FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Spiegelman, BM AF Spiegelman, BM TI Regulation of adipogenesis and energy expenditure through PPAR gamma and its coactivators SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 1433 BP 262A EP 262A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501430 ER PT J AU Lin, HJ de Carvalho, PS Kho, D Tai, CY Pellman, D AF Lin, HJ de Carvalho, PS Kho, D Tai, CY Pellman, D TI Requirement for Bik1p in kinetochore-microtubule attachment and for the viability of polyploid cells SO MOLECULAR BIOLOGY OF THE CELL 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 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 NOV PY 2001 VL 12 SU S MA 1742 BP 317A EP 317A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501738 ER PT J AU Criss, AK Silva, M McCormick, BA Casanova, JE AF Criss, AK Silva, M McCormick, BA Casanova, JE TI Regulation of Salmonella-induced neutrophil transmigration by activation of epithelial ARF6 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 1800 BP 328A EP 328A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501796 ER PT J AU Goldmann, WH Teodoridis, JM Hu, B Isenberg, G AF Goldmann, WH Teodoridis, JM Hu, B Isenberg, G TI Actin-related-protein (Arp2) inserts info reconstituted lipid layers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich, D-8000 Munich, Germany. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 1831 BP 333A EP 333A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501827 ER PT J AU Kegel, KB Meloni, AR Yi, Y Aronin, N DiFiglia, M AF Kegel, KB Meloni, AR Yi, Y Aronin, N DiFiglia, M TI Huntingtin interacts with the corepressor C-terminal binding protein and mutant huntingtin represses transcription SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Massachusetts, Med Ctr, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 1946 BP 354A EP 355A PG 2 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501942 ER PT J AU Campbell, KP Cohn, RD Henry, MD Barresi, R Saito, F Moore, SA Kahn, CR Williamson, R AF Campbell, KP Cohn, RD Henry, MD Barresi, R Saito, F Moore, SA Kahn, CR Williamson, R TI Tissue-specific disruption of dystroglycan: Insights into muscular dystrophy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. Univ Iowa, Howard Hughes Med Inst, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 NOV PY 2001 VL 12 SU S MA 2200 BP 400A EP 400A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372502196 ER PT J AU Guo, L Zhang, ZQ Green, K Lovewell, G Stanton, R AF Guo, L Zhang, ZQ Green, K Lovewell, G Stanton, R TI Suppression of IL1-beta-induced NO production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 2309 BP 419A EP 419A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372502304 ER PT J AU James, MF Beauchamp, RL Kazlauskas, A Ramesh, V AF James, MF Beauchamp, RL Kazlauskas, A Ramesh, V TI Functional significance of the MERM-interacting protein, Na+/H+ exchanger regulatory cofactor, in PDGF receptor initiated actin cytoskeletal signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2001 VL 12 SU S MA 2481 BP 450A EP 450A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372502476 ER PT J AU Yin, L Ohno, T Weichselbaum, R Kharbanda, S Kufe, D AF Yin, L Ohno, T Weichselbaum, R Kharbanda, S Kufe, D TI The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1H-2benzopyran-3-yl) propionic acid (NM-3) induces lethality of human carcinoma cells by generation of reactive oxygen species SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; P53; CYTOGENIN AB 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an isocoumarin derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low ten concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM-3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G(1)-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species-dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Microbiol, Tokyo 1058461, Japan. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60614 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802] NR 16 TC 14 Z9 16 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2001 VL 1 IS 1 BP 43 EP 48 PG 6 WC Oncology SC Oncology GA 606LW UT WOS:000178736300006 PM 12467237 ER PT J AU Puigserver, P Rhee, J Lin, JD Wu, ZD Yoon, JC Zhang, CY Krauss, S Mootha, VK Lowell, BB Spiegelman, BM AF Puigserver, P Rhee, J Lin, JD Wu, ZD Yoon, JC Zhang, CY Krauss, S Mootha, VK Lowell, BB Spiegelman, BM TI Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPAR gamma coactivator-1 SO MOLECULAR CELL LA English DT Article ID NF-KAPPA-B; INDUCED PHOSPHORYLATION; SIGNAL-TRANSDUCTION; SKELETAL-MUSCLE; RECEPTOR-GAMMA; CACHEXIA; EXPRESSION; CANCER; MDM2 AB Cachexia is a chronic state of negative energy balance and muscle wasting that is a severe complication of cancer and chronic infection. While cytokines such as IL-1 alpha, IL-1 beta, and TNF alpha can mediate cachectic states, how these molecules affect energy expenditure is unknown. We show here that many cytokines activate the transcriptional PPAR gamma coactivator-1 (PGC-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of PGC-1 protein. Cytokine or lipopolysaccharide (LPS)-induced activation of PGC-1 in cultured muscle cells or muscle in vivo causes increased respiration and expression of genes linked to mitochondrial uncoupling and energy expenditure. These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK54477] NR 39 TC 405 Z9 426 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2001 VL 8 IS 5 BP 971 EP 982 DI 10.1016/S1097-2765(01)00390-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494YA UT WOS:000172312400007 PM 11741533 ER PT J AU Alrutz, MA Srivastava, A Wong, KW D'Souza-Schorey, C Tang, M Ch'ng, LE Snapper, SB Isberg, RR AF Alrutz, MA Srivastava, A Wong, KW D'Souza-Schorey, C Tang, M Ch'ng, LE Snapper, SB Isberg, RR TI Efficient uptake of Yersinia pseudotuberculosis via integrin receptors involves a Rac1-Arp 2/3 pathway that bypasses N-WASP function SO MOLECULAR MICROBIOLOGY LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; FILAMENT BARBED ENDS; ACTIN-BASED MOTILITY; ARP2/3 COMPLEX; EPITHELIAL-CELLS; SYNDROME PROTEIN; NUCLEAR RESPONSES; INVASIN PROTEIN; MAMMALIAN-CELLS; MEDIATED UPTAKE AB Efficient uptake of Yersinia pseudotuberculosis into cultured mammalian cells is the result of high-affinity binding of invasin to beta (1) chain integrins. We demonstrate here that uptake requires Rac1 and Arp 2/3 function. Bacterial uptake was stimulated by GTP gammaS, but was inhibited in mammalian cells transfected with the interfering Rac1-N17 derivative. Rac1 was found to be activated in response to integrin engagement by invasin, whereas Rac1 and Arp 2/3 were found to be intensely localized around phagosomes bearing bacteria, indicating a specific role for Rac1 signalling from the nascent phagosome to downstream effectors. To determine whether the Arp 2/3 complex was a component of this proposed pathway, cells overproducing various derivatives of Scar1/WAVE1, an Arp 2/3-binding protein, were analysed. Sequestration of Arp 2/3 away from the phagocytic cup as a result of Scar1/WAVE1 overproduction dramatically inhibited uptake. To determine whether signalling from Rac1 to Arp 2/3 occurred via N-WASP, uptake was analysed in a cell line lacking expression of WASP and N-WASP. Uptake was unaffected by the absence of these proteins, indicating that beta (1) integrin signalling from Rac1 to Arp 2/3 can occur in the absence of N-WASP function. C1 Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Howard Hughes Med Inst, Boston, MA 02111 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Isberg, RR (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, 136 Harrison Ave M&V 409, Boston, MA 02111 USA. FU NHLBI NIH HHS [HL59561, HL03749]; NIAID NIH HHS [R01-AI23538, 5T32 AI107422]; NIDDK NIH HHS [P30DK34928] NR 43 TC 71 Z9 72 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2001 VL 42 IS 3 BP 689 EP 703 DI 10.1046/j.1365-2958.2001.02676.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 495LB UT WOS:000172341700009 PM 11722735 ER PT J AU Salehi-Ashtiani, K Szostak, JW AF Salehi-Ashtiani, K Szostak, JW TI In vitro evolution suggests multiple origins for the hammerhead ribozyme SO NATURE LA English DT Article ID HEPATITIS-DELTA-VIRUS; RNA; TRANSCRIPTS AB The hammerhead ribozyme was originally discovered in a group of RNAs associated with plant viruses, and has subsequently been identified in the genome of the newt (Notophthalamus viridescens)(1,2), in schistosomes(3) and in cave crickets (Dolichopoda species)(4). The sporadic occurrence of this self-cleaving RNA motif in highly divergent organisms could be a consequence of the very early evolution of the hammerhead ribozyme(4,5), with all extant examples being descended from a single ancestral progenitor. Alternatively, the hammerhead ribozyme may have evolved independently many times. To better understand the observed distribution of hammerhead ribozymes, we used in vitro selection to search an unbiased sample of random sequences for comparably active self-cleaving motifs. Here we show that, under near-physiological conditions, the hammerhead ribozyme motif is the most common (and thus the simplest) RNA structure capable of self-cleavage at biologically observed rates. Our results suggest that the evolutionary process may have been channelled, in nature as in the laboratory, towards repeated selection of the simplest solution to a biochemical problem. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 NR 16 TC 110 Z9 115 U1 0 U2 9 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 01 PY 2001 VL 414 IS 6859 BP 82 EP 84 DI 10.1038/35102081 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487VC UT WOS:000171898900046 PM 11689947 ER PT J AU de Jong, YP Abadia-Molina, AC Satoskar, AR Clarke, K Rietdijk, ST Faubion, WA Mizoguchi, E Metz, CN Al Sahli, M ten Hove, T Keates, AC Lubetsky, JB Farrell, RJ Michetti, P van Deventer, SJ Lolis, E David, JR Bhan, AK Terhorst, C AF de Jong, YP Abadia-Molina, AC Satoskar, AR Clarke, K Rietdijk, ST Faubion, WA Mizoguchi, E Metz, CN Al Sahli, M ten Hove, T Keates, AC Lubetsky, JB Farrell, RJ Michetti, P van Deventer, SJ Lolis, E David, JR Bhan, AK Terhorst, C TI Development of chronic colitis is dependent on the cytokine MIF SO NATURE IMMUNOLOGY LA English DT Article ID MIGRATION-INHIBITORY FACTOR; INFLAMMATORY BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; CROHNS-DISEASE; IN-VIVO; MACROPHAGE; MICE; CD45RB(HIGH); ACTIVATION AB The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease. C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Picower Inst Med Res, Manhasset, NY 11030 USA. Univ Amsterdam, Acad Med Ctr, Expt Med Lab, NL-1105 AZ Amsterdam, Netherlands. Yale Univ, Dept Pharmacol, New Haven, CT 06510 USA. RP Terhorst, C (reprint author), Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. FU NIAID NIH HHS [AI25532]; NIDDK NIH HHS [DK43351, DK47677, DK52510] NR 32 TC 215 Z9 217 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2001 VL 2 IS 11 BP 1061 EP 1066 DI 10.1038/ni720 PG 6 WC Immunology SC Immunology GA 490JY UT WOS:000172049800020 PM 11668338 ER PT J AU Tilly, JL AF Tilly, JL TI Commuting the death sentence: How oocytes strive to survive SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PROGRAMMED CELL-DEATH; ARYL-HYDROCARBON RECEPTOR; EMBRYO IMPLANTATION RATE; IN-VITRO FERTILIZATION; CURRENT PERSPECTIVES; FOLLICULAR ATRESIA; CIGARETTE-SMOKING; OVARIAN TOXICITY; IMMUNE-SYSTEM; ADVANCED AGE AB Programmed cell death claims up to 99.9% of the cells in the mammalian female germ line, which eventually drives irreversible infertility and ovarian failure - the menopause in humans. New insights into the mechanisms that underlie germ-cell apoptosis have been provided by the study of oocyte death in lower organisms and in genetically manipulated mice that lack apoptosis-regulatory proteins. With new therapeutic tools to control fertility, oocyte quality and ovarian lifespan on the horizon, understanding how and why the female body creates, only to delete, so many germ cells is imperative. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 103 TC 209 Z9 217 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2001 VL 2 IS 11 BP 838 EP 848 DI 10.1038/35099086 PG 11 WC Cell Biology SC Cell Biology GA 489RJ UT WOS:000172005200021 PM 11715050 ER PT J AU Nilsson, LNG Das, S Potter, H AF Nilsson, LNG Das, S Potter, H TI Effect of cytokines, dexamethazone and the A/T-signal peptide polymorphism on the expression of alpha(1)-antichymotrypsin in astrocytes: significance for Alzheimer's disease SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE alpha-1-antichymotrypsin; interleukin-1; interleukin-6; transforming growth factor beta-1; glucocorticoid; inflammation polymorphism; Alzheimer's disease ID ACUTE-PHASE RESPONSE; PROTEASE INHIBITOR ALPHA-1-ANTICHYMOTRYPSIN; HEPATOCYTE-STIMULATING FACTORS; AMYLOID-P-COMPONENT; APOLIPOPROTEIN-E; TRANSGENIC MICE; BETA-PROTEIN; CEREBROSPINAL-FLUID; PLASMA-PROTEINS; MESSENGER-RNA AB Proinflammatory cytokines and acute phase proteins, such as alpha (1)-antichymotrypsin. are over expressed in microglia and astrocytes in brain regions with abundant mature amyloid plaques, suggesting a glial cell-led brain acute phase response in the Alzheimer neuropathology. In this paper, we show that alpha (1)-antichymotrypsin gene expression in human astrocytes is elevated by interleukin-1 and interleukin-6, and further enhanced by glucocorticoid, while the homologous contrapsin gene in rat astrocytes is unaffected by these cytokines. These distinct gene regulation mechanisms might help to explain the differential susceptibility of humans and rodents to amyloid formation of the Alzheimer's type. In addition, we demonstrate that the alpha (1)-antichymotrypsin A-allele that encodes a different signal peptide and is a suggested risk factor for Alzheimer's disease gives rise to a reduced level of immature alpha (1)-antichymotrypsin in transfected cells. The physiological result would be an enhanced ability of the A-encoded alpha (1)-antichymotrypsin protein to become secreted and promote extracellular amyloid formation. We discuss our findings in terms of a model in which cytokine-induced alpha (1)-antichymotrypsin synthesis in astrocytes constitutes a specific inflammatory pathway that accelerates the development of Alzheimer's disease and could at least partly underlie the regional specificity and species restriction of the neuropathology. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Suncoast Gerontol Ctr, Tampa, FL 33612 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02143 USA. RP Nilsson, LNG (reprint author), Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Suncoast Gerontol Ctr, MDC07,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. FU NIA NIH HHS [AG09665] NR 71 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV-DEC PY 2001 VL 39 IS 5-6 BP 361 EP 370 DI 10.1016/S0197-0186(01)00043-2 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 490LE UT WOS:000172052700005 PM 11578771 ER PT J AU Peskind, ER Griffin, WST Akama, KT Raskind, MA Van Eldik, LJ AF Peskind, ER Griffin, WST Akama, KT Raskind, MA Van Eldik, LJ TI Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer's disease SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE cerebrospinal fluid S100B; elevated; earlier stages; Alzheimer's disease ID AMYLOID PRECURSOR PROTEIN; FIBRILLARY ACIDIC PROTEIN; NEURON-SPECIFIC ENOLASE; S-100 PROTEIN; TRANSGENIC MICE; DOWNS-SYNDROME; COGNITIVE STATE; S100-BETA; OVEREXPRESSION; ASTROCYTES AB Postmortem demonstration of increased expression of biologically active S100B in Alzheimer's disease (AD) and its relation to progression of neuropathological changes across the cortical regions suggests involvement of this astrocytic cytokine in the pathophysiology of AD. The hypothesis that the overexpression of S100B in Alzheimer brain is related to the progression of clinical symptoms was addressed in living persons by measuring S100B concentrations in cerebrospinal fluid (CSF) from AD patients with a broad range of clinical dementia severity and from healthy older persons. The effect of normal aging on CSF S100B concentrations also was estimated. CSF S100B did not differ between all 68 AD subjects (0.98 +/- 0.09 ng/ml (mean +/- S.E.M.)) and 25 healthy older subjects (0.81 +/- 0.13 ng/ml). When AD subjects were divided into mild/moderate stage and advanced stage clinical dementia severity by the established Clinical Dementia Rating Scale (CDR) criteria, S100B was significantly higher in the 46 mild/moderate stage AD subjects (1.17 +/-0.11 ng/ml) than in either the 22 advanced stage AD subjects (0.60 +/- 0.12 ng/ml) or the healthy older subjects. Consistent with higher CSF S100B in mild to moderate AD, there was a significant correlation among all AD subjects between CSF S100B and cognitive status as measured by the Mini Mental State Exam (MMSE) score. CSF S100B did not differ between healthy older subjects and healthy young subjects. These results suggest increased CNS expression of S100B in the earlier stages of AD, and are consistent with a role for S100B in the initiation and/or facilitation of neuritic plaque formation in AD brain. (C) 2001 Published by Elsevier Science Ltd. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. VA Med Ctr, Ctr Geriatr Res Educ & Clin, Little Rock, AR 72205 USA. Northwestern Univ, Sch Med, Inst Neurosci, Dept Mol & Cell Biol, Chicago, IL 60611 USA. NW Drug Doscovery Program, Chicago, IL 60611 USA. RP Peskind, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, 116MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, AG08419, AG12411, AG13939, AG15501]; NIGMS NIH HHS [GM08061] NR 40 TC 99 Z9 101 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV-DEC PY 2001 VL 39 IS 5-6 BP 409 EP 413 DI 10.1016/S0197-0186(01)00048-1 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 490LE UT WOS:000172052700010 PM 11578776 ER PT J AU Hersch, SM Rosas, HD AF Hersch, SM Rosas, HD TI The 10 most commonly asked questions about Huntington's disease SO NEUROLOGIST LA English DT Article C1 Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 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 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2001 VL 7 IS 6 BP 364 EP 368 DI 10.1097/00127893-200111000-00006 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 499QT UT WOS:000172582400006 PM 14649632 ER PT J AU Lee, SH Valtschanoff, JG Kharazia, VN Weinberg, R Sheng, M AF Lee, SH Valtschanoff, JG Kharazia, VN Weinberg, R Sheng, M TI Biochemical and morphological characterization of an intracellular membrane compartment containing AMPA receptors SO NEUROPHARMACOLOGY LA English DT Article DE glutamate receptors; GluR2/3; NMDA receptors; postsynaptic density; PSD-95; GRIP; syntaxin-13; recycling endosomes ID TUBULOVESICULAR RECYCLING ENDOSOMES; DOMAIN-CONTAINING PROTEINS; BRAIN MYOSIN-V; GLUTAMATE RECEPTORS; NMDA RECEPTORS; SYNAPTIC TRANSMISSION; POSTSYNAPTIC DENSITY; HIPPOCAMPAL-NEURONS; COMPLEX; PLASTICITY AB AMPA receptors cycle rapidly in and out of the postsynaptic membrane, while NMDA receptors are relatively immobile. Changing the distribution of AMPA receptors between intracellular and surface synaptic pools is an important means of controlling synaptic strength. However, little is known about the intracellular membrane compartments of neurons that contain AMPA receptors. Here we describe biochemical and morphological characteristics of an intracellular pool of AMPA receptors in rat brain. By velocity gradient centrifugation of microsomal light membranes from rat brain, we identified a membrane fraction enriched for AMPA receptor subunits GluR2/3 but lacking NMDA receptors. This membrane compartment sedimented. more slowly than synaptosomes but faster than synaptic vesicles and cofractionated with GRIP, PICK-1 and syntaxin-13. Morphological examination of this fraction revealed round and tubular vesicles ranging from similar to 50 to 300 nm in diameter. Immunocytochemistry of cultured hippocampal neurons showed that a significant portion of AMPA receptors colocalized with syntaxin-13 (a SNARE protein associated with tubulovesicular recycling endosomes) and with transferrin receptors. Taken together, these results suggest that a pool of intracellular GluR2/3 resides in a syntaxin 13-positive tubulovesicular membrane compartment, which might serve as a reservoir for the dendritic recycling of AMPA receptors. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Neurosci Res Ctr, Ctr Learning & Memory,RIKEN MIT, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Surg, Stanford, CA 94305 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 39444, NS 35050] NR 52 TC 51 Z9 52 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2001 VL 41 IS 6 BP 680 EP 692 DI 10.1016/S0028-3908(01)00124-1 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 490LC UT WOS:000172052500005 PM 11640922 ER PT J AU Zhang, KH Tarazi, FI Baldessarini, RJ AF Zhang, KH Tarazi, FI Baldessarini, RJ TI Role of dopamine D-4 receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE attention deficit-hyperactivity disorder; autoradiography; dopamine; D-4; 6-hydroxydopamine; motor activity ID ATTENTION-DEFICIT DISORDER; PREFRONTAL CORTEX; DRD4 GENE; BIOCHEMICAL-EVIDENCE; EXCITOTOXIC LESIONS; D-4-LIKE RECEPTORS; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; NOVELTY SEEKING; PRIMATE BRAIN AB The role of dopamine D-4 receptors in behavioral hyperactivity was investigated by assessing D-4 receptor expression in brain regions and behavioral effects of D-4 receptor-selective ligands in juvenile rats with neonatal 6-hydroxydopamine lesions, a laboratory model for attention deficit-hyperactivity disorder (ADHD). Autoradiographic analysis indicated that motor hyperactivity in lesioned rats was closely correlated with increases in D-4 but not D-2 receptor levels in caudate-putamen. D-4-selective antagonist CP-293,019 dose-dependently reversed lesion-induced hyperactivity, and D-4-agonist CP-226,269 increased it. These results indicate a physiological role of dopamine D-4 receptors in motor behavior, and may suggest much-needed innovative treatments for ADHD. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Zhang, KH (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. NR 51 TC 58 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2001 VL 25 IS 5 BP 624 EP 632 DI 10.1016/S0893-133X(01)00262-7 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 488TR UT WOS:000171952200002 PM 11682245 ER PT J AU Sackeim, HA Rush, AJ George, MS Marangell, LB Husain, MM Nahas, Z Johnson, CR Seidman, S Giller, C Haines, S Simpson, RK Goodman, RR AF Sackeim, HA Rush, AJ George, MS Marangell, LB Husain, MM Nahas, Z Johnson, CR Seidman, S Giller, C Haines, S Simpson, RK Goodman, RR TI Vagus nerve stimulation (VNS (TM)) for treatment-resistant depression: Efficacy, side effects, and predictors of outcome SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE vagus nerve stimulation; major depressive disorder; bipolar disorder; treatment-resistant depression; clinical trial; efficacy; side effects ID ELECTROCONVULSIVE-THERAPY; ATYPICAL DEPRESSION; LONG-TERM; PARTIAL SEIZURES; MEDICATION RESISTANCE; REFRACTORY EPILEPSY; CLINICAL-RESPONSE; MAJOR DEPRESSION; IMIPRAMINE; PHENELZINE AB This open pilot study of vagus nerve stimulation (VNS (TM)) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD28 measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-1 of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p = .0057), Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic bene fits and tolerability will be critical in determining its role in treatment-resistant depression. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 New York State Psychiat Inst & Hosp, Dept Biol Psychiat, Unit 126, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Neurosurg, New York, NY USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Neurosurg, Dallas, TX USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Baylor Coll Med, Dept Psychiat, Houston, TX USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. RP Sackeim, HA (reprint author), New York State Psychiat Inst & Hosp, Dept Biol Psychiat, Unit 126, 1051 Riverside Dr, New York, NY 10032 USA. RI Haines, Stephen/L-3209-2013; OI Haines, Stephen/0000-0002-4263-0268; Rush, Augustus/0000-0003-2004-2382 NR 42 TC 260 Z9 263 U1 4 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2001 VL 25 IS 5 BP 713 EP 728 DI 10.1016/S0893-133X(01)00271-8 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 488TR UT WOS:000171952200012 PM 11682255 ER PT J AU Siegel, JM Moore, R Thannickal, T Nienhuis, R AF Siegel, JM Moore, R Thannickal, T Nienhuis, R TI A brief history of hypocretin/orexin and narcolepsy SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE hypocretin; orexin; narcolepsy; sleep ID LOCUS-COERULEUS NEURONS; REM-SLEEP INDUCTION; EYE-MOVEMENT SLEEP; CANINE NARCOLEPSY; OREXIN-A; IMMUNOREACTIVE NEURONS; AFFECTIVE-ILLNESS; RATS; PROJECT; BRAIN AB The hypothalmic peptides named the orexins, or hypocretins, were discovered in 1998. In 1999 it was established that genetic narcolepsy could be caused by mutations in the genes synthesizing these peptides or their receptors. In September of 2000 it was found that most human narcolepsy is caused by loss of hypocretin cells, most likely as a result of a degenerative process. This paper reviews these events and their implications for our understanding of brain arousal and motor control systems. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Univ Calif Los Angeles, Dept Psychiat, North Hills, CA 91343 USA. Univ Calif Los Angeles, Brain Res Inst, North Hills, CA 91343 USA. VA GLAHCS, North Hills, CA 91343 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610] NR 54 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2001 VL 25 SU 5 BP S14 EP S20 DI 10.1016/S0893-133X(01)00317-7 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 490RZ UT WOS:000172066000004 PM 11682268 ER PT J AU Carpentieri, SC Waber, DP Scott, RM Goumnerova, LC Kieran, MW Cohen, LE Kim, F Billett, AL Tarbell, NJ Pomeroy, SL AF Carpentieri, SC Waber, DP Scott, RM Goumnerova, LC Kieran, MW Cohen, LE Kim, F Billett, AL Tarbell, NJ Pomeroy, SL TI Memory deficits among children with craniopharyngiomas SO NEUROSURGERY LA English DT Article DE craniopharyngioma; pediatric ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SEQUELAE; SURGERY; REMOVAL AB OBJECTIVE: To describe neuropsychological functioning (with a specific focus on cognition and memory) after surgical treatment of craniopharyngiomas. METHODS: Sixteen patients who were between 6 and 15 years of age at the time of surgery comprised the sample. Each child had been treated for a craniopharyngioma with surgery only, on Dana-Farber Cancer Institute Protocol 92-077. RESULTS: The overall level of cognitive functioning was well within the average range, with both language and visuospatial functioning being generally intact; however, specific memory problems, in both the language and visuospatial domains, were evident. CONCLUSION: Although general cognitive functioning was intact after the surgical treatment of craniopharyngiomas, difficulties in the retrieval of learned information were observed. Neuropsychological assessments, with a focus on memory recall, should be a component of the medical management plan for each child. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Carpentieri, SC (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 24 TC 61 Z9 63 U1 1 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 NOV PY 2001 VL 49 IS 5 BP 1053 EP 1057 DI 10.1097/00006123-200111000-00005 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 485NG UT WOS:000171760000007 PM 11846897 ER PT J AU Vasan, RS Larson, MG Leip, EP Evans, JC O'Donnell, CJ Kannel, WB Levy, D AF Vasan, RS Larson, MG Leip, EP Evans, JC O'Donnell, CJ Kannel, WB Levy, D TI Impact of high-normal blood pressure on the risk of cardiovascular disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ISOLATED SYSTOLIC HYPERTENSION; REGRESSION DILUTION; MEN; MORTALITY; WOMEN; RECOMMENDATIONS; METAANALYSIS; POPULATION; PREVENTION AB Background: Information is limited regarding the risk of cardiovascular disease in persons with high-normal blood pressure (systolic pressure of 130 to 139 mm Hg, diastolic pressure of 85 to 89 mm Hg, or both). Methods: We investigated the association between blood-pressure category at base line and the incidence of cardiovascular disease on follow-up among 6859 participants in the Framingham Heart Study who were initially free of hypertension and cardiovascular disease. Results: A stepwise increase in cardiovascular event rates was noted in persons with higher base-line blood-pressure categories. The 10-year cumulative incidence of cardiovascular disease in subjects 35 to 64 years of age who had high-normal blood pressure was 4 percent (95 percent confidence interval, 2 to 5 percent) for women and 8 percent (95 percent confidence interval, 6 to 10 percent) for men; in older subjects (those 65 to 90 years old), the incidence was 18 percent (95 percent confidence interval, 12 to 23 percent) for women and 25 percent (95 percent confidence interval, 17 to 34 percent) for men. As compared with optimal blood pressure, high-normal blood pressure was associated with a risk-factor-adjusted hazard ratio for cardiovascular disease of 2.5 (95 percent confidence interval, 1.6 to 4.1) in women and 1.6 (95 percent confidence interval, 1.1 to 2.2) in men. Conclusions: High-normal blood pressure is associated with an increased risk of cardiovascular disease. Our findings emphasize the need to determine whether lowering high-normal blood pressure can reduce the risk of cardiovascular disease. (N Engl J Med 2001;345:1291-7.) Copyright (C) 2001 Massachusetts Medical Society. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 5 Thurber St, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24 HL 04334-01A1, N01-HC-38038] NR 34 TC 950 Z9 1024 U1 3 U2 51 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 NOV 1 PY 2001 VL 345 IS 18 BP 1291 EP 1297 DI 10.1056/NEJMoa003417 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 487UX UT WOS:000171896300001 PM 11794147 ER PT J AU Ferris, TG Chang, YC Blumenthal, D Pearson, SD AF Ferris, TG Chang, YC Blumenthal, D Pearson, SD TI Leaving gatekeeping behind - Effects of opening access to specialists for adults in a health maintenance organization. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PRIMARY-CARE; MANAGED CARE; COSTS; HOSPITALIZATIONS; EXPENDITURES; PHYSICIANS; SERVICES; PLAN AB Background: Gatekeeping refers to the prior approval of referrals to specialists by a primary care physician. Although many health plans view gatekeeping as an essential tool for controlling costs and coordinating care, many patients and physicians object to it. Methods: On April 1, 1998, Harvard Vanguard Medical Associates, a large, multispecialty, capitated group practice previously known as Harvard Community Health Plan, eliminated a gatekeeping system that had been in place for over 25 years. We determined the effects of opening access to specialists on visits to primary care physicians and specialists by adults. In randomly selected cohorts of 10,000 members each, we analyzed visits during 6-month periods for the 3 years before and 18 months after gatekeeping was eliminated. Results: Adults visited a primary care physician an average of 1.21 times and 1.19 times per six-month period before and after the elimination of gatekeeping, respectively (P=0.05); the average number of visits to a specialist was 0.78 per six-month period both before and after its elimination (P=0.35). There was little change in the percentage of visits to specialists included in the analysis as a proportion of all visits (39.1 percent before the elimination of gatekeeping and 39.5 percent afterward). The percentage of first visits to specialists as a proportion of all visits to specialists included in the analysis increased from 24.7 to 28.2 percent (P<0.001). There were small increases in the numbers of visits to orthopedists and physical or occupational therapists. The proportion of visits to specialists for low back pain that were new consultations increased from 26.6 to 32.9 percent (P=0.01). Conclusions: In a capitated, multispecialty group practice, we found little evidence of substantial changes in the use of specialty services by adults in the first 18 months after the elimination of gatekeeping. (N Engl J Med 2001;345:1312-7.) Copyright (C) 2001 Massachusetts Medical Society. C1 Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp Partners Hlth Care Syst, Inst Hlth Policy, Div Gen Internal Med, Boston, MA USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Pearson, SD (reprint author), Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Fl, Boston, MA 02215 USA. FU NICHD NIH HHS [K12-HD00850] NR 25 TC 55 Z9 56 U1 3 U2 8 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 NOV 1 PY 2001 VL 345 IS 18 BP 1312 EP 1317 DI 10.1056/NEJMsa010097 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 487UX UT WOS:000171896300006 PM 11794151 ER PT J AU Mylonakis, E Calderwood, SB AF Mylonakis, E Calderwood, SB TI Medical progress: Infective endocarditis in adults. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PROSTHETIC VALVE ENDOCARDITIS; STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; AMERICAN-HEART-ASSOCIATION; PRACTICE GUIDELINES COMMITTEE; INTRAVENOUS-DRUG-USERS; DUKE CRITERIA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; NATIVE VALVE; BACTERIAL-ENDOCARDITIS; CLINICAL-FEATURES C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 99 TC 576 Z9 617 U1 4 U2 28 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 NOV 1 PY 2001 VL 345 IS 18 BP 1318 EP 1330 DI 10.1056/NEJMra010082 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 487UX UT WOS:000171896300007 PM 11794152 ER PT J AU Iwao, S Iwao, N Muller, DC Elahi, D Shimokata, H Andres, R AF Iwao, S Iwao, N Muller, DC Elahi, D Shimokata, H Andres, R TI Does waist circumference add to the predictive power of the body mass index for coronary risk? SO OBESITY RESEARCH LA English DT Article DE body mass index; waist circumference; coronary risk factor ID DENSITY-LIPOPROTEIN CHOLESTEROL; ABDOMINAL SAGITTAL DIAMETER; FAT DISTRIBUTION; CARDIOVASCULAR RISK; GLUCOSE-TOLERANCE; COMPUTED-TOMOGRAPHY; BLOOD-PRESSURE; POSTMENOPAUSAL WOMEN; PLASMA-INSULIN; SERUM-LIPIDS AB Objectives: To examine the power of the combined measurements of body mass index (BMI) and waist circumference (WC) for the prediction of abnormality in coronary heart disease risk factors and to determine whether the additional measurement of WC is predictive in older men and women. Research Methods and Procedures. 1190 men and 751 women of the Baltimore Longitudinal Study of Aging were dichotomized into younger (< 65 years) and older (65+ years) age groups. Coronary risk factors in the realms of glucose/insulin metabolism, blood pressure, and plasma lipids were assessed. The relationship of BMI and WC, singly and combined, to 10 risk factors for coronary heart disease was examined. Results: In younger and older men and women, BMI and WC are highly correlated (0.84 to 0.88). BMI and WC are also significantly correlated to all 10 coronary risk factors in younger men and women and to 8 of the 10 in the older men and women. Both partial correlation and logistic regression analyses revealed a modest but significant improvement in the prediction of coronary risk in younger men and women by WC after controlling for the level of BMI. There was no improvement in the older subjects. Discussion: WC adds only modestly to the prediction of coronary risk in younger subjects once BMI is known, and adds nothing to the production of risk in older subjects. C1 NIA, NIH, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Geriatr Res Lab, Boston, MA 02114 USA. Natl Inst Longev Sci, Longitudinal Study Aging, Nagoya, Aichi, Japan. RP Andres, R (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 51 TC 62 Z9 65 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2001 VL 9 IS 11 BP 685 EP 695 DI 10.1038/oby.2001.93 PG 11 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 493ZQ UT WOS:000172253700005 PM 11707535 ER PT J AU Wolf, M Kettyle, E Sandler, L Ecker, JL Roberts, J Thadhani, R AF Wolf, M Kettyle, E Sandler, L Ecker, JL Roberts, J Thadhani, R TI Obesity and preeclampsia: The potential role of inflammation SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID C-REACTIVE PROTEIN; INSULIN-RESISTANCE SYNDROME; APPARENTLY HEALTHY-MEN; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; ADIPOSE-TISSUE; RISK-FACTORS; PREGNANCY; WOMEN AB OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia. has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P = .04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P = .02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI .3, 4.3, P = .94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3,9.5, P = .01). CONCLUSION. In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia. (Obstet Gynecol 2001;98:757-62. (C) 2001 by the American College of Obstetricians and Gynecologists). C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. RP Wolf, M (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03804]; NICHD NIH HHS [HD39223] NR 31 TC 144 Z9 152 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2001 VL 98 IS 5 BP 757 EP 762 DI 10.1016/S0029-7844(01)01551-4 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 488TT UT WOS:000171952400009 PM 11704165 ER PT J AU Norwitz, ER Stern, HM Grier, H Lee-Parritz, A AF Norwitz, ER Stern, HM Grier, H Lee-Parritz, A TI Placenta percreta and uterine rupture associated with prior whole body radiation therapy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID IRRADIATION; PREGNANCY; PATIENT AB BACKGROUND: Injury to reproductive organs including the uterus is a known complication of ionizing radiation, but the risks to the mother and fetus during subsequent pregnancies are not well defined. CASE: A young woman with a remote history of whole body irradiation for childhood leukemia had uterine rupture at 17 weeks' gestation. Pathologic examination of the supracervical hysterectomy specimen revealed a posterior-fundal placenta percreta with a diffusely thinned myometrium (1-6 mm.). The clinicopathologic findings were consistent with prior radiation injury. CONCLUSION: Uterine irradiation may predispose to abnormal placentation and uterine rupture in a subsequent pregnancy. (Obstet Gynecol 2001;98:929-31. (C) 2001 by the American College of Obstetricians and Gynecologists.). C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Norwitz, ER (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2001 VL 98 IS 5 SU S BP 929 EP 931 DI 10.1016/S0029-7844(01)01435-1 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 490GP UT WOS:000172042300016 PM 11704208 ER PT J AU Johnson, EB Muto, MG Yanushpolsky, EH Mutter, GL AF Johnson, EB Muto, MG Yanushpolsky, EH Mutter, GL TI Phytoestrogen supplementation and endometrial cancer SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SOY AB BACKGROUND: Phytoestrogens are increasingly used by patients as "natural" alternatives to hormone replacement. Attention in scientific and lay literature has focused on their potential to prevent menopausal symptoms, bone loss, heart disease, or breast cancer. Less is known about effects on the endometrium, specifically, whether prolonged exposure to phytoestrogens could promote hyperplasia or neoplasia, as does unopposed estrogen. CASE: We report the case of a woman diagnosed with grade I endometrioid adenocarcinoma of the endometrium whose history was notable for extensive use of supplemental phytoestrogens. CONCLUSION: The effects of phytoestrogens on endometrial tissue are not known. Given their increasing popularity and availability in concentrated form as dietary supplements, additional research is warranted before we can counsel our patients regarding the safety of such supplements. (Obstet Gynecol 2001;98:947-50. (C) 2001 by the American College of Obstetricians and Gynecologists.). C1 Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Div Gynecol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Div Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dana Farber Canc Inst, Gillete Ctr Womens Canc, Boston, MA 02115 USA. RP Johnson, EB (reprint author), Univ Washington, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. RI Mutter, George/C-5819-2009 NR 7 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2001 VL 98 IS 5 SU S BP 947 EP 950 DI 10.1016/S0029-7844(01)01542-3 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 490GP UT WOS:000172042300024 PM 11704216 ER PT J AU Seddon, JM Afshari, MA Sharma, S Bernstein, PS Chong, S Hutchinson, A Petrukhin, K Allikmets, R AF Seddon, JM Afshari, MA Sharma, S Bernstein, PS Chong, S Hutchinson, A Petrukhin, K Allikmets, R TI Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull's-eye maculopathy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 24-27, 1999 CL ORLANDO, FLORIDA SP Amer Acad Ophthalmol ID EPITHELIAL DYSTROPHY; STARGARDT-DISEASE; DEGENERATION; ABCR; CLASSIFICATION AB Purpose: To study the presence, of Best macular dystrophy (VMD2) gene mutations in patients diagnosed with maculopathies other than; classic Best disease, and to describe the clinical characteristics of these subjects. Design. Case-comparison study of phenotype-genotype correlations. Methods. Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic, Best disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made. Main Outcome Measures; Presence of mutations, in the Best gene (VMD2; OMIM 153700) and the clinical phenotype. Results: Three of 259 patients (1%), with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216l), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull's-eye maculopathy (variant in exon 4; E119Q) and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in; exon 4; A146K). Conclusions. Novel mutations in the VMD2. gene were found inpatients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM. Ophthalmology 2001;108:2060-2067 (C) 2001 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, Boston, MA 02114 USA. Univ Utah, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Merck Res Labs, Dept Human Genet, W Point, PA USA. Columbia Univ, Dept Pathol, New York, NY USA. RP Seddon, JM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY11309, EY11600] NR 30 TC 64 Z9 66 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2001 VL 108 IS 11 BP 2060 EP 2067 DI 10.1016/S0161-6420(01)00777-1 PG 8 WC Ophthalmology SC Ophthalmology GA 488YL UT WOS:000171964500039 PM 11713080 ER PT J AU Lieber, CS AF Lieber, CS TI Alcoholic liver injury: pathogenesis and therapy in 2001 SO PATHOLOGIE BIOLOGIE LA English DT Article DE alcoholic liver disease; CYP2E1; diagnosis; dilinoleoylphosphatidylcholine (DLPC) polyenylphosphatidylcholine (PPC); S-adenosylmethionine (SAMe); therapy ID CHRONIC ETHANOL-CONSUMPTION; ADENOSYL-L-METHIONINE; HEPATIC VITAMIN-A; FAT-STORING CELLS; BETA-CAROTENE; RETINOIC ACID; RAT-LIVER; CYTOCHROME P-4502E1; OXIDIZING SYSTEM; DOUBLE-BLIND AB Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and promising prospects for even more effective treatments, It continues to be important to replenish nutritional deficiencies when present but it is crucial to recognize that, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to SAMe but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for administration of the products of the reaction. It might also be beneficial to add other compounds to such therapeutic regiment. Since free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise. Several have been investigated experimentally and PPC is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Anti-inflamatory agents are also required. In addition to down-regulators of cytokines and end toxic are being considered. Finally, since excess drinking is the crux of the issue, anticraving agents should be incorporated in any contemplated therapeutic cocktail, in view of the recent promising results obtained with some of these agents such as naltrexone and acamprosate. (C) 2001 Editions scientifiques et medicales Elsevier SAS. C1 Mt Sinai Sch Med, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. RP Lieber, CS (reprint author), Mt Sinai Sch Med, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA07275, AA05934, AA11115, AA11160] NR 97 TC 33 Z9 35 U1 1 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD NOV PY 2001 VL 49 IS 9 BP 738 EP 752 DI 10.1016/S0369-8114(01)00239-5 PG 15 WC Pathology SC Pathology GA 495VK UT WOS:000172360900011 PM 11762137 ER PT J AU Snoek, FJ van der Ven, NCW Lubach, CHC Chatrou, M Ader, HJ Heine, RJ Jacobson, AM AF Snoek, FJ van der Ven, NCW Lubach, CHC Chatrou, M Ader, HJ Heine, RJ Jacobson, AM TI Effects of cognitive behavioural group training (CBGT) in adult patients with poorly controlled insulin-dependent (type 1) diabetes: a pilot study SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE cognitive behaviour therapy; group training; type 1 diabetes; coping; glycaemic control; well-being ID SELF-CARE; METABOLIC CONTROL; CONTROLLED TRIAL; MELLITUS; EDUCATION; VALIDITY; DUTCH AB A substantial group of patients with type 1 diabetes has difficulty adhering to the treatment regimen, and as a consequence is at increased risk of developing microvascular complications. Cognitive behavioural interventions may help these patients to cope more effectively with their diabetes. We developed a 4 weeks cognitive behavioural. group training (CBGT) for patients with type I (insulin-dependent) diabetes in persistent poor glycaemic control, to help them overcome negative beliefs and attitudes towards diabetes and improve their self-care behaviours. Feasibility and efficacy of CBGT were tested in a non-randomised prospective study in 24 poorly-controlled type I diabetes patients (mean age 35.2 +/- 11.1 years; 15 female; mean HbA(1c) 9.3% (+/-1.2)), with assessments at 3 and 6 months follow-up. The program-me was delivered in small groups (n = 6-8), by a team of a diabetes nurse specialist and a psychologist. Primary outcome measures were glycosylated haemoglobin (HbA1(c)), diabetes-related emotional distress (PAID) and psychological well-being (WBQ-12). Chang diabetes self-care activities (DSCI) were documented, along with perceived barriers in diabetes questionniare (BDQ) and fear of hypoglycaemia survey (HFS). Data were analysed using repeated measures analysis of variance. The CBGT proved to be feasible in this selected group of patients and was well appreciated. Following CBGT, mean HbA(1c) dropped by 0.8% at 6 months from baseline, while emotional well-being was preserved, It is concluded that CBGT is a promising intervention that deserves further evaluation in randomised controlled trials. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Clin Epidemiol & Biostat, Amsterdam, Netherlands. Joslin Diabet Ctr, Sect Behav Res, Boston, MA 02215 USA. Joslin Diabet Ctr, Mental Hlth Unit, Boston, MA 02215 USA. RP Snoek, FJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, Amsterdam, Netherlands. NR 26 TC 39 Z9 41 U1 1 U2 5 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 NOV PY 2001 VL 45 IS 2 BP 143 EP 148 DI 10.1016/S0738-3991(01)00113-6 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 493YM UT WOS:000172251100009 PM 11687328 ER PT J AU Goetzl, L Cohen, A Frigoletto, F Ringer, SA Lang, JM Lieberman, E AF Goetzl, L Cohen, A Frigoletto, F Ringer, SA Lang, JM Lieberman, E TI Maternal epidural use and neonatal sepsis evaluation in afebrile mothers SO PEDIATRICS LA English DT Article DE epidural analgesia; pregnancy; labor; neonatal sepsis evaluation ID RANDOMIZED TRIAL; ANALGESIA; LABOR; FEVER AB Objective. Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women Methods. We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (< 100.4F). Neonatal sepsis evaluation generally was performed on the basis of the presence of 1 major or 2 minor criteria. Major criteria included rupture of membranes for >24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degreesF to 100.4 degreesF, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of <7 at 5 minutes. Results. Infants of afebrile women with epidural analgesia were more likely to be evaluated for sepsis than infants of women without epidural (20.4% vs 8.9%), although not more likely to have neonatal sepsis. An increased risk of sepsis evaluation persisted in regression analysis (odds ratio: 3.1; 95% confidence interval: 2.0, 4.7) after controlling for confounders and was not explained by longer labors with epidural. Women with epidural were significantly more likely to have major and minor criteria for sepsis evaluation, including fetal tachycardia (4.4% vs 0.4%), rupture of membranes for >24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degreesF to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. Conclusions. Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women. C1 Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77098 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Joint Program Neonatol Brigham & Womens Hosp Chil, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. RP Goetzl, L (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, 6550 Fannin St,9th Floor, Houston, TX 77098 USA. FU NICHD NIH HHS [R01-HD26813] NR 13 TC 17 Z9 19 U1 0 U2 0 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 NOV PY 2001 VL 108 IS 5 BP 1099 EP 1102 DI 10.1542/peds.108.5.1099 PG 4 WC Pediatrics SC Pediatrics GA 488FH UT WOS:000171925200026 PM 11694687 ER PT J AU Michelson, D Faries, D Wernicke, J Kelsey, D Kendrick, K Sallee, FR Spencer, T AF Michelson, D Faries, D Wernicke, J Kelsey, D Kendrick, K Sallee, FR Spencer, T CA Atomoxetine ADHD Study Grp TI Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: A randomized, placebo-controlled, dose-response study SO PEDIATRICS LA English DT Article DE atomoxetine; ADHD; dose-response; children; adolescents ID DEFICIT HYPERACTIVITY DISORDER; ADULTS; NORTRIPTYLINE AB Objective. Atomoxetine is an investigational, nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder (ADHD). It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain. We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD. Methods. A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, were randomized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day, 1.2 mg/kg/day, or 1.8 mg/kg/day for an 8-week period. ADHD symptoms, affective symptoms, and social and family functioning were assessed using parent and investigator rating scales. Results. Approximately 71% of children enrolled were male, approximately 67% met criteria for mixed subtype (both inattentive and hyperactive/impulsive symptoms), and the only common psychiatric comorbidity was oppositional defiant disorder (approximately 38% of the sample). At baseline, symptom severity was rated as moderate to severe for most children. At endpoint, atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other. The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses, suggesting a graded dose-response. Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children's ability to meet psychosocial role expectations and parental impact. Discontinuations as a result of adverse events were <5% for all groups. Conclusion. Among children and adolescents aged 8 to 18, atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms. Atomoxetine was associated with a graded dose-response, and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients. Treatment with atomoxetine was safe and well tolerated. C1 Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Cincinnati, Cincinnati, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Michelson, D (reprint author), Eli Lilly & Co, Lilly Corp Ctr, DC6026, Indianapolis, IN 46285 USA. NR 30 TC 312 Z9 319 U1 2 U2 15 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 NOV PY 2001 VL 108 IS 5 AR e83 DI 10.1542/peds.108.5.e83 PG 9 WC Pediatrics SC Pediatrics GA 488FH UT WOS:000171925200006 PM 11694667 ER PT J AU Raymond, JR Mukhin, YV Gelasco, A Turner, J Collinsworth, G Gettys, TW Grewal, JS Garnovskaya, MN AF Raymond, JR Mukhin, YV Gelasco, A Turner, J Collinsworth, G Gettys, TW Grewal, JS Garnovskaya, MN TI Multiplicity of mechanisms of serotonin receptor signal transduction SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE signal transduction; adenylyl cyclase; phospholipase; kinase; channel ID ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; C6 GLIOMA-CELLS; ADENYLYL-CYCLASE ACTIVITY; CYCLIC-AMP ACCUMULATION; HUMAN 5-HT1A RECEPTOR; DORSAL RAPHE NEURONS; RAT SEXUAL-BEHAVIOR; HUMAN 5-HYDROXYTRYPTAMINE(1A) RECEPTOR AB The serotonin (5-hydroxytryptamine, 5-HT) receptors have been divided into 7 subfamilies by convention, 6 of which include 13 different genes for G-protein-coupled receptors. Those subfamilies have been characterized by overlapping pharmacological properties, amino acid sequences, gene organization, and second messenger coupling pathways. Post-genomic modifications, such as alternative mRNA splicing or mRNA editing, creates at least 20 more G-protein-coupled 5-HT receptors, such that there are at least 30 distinct 5-HT receptors that signal through G-proteins, This review will focus on what is known about the signaling linkages of the G-protein-linked 5-HT receptors, and will highlight some fascinating new insights into 5-HT receptor signaling. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Div Gastroenterol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biol Mol, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Room 829 CSB,171 Ashley Ave, Charleston, SC 29425 USA. OI Gettys, Thomas/0000-0001-7125-7995 FU NIDDK NIH HHS [DK02694, DK053981, DK52448, DK54720] NR 419 TC 273 Z9 281 U1 1 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD NOV-DEC PY 2001 VL 92 IS 2-3 BP 179 EP 212 AR PII S0163-7258(01)00169-3 DI 10.1016/S0163-7258(01)00169-3 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 558PY UT WOS:000175976800008 PM 11916537 ER PT J AU Ripoll, J Ntziachristos, V Carminati, R Nieto-Vesperinas, M AF Ripoll, J Ntziachristos, V Carminati, R Nieto-Vesperinas, M TI Kirchhoff approximation for diffusive waves SO PHYSICAL REVIEW E LA English DT Article ID PHOTON DENSITY WAVES; FIELD DIFFRACTION TOMOGRAPHY; BOUNDARY-CONDITIONS; OPTICAL TOMOGRAPHY; TURBID MEDIA; SCATTERING; FLUORESCENCE; MAMMOGRAPHY; INTERFACES; REFLECTION AB Quantitative measurements of diffuse media, in spectroscopic or imaging mode. rely on the generation of appropriate forward solutions, independently of the inversion scheme employed. For complex boundaries, the use of numerical methods is generally preferred due to implementation simplicity, but usually results in great computational needs, especially in three dimensions. Analytical expressions are available, but are limited to simple geometries such as a diffusive slab, a sphere or a cylinder. An analytical approximation, the Kirchhoff approximation, also called the tangent-plane method is presented for the case of diffuse light. Using this approximation, analytical solutions of the diffusion equation for arbitrary boundaries and volumes can be derived. Also, computation time is minimized since no matrix inversion is involved. The accuracy of this approximation is evaluated on comparison with results from a rigorous numerical technique calculated for an arbitrary geometry. Performance of the approximation as a function of the optical properties and the size of the medium is examined and it is demonstrated that the computation time of the direct scattering model is reduced at least by two orders of magnitude. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Crete, Greece. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Ecole Cent Paris, Lab Energet Mol & Macroscop, CNRS, F-92295 Chatenay Malabry, France. CSIC, Inst Ciencia Mat, E-28049 Madrid, Spain. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion, Crete, Greece. EM jripoll@iesl.forth.gr RI Carminati, Remi/H-6882-2014; Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 34 TC 47 Z9 52 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD NOV PY 2001 VL 64 IS 5 AR 051917 DI 10.1103/PhysRevE.64.051917 PN 1 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 496QF UT WOS:000172406900100 PM 11735978 ER PT J AU Rorro, M Gastfriend, DR AF Rorro, M Gastfriend, DR TI Integrating addiction medicine with psychiatry: Clinical collaboration and resource parity SO PSYCHIATRIC ANNALS LA English DT Article ID ALCOHOLISM SCREENING TEST; DRUG-ABUSE; MENTAL-DISORDERS C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rorro, M (reprint author), 388 Commonwealth Ave,Lower Level, Boston, MA 02215 USA. NR 41 TC 1 Z9 1 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2001 VL 31 IS 11 BP 641 EP 647 PG 7 WC Psychiatry SC Psychiatry GA 490KH UT WOS:000172050700002 ER PT J AU Costes, S Sachs, R Hlatky, L Vannais, D Waldren, C Fouladi, B AF Costes, S Sachs, R Hlatky, L Vannais, D Waldren, C Fouladi, B TI Large-mutation spectra induced at hemizygous loci by low-LET radiation: Evidence for intrachromosomal proximity effects SO RADIATION RESEARCH LA English DT Article ID CHINESE-HAMSTER CELLS; RAY-INDUCED MUTATIONS; DOUBLE-STRAND BREAKS; HUMAN HPRT GENE; IONIZING-RADIATION; CHROMOSOME-ABERRATIONS; ANCHOR SYNTHESIS; MAMMALIAN-CELLS; LARGE DELETIONS; DOSE-RESPONSE AB A mathematical model is used to analyze mutant spectra for large mutations induced by low-LET radiation. The model equations are based mainly on two-break misrejoining that leads to deletions or translocations. It is assumed, as a working hypothesis, that the initial damage induced by low-LET radiation is located randomly in the genome. Specifically, we analyzed data for two hemizygous loci: CD59(-) mutants, mainly very large-scale deletions (>3 Mbp), in human-hamster hybrid cells, and data from the literature on those HPRT-mutants which involve at least deletion of the whole gene, and often of additional flanking markers (similar to 50-kbp to similar to4.4-Mbp deletions). For five data sets, we estimated f, the probability that two given breaks on the same chromosome will misrejoin to make a deletion, as a function of the separation between the breaks. We found that f is larger for nearby breaks than for breaks that are more widely separated; i.e., there is a "proximity effect". For acute irradiation, the values off determined from the data are consistent with the corresponding break misrejoining parameters found previously in quantitative modeling of chromosome aberrations. The value off was somewhat smaller for protracted irradiation than for acute irradiation at a given total dose; i.e., the mutation data show a decrease that was smaller than expected for dose protraction by fractionation or low dose rate. (C) 2001 by Radiation Research Society. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Colorado State Univ, Radiol Hlth Sci MRB, Ft Collins, CO 80523 USA. RP Costes, S (reprint author), NCI, Bldg 538, Frederick, MD 21702 USA. RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 FU NCI NIH HHS [CA 36447, CA 86823, 5T32 CA 09236]; NIGMS NIH HHS [GM 57245] NR 47 TC 11 Z9 11 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 NOV PY 2001 VL 156 IS 5 BP 545 EP 557 DI 10.1667/0033-7587(2001)156[0545:LMSIAH]2.0.CO;2 PN 1 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 489NZ UT WOS:000171999000012 PM 11604068 ER PT J AU El-Saden, SM Grant, EG Hathout, GM Zimmerman, PT Cohen, SN Baker, JD AF El-Saden, SM Grant, EG Hathout, GM Zimmerman, PT Cohen, SN Baker, JD TI Imaging of the internal carotid artery: The dilemma of total versus near total occlusion SO RADIOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting and Scientific-Assembly of the Radiological-Society-of-North-America (RSNA) CY NOV 28-DEC 03, 1999 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE angiography, comparative studies; carotid arteries, angiography; carotid arteries, stenosis or obstruction ID PSEUDO-OCCLUSION; MR-ANGIOGRAPHY; COLOR-FLOW; CEREBROVASCULAR-DISEASE; STRING SIGN; STENOSIS; DUPLEX; ENDARTERECTOMY; DOPPLER; ULTRASONOGRAPHY AB PURPOSE: To evaluate ultrasonography (US) and magnetic resonance (MR) angiography in the differentiation between occlusion and near occlusion of internal carotid artery (ICA). MATERIALS AND METHODS: Consecutive patients with occlusion or near occlusion of ICA at catheter angiography and who underwent MR angiography and US were included. MR angiography and US were compared with catheter angiography, the standard, for the ability to help distinguish occlusion from near occlusion. Noninvasive examinations were evaluated for the ability to classify near occlusions as having severe focal stenosis with distal luminal collapse versus diffuse nonfocal disease. The 95% Cls were calculated. RESULTS: In 55 of 274 patients with 548 ICAs, catheter angiography depicted 37 total occlusions and 21 near occlusions. US depicted all total occlusions; MR angiography depicted 34 (92%) (95% CI: 0.78, 0.98). US depicted 18 (86%) of 21 (95% CI: 0.64, 0.97) near occlusions; MR angiography depicted all (100%). Of 18 vessels that were determined to be patent at US, 17 (94%) (95% CI: 0.73, 0.99) were classified as having focal stenosis or diffuse disease. Because flow gaps were identified in vessels with focal and diffuse disease, MR angiography was not effective in helping to differentiate these lesions. CONCLUSION: Assuming US is the initial imaging examination, when occlusion is diagnosed, MR angiography can depict it. If occlusion is confirmed, no further imaging is necessary. US performed well in helping to differentiate vessels with focal severe stenosis from those with diffuse disease. MR angiography added little in this group. Catheter angiography remains beneficial for vessels with diffuse nonfocal narrowing. C1 W Los Angeles Vet Adm Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. W Los Angeles Vet Adm Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. W Los Angeles Vet Adm Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP El-Saden, SM (reprint author), W Los Angeles Vet Adm Med Ctr, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 25 TC 31 Z9 33 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 NOV PY 2001 VL 221 IS 2 BP 301 EP 308 DI 10.1148/radiol.2212001606 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489ZU UT WOS:000172023800005 PM 11687668 ER PT J AU Erickson, JK Rosenthal, DI Zaleske, DJ Gebhardt, MC Cates, JM AF Erickson, JK Rosenthal, DI Zaleske, DJ Gebhardt, MC Cates, JM TI Primary treatment of chondroblastoma with percutaneous radiofrequency heat ablation: Report of three cases SO RADIOLOGY LA English DT Article DE bone neoplasms, therapy; chondroblastoma; radio-frequency (RF) ablation ID CARCINOMA; ELECTRODE; BONE AB Chondroblastomas are benign cartilaginous lesions; however, intervention is necessary to stop progression and alleviate pain. The authors evaluated three patients in whom minimally invasive percutaneous radiofrequency heat ablation was used to treat pathologically proven chondroblastoma to determine whether this treatment demonstrated long-term success. The authors found that this approach may be an effective alternative to surgical intervention in some cases. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Bartlett 405, Boston, MA 02114 USA. RI Cates, Justin/D-5927-2014 OI Cates, Justin/0000-0002-7336-5196 NR 22 TC 43 Z9 47 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 NOV PY 2001 VL 221 IS 2 BP 463 EP 468 DI 10.1148/radiol.2212010262 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489ZU UT WOS:000172023800026 PM 11687691 ER PT J AU Bremer, C Bredow, S Mahmood, U Weissleder, R Tung, CH AF Bremer, C Bredow, S Mahmood, U Weissleder, R Tung, CH TI Optical imaging of matrix metalloproteinase-2 activity in tumors: Feasibility study in a mouse model SO RADIOLOGY LA English DT Article DE animals; enzymes; experimental study; molecular analysis; neoplasms, experimental studies ID GELATINASE-A MMP-2; IV COLLAGENASE; POOR-PROGNOSIS; TURBID MEDIA; EXPRESSION; CANCER; INHIBITOR; GROWTH; CELLS; CARCINOMA AB Purpose: To develop an optical imaging method to determine the expression level of tumoral matrix metalloproteinase-2 (MMP-2) in vivo. Materials and methods: An optical contrast agent was developed that was highly activatable by means of MMP-2-induced conversion. Signal characteristics of the probe were quantified ex vivo with a recombinant enzyme. Animal tumor models were established with MMP-2-positive (human fibrosarcoma cell line, n=4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n=4) tumor cell lines. Both tumors were implanted into nude mice and were optically imaged after intravenous administration of the MMP-2-sensitive probe. Results: The MMP-2-sensitive probe was activated by MMP-2 in vitro, producing up to an 850% increase in near-infrared fluorescent signal intensity. This activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors were easily identified as high-signal-intensity regions as early as 1 hour after intravenous injection of the MMP-2 probe, while contralateral MMP-2-negative tumors showed little to no signal intensity. A nonspecific control probe showed little to no activation in MMP-2-positive tumors. Conclusion: It is feasible to image MMP-2 enzyme activity in vivo by using near-infrared optical imaging technology and "smart" matrix metalloproteinase-sensitive probes. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Rm 5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R21/R33 CA088365] NR 41 TC 188 Z9 198 U1 2 U2 26 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 NOV PY 2001 VL 221 IS 2 BP 523 EP 529 DI 10.1148/radiol.2212010368 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489ZU UT WOS:000172023800034 PM 11687699 ER PT J AU Morton, S Rosen, C Larkin, E Tishler, P Aylor, J Redline, S AF Morton, S Rosen, C Larkin, E Tishler, P Aylor, J Redline, S TI Predictors of sleep-disordered breathing in children with a history of tonsillectomy and/or adenoidectomy SO SLEEP LA English DT Article DE sleep apnea syndromes; child; tonsillectomy; adenoidectomy; risk factors; blacks; health services accessibility ID OUTPATIENT TONSILLECTOMY; NOCTURNAL HYPOXEMIA; RACIAL-DIFFERENCES; APNEA; ADENOTONSILLECTOMY; ADOLESCENTS; SYMPTOMS; GROWTH; DISTURBANCES; PREVALENCE AB Study Objectives: To identify predictors of sleep-disordered breathing (SDB) in children who have undergone self-reported tonsillectomy and/or adenoidectomy (TA). Design: Observational study of pediatric participants in a longitudinal genetic-epidemiological cohort study of SDB Setting: Community-based; studies conducted at participants' homes Participants: 577 children age < 18 (10.8 +/-4.2 SD) years; 53% female; 48% Black; 76% with a family member identified with SDB Interventions: NA Measurements and Results: Medical history assessed by questionnaire. Physical measures made directly. SDB was assessed with overnight in-home cardio-respiratory monitoring. 10% of children (n=60) had had aTA 5.5 +/-4.6 yrs previously, An Apnea-Hypopnea Index (AHI, events/hr) greater than or equal to5 was found in a higher proportion of children with a reported TA than in children with no history of out surgery (35% vs. 13.7%, p < 001). A TA was reported more frequently for non-Blacks than for Blacks (13.6% non-Blacks, 6.9% Blacks, p=.02). Among children who had a TA, significant predictors of SDB (AHI greater than or equal to5) were: Black ethnicity (SDB in 57% vs. 24% of Blacks vs. non-Blacks; adjusted odds ratio (OR): 3.85; 95% Cl: 1.11, 13.33) and obesity (OR 3.98; 95% Cl: 1.05, 15.08). SDB also tended to be greater in children with a family member with SDB (OR 2.87; 95% Cl: 0.65, 12.07). Conclusions: Black children were less likely to have undergone TA but more likely to have SDB after TA surgery. These findings underscore the need to follow children post-TA and for evidence-based studies that define the role of TA in the management of pediatric adenotonsillar disease. C1 Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Redline, S (reprint author), Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM sxr15@po.cwru.edu FU NHLBI NIH HHS [NHLBI 46380, NHLBI 04426] NR 56 TC 40 Z9 41 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2001 VL 24 IS 7 BP 823 EP 829 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 484WK UT WOS:000171712400010 PM 11683485 ER PT J AU Cook, KF Ashton, CM Byrne, MM Brody, B Geraci, J Giesler, RB Hanita, M Souchek, J Wray, NP AF Cook, KF Ashton, CM Byrne, MM Brody, B Geraci, J Giesler, RB Hanita, M Souchek, J Wray, NP TI A psychometric analysis of the measurement level of the rating scale, time trade-off, and standard gamble SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE utility measurement; health-state preferences; cost utility analysis; cost-effectiveness; quality-adjusted life; preference weights; psychometrics ID HEALTH; UTILITIES; PREFERENCES; INTERVAL; QUALITY AB A fundamental assumption of utility-based analyses is that patient utilities for health states can be measured on an equal-interval scale. This assumption, however, has not been widely examined. The objective of this study was to assess whether the rating scale (RS), standard gamble (SG), and time trade-off (TTO) utility elicitation methods function as equal-interval level scales. We wrote descriptions of eight prostate-cancer-related health states. In interviews with patients who had newly diagnosed, advanced prostate cancer, utilities for the health states were elicited using the RS, SG, and TTO methods. At the time of the study, 77 initial and 73 follow-up interviews had been conducted with a consecutive sample of 77 participants. Using a Rasch model, the boundaries (Thurstone Thresholds) between four equal score sub-ranges of the raw utilities were mapped onto an equal-interval logit scale. The distance between adjacent thresholds in logit units was calculated to determine whether the raw utilities were equal-interval. None of the utility scales functioned as interval-level scales in our sample. Therefore, since interval-level estimates are assumed in utility-based analyses, doubt is raised regarding the validity of findings from previous analyses based on these scales. Our findings need to be replicated in other contexts, and the practical impact of non-interval measurement on utility-based analyses should be explored. If cost-effectiveness analyses are not found to be robust to violations of the assumption that utilities are interval, serious doubt will be cast upon findings from utility-based analyses and upon the wisdom of expending millions in research dollars on utility-based studies. Published by Elsevier Science Ltd. C1 Vet Affairs Med Ctr, Ctr Study Healthy Aging Disabil, A VA R&D Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, A VA Hlth Serv, R&D Ctr Excellence, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Ctr Eth Med & Publ Issues, Houston, TX 77030 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Indiana Univ, Sch Nursing, Indianapolis, IN USA. RP Cook, KF (reprint author), VA Med Ctr, Ctr Healthy Aging Disabil, 153,2002 Holcombe Blvd,Bldg 110T Res, Houston, TX 77030 USA. NR 28 TC 19 Z9 20 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2001 VL 53 IS 10 BP 1275 EP 1285 DI 10.1016/S0277-9536(00)00409-3 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 479QN UT WOS:000171415200002 PM 11676400 ER PT J AU Ogilvy, CS AF Ogilvy, CS TI Delayed diagnosis of intracranial aneurysms SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID SUBARACHNOID HEMORRHAGE C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurol Serv, 55 Fruit St,VBK 710, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 2001 VL 94 IS 11 BP 1052 EP 1052 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 505NL UT WOS:000172918800003 PM 11780672 ER PT J AU Basile, JN AF Basile, JN TI Hypertension 2001: Pearls for the clinician SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID RANDOMIZED TRIAL; CARDIOVASCULAR MORBIDITY; SYSTOLIC HYPERTENSION; MORTALITY; PRESSURE C1 Ralph H Johnson VA Med Ctr, Dept Primary Care, Charleston, SC 29401 USA. Med Univ S Carolina, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Basile, JN (reprint author), Ralph H Johnson VA Med Ctr, Dept Primary Care, 109 Bee St, Charleston, SC 29401 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 2001 VL 94 IS 11 BP 1054 EP 1057 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 505NL UT WOS:000172918800004 PM 11780673 ER PT J AU Collard, CL AF Collard, CL TI Thiazide diuretics SO SOUTHERN MEDICAL JOURNAL LA English DT Article C1 Ralph H Johnson VA Med Ctr, Dept Primary Care, Charleston, SC USA. RP Collard, CL (reprint author), Ralph H Johnson VA Med Ctr, Dept Primary Care, Charleston, SC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 2001 VL 94 IS 11 BP 1065 EP 1065 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 505NL UT WOS:000172918800006 PM 11780675 ER PT J AU Cohen, SP Lubin, E Stojanovic, M AF Cohen, SP Lubin, E Stojanovic, M TI Intravenous lidocaine in the treatment of hiccup SO SOUTHERN MEDICAL JOURNAL LA English DT Article AB The word "hiccup" refers to an involuntary, spasmodic contraction of the diaphragm that is followed by the abrupt closure of the glottis to produce the characteristic sound. Among the many documented causes of this occurrence are those due to neurogenic dysfunction. In the past few decades, lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms, including seizures, chronic pain, and arrhythmias. We describe a postsurgical patient in whom two successive intravenous infusions of lidocaine, 1.5 mg/kg followed the next day by 0.75 mg/kg, terminated his hiccup twice, whereas multiple other treatments failed to alleviate the problem. Various causes of this phenomenon are discussed, as well as a possible mechanism for the successful treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr,Dept Anesthesia & Crit Care, Boston, MA USA. RP Cohen, SP (reprint author), Walter Reed Army Med Ctr, Pain Management Ctr, Washington, DC 20307 USA. NR 10 TC 17 Z9 20 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 2001 VL 94 IS 11 BP 1124 EP 1125 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 505NL UT WOS:000172918800020 PM 11780683 ER PT J AU Ackerman, RH AF Ackerman, RH TI Cerebral blood flow and neurological change in chronic heart failure SO STROKE LA English DT Editorial Material DE blood viscosity; cerebral blood flow; cognition; heart failure, congestive; hematocrit ID CARDIAC TRANSPLANTATION; DILATED CARDIOMYOPATHY; CAROTID ENDARTERECTOMY; CAPTOPRIL C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Ackerman, RH (reprint author), Massachusetts Gen Hosp, Neurol Serv, Gray Bldg 254,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 12 Z9 14 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 NOV PY 2001 VL 32 IS 11 BP 2462 EP 2464 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 490PG UT WOS:000172059800003 PM 11692001 ER PT J AU Fisher, CM AF Fisher, CM TI A career in cerebrovascular disease - A personal account SO STROKE LA English DT Editorial Material DE stroke management; stroke, acute; stroke, ischemic; thrombolysis ID INFARCTS; ARTERIES C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St,VBK 910, Boston, MA 02114 USA. NR 38 TC 6 Z9 6 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 NOV PY 2001 VL 32 IS 11 BP 2719 EP 2724 DI 10.1161/hs1101.098765 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 490PG UT WOS:000172059800049 PM 11692045 ER PT J AU Nasseri, BA Ogawa, K Vacanti, JP AF Nasseri, BA Ogawa, K Vacanti, JP TI Tissue engineering: An evolving 21st-century science to provide biologic replacement for reconstruction and transplantation SO SURGERY LA English DT Article ID CHANNELS; SKIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Tissue Engn & Organ Fabricat Lab, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Tissue Engn & Organ Fabricat Lab, 55 Fruit St,Warren 1157, Boston, MA 02114 USA. NR 11 TC 22 Z9 26 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2001 VL 130 IS 5 BP 781 EP 784 DI 10.1067/msy.2001.112960 PG 4 WC Surgery SC Surgery GA 490AL UT WOS:000172026000001 PM 11685185 ER PT J AU Huerta, S Srivatsan, ES Venkatesan, N Peters, J Moatamed, F Renner, S Livingston, EH AF Huerta, S Srivatsan, ES Venkatesan, N Peters, J Moatamed, F Renner, S Livingston, EH TI Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion molecule SO SURGERY LA English DT Article ID FIBRONECTIN-TYPE-III; N-CAM; TUMOR-METASTASIS; DOMAIN; MUSCLE; LINES; NCAM; IDENTIFICATION; PROTEIN; TISSUES AB Background. The neural cell adhesion molecule (NCAM) has numerous isoforms resulting from alternative splicing of mRNA. The 3 major isoforms found in adult tissue are (1) a 120-kDa protein that is linked to the plasma membrane by glycosylphosphatidylinositol; (2) a 140-kDa form that has a transmembrane component and a cytoplasmic tail with unknown function; and (3) a 180-kDa isoform that has an intracellular protein that binds the cytoskeleton. NCAM is capable of homotypic binding and therefore plays a role in cell-cell adhesion for cells expressing the 180-kDa isoform by anchoring groups of cells into epithelial sheets. NCAM-180 is the isoform found in colonocytes, and loss of expression is associated with clinically aggressive colon cancers. Methods. Western blotting and reverse transcriptase-polymerase chain reaction were used to screen commercially, available cell lines for NCAM-180 expression. For cell-line pairs with differential. NCAM-180 expression, exon analysis was performed with reverse transcriptase-polymerase chain reaction to determine where the molecule was spliced, culminating in failed expression. These results were confirmed with exon analysis in colon cancers harvested at the time of laparotomy. Results. Analysis of a SW480 cell line (derived from a patient's primary colon cancer lesion) revealed, NCAM-180 expression, whereas no expression was found in the SW620 cell line (derived from a metastatic lesion from the same patient). Exon analysis of NCAM mRNA transcripts from SW620 revealed that the transcripts were truncated after exon 12. This region correlates to an area between 2 fibronectin-III domains on the NCAM protein. Conclusions. The most common site for NCAM alternative splicing is between the 2 fibronectin-III domains corresponding to the border between exons 12 and 13 of the NCAM gene. Loss of NCAM-180 expression in aggressive colon carcinoma results from a splice defect in the same area, which may result in defective intracellular adhesion between colonocytes. C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Hlth Care Syst, Dept Surg 10112, Los Angeles, CA 90073 USA. USC, Sch Med, Childrens Hosp, Dept Pediat, Los Angeles, CA USA. RP Livingston, EH (reprint author), Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Hlth Care Syst, Dept Surg 10112, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 43 Z9 46 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2001 VL 130 IS 5 BP 834 EP 843 DI 10.1067/msy.2001.116415 PG 10 WC Surgery SC Surgery GA 490AL UT WOS:000172026000010 PM 11685193 ER PT J AU Burke, JF AF Burke, JF TI View from the past SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Burke, JF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2001 VL 130 IS 5 BP 890 EP 890 DI 10.1067/msy.2001.117191 PG 1 WC Surgery SC Surgery GA 490AL UT WOS:000172026000016 PM 11685199 ER PT J AU Anaya, M Romero, T Sofia, RD Yunis, EJ AF Anaya, M Romero, T Sofia, RD Yunis, EJ TI Linkage disequilibrium of HLA-A11 and A1 with one of the polymorphisms of the gamma-aminobutyric acid receptor type B SO TISSUE ANTIGENS LA English DT Article DE GABA(B) receptor 1; HLA; linkage disequilibrium ID GABA(B) RECEPTORS; EXPRESSION; CLONING; GENE AB The gamma-aminobutyric acid receptor type B 1 (GABA(B) R1) is located approximately at 200 kb telomeric to HLA-A on chromosome 6. It has 11 single-nucleotide polymorphisms (SNPs). We studied the most common of its SNPs (T1974C) in a panel of 118 normal Caucasians from New England and 161 epileptic patients of Caucasian ancestry residing in USA. The frequency of the polymorphism did not differ between patients and controls. Here, we report that the allele C of this SNP in the GABAB R1 gene is in linkage disequilibrium with HLA-A11 (P<0.00001) and to a lesser extent with HLA-A1 (P<0.01). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Wallace Labs, Cranbury, NJ USA. RP Yunis, EJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29582]; NIAID NIH HHS [U24AI49213] NR 13 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2001 VL 58 IS 5 BP 324 EP 328 DI 10.1034/j.1399-0039.2001.580506.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 516MN UT WOS:000173557200006 PM 11844143 ER PT J AU Yamada, A Salama, AD Najafian, N Auchincloss, H Sayegh, MH AF Yamada, A Salama, AD Najafian, N Auchincloss, H Sayegh, MH TI TNF : TNF-R T-Cell costimulatory pathways in transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2001: A Transplant Odyssey Congress CY 2001 CL ISTANBUL, TURKEY SP Novartis ID RENAL-ALLOGRAFT REJECTION; CD28 RECEPTOR; CD40 LIGAND; EXPRESSION; ACTIVATION; CTLA-4; RESPONSES; ANTIBODY; PRIMATES; BLOCKADE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Nephrol, Boston, MA 02114 USA. RP Sayegh, MH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 NR 20 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD NOV-DEC PY 2001 VL 33 IS 7-8 BP 3070 EP 3071 DI 10.1016/S0041-1345(01)02309-0 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 509JA UT WOS:000173143600013 PM 11750320 ER PT J AU Mitsiades, N Poulaki, V Mitsiades, CS Koutras, DA Chrousos, GR AF Mitsiades, N Poulaki, V Mitsiades, CS Koutras, DA Chrousos, GR TI Apoptosis induced FasL and TRAIL/Apo2L in the pathogenesis of thyroid diseases SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID TRAIL-INDUCED APOPTOSIS; INDUCED-PROXIMITY MODEL; MEDIATED APOPTOSIS; FOLLICULAR CELLS; AUTOIMMUNE-THYROIDITIS; HASHIMOTOS-THYROIDITIS; LIGAND EXPRESSION; GRAVES-DISEASE; DEATH RECEPTORS; IMMUNE EVASION AB FasL and TRAIL/Apo2L participate in cell-mediated cytotoxicity by inducing apoptosis in susceptible cells via respective cell surface receptors. Normal and neoplastic thyroid tissues are resistant-to FasL-induced apoptosis but are sensitized by Th-1-type cytokines. In Hashimoto's thyroiditis, both FasL and its receptor, Fas, are strongly upregulated and their interaction leads to the suicidal/fratricidal death of thyrocytes. In Graves' disease, FasL expression in thyroid follicular cells is induced by thionamides and kills infiltrating lymphocytes. In this condition, Th-2-type cytokines upregulate the anti-apoptotic molecules FLIP and Bcl-x(L) and protect thyrocytes from apoptosis. FasL is expressed by neoplastic thyrocytes and induces apoptosis of infiltrating lymphocytes. TRAIL/Apo2L kills thyroid carcinoma cells but spares normal thyrocytes,thus providing a potential therapy for thyroid cancer. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Univ Athens, Sch Med, GR-11527 Athens, Greece. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Mitsiades, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer Bldg,Room M557,44 Binney St, Boston, MA 02115 USA. NR 60 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2001 VL 12 IS 9 BP 384 EP 390 DI 10.1016/S1043-2760(01)00441-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 487EJ UT WOS:000171860400014 PM 11595539 ER PT J AU Grinspoon, S AF Grinspoon, S TI Insulin resistance in the HIV-lipodystrophy syndrome SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; TUMOR-NECROSIS-FACTOR; PROTEASE INHIBITORS; DIABETES-MELLITUS; PERIPHERAL LIPODYSTROPHY; CONTROLLED TRIAL; TROGLITAZONE; METFORMIN; HYPERINSULINEMIA; THERAPY AB Insulin resistance is increasingly recognized among HIV-infected patients with fat redistribution (lipodystrophy) who are receiving highly active antiretroviral therapy. The mechanisms of insulin resistance in this population remain unknown, but could relate to a decrease in glucose transport caused by the direct effects of certain antiretroviral agents, such as the protease inhibitors, or to the effects of severe fat redistribution, including subcutaneous fat loss and increased visceral adiposity. Insulin resistance in patients with HIV lipodystrophy is associated with hyperlipidemia and impaired fibrinolysis, and might increase the risk of cardiovascular disease (CVD). Furthermore, insulin-sensitizing agents might improve insulin resistance and reduce the risk of CVD in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. NR 33 TC 33 Z9 34 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2001 VL 12 IS 9 BP 413 EP + DI 10.1016/S1043-2760(01)00472-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 487EJ UT WOS:000171860400019 PM 11595544 ER PT J AU Morris, AD Zietman, AL Althausen, AF Heney, NM Kaufman, DS Shipley, WU AF Morris, AD Zietman, AL Althausen, AF Heney, NM Kaufman, DS Shipley, WU TI The value of external beam radiation in node positive prostate cancer: a multivariate analysis SO UROLOGIC ONCOLOGY LA English DT Article DE external beam radiation; node positive prostate cancer; prostate cancer ID STAGE-D1 ADENOCARCINOMA; THERAPY; CARCINOMA AB Purpose: The goal of this study was to evaluate the effect of local/regional treatment, particularly external beam radiation alone vs. radical prostatectomy plus radiation therapy in patients with pathologic node positive prostate cancer on survival. Methods: Medical records of all 116 patients who received their initial treatment at the Massachusetts General Hospital between 1980 and 1996 for adenocarcinoma of the prostate with pathologic confirmed nodal metastases and no distant metastases were reviewed. The mean follow up was 5.5 years. Overall survival, time to PSA failure on endocrine therapy, and time to first intervention were evaluated. The effect of the different treatment options were compared using multivariate Cox proportional hazard models to adjust for tumor characteristics that might influence survival. These included clinical T stage, clinical N stage, Gleason grade, number and location of positive lymph nodes and pretreatment PSA. Results: The combined patient population had a 5-year survival rate of 74% and a 10-year survival rate of 48%. Patients receiving local/regional treatment had adjusted 5 year survival rates of 80% compared to 27% for patients receiving no local/regional treatment (p = .001) with corresponding cumulative intervention rates (CIR) of 11% vs. 73% (p = .01) Patients receiving external beam radiation (XRT) alone did not differ significantly from those receiving prostatectomy plus radiation therapy in terms of survival (75 vs. 82%, p = .23) or cumulative intervention rates (14% vs. 14%, p = .94) Conclusion: Although it appears that all patients with node positive prostate cancer will eventually develop failure, this paper suggests local/regional therapy offers a medium term survival advantage over no local/regional treatment. The addition of prostatectomy did not confer a demonstrable advantage over radiation alone. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 01890 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 01890 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 01890 USA. RP Morris, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St, Boston, MA 01890 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1078-1439 J9 UROL ONCOL JI Urol. Oncol. PD NOV-DEC PY 2001 VL 6 IS 6 BP 255 EP 260 DI 10.1016/S1078-1439(01)00122-3 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 496QG UT WOS:000172407000006 ER PT J AU Rosenblatt, L Block, SD AF Rosenblatt, L Block, SD TI Depression, decision making, and the cessation of life-sustaining treatment SO WESTERN JOURNAL OF MEDICINE LA English DT Article C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Rosenblatt, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 10 Z9 10 U1 0 U2 2 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD NOV PY 2001 VL 175 IS 5 BP 320 EP 325 DI 10.1136/ewjm.175.5.320 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 486WX UT WOS:000171840900017 PM 11694480 ER PT J AU Lalan, S Pomerantseva, I Vacanti, JP AF Lalan, S Pomerantseva, I Vacanti, JP TI Tissue engineering and its potential impact on surgery SO WORLD JOURNAL OF SURGERY LA English DT Article ID BIODEGRADABLE POLYMER SCAFFOLDS; HETEROTOPIC HEPATOCYTE TRANSPLANTATION; EPITHELIAL ORGANOID UNITS; CULTURED VASCULAR CELLS; SHORT-BOWEL SYNDROME; NATIVE SMALL-BOWEL; HUMAN BLOOD-VESSEL; PARENTERAL-NUTRITION; IN-VITRO; HEPATOTROPHIC STIMULATION AB The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in healthcare. Current treatment modalities include transplantation of organs, surgical reconstruction, use of mechanical devices, or supplementation of metabolic products. A new field, tissue engineering, applies the principles and methods of engineering, material science, and cell and molecular biology toward the development of viable substitutes which restore, maintain, or improve the function of human tissues. In this review, we outline the opportunities and challenges of this emerging interdisciplinary field and its attempts to provide solutions to tissue creation and repair. Within this context, we present our experience using the basic tools of tissue engineering to guide regeneration of diverse tissues that include the liver, small intestine, cardiovascular structures, nerve, and cartilage. And in addition, we discuss the necessity of finding new strategies to achieve vascularization of complex tissues for transplant and present our approaches utilizing MicroElectroMechanical Systems (MEMS) technology and three-dimensional printing. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 11,55 Fruit St, Boston, MA 02114 USA. NR 87 TC 56 Z9 59 U1 1 U2 13 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV PY 2001 VL 25 IS 11 BP 1458 EP 1466 PG 9 WC Surgery SC Surgery GA 494ZY UT WOS:000172316800017 PM 11760750 ER PT J AU Ohdan, H Swenson, KG Kitamura, H Yang, YG Sykes, M AF Ohdan, H Swenson, KG Kitamura, H Yang, YG Sykes, M TI Tolerization of Gal alpha 1,3Gal-reactive B cells in pre-sensitized alpha 1,3-galactosyltransferase-deficient mice by nonmyeloablative induction of mixed chimerism SO XENOTRANSPLANTATION LA English DT Article DE B cells; bone marrow; transplantation; Gal alpha 1,3Gal epitopes; tolerance; xenotransplantation ID MEDIATED HYPERACUTE REJECTION; HUMAN NATURAL ANTIBODIES; ANTI-GAL ANTIBODY; MONOCLONAL-ANTIBODIES; TRANSPLANTATION; TOLERANCE; EPITOPES; BABOONS; IGG; XENOTRANSPLANTATION AB Using a alpha1,3-galactosyltransferase wild-type (GalT(+/+)) to deficient (GalT(-/-)) mouse bone marrow transplantation model, we have previously demonstrated that a non-myeloablative conditioning regimen is capable of permitting induction of allogeneic and xenogeneic mixed chimerism. Chimerism is associated with the rapid and lasting tolerization of anti-Gal alpha1,3Gal (Gal) natural antibody (Ab)-producing B cells. However, one limitation of this model is that anti-Gal natural Ab levels are lower in GalT(-/-) mice than in humans and other primates. To overcome this limitation, we have now investigated the possibility of inducing such tolerance in GalT(-/-) mice that produce much higher levels of anti-Gal Abs due to presensitization with Gal-bearing xenogeneic cells. B6 GalT(-/-) mice that were pre-sensitized with rabbit red blood cells received non-myeloablative conditioning with depleting anti-CD4 and CD8 mAbs, 3Gy whole body and 7Gy thymic irradiation, and infusion of BALB/c GalT(+/+) bone marrow cells (BMC). Although engraftment of standard marrow doses was inhibited by the presensitization, longlasting mixed chimerism could be induced in recipients of a high dose [160 X 10(6)] of allogencic wild-type BMC. Achievement of persistent chimerism was associated with high levels of anti-Gal IgG(1) pretransplant, suggesting an inhibitory effect of non-complement-fixing IgG, Ab on anti-Gal-modiated marrow rejection. Induction of mixed chimerism was associated with a rapid disappearance of serum anti-Gal and tolerization of anti-Gal Ab-producing cells. B cells with anti-Gal receptors became undetectable in mixed chimeras. Mixed chimeras accepted subsequently transplanted donor-type GalT(+/+) hearts (> 140 days), whereas rapid (within 2 days) rejection of GalT(+/+) hearts occurred in conditioned control GalT(-/-) mice. In conclusion, when a high dose of GalT(+/+) BMC was administered to pre-sensitized GalT(-/-) mice, chimerism and tolerance were achieved. The absence of B cells with receptors recognizing Gal in mixed chimeras suggests a role for clonal deletion/receptor editing in the maintenance of B cell tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Marrow Transplantat Sect,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL18646, R01 HL49915] NR 44 TC 38 Z9 38 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2001 VL 8 IS 4 BP 227 EP 238 DI 10.1034/j.1399-3089.2001.00006.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 489TN UT WOS:000172007900002 PM 11737848 ER PT J AU Renno, RZ Miller, JW AF Renno, RZ Miller, JW TI Photosensitizer delivery for photodynamic therapy of choroidal neovascularization SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE photosensitizer delivery; photosensitizer circulation; liposomal formulation; delivery vehicles; antibody-targeted photolysis; photodynamic therapy; choroidal neovascularization; age-related macular degeneration; verteporfin; benzoporphyrin derivative; Lu-Tex; motexatin lutetium; tin ethyl purpurin ID RETINAL-PIGMENT EPITHELIUM; LOW-DENSITY-LIPOPROTEIN; STERICALLY STABILIZED LIPOSOMES; HUMAN-PLASMA-PROTEINS; MOUSE-TUMOR MODEL; PHOTOCHEMICAL INITIATION; MACULAR DEGENERATION; VASCULAR OCCLUSION; SINGLET OXYGEN; BENZOPORPHYRIN AB The present review examines the importance of improving photosensitizer delivery for choroidal neovascularization (CNV) in light of the clinical impact of photodynamic therapy (PDT) for CNV An overview of the classes of available photosensitizers is provided and the properties governing photosensitizer uptake and circulation in serum are discussed. Current delivery systems, for example liposomal formulations as well as the use of the promising strategy of antibody targeted delivery as a strategy to improve PDT selectivity and efficiency for CNV treatment are described. A summary of the work using Verteporfin, tin ethyl purpurin and Lu-Tex - photosensitizers currently in clinical trials for CNV - is given. (C) 2001 Elsevier Science B V. All rights rc;served. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv, Boston, MA 02115 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv, Boston, MA 02115 USA. NR 92 TC 41 Z9 45 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD OCT 31 PY 2001 VL 52 IS 1 BP 63 EP 78 DI 10.1016/S0169-409X(01)00195-8 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 497AV UT WOS:000172431300007 PM 11672876 ER PT J AU Henne, KR Kunze, KL Zheng, YM Christmas, P Soberman, RJ Rettie, AE AF Henne, KR Kunze, KL Zheng, YM Christmas, P Soberman, RJ Rettie, AE TI Covalent linkage of prosthetic heme to CYP4 family P450 enzymes SO BIOCHEMISTRY LA English DT Article ID PHENYL-IRON COMPLEXES; CRYSTAL-STRUCTURE; INSITU REARRANGEMENT; TOPOLOGICAL ANALYSIS; HEMOPROTEIN DOMAIN; CATALYTIC FUNCTION; ACTIVE-SITES; CYTOCHROME-P450; IDENTIFICATION; SUBSTRATE AB An extensive body of research on the structural properties of cytochrome P450 enzymes has established that these proteins possess a b-type heme prosthetic group which is noncovalently bound at the active site. Coordinate, electrostatic, and hydrogen bond interactions between the protein backbone and heme functional groups are readily overcome upon mild acid treatment of the enzyme, which releases free heme from the protein. In the present study, we have used a combination of HPLC, LC/ESI-MS, and SDS-PAGE techniques to demonstrate that members of the mammalian CYP4B, CYP4F, and CYP4A subfamilies bind their heme in an unusually tight manner. HPLC chromatography of CYP4B1 on a POROS R2 column under mild acidic conditions caused dissociation of less than one-third of the heme from the protein. Moreover, heme was not substantially removed from CYP4B1 under electrospray or electrophoresis conditions that readily release the prosthetic group from other non-CYP4 P450 isoforms. This was evidenced by an intact protein mass value of 59 217 +/- 3 amu for CYP4B1 (i.e., apoprotein plus heme) and extensive staining of this similar to 60 kDa protein with tetramethylbenzidine/H2O2 following SDS-PAGE. In addition, treatment of CYP4B1, CYP4F3, and CYP4A5/7 with strong base generated a new, chromatographically distinct, polar heme species with a mass of 632.3 amu rather than 616.2 amu. This mass shift is indicative of the incorporation of an oxygen atom into the heme nucleus and is consistent with the presence of a novel covalent ester linkage between the protein backbone of the CYP4 family of mammalian P450s and their heme catalytic center. C1 Univ Washington, Dept Med Chem, Sch Pharm, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rettie, AE (reprint author), Univ Washington, Dept Med Chem, Sch Pharm, Box 357610, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK59991]; NIGMS NIH HHS [GM61823, GM49054, GM07750] NR 43 TC 51 Z9 55 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 30 PY 2001 VL 40 IS 43 BP 12925 EP 12931 DI 10.1021/bi011171z PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488XL UT WOS:000171962100020 PM 11669629 ER PT J AU Schumacher, B Hofmann, K Boulton, S Gartner, A AF Schumacher, B Hofmann, K Boulton, S Gartner, A TI The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis SO CURRENT BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; FUNCTIONAL GENOMIC ANALYSIS; CAENORHABDITIS-ELEGANS; INDUCED PHOSPHORYLATION; RNA INTERFERENCE; GENETIC-CONTROL; DROSOPHILA P53; MUTATIONS; PROTEIN AB In mammals, one of the key regulators necessary for responding to genotoxic stress is the p53 transcription factor. p53 is the single most commonly mutated tumor suppressor gene in human cancers [1]. Here we report the identification of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosuppression technology, we show that C. elegans p53 (cep-1) is required for DNA damage-induced apoptosis in the C. elegans germline. However, cep-1 RNAi does not affect programmed cell death occurring during worm development and physiological (radiation-independent) germ cell death. The DNA binding domain of CEP-1 is related to vertebrate p53 members and possesses the conserved residues most frequently mutated in human tumors. Consistent with this, CEP-1 acts as a transcription factor and is able to activate a transcriptional reporter containing consensus human p53 binding sites. Our data support the notion that p53-mediated transcriptional regulation is part of an ancestral pathway mediating DNA damage-induced apoptosis and reveals C. elegans as a genetically tractable model organism for studying the p53 apoptotic pathway. C1 Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany. MEMOREC Stoffel GmbH, D-50829 Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Max Planck Inst Biochem, Dept Cell Biol, Klopferspitz 18A, D-82152 Martinsried, Germany. EM gartner@biochem.mpg.de RI Hofmann, Kay/D-6714-2011; Schumacher, Bjorn/I-4829-2013 OI Hofmann, Kay/0000-0002-2289-9083; Schumacher, Bjorn/0000-0001-6097-5238 NR 28 TC 203 Z9 226 U1 5 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD OCT 30 PY 2001 VL 11 IS 21 BP 1722 EP 1727 DI 10.1016/S0960-9822(01)00534-6 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 490PT UT WOS:000172060800027 PM 11696333 ER PT J AU Babich, JW Graham, W Femia, FJ Dong, Q Barzana, M Ferrill, K Fischman, AJ Zubieta, J AF Babich, JW Graham, W Femia, FJ Dong, Q Barzana, M Ferrill, K Fischman, AJ Zubieta, J TI 6-mercaptomethylpyridine-3-carboxylic acid (MEMNIC): a new reagent for peptide labeling with Tc-99m SO INORGANICA CHIMICA ACTA LA English DT Article DE Tc-99m-labeled mercaptomethylpyridine-3-carboxylate; rhenium(V) oxo core complexes; Tc-99m radiolabeled peptide conjugates; Tc-99m-labeled chemotactic peptides ID IMAGING FOCAL SITES; SMALL-MOLECULE RADIOPHARMACEUTICALS; DERIVATIZED CHEMOTACTIC PEPTIDES; IIB/IIIA-RECEPTOR ANTAGONIST; POLYCLONAL IMMUNOGLOBULIN-G; TECHNETIUM RADIOPHARMACEUTICALS; BACTERIAL-INFECTION; IN-VITRO; COMPLEXES; CRYSTAL AB As part of our ongoing research into the development of peptide based radiopharmaceuticals, we have explored 2-mercaptopyridines and 2-mercapto-pyrimidines (2MPs) as coligands to control the radiochemical speciation of Tc-99m-labeled hydrazinonicotinamide (HYNIC) derivatized chemotactic peptides. In an attempt to develop an aminothiol ligand with greater stability, we synthesized 6-mereaptomethylpyridine-3-carboxylic acid (MEMNIC), assuming a five-member chelate ring complex would be more stable than the four-membered ring possible with 2MPs. Initial experiments suggested that Tc-99m-MEMNIC was stable in vivo and led to our investigation of it as a bifunctional chelator for Tc-99m labeling of peptides. The utility of MEMNIC was tested in a rabbit model of infection. The N-epsilon MEMNIC derivative of For-MLFK was prepared using the N-hydroxysuccinimidyl ester of MEMNIC. For-MLFK-MEMNIC was labeled via Tc-99m-mannitol and its imaging and biodistribution properties compared to Tc-For-MLFK-HYNIC and Tc-For-MLFCys (labeled via the free thiol of cysteine). Sites of infection were produced in New Zealand white rabbits (n = 6/peptide) by injection of a suspension of Escherichia coli in a posterior thigh. Twenty-four hours after infection, the rabbits were injected intravenously with 0.5 mCi of HPLC purified Tc-99m-peptide and imaged at 2.5 and 18 h p.i. The animals were sacrificed at 18 h and tissue activity determined. At 2.5 and 18 It, the organ distribution of Tc-For-MLFK-HYNIC and Tc-For-MLFK-MEMNIC were qualitatively similar with the exception of higher renal accumulation of the latter, whereas Tc-For-MLFKCys showed rapid and prolonged accumulation in bowel. ROI analysis gave target/background ratios of 3.91 +/- 0.32 and 11.89 +/- 2.21 for Tc-For-MLFK-HYNIC, 5.09 +/- 0.66 and 9.88 +/- 1.12 for Tc-For-MLFK-MEMNIC and 2.59 +/- 0.16 and 1.70 +/- 0.37 for Tc-For-MLFCys, at 2.5 and 18 h. Tissue radioactivity measurements (18 h) demonstrated that compared to Tc-For-MLFK-HYNIC, the accumulation of Tc-For-MLFK-MEMNIC was less in all organs except in kidney which was greater. Direct labeling of the thiol group of cysteine led to lower accumulation in all organs compared to Tc-For-MLFK-MEMNIC, except in GI tract which was fivefold higher. While, Tc-For-MLFK-MEMNIC had half the accumulation of Tc-For-MLFK-HYNIC in infected muscle and pus, the lower accumulation in most organs and normal muscle resulted in good infection localization. These results indicate that MEMNIC can be successfully used to label peptides with Tc-99m while exhibiting good in vivo stability. The chemistry of MEMNIC with the {M(V)O}(3+) core characteristic of technetiun and its Group V congener rhenium was modeled by investigating the reactions of 2-mercaptomethylpyridine with appropriate Re(V)-oxo precursors in the presence of a variety of coligands, With diolate type tridentate donors of the class {X(CH2CH2O)(2)}(2-) (X = -NR, O, S), the '3+2' compounds [ReO{eta (3)-(OCH2CH2)(2)S}{eta (2)-SCH2C5H4N}] (2) and [ReO{eta (3)-(OCH2CH2)(2)NCH3}{eta (2) -SCH2C5H4N}] (3) were isolated. In contrast, with the more sterically demanding dirmercapto class of tridentate ligands {S(CH2CH2S)(2)}(2-), the '3+1' species [ReO{eta (3)-(SCH2CH2)(2)S}{eta (1)-(SCH2C5H4N)}] was isolated. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Biostream Inc, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Babich, JW (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. EM jazubiet@syr.edu NR 58 TC 6 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD OCT 29 PY 2001 VL 323 IS 1-2 BP 23 EP 36 DI 10.1016/S0020-1693(01)00600-4 PG 14 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 490WR UT WOS:000172077100004 ER PT J AU Andreassen, OA Ferrante, RJ Dedeoglu, A Beal, MF AF Andreassen, OA Ferrante, RJ Dedeoglu, A Beal, MF TI Lipoic acid improves survival in transgenic mouse models of Huntington's disease SO NEUROREPORT LA English DT Article DE antioxidants; excitotoxicity; Huntington's disease; alpha-lipoic acid; transgenic mice ID REPERFUSION INJURY; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; CAG REPEAT; IN-VIVO; RATS; PERFORMANCE; PROTECTS; MICE AB There is substantial evidence implicating excitotoxicity and oxidative damage in the pathogenesis of Huntington's disease (HD). We therefore examined whether the antioxidants 2-sulpho-tert-phenylbutyinitrone (S-PBN) and alpha -lipoic acid could exert neuroprotective effects in transgenic mouse models of HD. S-PBN showed no effects on either weight loss or survival in the R6/2 transgenic HD mice. alpha -Lipoic acid produced significant increases in survival in both R6/2 and N171-82Q transgenic mouse models of HD. These findings suggest that alpha -lipoic acid might have beneficial effects in HD patients. NeuroReport 12:3371-3373 (C) 2001 Lippincott Williams & Wilkins. C1 Cornell Univ, Weill Med Coll, New York Hosp, Cornell Med Ctr,Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, New York Hosp, Cornell Med Ctr,Dept Neurol & Neurosci, 525 E 68th St, New York, NY 10021 USA. FU NIA NIH HHS [AG12992, AG14390]; NINDS NIH HHS [NS38180] NR 25 TC 64 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 29 PY 2001 VL 12 IS 15 BP 3371 EP 3373 DI 10.1097/00001756-200110290-00044 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 487WT UT WOS:000171902600040 PM 11711888 ER PT J AU Wolpert, HA Anderson, BJ AF Wolpert, HA Anderson, BJ TI Management of diabetes: are doctors framing the benefits from the wrong perspective? SO BRITISH MEDICAL JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; GLUCOSE CONTROL; EDUCATION C1 Joslin Diabet Ctr, Sect Adult Diabet, Boston, MA 02215 USA. Joslin Diabet Ctr, Behav & Mental Hlth Res Unit, Boston, MA 02215 USA. RP Wolpert, HA (reprint author), Joslin Diabet Ctr, Sect Adult Diabet, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-46887, R01 DK046887] NR 23 TC 57 Z9 58 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD OCT 27 PY 2001 VL 323 IS 7319 BP 994 EP 996 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 488CU UT WOS:000171918500027 PM 11679393 ER PT J AU Ovuworie, CA Fox, ER Chow, CM Pascual, M Shih, VE Picard, MH Tolkoff-Rubin, NE AF Ovuworie, CA Fox, ER Chow, CM Pascual, M Shih, VE Picard, MH Tolkoff-Rubin, NE TI Vascular endothelial function in cyclosporine and tacrolimus treated renal transplant recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Nephrology CY OCT 11-16, 2000 CL TORONTO, CANADA SP Amer Soc Nephrol ID NITRIC-OXIDE; DYSFUNCTION; HOMOCYSTEINE; MECHANISMS; CORONARY; DISEASE; ARTERY AB Background. Endothelial dysfunction is an early key event in the development of arteriosclerotic cardiovascular disease (ASCVD), thus an early marker of subclinical ASCVD. Endothelial function is impaired in renal transplant recipients (RTR) treated with cyclosporine (CyA). Tacrolimus is associated with less hyperlipidemia and hypertension than CyA, however, there are no data on endothelial function in tacrolimus-treated RTR. Methods. High-resolution brachial ultrasonography was used to assess endothelium-dependent dilatation (EDD), and endothelium-independent dilatation (EID) in 20 stable RTR and a control group of 10 healthy subjects without clinical evidence of ASCVD. The RTR group included patients receiving CyA (n=10) and tacrolimus (n=10). EDD and EID were measured as percent increase in brachial artery diameter in response to reactive hyperemia and nitroglycerin, respectively. Results and Conclusions. EDD was significantly lower in RTR versus controls (1.7 +/-0.7 vs. 7.3 +/-0.7%, P <0.0001), whereas EID was similar in the two groups. No significant differences were found in EDD or in EID between CyA- and tacrolimus-treated RTR. Glomerular filtration rate, plasma homocysteine, blood pressure, and lipid profiles were similar in CyA- and tacrolimus-treated RTR. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Amino Acid Lab, Boston, MA 02114 USA. RP Tolkoff-Rubin, NE (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, GRB 858, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 16 TC 51 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2001 VL 72 IS 8 BP 1385 EP 1388 DI 10.1097/00007890-200110270-00009 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 488QV UT WOS:000171947900009 PM 11685108 ER PT J AU Massicot-Fisher, J Noel, P Madsen, JC AF Massicot-Fisher, J Noel, P Madsen, JC TI Recommendations of the National Heart, Lung and Blood Institute Heart and Lung Tolerance Working Group SO TRANSPLANTATION LA English DT Article ID BONE-MARROW INFUSION; MINIATURE SWINE; TRANSPLANTATION C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Dept Surg,Div Cardiac Surg, Boston, MA USA. RP Massicot-Fisher, J (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, 6701 Rockledge Dr,MSC 7940, Bethesda, MD 20892 USA. NR 9 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2001 VL 72 IS 8 BP 1467 EP 1470 DI 10.1097/00007890-200110270-00028 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 488QV UT WOS:000171947900028 PM 11685126 ER PT J AU Madsen, JC AF Madsen, JC TI Tailoring tolerance to prevent chronic rejection SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 5th Annual Winter Symposium of the American-Society-of-Transplantation CY FEB 15-18, 2001 CL MAUNA LANI, HAWAII SP Amer Soc Transplantat ID HUMAN CYTOMEGALO-VIRUS; CARDIAC ALLOGRAFTS; TRANSPLANT RECIPIENTS; INDIRECT RECOGNITION; INTERFERON-GAMMA; IMMUNOSUPPRESSION; PEPTIDES; ARTERIOSCLEROSIS; ALLORECOGNITION; AUTOIMMUNITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [2R01-HL54211-04] NR 29 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2001 VL 72 IS 8 SU S BP S10 EP S12 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 490GT UT WOS:000172042600004 PM 11888149 ER PT J AU Hayter, HL Pettus, BJ Ito, F Obeid, LM Hannun, YA AF Hayter, HL Pettus, BJ Ito, F Obeid, LM Hannun, YA TI TNF alpha-induced glutathione depletion lies downstream of cPLA(2) in L929 cells SO FEBS LETTERS LA English DT Article DE arachidonic acid; apoptosis; ceramide; glutathione; sphingomyelin ID TUMOR-NECROSIS-FACTOR; MITOCHONDRIAL RESPIRATORY-CHAIN; CYTOSOLIC PHOSPHOLIPASE A(2); CERAMIDE-INDUCED APOPTOSIS; ARACHIDONIC-ACID; NEUTRAL SPHINGOMYELINASE; MEDIATED APOPTOSIS; CYTOTOXIC ACTION; INVOLVEMENT; DEATH AB Both glutathione (GSH) depletion and arachidonic acid (AA) generation have been shown to regulate sphingomyelin (SM) hydrolysis and are known components in tumor necrosis factor alpha (TNF alpha)-induced cell death. In addition, both have hypothesized direct roles in activation of N-sphingomyelinase (SMase); however, it is not known whether these are independent pathways of N-SMase regulation or linked components of a single ordered pathway. This study was aimed at differentiating these possibilities using L929 cells. Depletion of GSH with L-buthionin-(S,R)-sulfoximine (BSO) induced 50% hydrolysis of SM at 12 h. In addition, TNF induced a depletion of GSH, and exogenous addition of GSH blocked TNF-induced SM hydrolysis as well as TNF-induced cell death. Together, these results establish GSH upstream of SM hydrolysis and ceramide generation in L929 cells. We next analyzed the L929 variant, C12, which lacks both cytosolic phospholipase A(2) (cPLA(2)) mRNA and protein, in order to determine the relationship of cPLA(2) and GSH. TNF did not induce a significant drop in GSH levels in the C12 line. On the other hand, AA alone was capable of inducing a 60% depletion of GSH in C12 cells, suggesting that these cells remain responsive to AA distal to the site of cPLA(2). Furthermore, depleting GSH with BSO failed to effect AA release, but caused a drop in SM levels, showing that the defect in these cells was upstream of the GSH drop and SMase activation. When cPLA(2) was restored to the C12 line by expression of the cDNA, the resulting CPL4 cells regained sensitivity to TNF. Treatment of the CPL4 cells with TNF resulted in GSH levels dropping to levels near those of the wildtype L929 cells. These results demonstrate that GSH depletion following TNF treatment in L929 cells is dependent on intact cPLA(2) activity, and suggest a pathway in which activation of cPLA(2) is required for the oxidation and reduction of GSH levels followed by activation of SMases. (C) 2000 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Setsunan Univ, Dept Biochem, Hirakata, Osaka 57301, Japan. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave,POB 250780, Charleston, SC 29425 USA. FU NIA NIH HHS [AG 16583]; NIGMS NIH HHS [GM 43825] NR 39 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 26 PY 2001 VL 507 IS 2 BP 151 EP 156 DI 10.1016/S0014-5793(01)02967-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 488HY UT WOS:000171922900007 PM 11684089 ER PT J AU Zhang, CWH Chishti, Y Hussey, RE Reinherz, EL AF Zhang, CWH Chishti, Y Hussey, RE Reinherz, EL TI Expression, purification, and characterization of recombinant HIV gp140 - The gp41 ectodomain of HIV or simian immunodeficiency virus is sufficient to maintain the retroviral envelope glycoprotein as a trimer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLUBLE CD4 BINDING; RECEPTOR-BINDING; CONFORMATIONAL-CHANGES; GP120-CD4 BINDING; ATOMIC-STRUCTURE; CLEAVAGE SITE; HTLV-III; SIV GP41; TYPE-1; PROTEIN AB Efforts to understand the molecular basis of human immunodeficiency virus (HM envelope glycoprotein function have been hampered by the inability to generate sufficient quantities of homogeneous material. We now report on the high level expression, purification, and characterization of soluble HIV gp140 ectodomain proteins in Chinese hamster ovary-Lec3.2.8.1 cells. Gel filtration and analytical ultracentrifugation show that the uncleaved ADA strain-derived gp140 proteins are trimeric without further modification required to maintain oligomers. These spike proteins are native as judged by soluble CD4 (sCD4) (K-D = 1-2 nm) and monoclonal antibody binding studies using surface plasmon resonance. CD4 ligation induces conformational change in the trimer, exposing the chemokine receptor binding site as assessed by 17b monoclonal antibody reactivity. Lack of anti-cooperativity in sCD4-ADA trimer interaction distinct from that observed with sCD4-SrV mac32H implies quaternary structural differences in ground states of their respective spike proteins. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 43649] NR 63 TC 66 Z9 67 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 26 PY 2001 VL 276 IS 43 BP 39577 EP 39585 DI 10.1074/jbc.M107147200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 485XR UT WOS:000171789200012 PM 11514580 ER PT J AU Aschenbach, WG Suzuki, Y Breeden, K Prats, C Hirshman, MF Dufresne, SD Sakamoto, K Vilardo, PG Steele, M Kim, JH Jing, SL Goodyear, LJ DePaoli-Roach, AA AF Aschenbach, WG Suzuki, Y Breeden, K Prats, C Hirshman, MF Dufresne, SD Sakamoto, K Vilardo, PG Steele, M Kim, JH Jing, SL Goodyear, LJ DePaoli-Roach, AA TI The muscle-specific protein phosphatase PP1G/R-GL(G(M)) is essential for activation of glycogen synthase by exercise SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; TARGETING SUBUNITS; PHOSPHORYLATION SITES; CONTRACTILE ACTIVITY; MOLECULAR MECHANISM; 3T3-L1 ADIPOCYTES; KINASE-B; IN-VIVO; INSULIN AB In skeletal muscle both insulin and contractile activity are physiological stimuli for glycogen synthesis, which is thought to result in part from the dephosphorylation and activation of glycogen synthase (GS). PP1G/R-GL(G(M)) is a glycogen/sarcoplasmic reticulum-associated type I phosphatase that was originally postulated to mediate insulin control of glycogen metabolism. However, we recently showed (Suzuki, Y., Lanner, C., Kim, J.-H., Vilardo, P. G., Zhang, H., Jie Yang, J., Cooper, L. D., Steele, M., Kennedy, A., Bock, C., Scrimgeour, A., Lawrence, J. C. Jr., L., and DePaoli-Roach, A. A. (2001) Mol. Cell. Biol. 21, 2683-2694) that insulin activates GS in muscle of R-GL(G(M)) knockout (KO) mice similarly to the wild type (WT). To determine whether PP1G is involved in glycogen metabolism during muscle contractions, RGL KO and overexpressors (OE) were subjected to two models of contraction, in vivo treadmill running and in situ electrical stimulation. Both procedures resulted in a 2-fold increase in the GS -/+ glucose-6-P activity ratio in WT mice, but this response was completely absent in the KO mice. The KO mice, which also have a reduced GS activity associated with significantly reduced basal glycogen levels, exhibited impaired maximal exercise capacity, but contraction-induced activation of glucose transport was unaffected. The R-GL OE mice are characterized by enhanced GS activity ratio and an similar to3-4-fold increase in glycogen content in skeletal muscle. These animals were able to tolerate exercise normally. Stimulation of GS and glucose uptake following muscle contraction was not significantly different as compared with WT littermates. These results indicate that although PP1G/R-GL is not necessary for activation of GS by insulin, it is essential for regulation of glycogen metabolism under basal conditions and in response to contractile activity, and may explain the reduced muscle glycogen content in the R-GL KO mice, despite the normal insulin activation of GS. C1 Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Res Div, Boston, MA 02215 USA. RP DePaoli-Roach, AA (reprint author), Indiana Univ, Sch Med, Dept Biochem & Mol Biol, 635 Barnhill Dr, Indianapolis, IN 46202 USA. RI Prats, Clara/F-5993-2014 FU NIAMS NIH HHS [AR 42238, AR 45670]; NIDDK NIH HHS [DK 36569, DK 59769] NR 69 TC 77 Z9 80 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 26 PY 2001 VL 276 IS 43 BP 39959 EP 39967 DI 10.1074/jbc.M105518200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 485XR UT WOS:000171789200062 PM 11522787 ER PT J AU Kimberly, WT Zheng, JB Guenette, SY Selkoe, DJ AF Kimberly, WT Zheng, JB Guenette, SY Selkoe, DJ TI The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a Notch-like manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-SECRETASE CLEAVAGE; C-TERMINAL FRAGMENTS; DISINTEGRIN-METALLOPROTEASE; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; GAMMA-SECRETASE; BINDING; RELEASE; NEURONS; GENE AB The beta -amyloid precursor protein (APP) is a ubiquitous receptor-like molecule without a known function. However, the recent recognition that APP and Notch undergo highly similar proteolytic processing has suggested a potential signaling function for APP. After ligand binding, Notch is cleaved by the ADAM-17 metalloprotease followed by an intramembrane cleavage mediated by gamma -secretase. The gamma -secretase cut releases the Notch intracellular domain (NICD), which enters the nucleus and modulates transcription. Because APP is processed similarly by ADAM-17 and gamma -secretase, we reasoned that the APP intracellular domain (AICD) has a role analogous to the NICD. We therefore generated a plasmid encoding the AICD sequence and studied the subcellular localization of the expressed protein (C60). Our results demonstrate that the cytoplasmic domain of APP is a highly labile fragment that is stabilized by forming complexes with Fe65 and can then enter the nucleus in neurons and non-neural cells. These findings strongly support the hypothesis that APP signals in the nucleus in a manner analogous to the function of Notch. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Selkoe, DJ (reprint author), Harvard Inst Med, Ctr Neurol Dis, 730,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIA NIH HHS [AG 06173] NR 33 TC 335 Z9 345 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 26 PY 2001 VL 276 IS 43 BP 40288 EP 40292 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 485XR UT WOS:000171789200104 PM 11544248 ER PT J AU Steveson, TC Zhao, GC Keutmann, HT Mains, RE Eipper, BA AF Steveson, TC Zhao, GC Keutmann, HT Mains, RE Eipper, BA TI Access of a membrane protein to secretory granules is facilitated by phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-AMIDATING MONOOXYGENASE; TRANS-GOLGI NETWORK; PEPTIDE-PROCESSING ENZYME; MANNOSE 6-PHOSPHATE RECEPTOR; CYTOSOLIC ROUTING DETERMINANTS; KINASE-II PHOSPHORYLATION; CYTOPLASMIC DOMAIN; PLASMA-MEMBRANE; CHROMOGRANIN-A; P-SELECTIN AB Peptidylglycine a-amidating monooxygenase (PAM), an integral membrane protein essential for the biosynthesis of amidated peptides, was used to assess the role of cytosolic acidic clusters in trafficking to regulated secretory granules. Casein kinase II phosphorylates Ser(949) and Thr(946) of PAM, generating a short, cytosolic acidic cluster. P-CIP2, a protein kinase identified by its ability to interact with several juxtamembrane determinants in the PAM cytosolic domain, also phosphorylates Ser(949). Antibody specific for phospho-Ser(949)-PAM-CD demonstrates that a small fraction of the PAM-1 localized to the perinuclear region bears this modification. Pituitary cell lines expressing PAM-1 mutants that mimic (TS/DD) or prevent (TS/AA) phosphorylation at these sites were studied. PAM-1 TS/AA yields a lumenal monooxygenase domain that enters secretory granules inefficiently and is rapidly degraded. In contrast, PAM-1 TS/DD is routed to regulated secretory granules more efficiently than wild-type PAM-1 and monooxygenase release is more responsive to secretagogue. Furthermore, this acidic cluster affects exit of internalized PAM-antibody complexes from late endosomes; internalized PAM-1 TS/DD accumulates in a late endocytic compartment instead of the trans-Golgi network. The increased ability of solubilized PAM-1 TS/DD to aggregate at neutral pH may play an important role in its altered trafficking. C1 Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. Georgetown Univ, Georgetown Med Ctr, Washington, DC 20007 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Eipper, BA (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurosci, MC 3401,263 Farmington Ave, Farmington, CT 06030 USA. FU NIDDK NIH HHS [DK-32949, DK-09520] NR 81 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 26 PY 2001 VL 276 IS 43 BP 40326 EP 40337 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 485XR UT WOS:000171789200110 PM 11524414 ER PT J AU Rui, LY Fisher, TL Thomas, J White, MF AF Rui, LY Fisher, TL Thomas, J White, MF TI Regulation of insulin/insulin-like growth factor-1 signaling by proteasome-mediated degradation of insulin receptor substrate-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; MAMMALIAN TARGET; KAPPA-B; 3T3-L1 ADIPOCYTES; MICE LACKING; IN-VITRO; RESISTANCE; PATHWAY; RAPAMYCIN; ALPHA AB Insulin and insulin-like growth factor-1 (IGF-1) regulate metabolism and body growth through homologous receptor tyrosine kinases that phosphorylate the insulin receptor substrate (IRS) proteins. IRS-2 is an important IRS protein, as it mediates peripheral insulin action and beta -cell survival. In this study, we show that insulin, IGF-1, or osmotic stress promoted ubiquitin/proteasome-mediated degradation of IRS-2 in 3T3-L1 cells, Fao hepatoma, cells and mouse embryo fibroblasts; however, insulin/IGF-1 did not promote degradation of IRS-1 in 3T3-L1 preadipocytes or mouse embryo fibroblasts. MG132 or lactacystin, specific inhibitors of 26S proteasome, blocked insulin/IGF-1-induced degradation of IRS-2 and enhanced the detection of ubiquitinated IRS-2. Insulin/IGF1-induced ubiquitination and degradation of IRS-2 was blocked by inhibitors of phosphatidylinositol 3-kinase (wortmannin or LY294002) or mTOR (rapamycin). Chronic insulin or IGF-1 treatment of IRS-1-deficient mouse embryo fibroblasts inhibited IRS-2-mediated activation of Akt and ERK1/2, which was reversed by lactacystin pretreatment. By contrast, IRS-I activation of Akt and ERK1/2 was not inhibited by chronic insulin/IGF-1 stimulation in IRS-2-deficient mouse embryo fibroblasts. Thus, we identified a novel negative feedback mechanism by which the ubiquitin/proteasome-mediated degradation of IRS-2 limits the magnitude and duration of the response to insulin or IGF-1. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 43808] NR 41 TC 139 Z9 148 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 26 PY 2001 VL 276 IS 43 BP 40362 EP 40367 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 485XR UT WOS:000171789200114 PM 11546773 ER PT J AU Ruvkun, G AF Ruvkun, G TI Molecular biology - Glimpses of a tiny RNA world SO SCIENCE LA English DT Editorial Material ID C-ELEGANS; REGULATORY RNA; GENE ACTS; INTERFERENCE; PLANTS; LIN-14; RDE-1 C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 20 TC 169 Z9 218 U1 4 U2 27 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 26 PY 2001 VL 294 IS 5543 BP 797 EP 799 DI 10.1126/science.1066315 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487AP UT WOS:000171851800029 PM 11679654 ER PT J AU Weir, MM Bell, DA AF Weir, MM Bell, DA TI Cytologic identification of serous neoplasms in peritoneal fluids SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Scientific Meeting of the American-Society-of-Cytopathology CY NOV 03-07, 1998 CL NASHVILLE, TENNESSEE SP Amer Soc Cytopthol DE peritoneal fluid cytology; reactive mesothelial cells; serous borderline tumor; serous carcinoma ID DIFFERENTIAL-DIAGNOSIS; OVARIAN-TUMORS; WASHINGS; CRITERIA AB BACKGROUND. Recognition of serous neoplasms in peritoneal fluids and their subclassification into serous borderline tumors (SBT) and serous carcinomas (SCA) may be difficult. The objective of this study was to determine whether morphologic criteria can distinguish reactive mesothelial cells (RM), SBT, and SCA (grades 1-3) in peritoneal fluids. METHODS. A blinded review of 42 peritoneal fluids from 40 patients with histologically confirmed RM (n = 10 patients), SBT (n = 7 patients; 3 with primary ovarian tumors and 4 with primary peritoneal tumors), and SCA (n = 23 patients; 7 with grade 1 tumors, 6 with grade 2 tumors, and 10 with grade 3 tumors; 12 with primary ovarian tumors and 11 with primary peritoneal tumors) evaluated papillae presence and size, intercellular windows, group contours, dyshesion, nuclear atypia, size and overlap, cell size, and nucleoli and nuclear-to-cytoplasmic ratios. From these parameters, specimens were classified as RM, SBT versus grade 1 SCA, or grade 2 SCA versus grade 3 SCA. RESULTS. RM were identified as groups of small cells with minimal nuclear atypia and overlap, intercellular windows, and irregular group borders without papillae. No features differentiated SBT from grade 1 SCA. Grade 2 and 3 SCA showed more nuclear atypia and overlap with larger nuclei and cells. Thirty-nine of 42 specimens (95%) were correctly identified as RM or serous neoplasm. Two SBT specimens and one grade 1 SCA specimen were overcalled, and three SCA specimens (two grade 2 and one grade 3) were undergraded. CONCLUSIONS. The distinction of RM from serous neoplasms in peritoneal fluids is possible in most patients by examination of cell group architecture, nuclear atypia, and nuclear size. Differentiation of SBT from grade 1 SCA is not reliable, meriting a differential diagnosis. Most high-grade SCA specimens can be identified by increased nuclear atypia, overlap, and size. (C) 2001 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, Toronto Gen Hosp, Hlth Network, Dept Pathol, Toronto, ON M5G 1L7, Canada. Univ Toronto, Toronto, ON, Canada. RP Bell, DA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 76 Fruit St, Boston, MA 02114 USA. NR 16 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2001 VL 93 IS 5 BP 309 EP 318 DI 10.1002/cncr.9045 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 483MC UT WOS:000171638000002 PM 11668465 ER PT J AU Dorvault, CC Weilbaecher, KN Yee, H Fisher, DE Chiriboga, LA Xu, Y Chhieng, DC AF Dorvault, CC Weilbaecher, KN Yee, H Fisher, DE Chiriboga, LA Xu, Y Chhieng, DC TI Microphthalmia transcription factor - A sensitive and specific marker for malignant melanoma in cytologic specimens SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-31, 2000 CL NEW ORLEANS, LOUISIANA SP US & Canadian Acad Pathol DE microphthalmia transcription factor; melanoma; S-100; HMB-45; cytology ID METASTATIC AMELANOTIC MELANOMAS; HMB-45 MONOCLONAL-ANTIBODY; PARAFFIN-EMBEDDED TISSUES; NEEDLE ASPIRATION BIOPSY; S-100 PROTEIN; GENE-PRODUCT; DIAGNOSIS; MART-1; TUMORS; IMMUNOPEROXIDASE AB BACKGROUND. The diagnosis of melanoma can be difficult because of shared cytomorphology with other malignant neoplasms. The most commonly used melanocytic markers, anti-S-100 protein and HMB-45 antigen, have limited specificity and sensitivity, respectively. Microphthalmia transcription factor (Mitf) is a nuclear transcription factor critical for the development and survival of melanocytes and has been shown as a sensitive and specific marker for melanoma in histologic specimens. METHODS. To evaluate the efficacy of Mitf as a marker for melanoma in cytologic preparations, 81 cell blocks from 44 patients with melanoma and 37 patients with nonmelanoma malignancies (29 patients with carcinoma, 4 patients with mesotheliomas, 2 patients with lymphoma, and 2 patients with islet cell tumors) were stained with monoclonal antibodies against Mitf (clone D5), S-100 protein, and HMB-45 antigen. The staining was evaluated blindly by three independent observers. The presence of nuclear staining for Mitf and cytoplasmic staining for S-100 protein or HMB-45 antigen in > 10% of tumor cells was considered positive staining for each antigen. RESULTS. Forty-four melanomas (100%), including all 3 spindle-cell melanomas, were positive for Mitf. All nonmelanoma neoplasms were negative with only one exception: One mammary carcinoma showed rare (< 10%), weak nuclear staining with Mitf. The sensitivity and specificity of Mitf as a marker for melanoma were both 100%, whereas the sensitivity of HMB-45 antigen was 90.4%, and the specificity of S-100 protein was 70.3%. CONCLUSIONS. Mitf is a sensitive and specific marker for malignant melanoma, including the spindle-cell variant, in cytologic specimens and may be superior to the current standard melanocytic markers, S-100 protein and HMB-45 antigen. (C) 2001 American Cancer Society. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35249 USA. Washington Univ, Div Oncol, St Louis, MO USA. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Chhieng, DC (reprint author), Univ Alabama, Dept Pathol, KB 627 619 19th St S, Birmingham, AL 35249 USA. OI Chiriboga, Luis/0000-0002-2028-6873 NR 47 TC 28 Z9 28 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2001 VL 93 IS 5 BP 337 EP 343 DI 10.1002/cncr.9049 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 483MC UT WOS:000171638000006 PM 11668469 ER PT J AU Shoham, S Halgren, E Maynard, EM Normann, RA AF Shoham, S Halgren, E Maynard, EM Normann, RA TI Motor-cortical activity in tetraplegics SO NATURE LA English DT Article ID CORTEX; REORGANIZATION C1 Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Shoham, S (reprint author), Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. OI Shoham, Shy/0000-0003-0376-3495 NR 13 TC 55 Z9 56 U1 0 U2 3 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 25 PY 2001 VL 413 IS 6858 BP 793 EP 793 DI 10.1038/35101651 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 485JA UT WOS:000171750200031 PM 11677592 ER PT J AU Niswender, KD Morton, GJ Stearns, WH Rhodes, CJ Myers, MG Schwartz, MW AF Niswender, KD Morton, GJ Stearns, WH Rhodes, CJ Myers, MG Schwartz, MW TI Intracellular signalling - Key enzyme in leptin-induced anorexia SO NATURE LA English DT Article ID RESISTANCE; ACTIVATION; MICE C1 Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Pacific NW Res Inst, Seattle, WA 98122 USA. RP Niswender, KD (reprint author), Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. RI Schwartz, Michael/H-9950-2012 NR 12 TC 405 Z9 420 U1 0 U2 6 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 25 PY 2001 VL 413 IS 6858 BP 794 EP 795 DI 10.1038/35101657 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 485JA UT WOS:000171750200033 PM 11677594 ER PT J AU Watanabe, T Nanez, JE Sasaki, Y AF Watanabe, T Nanez, JE Sasaki, Y TI Perceptual learning without perception SO NATURE LA English DT Article ID PRIMARY VISUAL-CORTEX; ATTENTIONAL MODULATION; ORIENTATION; MOTION; IMPROVEMENT; DISCRIMINATION; PLASTICITY; TASK; MT AB The brain is able to adapt rapidly and continually to the surrounding environment, becoming increasingly sensitive to important and frequently encountered stimuli(1-4). It is often claimed that this adaptive learning is highly task-specific, that is, we become more sensitive to the critical signals in the tasks we attend to(5-15). Here, we show a new type of perceptual learning, which occurs without attention, without awareness and without any task relevance. Subjects were repeatedly presented with a background motion signal so weak that its direction was not visible; the invisible motion was an irrelevant background to the central task that engaged the subject's attention. Despite being below the threshold of visibility and being irrelevant to the central task, the repetitive exposure improved performance specifically for the direction of the exposed motion when tested in a subsequent suprathreshold test. These results suggest that a frequently presented feature sensitizes the visual system merely owing to its frequency, not its relevance or salience. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Arizona State Univ W, Dept Social & Behav Sci, Phoenix, AZ 85069 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Watanabe, T (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. NR 29 TC 276 Z9 280 U1 5 U2 29 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 25 PY 2001 VL 413 IS 6858 BP 844 EP 848 DI 10.1038/35101601 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 485JA UT WOS:000171750200046 PM 11677607 ER PT J AU Tanzi, RE Bertram, L AF Tanzi, RE Bertram, L TI New frontiers in Alzheimer's disease genetics SO NEURON LA English DT Review ID ALPHA-2-MACROGLOBULIN GENE; APOLIPOPROTEIN-E; ONSET; AGE; METAANALYSIS; ASSOCIATION; PRESENILINS; GENOTYPE AB Alzheimer's disease (AD) is a genetically complex disorder that accounts for the majority of dementia in the elderly population. Over 100 rare, highly penetrant mutations have been described in three genes (APP, PSEN1, PSEN2) for early-onset familial AD. In the more common late-onset form, a polymorphism in the apolipoprotein E gene has been associated with increased susceptibility. However, recent studies suggest that these four genes account for less than 30% of the genetic variance for AD and that more genetic factors remain to be identified. In this review, we present a brief history of AD genetics and preview some of the next frontiers in Alzheimer gene discovery primarily focusing on chromosomes 12, 10, and 9. C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 22 TC 311 Z9 323 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 25 PY 2001 VL 32 IS 2 BP 181 EP 184 DI 10.1016/S0896-6273(01)00476-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 487UG UT WOS:000171893700004 PM 11683989 ER PT J AU Thompson, KW Wasterlain, CG AF Thompson, KW Wasterlain, CG TI Urethane anesthesia produces selective damage in the piriform cortex of the developing brain SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE development; piriform; anesthetics; toxicity; urethane ID LONG-TERM POTENTIATION; APOPTOTIC NEURODEGENERATION; RETROSPLENIAL CORTEX; IMMATURE BRAIN; NMDA; RAT; MK-801; STIMULATION; RELEVANCE; BLOCKADE AB The potential induction of neuronal death by neuroactive drugs at specific stages of embryonic or postnatal development is a serious concern in treating brain disease. Recent evidence indicates that NMDA antagonists, GABA agonists, ethanol and some anesthetics can all produce massive neuronal cell loss at critical times during development. We show here that the anesthetic urethane, once used clinically, produces a selective lesion of the piriform cortex, a region not previously implicated in such toxicity, in the developing brain. Young rats were injected with urethane at 1, 2, 3, and 4 weeks of age and brain damage was measured 1-4 days later. We found that urethane produces a large lesion in subfields of the piriform cortex and that the damage is most severe in 2 week-old animals. These data, together with other recent reports, show that there are multiple neuronal death-inducing pathways in the developing nervous system. It will be important to determine if anesthesties used in pregnant women and young children may have similar effects. (C) 2001 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Thompson, KW (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Bldg 114,Rm 137,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD OCT 24 PY 2001 VL 130 IS 2 BP 167 EP 171 DI 10.1016/S0165-3806(01)00228-0 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 499LV UT WOS:000172573400002 ER PT J AU Thompson, DC McPhillips, H Davis, RL Lieu, TL Homer, CJ Helfand, M AF Thompson, DC McPhillips, H Davis, RL Lieu, TL Homer, CJ Helfand, M TI Universal newborn hearing screening - Summary of evidence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID DEMONSTRATION PROJECT; EARLY IDENTIFICATION; OTOACOUSTIC EMISSION; OUTCOME MEASURES; OTITIS-MEDIA; CHILDREN; IMPAIRMENT; INTERVENTION; INFANTS; AGE AB Context Each year, approximately 5000 infants are born in the United States with moderate-to-profound, bilateral permanent hearing loss (PHL). Universal newborn hearing screening (UNHS) has been proposed as a means to speed diagnosis and treatment and thereby improve language outcomes in these children. Objectives To identify strengths, weaknesses, and gaps in the evidence supporting UNHS and to compare the additional benefits and harms of UNHS with those of selective screening of high-risk newborns. Data Sources We searched the MEDLINE, CINAHL, and PsychINFO databases for relevant articles published from 1994 to August 2001, using terms for hearing disorders, infants or newborns, screening, and relevant treatments. We contacted experts and reviewed reference lists to identify additional articles, including those published before 1994. Study Selection We included controlled and observational studies of (1) the accuracy, yield, and harms of screening using otoacoustic emissions (OAEs), auditory brainstem response (ABR), or both in the general newborn population and (2) the effects of screening or early identification and treatment on language outcomes. Of an original 340 articles identified, 19 articles, including 1 controlled trial, met these inclusion criteria. Data Extraction Data on population, test performance, outcomes, and methodological quality were extracted by 2 authors (D.C.T., H.M.) using prespecified criteria developed by the US Preventive Services Task Force. We queried authors when information needed to assess study quality was missing. Data Synthesis Good-quality studies show that from 2041 to 2794 low-risk and 86 to 208 high-risk newborns were screened to find 1 case of moderate-to-profound PHL. The best estimate of positive predictive value was 6.7%. Six percent to 15% of infants who are missed by the screening tests are subsequently diagnosed with bilateral PHL. In a trial of UNHS vs clinical screening at age 8 months, UN HS increased the proportion of infants with moderate-to-severe hearing loss diagnosed by age 10 months (57% vs 14%) but did not reduce the rate of diagnosis after age 18 months. No good-quality controlled study has compared UNHS with selective screening of high-risk new. borns. In fair- to poor-quality cohort studies, intervention before age 6 months was associated with improved language and communication skills by ages 2 to 5 years. These studies had unclear criteria for selecting subjects, and none compared an inception cohort of low-risk newborns identified by screening with those identified in usual care, making it impossible to exclude selection bias as an explanation for the results. In a mathematical model based on the literature review, we estimated that extending screening to low-risk infants would detect 1 additional case before age 10 months for every 1441 low-risk infants screened, and result in treatment before 10 months of 1 additional case for every 2401 low-risk infants screened. With UNHS, 254 newborns would be referred for audiological evaluation because of false-positive second-stage screening test results vs 48 for selective screening. Conclusions Modern screening tests for hearing Impairment can improve identification of newborns with PHL, but the efficacy of UNHS to improve long-term language outcomes remains uncertain. C1 Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. Harvard Pilgrim Hlth Care, Seattle, WA USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Thompson, DC (reprint author), Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, 325 9th Ave,Box 359960, Seattle, WA 98104 USA. FU PHS HHS [290-97-0018] NR 76 TC 164 Z9 176 U1 2 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 24 PY 2001 VL 286 IS 16 BP 2000 EP 2010 DI 10.1001/jama.286.16.2000 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 485JD UT WOS:000171750500024 PM 11667937 ER PT J AU Tal, DM Capasso, JM Munson, K Karlish, SJD AF Tal, DM Capasso, JM Munson, K Karlish, SJD TI Proximity of transmembrane segments M3 and M1 of the alpha subunit of Na+,K+-ATPase revealed by specific oxidative cleavage mediated by a complex of Cu2+ ions and 4,7-diphenyl-1,10-phenanthroline SO BIOCHEMISTRY LA English DT Article ID P-TYPE ATPASES; PROTEOLYZED NA,K-ATPASE; CATALYZED CLEAVAGE; NA+/K+-ATPASE; BETA-SUBUNIT; NA/K-ATPASE; CROSS-LINKS; TRANSPORT; PUMP; ORGANIZATION AB This paper describes a novel approach to specific oxidative cleavage of Na+, K+-ATPase, mediated by Cu2+ ions and a hydrophobic phenanthroline, 4,7-diphenyl-1,10-phenanthroline (DPP), in the presence of ascorbate and H2O2. The cleavage produces two major fragments of the a subunit, with apparent molecular masses of 96.5 and 76 kDa, and N-termini near the cytoplasmic entrance of transmembrane segments M1 and M3, respectively, The kinetics indicate that both cleavages are mediated by a single Cu2+-DPP complex. We infer that M3 and MI are in proximity near the cytoplasmic surface. The yields of 96.5 and 76 kDa fragments are not significantly affected by ligands that stabilize different E1 and E2 conformations. In E-2(K) and E2P conformations, a minor 5.5 kDa fragment with its N-terminus in M10 is also observed. The 96.5 and 76 kDa fragments are indistinguishable from two fragments near M3 and M I produced by Fe2+-catalyzed cleavage described previously [Goldshleger, R., and Karlish, S. J. D. (1999) J. Biol. Chem. 274, 16213-16221], whereas other Fe2+-catalyzed cleavage fragments in the cytoplasmic P and A domains are not observed with the Cu2+-DPP complex. These findings provide experimental support for the concept of two separate Fe2+ sites. A homology model, with Na+, K+-ATPase residues within transmembrane segments and connecting loops substituted into the crystal structure of Ca2+-ATPase, shows the proximity between the sequences HFIH in M3 and EVWK in M1, near the cytoplasmic surface. Thus, the model strongly supports the conclusions based on cleavages mediated by the Cu2+-DPP complex (or Fe2+ at site 2). As a corollary, the cleavages provide evidence for similar packing of M1 and M3 of Na+, K+-ATPase and Ca2+-ATPase. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. W Los Angeles Vet Affairs Med Ctr, Marine Biol Lab, Los Angeles, CA 90073 USA. RP Karlish, SJD (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NR 31 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 23 PY 2001 VL 40 IS 42 BP 12505 EP 12514 DI 10.1021/bi011167n PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486CP UT WOS:000171801100006 PM 11601974 ER PT J AU Lim, CC Pimental, D Cui, L Wang, J Kang, ZB Hajjer, RJ Liao, RL AF Lim, CC Pimental, D Cui, L Wang, J Kang, ZB Hajjer, RJ Liao, RL TI Expression of mutant troponin C identified from a patient with idiopathic dilated cardiomyopathy impairs contractility and relaxation in isolated rat cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 7 BP 2 EP 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000008 ER PT J AU Way, KJ Opland, DM Chou, E Jiang, Z Suzuma, I Suzuma, K Clermont, AC King, GL AF Way, KJ Opland, DM Chou, E Jiang, Z Suzuma, I Suzuma, K Clermont, AC King, GL TI Impaired insulin signaling may contribute to decreased cardiac expression of vascular endothelial growth factor in states of diabetes and insulin resistance. SO CIRCULATION LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 86 BP 19 EP 19 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000086 ER PT J AU Matsui, T Li, L Cook, SA Ahn, YK Tao, JZ Rosenzweig, A AF Matsui, T Li, L Cook, SA Ahn, YK Tao, JZ Rosenzweig, A TI Downstream effectors in Akt ischemic cardioprotection in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 93 BP 20 EP 21 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000093 ER PT J AU Barouch, LA Harrison, RW Cappola, TP Skaf, MM Crone, JP Rodriguez, ER Huang, PL Burnett, AL Lima, JAC Hare, JM AF Barouch, LA Harrison, RW Cappola, TP Skaf, MM Crone, JP Rodriguez, ER Huang, PL Burnett, AL Lima, JAC Hare, JM TI Independent contributions of neuronal and endothelial nitric oxide synthase in preventing age-related left ventricular hypertrophy and mortality SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 140 BP 30 EP 30 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000140 ER PT J AU Ahn, YK Matsui, T Meiler, S Tao, JZ Li, L Rosenzweig, A AF Ahn, YK Matsui, T Meiler, S Tao, JZ Li, L Rosenzweig, A TI In vivo cardiac gene transfer of dominant negative IKK beta reduces myocardial inflammation, apoptosis, and infarction after ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 167 BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000167 ER PT J AU Ammer, R Keane, D Aretz, T Ruskin, JN AF Ammer, R Keane, D Aretz, T Ruskin, JN TI Apoptosis in atrial myocytes is a transient phenomenon in persistent atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 368 BP 76 EP 76 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000365 ER PT J AU Carr, AN Schmidt, AG Suzuki, Y Del Monte, F Allen, PB Greengard, P Grupp, IL Holt, BD Hajjar, RJ Depaoli-Roach, AA Kranias, EG AF Carr, AN Schmidt, AG Suzuki, Y Del Monte, F Allen, PB Greengard, P Grupp, IL Holt, BD Hajjar, RJ Depaoli-Roach, AA Kranias, EG TI The type-1 phosphatase activity is a critical determinant of cardiac function and remodeling in heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Univ Cincinnati, Cincinnati, OH USA. Indiana Univ, Indianapolis, IN 46204 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 398 BP 82 EP 82 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000395 ER PT J AU Fitzgerald, ML Andersson, LP Su, H Freeman, MW AF Fitzgerald, ML Andersson, LP Su, H Freeman, MW TI Topological disposition of the ABCA1 central highly hydrophobic domain SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 467 BP 97 EP 97 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000464 ER PT J AU Rath, MR Stallone, J Lin, M Knuefermann, P Knowlton, AA AF Rath, MR Stallone, J Lin, M Knuefermann, P Knowlton, AA TI Gender differences in the expression of heat shock proteins: The effect of estrogen SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Texas A&M Univ, College Stn, TX 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 546 BP 113 EP 113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000543 ER PT J AU Schwartz, GG Xu, Y Lu, L Young, L Schwartz, GG AF Schwartz, GG Xu, Y Lu, L Young, L Schwartz, GG TI The PPAR-gamma activator, troglitazone, increases content of glucose transport proteins in hearts of non-diabetic pigs SO CIRCULATION LA English DT Meeting Abstract C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Yale Univ, New Haven, CT 06520 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 577 BP 120 EP 120 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000574 ER PT J AU Nemoto, S Diwan, A De Freitas, G Tanaka, R Sugawara, M Carabello, BA Mann, DL AF Nemoto, S Diwan, A De Freitas, G Tanaka, R Sugawara, M Carabello, BA Mann, DL TI Post-translational processing of tumor necrosis factor determines whether transgenic mice develop systolic or diastolic dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Winters Ctr Heart Failure Res, Houston, TX USA. Nihon Kohden Corp, Tokyo, Japan. Tokyo Womens Med Univ, Tokyo, Japan. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 610 BP 127 EP 127 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000606 ER PT J AU Beckman, JA Goldfine, AB Garrett, LA Gerhard-Herman, M Creager, MA AF Beckman, JA Goldfine, AB Garrett, LA Gerhard-Herman, M Creager, MA TI Insulin resistance is not associated with impaired endothelial function SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 727 BP 151 EP 151 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000723 ER PT J AU Kaprielian, R Lebeche, D Delmonte, F Hajjar, RJ AF Kaprielian, R Lebeche, D Delmonte, F Hajjar, RJ TI In vivo adenoviral gene transfer of Kv4.3 in rats following aortic banding SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 758 BP 157 EP 157 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000754 ER PT J AU Communal, C Sumandea, M Solaro, RJR Narula, J Hajjar, RJ AF Communal, C Sumandea, M Solaro, RJR Narula, J Hajjar, RJ TI Functional consequences of apoptosis in cardiac myocytes: Myofibrillar proteins are targets for caspase-3 SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Illinois, Chicago, IL USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. NR 0 TC 1 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 781 BP 162 EP 162 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000777 ER PT J AU Peng, CF Lee, P Deguzman, A Miao, WF Chandra, M Shirani, J Factor, S Lefer, D Condorelli, G Ardati, A Della Penna, K Zinkel, S Korsmeyer, SJ Tremp, G Zilberstein, A Kitsis, RN AF Peng, CF Lee, P Deguzman, A Miao, WF Chandra, M Shirani, J Factor, S Lefer, D Condorelli, G Ardati, A Della Penna, K Zinkel, S Korsmeyer, SJ Tremp, G Zilberstein, A Kitsis, RN TI Multiple independent mutations in apoptotic signaling pathways markedly decrease infarct size due to myocardial ischemia-reperfusion SO CIRCULATION LA English DT Meeting Abstract C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Louisiana State Univ, New Orleans, LA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Aventis, Frankfurt, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 898 BP 187 EP 187 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000893 ER PT J AU Wang, TJ Levy, D Leip, EP Benjamin, EJ Sutherland, P Wilson, PWF Vasan, RS AF Wang, TJ Levy, D Leip, EP Benjamin, EJ Sutherland, P Wilson, PWF Vasan, RS TI Determinants of natriuretic peptide levels in a healthy population and derivation of reference limits SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 906 BP 189 EP 189 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000900 ER PT J AU Haq, SE Kilter, H Tao, JZ Bhattacharya, K Picard, MH Bonventre, J Michael, A Force, T AF Haq, SE Kilter, H Tao, JZ Bhattacharya, K Picard, MH Bonventre, J Michael, A Force, T TI Cytosolic phospholipase A2 regulates IGF-1 signaling and cardiac growth SO CIRCULATION LA English DT Meeting Abstract C1 Mol Cardiol Res Inst, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Aberdeen Royal Infirm, Aberdeen, Scotland. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 933 BP 195 EP 195 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000927 ER PT J AU Hung, RR Matsui, T Rosenzweig, A AF Hung, RR Matsui, T Rosenzweig, A TI Role of Akt in IL-1 beta-induced NF-kappa B and endothelial activation SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 961 BP 200 EP 200 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000953 ER PT J AU Hung, RR Gerszten, RE Friedrich, E Kuhlencordt, P Matsui, T Huang, PL Rosenzweig, A AF Hung, RR Gerszten, RE Friedrich, E Kuhlencordt, P Matsui, T Huang, PL Rosenzweig, A TI Pro-inflammatory effects of Akt activation in endothelial nitric oxide synthase (eNOS) deficient mouse endothelium SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 962 BP 201 EP 201 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000954 ER PT J AU Chen, HC Bouchie, JL Feener, EP AF Chen, HC Bouchie, JL Feener, EP TI Cooperation of Sp1 and AP-1 elements in the PAI-1 promoter is essential for its response to the MEKK-1/MEK1,2 pathway SO CIRCULATION LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 982 BP 204 EP 204 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895000974 ER PT J AU Matsui, T Li, L Tao, JZ Cook, SA Wu, JC Picard, MH Liao, RL Rosenzweig, A AF Matsui, T Li, L Tao, JZ Cook, SA Wu, JC Picard, MH Liao, RL Rosenzweig, A TI Chronic cardiac expression of activated Akt in transgenic mice reduces ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Boston Univ, Sch Med, Boston, MA 02118 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1010 BP 210 EP 210 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001002 ER PT J AU Finn, AV Clermont, A Kolodgie, FD Weber, DK Yu, JC Hollenbach, S Giese, N Virmani, R Gold, H AF Finn, AV Clermont, A Kolodgie, FD Weber, DK Yu, JC Hollenbach, S Giese, N Virmani, R Gold, H TI An oral inhibitor of platelet derived growth factor limits neointimal formation after arterial balloon injury in a rat model of type II diabetes mellitus SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. COR, San Francisco, CA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1138 BP 236 EP 236 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001130 ER PT J AU Tian, R Musi, N Dean, D Park, HJ Ruderman, NB Goodyear, LJ AF Tian, R Musi, N Dean, D Park, HJ Ruderman, NB Goodyear, LJ TI Depletion of energy reserve in hypertrophied hearts leads to activation of AMPK SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1219 BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001208 ER PT J AU Kaji, EH Ryeom, S Wu, JC McKeon, FD AF Kaji, EH Ryeom, S Wu, JC McKeon, FD TI Transgenic overexpression of calcipressin 1 inhibits angiotensin II and thyroxine-induced cardiac hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1346 BP 280 EP 280 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001335 ER PT J AU Chao, W Li, L Rosenzweig, A AF Chao, W Li, L Rosenzweig, A TI Role of FADD in hypoxia- and serum deprivation-induced cardiomyocyte apoptosis SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CV Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1410 BP 293 EP 293 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001399 ER PT J AU Shiojima, L Yefremashvili, M Tao, JZ Rosenzweig, A Kahn, R Abel, ED Walsh, K AF Shiojima, L Yefremashvili, M Tao, JZ Rosenzweig, A Kahn, R Abel, ED Walsh, K TI Regulation of postnatal cardiac growth by insulin signaling SO CIRCULATION LA English DT Meeting Abstract C1 St Elizabeths Med Ctr, Boston, MA USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Charlestown, MA USA. Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1561 BP 324 EP 324 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001549 ER PT J AU Beckman, JA Goldfine, AB Garrett, LA Gordon, MB Creager, MA AF Beckman, JA Goldfine, AB Garrett, LA Gordon, MB Creager, MA TI Oral antioxidant therapy improves endothelial function in type 1 but not type 2 subjects with diabetes mellitus SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1576 BP 327 EP 327 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001564 ER PT J AU Glatter, KA Dorostkar, PC Yang, YF Lee, RJ Van Hare, GF Keung, E Modin, G Scheinman, MM AF Glatter, KA Dorostkar, PC Yang, YF Lee, RJ Van Hare, GF Keung, E Modin, G Scheinman, MM TI Electrophysiologic effects of ibutilide in patients with accessory pathways. SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1588 BP 331 EP 331 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001576 ER PT J AU Rinaldi, MJ Piana, RN Caputo, RP Gordon, PC Lopez, JJ Dauerman, HL Hammes, LN Shaikh, SR Ryan, TJ Warner, JJ Zidar, JP Kiernan, FJ Palacios, JF Cox, DA Lim, J Ho, KK Cutlip, DE Cohen, DJ AF Rinaldi, MJ Piana, RN Caputo, RP Gordon, PC Lopez, JJ Dauerman, HL Hammes, LN Shaikh, SR Ryan, TJ Warner, JJ Zidar, JP Kiernan, FJ Palacios, JF Cox, DA Lim, J Ho, KK Cutlip, DE Cohen, DJ TI Is clopidogrel superior to ticlopidine for the prevention of stent thrombosis? Results of a multicenter study SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. SJH Cardiol Assoc, Syracuse, NY USA. Miriam Hosp, Providence, RI 02906 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Mayo Clin, Rochester, MN USA. Maine Med Ctr, Portland, ME 04102 USA. Duke Univ, Med Ctr, Durham, NC USA. Hartford Hosp, Hartford, CT 06115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mid Carolina Cardiol, Charlotte, NC USA. Perfuse Core Lab, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1660 BP 348 EP 348 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001647 ER PT J AU O'Donnell, CJ Larson, MG Kupka, MJ Jaffer, FA Clouse, ME Levy, D Manning, WJ AF O'Donnell, CJ Larson, MG Kupka, MJ Jaffer, FA Clouse, ME Levy, D Manning, WJ TI Subclinical aortic atherosclerosis detected by MRI is associated with aortic and coronary calcification and carotid intimal medial thickness in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1788 BP 375 EP 375 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001773 ER PT J AU Harding, SA Hourigan, LA Walters, DL Keck, SA Dec, GWG Semigran, MJ AF Harding, SA Hourigan, LA Walters, DL Keck, SA Dec, GWG Semigran, MJ TI Percutaneous coronary intervention for cardiac transplant vasculopathy improves LV function despite a high rate of restenosis SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1882 BP 395 EP 395 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001864 ER PT J AU Bahlmann, EB McQuillan, BM Handschumacher, MD Chow, CM Guerrero, JL Weyman, AE Picard, MH Scherrer-Crosbie, M AF Bahlmann, EB McQuillan, BM Handschumacher, MD Chow, CM Guerrero, JL Weyman, AE Picard, MH Scherrer-Crosbie, M TI Destructive pulses: Influence of their duration on microbubble persistence. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013 OI McQuillan, Brendan/0000-0002-2130-8114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 1962 BP 412 EP 412 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895001944 ER PT J AU Perry, TE Kaushal, S Nasseri, BA Sutherland, FW Wang, J Guleserian, KJ Bischoff, J Vacanti, JP Sacks, M Mayer, JE AF Perry, TE Kaushal, S Nasseri, BA Sutherland, FW Wang, J Guleserian, KJ Bischoff, J Vacanti, JP Sacks, M Mayer, JE TI Peripheral blood as a cell source for tissue engineering heart valves SO CIRCULATION LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2052 BP 433 EP 433 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002034 ER PT J AU Cahalin, L Wagenaar, R Dec, GW Semigran, MJ AF Cahalin, L Wagenaar, R Dec, GW Semigran, MJ TI Endurance training in heart failure - A pilot study of the effects of cycle versus ventilatory muscle training SO CIRCULATION LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2149 BP 453 EP 453 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002131 ER PT J AU Tearney, GJ Schlendorf, KH Houser, SL Jang, IK Kang, DH Aretz, HT Shishkov, M Bouma, BE AF Tearney, GJ Schlendorf, KH Houser, SL Jang, IK Kang, DH Aretz, HT Shishkov, M Bouma, BE TI Characterization of human atherosclerotic plaques by optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2173 BP 458 EP 458 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002155 ER PT J AU Hoffmann, U Rosol, M Philp, M Hinton, D Enzweiler, C Nichols, S Lamuraglia, G Brady, TJ AF Hoffmann, U Rosol, M Philp, M Hinton, D Enzweiler, C Nichols, S Lamuraglia, G Brady, TJ TI In vitro calcium quantitation by multidetector computed tomography (MDCT) SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2261 BP 477 EP 477 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002243 ER PT J AU Smith, RN Grazette, L Houser, S AF Smith, RN Grazette, L Houser, S TI Quilty lesions are specific for cardiac allografts and not cyclosporine SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2272 BP 479 EP 480 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002254 ER PT J AU Bahlmann, EB McQuillan, BM Picard, MH Weyman, AE Handschumacher, MD Scherrer-Crosbie, M AF Bahlmann, EB McQuillan, BM Picard, MH Weyman, AE Handschumacher, MD Scherrer-Crosbie, M TI Effects of longer destructive pulse sequences on perfusion detection during myocardial perfusion imaging. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013 OI McQuillan, Brendan/0000-0002-2130-8114 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2350 BP 496 EP 496 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002332 ER PT J AU Butler, J Abraham, WT Forman, DE Gottlieb, SS Loh, E Massie, BM O'Connor, CM Rich, MW Stevenson, LW Wang, YF Young, JB Krumholz, HM AF Butler, J Abraham, WT Forman, DE Gottlieb, SS Loh, E Massie, BM O'Connor, CM Rich, MW Stevenson, LW Wang, YF Young, JB Krumholz, HM TI Relationship between heart failure treatment and development of worsening renal function among hospitalized patients SO CIRCULATION LA English DT Meeting Abstract C1 Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Univ Kentucky, Lexington, KY USA. Boston Med Ctr, Boston, MA USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Penn, Philadelphia, PA 19104 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Duke Univ, Durham, NC USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Yale Univ, Sch Med, New Haven, CT 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2486 BP 526 EP 526 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002467 ER PT J AU Ichinose, F Ullrich, R Sapirstein, A Jones, RC Bloch, KD Zapol, WM AF Ichinose, F Ullrich, R Sapirstein, A Jones, RC Bloch, KD Zapol, WM TI Cytosolic phospholipase A(2) modulates hypoxic pulmonary vasoconstriction. SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2502 BP 529 EP 529 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002483 ER PT J AU Go, AS Reed, GL Hylek, EM Phillips, KA Chang, Y Henault, LE Selby, JV Singer, DE AF Go, AS Reed, GL Hylek, EM Phillips, KA Chang, Y Henault, LE Selby, JV Singer, DE TI Factor v leiden mutation and risk of stroke in atrial fibrillation. The anticoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract C1 Kaiser Permanente No CA, Oakland, CA USA. Harvard Univ, Boston, MA 02115 USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2507 BP 530 EP 530 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002488 ER PT J AU Nasseri, BA Ullrich, R Bloch, KD Nakajima, H Aretz, HT Vacanti, JP Zapol, WM Picard, MH Scherrer-Crosbie, M AF Nasseri, BA Ullrich, R Bloch, KD Nakajima, H Aretz, HT Vacanti, JP Zapol, WM Picard, MH Scherrer-Crosbie, M TI Nitric oxide synthase 3 decreases left ventricular hypertrophy after myocardial infarction in mice SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2663 BP 563 EP 563 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002642 ER PT J AU Wu, JC Nasser, BA Bloch, KD Picard, MH Scherrer-Crosbie, M AF Wu, JC Nasser, BA Bloch, KD Picard, MH Scherrer-Crosbie, M TI Influence of gender on ventricular remodeling after myocardial infarction in mice. SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2666 BP 563 EP 563 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002645 ER PT J AU Palacios, IF Sanchez, PL Harrell, LC Salas, RE AF Palacios, IF Sanchez, PL Harrell, LC Salas, RE TI Learning curve of the Inoue technique of percutaneous mitral balloon valvuloplasty SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2753 BP 581 EP 582 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002731 ER PT J AU Palacios, IF Sanchez, PL Weyman, AE Block, PC AF Palacios, IF Sanchez, PL Weyman, AE Block, PC TI Which patients benefit from percutaneous mitral balloon valvuloplasty: Pre and post valvuloplasty variables that predict 15 year outcome SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2752 BP 581 EP 581 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002730 ER PT J AU Palacios, IF Sanchez, PL Rodriguez-Alemparte, M AF Palacios, IF Sanchez, PL Rodriguez-Alemparte, M TI The impact of age on mitral valvuloplasty results SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2754 BP 582 EP 582 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002732 ER PT J AU Jenkins, KJ Tan, PE Perry, SB Colan, SD Gauvreau, K Goff, DA Gonzalez, PC Kieran, MW AF Jenkins, KJ Tan, PE Perry, SB Colan, SD Gauvreau, K Goff, DA Gonzalez, PC Kieran, MW TI Proliferative pulmonary vein stenosis: Variable patterns of progression and preliminary results using adjunct chemotherapy SO CIRCULATION LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2779 BP 587 EP 587 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002757 ER PT J AU Peterson, ED Coombs, LP Ferguson, TBB Shroyer, L Delong, ER Edwards, FH AF Peterson, ED Coombs, LP Ferguson, TBB Shroyer, L Delong, ER Edwards, FH TI Patient factors that influence early discharge or prolonged length of stay after bypass surgery SO CIRCULATION LA English DT Meeting Abstract C1 Duke Clin Res Inst, Durham, NC USA. Louisiana State Univ, Hlth Sci Ctr, Marrero, LA USA. Denver VA Med Ctr, Denver, CO USA. Univ Florida, Jacksonville, FL 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2821 BP 596 EP 596 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002799 ER PT J AU Januzzi, J Lewandrowski, K Macgillivray, T Kathiresan, S Servoss, S Lewandrowski, E AF Januzzi, J Lewandrowski, K Macgillivray, T Kathiresan, S Servoss, S Lewandrowski, E TI Troponin T is superior to CK-MB for patient evaluation and risk stratification following cardiac surgery. SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 2822 BP 597 EP 597 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895002800 ER PT J AU Rumsfeld, JS Magid, DJ Plomondon, ME Spertus, JA O'Brien, MM Every, NR Sales, AE AF Rumsfeld, JS Magid, DJ Plomondon, ME Spertus, JA O'Brien, MM Every, NR Sales, AE TI Depression is associated with anginal frequency, anginal stability, physical limitation, and quality of life following acute coronary syndromes SO CIRCULATION LA English DT Meeting Abstract C1 Denver VA Med Ctr, Denver, CO USA. Colorado Permanente Med Grp, Denver, CO USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3069 BP 649 EP 649 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003045 ER PT J AU McNamara, DM Starling, RC Dec, GWW Loh, E Torre-Amione, G Gass, A Villanueva, FS Janosko, KM Holubkov, R AF McNamara, DM Starling, RC Dec, GWW Loh, E Torre-Amione, G Gass, A Villanueva, FS Janosko, KM Holubkov, R TI Left ventricular diameter at presentation predicts subsequent recovery for patients with recent-onset dilated cardiomyopathy: Results from the IMAC trial SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wyeth Ayerst Res, Radnor, PA USA. Baylor Coll Med, Houston, TX 77030 USA. Mt Sinai Med Ctr, New York, NY 10029 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3108 BP 658 EP 658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003083 ER PT J AU Playford, DA Levine, RA Picard, MH Handschumacher, MD AF Playford, DA Levine, RA Picard, MH Handschumacher, MD TI The illusion of contraction from out-of-plane translation: Can tissue Doppler velocities resolve it? SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3178 BP 673 EP 673 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003153 ER PT J AU Buck, T Mucci, RA Plicht, B Hunold, P Barkhausen, J Levine, RA AF Buck, T Mucci, RA Plicht, B Hunold, P Barkhausen, J Levine, RA TI Automated quantification of mitral regurgitant volume: Practical application of backscattered acoustic power analysis of the vena contracta Doppler spectrum SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Essen Gesamthsch, D-4300 Essen 1, Germany. RI Barkhausen, Joerg/E-3921-2010 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3185 BP 675 EP 675 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003160 ER PT J AU Buck, T Plicht, B Hunold, P Barkhausen, J Mucci, RA Levine, RA AF Buck, T Plicht, B Hunold, P Barkhausen, J Mucci, RA Levine, RA TI The power-velocity integral at the vena contracta for automated regurgitant flow quantification: Clinical validation against existing techniques SO CIRCULATION LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, D-4300 Essen 1, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Barkhausen, Joerg/E-3921-2010 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3191 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003166 ER PT J AU Deague, JA Holmvang, G King, MEE Liberthson, RR Hung, J AF Deague, JA Holmvang, G King, MEE Liberthson, RR Hung, J TI Effect of afterload reduction an systemic right ventricular function in patients with atrial switch operations for D-transposition of the great arteries. SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3209 BP 680 EP 680 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003183 ER PT J AU Gottlieb, SS Abraham, WT Butler, J Forman, D Krumholz, HM Loh, E Massie, B Rich, M Stevenson, LW Young, JB AF Gottlieb, SS Abraham, WT Butler, J Forman, D Krumholz, HM Loh, E Massie, B Rich, M Stevenson, LW Young, JB TI The impact of different definitions of worsening renal function in CHF SO CIRCULATION LA English DT Meeting Abstract C1 Univ Maryland, Baltimore, MD 21201 USA. Univ Kentucky, Lexington, KY 40506 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Boston Univ, Boston, MA 02215 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Penn, Philadelphia, PA 19104 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Washington Univ, St Louis, MO 63130 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3251 BP 688 EP 689 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003224 ER PT J AU Tawakol, A Demel, K Al Rodhan, N Gewirtz, H Muller, J Fischman, AJ AF Tawakol, A Demel, K Al Rodhan, N Gewirtz, H Muller, J Fischman, AJ TI Detection of experimental atherosclerotic plaques using macrophage-targeting radionuclide technology SO CIRCULATION LA English DT Meeting Abstract 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3273 BP 693 EP 693 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003246 ER PT J AU Rinaldi, MJ Piana, RN Caputo, RP Gordon, PC Lopez, JJ Dauerman, HL Hammes, LN Holmes, DR Shaikh, SR Ryan, TJ Warner, JJ Zidar, JP Kiernan, FJ Moussa, I Palacios, IF Cox, DA Lim, J Ho, KK Cutlip, DE Gibson, M Cohen, DJ AF Rinaldi, MJ Piana, RN Caputo, RP Gordon, PC Lopez, JJ Dauerman, HL Hammes, LN Holmes, DR Shaikh, SR Ryan, TJ Warner, JJ Zidar, JP Kiernan, FJ Moussa, I Palacios, IF Cox, DA Lim, J Ho, KK Cutlip, DE Gibson, M Cohen, DJ TI Do GpIIb/IIIa inhibitors reduce stent thrombosis? Results of a multicenter study SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. SJH Cardiol Assoc, Syracuse, NY USA. Miriam Hosp, Providence, RI 02906 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Mayo Clin, Rochester, MN USA. Maine Med Ctr, Portland, ME 04102 USA. Duke Univ, Med Ctr, Durham, NC USA. Hartford Hosp, Hartford, CT 06115 USA. Lenox Hill Hosp, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mid Carolina Cardiol, Charlotte, NC USA. Perfuse Core Lab, Boston, MA USA. Harvard Clin Res Inst, Boston, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3328 BP 705 EP 705 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003300 ER PT J AU Mangat, I Yang, YF Tschopp, D Cheng, J Keung, E Scheinman, MM AF Mangat, I Yang, YF Tschopp, D Cheng, J Keung, E Scheinman, MM TI Atrial flutter ablation: Optimizing the detection of bidirectional block across the flutter isthmus SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Thorac & CV Inst, E Lansing, MI USA. San Francisco VA Med Ctr, San Francisco, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3376 BP 715 EP 716 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003348 ER PT J AU Oesterle, SN Kuntz, RE Nordhausen, CT Ulm, MJ Vonesh, MJ Macri, NP AF Oesterle, SN Kuntz, RE Nordhausen, CT Ulm, MJ Vonesh, MJ Macri, NP TI In-vivo evaluation of a novel ePTFE lined self-expanding stent for treatment of diseased saphenous vein bypass grafts. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. W L Gore & Associates Inc, Flagstaff, AZ 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3505 BP 742 EP 743 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003476 ER PT J AU Hylek, EM Go, AS Chang, YC Phillips, KA Henault, LE Selby, JV Singer, DE AF Hylek, EM Go, AS Chang, YC Phillips, KA Henault, LE Selby, JV Singer, DE TI Anticoagulation intensity and risk of stroke and intracranial hemorrhage in atrial fibrillation: The Anticoaguation and Risk Factors in Atrial Fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Kaiser Permanente No CA, Oakland, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3730 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003700 ER PT J AU Albert, CM Manson, JE Jeremy, RN Gaziano, MM AF Albert, CM Manson, JE Jeremy, RN Gaziano, MM TI Moderate alcohol consumption and risk of atrial fibrillation in the physicians' health study. SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3738 BP 796 EP 796 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003708 ER PT J AU Deswal, A Petersen, NJ Ashton, CM Ku-Goto, M Wray, NP AF Deswal, A Petersen, NJ Ashton, CM Ku-Goto, M Wray, NP TI Differences in outcomes in African Americans and white veterans with heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX USA. VA Med Ctr, Houston, TX 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 SU S MA 3883 BP 830 EP 830 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487UW UT WOS:000171895003853 ER PT J AU Yuan, C Mitsumori, LM Ferguson, MS Polissar, NL Echelard, D Ortiz, G Small, R Davies, JW Kerwin, WS Hatsukami, TS AF Yuan, C Mitsumori, LM Ferguson, MS Polissar, NL Echelard, D Ortiz, G Small, R Davies, JW Kerwin, WS Hatsukami, TS TI In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques SO CIRCULATION LA English DT Article DE magnetic resonance imaging; lipids; atherosclerosis; carotid arteries ID ATHEROSCLEROTIC PLAQUE; IN-VIVO; RUPTURE; LESIONS; CLASSIFICATION; DISRUPTION; STENOSIS AB Background-High-resolution MRI has been shown to be capable of identifying plaque constituents, such as the necrotic core and intraplaque hemorrhage, in human carotid atherosclerosis. The purpose of this study was to evaluate differential contrast-weighted images, specifically a multispectral MR technique, to improve the accuracy of identifying the lipid-rich necrotic core and acute intraplaque hemorrhage in vivo. Methods and Results-Eighteen patients scheduled for carotid endarterectomy underwent a preoperative carotid MRI examination in a 1.5-T GE Signa scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MR images of the vessel wall were examined for the presence of a lipid-rich necrotic core and/or intraplaque hemorrhage. Ninety cross sections were compared with matched histological sections of the excised specimen in a double-blinded fashion. Overall accuracy (95% CI) of multispectral MRI was 87% (80% to 94%), sensitivity was 85% (78% to 92%), and specificity was 92% (86% to 98%). There was good agreement between MRI and histological findings, with a value of kappa =0.69 (0.53 to 0.85). Conclusions-Multispectral MRI can identify the lipid-rich necrotic core in human carotid atherosclerosis in vivo with high sensitivity and specificity. This MRI technique provides a noninvasive tool to study the pathogenesis and natural history of carotid atherosclerosis. Furthermore, it will permit a direct assessment of the effect of pharmacological therapy, such as aggressive lipid lowering, on plaque lipid composition. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Marina Merguson Inc, Seattle, WA USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yuan, C (reprint author), Univ Washington, Dept Radiol, Box 357115,1959 NE Pacific Ave, Seattle, WA 98195 USA. FU NHLBI NIH HHS [HL-56874, R01-HL-60213, R01-HL-61851] NR 31 TC 444 Z9 478 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2001 VL 104 IS 17 BP 2051 EP 2056 DI 10.1161/hc4201.097839 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 486QQ UT WOS:000171828800014 PM 11673345 ER PT J AU Schiff, D O 'Neill, B Wijdicks, E Antin, JH Wen, PY AF Schiff, D O 'Neill, B Wijdicks, E Antin, JH Wen, PY TI Gliomas arising in organ transplant recipients: An unrecognized complication of transplantation? SO NEUROLOGY LA English DT Article ID NERVOUS-SYSTEM TUMOR; MALIGNANCIES; DONORS AB Reported are six cases of glioma, diagnosed in the last 10 years, arising in organ transplant recipients. Five transplant recipients developed glioblastoma, and one developed oligodendroglioma. None had other risk factors for glioma. Gliomas must be considered in the differential diagnosis of space-occupying lesions in transplant recipients. Although these cases may represent coincidence, the putative HIV-glioma association suggests a pathogenetic link to immunosuppression. C1 Univ Pittsburgh, Med Ctr, Neurooncol Program, Dept Neurol Surg, Pittsburgh, PA 15213 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Schiff, D (reprint author), Univ Pittsburgh, Med Ctr, Neurooncol Program, Dept Neurol Surg, 3471 5th Ave,Kaufmann Bldg,Suite 802, Pittsburgh, PA 15213 USA. NR 10 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 23 PY 2001 VL 57 IS 8 BP 1486 EP 1488 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 484GH UT WOS:000171681500025 PM 11673595 ER PT J AU Zhou, ZQ Manguino, D Kewitt, K Intano, GW McMahan, CA Herbert, DC Hanes, M Reddick, R Ikeno, Y Walter, CA AF Zhou, ZQ Manguino, D Kewitt, K Intano, GW McMahan, CA Herbert, DC Hanes, M Reddick, R Ikeno, Y Walter, CA TI Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O-6-methylguanine-DNA methyltransferase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID O(6)-METHYLGUANINE DNA METHYLTRANSFERASE; MISMATCH REPAIR DEFICIENCY; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; GENETIC SUSCEPTIBILITY; MUTATOR PHENOTYPE; ESCHERICHIA-COLI; EXPRESSION; CELLS; HEPATOCARCINOGENESIS; MUTATIONS AB O-6-methylguanine (O(6)mG) is a potent mutagenic and procarcinogenic DNA lesion. Organisms have evolved with a DNA repair mechanism that largely ameliorates the deleterious effects of O(6)mG through a direct reversal mechanism by a protein termed O-6-methylguanine-DNA methyltransferase (MGMT). However, the contribution of O(6)mG to carcinogenesis, in the absence of known exposure to agents that produce it, has not been defined. Nontransgenic C3HeB male mice have a high frequency of spontaneous liver tumors. Transgenic CeHeB/FeJ mice expressing human MGMT (hMGMT) were generated that had elevated hepatic MGMT activity. The spontaneous development of hepatocellular carcinoma was significantly reduced in those mice expressing hMGMT compared with nontransgenic C3HeB/FeJ male mice. No differences were detected in spontaneous mutant frequencies in lacl transgenes in mice carrying hMGMT compared with that without hMGMT but the proportion of GC to AT transition mutations was lower in the transgenic mice carrying hMGMT as well as lacl. Tumors that arose in C3HeB/FeJ transgenic mice were largely deficient in hMGMT protein as determined by immunohistochemistry with a monoclonal antibody directed against hMGMT. Together these data indicate that spontaneous O(6)mG lesions induced hepatocellular carcinogenesis in C3HeB/FeJ male mice. These transgenic mice represent a rare example of reduced spontaneous carcinogenesis. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Lab Anim Resources, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIEHS NIH HHS [ES05798] NR 61 TC 37 Z9 42 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2001 VL 98 IS 22 BP 12566 EP 12571 DI 10.1073/pnas.221232998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 486EU UT WOS:000171806100051 PM 11606727 ER PT J AU Cole, SW Naliboff, BD Kemeny, ME Griswold, MP Fahey, JL Zack, JA AF Cole, SW Naliboff, BD Kemeny, ME Griswold, MP Fahey, JL Zack, JA TI Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-A; ANTIRETROVIRAL THERAPY; VIRUS-REPLICATION; IMMUNE-SYSTEM; TNF-ALPHA; CAMP; EXPRESSION; RESERVOIR; PATHWAYS; LINEAGE AB Neurotransmitters can accelerate HIV-1 replication in vitro, leading us to examine whether differences in autonomic nervous system (ANS) activity might promote residual HIV-1 replication in patients treated with highly active antiretroviral therapy. Patients who showed constitutively high levels of ANS activity before highly active antiretroviral therapy experienced poorer suppression of plasma viral load and poorer CD4(+) T cell recovery over 3-11 months of therapy. ANS activity was not related to demographic or behavioral characteristics that might influence pathogenesis. However, the ANS neurotransmitter norepinephrine enhanced replication of both CCR5- and CXCR4-tropic strains of HIV-1 in vitro via chemokine receptor up-regulation and enhanced viral gene expression, suggesting that neural activity may directly promote residual viral replication. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Area Healthcare Syst, Los Angeles, CA 90073 USA. Consolidated Lab Serv, Van Nuys, CA 91406 USA. RP Cole, SW (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI 33259, AI 49135, R01 AI036554, AI 36554] NR 29 TC 84 Z9 85 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2001 VL 98 IS 22 BP 12695 EP 12700 DI 10.1073/pnas.221134198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 486EU UT WOS:000171806100073 PM 11675501 ER PT J AU Dijkhuizen, RM Ren, JM Mandeville, JB Wu, ON Ozdag, FM Moskowitz, MA Rosen, BR Finklestein, SP AF Dijkhuizen, RM Ren, JM Mandeville, JB Wu, ON Ozdag, FM Moskowitz, MA Rosen, BR Finklestein, SP TI Functional magnetic resonance imaging of reorganization in rat brain after stroke SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-VOLUME; ARTERY OCCLUSION; WATER DIFFUSION; CARDIAC-ARREST; MOTOR FUNCTION; ADULT-RATS; RECOVERY; MRI; ACTIVATION AB Functional recovery after stroke has been associated with brain plasticity; however, the exact relationship is unknown. We performed behavioral tests, functional MRI, and histology in a rat stroke model to assess the correlation between temporal changes in sensorimotor function, brain activation patterns, cerebral ischemic damage, and cerebrovascular reactivity. Unilateral stroke induced a large ipsilateral infarct and acute dysfunction of the contralateral forelimb, which significantly recovered at later stages. Forelimb impairment was accompanied by loss of stimulus-induced activation in the ipsilesional sensorimotor cortex; however, local tissue and perfusion were only moderately affected and cerebrovascular reactivity was preserved in this area. At 3 days after stroke, extensive activation-induced responses were detected in the contralesional hemisphere. After 14 days, we found reduced involvement of the contralesional hemisphere, and significant responses in the infarction periphery. Our data suggest that limb dysfunction is related to loss of brain activation in the ipsilesional sensorimotor cortex and that restoration of function is associated with biphasic recruitment of peri- and contralesional functional fields in the brain. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH NMR Ctr,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci,Dept Neurosurg, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNS Growth Factor Res Lab,Dept Neurol, Boston, MA 02114 USA. RP Dijkhuizen, RM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH NMR Ctr,Dept Radiol, 13th St,Bldg 149, Charlestown, MA 02129 USA. RI Dijkhuizen, Richard/A-6506-2008; Moskowitz, Michael/D-9916-2011 FU NCI NIH HHS [P01-CA48729]; NCRR NIH HHS [P41 RR014075, P41-RR14075]; NHLBI NIH HHS [R01 HL039810, R01-HL39810]; NINDS NIH HHS [P50 NS010828, P50-NS10828, R01 NS038477, R01-NS38477] NR 36 TC 179 Z9 199 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2001 VL 98 IS 22 BP 12766 EP 12771 DI 10.1073/pnas.231235598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 486EU UT WOS:000171806100085 PM 11606760 ER PT J AU Kim, YJ Yi, Y Sapp, E Wang, YM Cuiffo, B Kegel, KB Qin, ZH Aronin, N DiFiglia, M AF Kim, YJ Yi, Y Sapp, E Wang, YM Cuiffo, B Kegel, KB Qin, ZH Aronin, N DiFiglia, M TI Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTRANUCLEAR INCLUSIONS; POLYGLUTAMINE TRACT; EXPRESSION; CLEAVAGE; DEATH; CELLS; APOPTOSIS; INTERACTS; AUTOPHAGY; PROTEASES AB The Huntington's disease (HD) mutation is a polyglutamine expansion in the N-terminal region of huntingtin (N-htt). How neurons die in HD is unclear. Mutant N-htt aggregates in neurons in the HD brain; expression of mutant N-htt in vitro causes cell death. Other in vitro studies show that proteolysis by caspase 3 could be important in regulating mutant N-htt function, but there has been no direct evidence for caspase 3-cleaved N-htt fragments in brain. Here, we show that N-htt fragments consistent with the size produced by caspase 3 cleavage in vitro are resident in the cortex, striatum, and cerebellum of normal and adult onset HD brain and are similar in size to the fragments seen after exogenous expression of human huntingtin in mouse clonal striatal neurons. HD brain extracts treated with active caspase 3 had increased levels of N-htt fragments. Compared with the full-length huntingtin, the caspase 3-cleaved N-htt fragments, especially the mutant fragment, preferentially segregated with the membrane fraction. Partial proteolysis of the human caspase 3-cleaved N-htt fragment by calpain occurred in vitro and resulted in smaller N-terminal products; products of similar size appeared when mouse brain protein extracts were treated with calpain. Results support the idea that sequential proteolysis by caspase 3 and calpain may regulate huntingtin function at membranes and produce N-terminal mutant fragments that aggregate and cause cellular dysfunction in HD. C1 Massachusetts Gen Hosp, MGH East, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, Worcester, MA 01665 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp, MGH East, 114 16th St, Charlestown, MA 02129 USA. RI Kim, Yun Joong/E-7117-2015 OI Kim, Yun Joong/0000-0002-2956-1552 FU NINDS NIH HHS [P50 NS016367, NS16367, NS35711, NS38194, R01 NS035711, R01 NS038194] NR 30 TC 241 Z9 247 U1 2 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2001 VL 98 IS 22 BP 12784 EP 12789 DI 10.1073/pnas.221451398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 486EU UT WOS:000171806100088 PM 11675509 ER PT J AU Stafford, RS Misra, B AF Stafford, RS Misra, B TI Variation in routine electrocardiogram use in academic primary care practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHEST PAIN; IMPACT; RATES AB Background: Lack of practical consensus regarding routine electrocardiogram (ECG) ordering in primary care led us to hypothesize that nonclinical variations in ordering would exist among primary care providers. Methods: We used 2 computerized billing systems to measure ECG ordering at visits to providers in 10 internal medicine group practices affiliated with a large, urban teaching hospital from October 1, 1996, to September 30, 1997. To focus on screening or routine ECGs, patients with known cardiac disease or suggestive symptoms were excluded, as were providers with fewer than 200 annual patient visits. Included were 69 921 patients making 190 238 visits to 125 primary care providers. Adjusted rates of ECG ordering accounted for patient age, sex, and 5 key diagnoses. Logistic regression evaluated additional predictors of ECG ordering. Results: Electrocardiograms were ordered in 4.4% of visits to patients without reported cardiac disease. Among the 10 group practices, ECG ordering varied from 0.5% to 9.6% of visits (adjusted rates, 0.8%-8.6%). Variations between individual providers were even more dramatic: adjusted rates ranged from 0.0% to 24% of visits, with an interquartile range of 1.4% to 4.7% and a coefficient of variation of 88%. Significant predictors of ECG use were older patient age, male sex, and the presence of clinical comorbidities. Additional nonclinical predictors included Medicare as a payment source, older male providers, and providers who billed for ECG interpretation. Conclusions: Variations in ECG ordering are not explained by patient characteristics. The tremendous nonclinical variations in ECG test ordering suggest a need for greater consensus about use of screening ECGs in primary care. C1 Massachusetts Gen Hosp, Primary Care Operat Improvement Team, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Howard Univ, Coll Med, Washington, DC USA. RP Stafford, RS (reprint author), Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, 1000 Welch Rd, Palo Alto, CA 94304 USA. NR 24 TC 12 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 22 PY 2001 VL 161 IS 19 BP 2351 EP 2355 DI 10.1001/archinte.161.19.2351 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 483RL UT WOS:000171649600009 PM 11606151 ER PT J AU Vergis, EN Brennen, C Wagener, M Muder, RR AF Vergis, EN Brennen, C Wagener, M Muder, RR TI Pneumonia in long-term care - A prospective case-control study of risk factors and impact on survival SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NURSING-HOME RESIDENTS; NOSOCOMIAL INFECTIONS; ACQUIRED PNEUMONIA; SURVEILLANCE; FACILITIES; MORTALITY; HOSPITALIZATION; VALIDATION; PREVALENCE; MANAGEMENT AB Background: Pneumonia is a major cause of morbidity and mortality in long-term care facilities. Prior studies of pneumonia have failed to identify risk factors potentially amenable to intervention. Our objectives were to (1) identify modifiable risk factors for the occurrence of pneumonia and (2) determine the long-term impact of pneumonia on survival. Methods: We performed a case-control study among residents of a Veterans Affairs long-term care facility. Case patients included all patients developing pneumonia from 2 days to 1 year after admission. Control subjects were matched for admission date, level of nursing care, and dependence in activities of daily living. Patients were followed up for 2 years or until death or discharge from the facility. Results: We identified 104 case-control pairs. Risk factors significantly associated with pneumonia included witnessed aspiration (odds ratio, 13.9; 95% confidence interval, 1.7-111.0; P=.01), sedative medication (odds ratio, 2.6; 95% confidence interval, 1.2-5.4; P=.01), and comorbidity score (odds ratio, 1.2; 95% confidence interval, 1.0-1.4;P=.05). Mortality due to pneumonia was 23% at 14 days. Patients with pneumonia had a significantly higher mortality than did controls at 1 year (75% vs 40%; P < .001); survival curves converged at 2 years. In a Cox proportional hazards regression model, an episode of pneumonia was independently associated with mortality during follow-up (odds ratio, 2.6; 95% confidence interval, 1.7-3,9; P < .001). Conclusions: Among long-term care patients closely matched for age, level of dependency, and duration of institutionalization, an episode of pneumonia is associated with significant excess mortality that persists for up to 2 years, Two identified risk factors, large-volume aspiration and receipt of sedating medication, are potentially amenable to intervention. C1 VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Med Ctr, Div Infect Dis, Dept Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Div Infect Dis, Univ Dr C, Pittsburgh, PA 15240 USA. NR 31 TC 74 Z9 78 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 22 PY 2001 VL 161 IS 19 BP 2378 EP 2381 DI 10.1001/archinte.161.19.2378 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 483RL UT WOS:000171649600013 PM 11606155 ER PT J AU Sasaki, H Auclair, D Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y Chen, LB AF Sasaki, H Auclair, D Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y Chen, LB TI Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients SO CANCER LETTERS LA English DT Article DE periostin; chemiluminescence; thymoma; invasive thymoma ID GROWTH-FACTOR-BETA; PROGNOSTIC FACTORS; SEQUENCE-ANALYSIS; GENE-EXPRESSION; FASCICLIN-I; METASTASIS; DISEASE; PROTEIN; CLONING; THYMUS AB Periostin protein shares structural and sequence homology with fasciclin 1, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients. and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4 +/- 122.9 ng/ml) and the normal control (962.0 +/- 118.6 ng/ml) (P = 0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0 +/- 285.8 ng/ml) was significantly higher than normal control (P = 0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, 1 Kawasumi, Nagoya, Aichi 4678601, Japan. NR 27 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 22 PY 2001 VL 172 IS 1 BP 37 EP 42 DI 10.1016/S0304-3835(01)00633-4 PG 6 WC Oncology SC Oncology GA 476PX UT WOS:000171238900005 PM 11595127 ER PT J AU Vaziri, H Dessain, SK Eagon, EN Imai, SI Frye, RA Pandita, TK Guarente, L Weinberg, RA AF Vaziri, H Dessain, SK Eagon, EN Imai, SI Frye, RA Pandita, TK Guarente, L Weinberg, RA TI hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase SO CELL LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; DNA-DAMAGE; IONIZING-RADIATION; SILENCING PROTEIN; STRAND BREAKS; SIR2 PROTEIN; CELL-LINES; PHOSPHORYLATION; ACTIVATION; ACETYLATION AB DNA damage-induced acetylation of p53 protein leads to its activation and either growth arrest or apoptosis. We show here that the protein product of the gene hSIR2(SIRT1), the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue, modification of which has been implicated in the activation of p53 as a transcription factor. Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53. In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. We propose that hSir2 is involved in the regulation of p53 function via deacetylation. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Vet Adm Med Ctr, Pittsburgh, PA 15240 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [R01 CA78461]; NHLBI NIH HHS [K08HL04463]; NINDS NIH HHS [NS34746] NR 34 TC 1534 Z9 1617 U1 14 U2 90 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 19 PY 2001 VL 107 IS 2 BP 149 EP 159 DI 10.1016/S0092-8674(01)00527-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 484MU UT WOS:000171694800005 PM 11672523 ER PT J AU Nadol, JB Merchant, SN AF Nadol, JB Merchant, SN TI Histopathology and molecular genetics of hearing loss in the human SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Review DE hearing loss; molecular genetics; histopathology; human ID HUP2 PAIRED DOMAIN; SYNDROME TYPE-I; WAARDENBURG-SYNDROME; MITOCHONDRIAL-DNA; TEMPORAL BONE; INNER-EAR; FRIEDREICHS ATAXIA; MENTAL DEFICIENCY; USHER-SYNDROME; HUMAN HOMOLOG AB Hearing loss is among the most common disabilities of man. It has been estimated that over 70 million individuals in the world are hearing impaired with pure tone averages greater than 55 dB. A genetic etiology is thought to be responsible for over half of early onset hearing loss and at least one third of late onset hearing loss. In this review, examples of the histopathology of the inner ear in known genetic syndromes in the human will be presented in order to provide a structural basis for understanding molecular mechanisms of development and maintenance in the inner ear, and to serve the essential function of validating the applicability of animal genetic models of hearing loss to the human condition. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 51 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD OCT 19 PY 2001 VL 61 IS 1 BP 1 EP 15 DI 10.1016/S0165-5876(01)00546-8 PG 15 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 481JC UT WOS:000171515300001 PM 11576626 ER PT J AU Babcock, GJ Mirzabekov, T Wojtowicz, W Sodroski, J AF Babcock, GJ Mirzabekov, T Wojtowicz, W Sodroski, J TI Ligand binding characteristics of CXCR4 incorporated into paramagnetic proteoliposomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTORS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; HIV-1 ENTRY; CHEMOKINE RECEPTORS; V3 LOOP; EXPRESSION; CCR5; CD4 AB The G protein-coupled receptor CXCR4 is a coreceptor, along with CD4, for the human immunodeficiency virus type 1 (HIV-1) and has been implicated in breast cancer metastasis. We studied the binding of the HIV-1 gp120 envelope glycoprotein (gp) to CXCR4 but found that the gp120s from CXCR4-using HIV-1 strains bound nonspecifically to several cell lines lacking human CXCR4 expression. Therefore, we constructed paramagnetic proteoliposomes (CXCR4-PMPLs) containing pure, native CXCR4. CXCR4-PMPLs specifically bound the natural ligand, SDF-1 alpha, and the gp120s from CXCR4-using HIV-1 strains. Conformation-dependent anti-CXCR4 antibodies and the CXCR4 antagonist AMD3100 blocked HIV-1 gp120 binding to CXCR4-PMPLs. The gp120-CXCR4 interaction was blocked by anti-gp120 antibodies directed against the third variable (V3) loop and CD4-induced epitopes, structures that have also been implicated in the binding of gp120 to the other HIV-1 coreceptor, CCR5. Compared with the binding of R5 HIV-1 gp120s to CCR5, the gp120-CXCR4 interaction exhibited a lower affinity (K-d = 200 nM) and was dependent upon prior CD4 binding, even at low temperature. Thus, although similar regions of X4 and R5 HIV-1 gp120s appear to be involved in binding CXCR4 and CCR5, respectively, differences exist in nonspecific binding to cell surfaces, affinity for the chemokine receptor, and CD4 dependence at low temperature. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31783, AI41851, AI42848, AI46725] NR 41 TC 77 Z9 79 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2001 VL 276 IS 42 BP 38433 EP 38440 DI 10.1074/jbc.M106229200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484CT UT WOS:000171673200016 PM 11489906 ER PT J AU Gama, L Wilt, SG Breitwieser, GE AF Gama, L Wilt, SG Breitwieser, GE TI Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CA2+ RECEPTOR; EXTRACELLULAR CA2+-SENSING RECEPTOR; CELL-SURFACE EXPRESSION; N-LINKED GLYCOSYLATION; OUTWARD K+ CHANNEL; SYNAPTIC CLEFT; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; HETEROMERIC COMPLEXES; MUSCARINIC RECEPTORS AB Calcium sensing (CaR) and Group I metabotropic glutamate receptors exhibit overlapping expression patterns in brain, and share common signal transduction pathways. To determine whether CaR and Group I metabotropic glutamate receptors (mGluRs) (mGluR1 alpha and mGluR5) can form heterodimers, we immunoprecipitated CaR from bovine brain and observed co-precipitation of mGluR1a. CaR and mGluR1 alpha co-localize in hippocampal and cerebellar neurons, but are expressed separately in other brain regions. In vitro transfection studies in HEK-293 cells established the specificity and disulfide-linked nature of the CaR:mGluR1 alpha (CaR: mGluR5) interactions. CaR:mGluR1 alpha (CaR:mGluR5) heterodimers exhibit altered trafficking via Homer 1c when compared with CaR:CaR homodimers. CaR becomes sensitive to glutamate-mediated internalization when present in CaR:mGluR1 alpha heterodimers. These results demonstrate cross-family covalent heterodimerization of CaR with Group I mGluRs, and increase the potential role(s) for CaR in modulating neuronal function. C1 Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Bronx Vet Affairs Med Ctr, Res Serv, Bronx, NY 10468 USA. RP Breitwieser, GE (reprint author), Syracuse Univ, Dept Biol, 122 Lyman Hall,108 Coll Pl, Syracuse, NY 13244 USA. OI Gama, Lucio/0000-0001-9511-012X FU NIGMS NIH HHS [GM58578] NR 69 TC 95 Z9 96 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2001 VL 276 IS 42 BP 39053 EP 39059 DI 10.1074/jbc.M105662200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484CT UT WOS:000171673200095 PM 11489900 ER PT J AU Linseman, DA Laessig, T Meintzer, MK McClure, M Barth, H Aktories, K Heidenreich, KA AF Linseman, DA Laessig, T Meintzer, MK McClure, M Barth, H Aktories, K Heidenreich, KA TI An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; GTP-BINDING PROTEINS; RHO-FAMILY GTPASES; N-TERMINAL KINASE; DIFFICILE TOXIN-B; C-JUN; CLOSTRIDIUM-DIFFICILE; GROWTH-FACTOR; SYMPATHETIC NEURONS; INDUCED APOPTOSIS AB Rho family GTPases are critical molecular switches that regulate the actin cytoskeleton and cell function. In the current study, we investigated the involvement of Rho GTPases in regulating neuronal survival using primary cerebellar granule neurons. Clostridium difficile toxin B, a specific inhibitor of Rho, Rac, and Cdc42, induced apoptosis of granule neurons characterized by c-Jun phosphorylation, caspase-3 activation, and nuclear condensation. Serum and depolarization-dependent survival signals could not compensate for the loss of GTPase function. Unlike trophic factor withdrawal, toxin B did not affect the antiapoptotic kinase Akt or its target glycogen synthase kinase-3 beta. The proapoptotic effects of toxin B were mimicked by Clostridium sordellii lethal toxin, a selective inhibitor of Rac/Cdc42. Although Rac/Cdc42 GTPase inhibition led to F-actin disruption, direct cytoskeletal disassembly with Clostridium botulinum C2 toxin was insufficient to induce c-Jun phosphorylation or apoptosis. Granule neurons expressed high basal JNK and low p38 mitogen-activated protein kinase activities that were unaffected by toxin B. However, pyridyl imidazole inhibitors of JNK/p38 attenuated c-Jun phosphorylation. Moreover, both pyridyl imidazoles and adenoviral dominant-negative c-Jun attenuated apoptosis, suggesting that JNK/c-Jun signaling was required for cell death. The results indicate that Rac/Cdc42 GTPases, in addition to trophic factors, are critical for survival of cerebellar granule neurons. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Freiburg, Inst Pharmakol & Toxikol, D-79104 Freiburg, Germany. RP Linseman, DA (reprint author), Denver VAMC 111H, 1055 Clermont St, Denver, CO 80220 USA. RI Barth, Holger/E-7920-2013 NR 57 TC 58 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2001 VL 276 IS 42 BP 39123 EP 39131 DI 10.1074/jbc.M103959200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484CT UT WOS:000171673200104 PM 11509562 ER PT J AU Li, SL Valente, AJ Wang, L Gamez, MJ Clark, RA AF Li, SL Valente, AJ Wang, L Gamez, MJ Clark, RA TI Transcriptional regulation of the p67(phox) gene - Role of AP-1 in concert with myeloid-specific transcription factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CCAAT DISPLACEMENT PROTEIN; SEQUENCE-BINDING PROTEIN; NADPH OXIDASE; RESPIRATORY BURST; GP91(PHOX) EXPRESSION; PROMOTER ACTIVITY; RETINOIC ACID; DNA-BINDING; HL-60 CELLS AB We have investigated the myeloid-specific transcriptional regulation of p67(phox), an essential component of phagocyte respiratory burst NADPH oxidase. Analysis was carried out on the p67(phox), 5'-flanking region from -3669 to -4 (relative to ATG), including the first exon and intron and part of the second exon. The construct extending from -985 to -4 produced the highest luciferase activity in myeloid HL-60 cells but was not active in HeLa or Jurkat cells, indicating myeloid-specific expression. Four active elements were identified: Sp1/Sp3 at -694, PU.1 at -289, AP-1 at -210, and PU.1/HAF1 at -182, the latter three being in the first intron. These cis elements bound their cognate transacting factors both in vitro and in vivo. Mutation of the Sp1, PU.1, or PU.1/ HAFT site each decreased promoter activity by 35-50%. Mutations in all three sites reduced promoter activity by 90%. However, mutation of the AP-1 site alone nearly abolished promoter activity. The AP-1 site bound Jun and Fos proteins from HL-60 cell nuclear extract. Coexpression with Jun B in AP-1-deficient cells increased promoter activity by 3-fold. These data show that full p67(phox) promoter activity requires cooperation between myeloid-specific and nonmyeloid transcription factors, with AP-1 being the most critical for function. 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. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [R01 AG019519]; NIAID NIH HHS [AI20866, R01 AI020866, R37 AI020866] NR 42 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2001 VL 276 IS 42 BP 39368 EP 39378 DI 10.1074/jbc.M106111200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484CT UT WOS:000171673200136 PM 11483614 ER PT J AU Bahary, N Zon, LI AF Bahary, N Zon, LI TI Development - Endothelium - Chicken soup for the endoderm SO SCIENCE LA English DT Editorial Material ID GROWTH-FACTOR; CELLS C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Dept Hematol Oncol, Boston, MA 02115 USA. RP Bahary, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. EM zon@genetics.med.harvard.edu NR 13 TC 24 Z9 27 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 19 PY 2001 VL 294 IS 5542 BP 530 EP 531 DI 10.1126/science.1066282 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484NC UT WOS:000171695600030 PM 11577202 ER PT J AU Clarke, P Meintzer, SM Spalding, AC Johnson, GL Tyler, KL AF Clarke, P Meintzer, SM Spalding, AC Johnson, GL Tyler, KL TI Caspase 8-dependent sensitization of cancer cells to TRAIL-induced apoptosis following reovirus-infection SO ONCOGENE LA English DT Article DE apoptosis; TRAIL; reovirus; caspase 8; chemotherapy ID INFLUENZA-VIRUS INFECTION; NECROSIS-FACTOR-ALPHA; TUMORICIDAL ACTIVITY; SIGNALING PATHWAY; DEATH RECEPTORS; MOLECULAR-BASIS; LIGAND; EXPRESSION; ACTIVATION; MODULATION AB TRAIL (TNF-related apoptosis-inducing ligand) induces apoptosis in susceptible cells by binding to death receptors 4 (DR4) and 5 (DR5). TRAIL preferentially induces apoptosis in transformed cells and the identification of mechanisms by which TRAIL-induced apoptosis can be enhanced may lead to novel cancer chemotherapeutic strategies. Here we show that reovirus infection induces apoptosis in cancer cell lines derived from human breast, lung and cervical cancers. Reovirus-induced apoptosis is mediated by TRAIL and is associated with the release of TRAIL from infected cells. Reovirus infection synergistically and specifically sensitizes cancer cell lines to killing by exogenous TRAIL. This sensitization both enhances the susceptibility of previously resistant cell lines to TRAIL-induced apoptosis and reduces the amount of TRAIL needed to kill already sensitive lines. Sensitization is not associated with a detectable change in the expression of TRAIL. receptors in reovirus-infected cells. Sensitization is associated with an increase in the activity of the death receptor-associated initiator caspase. caspase 8, and is inhibited by the peptide IETD-fmk, suggesting that reovirus sensitizes cancer cells to TRAIL-induced apoptosis in a caspase 8-dependent manner. Reovirus-induced sensitization of cells to TRAIL is also associated with increased cleavage of PARP, a substrate of the effector caspases 3 and 7. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1RO1AG14071]; NIGMS NIH HHS [GM30324] NR 43 TC 41 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 18 PY 2001 VL 20 IS 47 BP 6910 EP 6919 DI 10.1038/sj.onc.1204842 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 483NK UT WOS:000171641000012 PM 11687970 ER PT J AU Holmes, WC Conare, KR AF Holmes, WC Conare, KR TI Twenty years into the HIV epidemic, do we CARE enough to manage it well? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. ActionAIDS Inc, Philadelphia, PA 19107 USA. RP Holmes, WC (reprint author), 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 610 EP 612 PN 1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 481VY UT WOS:000171542200007 PM 11601933 ER PT J AU Fihn, SD Williams, SV Daley, J Gibbons, RJ AF Fihn, SD Williams, SV Daley, J Gibbons, RJ TI Guidelines for the management of patients with chronic stable angina: Treatment SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; TOTAL ISCHEMIC BURDEN; RANDOMIZED CONTROLLED TRIAL; DENSITY-LIPOPROTEIN CHOLESTEROL; PATIENTS RECEIVING PROPRANOLOL; ESTROGEN REPLACEMENT THERAPY; ACC/AHA/ACP-ASIM GUIDELINES; BETA-ADRENERGIC-BLOCKADE AB The dual alms of treating patients with chronic stable angina are 1) to reduce morbidity and mortality and 2) to eliminate angina with minimal adverse effects and allow the patient to return to normal activities. In the absence of contraindications, is-blockers are recommended as initial therapy. All beta -blockers seem to be equally effective. If the patient has serious contraindications to beta -blockers, unacceptable side effects, or persistent angina, calcium antagonists should be administered. Long-acting dihydropyridine and nondihydropyridine agents are generally as effective as beta -blockers in relieving angina. Long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid developing tolerance. All long-acting nitrates seem to be equally effective. Patients with angina should take 75 to 325 mg of aspirin daily unless they have contraindications. Such risk factors as, smoking, elevated low-density lipoprotein cholesterol level, diabetes, and hypertension should be treated appropriately. Coronary revascularization has not been shown to improve survival for most patients with chronic angina but may be required to control symptoms. However, coronary artery bypass grafting (CABG) is often indicated for symptomatic patients with left-main disease, three-vessel disease, or two-vessel disease including proximal stenosis of the left anterior descending coronary artery; it improves their survival. Percutaneous transluminal coronary angioplasty is an alternative to CABG for patients with normal left ventricular function and favorable angiographic features. Coronary artery bypass grafting is initially more effective in relieving angina than medical therapy, but the two procedures yield similar results after 5 to 10 years. Eighty percent of patients who undergo CABG remain angina-free 5 years after surgery. In low-risk patients, percutaneous transluminal coronary angioplasty seems to control angina better than medical therapy, but recurrent angina and repeated procedures are more likely than with CABG. Patient education is an important component of. management. Long-term follow-up should be individualized to ascertain clinical stability at regular intervals and to reassess prognosis when warranted. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Massachusetts Gen Hosp, Partners Hlth Care Syst, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 191 TC 32 Z9 33 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 616 EP 632 PN 1 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 481VY UT WOS:000171542200009 PM 11601935 ER PT J AU Shekelle, PG MacLean, CH Morton, SC Wenger, NS AF Shekelle, PG MacLean, CH Morton, SC Wenger, NS TI Assessing Care of Vulnerable Elders: Methods for developing quality indicators SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID VALIDITY; CRITERIA; UNDERUSE; TRIALS C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Rand Stat Grp, San Francisco, CA USA. RAND Hlth, Santa Monica, CA USA. RAND Stat Grp, Santa Monica, CA USA. RP Shekelle, PG (reprint author), RAND Corp, 1700 Main St,Box 2138, Santa Monica, CA 90407 USA. NR 21 TC 128 Z9 129 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 647 EP 652 PN 2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 481WA UT WOS:000171542400003 PM 11601947 ER PT J AU Wenger, NS Rosenfeld, K AF Wenger, NS Rosenfeld, K TI Quality indicators for end-of-life care in vulnerable elders SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CRITICALLY ILL PATIENTS; NURSING-HOME RESIDENTS; ADVANCE DIRECTIVES; SUSTAINING TREATMENT; RESUSCITATION PREFERENCES; CLINICAL MANAGEMENT; DYING PATIENTS; PHYSICIANS; DECISIONS; DEATH C1 Univ Calif Los Angeles, Dept Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Health Care Syst, Los Angeles, CA USA. RP Wenger, NS (reprint author), Univ Calif Los Angeles, Dept Med, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90095 USA. NR 64 TC 46 Z9 46 U1 8 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 677 EP 685 PN 2 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 481WA UT WOS:000171542400006 PM 11601950 ER PT J AU Chodosh, J Ferrell, BA Shekelle, PG Wenger, NS AF Chodosh, J Ferrell, BA Shekelle, PG Wenger, NS TI Quality indicators for pain management in vulnerable elders SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CHRONIC MUSCULOSKELETAL PAIN; PLACEBO-CONTROLLED TRIAL; GENERAL-POPULATION; NUTRITION EXAMINATION; DEPRESSIVE SYMPTOMS; DIABETIC NEUROPATHY; RANDOMIZED TRIAL; NATIONAL-HEALTH; PEPTIC-ULCER; DRUG-USE C1 Univ Calif Los Angeles, Div Geriatr, Dept Med, Los Angeles, CA 90095 USA. RAND Corp, Hlth, Santa Monica, CA 90406 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Chodosh, J (reprint author), Univ Calif Los Angeles, Div Geriatr, Dept Med, Los Angeles, CA 90095 USA. NR 38 TC 24 Z9 24 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 731 EP 735 PN 2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 481WA UT WOS:000171542400012 PM 11601956 ER PT J AU Rhew, DC AF Rhew, DC TI Quality indicators for the management of pneumonia in vulnerable elders SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; PNEUMOCOCCAL POLYSACCHARIDE VACCINE; PROSPECTIVE PAYMENT SYSTEM; INFLUENZA VACCINATION; HOSPITALIZED-PATIENTS; PRACTICE GUIDELINE; EARLY SWITCH; LOW-RISK; IMMUNIZATION; EFFICACY C1 Zynx Hlth Inc, Beverly Hills, CA 90212 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Rhew, DC (reprint author), Zynx Hlth Inc, 9100 Wilshire Blvd,Suite 655 E Tower, Beverly Hills, CA 90212 USA. NR 53 TC 16 Z9 18 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 736 EP 743 PN 2 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 481WA UT WOS:000171542400013 PM 11601957 ER PT J AU Schnelle, JF Smith, RL AF Schnelle, JF Smith, RL TI Quality indicators for the management of urinary incontinence in vulnerable community-dwelling elders SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INTRINSIC SPHINCTERIC DEFICIENCY; GENUINE STRESS-INCONTINENCE; RANDOMIZED CONTROLLED TRIAL; MUSCLE EXERCISE TREATMENT; DETRUSOR INSTABILITY; OLDER WOMEN; OXYBUTYNIN CHLORIDE; SURGICAL-TREATMENT; FOLLOW-UP; FEMALE C1 Anna & Harry Borun Ctr Gerontol Res, Reseda, CA 91335 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Los Angeles Jewish Home Aging, Los Angeles, CA USA. Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Schnelle, JF (reprint author), Anna & Harry Borun Ctr Gerontol Res, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 61 TC 23 Z9 23 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 16 PY 2001 VL 135 IS 8 BP 752 EP 758 PN 2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 481WA UT WOS:000171542400015 PM 11601959 ER PT J AU Glatter, KA Dorostkar, PC Yang, YF Lee, RJ Van Hare, GF Keung, E Modin, G Scheinman, MM AF Glatter, KA Dorostkar, PC Yang, YF Lee, RJ Van Hare, GF Keung, E Modin, G Scheinman, MM TI Electrophysiological effects of ibutilide in patients with accessory pathways SO CIRCULATION LA English DT Article; Proceedings Paper CT 20th Scientific Session of the North-American-Society-of-Pacing-and-Electrophysiology CY MAY 12-14, 1999 CL TORONTO, CANADA SP N Amer Soc Pacing & Electrophysiol DE Wolff-Parkinson-White syndrome; fibrillation; antiarrhythmia agents ID PARKINSON-WHITE-SYNDROME; ATRIAL-FIBRILLATION; INTRAVENOUS IBUTILIDE; EFFICACY; FLUTTER; TERMINATION; CONVERSION; SAFETY AB Background-Atrial fibrillation (AF) may cause life-threatening ventricular arrhythmias in patients with Wolff-Parkinson-White syndrome. We prospectively evaluated the effects of ibutilide on the conduction system in patients with accessory pathways (AP). Methods and Results-In part I, we gave ibutilide to 22 patients (18 men, 31 +/-3 years of age) who had AF during electrophysiology study, including 6 pediatric patients less than or equal to 18 years of age. Ibutilide terminated AF in 21 of 22 patients (95%) during or 8 +/-5 minutes after infusion and prolonged the shortest preexcited R-R interval during AF. Successful ablation was performed in all patients. In part II, ibutilide was given to 18 patients ( 14 men, 28 +/- 21 years) to assess its effects on the AP and conduction system. Ibutilide prolonged the antegrade atrioventricular node effective refractory period (ERP) (from 252 +/- 60 to 303 +/- 70 ms; P <0.02). Ibutilide caused transient loss of the delta wave in 1 patient and abolished inducible tachycardia in 2 patients, although retrograde mapping still allowed for successful AP ablation. The antegrade AP ERP prolonged from 275 +/- 40 to 320 +/- 60 ms (P <0.01), as did the antegrade AP block cycle length; the retrograde AP ERP and block cycle length similarly prolonged with ibutilide. The relative and effective refractory period of the His-Purkinje system increased in 61% of patients after ibutilide. There were no adverse side effects. Conclusions-We report the use of ibutilide in terminating AP-mediated AF, including the first report in the pediatric population. Ibutilide prolonged refractoriness of the atrioventricular node, His-Purkinje system, and AP. C1 Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sect Adult & Pediat Cardiac Electrophysiol, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Scheinman, MM (reprint author), Univ Calif San Francisco, Inst Cardiovasc Res, 500 Parnassus Ave,MU E 4S Box 1354, San Francisco, CA 94143 USA. NR 19 TC 31 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2001 VL 104 IS 16 BP 1933 EP 1939 DI 10.1161/hc4101.097538 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 486QP UT WOS:000171828700014 PM 11602497 ER PT J AU Messas, E Guerrero, JL Handschumacher, MD Chow, CM Sullivan, S Schwammenthal, E Levine, RA AF Messas, E Guerrero, JL Handschumacher, MD Chow, CM Sullivan, S Schwammenthal, E Levine, RA TI Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction - Insights from three-dimensional and contrast echocardiography with strain rate measurement SO CIRCULATION LA English DT Article DE mitral valve; regurgitation; remodeling; myocardial infarction; echocardiography ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; VALVE PROLAPSE; MECHANISM; RECONSTRUCTION; CLOSURE; HEART AB Background-Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. Methods and Results-We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2 +/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2 +/-0.3 to 1.4 +/-0.3 mL; +3.8 +/-0.5 min to -2.2 +/-0.7 turn axially relative to baseline; P <0.001) as PM strain rate decreased from +0.78 +/-0.07 per second (contraction) to -0.42 +/-0.06 per second (elongation, P <0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with interior ischemia and recurred with PM ischemia. Conclusions-PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy. C1 Harvard Univ, Cardiac Ultrasound Lab, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Sch Med, Massachusetts Gen Hosp, VBK508, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38176, HL-53702, K24 HL67434] NR 34 TC 75 Z9 78 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2001 VL 104 IS 16 BP 1952 EP 1957 DI 10.1161/hc4101.097112 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 486QP UT WOS:000171828700017 PM 11602500 ER PT J AU Messas, E Guerrero, JL Handschumacher, MD Conrad, C Chow, CM Sullivan, S Yoganathan, AP Levine, RA AF Messas, E Guerrero, JL Handschumacher, MD Conrad, C Chow, CM Sullivan, S Yoganathan, AP Levine, RA TI Chordal cutting - A new therapeutic approach for ischemic mitral regurgitation SO CIRCULATION LA English DT Article; Proceedings Paper CT 73rd Scientific Sessions of the American-Heart-Association CY NOV 12-15, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc DE mitral valve; regurgitation; remodeling; myocardial infarction; echocardiography ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; PAPILLARY-MUSCLE DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; MECHANISM; APPARATUS; PROLAPSE; INSIGHTS; REPAIR; VALVE AB Background-Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. Methods and Results-In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8 +/-0.2 to 7.1 +/-0.5 mL/beat after infarction and then decreased to 0.9 +/-0.1 mL/beat with chordal cutting (P <0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). Conclusions-Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Cardiovasc Lab, Boston, MA 02114 USA. Georgia Inst Technol, Sch Chem Engn, Biofluid Dynam Lab, Atlanta, GA 30332 USA. RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK508, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL38176, HL53702, K24 HL67434] NR 35 TC 180 Z9 185 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2001 VL 104 IS 16 BP 1958 EP 1963 DI 10.1161/hc4201.097135 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 486QP UT WOS:000171828700018 PM 11602501 ER PT J AU Siegel, AJ Stec, JJ Lipinska, I Van Cott, EM Lewandrowski, KB Ridker, PM Tofler, GH AF Siegel, AJ Stec, JJ Lipinska, I Van Cott, EM Lewandrowski, KB Ridker, PM Tofler, GH TI Effect of marathon running on inflammatory and hemostatic markers SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; SUDDEN-DEATH; EXERTION; MEN; ACTIVATION; MORTALITY; EXERCISE; EVENTS; RISK AB Although increasing levels of regular physical activity are incrementally cardioprotective,(1,2) prolonged strenuous exercise such as marathon running may trigger acute myocardial infarction(3) and sudden cardiac death.(4,5) The mechanism of such events is not well understood but may be due to hemodynamic, vasoconstrictive, and prothrombotic effects with disruption of unstable coronary plaques leading to acute coronary thrombosis.(6,7) Although several studies have demonstrated exercise-induced activation of fibrinolysis and coagulation,(8) the effect of marathon running on hemostatic balance has not been well studied. We therefore measured changes in C-reactive protein (CRP), von Willebrand factor (vWF), D-dimer, fibrinogen, fibrinolytic activity, white blood cell (WBC) counts, and platelet activation in middle-aged runners before and after the Boston Marathon. An imbalance in prothrombotic and fibrinolytic factors after strenuous physical exertion may transiently increase the risk for intravascular-including coronary-thrombosis and trigger acute ischemic events. C1 McLean Hosp, Dept Med, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Inst Prevent Cardiovasc Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Siegel, AJ (reprint author), McLean Hosp, Dept Internal Med, 115 Mill St, Belmont, MA 02478 USA. NR 20 TC 61 Z9 65 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2001 VL 88 IS 8 BP 918 EP + DI 10.1016/S0002-9149(01)01909-9 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 483KU UT WOS:000171635200024 PM 11676965 ER PT J AU Siegel, AJ Lewandrowski, EL Chun, KY Sholar, MB Fischman, AJ Lewandrowski, KB AF Siegel, AJ Lewandrowski, EL Chun, KY Sholar, MB Fischman, AJ Lewandrowski, KB TI Changes in cardiac markers including B-natriuretic peptide in runners after the Boston marathon SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CREATINE-KINASE-MB; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; TROPONIN-I; INJURY; GUIDELINES; MANAGEMENT; ISOENZYME; EXERCISE AB In contrast to nonspecific elevations of myoglobin and creatine kinase-MB (CK-MB) in athletes due to exertional rhabdomyolysis of trained skeletal muscle.(1,2) reported increases in cardiospecific troponins after competition may indicate silent injury to the myocardium.(3-8) We therefore undertook serial testing of multiple cardiac markers used to diagnose early- and late-stage myocardial injury in the same group of middle-aged runners before and sequentially after 5 Boston marathons over 4 years. In addition to CK-MB and myoglobin, cardiac troponin I (cTnI) was tested by a qualitative rapid assay in 1997, a high-sensitivity reference method in 1998 to 2000, and a rapid quantitative method to detect acute myocardial infarction (AMI) in 2001 together with cTnT. Selective postrace single-photon emission computed tomography (SPECT) with technetium-99m sestamibi myocardial scintigraphy and B-natriuretic peptide (BNP) levels were used to assess microinfarction and transient left ventricular dysfunction, respectively. C1 Massachusetts Gen Hosp, Dept Clin Labs, Clin Lab Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lewandrowski, EL (reprint author), Massachusetts Gen Hosp, Dept Clin Labs, Clin Lab Div, Gray 5,Fruit St, Boston, MA 02114 USA. NR 20 TC 69 Z9 70 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2001 VL 88 IS 8 BP 920 EP + DI 10.1016/S0002-9149(01)01910-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 483KU UT WOS:000171635200025 PM 11676966 ER PT J AU Faraone, SV Biederman, J Mick, E Doyle, AE Wilens, T Spencer, T Frazier, E Mullen, K AF Faraone, SV Biederman, J Mick, E Doyle, AE Wilens, T Spencer, T Frazier, E Mullen, K TI A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; gender differences; genetics; comorbidity ID DEFICIT HYPERACTIVITY DISORDER; SEX-DIFFERENCES; ENVIRONMENTAL-INFLUENCES; DIAGNOSTIC-CRITERIA; ADHD; PROBANDS; CHILDREN; SUBTYPES; SAMPLE; RELATIVES AB Background: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. Methods: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. Results: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. Conclusions: Our results suggest that boys and girls do not differ in the familiar risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differenceS in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects. (C) 2001 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 30 TC 35 Z9 35 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2001 VL 50 IS 8 BP 586 EP 592 DI 10.1016/S0006-3223(01)01146-5 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 486HQ UT WOS:000171812700004 PM 11690593 ER PT J AU Morii, E Ogihara, H Oboki, K Kataoka, TR Maeyama, K Fisher, DE Lamoreux, ML Kitamura, Y AF Morii, E Ogihara, H Oboki, K Kataoka, TR Maeyama, K Fisher, DE Lamoreux, ML Kitamura, Y TI Effect of a large deletion of the basic domain of mi transcription factor on differentiation of mast cells SO BLOOD LA English DT Article ID MI/MI GENOTYPE; MUTANT MICE; C-KIT; GENE-EXPRESSION; MICROPHTHALMIA; LOCUS; FIBROBLASTS; DEFICIENCY; MUTATIONS; PHENOTYPE AB The mi transcription factor (MITF) is a basic-helix-loop-helix-leucine zipper transcription factor that is important for the development of mast cells. Cultured mast cells (CMCs) of mi/mi genotype express abnormal MITF (mi-MITF), but CMCs of tg/tg genotype do not express any MITFs. It was previously reported that mi/mi CMCs showed more severe abnormalities than tg/tg CMCs, indicating that mi-MITF had inhibitory function. Whereas mi-MITF contains a single amino acid deletion in the basic domain, MITF encoded by mi(ew) allele (ew-MITE) deletes 16 of 21 amino acids of the basic domain. Here the effect of a large deletion of the basic domain was examined. In mi(ew)/mi(ew) CMCs, the expression pattern of genes whose transcription was affected by MITF was comparable to that of tg/tg CMCs rather than to that of mi/mi CMCs. This suggested that ew-MITF lacked any functions. The part of the basic domain deleted in ew-MITF appeared necessary for either transactivation or inhibition of transactivation. (Blood. 2001;98:2577-2579) (C) 2001 by The American Society of Hematology. C1 Osaka Univ, Sch Med, Dept Pathol, Suita, Osaka 5650871, Japan. Ehime Univ, Sch Med, Dept Pharmacol, Matsuyama, Ehime 790, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA. RP Morii, E (reprint author), Osaka Univ, Sch Med, Dept Pathol, Rm C2,Yamadaoka 2-2, Suita, Osaka 5650871, Japan. NR 25 TC 16 Z9 16 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2001 VL 98 IS 8 BP 2577 EP 2579 DI 10.1182/blood.V98.8.2577 PG 3 WC Hematology SC Hematology GA 482PG UT WOS:000171584000041 PM 11588059 ER PT J AU Fishman, JA AF Fishman, JA TI Prevention of infection caused by Pneumocystis carinii in transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID BONE-MARROW TRANSPLANTATION; INOCULATED MOUSE MODEL; SELF-SPLICING INTRON; RIBOSOMAL-RNA GENE; GROUP-I INTRON; TRIMETHOPRIM-SULFAMETHOXAZOLE; PRIMARY PROPHYLAXIS; AEROSOLIZED PENTAMIDINE; RENAL-TRANSPLANTATION; AIDS PATIENTS AB Pneumocystis carinii remains an important pathogen in patients who undergo solid-organ and hematopoietic transplantation. Infection results from reactivation of latent infection and via de novo acquisition of infection from environmental sources. The risk of infection depends on the intensity and duration of immunosuppression and underlying immune deficits. The risk is greatest after lung transplants, in individuals with invasive cytomegalovirus disease, during intensive immunosuppression for allograft rejection, and during periods of neutropenia. Prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) prevents many opportunistic infections, including infection with P. carinii, Toxoplasma gondii, and community-acquired respiratory, gastrointestinal, and urinary tract pathogens. Intolerance of TMP-SMZ is common; desensitization is useful less often in transplant patients than in patients with AIDS. Alternative agents provide a narrower spectrum of protection than does TMP-SMZ and less adequate protection against Pneumocystis species. Clinically, the diagnosis of breakthrough Pneumocystis pneumonia often requires invasive procedures. Strategies for the prevention of Pneumocystis infection must be individualized on the basis of a stratification of risk for each patient. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 111 TC 63 Z9 67 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2001 VL 33 IS 8 BP 1397 EP 1405 DI 10.1086/323129 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476NZ UT WOS:000171235600021 PM 11565082 ER PT J AU Robertson, NG Resendes, BL Lin, JS Lee, C Aster, JC Adams, JC Morton, CC AF Robertson, NG Resendes, BL Lin, JS Lee, C Aster, JC Adams, JC Morton, CC TI Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9 SO HUMAN MOLECULAR GENETICS LA English DT Article ID TEMPORAL BONE FINDINGS; HEARING-LOSS; EXTRACELLULAR-MATRIX; A-DOMAIN; FACTOR-C; GENE; MODULE; SUPERFAMILY; DYSFUNCTION; MUTATIONS AB Missense mutations in the COCH gene, which is expressed preferentially at high levels in the inner ear, cause the autosomal dominant sensorineural deafness and vestibular disorder, DFNA9 (OMIM 601369). By in situ hybridization of mouse and human inner ear sections, we find high-level expression of COCH mRNA in the fibrocytes of the spiral limbus and of the spiral ligament in the cochlea, and in the fibrocytes of the connective tissue stroma underlying the sensory epithelium of the crista ampullaris of the semicircular canals. A polyclonal antibody against the human COCH protein product, cochlin, was raised against the N-terminal 135 amino acid residues of cochlin, corresponding to the Limulus factor C-homology (cochFCH) domain; this domain harbors all five known point mutations in DFNA9. On western blots of human fetal cochlear extracts, anti-cochlin reacts with a cochlin band of the predicted full-length size as well as a smaller isoform. Immunohistochemistry performed with anti-cochlin shows staining predominantly in the regions of the fibrocytes of the spiral limbus and of the spiral ligament in mouse and in human fetal and adult tissue sections. These sites correspond to those areas that express COCH mRNA as determined by in situ hybridization, and to the regions of the inner ear which show histological abnormalities in DFNA9. The fibrocytes expressing mRNA and protein products of COCH are the very cell types which are either absent or markedly reduced and replaced by eosinophilic acellular material in temporal bone sections of individuals affected with DFNA9. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA82308]; NIDCD NIH HHS [DC03402, DC03929, F32 DC00405] NR 34 TC 56 Z9 59 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2001 VL 10 IS 22 BP 2493 EP 2500 DI 10.1093/hmg/10.22.2493 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 497GD UT WOS:000172446300003 PM 11709536 ER PT J AU Funke, B Epstein, JA Kochilas, LK Lu, MM Pandita, RK Liao, J Bauerndistel, R Schuler, T Schorle, H Brown, MC Adams, J Morrow, BE AF Funke, B Epstein, JA Kochilas, LK Lu, MM Pandita, RK Liao, J Bauerndistel, R Schuler, T Schorle, H Brown, MC Adams, J Morrow, BE TI Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects SO HUMAN MOLECULAR GENETICS LA English DT Article ID DIGEORGE-SYNDROME REGION; HOLT-ORAM SYNDROME; CHROMOSOMAL REGION; T-GENE; EXPRESSION; MUTATIONS; MOUSE; FAMILY; LIMB AB Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is a congenital anomaly disorder associated with hemizygous 22q11 deletions. We previously showed that bacterial artificial chromosome (BAC) transgenic mice overexpressing four transgenes, PNUTL1, (CDCrel-1), GP1B beta, TBX1 and WDR14, had reduced viability, cardiovascular malformations and thymus gland hypoplasia. Since these are hallmark features of VCFS/DGS, we analyzed the mice for additional anomalies. We found that the mice have important defects in the middle and inner ear that are directly relevant to the disorder. The most striking defect was the presence of chronic otitis media, a common finding in VCFS/DGS patients. In addition, the mice had a hyperactive circling behavior and sensorineural hearing loss. This was associated with middle and inner ear malformations, analogous to Mondini dysplasia in humans reported to occur in VCFS/DGS patients. We propose that overexpression of one or more of the transgenes is responsible for the etiology of the ear defects in the mice. Based upon its pattern of expression in the ear and functional studies of the gene, TbX1 likely plays a central role. Haploinsufficiency of TBX1 may be responsible for ear disorders in VCFS/DGS patients. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. Forschungszentrum Karlsruhe, Inst Genet & Toxikol, D-76133 Karlsruhe, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Eaton Peabody Lab, Boston, MA 02114 USA. RP Morrow, BE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Schorle, Hubert/M-5001-2016 OI Schorle, Hubert/0000-0001-8272-0076 FU NHLBI NIH HHS [HL61465, R0-1 HL62974]; NICHD NIH HHS [P0-1 HD34980-3]; NIDCD NIH HHS [DC03929] NR 36 TC 55 Z9 57 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2001 VL 10 IS 22 BP 2549 EP 2556 DI 10.1093/hmg/10.22.2549 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 497GD UT WOS:000172446300009 PM 11709542 ER PT J AU Lechler, T Jonsdottir, GA Klee, SK Pellman, D Li, R AF Lechler, T Jonsdottir, GA Klee, SK Pellman, D Li, R TI A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast SO JOURNAL OF CELL BIOLOGY LA English DT Article DE polarity; Cdc42; actin polymerization; formin; Arp2/3 complex ID ALDRICH-SYNDROME PROTEIN; CORTICAL ACTIN CYTOSKELETON; ARP2/3 COMPLEX; MYOSIN-I; SACCHAROMYCES-CEREVISIAE; N-WASP; CELL POLARITY; BINDING-PROTEIN; BUDDING-YEAST; POLYMERIZATION AB The establishment of cell polarity in budding yeast involves assembly of actin filaments at specified cortical domains. Elucidation of the underlying mechanism requires an understanding of the machinery that controls actin polymerization and how this machinery is in turn controlled by signaling proteins that respond to polarity cues. We showed previously that the yeast orthologue of the Wiskott-Aldrich Syndrome protein, Bee1/Las17p, and the type I myosins are key regulators of cortical actin polymerization. Here, we demonstrate further that these proteins together with Vrp1p form a multivalent Arp2/3-activating complex. During cell polarization, a bifurcated signaling pathway downstream of the Rho-type GTPase Cdc42p recruits and activates this complex, leading to local assembly of actin filaments. One branch, which requires formin homologues, mediates the recruitment of the Bee1p complex to the cortical site where the activated Cdc42p resides. The other is mediated by the p21-activated kinases, which activate the motor activity of myosin-I through phosphorylation. Together, these findings provide insights into the essential processes leading to polarization of the actin cytoskeleton. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Stuttgart, Inst Biochem, D-70569 Stuttgart, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol, Boston, MA 02115 USA. RP Li, R (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA47135, R01 CA047135]; NIGMS NIH HHS [R01 GM061345, R01 GM057063, GM57063-01, GM61345-01, R37 GM061345] NR 48 TC 84 Z9 86 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 15 PY 2001 VL 155 IS 2 BP 261 EP 270 DI 10.1083/jcb.200104094 PG 10 WC Cell Biology SC Cell Biology GA 483TH UT WOS:000171651600010 PM 11604421 ER PT J AU Smith, LM Anderson, JR Qualman, SJ Crist, WM Paidas, CN Teot, LA Pappo, AS Link, MP Grier, HE Wiener, ES Breneman, JC Raney, RB Maurer, HM Donaldson, SS AF Smith, LM Anderson, JR Qualman, SJ Crist, WM Paidas, CN Teot, LA Pappo, AS Link, MP Grier, HE Wiener, ES Breneman, JC Raney, RB Maurer, HM Donaldson, SS TI Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERGROUP RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; PRIMARY CHEMOTHERAPY; PROGNOSTIC FACTORS AB Purpose: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. Patients and Methods: Six hundred ninety-five patients with group II tumors received. chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of, microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). Results: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506, IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%, P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. Conclusion: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy. C1 Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Columbus Childrens Hosp, Columbus, OH USA. Barrett Clin Canc Ctr, Cincinnati, OH USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Rochester, Rochester, NY USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. MD Anderson Canc Ctr, Houston, TX USA. RP Smith, LM (reprint author), Childrens Oncol Grp, POB 60012, Arcadia, CA USA. FU NCI NIH HHS [CA-24507, CA-72989] NR 21 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2001 VL 19 IS 20 BP 4058 EP 4064 PG 7 WC Oncology SC Oncology GA 483KH UT WOS:000171634200009 PM 11600608 ER PT J AU Baron, C McMorrow, I Sachs, DH LeGuern, C AF Baron, C McMorrow, I Sachs, DH LeGuern, C TI Persistence of dominant T cell clones in accepted solid organ transplants SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DISPARATE RENAL-ALLOGRAFTS; RECEPTOR REPERTOIRE USAGE; MINIATURE SWINE; CLASS-I; KIDNEY ALLOGRAFTS; MONONUCLEAR-CELLS; TOLERANCE; REJECTION; INDUCTION; DIVERSITY AB Donor/recipient MHC class II matching is beneficial to the survival of allogeneic kidneys in humans and swine. In the latter, tolerance to class I-disparate grafts can be induced by a short course of immunosuppression, a peripheral mechanism that implicates regulatory T cells. Absence of treatment will lead to prompt rejection. Rejected grafts are infiltrated by dominant alloaggressive T cells, whereas there is still speculation on the specificity and function of T cells invading accepted tissues. To characterize the TCR repertoire of graft-infiltrating T cells (GITC) in accepted kidneys, we have used the RT-PCR-based spectratyping technique to assess the length polymorphism of the porcine TCR beta chain complementary-determining region 3 (CDR3). Results show that T cells infiltrating accepted kidneys (n = 5) express a restricted polymorphism of the CDR3 length, whereas PBL from the same animal have the polymorphic distribution of CDR3 lengths found in naive animals; that the skewed V beta repertoire in accepted grafts involved distinct V beta subfamilies in otherwise MHC-identical recipient animals; that GITC clonal dominance is not caused by immunosuppression because a second kidney, accepted without drug treatment, exhibits the same TCR V beta CDR3 profiles than those detected in the first graft; and that intragraft clonal dominance intensifies with time, indicating progressive preeminence of nonaggressive GITC clones. Collectively, these data represent the first example, in a preclinical model, of the emergence of nonaggressive intragraft clones, which may be involved in the induction/maintenance of local tolerance to allogeneic tissues. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E, Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 38 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2001 VL 167 IS 8 BP 4154 EP 4160 PG 7 WC Immunology SC Immunology GA 487DL UT WOS:000171858300004 PM 11591735 ER PT J AU Stanislaus, R Singh, AK Singh, I AF Stanislaus, R Singh, AK Singh, I TI Lovastatin treatment decreases mononuclear cell infiltration into the CNS of Lewis rats with experimental allergic encephalomyelitis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; macrophages; Lovastatin; cytokines; CNS; statins ID NITRIC-OXIDE SYNTHASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; ASTROCYTES; MICROGLIA; AMINOGUANIDINE; PEROXYNITRITE; DEMYELINATION; LYMPHOCYTES; MACROPHAGES AB Mononuclear cell infiltration into the CNS and induction of inflammatory cytokines and NOS in diseases like multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) have been implicated in subsequent disease pathogenesis and progression. We report that Lovastatin treatment blocks the clinical disease and induction of inflammatory cytokines; and NOS in spinal cords of MBP induced EAE rats. A significant number of the infiltrating cells in CNS were ED1+ cells of monocyte/macrophage lineage. To understand the mechanism of efficacy of Lovastatin against EAE, we examined the effect of Lovastatin on the transmigration of mononuclear cells into EAE spinal cord. The data presented here documents that Lovastatin treatment attenuates the transmigration of mononuclear cells possibly by down regulating the expression of LFA-1, a ligand for ICAM, in endothelial-leukocyte interaction. These results indicate that Lovastatin treatment prevents infiltration by mononuclear cells into the CNS of rats induced for EAE, thereby lessening the histological changes and clinical signs and thus ameliorating the disease. These observations indicate that Lovastatin treatment may be of therapeutic value against inflammatory disease process associated with infiltration of activated mononuclear cells into the tissue. (C) 2001 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Pediat & Pathol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40810] NR 35 TC 103 Z9 107 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 2001 VL 66 IS 2 BP 155 EP 162 DI 10.1002/jnr.1207 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 477RL UT WOS:000171298000002 PM 11592110 ER PT J AU Rodriguez-Barbosa, JI Zhao, Y Barth, R Zhao, G Arn, JS Sachs, DH Sykes, M AF Rodriguez-Barbosa, JI Zhao, Y Barth, R Zhao, G Arn, JS Sachs, DH Sykes, M TI Enhanced CD4 reconstitution by grafting neonatal porcine tissue in alternative locations is associated with donor-specific tolerance and suppression of preexisting xenoreactive T cells SO TRANSPLANTATION LA English DT Article ID PIG THYMUS GRAFTS; CLASS II+ CELLS; TRANSPLANTATION TOLERANCE; XENOGENEIC TRANSPLANTATION; ANTIGEN DEPENDENCY; THYMECTOMIZED MICE; MINIATURE SWINE; INDUCTION; LYMPHOCYTES; ALLOGRAFTS AB Background. Donor-specific xenograft tolerance can be achieved by grafting fetal porcine thymus tissue to thymectomized (ATX) mice treated with natural killer (NK) and T-cell-depleting monoclonal antibodies plus 3 Gy of total body irradiation (TBI). Grafting of neo. natal, instead of fetal, thymus, along with neonatal pig spleen, leads to a lower level of mouse CD4 cell reconstitution, with less reliable tolerance induction. For a number of reasons, it would be advantageous to use neonatal rather than fetal pigs as donors. We therefore investigated the possibility that grafting larger amounts of neonatal porcine thymus tissue to different sites could allow improved outcomes to be achieved. Materials and methods. Multiple or single fragments of neonatal porcine thymus tissue were grafted with a splenic fragment to different sites (mediastinum, mesentery, and kidney capsule) of ATX B6 mice treated with T- and NK-cell-depleting antibodies and 3Gy TBI. Mice also received an intraperitoneal injection containing 1 x 10(7) donor splenocytes. Donor-specific skin graft tolerance was evaluated, and CD4 reconstitution and mouse anti-donor xenoantibodies were followed by flow cytometry. Results. Peripheral repopulation of CD4(+) cells occurred by 7 weeks after transplantation in mice grafted with four fragments of neonatal porcine tissue in either the mediastinum or the mesentery, but not in mice grafted under both kidney capsules with the same amount of tissue. The level of CD4 reconstitution correlated with skin graft tolerance and an absence of induced anti-donor xenoantibodies. Seventy-five per. cent of mice with >20% of CD4(+) cells among peripheral blood lymphocytes (PBL) by 13 weeks posttransplantation accepted donor porcine skin, while rejecting either non-donor neonatal porcine or mouse BALB/c skin allografts. In contrast, only 29% of grafted mice with <20% CD4(+) cells in the peripheral blood at 13 weeks accepted donor porcine skin. Grafted mice with poor reconstitution showed either low or high levels of anti-pig xenoantibodies of the IgM, IgG(1), and IgG(2a) isotypes. Grafted mice with >20% CD4(+) cells all had low levels of anti-pig xenoantibodies of these isotypes and displayed mixed lymphocyte reaction (MIR) tolerance to donor pig major histocompatibility complex (MHC), with responsiveness to allogeneic mouse stimulators. Conclusion. Grafting neonatal porcine thymus into either the mediastinum or mesentery provides earlier and more efficient reconstitution of the CD4 compartment than does grafting under the kidney capsule. Good CD4 reconstitution was associated with optimal donor-specific skin graft tolerance and avoidance of the anti-donor xenoantibody responses observed in mice with poor CD4 reconstitution. These results also suggest that there is a suppressive component to the porcine xenograft tolerance induced with this approach. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Transplantat Biol Res Ctr,BMT Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Transplantat Biol Res Ctr,BMT Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011 FU NHLBI NIH HHS [P0I HL18646]; NIAID NIH HHS [P01 AI139755] NR 43 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1223 EP 1231 DI 10.1097/00007890-200110150-00007 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100007 PM 11602846 ER PT J AU El Khoury, J Stikkelbroeck, MML Goodman, A Rubin, RH Cosimi, AB Fishman, JA AF El Khoury, J Stikkelbroeck, MML Goodman, A Rubin, RH Cosimi, AB Fishman, JA TI Postmenopausal tubo-ovarian abscess due to Pseudomonas aeruginosa in a renal transplant patient - A case report and review of the literature SO TRANSPLANTATION LA English DT Article ID RUPTURED TUBOOVARIAN ABSCESS; STREPTOCOCCUS-PNEUMONIAE; INTRAUTERINE-DEVICE; EMBRYO-TRANSFER; PERITONITIS; ACTINOMYCOSIS; ASSOCIATION; FEMALE; WOMAN; WOMEN AB Background. Pseudomonas aeruginosa is an uncommon cause of infection in the female genital tract. We report a case of postmenopausal tubo-ovarian abscess (TOA) due to P. aeruginosa. in a renal transplant recipient. The presentation included mild abdominal symptoms with rapid progression of peritonitis and surgical abscess drainage. This is the first such case in an organ transplant recipient described in the English literature. Methods and Results. Published reports of 1040 cases of TOA were reviewed. The most common features were a history of sexually transmitted disease or pelvic inflammatory disease, and symptoms including abdominal pain and fever. Escherichia. coli, Bacteroides spp., and Klebsiella pneumoniae were the most frequently encountered pathogens. Neisseria gonorrhoeae and Chlamydia trachomatis, which are frequently isolated from cervical cultures, are uncommonly isolated from tubo-ovarian abscesses. Forty percent of patients were treated with antibiotics alone, 18.8% with abdominal surgery, and 32% with surgery and antimicrobial therapy. Conclusion. This report illustrates the muted presentation and atypical microbiology of gynecologic infection in an organ transplant recipient. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div,GRJ 504, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div,GRJ 504, Boston, MA 02114 USA. RI Stikkelbroeck, M.M.L./L-4676-2015 NR 59 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1241 EP 1244 DI 10.1097/00007890-200110150-00010 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100010 PM 11602849 ER PT J AU Basker, M Alwayn, IPJ Buhler, L Harper, D Abraham, S Gray, HK DeAngelis, H Awwad, M Down, J Rieben, R White-Scharf, ME Sachs, DH Thall, A Cooper, DKC AF Basker, M Alwayn, IPJ Buhler, L Harper, D Abraham, S Gray, HK DeAngelis, H Awwad, M Down, J Rieben, R White-Scharf, ME Sachs, DH Thall, A Cooper, DKC TI Clearance of mobilized porcine peripheral blood progenitor cells is delayed by depletion of the pragocytic reticuloendothelial system in baboons SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; INTRAVENOUS GAMMA-GLOBULIN; RENAL-ALLOGRAFT TOLERANCE; MIXED CHIMERISM; TRANSPLANTATION TOLERANCE; CONDITIONING REGIMEN; CYNOMOLGUS MONKEYS; RAT MODEL; LONG-TERM; REJECTION AB Introduction. Attempts to achieve immunological tolerance to porcine tissues in nonhuman primates through establishment of mixed hematopoietic chimerism are hindered by the rapid clearance of mobilized porcine leukocytes, containing progenitor cells (pPBPCs), from the circulation. Eighteen hours after infusing 1-2x10(10) pPBPC/kg into baboons that had been depleted of circulating anti-alpha Gal and complement, these cells are almost undetectable by flow cytometry. The aim of the present study was to identify mechanisms that contribute to rapid clearance of pPBPCs in the baboon. This was achieved by depleting, or blocking the Fc-receptors of, cells of the phagocytic reticuloendothelial system (RES) using medronate liposomes (MLs) or intravenous immunoglobulin (Mg), respectively. Methods. Baboons (preliminary studies, n=4) were used in a dose-finding and toxicity study to assess the effect of MLs on macrophage depletion in vivo. In another study, baboons (n=9) received a nonmyeloablative conditioning regimen (NMCR) aimed at inducing immunological tolerance, including splenectomy, whole body irradiation (300 cGy) or cyclophosphamide (80 mg/kg), thymic irradiation (700 cGy), T-cell depletion, complement depletion with cobra venom factor, mycophenolate mofetil, anti-CD154 monoclonal antibody, and multiple extracorporeal immunoadsorptions of anti-aGal antibodies. The baboons were divided into three groups: Group 1 (n=5) NMCR+pPBPC transplantation; Group 2 (n=2) NMCR+ML+pPBPC tranplantation; and Group 3 (n=2) NMCR+IVIg+pPBPC transplantation. Detection of pig cells in the blood was assessed by fluorescence-activated cell sorter and polymerase chain reaction (PCR). Results. Preliminary studies: ML effectively depleted macrophages from the circulation in a dose-dependent manner. Group 1: On average, 14% pig cells were detected 2 hr postinfusion of 1x10(10) pPBPC/kg. After 18 hr, there were generally less than 1.5% pig cells detectable. Group 2: Substantially higher levels of pig cell chimerism (55-78%) were detected 2 hr postinfusion, even when a smaller number (0.5-1 x 10(10)/ kg) of pPBPCs had been infused, and these levels were better sustained IS hr later (10-52%). Group 3: In one baboon, 4.4% pig cells were detected 2 hr after infusion of 1x10(10) pPBPC/kg. After 18 hr, however, 7.4% pig cells were detected. A second baboon died 2 hr after infusion of 4 x 10(10) pPBPC/kg, with a total white blood cell count of 90,000, of which 70% were pig cells. No differences in microchimerism could be detected between the groups as determined by PCR. Conclusions. This is the first study to report an efficient decrease of phagocytic function by depletion of macrophages with MLs in a large-animal model. Depletion of macrophages with MLs led to initial higher chimerism and prolonged the survival of circulating pig cells in baboons. Blockade of macrophage function with IVIg had a more modest effect. Cells of the RES, therefore, play a major role in clearing pPBPCs from the circulation in baboons. Depletion or blockade of the RES may contribute to achieving mixed hematopoietic chimerism and induction of tolerance to a discordant xenograft. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Boston, MA USA. Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU PHS HHS [5P01 A139755] NR 42 TC 35 Z9 36 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1278 EP 1285 DI 10.1097/00007890-200110150-00017 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100017 PM 11602856 ER PT J AU Appel, JZ Alwayn, IPJ Buhler, L DeAngelis, HA Robson, SC Cooper, DKC AF Appel, JZ Alwayn, IPJ Buhler, L DeAngelis, HA Robson, SC Cooper, DKC TI Modulation of platelet aggregation in baboons: Implications for mixed chimerism in xenotransplantation. I. The roles of individual components of a transplantation conditioning regimen and of pig peripheral blood progenitor cells SO TRANSPLANTATION LA English DT Article ID ACUTE CORONARY SYNDROMES; ADHESION MOLECULES; ENDOTHELIAL-CELLS; CD40 LIGAND; THROMBOSIS; TOLERANCE; MOBILIZATION; INHIBITION; CYTOKINES; INDUCTION AB Background. The induction of tolerance to pig antigens in primates may facilitate the development of successful clinical xenotransplantation protocols. The infusion of mobilized porcine peripheral blood leukocytes (PBPCs, comprised of approximately 2% peripheral blood progenitor cells) into splenectomized preconditioned baboons, intended to induce mixed hematopoietic cell chimerism, however, results in a severe thrombotic microangiopathy (TM) that includes pronounced thrombocytopenia. Because the mechanisms responsible for this phenomenon are unclear, we have explored the effects of individual components of the conditioning regimen, of therapeutic adjuncts, and of PBPCs on platelet aggregation. Methods. Groups of splenectomized baboons (n = at least 2 in each group) were treated with single components of the conditioning regimen-whole body irradiation (WBI), antithymocyte globulin (ATG), extracorporeal immunoadsorption (EI), mycophenolate mofetil (MMF), anti-CD40L monoclonal antibody (mAb), cobra venom factor (CVF), pig hematopoietic growth factors (interleukin-3 (pIL3) and stem cell factor (pSCF))-or with potential adjuncts, prostacyclin (PGI2), heparin, methylprednisolone, and eptifibatide (a GPIIb/IIIa antagonist). Blood samples were collected and platelet-rich plasma (PRP) was prepared. Using light transmission aggregometry, the extent of aggregation induced by platelet agonists (thrombin, adenosine diphosphate (ADP), collagen, ristocetin, and arachidonic acid) was determined in vitro. PRP was also prepared from untreated baboons, PBPCs were added, and platelet aggregation was measured in the absence of exogenous platelet agonists. Results. WBI, ATG, MMF, anti-CD40L mAb, CVF, pIL3, pSCF, and PGI2 had no effect on purified baboon platelet aggregation profiles in vitro. Eptifibatide markedly inhibited platelet aggregation induced by all standard agonists. El or heparin inhibited thrombin-induced platelet aggregation, and methylprednisolone inhibited ADP-induced aggregation to some extent. In vitro addition of PBPCs to PRP stimulated platelet aggregation in the absence of any agonists. Prior treatment of baboons with eptifibatide, however, inhibited this effect by 70% to 80%. Conclusions. Aggregation of baboon platelets and TM is directly induced by PBPCs, but not by individual components of the conditioning regimen. GPIIb/ IIIa antagonists, such as eptifibatide, interfere directly with xenogeneic PBPC-platelet interactions and may further ameliorate TM in the pig-to-primate model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 01129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunol, Boston, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL57307, HL63972] NR 40 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1299 EP 1305 DI 10.1097/00007890-200110150-00020 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100020 PM 11602859 ER PT J AU Appel, JZ Alwayn, IPJ Correa, LE Cooper, DKC Robson, SC AF Appel, JZ Alwayn, IPJ Correa, LE Cooper, DKC Robson, SC TI Modulation of platelet aggregation in baboons: Implications for mixed chimerism in xenotransplantation. II. The effects of cyclophosphamide on pig peripheral blood progenitor cell-induced aggregation SO TRANSPLANTATION LA English DT Article ID THROMBOTIC THROMBOCYTOPENIC PURPURA; HIGH-DOSE CHEMOTHERAPY; ALLOGRAFT TOLERANCE; PULSE THERAPY; TRANSPLANTATION; DISORDERS; INDUCTION; DEFECT; DONOR AB Background. The induction of tolerance to pig antigens in primates may facilitate the development of successful clinical xenotransplantation protocols. The infusion of mobilized porcine peripheral blood leukocytes (PBPCs, comprised of approximately 2% peripheral blood progenitor cells) into splenectomized preconditioned (whole body irradiation (WBI)-based) baboons, intended to induce mixed hematopoietic cell chimerism, however, results in a severe thrombotic microangiopathy (TM) that includes pronounced thrombocytopenia. Previous studies have indicated that the infused PBPCs initiate platelet aggregation, but that the various individual components of the conditioning regimen are not associated with the development of aggregation. We have now investigated the effects of cyclophosphamide (CPP) as an alternative to WBI on platelet aggregation. Methods. Splenectomized baboons (n=3) were treated with CPP. Blood samples were collected and platelet-rich plasma (PRP) was prepared. Using light transmission aggregometry, the extent of aggregation induced by platelet agonists (thrombin, adenosine diphosphate (ADP), collagen, ristocetin, and arachidonic acid) was determined in vitro. PRP was also prepared from untreated baboons and from baboons receiving CPP, PBPCs were added, and platelet aggregation was measured in the absence of exogenous platelet agonists. Results, CPP markedly inhibited platelet aggregation induced by all standard agonists. In vitro addition of PBPCs to PRP stimulated platelet aggregation in the absence of any agonists. Prior treatment of baboons with CPP, however, inhibited this effect by 55% to 65%. TM was not evident in baboons receiving a conditioning regimen that included CPP instead of WBI. Conclusions. Aggregation of baboon platelets and TM is directly induced by PBPCs. CPP has direct antiaggregatory properties and may provide an alternative strategy to WBI in this pig-to-primate model intended to induce mixed hematopoietic cell chimerism. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 01129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunol, Boston, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL63972, HL57307] NR 19 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1306 EP 1310 DI 10.1097/00007890-200110150-00021 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100021 PM 11602860 ER PT J AU Marsh, JE Farmer, CKT Jurcevic, S Wang, Y Carroll, MC Sacks, SH AF Marsh, JE Farmer, CKT Jurcevic, S Wang, Y Carroll, MC Sacks, SH TI The allogeneic T and B cell response is strongly dependent on complement components C3 and C4 SO TRANSPLANTATION LA English DT Article ID HUMORAL IMMUNE-RESPONSE; ANTIBODY-RESPONSE; ALLOGRAFT-REJECTION; ACQUIRED-IMMUNITY; MICE DEFICIENT; GUINEA-PIGS; EXPRESSION; ANTIGEN; INFLAMMATION; RECEPTOR-1 AB Background. The mechanisms controlling the production of antibodies against histocompatibility antigens are of prime importance in organ transplantation. Methods. We investigated the role of complement in the response to allogeneic stimulation, using mice deficient in C3, C4, or C5 to dissect the role of the alternative, classical, and terminal complement pathways. Results. After fully major histocompatibility complex disparate skin grafts, the allospecific immunoglobulin (Ig)G response was markedly impaired in C3-and C4-, but not in C5-deficient mice. This defect was most pronounced for second set responses. C3-deficient mice also demonstrated a decreased range of IgG isotypes. In contrast, there was no impairment of the allospecific IgM response. In functional T cell assays, the proliferative response and interferon-gamma secretion of recipient lymphocytes restimulated in vitro with donor antigen was decreased two- to threefold in C3-deficient mice. Conclusions. These data show impairment of allogeneic T cell and B cell function in mice with defective complement activation and suggest a predominant role for the classical pathway in stimulating alloimmunity. The terminal pathway seems unimportant in this regard. This extends the results reported for soluble protein antigens and demonstrates a surprisingly marked effect on the alloresponse despite the presence of a stringent antigenic stimulus. These results have implications for the prevention of sensitization in naive transplant recipients. C1 Univ London Kings Coll, Guys Hosp, Dept Nephrol & Transplantat, London SE1 9RT, England. Alexion Pharmaceut Inc, Immunobiol Program, New Haven, CT 06511 USA. Ctr Blood Res, Boston, MA USA. RP Sacks, SH (reprint author), Univ London Kings Coll, Guys Hosp, Dept Nephrol & Transplantat, Floor 5,Thomas Guy House, London SE1 9RT, England. NR 39 TC 65 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2001 VL 72 IS 7 BP 1310 EP 1318 DI 10.1097/00007890-200110150-00022 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 485EG UT WOS:000171740100022 PM 11602861 ER PT J AU Patan, S Munn, LL Tanda, S Roberge, S Jain, RK Jones, RC AF Patan, S Munn, LL Tanda, S Roberge, S Jain, RK Jones, RC TI Vascular morphogenesis and remodeling in a model of tissue repair - Blood vessel formation and growth in the ovarian pedicle after ovariectomy SO CIRCULATION RESEARCH LA English DT Article DE angiogenesis; endothelial cell; intussusceptive microvascular growth; tissue repair; restenosis ID INTUSSUSCEPTIVE MICROVASCULAR GROWTH; CHORIOALLANTOIC MEMBRANE CAM; EMBRYONIC ANGIOGENESIS; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; CAPILLARY GROWTH; PILLAR FORMATION; TIE2 RECEPTOR; MECHANISM; RAT AB To investigate mechanisms of vascular morphogenesis in tissue repair, we performed ovariectomy with resection of the corresponding branches of the ovarian vessels in nude mice. This induces a vascular network remodeling response in the healing ovarian pedicle. Reconstruction of 2000 histological serial sections demonstrated that a new vascular network composed of venous-venous loops forms in the wall of the dilated ovarian vein. Preexisting veins of all sizes, including a branch of the main artery, are subjected to segmentation. Loop formation and segmentation are based on intussusceptive microvascular growth. Loop formation is followed by elongation. Loop remodeling occurs also by intussusception and results in the formation of compound loop systems. All loop systems observed were completely patent. Blind-ending sprouts were extremely rare. Anastomoses between the preexisting vessels subjected to segmentation and the loop systems were established to include the newly formed vessels into the preexisting vascular network. The formation of an increasing number of patent loop systems likely decreases hypoxia and subsequently arrests angiogenesis with transformation of the granulation tissue into a scar. Loop formation also occurred inside a large thrombus that occluded a part of the lumen of the main vein. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Patan, S (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cardiol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA56591] NR 23 TC 47 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 12 PY 2001 VL 89 IS 8 BP 723 EP 731 DI 10.1161/hh2001.097870 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 483JZ UT WOS:000171633400013 PM 11597996 ER PT J AU Patan, S Tanda, S Roberge, S Jones, RC Jain, RK Munn, LL AF Patan, S Tanda, S Roberge, S Jones, RC Jain, RK Munn, LL TI Vascular morphogenesis and remodeling in a human tumor xenograft - Blood vessel formation and growth after ovariectomy and tumor implantation SO CIRCULATION RESEARCH LA English DT Article DE angiogenesis; colon adenocarcinoma (LS174T); endothelial cell; intussusceptive microvascular growth; restenosis ID INTUSSUSCEPTIVE MICROVASCULAR GROWTH; CHORIOALLANTOIC MEMBRANE CAM; EMBRYONIC ANGIOGENESIS; PERMEABILITY FACTOR; CAPILLARY GROWTH; PILLAR FORMATION; TIE2 RECEPTOR; SOLID TUMORS; CELL-DEATH; RAT AB To determine mechanisms of blood vessel formation and growth in solid tumors, we used a model in which LS174T human colon adenocarcinomas are grown in the isolated ovarian pedicle of nude mice. Reconstruction of 3500 histological serial sections demonstrated that a new vascular network composed of venous-venous loops of varying sizes grows inside the tumor from the wall of the adjacent main vein. Loops elongate and remodel to establish complex loop systems. The mechanisms of loop formation and remodeling correspond to intussusceptive microvascular growth (IMG). In the tissue surrounding the tumor segmentation, another mechanism of IMG is prevalent in venous vessels. Comparison to vascular morphogenesis in the ovariectomized pedicle not only confirms the existence of corresponding mechanisms in both systems, but also reveals numerous sprouts that are superimposed onto loop systems and pathological deviations of loop formation, remodeling, and segmentation in the tumor. These pathological mechanisms interfere with vessel patency that likely cause heterogenous perfusion and hypoxia thus perpetuating angiogenesis. Blood vessel formation based on IMG was also detected in a large thrombus that completely occluded a part of an ovarian artery branch. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Patan, S (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cardiol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA56591, P01 CA080124, P01 CA080124-029001, P01 CA080124-030002]; NHLBI NIH HHS [R01 HL064240, K02 HL073237-03, R01 HL064240-03, K02 HL073237] NR 40 TC 52 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 12 PY 2001 VL 89 IS 8 BP 732 EP 739 DI 10.1161/hh2001.097872 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 483JZ UT WOS:000171633400014 PM 11597997 ER PT J AU Rosen, ED Spiegelman, BM AF Rosen, ED Spiegelman, BM TI PPAR gamma: a nuclear regulator of metabolism, differentiation, and cell growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ACTIVATED RECEPTOR-GAMMA; INHIBITS ADIPOCYTE DIFFERENTIATION; IMPROVED INSULIN-SENSITIVITY; RETINOID-X-RECEPTOR; ADIPOSE-TISSUE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); LIGAND ACTIVATION; OXIDIZED LDL; COLON-CANCER; C/EBP-ALPHA C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. FU NIDDK NIH HHS [4R37DK31405, 5R01DK57670, DK0802535] NR 72 TC 833 Z9 882 U1 7 U2 55 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2001 VL 276 IS 41 BP 37731 EP 37734 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481NU UT WOS:000171526500001 PM 11459852 ER PT J AU Aarts, MM Davidson, D Corluka, A Petroulakis, E Guo, J Bringhurst, FR Galipeau, J Henderson, JE AF Aarts, MM Davidson, D Corluka, A Petroulakis, E Guo, J Bringhurst, FR Galipeau, J Henderson, JE TI Parathyroid hormone-related protein promotes quiescence and survival of serum-deprived chondrocytes by inhibiting rRNA synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYPE-1 PTH/PTHRP RECEPTOR; SMOOTH-MUSCLE CELLS; HYPERTROPHIC CHONDROCYTES; BONE-FORMATION; NUCLEOLAR-LOCALIZATION; NUCLEAR-LOCALIZATION; PEPTIDE GENE; GROWTH; EXPRESSION; CARTILAGE AB Parathyroid hormone-related protein (PTHrP) was initially recognized for its ability to promote parathyroid hormone-like bioactivity in kidney, bone, and squamous epithelial cells. PTHrP is a multifunctional protein in which bioactivity is mediated by two distinct pathways. Its classic parathyroid hormone-like activity results from binding of its amino terminus to cell surface PTH1R and activation of signal transduction pathways. Another less well recognized pathway involves translocation of PTHrP to the nucleus via a mid-region bipartite nuclear targeting sequence (NTS), similar in structure and function to those found in retroviral regulatory proteins. PTHrP was identified in the nucleus of several different cell types in vivo and in vitro, where it has been implicated in cell cycle progression, cellular differentiation, and apoptosis. In previous work we showed that nuclear translocation of PTHrP enhanced the survival of serum-deprived chondrogenic cells, associated with RNA, and localized to a region of the nucleus rich in complexes of newly transcribed ribosomal RNA and protein. In this work we have used two chondrogenic cell lines, CFK2 (PTH1R+) and 27m21 (PTH1R-) to further explore mechanisms whereby PTHrP rescues immature chondrocytes from apoptosis. Endogenous PTHrP and exogenous PTHrP NTS peptide protected serum-deprived cells from apoptosis, in the presence and absence of PTH1R. The survival of cells expressing PTHrP and those treated with PTHrP NTS peptide was associated with a rapid shift into G(o)/G(1) accompanied by a significant down-regulation of rRNA synthesis and a decrease in the number of actively translating polyribosome complexes. Together with our previous observations, this work predicts a role for PTHrP in modulating ribosome biogenesis and preventing chondrogenic cells from progressing through the cell cycle in an unfavorable environment. C1 McGill Univ, Lady Davis Inst Med Res, Sir Mortimer B Davis Jewish Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Lady Davis Inst Med Res, Sir Mortimer B Davis Jewish Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Henderson, JE (reprint author), Lady Davis Inst Med Res, Rm 602,3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. RI Aarts, Michelle/C-5766-2008 OI Aarts, Michelle/0000-0002-9171-0571 NR 56 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2001 VL 276 IS 41 BP 37934 EP 37943 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481NU UT WOS:000171526500031 PM 11489898 ER PT J AU Christmas, P Jones, JP Patten, CJ Rock, DA Zheng, YM Cheng, SM Weber, BM Carlesso, N Scadden, DT Rettie, AE Soberman, RJ AF Christmas, P Jones, JP Patten, CJ Rock, DA Zheng, YM Cheng, SM Weber, BM Carlesso, N Scadden, DT Rettie, AE Soberman, RJ TI Alternative splicing determines the function of CYP4F3 by switching substrate specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID B-4 OMEGA-HYDROXYLASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; HUMAN SEMINAL-VESICLES; 20-HYDROXYEICOSATETRAENOIC ACID; MESSENGER-RNA; HUMAN LIVER; MOLECULAR-CLONING; ARACHIDONIC-ACID; CDNA CLONING; HUMAN KIDNEY AB Diversity of cytochrome P450 function is determined by the expression of multiple genes, many of which have a high degree of identity. We report that the use of alternate exons, each coding for 48 amino acids, generates isoforms of human CYP4F3 that differ in substrate specificity, tissue distribution, and biological function. Both isoforms contain a total of 520 amino acids. CYP4F3A, which incorporates exon 4, inactivates LTB4 by omega -hydroxylation (K-m = 0.68 mum) but has low activity for arachidonic acid (K-m = 185 mum); it is the only CYP4F isoform expressed in myeloid cells in peripheral blood and bone marrow. CYP4F3B incorporates exon 3 and is selectively expressed in liver and kidney; it is also the predominant CYP4F isoform in trachea and tissues of the gastrointestinal tract. CYP4F3B has a 30-fold higher K-m for LTB4 compared with CYP4F3A, but it utilizes arachidonic acid as a substrate for omega -hydroxylation (K-m = 22 mum) and generates 20-HETE, an activator of protein kinase C and Ca2+/calmodulin-dependent kinase II. Homology modeling demonstrates that the alternative exon has a position in the molecule which could enable it to contribute to substrate interactions. The results establish that tissue-specific alternative splicing of pre-mRNA can be used as a mechanism for changing substrate specificity and increasing the functional diversity of cytochrome P450 genes. C1 Massachusetts Gen Hosp E, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. Washington State Univ, Dept Chem, Pullman, WA 99164 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Gentest Corp, Woburn, MA 01801 USA. RP Christmas, P (reprint author), Massachusetts Gen Hosp E, Ctr Immunol & Inflammatory Dis, 149 Navy Yard,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [5R01HL55718]; NIDDK NIH HHS [1K01DK59991-01, 5R01DK52234]; NIEHS NIH HHS [ES09122]; NIGMS NIH HHS [5R01GM-61823, 5R01GM9054-09] NR 42 TC 92 Z9 98 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2001 VL 276 IS 41 BP 38166 EP 38172 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481NU UT WOS:000171526500060 PM 11461919 ER PT J AU Xiong, JP Stehle, T Diefenbach, B Zhang, RG Dunker, R Scott, DL Joachimiak, A Goodman, SL Arnaout, MA AF Xiong, JP Stehle, T Diefenbach, B Zhang, RG Dunker, R Scott, DL Joachimiak, A Goodman, SL Arnaout, MA TI Crystal structure of the extracellular segment of integrin alpha V beta 3 SO SCIENCE LA English DT Article ID IIB-IIIA COMPLEX; CD11B A-DOMAIN; LIGAND-BINDING; CELL-ADHESION; CONFORMATIONAL-CHANGES; ELECTRON-MICROSCOPY; AFFINITY; SITES; FIBRINOGEN; ACTIVATION AB Integrins are alpha beta heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin alphaV beta3 at 3.1 Angstrom resolution. Its 12 domains assemble into an ovoid "head" and two "tails." In the crystal, alphaV beta3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main intersubunit interface ties within the head, between a seven-bladed beta -propeller from alphaV and an A domain from beta3, and bears a striking resemblance to the G alpha /G beta interface in G proteins. A metal ion-dependent adhesion site (MIDAS) in the betaA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and betaA domains. MIDAS ties adjacent to a calcium-binding site with a potential regulatory function. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Merck KGaA, Dept Biotechnol, D-64271 Darmstadt, Germany. Merck KGaA, Dept Biomed Res Immunol Oncol, D-64271 Darmstadt, Germany. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL54227]; NIAID NIH HHS [AI45716]; NIDDK NIH HHS [DK48549, DK50305]; NIGMS NIH HHS [P50 GM062414-02, P50 GM062414] NR 45 TC 878 Z9 913 U1 3 U2 52 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 12 PY 2001 VL 294 IS 5541 BP 339 EP 345 DI 10.1126/science.1064535 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482WZ UT WOS:000171601400034 PM 11546839 ER PT J AU Ren, DJ Navarro, B Perez, G Jackson, AC Hsu, SF Shi, Q Tilly, JL Clapham, DE AF Ren, DJ Navarro, B Perez, G Jackson, AC Hsu, SF Shi, Q Tilly, JL Clapham, DE TI A sperm ion channel required for sperm motility and male fertility SO NATURE LA English DT Article ID MOUSE SPERM; ACROSOME REACTION; CALCIUM CHANNELS; ZONA-PELLUCIDA; CA2+ CHANNELS; ENTRY; SPERMATOZOA; EXPRESSION; INCREASE AB Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca2+-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper(-/-) mice, and CatSper(-/-) sperm are unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca2+ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Clapham, DE (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Enders 1309,320 Longwood Ave, Boston, MA 02115 USA. EM dclapham@rascal.med.harvard.edu NR 21 TC 427 Z9 440 U1 6 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 11 PY 2001 VL 413 IS 6856 BP 603 EP 609 DI 10.1038/35098027 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 480WE UT WOS:000171485700041 PM 11595941 ER PT J AU Zhuang, SG Demirs, JT Kochevar, IE AF Zhuang, SG Demirs, JT Kochevar, IE TI Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation SO ONCOGENE LA English DT Article DE protein kinase C; singlet oxygen; caspase-8; Fas; apoptosis; p38 ID RECEPTOR-INDUCED APOPTOSIS; PROGRAMMED CELL-DEATH; RADIATION-INDUCED APOPTOSIS; PEROXIDE-INDUCED APOPTOSIS; THERAPY-INDUCED APOPTOSIS; PHOTODYNAMIC THERAPY; CYTOCHROME-C; HL-60 CELLS; HYDROGEN-PEROXIDE; MEDIATED APOPTOSIS AB Although activation of protein kinase C (PKC) inhibits apoptosis induced by a variety of stimuli including singlet oxygen, the step at which PKC activation interferes with apoptotic signaling is not well defined. We have shown previously that caspase-8 and p38 mediate singlet oxygen-induced apoptosis in HL-60 cells. In this study, we investigated the influence of PKC on regulation of the caspase-8 and p38 pathways initiated by singlet oxygen. Singlet oxygen induced Fas clustering and subsequent recruitment of FADD and caspase-8. Treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, did not affect the binding of caspase-8 to the aggregated Fas. Surprisingly, under the same conditions PKC activation was still able to prevent singlet oxygen-induced activation of caspase-8 and block its downstream signaling events including cleavage of Bid and caspase-3, decrease in mitochondrial transmembrane potential and release of cytochrome c from mitochondria. Inhibition of PKC by GF109203 or H7 counteracted the TPA-mediated effects on the cleavage of caspases -3 and -8. However, neither activation nor inhibition of PKC affected p38 phosphorylation. These data indicate that PKC inhibits singlet oxygen-induced apoptosis by blocking activation of caspase-8. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, WEL-224,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM 30755] NR 83 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 11 PY 2001 VL 20 IS 46 BP 6764 EP 6776 DI 10.1038/sj.onc.1204867 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 482AA UT WOS:000171551600013 PM 11709711 ER PT J AU White, J Keller, P Stelzer, EHK AF White, J Keller, P Stelzer, EHK TI Spatial partitioning of secretory cargo from Golgi resident protein in live cells SO BMC CELL BIOLOGY LA English DT Article ID PLASMA-MEMBRANE PROTEINS; LIVING CELLS; FREE SYSTEM; INTERCOMPARTMENTAL TRANSPORT; INTRACELLULAR MEMBRANES; ELECTRON-MICROSCOPY; SURFACE TRANSPORT; HELA-CELLS; APPARATUS; PATHWAY AB Background: To maintain organelle integrity, resident proteins must segregate from itinerant cargo during secretory transport. However, Golgi resident enzymes must have intimate access to secretor cargo in order to carr out glycosylation reactions. The amount of cargo and associated membrane ma be significant compared to the amount of Golgi membrane and resident protein, but upon Golgi exit, cargo and resident are efficiently sorted. How this occurs in live cells is not known. Results: We observed partitioning of the fluorescent Golgi resident T2-CFP and fluorescent cargo proteins VSVG3-YFP or VSVG3-SP-YFP upon Golgi exit after a synchronous pulse of cargo was released from the ER. Golgi elements remained stable in overall size, shape and relative position as cargo emptied. Cargo segregated from resident rapidly by blebbing into micron-sized domains that contained little or no detectable resident protein and that appeared to be continuous with the parent Golgi element. Post-Golgi transport carriers (TCs) exited repeatedly from these domains. Alternatively, entire cargo domains exited Golgi elements, forming large TCs that fused directly with the plasma membrane. However, domain formation did not appear to be an absolute prerequisite for TC exit, since TCs also exited directly from Golgi elements in the absence of large domains. Quantitative cargo-specific photobleaching experiments revealed transfer of cargo between Golgi regions, but no discrete intra-Golgi TCs were observed. Conclusions: Our results establish domain formation via rapid lateral partitioning as a general cellular strategy for segregating different transmembrane proteins along the secretor pathway and provide a framework for consideration of molecular mechanisms of secretor transport. C1 European Mol Biol Lab, Light Microscopy Grp, Heidelberg, Germany. European Mol Biol Lab, Cell Biol & Biophys Programme, Heidelberg, Germany. Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. RP White, J (reprint author), European Mol Biol Lab, Light Microscopy Grp, Meyerhofstr, Heidelberg, Germany. RI Stelzer, Ernst/A-7648-2011 OI Stelzer, Ernst/0000-0003-1545-0736 NR 52 TC 40 Z9 42 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD OCT 10 PY 2001 VL 2 AR 19 DI 10.1186/1471-2121-2-19 PG 15 WC Cell Biology SC Cell Biology GA 501NL UT WOS:000172690700001 PM 11707151 ER PT J AU Reue, K Glueck, SB AF Reue, K Glueck, SB TI Accumulating evidence for differences during preadipocyte development - Focus on "Differential gene expression in white and brown preadipocytes" SO PHYSIOLOGICAL GENOMICS LA English DT Editorial Material C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, Dept Med, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT 10 PY 2001 VL 7 IS 1 BP 1 EP 2 PG 2 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 481BV UT WOS:000171500000001 PM 11595786 ER PT J AU Pion, M Liska, V Chenine, AL Hofmann-Lehmann, R Vlasak, J Gondois-Rey, F Ruprecht, RM Hirsch, I AF Pion, M Liska, V Chenine, AL Hofmann-Lehmann, R Vlasak, J Gondois-Rey, F Ruprecht, RM Hirsch, I TI Extensively deleted simian immunodeficiency virus (SIV) DNA in macaques inoculated with supercoiled plasmid DNA encoding full-length SIVmac239 SO VIROLOGY LA English DT Article DE truncated SIV DNA; intramuscular inoculation of proviral DNA; SIV replication in vivo; lymph nodes. ID T-CELL DEPLETION; LYMPHOID-TISSUE; LEUKEMIA-VIRUS; INFECTION; REPLICATION; DISEASE; TYPE-1; HIV-1; LYMPHOCYTES; RESPONSES AB Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding intact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculation onward, we detected extensively deleted proviral genomes along with full-length viral genomes in peripheral blood mononuclear cells (PBMC) in adult macaques, During their chronic asymptomatic phase of infection, the frequency of deleted proviral genomes was similar in PBMC and lymph nodes. The latter, however, harbored significantly more full-length proviral DNA than PBMC, consistent with the lack of effective antiviral cytotoxic T-cell activity in lymph nodes described by others during human immunodeficiency virus infection. After the macaques progressed to AIDS, full-length proviral DNA became equally abundant in lymph nodes and in PBMC. We have demonstrated that although a single molecular species of proviral DNA was inoculated, genomic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo. (C) 2001 Academic Press. C1 INSERM U372, Unite Pathogenie Infect Lentivirus, F-13273 Marseille, France. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hirsch, I (reprint author), INSERM U372, Lab Pathogenie Infect Lentivirus, 163,Ave Luminy,BP 178, F-13276 Marseille 9, France. RI Hofmann-Lehmann, Regina/C-6528-2009; Pion, Marjorie/D-8139-2012; Hirsch, Ivan/J-7726-2015 OI Pion, Marjorie/0000-0002-6406-747X; FU NCRR NIH HHS [1R01 RR14180]; NIAID NIH HHS [R01AI32330] NR 31 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2001 VL 289 IS 1 BP 103 EP 113 DI 10.1006/viro.2001.1079 PG 11 WC Virology SC Virology GA 488QT UT WOS:000171947700012 PM 11601922 ER PT J AU Joukov, V Chen, J Fox, EA Green, JBA Livingston, DM AF Joukov, V Chen, J Fox, EA Green, JBA Livingston, DM TI Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMARY EPITHELIAL-CELLS; DNA-DAMAGE; GENETIC INSTABILITY; MEIOTIC CELLS; EMBRYO; REPAIR; BREAST; MORPHOGENESIS; ASSOCIATION; EXPRESSION AB The breast and ovarian susceptibility protein 1 (BRCA1) heterodimerizes with its structural relative, the BRCA1-associated RING domain protein (BARD1), which may have tumor suppressing function in its own right. Both proteins have evolved from a common evolutionary ancestor, and both exist in Xenopus laevis where, similar to their mammalian homologs, they form functional heterodimers. Depleting frog embryos of either BARD1 or BRCA1 led to similar and widely defective developmental phenotypes as well as depletion of the other polypeptide due to its decreased stability, Thus, each protein, in part, controls the abundance, stability, and function of the other, and these effects are heterodimerization-dependent. The interdependent nature of BRCA1 and BARD1 function supports the view that BARD1/BRCA1 heterodimers play a major role in breast and ovarian cancer suppression. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 NR 38 TC 101 Z9 103 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12078 EP 12083 DI 10.1073/pnas.211427098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900047 PM 11593018 ER PT J AU Ishii, T Ohnuma, K Murakami, A Takasawa, N Kobayashi, S Dang, NH Schlossman, SF Morimoto, C AF Ishii, T Ohnuma, K Murakami, A Takasawa, N Kobayashi, S Dang, NH Schlossman, SF Morimoto, C TI CD26-mediated signaling for T cell activation occurs in lipid rafts through its association with CD45RO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DIPEPTIDYL PEPTIDASE-IV; TYROSINE-PHOSPHATASE; MEMBRANE DOMAINS; NEGATIVE REGULATION; ANTIGEN RECEPTOR; PROTEIN-KINASE; LYMPHOCYTES-T; CD26 ANTIGEN; EXPRESSION; SURFACE AB CD26 is a T cell activation antigen that contains dipeptidyl peptidase IV activity and is known to bind adenosine deaminase. The mechanism by which CD26 costimulation potentiates T cell receptor-mediated T cell activation, leading to subsequent exertion of T cell effector function, is still not clearly defined. In this article, we demonstrate that CD26 localizes into lipid rafts, and targeting of CD26 to rafts is necessary for signaling events through CD26. Importantly, aggregation of CD26 by anti-CD26 mAb crosslinking also causes coaggregation of CD45 into rafts. Moreover, we show that CD26 directly binds to the cytoplasmic domain of CD45. Our results therefore indicate a mechanism whereby CD26 engagement promotes aggregation of lipid rafts and facilitates colocalization of CD45 to T cell receptor signaling molecules p56(Lck), ZAP-70, and TCR zeta, thereby enhancing protein tyrosine phosphorylation of various signaling molecules and subsequent interleukin-2 production. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Dept Clin Immunol,Minato Ku, Tokyo 1088639, Japan. MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. RP Morimoto, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR33713] NR 44 TC 106 Z9 107 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12138 EP 12143 DI 10.1073/pnas.211439098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900058 PM 11593028 ER PT J AU Brown, EN Nguyen, DP Frank, LM Wilson, MA Solo, V AF Brown, EN Nguyen, DP Frank, LM Wilson, MA Solo, V TI An analysis of neural receptive field plasticity by point process adaptive filtering SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID UNIT-ACTIVITY; SPATIAL MAP; HIPPOCAMPUS; CORTEX; ADULT; RAT; REPRESENTATIONS; POSITION; MONKEYS AB Neural receptive fields are plastic: with experience, neurons in many brain regions change their spiking responses to relevant stimuli. Analysis of receptive field plasticity from experimental measurements is crucial for understanding how neural systems adapt their representations of relevant biological information. Current analysis methods using histogram estimates of spike rate functions in nonoverlapping temporal windows do not track the evolution of receptive field plasticity on a fine time scale. Adaptive signal processing is an established engineering paradigm for estimating time-varying system parameters from experimental measurements. We present an adaptive filter algorithm for tracking neural receptive field plasticity based on point process models of spike train activity. We derive an instantaneous steepest descent algorithm by using as the criterion function the instantaneous log likelihood of a point process spike train model. We apply the point process adaptive filter algorithm in a study of spatial (place) receptive field properties of simulated and actual spike train data from rat CA1 hippocampal neurons. A stability analysis of the algorithm is sketched in the Appendix. The adaptive algorithm can update the place field parameter estimates on a millisecond time scale. It reliably tracked the migration, changes in scale, and changes in maximum firing rate characteristic of hippocampal place fields in a rat running on a linear track. Point process adaptive filtering offers an analytic method for studying the dynamics of neural receptive fields. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW 2052, Australia. MIT, Dept Brain & Cognit Sci, Ctr Res Neurosci, MIT,Ctr Learning & Mem,Riken, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. OI Frank, Loren/0000-0002-1752-5677 FU NIMH NIH HHS [R01 MH059733, K02 MH061637, MH59733, MH61637] NR 28 TC 84 Z9 84 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12261 EP 12266 DI 10.1073/pnas.201409398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900079 PM 11593043 ER PT J AU Sun, YT Huang, PL Li, JJ Huang, YQ Zhang, L Huang, PL Lee-Huang, S AF Sun, YT Huang, PL Li, JJ Huang, YQ Zhang, L Huang, PL Lee-Huang, S TI Anti-HIV agent MAP30 modulates the expression profile of viral and cellular genes for proliferation and apoptosis in AIDS-related lymphoma cells infected with Kaposi's sarcoma-associated virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AIDS-related tumor; MAP30; KSHV/HHV8 viral genes vCD/vIL-6/vFLIP; cDNA microarray; mitogenesis, tumorigenesis, and inhibition of apoptosis in NF kappa B and p53 signaling pathway-related genes egr-, ATF-2, hsp27, hsp90, I kappa B, mdm2, Skp1, Bax, CRADD, and caspase-3 ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTICENTRIC CASTLEMANS-DISEASE; DNA-SEQUENCES; IN-VITRO; HUMAN HERPESVIRUS-8; PROTEINS MAP30; CANCER; HUMAN-HERPESVIRUS-8; INHIBITION; GROWTH AB The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line derived from an AIDS patient. BC-2 cells are latently infected with Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8). We examined the effect of MAP30 on the expression of viral and cellular genes in BC-2 during latent and lytic states of the viral life cycle. By Northern analysis and RT-PCR, we found that MAP30 downregulates the expression of viral cyclin D (vCD), viral interleukin-6 (vIL-6), and viral FLIP (vFLIP), genes involved in cell cycle regulation, viral pathogenesis, and apoptosis. By pathway-specific cDNA microarray analysis, we found that BC-2 cells express high levels of egr-1, ATF-2, hsp27, hsp90, I kappaB, mdm2, skp1, and IL-2, cellular genes involved in mitogenesis, tumorigenesis, and inhibition of apoptosis in NF kappaB and p53 signaling pathways. These results define for the first time the specific cellular pathways involved in AIDS-related tumorigenesis and suggest specific novel targets for the treatment. Furthermore, we found that MAP30 downregulates the expression of egr-1, ATF-2, hsp27, hsp90, I kappaB, mdm2, and Skp1, while it upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus, MAP30 modulates the expression of both viral and cellular genes involved in KS pathogenesis. These results provide valuable insight into the molecular mechanisms of MAP30 anti-KS action and suggest its utility as a therapeutic agent against AIDS-related tumors. (C) 2001 Academic Press. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Sch Med, Dept Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. OI Lee-Huang, Sylvia/0000-0003-3302-241X NR 56 TC 43 Z9 54 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 5 PY 2001 VL 287 IS 4 BP 983 EP 994 DI 10.1006/bbrc.2001.5689 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 481CY UT WOS:000171503400031 PM 11573962 ER PT J AU Re, F Strominger, JL AF Re, F Strominger, JL TI Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNATE IMMUNE-SYSTEM; HUMAN MONOCYTES; CUTTING EDGE; SIGNALING PATHWAYS; WALL COMPONENTS; HOST-DEFENSE; KAPPA-B; RECOGNITION; EXPRESSION; CHEMOKINE AB Toll-like receptors (TLRs) mediate cell activation by various microbial products. Here, we demonstrate that activation of dendritic cells by TLR2 or TLR4 agonists, although it led to comparable activation of NF-kappaB and mitogen-activated protein kinase (MAPK) family members, resulted in striking differences in cytokine and chemokine gene transcription, suggesting that TLR2 and TLR4 signaling is not equivalent. A TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10, which is also associated to Th1 responses. In contrast, TLR2 stimulation failed to induce IL-12 p70 and interferon-gamma inducible protein (IP)-10 but resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development. TLR2 stimulation also resulted in preferential induction of IL-8 and p19/IL-23. Involvement of phosphatidylinositol 3-kinase and p38 MAPK in the TLR-mediated induction of several cytokine and chemokine messages was demonstrated using specific inhibitors. Thus, TLRs can translate the information regarding the nature of pathogens into differences in the cytokines and chemokines produced by dendritic cells and therefore may contribute to the polarization of the acquired immune response. 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), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5R35-CA47554] NR 34 TC 456 Z9 483 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37692 EP 37699 DI 10.1074/jbc.M105927200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700108 PM 11477091 ER PT J AU Mok, SC Chao, J Skates, S Wong, KK Yiu, GK Muto, MG Berkowitz, RS Cramer, DW AF Mok, SC Chao, J Skates, S Wong, KK Yiu, GK Muto, MG Berkowitz, RS Cramer, DW TI Prostasin, a potential serum marker for ovarian cancer: Identification through microarray technology SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL CARCINOMA; EXPRESSION; BREAST; LOCALIZATION; COMBINATION; ANTIGEN AB Background: Screening biomarkers for ovarian cancer are needed because of its late stage at diagnosis and poor survival. We used microarray technology to identify overexpressed genes for secretory proteins as potential serum biomarkers and selected prostasin, a serine protease normally secreted by the prostate gland, for further study. Methods: RNA was isolated and pooled from three ovarian cancer cell lines and from three normal human ovarian surface epithelial (HOSE) cell lines. Complementary DNA generated from these pools was hybridized to a microarray slide, and genes overexpressed in the cancer cells were identified. Real-time quantitative polymerase chain reaction was used to examine prostasin gene expression in ovarian cancer and HOSE cell lines. Anti-prostasin antibodies were used to examine prostasin expression and to measure serum prostasin by an enzyme-linked immunosorbent assay in 64 case patients with ovarian cancer and in 137 control subjects. Previously determined levels of CA 125, an ovarian cancer marker, were available from about 70% of all subjects. All statistical tests were two-sided. Results: Prostasin was detected by immunostaining more strongly in cancerous ovarian epithelial cells and stroma than in normal ovarian tissue. The mean level of serum prostasin was 13.7 mug/mL (95% confidence interval [CI] = 10.5 to 16.9 mug/mL) in 64 case patients with ovarian cancer and 7.5 mug/mL (95% CI = 6.6 to 8.3 mug/mL) in 137 control subjects (P < .041, after adjustment for the subject's age, year of collection, and specimen quality). In 14 of 16 case patients with both preoperative and postoperative serum samples, postoperative prostasin levels were statistically significantly lower than preoperative levels (P =.004). In 37 case patients with nonmucinous ovarian cancer and in 100 control subjects for whom levels of CA 125 and prostasin were available, the combination of markers gave a sensitivity of 92% (95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%) for detecting ovarian cancer. Conclusions: Prostasin is overexpressed in epithelial ovarian cancer and should be investigated further as a screening or tumor marker, alone and in combination with CA 125. C1 Harvard Univ, Lab Gynecol Oncol, Brigham & Womens Hosp, Sch Med,Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA USA. RP Mok, SC (reprint author), Harvard Univ, Lab Gynecol Oncol, Brigham & Womens Hosp, Sch Med,Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave,BLI 449, Boston, MA 02115 USA. OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [U10CA86381] NR 21 TC 185 Z9 193 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 3 PY 2001 VL 93 IS 19 BP 1458 EP 1464 DI 10.1093/jnci/93.19.1458 PG 7 WC Oncology SC Oncology GA 477DA UT WOS:000171266800009 PM 11584061 ER PT J AU Vergis, EN Hayden, MK Chow, JW Snydman, DR Zervos, MJ Linden, PK Wagener, MM Schmitt, B Muder, RR AF Vergis, EN Hayden, MK Chow, JW Snydman, DR Zervos, MJ Linden, PK Wagener, MM Schmitt, B Muder, RR TI Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia - A prospective multicenter study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BLOOD-STREAM INFECTIONS; FAECIUM BACTEREMIA; RISK-FACTORS; CLINICAL-FEATURES; GENTAMICIN-RESISTANT; SURGICAL PATIENTS; FAECALIS; LEVEL; ENDOCARDITIS; GENE AB Background: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance Is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. Objective: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. Design: Prospective observational study. Setting: Four academic medical centers and a community hospital. Patients: All patients with enterococcal bacteremia. Measurements: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. Results: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or Intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% Cl, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [Cl, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [Cl, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [Cl, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [Cl, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [Cl, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [Cl, 0.06 to 0.80]; P = 0.02). Conclusions: vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival. C1 Univ Pittsburgh, Med Ctr, Vet Affairs Med Ctr, Pittsburgh, PA USA. Rush Presbyterian St Lukes Med Ctr, Rush Med Coll, Chicago, IL 60612 USA. Wayne State Univ, Sch Med, Detroit, MI USA. John D Dingell Vet Affairs Med Ctr, Detroit, MI USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Muder, RR (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 48 TC 192 Z9 199 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 2 PY 2001 VL 135 IS 7 BP 484 EP 492 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 477EF UT WOS:000171269600002 PM 11578151 ER PT J AU Williams, SV Fihn, SD Gibbons, RJ AF Williams, SV Fihn, SD Gibbons, RJ TI Guidelines for the management of patients with chronic stable angina: Diagnosis and risk stratification SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; MEDICALLY TREATED PATIENTS; BUNDLE-BRANCH BLOCK; INCREMENTAL PROGNOSTIC VALUE; LEFT-VENTRICULAR FUNCTION; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; HIGH-DOSE DIPYRIDAMOLE AB Patients with suspected chronic stable angina can be evaluated in three stages. In stage one, the clinician uses information from the history, physical examination, laboratory tests for diabetes and hyperlipidemia, and resting electrocardiography to estimate the patient's probability of coronary artery disease (CAD). In stage two, additional testing for patients with a low probability of CAD focuses on diagnosing noncoronary causes of chest pain. Patients with a high probability of CAD have stress tests to assess their risk from CAD, and patients with an intermediate probability of CAD have stress tests to estimate the probability of CAD and assess their risk from CAD. Most patients with new-onset angina can start stress testing with exercise electrocardiography. The initial stress test should be a stress imaging procedure for patients with rest ST-segment depression greater than 1 mm, complete left bundle-branch block, ventricular paced rhythm, preexcitation syndrome, or previous revascularization with percutaneous coronary angioplasty or coronary artery bypass grafting. Patients who cannot exercise can have an imaging procedure with stress induced by pharmacologic agents. In stage three, patients with a predicted average annual cardiac mortality rate between 1% and 3% should have a stress Imaging study or coronary angiography with left ventriculography. Those with a known left ventricular dysfunction should have cardiac catheterization. Patients with CAD who have an estimated annual mortality rate greater than 3% should have cardiac catheterization to determine whether their anatomy is suitable for revascularization. Patients with an estimated annual mortality rate less than 1% can begin to receive medical therapy. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Med Ctr, Rochester, MN USA. RP Williams, SV (reprint author), 1220 Blockley Hall,423 Guadrian Dr, Philadelphia, PA 19104 USA. NR 159 TC 32 Z9 35 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 2 PY 2001 VL 135 IS 7 BP 530 EP 547 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 477EF UT WOS:000171269600009 PM 11578158 ER PT J AU Tian, R Musi, N D'Agostino, J Hirshman, MF Goodyear, LJ AF Tian, R Musi, N D'Agostino, J Hirshman, MF Goodyear, LJ TI Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy SO CIRCULATION LA English DT Article DE hypertrophy; muscles; proteins; glucose; myocardium; metabolism ID LEFT-VENTRICULAR HYPERTROPHY; SKELETAL-MUSCLE; CARDIAC-HYPERTROPHY; GLUCOSE-TRANSPORT; CREATINE-KINASE; INSULIN; TRANSLOCATION; GLYCOLYSIS; MECHANISM; ISOFORM AB Background-Recent reports suggest that activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), in response to acute changes in cellular energy status in cardiac and skeletal muscles, results in altered substrate utilization. We hypothesized that chronic alterations in myocardial energetics in hypertrophied hearts (left ventricular hypertrophy, LVH) will lead to elevated AMPK activity, which in turn regulates substrate utilization. Methods and Results-Using P-31 NMR spectroscopy and biochemical assays, we found that in LVH hearts, adenosine triphosphate (ATP) concentration decreased by 10%, phosphocreatine concentration decreased by 30%, and total creatine concentration was unchanged. Thus, the ratio of phosphocreatine/creatine decreased to one third of controls, and the ratio of AMP/ATP increased to 5 times above controls. These changes were associated with increased alpha (1) and alpha (2) AMPK activity (3.5- and 4.8-fold above controls, respectively). The increase in AMPK a, activity was accompanied by a 2-fold increase in alpha (1) expression, whereas a2 expression was decreased by 30% in LVH. The basal rate of 2-deoxyglucose uptake increased by 3-fold in LVH, which was associated with an increased amount of glucose transporters present on the plasma membrane. Conclusions-These results demonstrate for the first time that chronic changes in myocardial energetics in hypertrophied hearts are accompanied by significant elevations in AMPK activity and isoform-specific alterations in AMPK expression. It also raises the possibility that AMPK signaling plays an important role in regulating substrate utilization in hypertrophied hearts. C1 NMR Lab Physiol Chem, Div Cardiovasc Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tian, R (reprint author), NMR Lab Physiol Chem, Div Cardiovasc Med, 221 Longwood Ave,Room 229, Boston, MA 02115 USA. OI Tian, Rong/0000-0002-3676-3830 FU NHLBI NIH HHS [HL-59246]; NIA NIH HHS [AG-00837]; NIAMS NIH HHS [AR-42238, AR-45670] NR 30 TC 190 Z9 201 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 2 PY 2001 VL 104 IS 14 BP 1664 EP 1669 DI 10.1161/hc4001.097183 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 479RG UT WOS:000171416900018 PM 11581146 ER PT J AU Peterson, RT Mably, JD Chen, JN Fishman, MC AF Peterson, RT Mably, JD Chen, JN Fishman, MC TI Convergence of distinct pathways to heart patterning revealed by the small molecule concentramide and the mutation heart-and-soul SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; ZEBRAFISH DANIO-RERIO; CAENORHABDITIS-ELEGANS; CARDIOVASCULAR-SYSTEM; PIGMENTED EPITHELIUM; CELL-POLARITY; GENE; EXPRESSION; LAMBDA; RETINA AB Background: One of the earliest steps in heart formation is the generation of two chambers, as cardiogenic cells deployed in the epithelial sheet of mesoderm converge to form the nascent heart tube. What guides this transformation to organotypic form is not known. Results: We have identified a small molecule, concentramide, and a genetic mutation called heart-and-soul (has) that disrupt heart patterning. Both cause the ventricle to form within the atrium. Here, we show that the has gene encodes PKC lambda. The effect of the has mutation is to disrupt epithelial cell-cell interactions in a broad range of tissues. Concentramide does not disrupt epithelial interactions, but rather shifts the converging heart field rostrally. What is shared between the concentramide and has effects is a reversal of the order of fusion of the anterior and posterior ends of the heart field. Conclusions: The polarity of cardiac tube assembly is a critical determinant of chamber orientation and is controlled by at least two distinct molecular pathways. Combined chemical/genetic dissection can identify nodal points in development, of especial importance in understanding the complex patterning events of organogenesis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA 02139 USA. RP Fishman, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Cambridge, MA 02139 USA. EM fishman@cvrc.mgh.harvard.edu OI Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [HL49579, HL63206]; NIDDK NIH HHS [DK55383] NR 51 TC 122 Z9 124 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 2 PY 2001 VL 11 IS 19 BP 1481 EP 1491 DI 10.1016/S0960-9822(01)00482-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 478ZJ UT WOS:000171379200016 PM 11591315 ER PT J AU Legome, E AF Legome, E TI Clinical pearls: Cold feet SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID BLUE TOE SYNDROME; EMBOLIZATION; WARFARIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Residency Off, Dept Emergency Med,Harvard Affiliated Residency E, Boston, MA 02114 USA. RP Legome, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Residency Off, Dept Emergency Med,Harvard Affiliated Residency E, Founders 150, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2001 VL 8 IS 10 BP 998 EP + DI 10.1111/j.1553-2712.2001.tb01101.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 480CN UT WOS:000171444600012 PM 11581088 ER PT J AU Haidet, P Dains, JE Paterniti, DA Chang, T Tseng, E Rogers, JC AF Haidet, P Dains, JE Paterniti, DA Chang, T Tseng, E Rogers, JC TI Medical students' attitudes toward patient-centered care and standardized patients' perceptions of humanism: A link between attitudes and outcomes SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 40th Annual Conference of the Research in Medical Education CY NOV 04-07, 2001 CL WASHINGTON, D.C. ID PHYSICIAN C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. RP Haidet, P (reprint author), Baylor Coll Med, Houston VAMC, 2002 Holcombe Blvd 152A, Houston, TX 77030 USA. NR 14 TC 23 Z9 24 U1 0 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2001 VL 76 IS 10 SU S BP S42 EP S44 DI 10.1097/00001888-200110001-00015 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 482TX UT WOS:000171592300015 PM 11597869 ER PT J AU Gleason, S Furie, KL Lev, MH O'Donnell, J McMahon, PM Beinfeld, MT Halpern, E Mullins, M Harris, G Koroshetz, WJ Gazelle, GS AF Gleason, S Furie, KL Lev, MH O'Donnell, J McMahon, PM Beinfeld, MT Halpern, E Mullins, M Harris, G Koroshetz, WJ Gazelle, GS TI Potential influence of acute CT on inpatient costs in patients with ischemic stroke SO ACADEMIC RADIOLOGY LA English DT Article DE brain, CT; brain, ischemia; computed tomography (CT); angiography; efficacy study, CT ID RANDOMIZED CONTROLLED TRIAL; ANGIOGRAPHY; DISCHARGE; HOME AB Rationale and Objectives. Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. Materials and Methods. By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography, CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a nonacute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. Results. The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the $1.2 billion range (-$154 million to $2.1 billion) when patients with lacunar strokes are treated nonacutely and $1.8 billion when those patients are admitted for acute care. Conclusion. The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke. C1 Trinity Coll, Dept Econ, Hartford, CT 06106 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Innovated Minimally Invas Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Comp Aided Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA USA. RP Gazelle, GS (reprint author), Trinity Coll, Dept Econ, 600 Summit St, Hartford, CT 06106 USA. NR 23 TC 24 Z9 24 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2001 VL 8 IS 10 BP 955 EP 964 DI 10.1016/S1076-6332(03)80639-6 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 478QM UT WOS:000171356900003 PM 11699848 ER PT J AU Keilhoff, G Seidel, B Reiser, M Stanarius, A Huang, PL Bogerts, B Wolf, G Bernstein, HG AF Keilhoff, G Seidel, B Reiser, M Stanarius, A Huang, PL Bogerts, B Wolf, G Bernstein, HG TI Lack of neuronal NOS has consequences for the expression of POMC and POMC-derived peptides in the mouse pituitary SO ACTA HISTOCHEMICA LA English DT Article DE alpha-MSH; beta-END; ACTH; immunohistochemistry; in situ hybridization; NOS knock-out mice ID NITRIC-OXIDE SYNTHASE; BETA-ENDORPHIN; RAT PITUITARY; MESSENGER-RNA; HYPOTHALAMUS; SECRETION; CELLS; NUCLEUS; RELEASE; GLAND AB The relevance of NO in neuroendocrine signalling has been investigated by analysis of cellular expression of pro-opiomelanocortin (POMC) and the POMC-derived peptides beta -endorphin, alpha -melanocyte stimulating hormone and adrenocorticotropin. Expression patterns were studied in the pituitary gland of 150-day old wild-type and neuronal-NOS (nNOS) knock-out mice by using immunohistochemistry, in situ hybridization and Northern blot analysis. Remaining NO-generating capacities in the knock-out mice were demonstrated by immunohistochemical localization of inducible, endothelial and neuronal NOS isoforms. Quantitative analysis revealed that cellular expression of POW mRNA was drastically reduced in the pituitary of knock-out mice in comparison to controls. In situ hybridization studies demonstrated that this reduction was most pronounced in the intermediate lobe, while the anterior lobe was much less affected. Immunostaining for the proteolytic fragments of POW was significantly reduced in the intermediate lobe cells of knock-out mice. A moderate reduction of immunostaining for these peptides was also observed in adenopituitary cells of nNOS knock-out mice. Our data demonstrate that the lack of nNOS substantially affects cellular levels of pituitary opioid peptides, which may have consequences for the response of these animals to stress and pain. C1 Univ Magdeburg, Inst Med Neurobiol, D-39120 Magdeburg, Germany. Univ Magdeburg, Dept Psychiat, D-39120 Magdeburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. RP Keilhoff, G (reprint author), Univ Magdeburg, Inst Med Neurobiol, Leipziger Str 44, D-39120 Magdeburg, Germany. NR 47 TC 9 Z9 9 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0065-1281 J9 ACTA HISTOCHEM JI Acta Histochem. PD OCT PY 2001 VL 103 IS 4 BP 397 EP 412 DI 10.1078/0065-1281-00611 PG 16 WC Cell Biology SC Cell Biology GA 487LH UT WOS:000171876200005 PM 11700945 ER PT J AU Primavera, J Nikas, DC Zamani, AA Shafman, T Alexander, E De Girolami, U Louis, DN AF Primavera, J Nikas, DC Zamani, AA Shafman, T Alexander, E De Girolami, U Louis, DN TI Clear cell pleomorphic xanthoastrocytoma: case report SO ACTA NEUROPATHOLOGICA LA English DT Article DE astrocytoma; diagnosis; glioma; pleomorphic xanthoastrocytoma ID DIAGNOSIS; TUMORS AB Pleomorphic xanthoastrocytoma (PXA) is a well-described astrocytic neoplasm with distinctive clinical and pathological features. Although most patients with PXAs are cured by surgical excision, other patients experience malignant progression and tumor recurrence. We describe a 47-year-old woman with a left temporal lobe PXA that had classic histopathological characteristics as well as extensive clear cell and focal papillary changes, and some anaplastic findings. The patient has now suffered two recurrences after complete resection. The case illustrates a rare, previously undescribed histological variant of PXA, with a prominent clear cell and focal papillary morphology. The study of histologically similar cases is needed to determine whether this variant is always associated with a greater likelihood of recurrence. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Neurosurg Labs, Brain Tumor Ctr, Div Neuropathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neuroradiol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. RP De Girolami, U (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD OCT PY 2001 VL 102 IS 4 BP 404 EP 408 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 477FW UT WOS:000171273400016 PM 11603818 ER PT J AU Jansson, M Backstrom, E Scarlatti, G Bjorndal, A Matsuda, S Rossi, P Albert, J Wigzell, H AF Jansson, M Backstrom, E Scarlatti, G Bjorndal, A Matsuda, S Rossi, P Albert, J Wigzell, H TI Length variation of glycoprotein 120 V2 region in relation to biological phenotypes and coreceptor usage of primary HIV type 1 isolates SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; 2ND VARIABLE REGION; MT-2 CELL TROPISM; REVERSE-TRANSCRIPTASE; IN-VIVO; T-CELLS; ENVELOPE; GP120; INFECTION AB Conflicting data have been published concerning the correlation between the length of the second variable region (V2) in the HIV-1 envelope and the biological phenotype of the virus. Here the V2 region length of primary HIV-1 isolates was compared with biological phenotype and coreceptor usage. The V2 region variation was determined by DNA fragment length analysis, virus biological phenotype by the MT-2 cell assay, and coreceptor usage by infection of U87.CD4 cells expressing CCR3, CCR5, or CXCR4. Ninety-three primary virus isolates from 40 patients were analyzed. This panel of viruses included sequential isolates obtained from patients who progressed to AIDS with or without a virus phenotypic switch. We found that NSI MT-2-negative isolates had significantly shorter V2 regions than SI MT-2-positive isolates. However, when V2 region lengths of viruses were analyzed in more detail, we observed that NSI isolates obtained from patients shortly before the phenotypic switch had V2 region lengths similar to those of SI isolates. V2 regions of NSI isolates obtained from patients who progressed to AIDS without a virus phenotypic switch had, in contrast, shorter V2 region than isolates obtained just before virus phenotypic switch. Coreceptor analysis revealed that CCR5-using (R5) isolates generally had shorter V2 regions than virus isolates with the ability to enter CXCR4-expressing cells. Moreover, no significant difference in V2 region length was observed between monotropic SI isolates, that is, X4 isolates, and multitropic SI isolates, that is, R3R5X4 or R5X4 isolates. Thus, we conclude that R5 NSI isolates obtained from patients with stable virus phenotype through the whole disease course display shorter V2 regions than isolates obtained from patients at switch of virus phenotype, suggesting that V2 region length may influence virus coreceptor usage. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Univ Roma Tor Vergata, Ctr Pediat Immunol, I-00133 Rome, Italy. San Raffaele Sci Inst, DIBIT, Unit Immunobiol HIV, I-20132 Milan, Italy. Kure Natl Hosp, Inst Clin Res, Hiroshima 7370023, Japan. Karolinska Inst, Swedish Inst Infect Dis Control, S-17177 Stockholm, Sweden. RP Jansson, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDs, 44 Binney St,Smith 718, Boston, MA 02115 USA. RI rossi, paolo/D-6504-2012; OI ROSSI, PAOLO/0000-0003-2620-7918 NR 55 TC 30 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2001 VL 17 IS 15 BP 1405 EP 1414 DI 10.1089/088922201753197079 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 487CX UT WOS:000171857000005 PM 11679153 ER PT J AU Liu, QN Reddy, S Sayre, JW Pop, V Graves, MC Fiala, M AF Liu, QN Reddy, S Sayre, JW Pop, V Graves, MC Fiala, M TI Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NITRIC-OXIDE SYNTHASE; HUMAN-IMMUNODEFICIENCY-VIRUS; EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; POLYMERASE-CHAIN-REACTION; PROSTAGLANDIN SYNTHASE-2; ADHESION MOLECULES; MESSENGER-RNA; INFECTION; HEART; CARDIOMYOPATHY AB HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2- activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, RNRC, Rm 2150,710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL63639, HL63065]; NIDA NIH HHS [DA10442] NR 49 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2001 VL 17 IS 15 BP 1423 EP 1433 DI 10.1089/088922201753197097 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 487CX UT WOS:000171857000007 PM 11679155 ER PT J AU Bradley, KA Kivlahan, DR Bush, KR McDonell, MB Fihn, SD AF Bradley, KA Kivlahan, DR Bush, KR McDonell, MB Fihn, SD CA Ambulatory Care Quality Improveme TI Variations on the CAGE alcohol screening questionnaire: Strengths and limitations in VA general medical patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol screening ID PRIMARY-CARE; PROBLEM DRINKING; USE DISORDERS; CONSUMPTION QUESTIONS; BRIEF INTERVENTIONS; PROBLEM DRINKERS; BINGE-DRINKING; AUDIT; BIAS; FREQUENCY AB Background: Several variations on the CAGE alcohol screening questionnaire have been recommended. This report evaluates modifications and additions to the CAGE. Methods: Alcohol screening questionnaires were evaluated in male VA general medicine patients (n=227; mean age, 65.8). Mailed questionnaires included two scoring options for the CAGE (standard and last-year time frames), questions about quantity and frequency of drinking, two questions about episodic heavy drinking, and the question "Have you ever had a drinking problem?" Main analyses compared alcohol screening questions, at various cut-points, to a gold standard of hazardous drinking during the past year (greater than or equal to 14 drinks/week or greater than or equal to5 drinks on an occasion) and/or DSM-III-R alcohol abuse or dependence, based on standardized interviews. Results: The CAGE questionnaire with a past-year time frame was much less sensitive (0.57 vs. 0.77) but more specific (0.82 vs. 0.59) than the standard CAGE for detecting hazardous drinking during the past year and/or DSM-III-R alcohol abuse or dependence. An eight-item questionnaire that included the standard CAGE was most sensitive (0.92) but had low specificity (0.50). A single question about the frequency of drinking greater than or equal to6 drinks on an occasion, included in the eight-item questionnaire, was both relatively sensitive (0.77), and specific (0.83). Conclusion: The CAGE questionnaire with a past-year time frame was an insensitive alcohol-screening test. An eight-item augmented version of the standard CAGE was the most sensitive. A question about the frequency of drinking greater than or equal to6 drinks on an occasion performed better than the standard CAGE, which made it the optimal brief screening test for at-risk drinking. C1 VA Puget Sound Hlth Care Syst, HSR&D 152, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 152, NW Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [K23AA00313] NR 40 TC 43 Z9 45 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2001 VL 25 IS 10 BP 1472 EP 1478 DI 10.1111/j.1530-0277.2001.tb02149.x PG 7 WC Substance Abuse SC Substance Abuse GA 483YJ UT WOS:000171663200010 PM 11696667 ER PT J AU Mela, T McGovern, BA Garan, H Vlahakes, GJ Torchiana, DF Ruskin, J Galvin, JM AF Mela, T McGovern, BA Garan, H Vlahakes, GJ Torchiana, DF Ruskin, J Galvin, JM TI Long-term infection rates associated with the pectoral versus abdominal approach to cardioverter-defibrillator implants SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; COMPLICATIONS; SYSTEMS; RISK AB Infection is an uncommon (0% to 6.7%) but serious complication after implantable cardioverter-defibrillator (ICD) implantation. All ICD primary implants, replacements, or revisions performed at the Massachusetts General Hospital between April 1983 and May 1999 were reviewed. A total of 21 ICD-related infections (1.2%) were identified among 1,700 procedures affecting 1.8% of the 1, 170 patients who underwent a primary implant, a generator change, or a revision of their systems. The mean follow-up time was 35 +/- 33 months. Of the 959 patients with long-term follow-up, 19 of the 584 patients (3.2%) with abdominal and 2 of the 375 patients (0.5%) with pectoral systems developed ICD-related infections (p = 0.03). There was no significant difference between the infection rate among the 959 primary ICD implants and the 447 replacements or system revisions. Only 5 of the patients (24%) had systemic signs of infection, including fever (T> 100.5) and elevated white blood count > 12,000. Cultures from the wound revealed staphylococcal species in 16 patients (76%). Nineteen patients were treated with removal of the entire ICD system in addition to intravenous antibiotics for 2 to 4 weeks. A decrease in the incidence of ICD-related infection has occurred since the advent of transvenous pectoral systems. The main organism responsible for ICD infection is Staphylococcus. The mainstay of ICD infection management consists of complete removal of the entire implanted system. (C) 2001 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Mela, T (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 62 Z9 63 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2001 VL 88 IS 7 BP 750 EP 753 DI 10.1016/S0002-9149(01)01845-8 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 478XR UT WOS:000171374300006 PM 11589841 ER PT J AU Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA TI Evaluation of sex-related differences in survival after hospitalization for acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TERM; PROGNOSIS; WOMEN; DEATH; MEN AB In a study of 1,935 early survivors of acute myocardial infarction, we found that age modifies the relation of sex with long-term survival. Mortality rates are higher among women aged <50 years, similar among men and women between ages 50 and 69, and higher among men aged 70. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [K23AA00299] NR 11 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2001 VL 88 IS 7 BP 768 EP + DI 10.1016/S0002-9149(01)01848-3 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 478XR UT WOS:000171374300010 PM 11589845 ER PT J AU Rumsfeld, JS Magid, DJ Plomondon, ME O'Brien, MM Spertus, JA Every, NR Sales, AE AF Rumsfeld, JS Magid, DJ Plomondon, ME O'Brien, MM Spertus, JA Every, NR Sales, AE TI Predictors of quality of life following acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-LIFE; ARTERY DISEASE; DEPRESSION; BIAS; ANXIETY; ANGINA; TRIAL AB We determined the predictors of physical and mental health status 7 months after admission for an acute coronary syndrome in a cohort of 1,660 Veterans Administration patients. Noncardiac variables were stronger predictors of quality of life than cardiac variables, depression was associated with worse physical and mental health status, and revascularization was associated with better physical and mental health status. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. Univ Missouri, Div Cardiol, Kansas City, MO 64110 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol Sect, 1055 Clermont St, Denver, CO 80220 USA. OI Sales, Anne/0000-0001-9360-3334 NR 20 TC 32 Z9 32 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2001 VL 88 IS 7 BP 781 EP + DI 10.1016/S0002-9149(01)01852-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 478XR UT WOS:000171374300014 PM 11589849 ER PT J AU Chan, JM Stampfer, MJ Ma, J Gann, PH Gaziano, JM Giovannucci, EL AF Chan, JM Stampfer, MJ Ma, J Gann, PH Gaziano, JM Giovannucci, EL TI Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dairy products; calcium; prostate cancer; vitamin D; diet; Physicians' Health Study; 1,25-dihydroxyvitamin D(3) ID VITAMIN-D-RECEPTOR; UNITED-STATES; BETA-CAROTENE; D METABOLITES; CELL-LINES; SUBSEQUENT DEVELOPMENT; GENE POLYMORPHISM; ANDROGEN RECEPTOR; DIET; PROLIFERATION AB Background: A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive. Objective: We investigated the association between dairy product and calcium intakes and prostate cancer risk in the Physicians' Health Study, a cohort of male US physicians. Design: At baseline, the men answered abbreviated dietary questionnaires. During 11 y of follow-up, we documented 1012 incident cases of prostate cancer among 20885 men. We estimated dairy calcium intake on the basis of consumption of 5 major dairy products and used logistic regression to estimate relative risk. Results: At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)2D3 concentrations than did those consuming less than or equal to 150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL); P=0.005]. Compared with men consuming less than or equal to0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 (95% CI: 1.04, 1.71) after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming less than or equal to 150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer (95% CI: 1.08, 1.63). Conclusions: These results support the hypothesis that dairy products and calcium are associated with a greater risk of prostate cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. VA Boston Hlth Care Syst, Massachusetts Vet Epidemiol & Informat Ctr, Boston, MA USA. RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 3333 Calif St,Suite 280, San Francisco, CA 94143 USA. EM june.chan@channing.harvard.edu FU NCI NIH HHS [CA58684, CA34944, CA40360, CA42182, T32-CA-09001]; NHLBI NIH HHS [HL26490, HL34595] NR 48 TC 142 Z9 145 U1 4 U2 25 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2001 VL 74 IS 4 BP 549 EP 554 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 473LH UT WOS:000171045100021 PM 11566656 ER PT J AU Linson, PW Lee, AK Doytchinova, T Chen, MH Weinstein, MH Richie, JP D'Amico, AV AF Linson, PW Lee, AK Doytchinova, T Chen, MH Weinstein, MH Richie, JP D'Amico, AV TI Percentage of core lengths involved with prostate cancer: Does it add to the percentage of positive prostate biopsies in predicting postoperative PSA outcome for men with intermediate-risk prostate cancer? SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2001 VL 116 IS 4 MA 41 BP 600 EP 600 PG 1 WC Pathology SC Pathology GA 478HW UT WOS:000171341800057 ER PT J AU Messersmith, WA Brown, DFM Barry, MJ AF Messersmith, WA Brown, DFM Barry, MJ TI The prevalence and implications of incidental findings on ED abdominal CT scans SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE incidental finding; computed tomography; nephrolithiasis ID HELICAL CT; APPENDICITIS; DIVERTICULITIS AB We reviewed reports from 321 consecutive emergency department (ED) noncontrast, helical "renal stone" abdominal CT scans obtained at a single medical center between April 1996 to June 1997 for incidental findings. Incidental findings were common (45% of scans), and approximately half were rated of "moderate" or "serious" concern by 2 independent reviewers (kappa = 0.72). ED records indicated that only 21% of incidental findings were documented, and only 11 (18%) of cases with findings of "moderate/severe" concern had evidence of follow-up on hospital chart review. Although work-up of these 11 cases did not yield any serious diagnoses, many potentially serious incidental findings without follow-up remain worrisome. Copyright (C) 2001 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit,Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 11 TC 60 Z9 60 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2001 VL 19 IS 6 BP 479 EP 481 DI 10.1053/ajem.2001.27137 PG 3 WC Emergency Medicine SC Emergency Medicine GA 481NG UT WOS:000171525300005 PM 11593466 ER PT J AU Horton, NJ Laird, NM Murphy, JM Monson, RR Sobol, AM Leighton, AH AF Horton, NJ Laird, NM Murphy, JM Monson, RR Sobol, AM Leighton, AH TI Multiple informants: Mortality associated with psychiatric disorders in the stirling county study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE estimating equation; missing data; regression ID NATIONAL-COMORBIDITY-SURVEY; LONGITUDINAL DATA-ANALYSIS; MISSING COVARIATE DATA; ESTIMATING EQUATION; GENERAL-POPULATION; PREVALENCE; DEPRESSION; COMMUNITY; CHILD; OUTCOMES AB This paper applies new statistical procedures for analyzing multiple-source information about the relation of psychiatric diagnoses to mortality. The data come from the Stirling County Study, a longitudinal community investigation of adults, that collected multiple-source reports (self-report and physician-report) about psychiatric disorders. These reports are used as predictors of mortality risk over a 16-year follow-up period (1952-1968). Despite extensive efforts, one or both of these reports were sometimes missing. Missingness of self-report was related to demographic characteristics as well as to physician-reports of psychiatric diagnosis. The statistical procedures used here draw together into a single frame of reference both informant reports for the initial Stirling survey and relate these to mortality risk using weighted generalized estimating equation regression models for time to event data. This unified method has two advantages over traditional approaches: 1) the relative predictiveness of each informant can be assessed and 2) all subjects contribute to the analysis. The methods are applicable to other areas of epidemiology where multiple informant reports are used. The results for self-reports and physician-reports of disorders were comparable: Psychiatric diagnosis was associated with higher mortality, particularly among younger subjects. C1 Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dalhousie Univ, Fac Med, Dept Psychiat, Halifax, NS, Canada. Dalhousie Univ, Fac Med, Dept Community Hlth & Epidemiol, Halifax, NS, Canada. RP Horton, NJ (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 715 Albany St T3E, Boston, MA 02118 USA. RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NIMH NIH HHS [R01-MH39576, R01-MH54693, T32-MH17119] NR 49 TC 26 Z9 26 U1 5 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2001 VL 154 IS 7 BP 649 EP 656 DI 10.1093/aje/154.7.649 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 477LY UT WOS:000171286100008 PM 11581099 ER PT J AU Bolk, S Higgins, J Moore, J Nguyen, H Roy, J Schaffner, S Lander, ES Daly, MJ Altshuler, D AF Bolk, S Higgins, J Moore, J Nguyen, H Roy, J Schaffner, S Lander, ES Daly, MJ Altshuler, D TI The extent and diversity of common human haplotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. MIT, Dept Biol, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011 OI Altshuler, David/0000-0002-7250-4107; NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 6 BP 176 EP 176 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900007 ER PT J AU Zeng, W Al-Yamani, E Acierno, JS Ozand, P Gusella, JF AF Zeng, W Al-Yamani, E Acierno, JS Ozand, P Gusella, JF TI Mutations in SLC19A3 encoding a novel transporter cause biotin-responsive basal ganglia disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 101 BP 195 EP 195 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900100 ER PT J AU Bruner, GR Scofield, RH Kelly, JA Kilpatrick, J Klein, DK Nath, SK Lam, T Reid, JS James, JA Harley, JB AF Bruner, GR Scofield, RH Kelly, JA Kilpatrick, J Klein, DK Nath, SK Lam, T Reid, JS James, JA Harley, JB TI Linkages associated with thrombocytopenia in pedigrees multiplex for lupus are potentially related to lupus morbidity and mortality. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 117 BP 199 EP 199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900118 ER PT J AU Chen, S Price, BD AF Chen, S Price, BD TI The Leucine Zipper of the ATM protein regulates cellular sensitivity to DNA damage. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 143 BP 204 EP 204 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900144 ER PT J AU Mankodi, AK Takahashi, M Beck, C Cannon, S Thornton, CA AF Mankodi, AK Takahashi, M Beck, C Cannon, S Thornton, CA TI Myotonia is associated with loss of transmembrane chloride conductance and aberrant splicing of Clcn1, the skeletal muscle chloride channel, in a transgenic model of myotonic dystrophy (DM1). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Rochester, Rochester, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 180 BP 211 EP 211 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900182 ER PT J AU Blau, N Bonafe, L Penzien, JM Czarnecki, B Friedman, J Maccollin, M Thony, B AF Blau, N Bonafe, L Penzien, JM Czarnecki, B Friedman, J Maccollin, M Thony, B TI Sepiapterin reductase deficiency: a novel tetrahydrobiopterin-dependent monoamine neurotransmitter deficiency without hyperphenylalaninemia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Zurich, Childrens Hosp, Div Clin Chem & Biochem, CH-8032 Zurich, Switzerland. Univ Zurich, Childrens Hosp, Div Metab & Mol Pediat, Zurich, Switzerland. Childrens Hosp, Augsburg, Germany. Childrens Hosp Knigsborn, Unna, Germany. Massachusetts Gen Hosp, Neurogenet Dept, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 209 BP 217 EP 217 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900209 ER PT J AU Lu, K Dinh, M Kohlmann, W Watson, P Green, J Syngal, S Bandipalliam, P Chen, L Allen, B Conrad, P Terdiman, J Burke, T Gershenson, D Lynch, H Lynch, P Broaddus, R AF Lu, K Dinh, M Kohlmann, W Watson, P Green, J Syngal, S Bandipalliam, P Chen, L Allen, B Conrad, P Terdiman, J Burke, T Gershenson, D Lynch, H Lynch, P Broaddus, R TI Gynecological malignancy as a "sentinel cancer" for women with HNPCC. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Creighton Univ, Omaha, NE 68178 USA. Mem Univ Newfoundland, St Johns, NF A1C 5S7, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 394 BP 251 EP 251 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900394 ER PT J AU Jaju, M Sepulveda, AR Graham, DY Peterson, LE AF Jaju, M Sepulveda, AR Graham, DY Peterson, LE TI Database to study genetic susceptibility to Gastric Cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Baylor Coll Med, Dept Med, Chron Dis Prevent & Control Res Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 412 BP 254 EP 254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900412 ER PT J AU Heinrich, B Hartmann, C MacCollin, M AF Heinrich, B Hartmann, C MacCollin, M TI The molecular genetic basis of multiple meningiomas. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 435 BP 258 EP 258 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900438 ER PT J AU Meyn, MS D'Andrea, A Grompe, M Wang, W AF Meyn, MS D'Andrea, A Grompe, M Wang, W TI The involvement of Fanconi anaemia proteins in homologous genetic recombination. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Dana Faber Canc Inst, Boston, MA USA. OHSU, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 750 BP 311 EP 311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900748 ER PT J AU Higgins, AW Lemyre, E Bruns, GAP Farra, C Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL MacDonald, ME Michelson, AM Quade, BJ Rooryck, C Tihy, F Morton, CC AF Higgins, AW Lemyre, E Bruns, GAP Farra, C Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL MacDonald, ME Michelson, AM Quade, BJ Rooryck, C Tihy, F Morton, CC TI Developmental genome anatomy project: Breakpoint localization updates. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Montreal, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 884 BP 334 EP 334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900884 ER PT J AU Robertson, NG Resendes, BL Lin, JS Lee, C Aster, JC Adams, JC Morton, CC AF Robertson, NG Resendes, BL Lin, JS Lee, C Aster, JC Adams, JC Morton, CC TI Inner ear localization of mRNA and protein products of COCH, mutated in the sensorineural deafness and vestibular disorder, DFNA9. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Ob Gyn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 968 BP 348 EP 348 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900966 ER PT J AU Falardeau, JL Kennedy, JC Acierno, JS Slaugenhaupt, SA AF Falardeau, JL Kennedy, JC Acierno, JS Slaugenhaupt, SA TI Cloning and characterization of novel members of the TRP superfamily in man and mouse: the MCOLN gene family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Inst Human Genet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1046 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901044 ER PT J AU Schneider, KA Chittenden, AB DiGianni, LM Patenaude, AF Gelman, R Garber, JE AF Schneider, KA Chittenden, AB DiGianni, LM Patenaude, AF Gelman, R Garber, JE TI Levels of genetics knowledge and distress: A comparison of cancer survivors and unaffected women in a BRCA1/2 testing program. SO AMERICAN JOURNAL OF HUMAN GENETICS 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 UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1142 BP 378 EP 378 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901142 ER PT J AU Gill, SP Leyne, M Mull, J Cuajungco, MP Robbins, CM Makalowska, I Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA AF Gill, SP Leyne, M Mull, J Cuajungco, MP Robbins, CM Makalowska, I Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA TI Survey of Ashkenazi Jewish SNPs in a 471 kb region of chromosome 9q31 as compared to the public SNP database (dbSNP). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Inst Human Genet, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RI Brownstein, Michael/B-8609-2009; Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1264 BP 398 EP 398 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901264 ER PT J AU Reid, SJ Rees, MI van Roon-Mom, WMC Jones, AL McDonald, ME Sutherland, GT Owen, MJ Dragunow, M Snell, RG AF Reid, SJ Rees, MI van Roon-Mom, WMC Jones, AL McDonald, ME Sutherland, GT Owen, MJ Dragunow, M Snell, RG TI Expression and population studies of the TATA-box binding protein polyglutamine region at normal and expanded lengths. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Auckland, Sch Med, Dept Mol Med, Auckland, New Zealand. Univ Auckland, Sch Med, Dept Anat & Radiol, Auckland, New Zealand. Univ Auckland, Sch Med, Dept Pharmacol, Auckland, New Zealand. Univ Wales Coll Med, Dept Psychol Med & Med Genet, Cardiff CF4 4XN, S Glam, Wales. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RI turton, miranda/F-4682-2011; Reid, Suzanne/H-7082-2012; Rees, Mark/J-3129-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1420 BP 424 EP 424 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901420 ER PT J AU Nguyen, HO Heinrich, B MacCollin, M AF Nguyen, HO Heinrich, B MacCollin, M TI The use of unequal expression as a rapid diagnostic tool for neurofibromatosis 2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1433 BP 427 EP 427 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901433 ER PT J AU Bove, BA Ozcelik, H Neuhausen, S Boyd, J Southey, M Santella, R Venter, D Beck, J Li, F Buys, S Andrulis, IL Godwin, AK Whittemore, A AF Bove, BA Ozcelik, H Neuhausen, S Boyd, J Southey, M Santella, R Venter, D Beck, J Li, F Buys, S Andrulis, IL Godwin, AK Whittemore, A CA CFRBCS TI Comparison of methods for detection of mutations in the BRCA1 gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Toronto, Toronto, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Utah, Salt Lake City, UT 84112 USA. Columbia Univ, New York, NY 10027 USA. Stanford Univ, Stanford, CA 94305 USA. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1508 BP 440 EP 440 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901507 ER PT J AU Yi, CH Schinke, M Kim, JH Jay, P Shioi, T Wripple, M Butte, A Riggi, L Chen, DIB Kohane, IS Izumo, S AF Yi, CH Schinke, M Kim, JH Jay, P Shioi, T Wripple, M Butte, A Riggi, L Chen, DIB Kohane, IS Izumo, S TI Expression profiling of the cardiovascular system by the microarray technology. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Informat Program, Boston, MA 02215 USA. RI Kim, Ju Han/E-5983-2012; Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1589 BP 453 EP 453 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901589 ER PT J AU Elias, ER Kochevar, IE Taylor, CR AF Elias, ER Kochevar, IE Taylor, CR TI Photosensitivity in patients with the Smith-Lemli-Opitz Syndrome (SLOS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Hosp, Special Care Clin, Denver, CO 80218 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1734 BP 478 EP 478 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901733 ER PT J AU Blacker, D Bertram, L Saunders, AJ Moscarillo, TJ Albert, MS Wiener, H Perry, R Go, RCP Mahoney, A Beaty, T Fallin, MD Bassett, SS Pugh, EW Doheny, KF Tanzi, RE AF Blacker, D Bertram, L Saunders, AJ Moscarillo, TJ Albert, MS Wiener, H Perry, R Go, RCP Mahoney, A Beaty, T Fallin, MD Bassett, SS Pugh, EW Doheny, KF Tanzi, RE TI Results of a high resolution genome screen in 443 Alzheimer's disease families: the NIMH Genetics Initiative. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Ctr Inherited Dis Res, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1851 BP 498 EP 498 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901850 ER PT J AU Yang, Q Tofler, GH Cupples, LA Larson, MG Levy, D D'Agostino, RB O'Donnell, CJ AF Yang, Q Tofler, GH Cupples, LA Larson, MG Levy, D D'Agostino, RB O'Donnell, CJ TI A genome-wide scan for circulating levels of fibrinogen in the Framingham Heart Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Boston Univ, Sch Publ Hlth, Boston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1877 BP 502 EP 502 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901875 ER PT J AU Marneros, AG Norris, JEC Olsen, BR Reichenberger, E AF Marneros, AG Norris, JEC Olsen, BR Reichenberger, E TI Genetics of familial keloids. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, Sch Dent, Harvard Forsyth Dept Oral Biol, Boston, MA USA. Forsyth Inst, Boston, MA USA. St Lukes Roosevelt Hosp, Dept Plast Surg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1892 BP 505 EP 505 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901894 ER PT J AU DelBono, EA Lynch, S Yanagi, G Maselli, M Bradford, Y Haines, JL Wiggs, JL AF DelBono, EA Lynch, S Yanagi, G Maselli, M Bradford, Y Haines, JL Wiggs, JL TI Genomic screen for genes responsible for early onset open angle glaucoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1905 BP 507 EP 507 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901904 ER PT J AU Kelly, J Kilpatrick, J Nath, SK Namjou-Khales, B Bruner, GR Scofield, RH Harley, JB AF Kelly, J Kilpatrick, J Nath, SK Namjou-Khales, B Bruner, GR Scofield, RH Harley, JB TI Pedigree selection may increase genetic homogeneity in complex phenotypes: an example from lupus with hemolytic anemia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1915 BP 509 EP 509 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901915 ER PT J AU Li, J Niu, T Xu, X Rogus, J Yang, J Schork, N Fang, Z Xu, X AF Li, J Niu, T Xu, X Rogus, J Yang, J Schork, N Fang, Z Xu, X TI Genome search for QTL controlling pulse pressure: A practical application of the unified Haseman-Elston algorithm. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Prog Populat Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA USA. Anhui Med Univ, Inst Biomed, Hefei, Peoples R China. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Genset Corp, La Jolla, CA USA. Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1921 BP 510 EP 510 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901921 ER PT J AU Perry, R Collins, J Harrell, L Blacker, D Tanzi, R McInnis, M Bassett, S Go, R AF Perry, R Collins, J Harrell, L Blacker, D Tanzi, R McInnis, M Bassett, S Go, R TI Investigation of association of polymorphisms in TNFR1 and TNFR2 in Alzheimers disease patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1944 BP 513 EP 513 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901944 ER PT J AU Allingham, RR Wiggs, JL LaRocque, KR Hauser, MA Graham, FL Broomer, B del Bono, EA Bailey, R Haines, JL Pericak-Vance, MA AF Allingham, RR Wiggs, JL LaRocque, KR Hauser, MA Graham, FL Broomer, B del Bono, EA Bailey, R Haines, JL Pericak-Vance, MA TI Phenotype stratification of linkage analysis in primary open-angle glaucoma (POAG): Evidence for age of onset heterogeneity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1962 BP 516 EP 516 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901962 ER PT J AU Gao, H Espinola, J Lerner, T Boustany, RM MacDonald, ME AF Gao, H Espinola, J Lerner, T Boustany, RM MacDonald, ME TI Narrowing the CLN6 region on chromosome 15. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1967 BP 517 EP 517 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901965 ER PT J AU Edberg, JC Langefeld, CD Moser, KL Kelly, J Kaufman, JM Rich, SS Harley, JB Kimberly, RP AF Edberg, JC Langefeld, CD Moser, KL Kelly, J Kaufman, JM Rich, SS Harley, JB Kimberly, RP CA SCOR Genet SLE TI Linkage and association of a functional single nucleotide polymorphism (SNP) in the Fc gamma RIIIA gene with SLE. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Minnesota, Minneapolis, MN USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1979 BP 519 EP 519 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901977 ER PT J AU Hirschhorn, JN Altshuler, D Daly, MJ Lindgren, CM Burtt, NP Loomer, M Villapakkam, A Bolk, S O'Donnell, CJ Crews, JD Groop, LC Lander, ES AF Hirschhorn, JN Altshuler, D Daly, MJ Lindgren, CM Burtt, NP Loomer, M Villapakkam, A Bolk, S O'Donnell, CJ Crews, JD Groop, LC Lander, ES TI Linkage disequilibrium at PPARG and other genes assessed with dense sets of SNPs.. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Lund Univ, Div Endocrinol, Malmo, Sweden. NHLBI, Framingham Heart Study, Framingham, MA USA. MIT, Dept Biol, Cambridge, MA USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1997 BP 522 EP 522 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901995 ER PT J AU Keen, D Ferrie, A Zielenski, J Tsui, LC Parad, R Chung, R Menon, A Ramos-Arroyo, M Baas, F Kushner, J Housman, D AF Keen, D Ferrie, A Zielenski, J Tsui, LC Parad, R Chung, R Menon, A Ramos-Arroyo, M Baas, F Kushner, J Housman, D TI Determination of linkage disequilibrium patterns and mutation rate by high density SNP genotyping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Variagen Inc, Cambridge, MA USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Hosp Virgin Camino, Pamplona, Spain. Neurol Acad Med Ctr, Amsterdam, Netherlands. Univ Utah, Salt Lake City, UT 84112 USA. RI Tsui, Lap-chee/A-1081-2010; Parad, Richard/E-8559-2010; Baas, Frank/F-9574-2010 OI Baas, Frank/0000-0003-3912-5428 NR 0 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1994 BP 522 EP 522 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901996 ER PT J AU Chen, H Ross, CA Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, J Simpson, SG Chen, J Wang, S McMahon, FJ DePaulo, JR McInnis, MG AF Chen, H Ross, CA Wang, N Huo, Y Sklar, P MacKinnon, DF Potash, J Simpson, SG Chen, J Wang, S McMahon, FJ DePaulo, JR McInnis, MG TI Developing of full-length cDNA for novel genes expressed in brain from chromosome 18q21 to create a gene panel for variation/mutation screen in bipolar disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2139 BP 546 EP 546 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902138 ER PT J AU Andresen, JM Cardon, LR Cherny, SS Gusella, JF MacDonald, ME Housman, DE Wexler, NS AF Andresen, JM Cardon, LR Cherny, SS Gusella, JF MacDonald, ME Housman, DE Wexler, NS TI Variance in age of onset of Huntington's disease that is independent of CAG repeat length remains highly heritable. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Oxford, Oxford OX1 2JD, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Columbia Univ, New York, NY 10027 USA. RI Cherny, Stacey/B-3315-2008 OI Cherny, Stacey/0000-0002-0269-3352 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2145 BP 547 EP 547 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902144 ER PT J AU Wheeler, VC Gutekunst, CA Vrbanac, V Lebel, L Vonsattel, JP Gusella, JF MacDonald, ME AF Wheeler, VC Gutekunst, CA Vrbanac, V Lebel, L Vonsattel, JP Gusella, JF MacDonald, ME TI Neurodegeneration and mild gait abnormalities in Huntington's disease knock-in mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Columbia Univ Coll Phys & Surg, Div Neuropathol, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2170 BP 551 EP 551 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902171 ER PT J AU Wiggs, JL Allingham, RR Bailey, LR Auguste, J DeBono, EA Broomer, B Grahm, FL Hauser, M Pericak-Vance, MA Haines, JL AF Wiggs, JL Allingham, RR Bailey, LR Auguste, J DeBono, EA Broomer, B Grahm, FL Hauser, M Pericak-Vance, MA Haines, JL TI Genomic Screen for POAG susceptibility genes: Follow-up studies and candiddate gene evaluation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. Duke Univ, Sch Med, Ctr Human Genet, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2223 BP 560 EP 560 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902222 ER PT J AU Volta, M Hsueh, Y Sheng, M Roberts, RG AF Volta, M Hsueh, Y Sheng, M Roberts, RG TI Characterization of the interaction between neurofibromin and members of the syndecan family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Guys Hosp, Div Med & Mol Genet, London SE1 9RT, England. Acad Sinica, Inst Mol Biol, Taipei, Taiwan. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RI Roberts, Roland/C-3596-2009; Volta, Manuela/D-2147-2012 OI Volta, Manuela/0000-0001-8468-0346 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2471 BP 602 EP 602 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902473 ER PT J AU Hepburn, M Liyanage, H Furu, L Somolo, S Vaughn, C Basson, C Xin, W Sims, K Affourtit, J Seymour, A AF Hepburn, M Liyanage, H Furu, L Somolo, S Vaughn, C Basson, C Xin, W Sims, K Affourtit, J Seymour, A TI The WAVE (R) Nucleic Acid Fragment Analysis System: A versatile analytical tool for mutation detection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Transgenom Inc, Appl Genom & Mol Genet, Decatur, GA USA. Transgenom Inc, Appl Genom & Mol Genet, Cambridge, MA USA. Yale Univ, Dept Internal Med & Nephrol, New Haven, CT USA. Cornell Univ, Weill Med Coll Lab, New York, NY USA. Massachusetts Gen Hosp, Pediat Neurogenet Lab, Charlestown, MA USA. Pfizer Inc, Groton, CT 06340 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2491 BP 605 EP 605 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902492 ER PT J AU Liu, S Lu, W Kuida, S Obara-Ishihara, T Drummond, I Beier, DR AF Liu, S Lu, W Kuida, S Obara-Ishihara, T Drummond, I Beier, DR TI A defect in a novel Nek-family kinase causes cystic disease in the mouse and in zebrafish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA USA. Massachusetts Gen Hosp, Div Renal, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2567 BP 618 EP 618 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902569 ER PT J AU Bastepe, M Feig, D Juppner, H AF Bastepe, M Feig, D Juppner, H TI GNAS1 loss-of-methylation defect in a PHP-lb kindred with linkage discordance to the chromosomal region 20q13.3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Massachusetts Gen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2660 BP 633 EP 633 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902658 ER PT J AU Astuti, D Latif, F Morgan, N Martinsson, T Dallol, A Dahia, P Douglas, F George, E Skoldberg, F Husebye, E Eng, C Maher, ER AF Astuti, D Latif, F Morgan, N Martinsson, T Dallol, A Dahia, P Douglas, F George, E Skoldberg, F Husebye, E Eng, C Maher, ER TI Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Birmingham, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. Gothenburg Univ, Dept Clin Genet, Gothenburg, Sweden. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Royal Victoria Infirm, No Reg Genet Serv, Newcastle Upon Tyne NE2, Tyne & Wear, England. Kings Lynn Hosp, Dept Med, Norfolk, England. Univ Uppsala, Dept Med Sci, S-75105 Uppsala, Sweden. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Div Human Genet, Columbus, OH 43210 USA. RI Martinsson, Tommy/J-4140-2013 OI Martinsson, Tommy/0000-0002-9403-3123 NR 0 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2701 BP 640 EP 640 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902702 ER PT J AU Slaugenhaupt, SA Leyne, M Mull, J Gill, SP Cuajungco, MP Gusella, JF Dormand, N Reed, R AF Slaugenhaupt, SA Leyne, M Mull, J Gill, SP Cuajungco, MP Gusella, JF Dormand, N Reed, R TI Characterization of the splicing mutation in IKBKAP that causes Familial Dysautonomia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Inst Human Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2763 BP 650 EP 650 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902763 ER PT J AU Lopes, HF Stojiljkovic, MP Zhang, D Goodfriend, TL Egan, BM AF Lopes, HF Stojiljkovic, MP Zhang, D Goodfriend, TL Egan, BM TI The pressor response to acute hyperlipidemia is enhanced in lean normotensive offspring of hypertensive parents SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE family history of hypertension; blood pressure; nonesterified fatty acids ID FREE FATTY-ACIDS; BAROREFLEX SENSITIVITY; ARTERIAL COMPLIANCE; HDL CHOLESTEROL; FAMILY HISTORY; BLOOD-PRESSURE; CHILDREN; PLASMA; PREDISPOSITION; VASODILATION AB Family history is an important predictor of the cardiovascular risk factor cluster associated with insulin resistance. The dyslipidemia associated with insulin resistance may contribute to elevated blood pressure (BP). This study was undertaken to further explore the link between family history, dyslipidemia, and BP regulation. Twenty-three lean normal volunteers with a negative family history (FH -, n = 11) or positive family history (FH +, n = 12) of hypertension were evaluated under baseline conditions and during a 4-h infusion of intralipid and heparin (acute hyperlipidemia). Fasting blood was drawn for lipids including nonesterified fatty acids (NEFA). After 2 and 4 h of intralipid and heparin, blood was drawn for NEFA. The BP was measured at baseline and every 30 min after starting the intralipid and heparin infusion. Baseline triglycerides and very low density lipoprotein cholesterol concentrations were higher in FH+ than FH- subjects (P < .05). However, NEFA increased similarly in both groups during the infusion of intralipid and heparin. The BP and heart rate increased with acute hyperlipidemia in all subjects combined (P < .05). Despite the similar increase of NEFA, mean BP, pulse pressure, and pressure-rate product increased significantly in FH+ subjects but not in FH- volunteers with acute hyperlipidemia. Although systolic BP increased in both groups, the increase was greater in FH+ than in FH- volunteers during acute hyperlipidemia (14 +/- 2 v 10 +/- 2 mm Hg, P < .05). These results suggest that higher plasma lipids combined with a greater pressor response to hyperlipidemia may contribute to the development of high BP in subjects with a family history of hypertension. Am J Hypertens 2001;14:1032-1037 (C) 2001 American Journal of Hypertension, Ltd. C1 Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Clin Pharmacol, Charleston, SC 29425 USA. USP, HCFMC, Inst Heart, Unidade Hipertensao, BR-09500900 Sao Paulo, Brazil. Mil Med Acad, Dept Pharmacol & Toxicol, YU-11002 Belgrade, FR, Yugoslavia. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Med, Madison, WI USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Pharmacol, Madison, WI USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, 96 Jonathan Lucas St,CSB 826H, Charleston, SC 29425 USA. FU NCRR NIH HHS [RR-01070]; NHLBI NIH HHS [R01 HL58794, K24 HL04920, P01 HL55782] NR 32 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2001 VL 14 IS 10 BP 1032 EP 1037 DI 10.1016/S0895-7061(01)02166-5 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 485BV UT WOS:000171734400009 PM 11710782 ER PT J AU Kraut, JA Kurtz, I AF Kraut, JA Kurtz, I TI Use of base in the treatment of severe acidemic states SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE bicarbonate; metabolic acidosis; tris-hydroxymethyl aminomethane (THAM); Carbicarb ID SEVERE DIABETIC-KETOACIDOSIS; HYPOXIC LACTIC-ACIDOSIS; LEFT-VENTRICULAR CONTRACTILITY; SODIUM-BICARBONATE; METABOLIC-ACIDOSIS; INTRACELLULAR PH; CARDIAC-ARREST; RAT-HEART; CARDIOPULMONARY-RESUSCITATION; MYOCARDIAL-CONTRACTILITY AB Severe acidemia (blood pH < 7.1 to 7.2) suppresses myocardial contractility, predisposes to cardiac arrhythmias, causes venoconstriction, and can decrease total peripheral vascular resistance and blood pressure, reduce hepatic blood flow, and impair oxygen delivery. These alterations in organ function can contribute to increased morbidity and mortality. Although it seemed logical to administer sodium bicarbonate to attenuate acidemia and therefore lessen the impact on cardiac function, the routine use of bicarbonate in the treatment of the most common causes of severe acidemia, diabetic ketoacidosis, lactic acidosis, and cardiac arrest, has been an issue of great controversy. Studies of animals and patients with these disorders have reported conflicting data on the benefits of bicarbonate, showing both beneficial and detrimental effects. Alternative alkalinizing agents, tris-hydroxymethyl aminomethane and Carbicarb, have shown some promise in studies of animals and humans, and reevaluation of these buffers in the treatment of severe acidemic states seems warranted. The potential value of base therapy in the treatment of severe acidemia remains an important Issue, and further studies are required to determine which patients should be administered base therapy and what base should be used. (C) 2001 by the National Kidney Foundation, Inc. C1 VA Greater Los Angeles Hlth Care Syst, Nephrol Sect 691 1111, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Nephrol, Ctr Hlth Sci, Los Angeles, CA 90024 USA. RP Kraut, JA (reprint author), VA Greater Los Angeles Hlth Care Syst, Nephrol Sect 691 1111, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK54221, DK58563] NR 135 TC 43 Z9 47 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2001 VL 38 IS 4 BP 703 EP 727 DI 10.1053/ajkd.2001.27688 PG 25 WC Urology & Nephrology SC Urology & Nephrology GA 476KQ UT WOS:000171226600001 PM 11576874 ER PT J AU Ecker, JL Chen, KT Cohen, AP Riley, LE Lieberman, ES AF Ecker, JL Chen, KT Cohen, AP Riley, LE Lieberman, ES TI Increased risk of cesarean delivery with advancing maternal age: Indications and associated factors in nulliparous women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Medicine DE age; cesarean delivery; induction AB OBJECTIVE: To investigate factors that contribute to the increased risk of cesarean delivery with advancing maternal age. STUDY DESIGN: We reviewed demographic and ante- and intrapartum variables from a data set of term, nulliparous women who delivered at Brigham and Women's Hospital in 1998 (n = 3715). RESULTS: Cesarean delivery rates Increased with advancing maternal age (< 25 years, 11.6%; greater than or equal to 40 years, 43.1 Older women were more likely to have cesarean delivery without labor (< 25 years, 3.6%; greater than or equal to 40 years, 21.1 Malpresentation and prior myomectomy were the indications for cesarean delivery without labor that were more prevalent in our older population as compared to our younger population. Even among women with spontaneous or induced labor, cesarean delivery rates increased with maternal age (< 25 years, 8.3%; greater than or equal to 40 years, 30.6%). Cesarean delivery rates were higher with induced labor, and rates of induction rose directly and continuously with maternal age, especially the rate of elective induction. Cesarean delivery for failure to progress or fetal distress was more common among older parturients, regardless of whether labor was spontaneous or induced. Among women who underwent cesarean delivery because of failure to progress, use of oxytocin and length of labor did not vary with age. CONCLUSIONS: Older women are at higher risk for cesarean delivery In part because they are more likely to have cesarean delivery without labor. However, even among those women who labor, older women are more likely to undergo cesarean delivery, regardless of whether labor is spontaneous or induced. Part of the higher rate among older women who labor is explained by a higher rate of induction, particularly elective induction. Among women In both spontaneous and induced labor, cesarean delivery for the diagnoses of failure to progress and fetal distress was more frequent in older patients, although management of labor dystocia for these patients was similar to that for younger patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. RP Ecker, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. NR 10 TC 91 Z9 97 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2001 VL 185 IS 4 BP 883 EP 887 DI 10.1067/mob.2001.117364 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 485BQ UT WOS:000171734000021 PM 11641671 ER PT J AU Zelop, CM Shipp, TD Repke, JT Cohen, A Lieberman, E AF Zelop, CM Shipp, TD Repke, JT Cohen, A Lieberman, E TI Outcomes of trial of labor following previous cesarean delivery among women with fetuses weighing < 4000 g SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Medicine DE large-for-gestational-age fetuses; trial of labor; uterine rupture ID PREVIOUS VAGINAL DELIVERY; UTERINE RUPTURE; SECTION; BIRTH AB OBJECTIVE: To compare outcomes at term of a trial of labor in women with previous cesarean delivery who delivered neonates weighing > 4000 g versus women with those weighing less than or equal to 4000 g. STUDY DESIGN: We reviewed medical records for all women undergoing a trial of labor after prior cesarean delivery during a 12-year period. The current analysis was limited to women at term with one prior cesarean and no other deliveries. The rates of cesarean delivery and symptomatic uterine rupture for women with infants weighing > 4000 g were compared to the rates for women with infants weighing less than or equal to 4000 g. Logistic regression was used to control for the potential confounding by use of epidural, maternal age, labor induction, labor augmentation, indication for previous cesarean, type of uterine hysterotomy, year of delivery, receiving public assistance, and maternal race. Adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: Of 2749 women, 13% (365) had infants with birth weights > 4000 g. Cesarean delivery rate associated with birth weights less than or equal to 4000 g was 29% versus 40% for those with birth weights > 4000 g (P =.001) With use of logistic regression, we found that birth weight > 4000 g was associated with a 1.7-fold increase in risk of cesarean delivery (95% Cl, 1.3-2.2). The rate of uterine rupture for women with infants weighing less than or equal to 4000 g was 1.0% versus a 1.6% rate for those with infants weighing > 4000 g (P=.24). Although the logistic regression analysis revealed a somewhat higher rate of uterine rupture associated with birth weights of > 4000 g (adjusted OR, 1.6; 95% Cl, 0.7-4.1), this difference was not statistically significant. The rate of uterine rupture was 2.4% for women with infants weighing > 4250 g, but this rate did not differ significantly from the rate of uterine rupture associated with birth weights less than or equal to 4250 g (P=.1). CONCLUSION: A trial of labor after previous cesarean delivery may be a reasonable clinical option for pregnant women with suspected birth weights of > 4000 g, given that the rate of uterine rupture associated with these weights does not appear to be substantially increased when compared to lower birth weights. However, some caution may apply when considering a trial of labor in women with infants weighing. > 4250 g. In these women with infants weighing > 4000 g, the likelihood of successful vaginal delivery, although lower than for neonates weighing less than or equal to 4000 g, is still 60%. C1 Lenox Hill Hosp, Dept Obstet, New York, NY USA. Lenox Hill Hosp, Dept Obstet & Gynecol, New York, NY USA. Univ Nebraska, Dept Obstet & Gynecol, Ctr Med, Omaha, NE USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Ctr Med, Boston, MA USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Med, Omaha, NE USA. RP Zelop, CM (reprint author), Univ Connecticut, Ctr Hlth, Dept Maternal Fetal Med, 263 Farmington Ave, Farmington, CT 06030 USA. NR 11 TC 44 Z9 48 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2001 VL 185 IS 4 BP 903 EP 905 DI 10.1067/mob.2001.117361 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 485BQ UT WOS:000171734000025 PM 11641675 ER PT J AU O'Connor, P Fleming, P Gray, T Jacobs, L Miller, C Munschauer, F Kinkel, RP Bolibrush, D Cohen, J Freedman, M Webb, U Rabinowicz, H Metz, LM Patry, D Yeung, M Peters, S Hashimoto, S Morrison, W Oger, J Panitch, H Costello, K Bever, C Stuart, W Court, D Stuart, D Tornatore, C Bartlett, D Richert, J Duquette, P Dubois, R Bernier, G Scott, T Pappert, L Brillman, J Felton, W Anderson, T Astruc, J Rose, J Kline, J Burns, J Murray, T Weldon, P Bhan, V Maxner, CE Wall, M Vining, L Grabowski, T Apatoff, B Arapello, K Friedman, J Galetta, S Pfohl, D Liu, G Rice, G Bental, T Mandalfino, P Eggenberger, E Snider, D Kaufman, D Guarnaccia, J Shepard, M Goldstein, J Reiss, M Carter, E Glista, G Rolak, L Scheller, L Jacobson, D Warner, J Goodman, A Petrie, M Mattson, D Karlin, K Wallin, A Stefoski, D Brod, S Cerretta, E Wolinsky, J Arnold, D Arnoutelis, R Durcan, L Kupersmith, M Cappolino, L Herbert, J Rosenberg, J McHugh, D Blumenfeld, A Smith, C Kuder, D Hamilton, S Thurston, S McGee, J O'Bannon, J Kaufman, M Butler, M Putnam, S Rammohan, K Siffort, A Lynn, J Selhorst, J Holzemer, E Hayat, G Tselis, A Coon, C Lisak, R Wray, S Sexton, P Lehrich, J Cook, S Jotkowitz, A Bansil, S Newman, N Brown, J Pennell, P Gilmore, J Carter, J Buckner, J Caselli, R Kerson, L Camasso, M Donneief, G Cooper, J Richardson, B Kung, C Goodwin, J Johnson, T Gulati, A Hedges, T Yardley, C Tran, T Brown, W Ehrenberg, B Horowitz, S Bonnett, A Burger, R Javerbaum, J Griffin, C Whaley, RJ Jeffery, D Jackson, SE Bastings, E Kasper, L Ryan, K Bernat, J Mass, M Hanel, SC Bourdette, D Guy, J Wilson, M Greer, M Lucchinetti, C Botten, M Noseworthy, J Walker, A Muntz, B Tyor, W Simon, J Meyer, M Leek, R Gustafson, C Singel, D Quandt, B Miller, DE Coombs, B Cajade-Law, A Lajaunie, M Escott, E Miller, A Richert, J Cohen, J Vollmer, T Oger, J Jacobs, L Beck, R Kinkel, RP Brownscheidle, C Murray, TJ Simon, J Antel, J Myers, L Birnbaum, G Reingold, S Burde, R Sibley, W Ware, J Blanchard, N Lloyd, K Park, H Sandrock, A Simonian, N Slasor, P Votruba, F White, K Beck, R Chandler, DL Cole, S Felton, W Galetta, S Jacobs, L Kinkel, RP Kupersmith, M Murray, TJ Newman, N Sandrock, A Simon, J Simonian, N AF O'Connor, P Fleming, P Gray, T Jacobs, L Miller, C Munschauer, F Kinkel, RP Bolibrush, D Cohen, J Freedman, M Webb, U Rabinowicz, H Metz, LM Patry, D Yeung, M Peters, S Hashimoto, S Morrison, W Oger, J Panitch, H Costello, K Bever, C Stuart, W Court, D Stuart, D Tornatore, C Bartlett, D Richert, J Duquette, P Dubois, R Bernier, G Scott, T Pappert, L Brillman, J Felton, W Anderson, T Astruc, J Rose, J Kline, J Burns, J Murray, T Weldon, P Bhan, V Maxner, CE Wall, M Vining, L Grabowski, T Apatoff, B Arapello, K Friedman, J Galetta, S Pfohl, D Liu, G Rice, G Bental, T Mandalfino, P Eggenberger, E Snider, D Kaufman, D Guarnaccia, J Shepard, M Goldstein, J Reiss, M Carter, E Glista, G Rolak, L Scheller, L Jacobson, D Warner, J Goodman, A Petrie, M Mattson, D Karlin, K Wallin, A Stefoski, D Brod, S Cerretta, E Wolinsky, J Arnold, D Arnoutelis, R Durcan, L Kupersmith, M Cappolino, L Herbert, J Rosenberg, J McHugh, D Blumenfeld, A Smith, C Kuder, D Hamilton, S Thurston, S McGee, J O'Bannon, J Kaufman, M Butler, M Putnam, S Rammohan, K Siffort, A Lynn, J Selhorst, J Holzemer, E Hayat, G Tselis, A Coon, C Lisak, R Wray, S Sexton, P Lehrich, J Cook, S Jotkowitz, A Bansil, S Newman, N Brown, J Pennell, P Gilmore, J Carter, J Buckner, J Caselli, R Kerson, L Camasso, M Donneief, G Cooper, J Richardson, B Kung, C Goodwin, J Johnson, T Gulati, A Hedges, T Yardley, C Tran, T Brown, W Ehrenberg, B Horowitz, S Bonnett, A Burger, R Javerbaum, J Griffin, C Whaley, RJ Jeffery, D Jackson, SE Bastings, E Kasper, L Ryan, K Bernat, J Mass, M Hanel, SC Bourdette, D Guy, J Wilson, M Greer, M Lucchinetti, C Botten, M Noseworthy, J Walker, A Muntz, B Tyor, W Simon, J Meyer, M Leek, R Gustafson, C Singel, D Quandt, B Miller, DE Coombs, B Cajade-Law, A Lajaunie, M Escott, E Miller, A Richert, J Cohen, J Vollmer, T Oger, J Jacobs, L Beck, R Kinkel, RP Brownscheidle, C Murray, TJ Simon, J Antel, J Myers, L Birnbaum, G Reingold, S Burde, R Sibley, W Ware, J Blanchard, N Lloyd, K Park, H Sandrock, A Simonian, N Slasor, P Votruba, F White, K Beck, R Chandler, DL Cole, S Felton, W Galetta, S Jacobs, L Kinkel, RP Kupersmith, M Murray, TJ Newman, N Sandrock, A Simon, J Simonian, N CA CHAMPS Study Grp TI Interferon beta-1 a for optic neuritis patients at high risk for multiple sclerosis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CLINICALLY ISOLATED SYNDROMES; MAGNETIC-RESONANCE; FOLLOW-UP; BRAIN; CORTICOSTEROIDS; MRI; CRITERIA; LESIONS AB PURPOSE: To evaluate the effect of treatment with interferon beta -1a (Avonex) initiated at the time of a first episode of optic neuritis in patients at high risk for multiple sclerosis (MS). DESIGN: Randomized clinical trial METHODS: Prospective. SETTING: Fifty clinical centers throughout the US and Canada. STUDY POPULATION: After the onset of a first episode of optic neuritis treated with intravenous and oral corticosteroids, 192 patients with brain magnetic resonance imaging (MRI) evidence of subclinical demyelination were randomly assigned to receive weekly intramuscular injections of 30 mug interferon beta -1a or placebo. MAIN OUTCOME MEASURE: The study outcomes were the development of clinically definite MS within 3 years of follow,up and brain MRI changes at 6, 12, and 18 months. RESULTS: The rates of clinically definite MS and of a combined MS/MRI outcome were lower in the interferon beta -1a group than in the placebo group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50, 95% confidence interval 0.34 to 0.73, respectively). Compared with the placebo group, on the 18,month brain MRI the interferon beta -1a group had a smaller change from baseline in T2 lesion volume (P = .02), fewer new or enlarging T2 lesions (P < .001), and a lower frequency of Gd-enhancing lesions (P < .001). CONCLUSION: The clinical and brain MRI results of this trial support initiating interferon beta -1a treatment at the time of a first episode of optic neuritis occurring in patients at high risk for MS based on the presence of subclinical brain MRI lesions. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Univ Toronto, Toronto, ON, Canada. Buffalo Gen Hosp, Buffalo, NY 14203 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Univ Maryland Hosp, Baltimore, MD 21201 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Notre Dame Hosp, Montreal, PQ, Canada. Allegheny Neurol Associates, Pittsburgh, PA USA. Richmond Eye & Ear Hosp, Med Coll Virginia, Richmond, VA USA. Vet Adm Med Ctr, Salt Lake City, UT 84148 USA. Victoria Gen Hosp, Halifax, NS B3H 2Y9, Canada. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. New York Hosp, Cornell Med Ctr, New York, NY USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ Western Ontario, Univ Hosp, London Hlth Sci Ctr, London, ON N6A 5A5, Canada. Yale Univ, Sch Med, New Haven, CT USA. Beta Res Inc, Westmont, IL USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Univ Rochester, Rochester, NY 14627 USA. Montreal Neurol Inst, Montreal, PQ, Canada. Beth Israel Med Ctr, New York, NY 10003 USA. Swedish Med Ctr, Seattle, WA USA. Neurol Associates, Richmond, VA USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Ohio State Univ, Columbus, OH 43210 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. UMD New Jersey Med Sch, Piscataway, NJ USA. Emory Univ, Sch Med, Atlanta, GA USA. Mayo Clin Arizona, Scottsdale, AZ USA. Neurol Grp, Norristown, PA USA. East Bay Neurol, Berkeley, CA USA. Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Univ Missouri, Columbia, MO USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Florida, Gainesville, FL 32611 USA. Mayo Clin Rochester, Rochester, MN USA. RP Beck, R (reprint author), Jaebs Ctr Hlth Res, CHAMPS Anal Ctr, 3010 E 138th Ave,Suite 9, Tampa, FL 33613 USA. NR 28 TC 40 Z9 40 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2001 VL 132 IS 4 BP 463 EP 471 PG 9 WC Ophthalmology SC Ophthalmology GA 481QJ UT WOS:000171530700001 ER PT J AU Zacks, DN Pinnolis, MK Berson, EL Gragoudas, ES AF Zacks, DN Pinnolis, MK Berson, EL Gragoudas, ES TI Melanoma-associated retinopathy and recurrent exudative retinal detachments in a patient with choroidal melanoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report a patient who presented with photopsias, night blindness, exudative retinal detachments, and melanoma-associated retinopathy in her right eye 23 years after the left eye was enucleated for a choroidal melanoma. METHODS: Assessment of fundus findings, fluorescein angiograms, and electroretinograms. RESULTS: The patient had recurrent exudative detachments of the macula in her right eye and electroretinogram responses consistent with the diagnosis of melanoma-associated retinopathy. The abdominal computed tomography (CT) scan was negative, but 13 months later, CT scanning revealed many masses in her liver. Fine-needle biopsy confirmed the diagnosis of metastatic melanoma. CONCLUSION: To our knowledge, this is the first report of melanoma-associated retinopathy in a patient with a previous choroidal melanoma. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Zacks, DN (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 3 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2001 VL 132 IS 4 BP 578 EP 581 DI 10.1016/S0002-9394(01)01086-8 PG 4 WC Ophthalmology SC Ophthalmology GA 481QJ UT WOS:000171530700023 PM 11589887 ER PT J AU Mei, Q Mundinger, TO Kung, D Baskin, DG Taborsky, GJ AF Mei, Q Mundinger, TO Kung, D Baskin, DG Taborsky, GJ TI Fos expression in rat celiac ganglion: an index of the activation of postganglionic sympathetic nerves SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hypoglycemia; nicotine; nerve stimulation; deoxyglucose; insulin ID SUPERIOR CERVICAL-GANGLION; FUNCTIONAL VAGAL INPUT; NERVOUS-SYSTEM; STIMULATION; DOG; NOREPINEPHRINE; GLUCAGON; LIVER; NEURONS; IMMUNOREACTIVITY AB To develop an index of the activation of abdominal sympathetic nerves, we used Fos immunostaining of the celiac ganglion (CG) taken from rats receiving nicotine, preganglionic nerve stimulation, or glucopenic agents. Subcutaneous nicotine injection moderately increased Fos expression in the principal ganglionic cells of the CG (17 +/- 4 Fos+ per mm(2), similar to 12% of all principal CG cells), whereas subcutaneous saline had no effect (0 +/- 0 Fos+ per mm(2); n = 7; P < 0.01). Greater Fos expression was obtained by applying nicotine topically to the CG (71 8 Fos+ per mm(2); 52% of all principal CG cells, n = 5; P < 0.01 vs. topical saline, n = 4) and by preganglionic nerve stimulation (126 9 Fos+ per mm(2); 94% of all principal CG cells, n = 11; P < 0.01 vs. nerve isolation, n = 7). Moderate Fos expression was also observed in the CG after intraperitoneal 2-deoxy-D-glucose (2DG) injection (21 2 Fos+ per mm(2); 16%,of all principal CG cells, n = 5; P < 0.01 vs. saline ip) or insulin injection (16 Fos+ per mm(2); similar to 12% of all principal CG cells, n = 6; P < 0.01 vs. saline ip). Furthermore, Fos expression induced by 2DG was dose and time dependent. These data demonstrate significant Fos expression in the CG in response to chemical, electrical, and reflexive stimulation. Thus Fos expression in the CG may be a useful index to describe various levels of activation of its postganglionic sympathetic neurons. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98159 USA. RP Mei, Q (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-12047, DK-12829, DK-50154] NR 43 TC 6 Z9 6 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2001 VL 281 IS 4 BP E655 EP E664 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 482NY UT WOS:000171583200002 PM 11551840 ER PT J AU Colucci, R Fleming, JV Xavier, R Wang, TC AF Colucci, R Fleming, JV Xavier, R Wang, TC TI L-Histidine decarboxylase decreases its own transcription through downregulation of ERK activity SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE extracellular signal-related kinase; gastrin; gastrin response element-binding protein ID PHORBOL 12-MYRISTATE 13-ACETATE; GASTRIC-CANCER CELLS; RAT STOMACH; GENE-EXPRESSION; HISTAMINE SYNTHESIS; H-3 RECEPTORS; ACTIVATION; MESSENGER; PROMOTER; INHIBITION AB A poorly defined negative feedback loop decreases transcription of the L-histidine decarboxylase (HDC) gene. To help understand this regulation, we have studied the effect of HDC protein expression on HDC gene transcription in transfected AGS-B cells. Expression of the rat HDC protein inhibited HDC promoter activity in a dose-dependent fashion. The region of the HDC promoter mediating this inhibitory effect corresponded to a previously defined gastrin and extracellular signal-related kinase (ERK)-1 response element. Overexpression of the HDC protein reduced nuclear factor binding in this region. Experiments employing specific histamine receptor agonists indicated that the inhibitory effect was not dependent on histamine production, and studies with the HDC inhibitor alpha -fluoromethylhistidine revealed that inhibition was unrelated to enzyme activity. Instead, an enzymatically inactive region at the amino terminal of the HDC enzyme (residues 1-271) was shown to mediate inhibition. Fluorescent chimeras containing this domain were not targeted to the nucleus, arguing against specific inhibition of the HDC transcription machinery. Instead, we found that overexpression of HDC protein decreased ERK protein levels and ERK activity and that the inhibitory effect of HDC protein could be overcome by overexpression of ERK1. These data suggest a novel feedback-inhibitory role for amino terminal sequences of the HDC protein. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Wang, TC (reprint author), Univ Massachusetts, Med Ctr, Div Gastroenterol, Biotech 2 Suite 202,373 Plantat St, Worcester, MA 01605 USA. FU NIDDK NIH HHS [R01-DK-48077] NR 40 TC 13 Z9 13 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2001 VL 281 IS 4 BP G1081 EP G1091 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 483RA UT WOS:000171648600025 PM 11557529 ER PT J AU Lloyd, KCK Wang, JF Solomon, TE AF Lloyd, KCK Wang, JF Solomon, TE TI Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastric acid secretion; enterogastrone; intestinal phase; cholecystokinin; peptone meal ID STIMULATED GASTRIC-ACID; FOS PROTEIN EXPRESSION; FAT-INDUCED INHIBITION; SOLITARY TRACT; PEPTIDE-YY; BRAIN-STEM; OLEIC-ACID; AWAKE RATS; CHOLECYSTOKININ; SECRETION AB We examined the role of CCK-A receptors in acid inhibition by intestinal nutrients. Gastric acid and plasma CCK and gastrin levels were measured in rats with gastric and duodenal fistulas during intragastric 8% peptone and duodenal perfusion with saline, complete liquid diet (CLD; 20% carbohydrate, 6% fat, and 5% protein), and the individual components of CLD. Acid output was significantly inhibited (50-60%) by CLD, lipid, and dextrose. Plasma CCK was significantly increased by CLD (from 2.6 +/-0.3 to 4.8 +/-0.5 pM) and lipid (4.6 +/-0.5 pM). CCK levels 50-fold higher (218 +/- 33 pM) were required to achieve similar acid inhibition by exogenous CCK-8 (10 nmol.kg(-1).h(-1) iv). Intestinal soybean trypsin inhibitor elevated CCK (10.9 +/-2.5 pM) without inhibiting acid secretion. The CCK-A antagonist MK-329 (1 mg/kg iv) reversed acid inhibition caused by CLD, lipid, and dextrose. Peptone-stimulated gastrin (21.7 +/-1.9 pM) was significantly inhibited by CLD (14.5 +/-3.6 pM), lipid (12.3 +/-2.2 pM), and dextrose (11.9 +/-1.5 pM). Lipid and carbohydrate inhibit acid secretion by activating CCK-A receptors but not by altering plasma CCK concentrations. C1 Univ Calif Davis, Ctr Comparat Med, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. RP Lloyd, KCK (reprint author), Univ Calif Davis, Ctr Comparat Med, Sch Vet Med, Dept Anat Physiol & Cell Biol, 1 Shields Ave, Davis, CA 95616 USA. FU NIDDK NIH HHS [DK-45752, DK-41301] NR 34 TC 4 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2001 VL 281 IS 4 BP G924 EP G930 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 483RA UT WOS:000171648600008 PM 11557512 ER PT J AU Warren, KS Baker, K Fishman, MC AF Warren, KS Baker, K Fishman, MC TI The slow mo mutation reduces pacemaker current and heart rate in adult zebrafish SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE bradycardia; genetic screen; Ih ID HYPERPOLARIZATION-ACTIVATED CURRENT; I-H; CARDIOVASCULAR-SYSTEM; OPIOID INHIBITION; NODE CELLS; VERTEBRATES; MYOCYTES; CHANNELS; CATION; I(F) AB Genetic studies in zebrafish have focused on embryonic mutations, but many physiological mechanisms continue to mature after embryogenesis. We report here that zebrafish homozygous for the mutation slow mo can be raised to adulthood. In the embryo, the slow mo gene is needed to regulate heart rate, and its mutation causes a reduction in pacemaker current (I-h) and slowing of heart rate (bradycardia). The homozygous adult slow mo fish continues to manifest bradycardia, without other evident ill effects. Patch-clamp analysis of isolated adult cardiomyocytes reveals that I-h has chamber-specific properties such that the atrial current density of I-h is far greater than the ventricular current density of I-h. I-h is markedly diminished in cardiomyocytes from both chambers of slow mo mutant fish. Thus I-h continues to be a critical determinant of pacemaker rate even after adult neural and humoral influences have developed. It is clear that zebrafish may be used for genetic dissection of selected physiological mechanisms in the adult. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL-63206, R01-HL-49579]; NIDDK NIH HHS [R01-DK-55383] NR 38 TC 40 Z9 42 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2001 VL 281 IS 4 BP H1711 EP H1719 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 476KZ UT WOS:000171227400030 PM 11557562 ER PT J AU West, CA He, CF Su, M Secomb, TW Konerding, MA Young, AJ Mentzer, SJ AF West, CA He, CF Su, M Secomb, TW Konerding, MA Young, AJ Mentzer, SJ TI Focal topographic changes in inflammatory microcirculation associated with lymphocyte slowing and transmigration SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE oxazolone; sheep; migration ID ENDOTHELIAL-CELLS; CAPILLARY LOOPS; DERMAL PAPILLAE; DENDRITIC CELL; ULTRASTRUCTURE; ARREST; ORGANIZATION; CHEMOKINES; OXAZOLONE; MIGRATION AB Microcirculation is the primary mechanism for delivering lymphocytes to inflammatory tissues. Blood flow within microvessels ensures a supply of lymphocytes at the blood-endothelial interface. Whether the structure of the inflammatory microcirculation facilitates lymphocyte transmigration is less clear. To illuminate the microcirculatory changes associated with lymphocyte transmigration, we used intravital videomicroscopy to examine the dermal microcirculation after application of the epicutaneous antigen oxazolone. Intravascular injection of fluorescein-labeled dextran demonstrated focal topographic changes in the microcirculation. These focal changes had the appearance of loops or hairpin turns in the oxazolone-stimulated skin. Changes were maximal at 96 h and coincided with peak lymphocyte recruitment. To determine whether these changes were associated with lymphocyte transmigration, lymphocytes obtained from efferent lymph of draining lymph nodes at 96 h were fluorescently labeled and reinjected into inflammatory microcirculation. Epifuorescence intravital video microscopy demonstrated focal areas were associated with lymphocyte slowing and occasional transmigration. In contrast, focal loops and lymphocyte slowing were rarely observed in the contralateral control microcirculation. Results suggest that structural adaptations in inflammatory microcirculation represented by focal topographic changes may contribute to regulation of tissue entry by recirculating lymphocytes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab,Harvard Surg Res Labs, Boston, MA 02115 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. Univ Mainz, Dept Anat, D-5509 Mainz, Germany. RP Mentzer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunophysiol Lab,Harvard Surg Res Labs, Rm G09,44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-47078] NR 39 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2001 VL 281 IS 4 BP H1742 EP H1750 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 476KZ UT WOS:000171227400034 PM 11557566 ER PT J AU Kraut, JA Helander, KG Helander, HF Iroezi, ND Marcus, EA Sachs, G AF Kraut, JA Helander, KG Helander, HF Iroezi, ND Marcus, EA Sachs, G TI Detection and localization of H+-K+-ATPase isoforms in human kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renal hydrogen-potassium-adenosinetriphosphatase; hydrogen; potassium; immunohistochemistry ID MEDULLARY COLLECTING DUCT; H,K-ATPASE ALPHA-SUBUNIT; GASTRIC H,K-ATPASE; DISTAL COLON; H+,K+-ATPASE; IMMUNOREACTIVITY; EXPRESSION; TRANSPORT; SECRETION; ACIDOSIS AB An H+-K+-ATPase contributes to hydrogen secretion and potassium reabsorption by the rat and rabbit collecting ducts. Transport of these ions appears to be accomplished by one or both of two isoforms of the H+-K+-ATPase, HK alpha (1) and HK alpha (2), because both isoforms are found in the collecting ducts and transport of hydrogen and potassium is attenuated by exposure to inhibitors of these transport proteins. To evaluate whether an H+-K+-ATPase is present in the human kidney, immunohistochemical studies were performed using normal human renal tissue probed with antibodies directed against epitopes of three of the known isoforms of the H+-K+-ATPase, HK alpha (1), HK alpha (2), and HK alpha (4), and the V-type H+-ATPase. Cortical and medullary tissue probed with antibodies against HK alpha (1) showed cytoplasmic staining of intercalated cells that was less intense than that observed in the parietal cells of normal rat stomach stained with the same antibody. Also, weak immunoreactivity was detected in principal cells of the human collecting ducts. Cortical and medullary tissue probed with antibodies directed against HK alpha (4) revealed weak, diffuse staining of intercalated cells of the collecting ducts and occasional light staining of principal cells. Cortical and medullary tissue probed with antibodies directed against the H+-ATPase revealed staining of intercalated cells of the collecting ducts and some cells of the proximal convoluted tubules. By contrast, no discernible staining was noted with the use of the antibody against HK alpha (2), These data indicate that HK alpha (1). and HK alpha (4) are present in the collecting ducts of the human kidney. In this location, these isoforms might contribute to hydrogen and potassium transport by the kidney. C1 VA Greater Los Angeles Hlth Care Syst, Div Nephrol 691 111L, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Res Serv, Membrane Biol Lab, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Care Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. AstraZeneca, Molndal, Sweden. Univ Gothenburg, Dept Biomed Lab Sci, Gothenburg, Sweden. RP Kraut, JA (reprint author), VA Greater Los Angeles Hlth Care Syst, Div Nephrol 691 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu NR 33 TC 23 Z9 25 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2001 VL 281 IS 4 BP F763 EP F768 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 477LL UT WOS:000171285000019 PM 11553523 ER PT J AU Winickoff, JP Hibberd, PL Case, B Sinha, P Rigotti, NA AF Winickoff, JP Hibberd, PL Case, B Sinha, P Rigotti, NA TI Child hospitalization - An opportunity for parental smoking intervention SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE child, hospitalized; parents; smoking; smoking cessation; tobacco ID ENVIRONMENTAL TOBACCO-SMOKE; RANDOMIZED CONTROLLED TRIAL; MATERNAL SMOKING; PASSIVE SMOKING; ASTHMATIC-CHILDREN; CESSATION PROGRAM; EXPOSURE; RELAPSE; IMPACT AB Background: Hospitalization with tobacco-related illness increases smokers' interest in cessation. Because parental smoking increases the child's risk of developing respiratory and other illnesses, a child's hospitalization might motivate a smoking parent to consider changing smoking behavior. It is unclear if parents would be receptive to smoking-cessation interventions at the time when their child is hospitalized. Methods: In March 1999, parents of 298 consecutive children admitted to the medical services at Children's Hospital Boston were interviewed to determine the smoking status of household members. Smoking parents were invited to complete a 35-item questionnaire regarding personal smoking history and acceptability of three types of cessation interventions. Results: Sixty-five smoking parents were identified among the 298 admissions; 62 of 65 (95%) participated in the survey. Among respondents, only 15% had ever participated in any smoking-cessation program, and only 31% had ever used a medication to try to quit. Although 78% of parents were willing to speak with a counselor about their smoking while their child was in the hospital, and 74% would enroll in a telephone-based smoking-cessation program, only 26% were interested in a free program requiring travel back to the hospital. All parents believed that pediatricians should offer parental smokers the chance to participate in a smoking-cessation program. Conclusions: At the time of a child's hospitalization, parents are willing to enroll in smoking interventions that include in-hospital and telephone counseling but not to travel back to the hospital. A child's hospitalization may provide a unique opportunity to enroll parents who smoke into cessation programs. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Boston Childrens Hosp, Clin Res Core Programs Off, Boston, MA USA. Harvard Univ, Sch Med, Clin Res Core Programs Off, Boston, MA USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. RI Case, Brady/M-1879-2015 OI Case, Brady/0000-0001-9512-0416 FU AHRQ HHS [T32-HS00063]; NHLBI NIH HHS [K24-HL04440] NR 25 TC 33 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2001 VL 21 IS 3 BP 218 EP 220 DI 10.1016/S0749-3797(01)00355-5 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 477UC UT WOS:000171301800011 PM 11567844 ER PT J AU Doyle, AE Faraone, SV DuPre, EP Biederman, J AF Doyle, AE Faraone, SV DuPre, EP Biederman, J TI Separating attention deficit hyperactivity disorder and learning disabilities in girls: A familial risk analysis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LA-TOURETTES SYNDROME; READING-DISABILITY; GENETIC-RELATIONSHIP; MULTIPLE THRESHOLDS; COMORBIDITY; ADHD; ETIOLOGY; TRANSMISSION; TRAITS; SAMPLE AB Objective: Familial risk analysis was used to clarify the relationship in girls between attention deficit hyperactivity disorder (ADHD) and learning disabilities in either mathematics or reading. Method: The authors assessed the presence of ADHD and learning disabilities in 679 first-degree relatives of three groups of index children: girls with ADHD and a comorbid learning disability, girls with ADHD but no learning disabilities, and a comparison group of girls without ADHD. Results: The risk for ADHD was similarly higher in families of ADHD probands with and without learning disabilities, both groups had significantly higher rates of ADHD than did families of the comparison girls. In contrast, only among relatives of ADHD probands with a learning disability was there a higher risk for learning disabilities. A strong (although statistically nonsignificant) difference emerged that suggested at least some degree of cosegregation of ADHD and learning disabilities in family members. There was no evidence of nonrandom mating between spouses with ADHD and learning disabilities. Conclusions: These results extend previously reported findings regarding the relationship of ADHD and learning disabilities to female subjects and raise the possibility that, in girls, the relationship between ADHD and learning disabilities is due to shared familial risk factors. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit Acc 725, Child Pediat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Doyle, AE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit Acc 725, Child Pediat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314] NR 36 TC 34 Z9 36 U1 3 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2001 VL 158 IS 10 BP 1666 EP 1672 DI 10.1176/appi.ajp.158.10.1666 PG 7 WC Psychiatry SC Psychiatry GA 478XU UT WOS:000171374500021 PM 11579000 ER PT J AU Biederman, J Hirshfeld-Becker, DR Rosenbaum, JF Herot, C Friedman, D Snidman, N Kagan, J Faraone, SV AF Biederman, J Hirshfeld-Becker, DR Rosenbaum, JF Herot, C Friedman, D Snidman, N Kagan, J Faraone, SV TI Further evidence of association between behavioral inhibition and social anxiety in children SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PANIC DISORDER; YOUNG-CHILDREN; PARENTS; DEPRESSION; CHILDHOOD; RISK; FAMILY; PSYCHOPATHOLOGY; AGORAPHOBIA; UNFAMILIAR AB Objective: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. Method. Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2-6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children greater than or equal to5 years was compared between children with behavioral inhibition (N=64) and without (N=152). Results: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). Conclusions: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit WACC 725, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit WACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-01538, MH-47077] NR 41 TC 323 Z9 331 U1 9 U2 44 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2001 VL 158 IS 10 BP 1673 EP 1679 DI 10.1176/appi.ajp.158.10.1673 PG 7 WC Psychiatry SC Psychiatry GA 478XU UT WOS:000171374500022 PM 11579001 ER PT J AU Biederman, J Hirshfeld-Becker, DR Rosenbaum, JF Perenick, SG Wood, J Faraone, SV AF Biederman, J Hirshfeld-Becker, DR Rosenbaum, JF Perenick, SG Wood, J Faraone, SV TI Lack of association between parental alcohol or drug addiction and behavioral inhibition in children SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PANIC DISORDER AB Objective: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2-6 years)-offspring of parents with panic and depressive disorders-who had been assessed for behavioral inhibition through laboratory-based observations. Method: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. Results. Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. Conclusions. These results are not consistent with the hypothesis linking behavioral inhibition to addictions. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit WACC 725, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Unit Clin Pyschopharmacol, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit WACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-01538, MH-47077] NR 8 TC 9 Z9 9 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2001 VL 158 IS 10 BP 1731 EP 1733 DI 10.1176/appi.ajp.158.10.1731 PG 3 WC Psychiatry SC Psychiatry GA 478XU UT WOS:000171374500034 PM 11579013 ER PT J AU Takeuchi, M Sedeek, KA Schettino, GPP Suchodolski, K Kacmarek, RM AF Takeuchi, M Sedeek, KA Schettino, GPP Suchodolski, K Kacmarek, RM TI Peak pressure during volume history and pressure-volume curve measurement affects analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE respiratory function tests; adult respiratory distress syndrome; lung compliance; pressure-volume curve; volume history ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; LOWER INFLECTION POINT; REGIONAL DISTRIBUTION; ALVEOLAR RECRUITMENT; GAS-EXCHANGE; MATHEMATICAL-MODEL; TIDAL VOLUME; VENTILATION AB A previous volume history should be established prior to pressure-volume (P-V) curve measurement, however the effect of the volume history and the peak inspiratory pressure (PIP) during the P-V measurement has not been explored. Lung injury was created by lavage in nine sheep (25-35 kg). After stabilization, four P-V curves were sequentially obtained with PIP of 40, 50, 60, and 40 cm H2O. Prior to each P-V measurement the PIP delivered for 1 min was the same as during P-V measurement. We compared the lower inflection point (Pflex), upper inflection point (UIP), compliance below Pflex (Cstart), compliance between Pflex. and UIP (Cinf), and compliance between UIP and peak pressure (Cend) for the inflation limb, and the point of maximum curvature on the deflation limb (Pmc), compliance between peak pressure and Pmc (Ctop), and maximum compliance (Cdef) for the deflation limb. In two sheep, Pflex at PIP 40 cm H2O could not be identified but appeared when PIP was raised. Pflex, Cstart, Cend, and Ctop were not affected by the PIP. However, UIP, Pmc, Cinf, and Cdef increased as the PIP increased. Volume history and the PIP during P-V curve measurements affect both the inflation and deflation P-V curves. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Resp Care, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Resp Care, Ellison 401, Boston, MA 02114 USA. NR 41 TC 23 Z9 24 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2001 VL 164 IS 7 BP 1225 EP 1230 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 489VM UT WOS:000172013200029 PM 11673214 ER PT J AU Jhaveri, KS Saini, S Levine, LA Piazzo, DJ Doncaster, RJ Halpern, EF Jordan, PF Thrall, JH AF Jhaveri, KS Saini, S Levine, LA Piazzo, DJ Doncaster, RJ Halpern, EF Jordan, PF Thrall, JH TI Effect of multislice CT technology on scanner productivity SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HELICAL CT; PROTOCOLS AB OBJECTIVE. In this study we analyzed the impact of multislice CT technology on scanner productivity in a tertiary care medical center. MATERIALS AND METHODS. We compared the productivity of two diagnostic CT scanners during the periods January 1 to August 31, 1999 (when both scanners had single-slice CT capability) and January 1 to August 31, 2000 (when one of these scanners was replaced with a multislice CT scanner). The scanners were used primarily for outpatients during the day shift and for inpatients during the evening shift; the demand for CT services was stable. For this analysis, we queried the hospital's radiology information system and identified the number of CT examinations performed during the two analysis periods. We also determined the examination mix, including proportion of enhanced and unenhanced examinations and the anatomic region examined, to ensure comparable patient populations. Statistical analysis was performed. RESULTS. The number of CT studies performed on the two scanners increased by 1772 (13.1%) from 13,548 (before multislice CT) to 15,320 (when multislice CT was available). The number of examinations enhanced with contrast media increased from 52% to 65%. Between 9:00 A.M. and 5:00 P.m., the number of CT examinations was similar on the single-slice scanners in the two periods (p > 0.05). However, in the period when multislice CT was available, the number of studies performed on the multislice scanner (5919) was 51.9% higher than those performed using the single-slice scanner (3896) (p < 0.0006). CONCLUSION. Using a multislice CT scanner leads to an increase in CT productivity, even though multislice studies are performed using more complicated protocols than are used on a single-slice CT scanner. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 9 TC 24 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2001 VL 177 IS 4 BP 769 EP 772 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 475CT UT WOS:000171144700005 PM 11566670 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Reusing catheters and other medical devices SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SINGLE-USE; LIABILITY C1 Rush Med Coll, Chicago, IL 60612 USA. Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 15 TC 3 Z9 4 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2001 VL 177 IS 4 BP 773 EP 776 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 475CT UT WOS:000171144700006 PM 11566671 ER PT J AU Kaushik, S Erickson, JK Palmer, WE Winalski, CS Kilpatrick, SJ Weissman, BN AF Kaushik, S Erickson, JK Palmer, WE Winalski, CS Kilpatrick, SJ Weissman, BN TI Effect of chondrocalcinosis on the MR imaging of knee menisci SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CRYSTAL DEPOSITION DISEASE; HIGH SIGNAL INTENSITY; ARTICULAR CHONDROCALCINOSIS; CALCIFICATION; DIAGNOSIS; TEARS; PREVALENCE; IMAGES AB OBJECTIVE. Our goal was to determine the influence of chondrocalcinosis on MR imaging in the detection of meniscal tears. MATERIALS AND METHODS. A retrospective review was performed of knee MR imaging and arthroscopy records from two university hospitals between 1996 and 1998. Seventy individuals had radiographic evidence of chondrocalcinosis and underwent knee MR imaging. Thirty-seven of these individuals had undergone arthroscopy for further evaluation of their symptoms. MR imaging sensitivity and specificity in the detection of medial and lateral meniscal tears were calculated in these 37 patients who had radiographic evidence of chondrocalcinosis and in a control group of 34 patients who underwent MR imaging and arthroscopy but did not have knee chondrocalcinosis. RESULTS. In the chondrocalcinosis group, MR imaging sensitivity, specificity, and accuracy for meniscal tear were 78%, 71%, and 78%, respectively, for the lateral meniscus, and 89%,72%, and 81% for the medial meniscus. The control group showed sensitivity, specificity, and accuracy of 93%, 100%, and 97%, respectively, for the lateral meniscus and 100% in all cases for the medial meniscus. The MR imaging detection of meniscal tears in both the lateral and medial compartments combined is significantly poorer in the presence of chondrocalcinosis (p < 0.005). CONCLUSION. MR imaging sensitivity and specificity for detection of meniscal tear is decreased in the presence of meniscal chondrocalcinosis. Chondrocalcinosis appeared as a high-signal-intensity region on Tl-weighted, intermediate-weighted, and inversion recovery sequences. The high signal of chondrocalcinosis on inversion recovery sequence is an interesting observation that to our knowledge has not been previously reported. Radiographic correlation with the MR imaging examination can help prevent overdiagnosing meniscal tears. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Biostat, Richmond, VA 23298 USA. RP Kaushik, S (reprint author), Med Coll Virginia Hosp, Dept Radiol, 401 N 12th St,Rm 3-407B,POB 980615, Richmond, VA 23298 USA. NR 25 TC 20 Z9 20 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2001 VL 177 IS 4 BP 905 EP 909 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 475CT UT WOS:000171144700031 PM 11566703 ER PT J AU Hwang, BJ Connelly, MM Lev, MH AF Hwang, BJ Connelly, MM Lev, MH TI Distinctive MR imaging appearance of hemorrhagic cerebral aneurysms associated with atrial myxoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GRADIENT-ECHO; SPIN-ECHO C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. NR 8 TC 9 Z9 9 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2001 VL 177 IS 4 BP 925 EP 927 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 475CT UT WOS:000171144700034 PM 11566707 ER PT J AU de Leval, L Ferry, JA Falini, B Shipp, M Harris, NL AF de Leval, L Ferry, JA Falini, B Shipp, M Harris, NL TI Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma - Evidence for derivation from germinal center B cells? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE diffuse large B-cell lymphoma; mediastinum; thymus; germinal center; bcl-6; CD10 ID DIFFUSE LARGE-CELL; PROBABLE THYMIC ORIGIN; NON-HODGKINS LYMPHOMA; PROTEIN EXPRESSION; PARAFFIN SECTIONS; SOMATIC MUTATION; GENE; REGION; TISSUE; CLASSIFICATION AB Primary mediastinal large B-cell lymphomas (LBCLs) constitute a unique subtype of diffuse LBCLs, with distinct clinical, immunophenotypic, and morphologic features. These lymphomas are thought to originate from the thymus, and it has been hypothesized that they derive from a population of B lymphocytes normally present in the thymic medulla. Most diffuse LBCLs harbor somatic mutations in their immunoglobulin genes, suggesting that they have been exposed to the germinal center. To investigate the possible relationship of mediastinal LBCLs to germinal center B cells, we analyzed the expression of bcl-6 and CD10 in 19 mediastinal LBCLs, using an immunoperoxidase technique on formalin-fixed tissue. We found that 19 of 19 (100%) mediastinal LBCLs were bcl-6+ and 6 of 19 (32%) mediastinal LBCLs were CD10+. Because mediastinal LBCLs usually lack BCL-6 gene rearrangement or mutations, expression of bcl-6 and CD10 in these tumors tends to support a germinal center derivation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Perugia, Dept Pathol, I-06100 Perugia, Italy. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 44 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2001 VL 25 IS 10 BP 1277 EP 1282 DI 10.1097/00000478-200110000-00008 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 476JG UT WOS:000171222100008 PM 11688462 ER PT J AU Korrick, SA Chen, CZ Damokosh, AI Ni, JT Liu, X Cho, SI Altshul, L Ryan, L Xu, XP AF Korrick, SA Chen, CZ Damokosh, AI Ni, JT Liu, X Cho, SI Altshul, L Ryan, L Xu, XP TI Association of DDT with spontaneous abortion: A case-control study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE pesticides; organochlorines; DDT; DDE; PCBs; spontaneous abortion ID POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; WOMEN; RESIDUES; MILK; HYDROCARBONS; POPULATION; PREGNANCY; SPECIMENS; LACTATION AB PURPOSE: Spontaneous abortion (SAB), the most common adverse pregnancy outcome, affects similar to 15% of clinically recognized pregnancies. Except for advanced maternal age and smoking, there are not well-established risk factors for SAB. Animal models associate increased fetal resorption or abortion with exposure to the pesticide dichlorodiphenyl trichloroethane (DDT), but epidemiologic investigations of DDT and SAB are inconsistent. We undertook a pilot investigation of the hypothesized association of DDT with SAB. METHODS: Participants in this case-control study were selected from a longitudinal study of reproductive effects of rotating shifts among female Chinese textile workers who were married, ages 22-34, nulliparous without history of SAB or infertility, and planning pregnancy. From 412 pregnancies, 42 of which ended in SAB, 15 SAB cases and 15 full-term controls were randomly selected and phlebotomized. Serum was analyzed for p,p ' -DDT, o,p ' -DDT, their metabolites (DDE and DDD), and other organochlorines including polychlorinated biphenyls. RESULTS: Cases and controls were nonsmokers and did not differ in age (mean 25 years), body mass index (BMI), passive smoke exposure, or workplace exposures. Cases had significantly (p < 0.05) higher serum levels of p,p ' -DDE (22 vs. 12 ng/g) and o,p ' -DDE (0.09 vs. 0.05 ng/g) than controls. After adjustment for age and BMI, each ng/g serum increase in p,p ' -DDE was associated with a 1.13 (Cl, 1.02-1.26) increased odds of SAB. With adjustment of serum DDE levels for excretion via breastfeeding, DDE-associated increased odds of SAB remained significant with up to 7% declines in maternal serum DDE levels for each month of breastfeeding. CONCLUSIONS: A potential increased risk of SAB is associated with maternal serum DDE levels. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. Anhui Inst Biomed & Environm Hlth, Anhui, Peoples R China. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Korrick, SA (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [HD32505]; NIEHS NIH HHS [ES05947, ES00002, ES08074] NR 32 TC 79 Z9 81 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2001 VL 11 IS 7 BP 491 EP 496 DI 10.1016/S1047-2797(01)00239-3 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475LH UT WOS:000171165100007 PM 11557181 ER PT J AU Netscher, DT Eladoumikdachi, F Schneider, A AF Netscher, DT Eladoumikdachi, F Schneider, A TI A case study of a patient with closed avulsion rupture of a single slip of the flexor digitorum superficialis tendon SO ANNALS OF PLASTIC SURGERY LA English DT Article AB A case of a closed rupture of a single slip of flexor digitorum superficialis to the little finger is described. Closed rupture injuries of the flexor digitorum profundus tendon are quite common, but closed injuries to the superficialis tendon have been rarely reported, A single slip avulsion rupture of this tendon would seem to be very uncommon. The clinical presentation is reviewed. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 2001 VL 47 IS 4 BP 431 EP 434 DI 10.1097/00000637-200110000-00012 PG 4 WC Surgery SC Surgery GA 479MD UT WOS:000171407400012 PM 11601580 ER PT J AU Kuo, EY Chang, YC Wright, CD AF Kuo, EY Chang, YC Wright, CD TI Impact of hospital volume on clinical and economic outcomes for esophagectomy SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 29-31, 2001 CL NEW ORLEANS, LOUISIANA SP Soc Thorac Surgeons ID CANCER-SURGERY; SURGICAL EXPERIENCE; MORTALITY; CARCINOMA; MORBIDITY AB Background. Several complex surgical procedures had a reduction in mortality when they were performed at high volume centers. We hypothesized esophagectomy procedures for cancer performed at high volume hospitals in the state of Massachusetts would show a similar relationship. Methods. Data were obtained from the Massachusetts Health Data Consortium on discharge information for all acute care hospitals in Massachusetts regardless of payer from 1992 to 2000. The influence of hospital volume was related to days in the intensive care unit, length of stay, discharge disposition, hospital mortality, and total cost. Hospitals were stratified to low volume hospitals (< 6 cases per year) and high volume hospitals (> 6 cases per year). Results. One thousand one hundred ninety-three patients underwent esophagectomy during this 8-year study period in Massachusetts. Three high volume hospitals performed 56.5% of all resections (674 of 1,193). Sixty-one low volume hospitals performed 43.5% of the resections (519 of 1,193) with an average volume of only 1 case of esophagectomy per year. High volume hospitals were associated with a 2-day decrease in median length of stay (p < 0.001), a 3-day reduction in median intensive care unit stay (p < 0.001), an increased rate of home discharges (as opposed to rehabilitation hospitals) (p < 0.001), and a 3.7-fold decrease in hospital mortality (9.2% vs 2.5%; p < 0.001). The odds ratio of death at a low volume hospital was 4.3 (95% confidence interval, 2.3 to 7.7; p < 0.001). The median cost was $755 dollars greater at high volume hospitals (p = not significant). Conclusions. Hospitals that perform a high volume of esophagectomies have better results with early clinical outcomes and marked reductions in mortality compared with low volume hospitals. (C) 2001 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. NR 20 TC 73 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2001 VL 72 IS 4 BP 1118 EP 1124 DI 10.1016/S0003-4975(01)02962-9 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 479MB UT WOS:000171407200004 PM 11603422 ER PT J AU Perea, S Lopez-Ribot, JL Kirkpatrick, WR McAtee, RK Santillan, RA Martinez, M Calabrese, D Sanglard, D Patterson, TF AF Perea, S Lopez-Ribot, JL Kirkpatrick, WR McAtee, RK Santillan, RA Martinez, M Calabrese, D Sanglard, D Patterson, TF TI Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMINO-ACID SUBSTITUTION; LANOSTEROL 14-ALPHA-DEMETHYLASE; OROPHARYNGEAL CANDIDIASIS; REDUCED AFFINITY; DRUG-RESISTANCE; MULTIPLE RESISTANCE; CHROMOGENIC AGAR; IN-VITRO; CONTRIBUTE; MUTATION AB Molecular mechanisms of azole resistance in Candida albicans, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in C albicans strains displaying high-level fluconazole resistance (MICs, greater than or equal to 64 mug/ml) isolated from human immunodeficiency virus (HM-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14 alpha -demethylase (ERG11) and efflux transporters (MDR) and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in C. albicans clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis,S Texas Ctr Biol Med, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. CHU Vaudois, CH-1011 Lausanne, Switzerland. RP Lopez-Ribot, JL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis,S Texas Ctr Biol Med, Texas Res Pk,15355 Lambda Dr, San Antonio, TX 78245 USA. RI Lopez-Ribot, Jose/D-2048-2010; OI Sanglard, Dominique/0000-0002-5244-4178 FU NCRR NIH HHS [M01 RR001346]; NIAID NIH HHS [1 R29 AI 42401]; NIDCR NIH HHS [3 R01 DE11381-04A2S2, 5 R01 DE 11381, R01 DE011381] NR 42 TC 259 Z9 287 U1 1 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2001 VL 45 IS 10 BP 2676 EP 2684 DI 10.1128/AAC.45.10.2676-2684.2001 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 475GQ UT WOS:000171154500002 PM 11557454 ER PT J AU Ince, D Hooper, DC AF Ince, D Hooper, DC TI Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DNA TOPOISOMERASE-IV; GYRASE-A-PROTEIN; STREPTOCOCCUS-PNEUMONIAE; QUINOLONE RESISTANCE; IN-VITRO; 6-FLUORO-8-METHOXY QUINOLONE; FLUOROQUINOLONE RESISTANCE; ANTIBACTERIAL ACTIVITY; ANTIMICROBIAL ACTIVITY; COUMARIN ACTIVITY AB Gatifloxacin, an 8-methoxyfluoroquinolone, was found to be two- to fourfold more active against wild-type Staphylococcus aureus ISP794 than its desmethoxy derivative, AM-1121, and ciprofloxacin, another desmethoxy fluoroquinolone. Single grlBA mutations caused two- to fourfold increases in the MIC of gatifloxacin, and a single gyrase mutation was silent. Double mutations in gyrA and grl4 or grlB caused a 32-fold increase in the MIC of gatifloxacin, in contrast to a 128-fold increase for ciprofloxacin and AM-1121. Overexpression of the NorA efflux pump had minimal effect on the MIC of gatifloxacin. The bactericidal activity of the three quinolones at four times the MIC differed only for a double mutant, with gatifloxacin exhibiting a killing pattern similar to that for ISP794, whereas ciprofloxacin and AM-1121 failed to show any killing. With gatifloxacin, selection of resistant mutants at twice the MIC was 100- to 1,000-fold less frequent than with the comparison quinolones, and mutants could rarely be selected at four times the MIC. The limit resistance in ISP74 was 512 times the MIC of gatifloxacin and 1,024 times the MICs of ciprofloxacin and AM-1121. Novel mutations in topoisomerase IV were selected in five of the six single-step mutants, three of which were shown to cause quinolone resistance by genetic studies. In conclusion, topoisomerase IV is the primary target of gatifloxacin. In contrast to comparison quinolones, mutations in both topoisomerase IV and gyrase are required for resistance to gatifloxacin by clinical breakpoints; and do not abolish bactericidal effect, further supporting the benefit of the 8-methoxy substituent in gatifloxacin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI23983] NR 55 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2001 VL 45 IS 10 BP 2755 EP 2764 DI 10.1128/AAC.45.10.2755-2764.2001 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 475GQ UT WOS:000171154500013 PM 11557465 ER PT J AU Wambaugh, JL Linebaugh, CW Doyle, PJ Martinez, AL AF Wambaugh, JL Linebaugh, CW Doyle, PJ Martinez, AL TI Effects of two cueing treatments on lexical retrieval in aphasic speakers with different levels of deficit SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Clinical Aphasiology Conference CY MAY, 2000 CL WAIKOLON, HAWAII ID NAMING DISORDERS; THERAPY; PRINCIPLES; ACCESS AB The effects of two cueing treatments for lexical retrieval were examined with three aphasic speakers who demonstrated different levels of lexical processing impairment (i.e., predominately semantic, predominately phonologic, and mixed semantic-phonologic). Each speaker received both treatments, with treatments being applied sequentially to different word lists in a multiple baseline design. Both treatments consisted of a prestimulation phase followed by the application of a response-contingent cueing hierarchy. One treatment employed semantic-level cueing, whereas the other treatment utilised phonologic-level cueing. All participants evidenced a positive response to both of the treatments and one participant (predominately phonologic-level deficit) showed a superior response to lexical-semantic treatment. C1 Univ Utah, Salt Lake City, UT 84112 USA. VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. George Washington Univ, Washington, DC USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. GRECC, Pittsburgh, PA USA. RP Wambaugh, JL (reprint author), Univ Utah, 1201 Behav Sci Bldg,390 S 1530 E, Salt Lake City, UT 84112 USA. NR 28 TC 49 Z9 49 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD OCT-NOV PY 2001 VL 15 IS 10-11 BP 933 EP 950 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA 483EW UT WOS:000171621600006 ER PT J AU McNeil, MR Doyle, PJ Fossett, TRD Park, GH Goda, AJ AF McNeil, MR Doyle, PJ Fossett, TRD Park, GH Goda, AJ TI Reliability and concurrent validity of the information unit scoring metric for the story retelling procedure SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Clinical Aphasiology Conference CY MAY, 2000 CL WAIKOLON, HAWAII ID CONNECTED SPEECH; DISCOURSE; APHASIA; ADULTS; TASKS AB This study reports the reliability and concurrent validity of the information units (IU) metric as an efficient method for quantifying the amount of information comprehended and reproduced on the Story Retelling Procedure (SRP) (Doyle et al., 2000). Subjects were 31 normal adults and 15 adults with aphasia. Significant and moderately high correlation coefficients were obtained for subjects with aphasia between %IUs and most linguistic measures including the correct information unit (Nicholas & Brookshire 1993, 1995) while low and non-significant correlations were found for many measures of language productivity, efficiency, and disruption. The %IUs among the four SRP forms within group was non-significant (p>.05) and correlations were significant and high. Normal speakers produced significantly greater %IUs than aphasic speakers. Standard error of measurement was low across forms for both groups (3-4%) and the range of individual subjects' performance overlapped between 20 and 27% for the group with aphasia and between 36 and 55% for the normal group. These results support the conclusion that %IU is a reliable and valid measure and differentiates aphasic from normal individuals better than normal individuals from persons with aphasia. C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 30 TC 32 Z9 32 U1 1 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD OCT-NOV PY 2001 VL 15 IS 10-11 BP 991 EP 1006 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 483EW UT WOS:000171621600010 ER PT J AU Unutzer, J Rubenstein, L Katon, WJ Tang, LQ Duan, N Lagomasino, IT Wells, KB AF Unutzer, J Rubenstein, L Katon, WJ Tang, LQ Duan, N Lagomasino, IT Wells, KB TI Two-year effects of quality improvement programs on medication management for depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TREATING MAJOR DEPRESSION; PRIMARY-CARE PATIENTS; LONG-TERM OUTCOMES; RANDOMIZED TRIAL; MENTAL-DISORDERS; GUIDELINES; INTERVENTIONS; STRATEGIES; IMPACT AB Background: Significant underuse of evidence-based treatments for depression persists in primary care. We examined the effects of 2 primary care-based quality improvement (QI) programs on medication management for depression. Methods: A total of 1356 patients with depressive symptoms (60% with depressive disorders and 40% with subthreshold depression) from 46 primary care practices in 6 nonacademic managed care organizations were enrolled in a randomized controlled trial of QI for depression. Clinics were randomized to usual care or to 1 of 2 QI programs that involved training of local experts who worked with patients' regular primary care providers (physicians and nurse practitioners) to improve care for depression. In the QI-medications program, depression nurse specialists provided patient education and assessment and followed up patients taking antidepressants for up to 12 months. In the QI-therapy program, depression nurse specialists provided patient education, assessment, and referral to study-trained psychotherapists. Results: Participants enrolled in both QI programs had significantly higher rates of antidepressant use than those in the usual care group during the initial 6 months of the study (52% in the QI-medications group, 40% in the QI-therapy group, and 33% in the usual care group). Patients in the QI-medications group had higher rates of antidepressant use and a reduction in long-term use of minor tranquilizers for up to 2 years, compared with patients in the QI-therapy or usual care group. Conclusions: Quality improvement programs for depression in which mental health specialists collaborate with primary care providers can substantially increase rates of antidepressant treatment. Active follow-up by a depression nurse specialist in the QI-medications program was associated with longer-term increases in antidepressant use than in the QI model without such follow-up. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, Los Angeles, CA 90024 USA. Charles R Drew Univ Med & Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90059 USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90059 USA. RAND Corp, Santa Monica, CA USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Unutzer, J (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. FU AHRQ HHS [R01-HS08349]; NIMH NIH HHS [P50 MH54623] NR 34 TC 76 Z9 77 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2001 VL 58 IS 10 BP 935 EP 942 DI 10.1001/archpsyc.58.10.935 PG 8 WC Psychiatry SC Psychiatry GA 478YB UT WOS:000171375400006 PM 11576031 ER PT J AU Kane, JM Marder, SR Schooler, NR Wirshing, WC Umbricht, D Baker, RW Wirshing, DA Safferman, A Ganguli, R McMeniman, M Borenstein, M AF Kane, JM Marder, SR Schooler, NR Wirshing, WC Umbricht, D Baker, RW Wirshing, DA Safferman, A Ganguli, R McMeniman, M Borenstein, M TI Clozapine and haloperidol in moderately refractory schizophrenia - A 6-month randomized and double-blind comparison SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID VIEW AB Background: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison With a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. Methods: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. Results: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine- treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. Conclusions: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms. C1 Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Dept Psychiat, Glen Oaks, NY 11004 USA. W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Zurich, Hosp Psychiat, Dept Psychiat, Zurich, Switzerland. Eli Lilly & Co, Indianapolis, IN 46285 USA. Pfizer Pharmaceut Inc, New York, NY USA. RP Kane, JM (reprint author), Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Dept Psychiat, Glen Oaks, NY 11004 USA. FU NIMH NIH HHS [MH46484, MH46613, MH46672] NR 30 TC 124 Z9 128 U1 4 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2001 VL 58 IS 10 BP 965 EP 972 DI 10.1001/archpsyc.58.10.965 PG 8 WC Psychiatry SC Psychiatry GA 478YB UT WOS:000171375400011 PM 11576036 ER PT J AU Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanley, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Camille, J Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Dubois-Moran, J Callahan, C Evans, C Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, NJ Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY AF Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanley, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Camille, J Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Dubois-Moran, J Callahan, C Evans, C Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, NJ Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY CA AREDS Res Grp TI A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BLUE MOUNTAINS EYE; BEAVER DAM EYE; VISUAL IMPAIRMENT; ORAL ZINC; MACULOPATHY; ANTIOXIDANT; PREVALENCE; PIGMENT; COHORT; RISK AB Background: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Measures: (1)Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline ( : 15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study. C1 Eye Ctr Mem, Albany, NY USA. Emory Univ, Atlanta, GA 30322 USA. Ingalls Mem Hosp, Harvey, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Ctr Clin, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Elman Retina Grp PA, Baltimore, MD USA. Univ Wisconsin, Reading Ctr, Madison, WI USA. Ctr Dis Control & Prevent, Cent Lab, Atlanta, GA USA. NEI, Project Off, Bethesda, MD 20892 USA. RP Kassoff, A (reprint author), Eye Ctr Mem, Albany, NY USA. NR 52 TC 1310 Z9 1344 U1 13 U2 113 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2001 VL 119 IS 10 BP 1417 EP 1436 PG 20 WC Ophthalmology SC Ophthalmology GA 481RD UT WOS:000171532700001 ER PT J AU Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanely, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Werner, JC Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, J Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY AF Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanely, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Werner, JC Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, J Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY CA AREDS Res Grp TI A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss - AREDS Report No. 9 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPACITIES CASE-CONTROL; LENS OPACITIES; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; NUTRIENT INTAKE; EYE DISEASE; RISK; EXTRACTION; PHYSICIANS; NUTRITION AB Background: Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract. Objective: To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss. Design: The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale. Main Outcome Measures: Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (greater than or equal to 15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P = .01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P = .55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment. Conclusion: Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss. C1 Eye Ctr Mem, Albany, NY USA. Emory Univ, Atlanta, GA 30322 USA. Ingalls Mem Hosp, Harvey, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Ctr Clin, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Elman Retina Grp PA, Baltimore, MD USA. Univ Wisconsin, Reading Ctr, Madison, WI 53706 USA. Ctr Dis Control & Prevent, Genet Lab, Atlanta, GA USA. NEI, Project Off, Bethesda, MD 20892 USA. RP Kassoff, A (reprint author), Eye Ctr Mem, Albany, NY USA. NR 49 TC 303 Z9 311 U1 3 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2001 VL 119 IS 10 BP 1439 EP 1452 PG 14 WC Ophthalmology SC Ophthalmology GA 481RD UT WOS:000171532700002 ER PT J AU Yueh, B Souza, PE McDowell, JA Collins, MP Loovis, CF Hedrick, SC Ramsey, SD Deyo, RA AF Yueh, B Souza, PE McDowell, JA Collins, MP Loovis, CF Hedrick, SC Ramsey, SD Deyo, RA TI Randomized trial of amplification strategies SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the American-Auditory-Society CY APR 08, 2000 CL SCOTTSDALE, ARIZONA SP Amer Audit Soc ID QUALITY-OF-LIFE; DIGITAL HEARING-AIDS; MENTAL STATE; IMPAIRMENT; EFFICACY AB Background: Little is known about quality of life after the use of specific types of hearing aids, so it is difficult to determine whether technologies such as programmable circuits and directional microphones are worth the added expense. Objective: To compare the effectiveness of an assistive listening device, a nonprogrammable nondirectional microphone hearing aid, with that of a programmable directional microphone hearing aid against the absence of amplification. Design: Randomized controlled trial. Setting: Audiology clinic at the VA Puget Sound Health Care System, Seattle, Wash. Patients: Sixty veterans with bilateral moderate to severe sensorineural hearing loss completed the trial. Half the veterans (n = 30) had hearing loss that the Veterans Affairs clinic determined was rated as "service connected," which meant that they were eligible for Veterans Affairs-issued hearing aids. Intervention: Veterans with non-service-connected hearing loss, who were ineligible for Veterans Affairs-issued hearing aids, were randomly assigned to no amplification (control arm) or to receive an assistive listening device. Veterans with service-connected loss were randomly assigned to receive either the nonprogrammable hearing aid that is routinely issued ("conventional") or a programmable aid with a directional microphone ("programmable"). Main Outcome Measures: Hearing-related quality of life, self-rated communication ability, adherence to use, and willingness to pay for the amplification devices (measured 3 months after fitting). Results: Clear distinctions were observed between all 4 arms. The mean improvement in hearing-related quality of life (Hearing Handicap Inventory for the Elderly) scores was small for control patients (2.2 points) and patients who received an assistive listening device (4.4 points), excellent for patients who received a conventional device (17.4 points), and substantial for patients who received a programmable device (31.1 points) (P<.001 by the analysis of variance test). Qualitative analyses of free-text diary entries, self-reported communication ability (Abbreviated Profile of Hearing Aid Benefit) scores, adherence to hearing aid use, and willingness to pay for replacement devices showed similar trends. Conclusions: A programmable hearing aid with a directional microphone had the highest level of effectiveness in the veteran population. A nonprogrammable hearing aid with an omnidirectional microphone was also effective compared with an assistive listening device or no amplification. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Ctr Cost & Outcomes REs, Seattle, WA 98195 USA. RP Yueh, B (reprint author), VA Puget Sound Hlth Care Syst, Surg Serv 112OTO, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 32 TC 43 Z9 45 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2001 VL 127 IS 10 BP 1197 EP 1204 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 480CJ UT WOS:000171444100006 PM 11587599 ER PT J AU Hartnick, CJ Hartley, BEJ Lacy, PD Liu, J Bean, JA Willging, P Myer, CM Cotton, RT AF Hartnick, CJ Hartley, BEJ Lacy, PD Liu, J Bean, JA Willging, P Myer, CM Cotton, RT TI Topical mitomycin application after laryngotracheal reconstruction - A randomized, double-blind, placebo-controlled trial SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the American-Society-for-Pediatric-Otolaryngology CY MAY 11, 2000 CL ARIZONA SP Amer Soc Pediatr Otolaryngol ID GLAUCOMA FILTRATION SURGERY; SUBGLOTTIC STENOSIS AB Objective: To explore the effect of mitomycin treatment on the pediatric airway following laryngotracheal reconstruction. Design: Randomized, double-blind, placebo-controlled trial. Patients: Children aged 2 to 17 years with subglottic or upper tracheal stenosis undergoing laryngotracheal reconstruction at a single, tertiary care, children's hospital. Intervention: At the time of extubation or stent removal, the children underwent bronchoscopy and 0.4 mg/mL (2 mL of a 0.2-mg/mL solution of either mitomycin or an equal volume of isotonic sodium chloride was directly applied to the subglottic region for a single application of 2 minutes. These children then underwent interval endoscopy at 2 weeks, 6 weeks, and 3 months postoperatively for assessment of their airways. Results: Granulation tissue was graded on a scale of 0 (none) to 4 (near-total or total occlusion). Videotapes of endoscopies were independently observed and graded by 3 pediatric otolaryngology fellows with a subsequent interobserver agreement of 91.6%. The results were then dichotomized to represent a single cohort in which further surgical intervention would be required and another separate cohort in which further surgery would not be required. At the 1-year mark, interim analysis was performed by a Data Safety and Monitoring Committee. At this time, 13 children had been randomized to the mitomycin-treated arm of the study and I I children to the placebo-treated arm. A 2-tailed Fisher exact test revealed a value of 1.00, The Data Monitoring and Safety Committee advised that the trial should be stopped because the distributions between the 2 populations were almost identical. Conclusion: We cannot reject the null hypothesis that a single topical dose of mitomycin exerts an equal benefit as does isotonic sodium chloride when applied to the pediatric airway after laryngotracheal reconstruction. C1 Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Dept Biostat, Cincinnati, OH 45229 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 55 Z9 62 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2001 VL 127 IS 10 BP 1260 EP 1264 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 480CJ UT WOS:000171444100016 PM 11587609 ER PT J AU Slominski, A Wortsman, J Carlson, AJ Matsuoka, LY Balch, CM Mihm, MC AF Slominski, A Wortsman, J Carlson, AJ Matsuoka, LY Balch, CM Mihm, MC TI Malignant melanoma - An update SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID POLYMERASE-CHAIN-REACTION; TUMOR-INFILTRATING LYMPHOCYTES; ACRAL LENTIGINOUS MELANOMA; PARAFFIN-EMBEDDED PRIMARY; TYROSINASE MESSENGER-RNA; FIBROBLAST GROWTH-FACTOR; STIMULATING HORMONE; CUTANEOUS MELANOMA; HAMSTER MELANOMA; ULTRAVIOLET-RADIATION AB Context.-The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. Objectives.-To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. Methods.-Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. Results.-Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. Conclusions.-(1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products alpha -melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy. C1 Univ Tennessee, Ctr Hlth Sci, Dept Pathol, Memphis, TN 38163 USA. So Illinois Univ, Sch Med, Dept Med, Springfield, IL 62708 USA. Albany Med Ctr, Dept Pathol & Lab Med, Albany, NY USA. Pacific Ctr Dermatol & Phototherapy, Honolulu, HI USA. Johns Hopkins Med Ctr, Dept Surg, Baltimore, MD USA. Johns Hopkins Med Ctr, Dept Oncol, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA. RP Slominski, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Pathol, 576 BMH,899 Madison Ave, Memphis, TN 38163 USA. OI Carlson, John Andrew/0000-0002-6866-6314 NR 168 TC 72 Z9 82 U1 0 U2 8 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2001 VL 125 IS 10 BP 1295 EP 1306 PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 482JX UT WOS:000171574000007 PM 11570904 ER PT J AU Peckham, PH Keith, MW Kilgore, KL Grill, JH Wuolle, KS Thrope, GB Gorman, P Hobby, J Mulcahey, MJ Carroll, S Hentz, VR Wiegner, A AF Peckham, PH Keith, MW Kilgore, KL Grill, JH Wuolle, KS Thrope, GB Gorman, P Hobby, J Mulcahey, MJ Carroll, S Hentz, VR Wiegner, A CA Implantable Neuroprothesis Res Grp TI Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: A multicenter study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE activities of daily living; electric stimulation; hand; neuroprosthesis; rehabilitation; spinal cord injuries ID FUNCTIONAL ELECTRICAL-STIMULATION; NEUROMUSCULAR STIMULATION; RELEASE; SYSTEM; INDIVIDUALS; ADOLESCENTS; PATIENT AB Objective: To evaluate an implanted neuroprosthesis that allows tetraplegic users to control grasp and release in 1 hand. Design: Multicenter cohort trial with at least 3 years of follow-up. Function for each participant was compared before and after implantation, and with and without the neuroprosthesis activated. Setting: Tertiary spinal cord injury (SCI) care centers, 8 in the United States, 1 in the United Kingdom, and 1 in Australia. Participants: Fifty-one tetraplegic adults with C5 or C6 SCIs. Intervention: An implanted neuroprosthetic system, in which electric stimulation of the grasping muscles of 1 arm are controlled by using contralateral shoulder movements, and concurrent tendon transfer surgery. Assessed participants' ability to grasp, move, and release standardized objects; degree of assistance required to perform activities of daily living (ADLs), device usage; and user satisfaction. Main Outcome Measures: Pinch force; grasp and release tests; ADL abilities test and ADL assessment test; and user satisfaction survey. Results: Pinch force was significantly greater with the neuroprosthesis in all available 50 participants, and grasp-release abilities were improved in 49. All tested participants (49/49) were more independent in performing ADLs with the neuroprosthesis than they were without it. Home use of the device for regular function and exercise was reported by over 90% of the participants, and satisfaction with the neuroprosthesis was high. Conclusions: The grasping ability provided by the neuroprosthesis is substantial and lasting. The neuroprosthesis is safe, well accepted by users, and offers improved independence for a population without comparable alternatives. C1 Metrohlth Med Ctr, Cleveland, OH 44109 USA. Dept Vet Affairs, Rehabil Res & Dev Serv, Cleveland, OH USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. NeuroControl Corp, Cleveland, OH USA. VA Maryland Healthcare Syst, Baltimore, MD USA. Univ Maryland Med Syst, Baltimore, MD USA. Salisbury Dist Hosp, Salisbury, Wilts, England. Philadelphia Shriners Hosp, Philadelphia, PA USA. Univ Melbourne, Melbourne, Vic, Australia. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Palo Alto Vet Affairs Hlth Care Serv, Palo Alto, CA USA. VA Boston Hlth Care Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Peckham, PH (reprint author), Metrohlth Med Ctr, Hamann 601,2500 MetroHlth Dr, Cleveland, OH 44109 USA. EM pxp2@po.cwru.edu OI Kilgore, Kevin/0000-0002-2642-9855 FU NCRR NIH HHS [5M01RR00080] NR 34 TC 118 Z9 122 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2001 VL 82 IS 10 BP 1380 EP 1388 DI 10.1053/apmr.2001.25910 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 479NQ UT WOS:000171410800006 PM 11588741 ER PT J AU Fitzgerald, SG Cooper, RA Boninger, ML Rentschler, AJ AF Fitzgerald, SG Cooper, RA Boninger, ML Rentschler, AJ TI Comparison of fatigue life for 3 types of manual wheelchairs SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE durable medical equipment; materials testing; reimbursement mechanisms; rehabilitation; United States AB Objectives: To examine 3 types of manual wheelchairs-ultralight wheelchairs (UWs), lightweight wheelchairs (LWs), and depot wheelchairs (DWs)-and to compare the fatigue life between the wheelchair types. Design: A database of different manual wheelchairs tested according to the International Organization for Standardization (ISO). Fatigue life was determined by using standards that define methods accepted internationally using double-drum and curb-drop testing equipment. Setting: A rehabilitation engineering center. Specimens: Sixty-one manual wheelchairs: 25 DWs, 22 UWs, and 14 LWs. Main Outcome Measures: Wheelchairs were examined for differences in fatigue life based on equivalent cycles. Unique survival curves were fit and compared for each wheelchair type. Results: The UWs lasted the longest, with a mean of 309,362 equivalent cycles. The DWs faired the worst, with a mean of 117,210 equivalent cycles. The Kaplan-Meier survival curves Were significantly different (p < .001). with the UWs having the longest fatigue life. Conclusion: Fatigue life for UWs is significantly greater (p < .05) than LWs and DWs, indicating wheelchairs differ in durability. C1 VA Pittsburgh Healthcare Syst, 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 Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 151-RI,7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 15 TC 33 Z9 34 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2001 VL 82 IS 10 BP 1484 EP 1488 DI 10.1053/apmr.2001.26139 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 479NQ UT WOS:000171410800023 PM 11588758 ER PT J AU Zhang, ZX Wu, X Limbaugh, BH Bridges, SL AF Zhang, ZX Wu, X Limbaugh, BH Bridges, SL TI Expression of recombination-activating genes and terminal deoxynucleotidyl transferase and secondary rearrangement of immunoglobulin kappa light chains in rheumatoid arthritis synovial tissue SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT Autoantibodies and Autoimmunity Workshop CY JUN 24-28, 1999 CL OSLO, NORWAY ID B-CELLS; RECEPTOR REVISION; GERMINAL-CENTERS; HEPATITIS-C; LYMPHOCYTES; MEMBRANE; PATIENT; DIFFERENTIATION; INTERLEUKIN-7; ANTIBODIES AB Objective. Lymphocytic infiltrates in rheumatoid arthritis (RA) synovium often resemble lymphoid follicles and contain clonally related Ig transcripts, suggesting in situ antigen-dependent B cell selection. Recent reports have shown expression of recombination-activating genes (RAGs) and concurrent secondary rearrangement of Ig genes in normal peripheral lymphoid organs (receptor revision). We sought to determine if RAG-mediated receptor revision of Ig kappa light chains occurs in B cells within the RA synovium. Because we previously reported enhanced N-region addition at V-L-J(L) joins in clonally expanded light-chain transcripts from RA synovium, we also sought expression of terminal deoxynucleotidyl transferase (TdT), which is normally expressed only in B cell precursors or immature B cells. Methods. Reverse transcription-polymerase chain reaction (PCR) was used to detect RAG and TdT transcripts from unselected and B cell-enriched synovial and peripheral blood mononuclear cells obtained from 12 RA patients. Activity of RAG protein was sought using ligation-mediated PCR to detect recombination intermediates, and immunohistochemistry was performed to identify RAG+ cells within synovia. Results. We found evidence of RAG-mediated secondary Ig ic light chain rearrangements in about one-third of RA synovia. TdT expression was found in several samples, but did not correlate with RAG expression. Conclusion. RAG-mediated secondary Ig rearrangements of kappa light chains may contribute to the local production of antibodies to autoantigens (e.g., rheumatoid factor) or exogenous antigens, or it may represent a failed attempt at immune tolerance. TdT expression suggests the presence of immature B cells in RA synovia. These findings have important implications for the local generation of antibodies in RA and other chronic inflammatory diseases. C1 Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Bridges, SL (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, 415 Lyons Harrison Res Bldg, Birmingham, AL 35294 USA. FU NIAMS NIH HHS [R29-AR-44243] NR 35 TC 30 Z9 31 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2001 VL 44 IS 10 BP 2275 EP 2284 DI 10.1002/1529-0131(200110)44:10<2275::AID-ART390>3.0.CO;2-K PG 10 WC Rheumatology SC Rheumatology GA 498CB UT WOS:000172491300010 PM 11665968 ER PT J AU Safren, SA Otto, MW Worth, JL Salomon, E Johnson, W Mayer, K Boswell, S AF Safren, SA Otto, MW Worth, JL Salomon, E Johnson, W Mayer, K Boswell, S TI Two strategies to increase adherence to HIV antiretroviral medication: Life-steps and medication monitoring SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE adherence; compliance; HIV; AIDS; antiretroviral therapy ID PROTEASE INHIBITORS; SOCIAL SUPPORT; ALCOHOL-CONSUMPTION; SEXUAL-BEHAVIOR; THERAPY; AIDS; INTERVENTION; PREVENTION; CLINICIAN; TRIAL AB Advances in the medical treatment of HIV have made it clear that adherence to highly active antiretroviral treatment is a crucial feature for treatment success. The present paper had two goals: (1) to examine psychosocial predictors of adherence in persons receiving HIV antiretroviral therapy; (2) to compared two minimal-treatment interventions to increase HIV medication adherence in a subset of persons who self-reported less than perfect adherence. One of the interventions, Life-Steps, is a single-session intervention utilizing cognitive-behavioral, motivational interviewing, and problem-solving techniques. The other intervention, self-monitoring, utilizes a pill-diary and an adherence questionnaire alone. Significant correlates of adherence included depression, social support, adherence self-efficacy, and punishment beliefs about HIV. Depression was a significant unique predictor of adherence over and above the other variables. Both interventions yielded improvement in adherence from baseline, and the Life-Steps intervention showed faster improvements in adherence for persons with extant adherence problems. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Fenway Community Hlth, Boston, MA USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. RI Manzotti, Grazia/C-5985-2008 NR 39 TC 152 Z9 154 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD OCT PY 2001 VL 39 IS 10 BP 1151 EP 1162 DI 10.1016/S0005-7967(00)00091-7 PG 12 WC Psychology, Clinical SC Psychology GA 477CK UT WOS:000171265400002 PM 11579986 ER PT J AU Viguera, AC Baldessarini, RJ Tondo, L AF Viguera, AC Baldessarini, RJ Tondo, L TI Response to lithium maintenance treatment in bipolar disorders: comparison of women and men SO BIPOLAR DISORDERS LA English DT Article DE bipolar I and II disorders; course of illness; depression; lithium; maintenance treatment; mania; sex ID MANIC-DEPRESSIVE ILLNESS; GENDER; RISK AB Objectives: Possible sex differences in responses to mood-stabilizing treatment remain poorly defined. Since women with bipolar disorder reportedly have more features that may predict a poor prognosis (depression and rapid cycling), we tested the hypothesis that women respond less well to lithium maintenance treatment. Methods: Clinical characteristics of 360 women and men with DSM-IV bipolar I or II disorder were compared before and during clinical lithium maintenance monotherapy in a mood disorders clinic by preliminary bivariate comparisons, multivariate analysis, and survival analysis of time stable during treatment. Results: Women (n = 229) versus men (n = 131) were: more likely to have type Il disorder (1.6 times), 3.2 years older at illness onset, more often depressed-before-manic (1.4 times), considered unipolar depressive 1.9 years longer and started maintenance treatment 5.5 years later. However, women differed little from men before treatment in overall morbidity, average episode frequency and risk of suicide attempts. Contrary to prediction, women showed non-significantly superior responses to lithium treatment, and a significant 60% longer median time before a first recurrence during treatment, despite 7% lower average serum lithium concentrations. Conclusions: Women were diagnosed as bipolar later than men with corresponding delay of lithium maintenance treatment that proved to be at least as effective as in men. C1 Massachusetts Gen Hosp, Psychiat Serv, Perinatal Psychopharmacol Unit, Boston, MA 02114 USA. Int Consortium Bipolar Disorder Res, Boston, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program, McLean Div, Boston, MA 02114 USA. RP Viguera, AC (reprint author), Massachusetts Gen Hosp, Psychiat Serv, Perinatal Psychopharmacol Unit, Fruit St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-01609, MH-47370] NR 30 TC 44 Z9 44 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2001 VL 3 IS 5 BP 245 EP 252 DI 10.1034/j.1399-5618.2001.30503.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 484VH UT WOS:000171709900003 PM 11903207 ER PT J AU John, MR Wickert, H Zaar, K Jonsson, KB Grauer, A Ruppersberger, P Schmidt-Gayk, H Murer, H Ziegler, R Blind, E AF John, MR Wickert, H Zaar, K Jonsson, KB Grauer, A Ruppersberger, P Schmidt-Gayk, H Murer, H Ziegler, R Blind, E TI A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and fibroblast growth factor-23 expressing sinusidal malignant schwannoma SO BONE LA English DT Article DE oneogenic osteomalacia; PHEX; fibroblast growth factor-23 (FGF-23); phosphate; malignant schwannoma ID TUMOR-INDUCED OSTEOMALACIA; X-LINKED HYPOPHOSPHATEMIA; RENAL PHOSPHATE-TRANSPORT; NERVE SHEATH TUMORS; PARATHYROID-HORMONE; RICKETS; GENE; CLONING; MICE; NEUROFIBROMATOSIS AB Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characterized biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D-3, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle weakness. We present a patient with a malignant schwannoma as the underlying cause of this disorder. A permanent cell line (HMS-97) derived from this tumor showed evidence of neuroendocrine differentiation by immunohistochemistry and of neurosecretory activity by electron microscopy. The cell line did express PHEX (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) and FGF-23 (fibroblast growth factor-23) transcripts on northern hybridization; however, none of the known mutations from the related mendelian disorders of X-linked hypophosphatemic rickets or autosomal-dominant hypophosphatemic rickets could be detected. Tumor cell (HMS-97)derived conditioned medium did not inhibit phosphate transport in a standard opossum kidney cell assay and in animal experiments. The medium also showed no PTH1- or PTH2-receptor-stimulating bioactivity. HMS-97 cells might be useful for further studies that aim to determine the genetic mechanism that leads to the observed PHEX and FGF-23 expression, both of which might have a direct role in the pathogenesis of oncogenic osteomalacia. In addition, these cells might be a useful tool for the investigation of neuroendocrine Schwarm cell function and autoimmune peripheral nerve disease. (Bone 29:393-402; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Heidelberg, Dept Internal Med 1, Heidelberg, Germany. Univ Heidelberg, Dept Anat & Cell Biol, Heidelberg, Germany. Harvard Univ, Sch Med, Boston, MA USA. Lab Grp, Heidelberg, Germany. Univ Zurich, Dept Anat, Zurich, Switzerland. Univ Wurzburg, Dept Med, Wurzburg, Germany. RP John, MR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,WEL 501, Boston, MA 02114 USA. NR 43 TC 26 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2001 VL 29 IS 4 BP 393 EP 402 DI 10.1016/S8756-3282(01)00586-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488CA UT WOS:000171916100012 PM 11595624 ER PT J AU Savage, CR Deckersbach, T Heckers, S Wagner, AD Schacter, DL Rauch, SL AF Savage, CR Deckersbach, T Heckers, S Wagner, AD Schacter, DL Rauch, SL TI Prefrontal systems underlying spontaneous and directed strategic processing during verbal learning SO BRAIN AND COGNITION LA English DT Meeting Abstract ID WORKING-MEMORY; FUNCTIONAL MRI; CORTEX C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 5 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT-NOV PY 2001 VL 47 IS 1-2 BP 116 EP 120 PG 5 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 489YR UT WOS:000172021100071 ER PT J AU Shelley, CS Da Silva, N Teodoridis, JM AF Shelley, CS Da Silva, N Teodoridis, JM TI During U937 monocytic differentiation repression of the CD43 gene promoter is mediated by the single-stranded DNA binding protein Pur alpha SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD43; Pur alpha; transcription; leucocyte adhesion; differentiation ID LEUKOCYTE INTEGRIN PROMOTER; T-LYMPHOCYTE ADHESION; TRANSCRIPTION FACTOR; HUMAN LEUKOSIALIN; SIALOPHORIN CD43; MAJOR SIALOGLYCOPROTEIN; DOWN-REGULATION; CD11B PROMOTER; NUCLEAR FACTOR; MYELOID CELLS AB Human CD43 is an abundant, heavily glycosylated molecule expressed exclusively on the surface of leucocytes. When leucocytes are at rest, CD43 acts to prevent intercellular interaction but during leucocyte differentiation such cell-cell interaction is facilitated by CD43. This change in the function of CD43 is mediated in part by a reduction in its level of expression. Previous studies have implicated proteolytic cleavage events at the cell surface in causing such reduction. Here, we report that, in an in vitro model of leucocyte differentiation, CD43 mRNA levels were also subject to reduction. Specifically, we demonstrated that within 48 h of the cell line U937 being induced to differentiate along the monocytic pathway, CD43 mRNA levels were reduced by 69%. This decline coincided with a decrease in the activity of the CD43 gene promoter mediated by the single-stranded DNA binding protein Pura. Previously, we have demonstrated that Pura mediates induction of the CD11c beta2 integrin promoter during U937 differentiation. Consequently, Pura represents a potential means by which the induction of pro-adhesive molecules and the repression of anti-adhesive molecules is coordinated during leucocyte differentiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Renal Unit, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. RP Shelley, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Renal Unit, Leukocyte Biol & Inflammat Program, 149 13th St, Charlestown, MA 02129 USA. EM shelley@receptor.mgh.harvard.edu FU NIDDK NIH HHS [P01 DK50305, R29 DK50779, P01 DK43351] NR 44 TC 20 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2001 VL 115 IS 1 BP 159 EP 166 DI 10.1046/j.1365-2141.2001.03066.x PG 8 WC Hematology SC Hematology GA 483JN UT WOS:000171632400029 PM 11722429 ER PT J AU Goodman, GE Schaffer, S Bankson, DD Hughes, MP Omenn, GS AF Goodman, GE Schaffer, S Bankson, DD Hughes, MP Omenn, GS CA CARET Co-Investigators TI Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EFFICACY TRIAL CARET; BETA-CAROTENE; ALPHA-TOCOPHEROL; VITAMIN-E; OXIDATIVE STRESS; TIN MINERS; PREVENTION; APOPTOSIS; TOENAILS; DISEASE AB Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (it = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 mug/dl versus 11.77 mug/dl) or prostate cancer cases versus controls (11.48 mug/dl versus 11.43 mug/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Swedish Med Ctr, Tumor Inst, Seattle, WA 98109 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Washington State Univ, Toxicol Lab, Seattle, WA 98195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Goodman, GE (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP859,POB 19024, Seattle, WA 98109 USA. OI Omenn, Gilbert S./0000-0002-8976-6074 FU NCI NIH HHS [2 U01 CA63673]; NIDDK NIH HHS [P30 DK35816] NR 37 TC 63 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1069 EP 1076 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900008 PM 11588133 ER PT J AU Zhong, WX Oberley, TD AF Zhong, WX Oberley, TD TI Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line SO CANCER RESEARCH LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; DNA-BINDING ACTIVITY; HUMAN TUMOR-CELLS; THIOREDOXIN REDUCTASE; CARCINOMA-CELLS; IN-VITRO; GLUTATHIONE PEROXIDASE; INTERVENTION TRIALS; MALIGNANT PHENOTYPE; NIH/3T3 FIBROBLASTS AB The effects of selenium exposure were studied in LNCaP human prostate cancer cells, and this same cell line adapted to selenium over 6 months to compare acute versus chronic effects of sodium selenite, the latter most closely resembling human clinical trials on the effects of selenium in cancer prevention and therapy. Our results demonstrated that oxidative stress was induced by sodium selenite at high concentrations in both acute and chronic treatments, but outcomes were different. After acute exposure to selenite, cells exhibited mitochondrial injury and cell death, mainly apoptosis. After chronic exposure to selenite, cells showed growth inhibition caused by cell cycle arrest, increased numbers of mitochondria and levels of mitochondrial enzymes, and only minimal induction of apoptosis. Immunoblotting analysis revealed that multiple proteins were up-regulated by chronic exposure to selenite. Among them, only up-regulation of manganese superoxide dismutase and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), proteins known to be redox sensitive and to have cell cycle regulatory functions, correlated with cell growth inhibition. Our results in selenite-adapted cells suggest that selenium may exert its effects in human prostate cancer cells by altering intracellular redox state, which subsequently results in cell cycle block. C1 William S Middleton Mem Vet Adm Med Ctr, Pathol Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. NR 56 TC 125 Z9 129 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7071 EP 7078 PG 8 WC Oncology SC Oncology GA 479PB UT WOS:000171411800021 PM 11585738 ER PT J AU Hamblin, MR Miller, JL Rizvi, I Ortel, B Maytin, EV Hasan, T AF Hamblin, MR Miller, JL Rizvi, I Ortel, B Maytin, EV Hasan, T TI Pegylation of a chlorin(e6) polymer conjugate increases tumor targeting of photosensitizer SO CANCER RESEARCH LA English DT Article ID PHOTODYNAMIC THERAPY; POLYETHYLENE-GLYCOL; OVARIAN-CANCER; SUBCELLULAR-LOCALIZATION; PHOTOPHYSICAL PROPERTIES; QUANTITATIVE-ANALYSIS; MONOCLONAL-ANTIBODY; XENOGRAFT MODEL; PHOTOFRIN-II; MURINE MODEL AB Photodynamic therapy is emerging as a viable modality for the treatment of many cancers. A limiting factor in its use against intracavity tumors such as disseminated ovarian cancer is insufficient selectivity of the photosensitizer for tumor compared with normal tissue. We report on an approach to improve tumor targeting by exploiting differences between cell types and by chemical modification of a photosensitizer conjugate. Attachment of polyethylene glycol (pegylation) to a polyacetylated conjugate between poly-l-lysine and chlorin(c6) increased the relative phototoxicity in vitro toward an ovarian cancer cell line (OVCAR-5) while reducing it toward a macrophage cell line (J774), compared with the nonpegylated conjugate. Surprisingly, the increased phototoxicity of the pegylated conjugate correlated with reduced oxygen consumption. Pegylation also reduced the tendency of the conjugate to aggregate and reduced the consumption of oxygen when the conjugates were illuminated in solution in serum containing medium, suggesting a switch in photochemical mechanism from type II (singlet oxygen) to type I (radicals or electron transfer). Pegylation led to more mitochondrial localization as shown by confocal fluorescence microscopy in OVCAR-5 cells, and, on illumination, produced a switch in cell death mechanism toward apoptosis not seen with J774 cells. Conjugates were injected i.p. into nude mice bearing i.p. OVCAR-5 tumors, and the pegylated conjugate gave higher amounts of photosensitizer in tumor and higher tumor:normal tissue ratios and increased the depth to which the chlorin(c6) penetrated into the peritoneal wall. Taken together, these results suggest that pegylation of a polymer-photosensitizer conjugate improves tumor-targeting and may increase the efficacy of photodynamic therapy for ovarian cancer. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Endocrinol, Boston, MA 02115 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol, 50 Blossom St WEL224, Boston, MA 02114 USA. OI Rizvi, Imran/0000-0001-9673-4700; Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [P01 CA084203, R01 CA083882]; NIAMS NIH HHS [R01 AR40352] NR 44 TC 100 Z9 105 U1 6 U2 27 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7155 EP 7162 PG 8 WC Oncology SC Oncology GA 479PB UT WOS:000171411800032 PM 11585749 ER PT J AU Ortiz, BH Ailawadi, M Colitti, C Muto, MG Deavers, M Silva, EG Berkowitz, RS Mok, SC Gershenson, DM AF Ortiz, BH Ailawadi, M Colitti, C Muto, MG Deavers, M Silva, EG Berkowitz, RS Mok, SC Gershenson, DM TI Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors SO CANCER RESEARCH LA English DT Article ID TERM FOLLOW-UP; PERITONEAL IMPLANTS; MOLECULAR ANALYSIS; EPITHELIAL TUMORS; CLONAL ORIGIN; HETEROZYGOSITY; IMMUNOREACTIVITY; TUMORIGENESIS; MALIGNANCY; BEHAVIOR AB The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients,p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol, Boston, MA 02115 USA. Univ Penn, Med Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19103 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gynecol Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Ortiz, BH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. NR 37 TC 41 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7264 EP 7267 PG 4 WC Oncology SC Oncology GA 479PB UT WOS:000171411800047 PM 11585764 ER PT J AU Wu, CL Kirley, SD Xiao, H Chuang, YN Chung, DC Zukerberg, LR AF Wu, CL Kirley, SD Xiao, H Chuang, YN Chung, DC Zukerberg, LR TI Cables enhances Cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers SO CANCER RESEARCH LA English DT Article ID HUMAN COLORECTAL CANCERS; TUMOR-SUPPRESSOR GENES; INSITU HYBRIDIZATION; SOMATIC ALTERATIONS; FREQUENT LOSS; DPC4 GENE; DCC GENE; CYCLIN-A; IN-VIVO; PROTEIN AB Cyclin-dependent kinase 2 (cdk2) is a small serine/threonine kinase that regulates cell cycle progression. Cdk2 activity is tightly controlled by several mechanisms, including phosphorylation and dephosphorylation events. Cables is a recently described novel cdk-interacting protein. In proliferating cells, Cables was predominantly localized in the nucleus by cell fractionation and immunostaining. Expression of Cables in HeLa cells inhibited cell growth and colony formation. Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1 protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase activity. The gene encoding Cables is located on human chromosome 18q11-12, a site that is frequently lost in squamous, colon, and pancreas cancers. We found that Cables was strongly expressed in normal human epithelial cells including squamous and glandular mucosa. Breast and pancreatic cancers show strong Cables expression; however, loss of Cables expression was found in approximately 50-60% of primary colon and head and neck cancer specimens. Lack of Cables expression was associated with loss of heterozygosity on chromosome 18q11. The data provide evidence for a Cables-mediated interplay between cdk2 and Wee1 that leads to inhibition of cell growth. Conversely, loss of Cables may cause uncontrolled cell growth and enhance tumor formation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 69198 USA. Univ Nebraska, Med Ctr, Eppley Canc Inst, Omaha, NE 69198 USA. RP Zukerberg, LR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2, Boston, MA 02114 USA. NR 43 TC 47 Z9 53 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7325 EP 7332 PG 8 WC Oncology SC Oncology GA 479PB UT WOS:000171411800056 PM 11585773 ER PT J AU Wise, JN Schaefer, RF Read, RC AF Wise, JN Schaefer, RF Read, RC TI Primary pulmonary plasmacytoma - A case report SO CHEST LA English DT Article DE primary pulmonary plasmacytoma; renal failure ID MYELOMA AB Most extramedullary plasmacytomas are associated with the upper respiratory tract. Primary pulmonary plasmacytomas are rare, and the treatment is surgical excision. This malignancy advances to multiple myeloma in a minority of patients. The patient in our case report is the first to experience renal failure due to hematologic monoclonal gammopathy. Postoperatively, serum protein electrophoresis reverted to normal. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Cent Arkansas Vet Healthcare Ctr, Dept Anat Pathol, Little Rock, AR USA. Cent Arkansas Vet Healthcare Ctr, Dept Gen Thorac Surg, Little Rock, AR USA. RP Wise, JN (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. NR 4 TC 11 Z9 14 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2001 VL 120 IS 4 BP 1405 EP + DI 10.1378/chest.120.4.1405 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 483KL UT WOS:000171634500057 PM 11591589 ER PT J AU Kamal, M Wakelin, D Ouellette, AJ Smith, A Podolsky, DK Mahida, YR AF Kamal, M Wakelin, D Ouellette, AJ Smith, A Podolsky, DK Mahida, YR TI Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T-spiralis-infected mice SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE innate immunity; defensin; goblet cells ID MOUSE SMALL INTESTINE; TRICHINELLA-SPIRALIS; METALLOPROTEINASE MATRILYSIN; TREFOIL FACTOR; GROWTH-FACTOR; HOST-DEFENSE; EPITHELIUM; LOCALIZATION; IMMUNITY; RENEWAL AB Secretions of Paneth, intermediate and goblet cells have been implicated in innate intestinal host defense. We have investigated the role of T cells in effecting alterations in small intestinal epithelial cell populations induced by infection with the nematode Trichinella spiralis. Small intestinal tissue sections from euthymic and athymic (nude) mice, and mice with combined deficiency in T-cell receptor beta and delta genes [TCR(beta/delta)(-/-)] infected orally with T. spiralis larvae, were examined by electron microscopy and after histochemical and lineage-specific immunohistochemical staining. Compared with uninfected controls, Paneth and intermediate cell numbers increased significantly in infected euthymic and nude mice but not infected TCR(beta/delta)(-/-) mice. Transfer of mesenteric lymph node cells before infection led to an increase in Paneth and intermediate cells in TCR(beta/delta)(-/-) mice. In infected euthymic mice, Paneth cells and intermediate cells expressed cryptdins (alpha -defensins) but not intestinal trefoil factor (ITF), and goblet cells expressed ITF but not cryptdins. In conclusion, a unique, likely thymic-independent population of mucosal T cells modulates innate small intestinal host defense in mice by increasing the number of Paneth and intermediate cells in response to T. spiralis infection. C1 Univ Nottingham, Sch Biol Sci, Nottingham NG7 2RD, England. Univ Nottingham, Div Gastroenterol, Nottingham NG7 2RD, England. Univ Calif Irvine, Dept Pathol, Irvine, CA 92717 USA. Inst Anim Hlth, Compton, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mahida, YR (reprint author), Univ Nottingham Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. NR 37 TC 57 Z9 63 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD OCT PY 2001 VL 126 IS 1 BP 117 EP 125 DI 10.1046/j.1365-2249.2001.01589.x PG 9 WC Immunology SC Immunology GA 485HW UT WOS:000171749200016 PM 11678907 ER PT J AU Hahn, WC AF Hahn, WC TI Telomerase and cancer: Where and when? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CATALYTIC SUBUNIT GENE; HUMAN TUMOR-CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 2001 VL 7 IS 10 BP 2953 EP 2954 PG 2 WC Oncology SC Oncology GA 482KD UT WOS:000171574600001 PM 11595681 ER PT J AU Miller, KK Daniels, GH AF Miller, KK Daniels, GH TI Association between lithium use and thyrotoxicosis caused by silent thyroiditis SO CLINICAL ENDOCRINOLOGY LA English DT Article ID PSYCHIATRIC-PATIENTS; HYPOTHYROID PATIENTS; LONG-TERM; THERAPY; DISEASE; THYROTROPIN; HYPERTHYROIDISM; EXPRESSION; DEPRESSION; PREVALENCE AB Objective To determine the incidence of silent thyroiditis in lithium users and characterize lithium-associated thyrotoxicosis. Design Retrospective record review. Patients 400 consecutive patients (300 with Graves' disease and 100 with silent thyroiditis) who underwent radioiodine scanning of the thyroid. Measurements Odds of lithium exposure. Results The odds of lithium exposure were increased 4.7-fold in patients with silent thyroiditis compared with those with Graves' disease (95% CI: 1.3, 17). Lithium-associated silent thyroiditis occurred with an incidence rate of approximately 1.3 cases per 1000 person-years, and lithium-associated thyrotoxicosis occurred with an incidence rate of approximately 2.7 cases per 1000 person-years, higher than the reported incidence rates of silent thyroiditis (< 0.03-0.28 cases per 1000 person-years) and of thyrotoxicosis (0.8-1.2 cases per 1000 person-years) in the general population. Conclusions Thyrotoxicosis caused by silent thyroiditis might be associated with lithium use. C1 Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Thyroid Associates,WACC 730 S, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Thyroid Associates,WACC 730 S, Boston, MA 02114 USA. NR 58 TC 41 Z9 42 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2001 VL 55 IS 4 BP 501 EP 508 DI 10.1046/j.1365-2265.2001.01381.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 482ZG UT WOS:000171606700012 PM 11678833 ER PT J AU Simko, JP Caliendo, A Versalovic, J AF Simko, JP Caliendo, A Versalovic, J TI Laboratory diagnosis of herpes simplex virus infections of the CNS by PCP: Correlation with clinical presentation and patient history SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Emory Univ, Sch Med, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 188 BP 1120 EP 1120 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900214 ER PT J AU Urban, AW Safdar, N Wand, PJ Brown-Elliott, BA Wallace, RJ AF Urban, AW Safdar, N Wand, PJ Brown-Elliott, BA Wallace, RJ TI A cluster of Mycobacterium lentiflavum clinical isolates originally identified as M. simiae complex SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Wisconsin, Sch Med, Madison, WI USA. Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. Univ Texas Hlth Ctr, Tyler, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 333 BP 1145 EP 1145 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900359 ER PT J AU Gorse, GJ O'Connor, TZ Young, SL Bradley, SF Nichol, KL Strickland, JH Paulson, DM Foster, RA Fulambarker, A Shigeoka, JW Stasek, JE Boardman, K Mendelman, PM AF Gorse, GJ O'Connor, TZ Young, SL Bradley, SF Nichol, KL Strickland, JH Paulson, DM Foster, RA Fulambarker, A Shigeoka, JW Stasek, JE Boardman, K Mendelman, PM TI Efficacy of live, cold-adapted, influenza virus vaccine, trivalent (CAIV-T) and inactivated influenza virus vaccine (TVV) in adults with chronic obstructive pulmonary disease (COPD): A VA cooperative study SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 St Louis Univ, St Louis, MO 63103 USA. Vet Adm Med Ctr, St Louis, MO 63125 USA. VA Cooperat Study Program, W Haven, CT USA. VA Med Ctr, Durham, NC USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. VA Med Ctr, Minneapolis, MN USA. Vet Adm Med Ctr, Birmingham, AL USA. Vet Adm Med Ctr, Richmond, VA 23249 USA. VA Med Ctr, Gainesville, FL USA. Vet Adm Med Ctr, N Chicago, IL 60064 USA. VA Med Ctr, Salt Lake City, UT USA. VA Med Ctr, Houston, TX USA. VA Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. Aviron, Mt View, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 364 BP 1150 EP 1150 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900390 ER PT J AU Wanahita, A Goldsmith, EA Musher, DM Clarridge, JE Rubio, J Trial, J AF Wanahita, A Goldsmith, EA Musher, DM Clarridge, JE Rubio, J Trial, J TI Interaction between human polymorphonuclear leukocytes (PMN) and Streptococcus milleri group bacteria SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 585 BP 1188 EP 1188 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900611 ER PT J AU Hajjeh, RA Sofair, A Harrison, L Lyon, GM Brandt, ME Arthington-Skaggs, BA Morgan, J Mirza, S Phelan, M Thomson-Sanza, L Huie, S Yeo, L Pass, M Warnock, DW AF Hajjeh, RA Sofair, A Harrison, L Lyon, GM Brandt, ME Arthington-Skaggs, BA Morgan, J Mirza, S Phelan, M Thomson-Sanza, L Huie, S Yeo, L Pass, M Warnock, DW TI Fluconazole resistance among Candida bloodstream isolates: Incidence and correlation with outcome from a population-based study SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 CDC, Atlanta, GA 30333 USA. CT Emerging Infect Program, Hartford, CT USA. MD Emerging Infect Program, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 641 BP 1197 EP 1197 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900667 ER PT J AU Islam, SA Cohen, GB Noble, N Lau, C He, S Altfeld, MA Rosenberg, ES Walker, BD Kalams, SA AF Islam, SA Cohen, GB Noble, N Lau, C He, S Altfeld, MA Rosenberg, ES Walker, BD Kalams, SA TI T-Cell receptor repertoire analysis of live-sorted antigen-specific T-cells SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 653 BP 1200 EP 1200 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900679 ER PT J AU Shelburne, SA Hamill, RJ Rodriguez-Barradas, MC Greenberg, SB Gathe, JC Trautner, B Visnegarwala, T Atmar, RL AF Shelburne, SA Hamill, RJ Rodriguez-Barradas, MC Greenberg, SB Gathe, JC Trautner, B Visnegarwala, T Atmar, RL TI Immune reconstitution inflammatory syndrome (IRS): Emergence of a unique syndrome during highly active antiretroviral therapy (HAART) SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. VAMC, Houston, TX USA. Ben Taub Gen Hosp, Houston, TX 77030 USA. Pk Plaza Hosp, Houston, TX USA. Thomas St Clin, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 660 BP 1201 EP 1201 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900686 ER PT J AU Stone, VE Sliney, A Smith, J Mayer, KH AF Stone, VE Sliney, A Smith, J Mayer, KH TI Lack of efficacy of a low-cost intervention to improve adherence to HAART SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Hosp Rhode Isl, Pawtucket, RI USA. NR 0 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 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 701 BP 1208 EP 1208 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900727 ER PT J AU Norris, PJ Moffett, HF Walker, BD Rosenberg, ES AF Norris, PJ Moffett, HF Walker, BD Rosenberg, ES TI Multiple effector functions of HIV-1-specific CD4+T cell clones SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 779 BP 1221 EP 1221 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900805 ER PT J AU Brown, SM Theobald, DA Sands, K Hahn, M Goldmann, DA AF Brown, SM Theobald, DA Sands, K Hahn, M Goldmann, DA TI Moving averages and cumulative sums in automated surveillance of resistant nosocomial infections SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vecna Technol Inc, Hyattsville, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 800 BP 1225 EP 1225 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900826 ER PT J AU Cornia, PB Amory, JK Fraser, S Saint, S Lipsky, BA AF Cornia, PB Amory, JK Fraser, S Saint, S Lipsky, BA TI Computerized order entry decreases duration of indwelling urinary catheterization SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 VA Puget Sound HCS, Seattle, WA USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 803 BP 1225 EP 1225 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900829 ER PT J AU Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW AF Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW TI Antifungal susceptibility testing: Practical aspects and current challenges SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID IN-VITRO SUSCEPTIBILITY; AMPHOTERICIN-B SUSCEPTIBILITY; BROTH MICRODILUTION METHODS; FLUCONAZOLE-RESISTANT CANDIDA; LABORATORY STANDARDS METHOD; MEDIATED GROWTH-INHIBITION; VIRUS-INFECTED PATIENTS; TIME-KILL METHODS; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX 77030 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. NCI, Pediat Branch, Infect Dis Sect, Bethesda, MD 20892 USA. New York State Dept Hlth, Albany, NY 12201 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. Inst Med Sci, Aberdeen, Scotland. Vet Adm Med Ctr, San Antonio, TX 78284 USA. Pfizer Inc, Pfizer Pharmaceut Grp, New York, NY 10017 USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. RP Rex, JH (reprint author), 6431 Fannin,1728 JFB, Houston, TX 77030 USA. NR 218 TC 260 Z9 284 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2001 VL 14 IS 4 BP 643 EP 658 DI 10.1128/CMR.14.4.643-658.2001 PG 16 WC Microbiology SC Microbiology GA 482KP UT WOS:000171575600001 PM 11585779 ER PT J AU Sorenson, SM Gentili, A AF Sorenson, SM Gentili, A TI Bladder herniation within the inguinal canal simulating Paget's disease SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE bladder diseases; bone scan; computed tomography; inguinal hernia C1 Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Sorenson, SM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Radiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2001 VL 26 IS 10 BP 864 EP 866 DI 10.1097/00003072-200110000-00014 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 499BE UT WOS:000172550000014 PM 11564928 ER PT J AU Herndon, JH AF Herndon, JH TI Integrated health systems: Success or failure? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB There continues to be an increasing number of healthcare delivery systems as a result of marketplace changes that include declining reimbursement and increasing costs for healthcare. However, the majority of these systems fail. Failures are a consequence of poor management, lack of a common mission and business rationale, individual's interests that outweigh the entity's interests, and the conflict of cultures. Incremental changes will continue, but the healthcare environment will remain unstable for the foreseeable future. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Herndon, JH (reprint author), Partners Orthopaed, 55 Fruit St,GRB 624, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2001 IS 391 BP 284 EP 287 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 481MT UT WOS:000171523600035 PM 11603682 ER PT J AU Tian, W Cohen, DM AF Tian, W Cohen, DM TI Signaling and gene regulation by urea in cells of the mammalian kidney medulla SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT European-Society-for-Comparative-Physiology-and-Biochemistry Congress CY JUL, 2000 CL LIEGE, BELGIUM SP European Soc Comparat Physiol & Biochem DE hypertonicity; expression array; signal transduction; NaCl; urea; kidney; heat shock ID OSMOTIC RESPONSE ELEMENT; RENAL EPITHELIAL-CELLS; COLLECTING DUCT CELLS; MDCK CELLS; HYPEROSMOTIC STRESS; DEPENDENT PATHWAY; BINDING PROTEIN; MIMCD3 CELLS; EXPRESSION; KINASE AB Signaling by urea, although incompletely understood, is relevant both to cells of the mammalian kidney inner medulla and to all cells of the organism in the setting of advanced renal failure with its attendant accumulation of urea in the systemic circulation. The molecular events initiated by urea stress are distinct from those occurring in response to hypertonic stress; urea. activates a characteristic subset of signaling events, which are in large part specific to cultured renal tubular epithelial cells. Interestingly, urea is protective of hypertonic NaCl-inducible apoptosis in this model. Details of this phenomenon are reviewed. The effect of urea has been likened to that of either hypertonicity or of a peptide mitogen. In preliminary expression array analyses, the profile of genes activated by urea stress in renal medullary cells, however, was found to be unique. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol, 3314 SW US Vet Hosp Rd,Mailcode PP262, Portland, OR 97201 USA. NR 29 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD OCT PY 2001 VL 130 IS 3 SI SI BP 429 EP 436 DI 10.1016/S1095-6433(01)00441-X PG 8 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 486NH UT WOS:000171823500009 PM 11913456 ER PT J AU Chen, KH Azar, D Joyce, NC AF Chen, KH Azar, D Joyce, NC TI Transplantation of adult human corneal endothelium ex vivo - A morphologic study SO CORNEA