martemyanov, KA (reprint author), Harvard Univ, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. FU NEI NIH HHS [EY 12859] NR 34 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER 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 390 BP 196 EP 209 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBF50 UT WOS:000225235700013 PM 15488179 ER PT J AU Fonda, SJ Fultz, NH Jenkins, KR Wheeler, LM Wray, LA AF Fonda, SJ Fultz, NH Jenkins, KR Wheeler, LM Wray, LA TI Relationship of body mass and net worth for retirement-aged men and women SO RESEARCH ON AGING LA English DT Article DE body weight; body mass index; SES; wealth; gender ID ECONOMIC CONSEQUENCES; SOCIOECONOMIC-STATUS; YOUNG ADULTHOOD; OBESITY; HEALTH; WEIGHT; OVERWEIGHT; EARNINGS; INDEX; LIFE AB This article examines linkages between body weight and socioeconomic status (SES) among Americans at or near retirement age. The authors hypothesize that (a) body weight relates negatively to SES, (b) this relationship is greater for women than men, and (c) the relationship attenuates when health, employment, and marital status are controlled. We use the 1992 Health and Retirement Study for this examination. SES is measured as net worth. Body weight is measured as body mass index and categorized as normal weight, overweight, and obese. Results indicate that, for women, overweight and obesity relate to lower logged net worth. This relationship attenuates once covariates are considered. For men, overweight and obesity relate to higher logged net worth, even when covariates are considered. The findings suggest that greater weight has different meanings for men and women in this cohort; it might be related to success for men but a sociocultural detriment for women. C1 Penn State Univ, University Pk, PA 16802 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Fonda, SJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Rm 185,1 Joslin Pl, Boston, MA 02215 USA. EM Stephanie.Fonda@joslin.harvard.edu NR 53 TC 16 Z9 16 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD JAN PY 2004 VL 26 IS 1 BP 153 EP 176 DI 10.1177/0164027503258739 PG 24 WC Gerontology SC Geriatrics & Gerontology GA 750WG UT WOS:000187021000008 ER PT J AU Rizzo, JF Goldbaum, S Shahin, M Denison, TJ Wyatt, J AF Rizzo, JF Goldbaum, S Shahin, M Denison, TJ Wyatt, J TI In vivo electrical stimulation of rabbit retina with a microfabricated array: Strategies to maximize responses for prospective assessment of stimulus efficacy and biocompatibility SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article ID VISUAL EVOKED-POTENTIALS; OPTIC-NERVE; CORTICAL RESPONSES; MICROELECTRODE; SYSTEM; THRESHOLDS; ACTIVATION; COMPONENTS; BRAIN; CELLS AB Purpose: Our primary goal was to assess the effects of varying stimulus parameters on the electrically evoked cortical potentials (EECPs) in rabbits, which we intend to use as one measure of biocompatibility of implanted retinal prosthetic devices. We also sought to exclude contamination of waveforms recorded over the occipital cortex from electrical activity from the retina and the degree of reproducibility of EECP recordings. Methods: A concentric bipolar platinum electrode or microfabricated 5 x 5 electrode array delivered current to the retina of 43 Dutch-belted rabbits while the EECP was recorded from extradural electrodes over the occipital cortex. Electroretinogram (ERG) and visual evoked cortical potential (VECP) recordings were routinely obtained. Verification that occipital cortical recordings were not heavily contaminated by electrical potentials from the retina (i.e. the "validity" of the cortical recordings) was made by recording retinal and brain responses before and after intravitreal injection of tetrodotoxin. Electrical stimulation of the retina was performed with monopolar (with distant return) or bipolar electrode configurations. Cortical responses were computer-averaged over 100 - 500 stimulations. The effect of variation in stimulus current, charge, duration, frequency, polarity and spatial orientation of stimulating electrodes on cortical responses was studied. Results: Progressive reduction of responses toward the anterior skull and abolition of posterior recordings by tetrodotoxin indicated that retinal activity did not significantly contaminate EECP recordings. Reproducibility testing revealed that interanimal variability within the first hour of testing across all animals was not significantly greater than that found during prolonged testing of a single animal. The lowest current that yielded a reproducible EECP with monopolar stimulation was 75 mu A (total current through 21 electrodes) using 200 mu sec pulses, which yielded a 45 mu V cortical response. Strength-duration curves were generally flat for fixed charge stimulation and linear for fixed current stimulation, at least up to a saturation point, which occurred at very high charge. Over 0.5-16 Hz stimulus frequencies, ERGs varied little but evoked potential responses showed a monotonic decline in amplitude at higher frequencies. Large negative-going initial pulses of a biphasic pair yielded the largest cortical amplitudes. EECP amplitudes varied significantly with the orientation of stimulating electrodes on the retina. Conclusions: This study provides novel data on the reproducibility of EECP recordings, and insight into stimulation parameters that affect retinal and cortical responses. This information can be used to improve the yield of retinal and evoked potential recordings, which will enhance the prospective assessment of the efficacy of stimulation and health of the stimulated tissues following implantation of a-prosthesis. These experiments also provided a valuable opportunity to develop methods of retinal stimulation that we subsequently used in psychophysical trials in humans. C1 Boston Vet Adm Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Rizzo, JF (reprint author), Boston Vet Adm Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. NR 39 TC 18 Z9 18 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2004 VL 22 IS 6 BP 429 EP 443 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 920JM UT WOS:000228685200003 PM 15798362 ER PT J AU Spires, TL Hyman, BT AF Spires, TL Hyman, BT TI Neuronal structure is altered by amyloid plaques SO REVIEWS IN THE NEUROSCIENCES LA English DT Review DE amyloid; transgenic; Alzheimer's disease; senile plaque; neurodegeneration; synapse ID FAMILIAL ALZHEIMERS-DISEASE; HIPPOCAMPAL DENTATE GYRUS; REGION-SPECIFIC STABILITY; CENTRAL-NERVOUS-SYSTEM; SYNAPTIC PATHOLOGY; SENILE DEMENTIA; TRANSGENIC MICE; PRECURSOR PROTEIN; DENDRITIC EXTENT; BETA-PROTEIN AB During the course of Alzheimer's disease (AD), neurons undergo extensive remodeling, contributing to the loss of function observed in the disease. Many brain regions in patients with AD show changes in axonal and dendritic fields, dystrophic neurites, synapse loss, and neuron loss. Accumulation of amyloid-beta protein, a pathological hallmark of the disease, contributes to many of these alterations of neuronal structure. Areas of the brain displaying a high degree of plasticity are particularly vulnerable to degeneration in Alzheimer's disease. This article describes neuronal changes that occur in AD, reviews evidence that amyloid-beta contributes to these changes, and finally discusses the recovery of amyloid-induced changes in the brains of transgenic mice, lending hope to the idea that therapeutic strategies which reduce amyloid-beta production will lead to functional recovery in patients with AD. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Spires, TL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Bldg 114,16th St,Room 2021, Charlestown, MA 02129 USA. EM tspires@partners.org FU NIA NIH HHS [NIA-5 T32 AG00277] NR 122 TC 61 Z9 64 U1 2 U2 4 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2004 VL 15 IS 4 BP 267 EP 278 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 863FI UT WOS:000224545900004 PM 15526551 ER PT J AU Schuepbach, D Hill, SK Sanders, RD Hell, D Keshavan, MS Sweeney, JA AF Schuepbach, D Hill, SK Sanders, RD Hell, D Keshavan, MS Sweeney, JA TI Early treatment induced improvement of negative symptoms predicts cognitive functioning in treatment naive first episode schizophrenia: A 2-year followup SO SCHIZOPHRENIA BULLETIN LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2001 CL NEW ORLEANS, LA SP Soc Biol Psychiat DE schizophrenia; followup; verbal memory; learning; neuropsychology ID 1ST EPISODE SCHIZOPHRENIA; TREATMENT RESPONSE; NEUROPSYCHOLOGICAL DEFICITS; DISORDER; FORMS AB Studying neuroleptic-naive first episode schizophrenia is a strategy for investigating clinical and neuropsychological abnormalities at a very early phase of the disease without confounding influences of illness duration and medication effects. We examined the clinical and neuropsychological time course over 2 years in 32 neuroleptic-naive first episode patients (20 males, 12 females) and 21 healthy individuals with similar sociodemographic characteristics. Early treatment-induced reduction of negative symptoms predicted superior cognitive performance throughout followup in the domains of verbal fluency, attention, and nonverbal learning and memory. There were no associations between psychotic or disorganized symptoms and cognitive variables. These findings suggest an important relationship between treatment efficacy of antipsychotic medication and the longer term course of cognitive deficits in schizophrenia. C1 Psychiat Univ Hosp Zurich, CH-8029 Zurich, Switzerland. Univ Illinois, Ctr Cognit Med, Dept Psychiat, Chicago, IL USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Illinois, Sch Med, Neurocognit Assessment & Brain Imaging Program, Chicago, IL USA. RP Schuepbach, D (reprint author), Psychiat Univ Hosp Zurich, POB 68, CH-8029 Zurich, Switzerland. EM daniel.schuepbach@puk.zh.ch FU NCRR NIH HHS [M01RR00056]; NIMH NIH HHS [MH01433, MH42969, MH45156, MH62134] NR 46 TC 13 Z9 13 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2004 VL 30 IS 4 BP 837 EP 848 PG 12 WC Psychiatry SC Psychiatry GA 910FN UT WOS:000227916000016 PM 15957199 ER PT J AU Reddy, RD Keshavan, MS Yao, JK AF Reddy, RD Keshavan, MS Yao, JK TI Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline SO SCHIZOPHRENIA BULLETIN LA English DT Article DE red blood cell; fatty acid composition; polyunsaturated fatty acids; first episode schizophrenia ID MAGNETIC-RESONANCE-SPECTROSCOPY; ETHYL-EICOSAPENTAENOIC ACID; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; DOCOSAHEXAENOIC ACID; ERYTHROCYTE-MEMBRANES; TARDIVE-DYSKINESIA; PHOSPHOLIPASE A(2); SKIN FIBROBLASTS; PLASMA AB There is emerging evidence in schizophrenia of membrane abnormalities, primarily reductions in the essential omega-3 and omega-6 series of polyunsaturated fatty acids (PUFA). Because previous studies have largely been in chronic patients, it is not known whether these membrane abnormalities also occur early in illness. In the present study, red blood cell membrane fatty acid levels were determined by capillary gas chromatography from 24 neuroleptic-naive patients with first episode schizophrenia or schizoaffective disorder and 31 age-matched normal controls. Relative to normal subjects, patients had significant reductions in total PUFA (-13%) but not in monounsaturated or saturated fatty acids. Specifically, significant reductions were found in arachidonic acid (-18%), docosapentaenoic acid (-36%), and docosahexaenoic acid (-26%) concentrations. These reductions were not related to age, gender, smoking status, or cotinine levels. These results confirm previous findings of membrane deficits in schizophrenia and show that significant PUFA reductions occur early in the illness, prior to initiation of treatment, raising the possibility that these deficits are trait related. The findings also suggest that membrane fatty acid losses are quite specific to the highly unsaturated fatty acids. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Reddy, RD (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, 3811 O Hara St, Pittsburgh, PA 15213 USA. EM reddyr@upmc.edu FU NIMH NIH HHS [MH-45203, MH-58141, MH-64118] NR 80 TC 85 Z9 87 U1 2 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2004 VL 30 IS 4 BP 901 EP 911 PG 11 WC Psychiatry SC Psychiatry GA 910FN UT WOS:000227916000020 PM 15957200 ER PT J AU Yao, JK Leonard, S Reddy, RD AF Yao, JK Leonard, S Reddy, RD TI Increased nitric oxide radicals in postmortem brain from patients with schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE nitric oxide; caudate; postmortem changes; schizophrenia ID ANTIOXIDANT DEFENSE SYSTEM; TARDIVE-DYSKINESIA; CEREBRAL EDEMA; VITAMIN-E; GLUTATHIONE-PEROXIDASE; REFLECT ABNORMALITIES; SERUM INTERLEUKIN-6; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION AB Alterations in antioxidant status in schizophrenia suggest free radical-mediated neurotoxicity; this finding can be a consequence of increased free radical production. There are multiple pathways to excess free radical generation and subsequent oxidative stress. One such pathway is the formation of peroxynitrite by a reaction of nitric oxide (NO) and superoxide radical. NO is formed from L-arginine by nitric oxide synthase (NOS). A constitutive cytosolic isoform, neuronal NOS (nNOS), appears to be fairly stable in the postmortem brain tissues. Utilizing a sensitive fluorometric assay, NO levels were measured by its stable metabolites, nitrate and nitrite, in the caudate region of postmortem brain tissues from patients and control subjects. In the human brain, NO is metabolized primarily in the form of nitrate. A significantly increased level of NO was found in schizophrenia patients (241 +/- 146 pmol/mg dry weight, n = 18) than was found in those of normal (142 +/- 65 pmol/mg dry weight, n = 20) and psychiatric controls without schizophrenia (125 +/- 83 pmol/mg dry weight, n = 16) (analysis of covariance [ANCOVA], F = 6.446, df = 2,51, p = 0.003). These findings were independent of age, brain weight, postmortem interval (PMI), sample storage time, or cigarette smoking. Elevated NO levels in the brains of schizophrenia patients lend further support for the free radical pathology in schizophrenia. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Bldg 13,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu NR 79 TC 75 Z9 78 U1 1 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2004 VL 30 IS 4 BP 923 EP 934 PG 12 WC Psychiatry SC Psychiatry GA 910FN UT WOS:000227916000022 PM 15954198 ER PT J AU Caplan, D AF Caplan, D TI Functional neuroimaging studies of written sentence comprehension SO SCIENTIFIC STUDIES OF READING LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SYNTACTIC COMPREHENSION; BROCAS AREA; FMRI; ACTIVATION; LANGUAGE; BRAIN; PET; CORTEX; SPEED AB Sentences convey relationships between the meanings of words, such as who is accomplishing an action or receiving it. Functional neuroimaging based on positron-emission tomography and functional magnetic resonance imaging has been used to identify areas of the brain involved in structuring sentences and determining aspects of meaning associated with sentences. This article reviews this literature, beginning with studies that compare sentences to low-level baselines, which identify brain regions involved in many language functions, and progressing to more narrowly constructed experiments that contrast one sentence type with another, which are designed to identify brain regions involved in quite specific sentence-level processing operations. These studies suggest that at least some syntactic and sentence-level interpretive operations, and/or the resource system that supports them, utilize the same brain areas regardless of whether language is spoken or written. They also suggest that several brain regions may provide support in these processes and that there are individual differences in what parts of the brain are involved in these functions. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org NR 29 TC 12 Z9 12 U1 2 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1088-8438 J9 SCI STUD READ JI Sci. Stud. Read. PY 2004 VL 8 IS 3 BP 225 EP 240 DI 10.1207/s1532799xssr0803_3 PG 16 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA 833YM UT WOS:000222377600003 ER PT J AU Misra, M Katzir, T Wolf, M Poldrack, RA AF Misra, M Katzir, T Wolf, M Poldrack, RA TI Neural systems for rapid automatized naming in skilled readers: Unraveling the RAN-reading relationship SO SCIENTIFIC STUDIES OF READING LA English DT Article ID INFERIOR PREFRONTAL CORTEX; WORD FORM AREA; DEVELOPMENTAL DYSLEXIA; HUMAN-BRAIN; ANATOMY; SPEED; SPECIALIZATION; DISABILITIES; RECOGNITION; ATTENTION AB The majority of children and adults with reading disabilities exhibit pronounced difficulties on naming-speed measures such as tests of rapid automatized naming (RAN). RAN tasks require speeded naming of serially presented stimuli and share key characteristics with reading, but different versions of the RAN task vary in their sensitivity: The RAN letters task successfully predicts reading ability, whereas the RAN objects task does not reliably predict reading after kindergarten. In this study we used functional magnetic resonance imaging to evaluate the neural substrates that may underlie performance on these tasks. In two scans during the same test session, adult, average readers covertly rapidly named objects or letters or passively viewed a fixation matrix of plus signs. For both rapid naming tasks compared with fixation, activation was found in neural areas associated with eye movement control and attention as well as in a network of structures previously implicated in reading tasks. This reading network included inferior frontal cortex, temporo-parietal areas, and the ventral visual stream. Whereas the inferior frontal areas of the network were similarly activated for both letters and objects, activation in the posterior areas varied by task. The letters task caused greater activation in the angular gyrus, superior parietal lobule, and medial extrastriate areas, whereas object naming only preferentially activated an area of the fusiform gyrus. These results confirm that RAN tasks recruit a network of neural structures also involved in more complex reading tasks and suggest that the RAN letters task specifically pinpoints key components of this network. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Tufts Univ, Dept Child Dev, Medford, MA 02155 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Univ Calif Los Angeles, Dept Psychol, Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM poldrack@ucla.edu NR 55 TC 64 Z9 65 U1 7 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1088-8438 EI 1532-799X J9 SCI STUD READ JI Sci. Stud. Read. PY 2004 VL 8 IS 3 BP 241 EP 256 DI 10.1207/s1532799xssr0803_4 PG 18 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA 833YM UT WOS:000222377600004 ER PT B AU Heckers, S AF Heckers, S BE Gattaz, WF Hafner, H TI The hippocampus and schizophrenia SO SEARCH FOR THE CAUSES OF THE SCHIZOPHRENIA, VOL 5 LA English DT Proceedings Paper CT 5th Symposium on the Search for the Causes of Schizophrenia CY APR, 2003 CL Guaruja, BRAZIL ID CEREBRAL BLOOD-FLOW; 1ST EPISODE SCHIZOPHRENIA; PARVALBUMIN-IMMUNOREACTIVE NEURONS; LEFT TEMPORAL-LOBE; 1ST-EPISODE SCHIZOPHRENIA; VOLUME REDUCTION; LIMBIC SYSTEM; CONSCIOUS RECOLLECTION; PARAHIPPOCAMPAL GYRUS; BRAIN ABNORMALITIES C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. EM heckers@psych.mgh.harvard.edu RI Gattaz, Wagner/C-4456-2012 NR 126 TC 0 Z9 0 U1 0 U2 0 PU STEINKOPFF DARMSTADT PI BERLIN 33 PA C/O SPRINGER VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY BN 3-7985-1451-8 PY 2004 BP 182 EP 200 PG 19 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BAN72 UT WOS:000222997900012 ER PT J AU Keeffe, EB Dienstag, JL AF Keeffe, EB Dienstag, JL TI HBV viral kinetics and clinical management: Key issues and current perspectives SO SEMINARS IN LIVER DISEASE LA English DT Editorial Material C1 Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Keeffe, EB (reprint author), Stanford Univ, Med Ctr, 750 Welch Rd,Suite 210, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PY 2004 VL 24 SU 1 BP 1 EP 2 DI 10.1055/s-2004-828671 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829XD UT WOS:000222083800001 ER PT J AU Dusso, AS Thadhani, R Slatopolsky, E AF Dusso, AS Thadhani, R Slatopolsky, E TI Vitamin D receptor and analogs SO SEMINARS IN NEPHROLOGY LA English DT Review ID DOXERCALCIFEROL 1-ALPHA-HYDROXYVITAMIN D-2; D RESPONSE ELEMENTS; GROWTH-FACTOR-ALPHA; SECONDARY HYPERPARATHYROIDISM; RENAL-FAILURE; PARATHYROID HYPERPLASIA; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; UREMIC RATS; 22-OXACALCITRIOL C1 Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dusso, AS (reprint author), Washington Univ, Sch Med, Div Renal, Campus Box 8126,660 S Euclid Ave, St Louis, MO 63110 USA. EM adusso@im.wustl.edu RI Dusso, Adriana/E-8617-2011 FU NIAMS NIH HHS [AR45283] NR 41 TC 34 Z9 38 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2004 VL 24 IS 1 BP 10 EP 16 DI 10.1053/j.semnephrol.2003.08.018 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 768RJ UT WOS:000188588600003 PM 14730505 ER PT J AU Salusky, IB Kuizon, BG Juppner, H AF Salusky, IB Kuizon, BG Juppner, H TI Special aspects of renal osteodystrophy in children SO SEMINARS IN NEPHROLOGY LA English DT Review ID INTERMITTENT CALCITRIOL THERAPY; GROWTH-HORMONE; SECONDARY HYPERPARATHYROIDISM; UREMIC RATS; PTH/PTHRP RECEPTOR; INDIAN HEDGEHOG; GENE-EXPRESSION; BONE-DISEASE; PEDIATRIC-PATIENTS; BINDING PROTEIN-3 C1 Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Dept Pediat,David Geffen Sch Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Salusky, IB (reprint author), Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Dept Pediat,David Geffen Sch Med, Box 951752, Los Angeles, CA 90095 USA. EM isalusky@mednet.ucla.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 71 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2004 VL 24 IS 1 BP 69 EP 77 DI 10.1053/j.semnephrol.2003.08.009 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 768RJ UT WOS:000188588600010 PM 14730512 ER PT J AU Stehman-Breen, C AF Stehman-Breen, C TI Osteoporosis and chronic kidney disease SO SEMINARS IN NEPHROLOGY LA English DT Review ID BONE-MINERAL DENSITY; STAGE RENAL-DISEASE; HIP FRACTURE; RISK-FACTORS; DIALYSIS PATIENTS; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; HORMONE; OSTEODYSTROPHY; HEMODIALYSIS C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Washington Univ, Seattle, WA USA. RP Stehman-Breen, C (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. EM cos@u.washington.edu NR 33 TC 29 Z9 29 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2004 VL 24 IS 1 BP 78 EP 81 DI 10.1053/j.semnephrol.2003.08.013 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 768RJ UT WOS:000188588600011 PM 14730513 ER PT J AU Chen, GTY Kung, JH Beaudette, KP AF Chen, GTY Kung, JH Beaudette, KP TI Artifacts in computed tomography scanning of moving objects SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID HELICAL CT; RADIATION-THERAPY; IMPROVEMENT; MOTION; SCANS C1 Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chen, GTY (reprint author), Harvard Univ, Dept Radiat Oncol, Sch Med, Massachusetts Gen Hosp, 100 Blossom St,Cox 346, Boston, MA 02114 USA. NR 14 TC 131 Z9 137 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2004 VL 14 IS 1 BP 19 EP 26 DI 10.1053/j.semradonc.2003.10.004 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 771ZL UT WOS:000188815900004 PM 14752730 ER PT J AU Bortfeld, T Jiang, SB Rietzel, E AF Bortfeld, T Jiang, SB Rietzel, E TI Effects of motion on the total dose distribution SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID INCORPORATING ORGAN MOTION; EXTERNAL-BEAM RADIOTHERAPY; SET-UP ERRORS; GATED RADIOTHERAPY; CONVOLUTION METHOD; TUMOR; IMRT; DELIVERY; LUNG; UNCERTAINTIES C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 36 TC 185 Z9 191 U1 0 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2004 VL 14 IS 1 BP 41 EP 51 DI 10.1053/j.semradonc.2003.10.011 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 771ZL UT WOS:000188815900006 PM 14752732 ER PT S AU Palevsky, PM AF Palevsky, PM BE Ronco, C Bellomo, R Brendolan, A TI CRRT: Selection of patients and starting criteria SO SEPSIS, KIDNEY AND MULTIPLE ORGAN DYSFUNCTION SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article; Proceedings Paper CT 3rd International Course on Critical Care Nephrology CY JUN 01-04, 2004 CL Vicenza, ITALY ID ACUTE-RENAL-FAILURE; CONTINUOUS VENOVENOUS HEMOFILTRATION; REPLACEMENT THERAPY; PROPHYLACTIC DIALYSIS; INTRACRANIAL-PRESSURE; INTERMITTENT; HEMODIALYSIS; EXPERIENCE; FILTRATION; ADSORPTION C1 Univ Pittsburgh, Dr Div, VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15240 USA. RP Palevsky, PM (reprint author), Univ Pittsburgh, Dr Div, VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123,111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 37 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 3-8055-7755-9 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2004 VL 144 BP 214 EP 221 PG 8 WC Critical Care Medicine; Urology & Nephrology SC General & Internal Medicine; Urology & Nephrology GA BAH25 UT WOS:000222209500018 PM 15264410 ER PT J AU Hellman, J Warren, HS Tesini, B Bagchi, A AF Hellman, J Warren, HS Tesini, B Bagchi, A TI Bacterial PAL and LPS synergistically activate cellular and systemic inflammation SO SHOCK LA English DT Meeting Abstract CT 6th World Congress on Trauma, Shock, Inflammation and Sepsis - Pathophysiology, Immune Consequences and Therapy CY MAR 02-06, 2004 CL Munich, GERMANY C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2004 VL 21 SU 1 MA 77 BP 20 EP 20 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 810FF UT WOS:000220689500079 ER PT J AU Felbinger, TW Hoffmeister, KM Falet, H Hartwig, JH Von Andrian, UH AF Felbinger, TW Hoffmeister, KM Falet, H Hartwig, JH Von Andrian, UH TI A mechanism for rapid clearance of transfused chilled platelets SO SHOCK LA English DT Meeting Abstract CT 6th World Congress on Trauma, Shock, Inflammation and Sepsis - Pathophysiology, Immune Consequences and Therapy CY MAR 02-06, 2004 CL Munich, GERMANY C1 Harvard Univ, Sch Med, CBR Inst Biochem Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Univ Munich, Med Ctr, Dept Anesthesiol, D-80539 Munich, Germany. EM felbinger@cbr.med.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2004 VL 21 SU 1 MA 100 BP 25 EP 25 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 810FF UT WOS:000220689500102 ER PT J AU Bagchi, A Warren, HS Trigilio, J Hellman, J AF Bagchi, A Warren, HS Trigilio, J Hellman, J TI Tolerizing and priming effects of bacterial peptidoglycan associated lipoprotein (PAL) and LPS SO SHOCK LA English DT Meeting Abstract CT 27th Annual Conference on Shock CY JUN 05-08, 2004 CL Halifax, CANADA C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2004 VL 21 SU 2 MA 84 BP 29 EP 29 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 826GC UT WOS:000221816300084 ER PT J AU Hellman, J Warren, S Tesini, B Bagchi, A AF Hellman, J Warren, S Tesini, B Bagchi, A TI Bacterial PAL activates inflammation through TLR2 and in synergy with LPS SO SHOCK LA English DT Meeting Abstract CT 27th Annual Conference on Shock CY JUN 05-08, 2004 CL Halifax, CANADA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PY 2004 VL 21 SU 2 MA 91 BP 31 EP 31 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 826GC UT WOS:000221816300091 ER PT S AU Doukas, AG AF Doukas, AG BE Furnish, MD Gupta, YM Forbes, JW TI Pressure waves in medicine: From tissue injury to drug delivery SO SHOCK COMPRESSION OF CONDENSED MATTER - 2003, PTS 1 AND 2, PROCEEDINGS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 13th Conference of the American-Physical-Society-Topical-Group on Shock Compression of Condensed Matter CY JUL 20-25, 2003 CL Portland, OR SP Amer Phys Soc Top Grp ID GENERATED STRESS WAVES; INDUCED SHOCK-WAVES; TRANSDERMAL DELIVERY; LASER LITHOTRIPSY; CELL-MEMBRANE; IN-VITRO; GRADIENT; IMPULSE; VIVO AB Pressure waves have the potential to cause injury to cells and tissue or enable novel therapeutic modalities, such as fragmentation of kidney stones and drug delivery. Research on the biological effects of pressure waves have shown that the biological response on depends the pressure-wave characteristics. One of the most prominent effects induced by pressure waves is the permeabilization of a number of barrier structures (cell plasma membrane, skin and microbial biofilms) and facilitate the delivery of macromolecules. The permeabilization of the barrier structure is transient and the barrier function recovers. Thus, pressure waves can induce delivery of molecular species that would not normally cross the barrier structure. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, 55 Fruit St,WEL 224, Boston, MA 02114 USA. EM adoukas@partners.org NR 20 TC 2 Z9 2 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0181-0 J9 AIP CONF PROC PY 2004 VL 706 BP 1431 EP 1435 PG 5 WC Materials Science, Multidisciplinary; Mechanics; Physics, Condensed Matter SC Materials Science; Mechanics; Physics GA BAT26 UT WOS:000223423000335 ER PT J AU Philips, N Burchill, D O'Donoghue, D Keller, T Gonzalez, S AF Philips, N Burchill, D O'Donoghue, D Keller, T Gonzalez, S TI Identification of benzene metabolites in dermal fibroblasts as nonphenolic: Regulation of cell viability, apoptosis, lipid peroxidation and expression of matrix metalloproteinase 1 and elastin by benzene metabolites SO SKIN PHARMACOLOGY & PHYSIOLOGY LA English DT Article DE toluene; benzaldehyde; aniline; benzoic acid; hydroquinone; t-butyl hydroquinone; phenol; hydrogen peroxide ID HUMAN LIVER-MICROSOMES; HUMAN BONE-MARROW; HUMAN-SKIN; PERCUTANEOUS-ABSORPTION; CIGARETTE-SMOKING; METHYL DONORS; DNA-DAMAGE; INDUCTION; TOLUENE; MOUSE AB The skin is exposed to benzene and its derivatives, prevalent environmental chemicals. They may impair the structural integrity of the skin by increased expression of matrix metalloproteinase 1 (MMP-1; degrades structural collagen) and elastin, synthesized primarily by the dermal fibroblasts. We examined the metabolism of benzene in dermal fibroblasts and identified the benzene metabolites as toluene, benzaldehyde, aniline and benzoic acid. These metabolites were not toxic to the cells with regard to cell viability, apoptosis and lipid peroxidation, unlike the phenolic benzene metabolites (hydroquinone, t-butyl hydroquinone and phenol) or hydrogen peroxide. Toluene and phenol, which compose cigarette smoke, and benzaldehyde stimulated MMP-1 and/or elastin expression. In summary, the dermal fibroblasts metabolize benzene to nonphenolic metabolites that are less toxic to the cellular components than the phenolic benzene derivatives. Toluene, benzaldehyde and phenol can directly cause facial wrinkling and impaired structural integrity by upregulating MMP-1 and/or elastin. Copyright (C) 2004 S. Karger AG, Basel. C1 Georgian Court Coll, Lakewood, NJ 08701 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Philips, N (reprint author), Georgian Court Coll, 900 Lakewood Ave, Lakewood, NJ 08701 USA. EM Philips@georgian.edu NR 37 TC 13 Z9 13 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-5527 J9 SKIN PHARMACOL PHYSI JI Skin Pharmacol. Physiol. PY 2004 VL 17 IS 3 BP 147 EP 152 DI 10.1159/000077242 PG 6 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 812UT UT WOS:000220865100007 PM 15087594 ER PT J AU Lu, JW Mann, GL Ross, R Morrison, AR Kubin, L AF Lu, JW Mann, GL Ross, R Morrison, AR Kubin, L TI REM sleep-suppressing effect of hypothalamic perifornical microperfusion with GABAA receptor antagonist, bicuculline, increases with the duration of sleep SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 031 BP 14 EP 14 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400033 ER PT J AU Gong, H McGinty, D Angara, C Xu, F Chew, K Szymusiak, R AF Gong, H McGinty, D Angara, C Xu, F Chew, K Szymusiak, R TI Retrograde labeling in the preoptic area of the hypothalamus following injections of fluoro-gold into perifornical lateral hypothalamus SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 VA Greater Los Angeles Hlth Syst, Sleeep Res Ctr, North Hills, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 036 BP 16 EP 17 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400038 ER PT J AU Lu, J Devor, M Saper, CB AF Lu, J Devor, M Saper, CB TI A lateral pontine tegmental flip-flop switch for regulation of REM sleep SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 039 BP 18 EP 18 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400041 ER PT J AU Jha, SK Pawlyk, AC Brennan, FX Ross, RJ Morrison, AR AF Jha, SK Pawlyk, AC Brennan, FX Ross, RJ Morrison, AR TI Conditioned fear cues suppress REM sleep in rats SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 062 BP 28 EP 28 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400064 ER PT J AU Wu, M Nienhuis, R John, J Maidment, NT Lam, HA Boehmer, LN Siegel, JM AF Wu, M Nienhuis, R John, J Maidment, NT Lam, HA Boehmer, LN Siegel, JM TI Effects of drugs affecting blood pressure and heart rate on the release of hypocretin in normal dogs SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 VA GLAHS Sepulveda, Neurobiol Res 151A3, North Hills, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 077 BP 35 EP 35 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400079 ER PT J AU Klerman, EB Hall, JE AF Klerman, EB Hall, JE TI Sleep related slowing of LH pulses in the luteal phase of the menstrual cycle SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 088 BP 40 EP 40 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400090 ER PT J AU Lyamin, O Mukhametov, L Siegel, J AF Lyamin, O Mukhametov, L Siegel, J TI Association between EEG asymmetry and eye state in bottlenose dolphins and northern fur seals SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Univ Calif Los Angeles, Dept Psychiat, North Hills, CA USA. VA GLAHS Sepulveda, North Hills, CA USA. Severtsov Inst Ecol & Evolut, Moscow, Russia. Utrish Dolphinarium, Moscow, Russia. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 184 BP 84 EP 84 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400186 ER PT J AU Lyamin, O Mukhametov, L Siegel, J AF Lyamin, O Mukhametov, L Siegel, J TI Deprivation of bilateral sleep induces EEG asymmetry in the fur seal SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 UCLS, Dept Psychiat, North Hills, CA USA. VA GLAHS Sepulveda, North Hills, CA USA. Severtsov Inst Ecol & Evolut, Moscow, Russia. Utrish Dolphinarium, Moscow, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 316 BP 145 EP 145 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400318 ER PT J AU Cordova, CA McCarley, RW Baxter, MG Chiba, AA Strecker, RE AF Cordova, CA McCarley, RW Baxter, MG Chiba, AA Strecker, RE TI Behavioral assessment of attentional deficits in sleep deprived rats SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Harvard Univ, Sch Med, Brockton, MA USA. VA Boston Healthcare Syst, Brockton, MA USA. UCSD, Cognit Sci, San Diego, CA USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 366 BP 167 EP 167 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400368 ER PT J AU Weaver, EM Maynard, C Yueh, B AF Weaver, EM Maynard, C Yueh, B TI Mortality of veterans with sleep apnea: Untreated versus treated SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 VA Puget Sound Healthcare Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Sleep Disorders Ctr, Seattle, WA 98104 USA. Univ Washington, Hlth Serv, Seattle, WA 98195 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 463 BP 208 EP 208 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400465 ER PT J AU Sharafkhaneh, A Sharafkhaneh, H Bozkurt, B Hirshkowitz, M AF Sharafkhaneh, A Sharafkhaneh, H Bozkurt, B Hirshkowitz, M TI Prevalence of self-reported sleepiness in patients with cardiac permanent pacemaker SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 474 BP 212 EP 213 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400476 ER PT J AU Gurubhagavatula, I Wheeler, M AF Gurubhagavatula, I Wheeler, M TI In-office screening for obstructive sleep apnea in primary care SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Univ Penn, Sch Med, Ctr Sleep & Resp Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Pulm & Crit Care Sect, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 491 BP 219 EP 220 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400493 ER PT J AU Westbrook, PR Berka, C Levendowski, DJ Lumicao, M Davis, G Olmstead, R Petrovic, M Yuksel, Y Ramsey, C Zivkovic, V AF Westbrook, PR Berka, C Levendowski, DJ Lumicao, M Davis, G Olmstead, R Petrovic, M Yuksel, Y Ramsey, C Zivkovic, V TI Quantification of alertness, memory and neurophysiological changes in sleep apnea patients following treatment with nCPAP SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Adv Brain Monitoring Inc, Carlsbad, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 499 BP 223 EP 223 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400502 ER PT J AU Lajos, LE Molina, PE Im, SS Gonzales, TA Garza, PC Ingmundson, PT AF Lajos, LE Molina, PE Im, SS Gonzales, TA Garza, PC Ingmundson, PT TI Continuous positive airway pressure adherence among veterans with and without posttraumatic stress disorder SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Audie Murphy VA Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 511 BP 228 EP 228 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400514 ER PT J AU Thomas, RJ Packard, A AF Thomas, RJ Packard, A TI The functional neurobiology of narcolepsy SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc 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 AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 563 BP 251 EP 251 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400566 ER PT J AU Martin, JL Webber, AP Josephson, KR Harker, JO Alessi, CA AF Martin, JL Webber, AP Josephson, KR Harker, JO Alessi, CA TI Observed versus actigraphically estimated daytime sleep in older adults undergoing subacute rehabilitation in a nursing home SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Greater Los Angeles VA Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 789 BP 353 EP 353 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400791 ER PT J AU Pawlyk, AC Jha, SK Brennan, FX Morrison, AR Ross, RJ AF Pawlyk, AC Jha, SK Brennan, FX Morrison, AR Ross, RJ TI The role of context in differential sleep architecture changes following footshock SO SLEEP LA English DT Meeting Abstract CT 18th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 05-10, 2004 CL Philadelphia, PA SP Associated Profess Sleep Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2004 VL 27 SU S MA 910 BP 407 EP 408 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OX UT WOS:000223169400912 ER PT J AU Nakashima, J McGuire, J Berman, S Daniels, W AF Nakashima, J McGuire, J Berman, S Daniels, W TI Developing programs for homeless veterans: Understanding driving forces in implementation SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE homelessness; housing; veterans; implementation AB Between 1992 and 2003, services for homeless veterans at the Veterans Affairs Greater Los Angeles Healthcare System went from inappropriate utilization of hospital medical and psychiatric beds, to a continuum of residential treatment, transitional housing, and employment programs through arrangements with private agencies. The authors use elements of Hasenfeld and Brock's Political Economy Model (1991) to explain this transformation in service delivery that was spearheaded by a VA social work leadership team. It is argued that three driving forces crucial to program implementation were present: technological certainty, economic stability, and concentration of power. Evidence of the implementation's impact includes creation of new homeless program beds, a reduction in use of medical/psychiatric beds, and a large number of formerly homeless veterans with housing and employment at program discharge. Study limitations and implications for future studies are discussed.(c) 2004 by The Haworth Press, Inc. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Comprehens Homeless Ctr, Los Angeles, CA 90073 USA. RP Nakashima, J (reprint author), VA Greater Los Angeles Healthcare Syst, Comprehens Homeless Ctr, 11301 Wilshire Blvd,Bldg 500,Mail Code W10H5, Los Angeles, CA 90073 USA. EM john.nakashima@med.va.gov; james.mcguire@med.va.gov; stephen.berman@med.va.gov; william.daniels@med.va.gov NR 14 TC 6 Z9 6 U1 1 U2 6 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2004 VL 40 IS 2 BP 1 EP 12 DI 10.1300/J010v40n02_01 PG 12 WC Social Work SC Social Work GA 920ZL UT WOS:000228733900001 PM 15774360 ER PT J AU Aschenbach, WG Sakamoto, K Goodyear, LJ AF Aschenbach, WG Sakamoto, K Goodyear, LJ TI 5 ' adenosine monophosphate-activated protein kinase, metabolism and exercise SO SPORTS MEDICINE LA English DT Review ID ACETYL-COA CARBOXYLASE; HUMAN SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; MALONYL-COA; GLYCOGEN-SYNTHASE; MITOCHONDRIAL BIOGENESIS; PHOSPHORYLASE-KINASE; GLUT4 TRANSLOCATION; GAMMA(2) SUBUNIT; AICA RIBOSIDE AB The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an a catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu FU NIAMS NIH HHS [AR42238, AR45670]; NIDDK NIH HHS [DK59769] NR 89 TC 42 Z9 44 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2004 VL 34 IS 2 BP 91 EP 103 DI 10.2165/00007256-200434020-00003 PG 13 WC Sport Sciences SC Sport Sciences GA 779AE UT WOS:000189272800003 PM 14965188 ER PT J AU Ryan, L Huang, WZ Thurston, SW Kelsey, KT Wiencke, JK Christiani, DC AF Ryan, L Huang, WZ Thurston, SW Kelsey, KT Wiencke, JK Christiani, DC TI On the use of biomarkers for environmental health research SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review ID CUMULATIVE CIGARETTE-SMOKING; CHROMATID EXCHANGE FREQUENCY; LUNG-CANCER SUSCEPTIBILITY; REGRESSION-MODELS; MOLECULAR EPIDEMIOLOGY; LOGISTIC-REGRESSION; LIKELIHOOD ANALYSIS; CLINICAL-TRIALS; COVARIATE DATA; END-POINTS AB This article discusses the growing interest in the use of biomarker data in environmental health research and considers some of the challenging statistical issues that arise. We specify a modeling framework that links environmental exposure, biomarkers and outcome, and discuss in Conceptual terms how such a formulation could be used to inform dose response modeling for the purpose of quantitative risk assessment. We then analyse some biomarker data from a case-control study designed to elucidate the mechanisms of smoking induced lung cancer. Because of sample size limitations, we use a likelihood-based analysis which subsumes both cohort and case-control designs as special cases. Our analysis allows us to 1) investigate the extent to which the markers explain the pathway from exposure to outcome; 2) quantify the degree to which biomarker data can improve on predicting outcome over and above exposure; and 3) estimate the association among multiple markers. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Millennium Operat, New York, NY USA. Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Ryan, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM lryan@hsph.harvard.edu RI Ryan, Louise/A-4562-2009; Kelsey, Karl/I-1252-2014 OI Ryan, Louise/0000-0001-5957-2490; FU NCI NIH HHS [CA48061, CA74386]; NIEHS NIH HHS [5 P42 ES05947, ES00002, ES011027, ES06717] NR 40 TC 3 Z9 3 U1 1 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2004 VL 13 IS 3 BP 207 EP 225 PG 19 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 827BP UT WOS:000221873600002 PM 15198487 ER PT J AU Lee, S Huang, H Zelen, M AF Lee, S Huang, H Zelen, M TI Early detection of disease and scheduling of screening examinations SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID BREAST-CANCER AB Special examinations exist for many chronic diseases, which can diagnose the disease while it is asymptomatic, with no signs or symptoms. The earlier detection of disease may lead to more cures or longer survival. This possibility has led to public health programs which recommend populations to have periodic screening examinations for detecting specific chronic diseases, for example, cancer, diabetes, cardiovascular disease and so on. Such examination schedules when embedded in a public health program are invariably costly and are ordinarily not chosen on the basis of possible trade-offs in costs and benefits for different screening schedules. The possible candidate number of examination schedules is so large that it is not feasible to carry out clinical trials to compare different schedules. Instead, this problem can be investigated by developing a theoretical model which can predict the eventual disease specific mortality for different examination schedules. We have developed such a model. It is a stochastic model which assumes that i) the natural history of the disease is progressive and ii) any benefit from earlier diagnosis is due to a change in the distribution of disease stages at diagnosis (stage shift). The model is general and can be applied to any chronic disease which satisfies our two basic assumptions. We discuss the basic ideas of schedule sensitivity and lifetime schedule sensitivity and its relation to the reduction in disease specific mortality. Our theory is illustrated by applications to breast cancer screening. The investigation of schedules compares not only examination schedules with equal intervals between examinations but also staggered schedules using the threshold method. (Examinations are carried out when an individual's risk status reaches a preassigned threshold value.). C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lee, S (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM sjlee@jimmy.harvard.edu FU NCI NIH HHS [CA88270] NR 6 TC 16 Z9 16 U1 0 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2004 VL 13 IS 6 BP 443 EP 456 DI 10.1191/0962280204sm377ra PG 14 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 871AU UT WOS:000225102100003 PM 15587433 ER PT J AU Hu, P Zelen, M AF Hu, P Zelen, M TI Planning of randomized early detection trials SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID BREAST-CANCER MORTALITY; FOLLOW-UP; SCREENING-PROGRAMS; DEATH RATES; MAMMOGRAPHY; DISEASE AB Consider a randomized clinical trial to evaluate the benefit of screening an asymptomatic population. Suppose that the subjects are randomized into a usual care and a study group. The study group receives one or more periodic early detection examinations aimed at diagnosing disease early, when there are no signs or symptoms. Early detection clinical trials differ from therapeutic trials in that power is affected by: i) the number of exams, ii) the time between exams and iii) the ages at which exams will be given. These design options do not exist in therapeutic trials. Furthermore; long-term follow-up may result in a reduction of power. In general, power increases with number of examinations, and the optimal follow-up time is dependent on the spacing between examinations. Clinical trials in which the usual care group receives benefit are also discussed. Two designs are discussed, for example the 'up-front design' in which all subjects receive an initial exam and then are randomized to the usual care and study groups and the 'close-out design' in which the usual care group receives an exam which is timed to be given at the same time as the last exam in the study group. Both families of designs significantly reduce the power. Power calculations are made for two clinical trials, which actually used these two designs. C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Hu, P (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM ph107y@nih.gov FU NCI NIH HHS [CA-88270] NR 23 TC 1 Z9 1 U1 1 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2004 VL 13 IS 6 BP 491 EP 506 DI 10.1191/0962280204sm379ra PG 16 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 871AU UT WOS:000225102100005 PM 15587435 ER PT J AU Caro, J Zon, LI AF Caro, J Zon, LI TI Allan J. Erslev, MD: Truly a great Dane - (1919-2003) - Memoriam SO STEM CELLS LA English DT Biographical-Item C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Dana Farber Canc Inst, Dept Med, Boston, MA USA. RP Caro, J (reprint author), Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 1 BP 121 EP 122 DI 10.1634/stemcells.22-1-121 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 756TE UT WOS:000187497200014 PM 14688399 ER PT J AU Daheron, L Opitz, SL Zaehres, H Lensch, WM Andrews, PW Itskovitz-Eldor, J Daley, GQ AF Daheron, L Opitz, SL Zaehres, H Lensch, WM Andrews, PW Itskovitz-Eldor, J Daley, GQ TI LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells SO STEM CELLS LA English DT Article DE human embryonic stem cells; leukemia inhibitory factor; STAT3; self-renewal ID HUMAN BLASTOCYSTS; STAT3; ACTIVATION; DIFFERENTIATION; TYROSINE; LINES; PHOSPHORYLATION; INTERLEUKIN-6; POLYPEPTIDES; PLURIPOTENCY AB Murine embryonic stem (mES) cells remain undifferentiated in the presence of leukemia inhibitory factor (LIF), and activation of signal transducer and activator of transcription 3 (STAT3) via LIF receptor (LIFR) signaling appears sufficient for maintenance of mES cell pluripotency. Anecdotal and contradictory accounts exist for the action of LIF in the culture of human embryonic stem cells, and the nature of LIF signaling and whether the LIF-STAT3 pathway is conserved in human embryonic stem cells (hESCs) has not been systematically explored. In this study, we show that the LIFRbeta and the signaling subunit gp130 are expressed in hESCs and that human LIF can induce STAT3 phosphorylation and nuclear translocation in hESCs. Nevertheless, despite the functional activation of the LIF-STAT3 signaling pathway, human LIF is unable to maintain the pluripotent state of hESCs. Feeder-free culture conditions that maintain hESCs in an undifferentiated state do not show activation of STAT3, suggesting that distinct signaling mechanisms govern the self-renewal of hESCs. C1 Harvard Univ, Sch Med, Div Pediat Hematol Oncol, Dept Biol Chem & Mol Pharmacol,Childrens Hosp, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England. Technion Univ, Rambam Med Ctr, Haifa, Israel. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Div Pediat Hematol Oncol, Dept Biol Chem & Mol Pharmacol,Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 30 TC 276 Z9 301 U1 2 U2 23 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 5 BP 770 EP 778 DI 10.1634/stemcells.22-5-770 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 851FE UT WOS:000223670200013 PM 15342941 ER PT J AU Dermott, JM Gooya, JM Asefa, B Weiler, SR Smith, M Keller, JR AF Dermott, JM Gooya, JM Asefa, B Weiler, SR Smith, M Keller, JR TI Inhibition of growth by p205: A nuclear protein and putative tumor suppressor expressed during myeloid cell differentiation SO STEM CELLS LA English DT Article DE IFI-200; tumor suppressor; myeliod; differentiation ID INTERFERON-INDUCIBLE PROTEIN; NIH 3T3 CELLS; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTORS; GENE-200 CLUSTER; DNA-SYNTHESIS; IFI 16; FAMILY; ANTIGEN; LOCALIZATION AB p205 belongs to a family of interferon-inducible proteins called the IFI-200 family, which have been implicated in the regulation of cell growth and differentiation. While p205 is induced in hematopoietic stem cells during myeloid cell differentiation, its function is not known. Therefore, the aim of this study was to determine the role of p205 in regulating proliferation in hematopoietic progenitor cells and in nonhematopoietic cell lines. We found that p205 localizes to the nucleus in hematopoietic and nonhematopoietic cell lines. Transient expression of p205 in murine IL-3-dependent BaF3 and 32D-C123 progenitor cell lines inhibited IL-3-induced growth and proliferation. The closely related IFI-200 family members, p204 and p202, similarly inhibited IL-3-dependent progenitor cell proliferation. p205 also inhibited the proliferation and growth of normal hematopoietic progenitor cells. In nonhematopoietic cell lines, p205 and p204 expression inhibited NIH3T3 cell colony formation in vitro, and microinjection of p205 expression vectors into NIH3T3 fibroblasts inhibited serum-induced proliferation. We have determined the functional domains of p205 necessary for activity, which were identified as the N-terminal domain in apoptosis and interferon response (DAPIN)/PYRIN domain, and the C-terminal retinoblastoma protein (Rb)-binding motif. In addition, we have demonstrated that a putative ataxia telangiectasia, mutated (ATM) kinase phosphorylation site specifically regulates the activity of p205. Taken together, these data suggest that p205 is a potent cell growth regulator whose activity is mediated by its protein-binding domains. We propose that during myelomonocytic cell differentiation, induction of p205 expression contributes to cell growth arrest, thus allowing progenitor cells to differentiate. C1 NCI, Basic Res Program, SAIC Frederick Inc, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Invitrogen Corp, Carlsbad, CA USA. RP Keller, JR (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Canc Res Ctr, Bldg 560,Room 12-03, Frederick, MD 21702 USA. EM kellerj@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 52 TC 13 Z9 15 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 5 BP 832 EP 848 DI 10.1634/stemcells.22-5-832 PG 17 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 851FE UT WOS:000223670200019 PM 15342947 ER PT J AU Kong, KY Ren, JM Kraus, M Finklestein, SP Brown, RH AF Kong, KY Ren, JM Kraus, M Finklestein, SP Brown, RH TI Human umbilical cord blood cells differentiate into muscle in sjl muscular dystrophy mice SO STEM CELLS LA English DT Article ID MARROW-DERIVED CELLS; ADULT BONE-MARROW; MDX MICE; MYOBLAST TRANSFER; STEM-CELLS; MIYOSHI MYOPATHY; SKELETAL-MUSCLE; IN-VIVO; TRANSPLANTATION; FUSION AB Limb girdle muscular dystrophy type 2B form (LGMD-2B) and Miyoshi myopathy (MM) are both caused by mutations in the dysferlin (dysf) gene. In this study, we used dysferlin-deficient sjl mice as a mouse model to study cell therapy for LGMD-2B and MM. A single-blind study evaluated the therapeutic potential of human Umbilical cord blood (HUCB) as a source of myogenic progenitor stern cells. Three groups of donor cells were used: unfractionated mononuclear HUCB cells, HUCB subfractionated to enrich for cells that were negative for lineage surface markers (LIN-) and substantially enriched for the CD34 surface marker (CD34(+)), and irradiated control spleen cells. We administrated 1 x 10(6) donor cells to each animal intravenously and euthanized them at different time points (1-12 weeks) after transplantation. All animals were immunosuppressed (FK506 and leflunomide) from the day before the injection until the time of euthanasia. Immunohistochemical analyses documented that a small number of human cells from the whole HUCB and LIN(-)CD34(+/-)-enriched HUCB subgroups engraft in the recipient muscle to express both dysferlin and human-specific dystrophin at 12 weeks after transplantation. We conclude that myogenic progenitor cells are present in the HUCB, that they can disseminate into muscle after intravenous administration, and that they are capable of myogenic differentiation in host muscle. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromusc Res Lab, Charlestown, MA 02129 USA. ViaCell Inc, Worcester, MA USA. RP Brown, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Neuromusc Res Lab, Bldg 114,Room 3125,16th St, Charlestown, MA 02129 USA. EM rhbrown@partners.org FU FDA HHS [5P01BS40828] NR 41 TC 34 Z9 38 U1 1 U2 4 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 6 BP 981 EP 993 DI 10.1634/stemcells.22-6-981 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 870XX UT WOS:000225093300012 PM 15536189 ER PT J AU Nowakowski, GS Dooner, MS Valinski, HM Mihaliak, AM Quesenberry, PJ Becker, PS AF Nowakowski, GS Dooner, MS Valinski, HM Mihaliak, AM Quesenberry, PJ Becker, PS TI A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells SO STEM CELLS LA English DT Article ID IN-VIVO; PROGENITOR CELLS; ADHESION; RECEPTOR; IDENTIFICATION; VASCULATURE; FIBRONECTIN; EXPRESSION; INTEGRINS; SELECTION AB Phage display peptide libraries have enabled the discovery of peptides that selectively target specific organs. Selection of organ-specific peptides is mediated through binding of peptides displayed on phage coat protein to adhesion molecules expressed within targeted organs. Hematopoietic stem cells selectively home to bone marrow, and certain adhesion receptors critical to this function have been demonstrated. Using a phage display library, we identified a specific peptide that trafficked to murine bone marrow in vivo. We independently isolated exactly the same heptapeptide from the entire library by in vitro biopanning on primitive lineage-depleted, Hoechst 33342(dull)/rhodamine 123(dull) murine bone marrow stem cells and confirmed peptide binding to these cells by immunofluorescence studies. We demonstrated bone marrow-specific homing of the peptide by an in vivo assay in which the animals were injected with the phage displaying peptide sequence, and immunofluorescence analysis of multiple organs was performed. We also showed that the peptide significantly decreased the homing of stem cells to the bone marrow but not to the spleen 3 hours after transplantation using fluorescently labeled Lin(-)Sca(+) hematopoietic cells in an in vivo homing assay. The peptide sequence has a partial (5/7) amino acid sequence homology with a region of CD84. This discovery represents the first application of the phage display methodology to the bone marrow and stem cells and led to the identification of a specific heptapeptide that homes to bone marrow, binds to primitive stem cells, and plays a role in stem cell homing. C1 Univ Washington, Div Hematol, Seattle, WA 98195 USA. Univ Massachusetts, Sch Med, Dept Med, Div Gene Therapy, Worcester, MA USA. Mayo Clin, Div Hematol, Rochester, MN USA. Roger Williams Med Ctr, Dept Res, Providence, RI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Becker, PS (reprint author), Univ Washington, Div Hematol, Box 357710,1959 NE Pacific St,HSB K-136, Seattle, WA 98195 USA. EM pbecker@u.wash-ington.edu FU NCRR NIH HHS [P20 RR018757]; NHLBI NIH HHS [R01 HL63184, P01 HL56920, R01 HL073749]; NIDDK NIH HHS [P01 DK50222, R01 DK27424, R01 DK60084] NR 32 TC 46 Z9 51 U1 2 U2 9 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 6 BP 1030 EP 1038 DI 10.1634/stemcells.22-6-1030 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 870XX UT WOS:000225093300016 PM 15536193 ER PT J AU Sherwood, RI Christensen, JL Weissman, IL Wagers, AJ AF Sherwood, RI Christensen, JL Weissman, IL Wagers, AJ TI Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells SO STEM CELLS LA English DT Article DE adult stem cells; bone marrow; hematopoietic stem cells; muscle stem cells; somatic stem cell transdifferentiation ID SATELLITE CELLS; FUSION; LINEAGE; MICE; REGENERATION; MOBILIZATION; RECRUITMENT; IDENTIFICATION; HEPATOCYTES; PROGENITORS AB To investigate the factors that regulate incorporation into uninjured or damaged skeletal muscle of donor markers derived from unfractionated bone marrow (BM) cells or from highly purified c-kit(+)Thy1.1(lo)Lin-Sca-1(+) hematopoietic stem cells (HSCs), we evaluated myofiber chimerism of multiple muscle groups in irradiated and transplanted recipient mice and in unirradiated parabiotic animals. Uninjured panniculus carnosus, diaphragm, and abdominal muscles infrequently incorporated donor markers into myofibers in a subset of animals after either BM or HSC transplantation; however, acute muscle injury was essential to elicit contributions to triceps surae (TS) and tibialis anterior muscles. The low level of incorporation of donor marker-expressing myofibers could not be enhanced either by transplantation into newborn recipients or by induced migration of HSCs into the periphery. Analysis of muscle chimerism in unirradiated animals joined surgically by parabiosis revealed that contributions of circulating cells to myofibers in the TS were injury dependent and that at least some circulating cells with the potential to contribute to regenerating muscle derive from BM, suggesting that hematoablative preconditioning is not required for such contributions. In all cases tested, donor-derived myofibers expressed both donor-specific and host-specific markers, suggesting that they arise by low-level fusion into skeletal muscle of cells that can include the progeny of HSCs. It is not yet clear whether such events represent a normal myogenic pathway or a pathological response to muscle damage. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu FU NCI NIH HHS [CA86065]; NIAID NIH HHS [5T32AI07290-16] NR 39 TC 61 Z9 64 U1 1 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2004 VL 22 IS 7 BP 1292 EP 1304 DI 10.1634/stemcells.2004-0090 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 879ZY UT WOS:000225759300016 PM 15579647 ER PT S AU Chen, TP Li, E AF Chen, TP Li, E BE Schatten, GP TI Structure and function of eukaryotic DNA methyltransferases SO STEM CELLS IN DEVELOPMENT AND DISEASE SE Current Topics in Developmental Biology LA English DT Review ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; HUMAN CANCER-CELLS; HISTONE H3 METHYLTRANSFERASE; X-CHROMOSOME INACTIVATION; CPG-BINDING-PROTEIN; NON-CG METHYLATION; IN-VIVO; CYTOSINE METHYLTRANSFERASE; ARABIDOPSIS-THALIANA AB DNA methylation is a common epigenetic modification found in eukaryotic organisms ranging from fungi to mammals. Over the past 15 years, a number of eukaryotic DNA methyltransferases have been identified from various model organisms. These enzymes exhibit distinct biochemical properties and biological functions, partly due to their structural differences. The highly variable N-terminal extensions of these enzymes harbor various evolutionarily conserved domains and motifs, some of which have been shown to be involved in functional specializations. DNA methylation has divergent functions in different organisms, consistent with the notion that it is a dynamically evolving mechanism that can be adapted to fulfill various functions. Genetic studies using model organisms have provided evidence suggesting the progressive integration of DNA methylation into eukaryotic developmental programs during evolution. (C) 2004 Elsevier Inc. C1 Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Chen, TP (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 183 TC 153 Z9 166 U1 3 U2 27 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 0-12-153160-0 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2004 VL 60 BP 55 EP 89 PG 35 WC Developmental Biology SC Developmental Biology GA BAJ27 UT WOS:000222499300003 PM 15094296 ER PT J AU Lensch, MW Daley, GQ AF Lensch, MW Daley, GQ TI Origins of mammalian hematopoiesis: In vivo paradigms and in vitro models SO STEM CELLS IN DEVELOPMENT AND DISEASE SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; LEUKEMIA INHIBITORY FACTOR; MURINE YOLK-SAC; ERYTHROID-POTENTIATING ACTIVITY; CHRONIC MYELOGENOUS LEUKEMIA; GONAD-MESONEPHROS REGION; PRIMORDIAL GERM-CELLS; COLONY-FORMING CELLS; MOUSE BONE-MARROW; PROLONGED UNDIFFERENTIATED GROWTH AB Though a topic of medical interest for centuries, our understanding of vertebrate hematopoietic or "blood-forming" tissue development has improved greatly only in recent years and given a series of scientific and technical milestones. Key among these observations was the description of procedures that allowed the transplantation of blood-forming activity. Beyond this, other advances include the creation of a variety of knock-out animals (mice and more recently zebrafish), microdissection of embryonic and fetal blood-forming tissues, hematopoietic stem (HSC) and progenitor cell (HPC) colony-forming assays, the discovery of cytokines with defined hematopoietic activities, gene transfer technologies, and the description of lineage-specific surface antigens for the identification and purification of pluripotent and differentiated blood cells. The availability of both murine and human embryonic stem cells (ESC) and the delineation of in. vitro systems to direct their differentiation have now been added to this analytical arsenal. Such tools have allowed researchers to interrogate the complex developmental processes behind both primitive (yolk sac or extraembryonic) and definitive (intraembryonic) hematopoietic tissue formation. Using ES cells, we hope to not only gain additional basic insights into hematopoietic development but also to develop platforms for therapeutic use in patients suffering from hematological disease. In this review, we will focus on points of convergence and divergence between murine and human hematopoiesis in vivo and in vitro, and use these observations to evaluate the literature regarding attempts to create hematopoietic tissue from embryonic stem cells, the pitfalls encountered therein, and what challenges remain. (C) 2004 Elsevier Inc. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Ctr Biotechnol Proc Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Lensch, MW (reprint author), Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA76418, CA86991]; NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 400 TC 41 Z9 43 U1 0 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2004 VL 60 BP 127 EP 196 PG 70 WC Developmental Biology SC Developmental Biology GA BAJ27 UT WOS:000222499300005 PM 15094298 ER PT J AU Rabinov, JD Brisman, JL Cole, AJ Lee, PL Bussiere, MR Chapman, PH Loeffler, JS Cosgrove, GR Chaves, T Gonzalez, RG AF Rabinov, JD Brisman, JL Cole, AJ Lee, PL Bussiere, MR Chapman, PH Loeffler, JS Cosgrove, GR Chaves, T Gonzalez, RG TI MRI changes in the rat hippocampus following proton radiosurgery SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE radiation injury; animal model; proton radiosurgery; MRI ID GAMMA-KNIFE IRRADIATION; ANIMAL-MODEL; BRAIN; SPECTROSCOPY; RADIATION; LESIONS; SYSTEM; BEAM; EPILEPSY AB Purpose: To define radiographic dose-response relationships for proton radiosurgery using a rat brain model. Methods and Materials: A group of 23 rats was treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray equivalents (CGE) were delivered to groups of 3 animals using single fraction technique. One extra animal was included at the 130- and 30-CGE doses. Animals were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo T-2-weighted coronal images ( TR 3,000 and TE 30/ 90). Animals were imaged at 1.5, 3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to evaluate areas of increased signal on T-2-weighted images, and signal change versus time curves were generated. Gadolinium-enhanced T-1-weighted imaging was also done at the 9-month time point to further evaluate tissue injury. The development of hydrocephalus was also examined. Results: Peak tissue injury was greater and occurred earlier with higher versus lower doses of radiation. Statistically significant differences were seen between the 130- and 90-CGE animals and between the 90- and 60-CGE animals ( p < 0.0016) using ANOVA. Signal changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent an intermediate zone of tissue injury and gliosis compared with greater tissue loss at higher doses and less injury at lower doses. Hydrocephalus developed first in the untreated hemisphere in 130- and 90- CGE animals as a result of mass effect while it occurred at a later time in the treated hemisphere in lower-dose animals. Conclusions: Following single-dose proton radiosurgery of rat hippocampus, serial MRIs show T-2 signal changes in animals ranging from 130 down to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships using proton radiosurgery in rats will be a helpful step in guiding further studies on radiation injury to brain tissue. Copyright (C) 2004 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol Harvard Cyclotron, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol Clin 363, 55 Fruit St, Boston, MA 02114 USA. EM jrabinov@partners.org NR 24 TC 6 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2004 VL 82 IS 4 BP 156 EP 164 DI 10.1159/000081639 PG 9 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 883XA UT WOS:000226047800005 PM 15499227 ER PT S AU Busuttil, RA Dolle, M Campisi, J Vijg, J AF Busuttil, RA Dolle, M Campisi, J Vijg, J BE DeGrey, ADN TI Genomic instability, aging, and cellular senescence SO STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th Congress of the International-Association-of-Biomedical-Gerontology CY SEP 19-23, 2003 CL Cambridge, ENGLAND SP Int Assoc Biomed Gerontol DE aging; cancer; oxidative damage; DNA damage; genomic integrity ID DIPLOID FIBROBLAST CELLS; TRANSGENIC MOUSE MODEL; REPLICATIVE LIFE-SPAN; OXIDATIVE DNA-DAMAGE; IN-VIVO MUTATIONS; SOMATIC MUTATIONS; CHROMOSOME-ABERRATIONS; OXYGEN; AGE; MICE AB Aging can be defined in practical terms as a series of time-related processes that ultimately bring life to a close. Genomic instability has been implicated as a major causal factor in aging. Here, we describe the use of a transgenic mouse model, harboring lacZ reporter genes as part of a plasmid construct integrated at one or more chromosomal locations, to study genomic instability during aging of different mouse organs and tissues as well as in mouse embryonic flbroblasts during primary culture. C1 Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. Buck Inst Age Res, Novato, CA 94945 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. EM vijg@uthscsa.edu NR 37 TC 28 Z9 31 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-496-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1019 BP 245 EP 255 DI 10.1196/annals.1297.041 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BAN77 UT WOS:000223002700041 PM 15247023 ER PT S AU Kishi, S AF Kishi, S BE DeGrey, ADN TI Functional aging and gradual senescence in zebrafish SO STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 10th Congress of the International-Association-of-Biomedical-Gerontology CY SEP 19-23, 2003 CL Cambridge, ENGLAND SP Int Assoc Biomed Gerontol DE zebrafish; aging; senescence; stress; indeterminate growth; telomerase; telomere ID AGE; FISHES AB Zebrafish (Danio rerio) has been recognized as a powerful model for genetic studies in developmental biology. Recently, the zebrafish system also has given insights into several human diseases such as neurodegenerative, hematopoietic, and cardiovascular disease, and cancer. Because aging processes affect these and various other human disorders, it is important to compare zebrafish and mammalian senescence. However, the aging process of zebrafish remains largely unexplored, and little is known about functional aging and senescence in zebrafish. In our initial studies to assess aging phenotypes in zebrafish, we have identified several potential aging biomarkers in an ongoing search for suitable ones on zebrafish aging. In aging zebrafish, we detected senescence-associated beta-galactosidase activity in skin and oxidized protein accumulation in muscle. On the other hand, we did not observe lipofuscin granules (aging pigments), which accumulate in postmitotic cells, in muscle of zebrafish with advancing age. Consistently, there were continuously proliferating myocytes that incorporated BrdU in muscle tissues of the aged fish. Moreover, we demonstrated that zebrafish have constitutively abundant telomerase activity in adult somatic tissues implicating unlimited replicative ability of cells throughout their lives. Although some stress-associated markers are upregulated and minor histological changes are observed during the aging process of zebrafish, our studies together with other evidence of remarkable reproductive and regenerative abilities suggest that zebrafish show very gradual senescence. By using those biological and biochemical aging markers already characterized in normal zebrafish, transgenic fish analyses and genetic mutant fish screens can be readily performed. These efforts will help to elucidate the role and molecular mechanisms of common or different pathways of aging among vertebrates from fish to humans and also will contribute to the discovery of potential drugs applicable to age-associated diseases in the future. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kishi, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM shuji_kishi@dfci.harvard.edu NR 33 TC 48 Z9 49 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-496-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1019 BP 521 EP 526 DI 10.1196/annals.1297.097 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BAN77 UT WOS:000223002700097 PM 15247079 ER PT J AU Kelly, PJ Kistler, JP Shih, VE Mandell, R Atassi, N Barron, M Lee, H Silveira, S Furie, KL AF Kelly, PJ Kistler, JP Shih, VE Mandell, R Atassi, N Barron, M Lee, H Silveira, S Furie, KL TI Inflammation, homocysteine, and vitamin B6 status after ischemic stroke SO STROKE LA English DT Article DE homocyst(e)ine; inflammation; nutrition; pyridoxine; stroke ID C-REACTIVE PROTEIN; PLASMA HOMOCYSTEINE; RISK; DISEASE; ACID; HOMOCYST(E)INE; ASSOCIATION; METABOLISM; ATTACK; FOLATE AB Background and Purpose - Epidemiological studies have described an association between low vitamin B6 ( measured as pyridoxal 5'-phosphate [PLP]) and ischemic stroke, independent of homocysteine (tHcy). We investigated B6 status, tHcy, and inflammation ( measured by C-reactive protein [CRP]) in patients with stroke and controls. Methods - Consecutive cases with new ischemic stroke were compared with matched controls. Fasting tHcy, PLP, and CRP were measured. Results - The adjusted odds ratio of low PLP in the highest compared with the lowest CRP quartile was 16.6 (2, 139.9, P = 0.01). Age, CRP, supplemental vitamin use, and albumin were independent predictors of PLP ( P < 0.05 for all). No relationship was observed between CRP and tHcy. Conclusion - The relationship between inflammation and low B6 status may partially explain the findings of previous epidemiological studies. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Amino Acid Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK 802,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066] NR 15 TC 46 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 12 EP 15 DI 10.1161/01.STR.0000106481.59944.2F PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500003 PM 14657454 ER PT J AU Cramer, SC Rordorf, G Maki, JH Kramer, LA Grotta, JC Burgin, WS Hinchey, JA Benesch, C Furie, KL Lutsep, HL Kelly, E Longstreth, WT AF Cramer, SC Rordorf, G Maki, JH Kramer, LA Grotta, JC Burgin, WS Hinchey, JA Benesch, C Furie, KL Lutsep, HL Kelly, E Longstreth, WT TI Increased pelvic vein thrombi in cryptogenic stroke - Results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study SO STROKE LA English DT Article DE deep vein thrombosis; embolism, paradoxical; etiology; pathophysiology ID PATENT FORAMEN OVALE; DEEP VENOUS THROMBOSIS; CONTRAST VENOGRAPHY; PULMONARY-EMBOLISM; ULTRASONOGRAPHY; DIAGNOSIS; THROMBOEMBOLISM; ANGIOGRAPHY; FREQUENCY AB Background and Purpose - Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke ( PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT). Methods - At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans. Results - The 95 patients who met entry criteria were scanned. Their mean +/- SD age was 46 +/- 10 years, and time from stroke onset to pelvic MRV scan was 49 +/- 16 hours. Compared with those with stroke of determined origin (n = 49), patients with cryptogenic stroke ( n = 46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P < 0.03), with most having an appearance of a chronic DVT. Conclusions - In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke. C1 Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, Houston, TX USA. Univ Rochester, Rochester, NY USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Cramer, SC (reprint author), Univ Calif Irvine, Dept Neurol, UCI Med Ctr, 101 City Dr S,Bldg 53,Room 203, Orange, CA 92868 USA. NR 38 TC 108 Z9 117 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 46 EP 50 DI 10.1161/01.STR.0000106137.42649.AB PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500010 PM 14657451 ER PT J AU Huang, ZH Moskowitz, MA Jin, HW Rikitake, Y Liao, JK AF Huang, ZH Moskowitz, MA Jin, HW Rikitake, Y Liao, JK TI Inhibition of Rho-kinase leads to decreased cerebral infarct size after focal ischemia by eNOS-dependent mechanism SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 238 EP 238 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500068 ER PT J AU Wang, HH Menezes, NM Zhu, MW Vangel, MG Lopez, CJ Ay, H Koroshetz, WJ Aronen, HJ Karonen, JO Liu, YW Nuutinen, J Sorensen, AG AF Wang, HH Menezes, NM Zhu, MW Vangel, MG Lopez, CJ Ay, H Koroshetz, WJ Aronen, HJ Karonen, JO Liu, YW Nuutinen, J Sorensen, AG TI Variance in perfusion-weighted MRI: An indicator of tissue response to ischemia? SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 MIT, Dept Phys, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, HST Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Kuopio Univ Hosp, Dept Radiol, SF-70210 Kuopio, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 248 EP 248 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500117 ER PT J AU Bruno, A McConnell, JP Cohen, SN Tietjen, GE Wallis, RA Gorelick, PB Bang, NU AF Bruno, A McConnell, JP Cohen, SN Tietjen, GE Wallis, RA Gorelick, PB Bang, NU TI Serial urinary 11-dehydrothromboxane B2 measurements in African Americans after cerebral infarction: Correlation with aspirin dose and vascular events SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Mayo Clin, Rochester, MN USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 257 EP 257 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500162 ER PT J AU Howard, G Hobson, RW Brott, TG Cohen, SN Howard, VJ Petrossian, G Levy, D Mishkel, G Barnwell, SL AF Howard, G Hobson, RW Brott, TG Cohen, SN Howard, VJ Petrossian, G Levy, D Mishkel, G Barnwell, SL CA CREST Investigators TI Does the stroke risk of stenting increase at older ages? Thirty-day stroke-death rates in the CREST lead-in phase SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. St Francis Hosp, Port Washington, NY USA. Kaiser Permanente Med Ctr, San Diego, CA USA. St Johns Hosp, Springfield, IL USA. Mem Med Ctr, Springfield, IL 62781 USA. Oregon Hlth Sci Univ, Portland, OR USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 258 EP 258 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500169 ER PT J AU Menezes, NM Ay, H Lopez, CJ Vangel, MG Zhu, MW Oner, B Singhal, AB Koroshetz, WJ Aronen, HJ Karonen, JO Liu, YW Nuutinen, JH Sorensen, AG AF Menezes, NM Ay, H Lopez, CJ Vangel, MG Zhu, MW Oner, B Singhal, AB Koroshetz, WJ Aronen, HJ Karonen, JO Liu, YW Nuutinen, JH Sorensen, AG TI Atlas-based MRI assessment of cerebral infarct predicts clinical outcome SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, HST Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Kuopio Univ Hosp, Dept Radiol, SF-70210 Kuopio, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 259 EP 259 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500174 ER PT J AU Lorenz, C Benner, T Menezes, NM Chen, PJ Lopez, CJ Koroshetz, W Nuutinen, J Aronen, HJ Karonen, JO Liu, YW Sorensen, AG AF Lorenz, C Benner, T Menezes, NM Chen, PJ Lopez, CJ Koroshetz, W Nuutinen, J Aronen, HJ Karonen, JO Liu, YW Sorensen, AG TI Automated perfusion-weighted imaging MRI metrics using localized arterial input functions SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, HST Martinos Ctr Biomed Imaging, Charlestown, MA USA. Kuopio Univ Hosp, SF-70210 Kuopio, Finland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 261 EP 261 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500186 ER PT J AU Zhu, MW Ay, H Lopez, CJ Martino, AA Aronen, H Karonen, J Liu, YW Nuutinen, J Singhal, AB Koroshetz, WJ Sorensen, AG AF Zhu, MW Ay, H Lopez, CJ Martino, AA Aronen, H Karonen, J Liu, YW Nuutinen, J Singhal, AB Koroshetz, WJ Sorensen, AG TI Is there potentially salvageable tissue in regions with low cerebral blood volume? SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Ctr Biomed Imaging, Charlestown, MA USA. Helsinki Cent Univ Hosp, Helsinki, Finland. Kuopio Univ Hosp, SF-70210 Kuopio, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 264 EP 264 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500199 ER PT J AU Romero, JM Lev, MH Chau, AS Dwyer-McNally, C Endale, B Li, CD Gonzalez, RG AF Romero, JM Lev, MH Chau, AS Dwyer-McNally, C Endale, B Li, CD Gonzalez, RG TI Does signal dropout on two-dimensional time of flight magnetic resonance angiography represent a "critical" stenosis of the internal carotid arteries? Reassessment of the technique based on the different echo time values SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 265 EP 265 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500203 ER PT J AU Ay, H Koroshetz, WJ Benner, T Vangel, M Oner, B Schwamm, LH Sorensen, G AF Ay, H Koroshetz, WJ Benner, T Vangel, M Oner, B Schwamm, LH Sorensen, G TI Footprints of transient ischemic attacks: How small are they? Volumetric analysis of TIA-related infarctions SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 267 EP 267 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500211 ER PT J AU Furie, KL Singhal, AB McCarthy, CJ Ay, H Perlov, D Lev, MH Harris, GJ Smith, WS Koroshetz, WJ AF Furie, KL Singhal, AB McCarthy, CJ Ay, H Perlov, D Lev, MH Harris, GJ Smith, WS Koroshetz, WJ TI STOPStroke study: Utility of early contrast computed tomography in assessing stroke mechanism SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 269 EP 269 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500224 ER PT J AU Roccatagliata, L Lev, MH Venkatesan, A Murphy, EK Koroshetz, WJ Schwamm, L Schaefer, PW Gonzalez, GR AF Roccatagliata, L Lev, MH Venkatesan, A Murphy, EK Koroshetz, WJ Schwamm, L Schaefer, PW Gonzalez, GR TI CTA source images in hyperacute stroke correlate with CT-CBV and MR-DWI but not CT-CBF SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 269 EP 269 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500221 ER PT J AU Wu, O Sumii, T Asahi, M Sasamata, M Sorensen, AG Ostergaard, L Rosen, BR Lo, EH Dijkhuizen, RM AF Wu, O Sumii, T Asahi, M Sasamata, M Sorensen, AG Ostergaard, L Rosen, BR Lo, EH Dijkhuizen, RM TI Predicting histological outcome using combined acute DWI and PWI in a rat embolic stroke model with delayed rtPA treatment. SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Image Sci Inst, Utrecht, Netherlands. Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Tsukuba, Ibaraki, Japan. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. CFIn, Dept Neuroradiol, Aarhus, Denmark. RI Dijkhuizen, Richard/A-6506-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 274 EP 275 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500251 ER PT J AU Atochin, DN Ayata, C Salomone, S Noda, F Moskowitz, MA Huang, PL AF Atochin, DN Ayata, C Salomone, S Noda, F Moskowitz, MA Huang, PL TI Abnormal vascular responses and cerebral reperfusion injury in ApoE-deficient mice on Western diet. SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. RI Atochin, Dmitriy/Q-3150-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 279 EP 279 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500271 ER PT J AU Singhal, AB Benner, T Roccatagllata, L Schaefer, PW Koroshetz, WJ Buonanno, FS Lo, EH Gonzalez, RG Sorensen, AG AF Singhal, AB Benner, T Roccatagllata, L Schaefer, PW Koroshetz, WJ Buonanno, FS Lo, EH Gonzalez, RG Sorensen, AG TI Normobaric Hyperoxia therapy in hyperacute human stroke: Attenuation of DWI abnormalities and improved NIHSS scores SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 293 EP 294 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500345 ER PT J AU Sims, JR Rordorf, G Koroshetz, WJ Lev, MH Buonanno, F Schwamm, LH AF Sims, JR Rordorf, G Koroshetz, WJ Lev, MH Buonanno, F Schwamm, LH TI Early CT angiogram predicts stroke score and acute thrombolytic outcomes SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 297 EP 298 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500365 ER PT J AU Ning, MM Lo, EH Furie, KL Koroshetz, WJ Wang, XY Stevenson, E Sleeper, L Kelly, PJ AF Ning, MM Lo, EH Furie, KL Koroshetz, WJ Wang, XY Stevenson, E Sleeper, L Kelly, PJ TI t-PA-mediated increase in matrix metalloproteinase-9 in acute ischemic stroke is independent of inflammatory response SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 298 EP 298 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500369 ER PT J AU Saam, T Ferguson, MS Yarnykh, VL Hatsukami, TS Yuan, C AF Saam, T Ferguson, MS Yarnykh, VL Hatsukami, TS Yuan, C TI Carotid atherosclerotic plaque composition has a direct impact on plaque burden and lumen narrowing SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RI Yarnykh, Vasily/G-8757-2016; Yarnykh, Vasiliy/N-7635-2014 OI Yarnykh, Vasily/0000-0002-1583-8979; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 307 EP 307 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500414 ER PT J AU Seshadri, S Beiser, A Vasan, RS DeCarli, C Wang, TJ Au, R Larson, MG Levy, D Wolf, PA AF Seshadri, S Beiser, A Vasan, RS DeCarli, C Wang, TJ Au, R Larson, MG Levy, D Wolf, PA TI Association of plasma atrial and B-type natriuretic peptides with silent cerebral infarcts and white matter hyperintensity on brain magnetic resonance imaging. SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RI DeCarli, Charles/B-5541-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 314 EP 314 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500451 ER PT J AU Nogueira, RG Topcuoglu, MA Koroshetz, WJ Betensky, RA Bodock, MJ O'Donnell, J Buckley, DA Amin-Hanjani, S Carter, BS Ogilvy, CS Buonanno, FS AF Nogueira, RG Topcuoglu, MA Koroshetz, WJ Betensky, RA Bodock, MJ O'Donnell, J Buckley, DA Amin-Hanjani, S Carter, BS Ogilvy, CS Buonanno, FS TI High-dose bosentan in the prevention and treatment of subarachnoid hemorrhage-induced cerebral vasospasm: An open-label pilot study SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 332 EP 333 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500547 ER EF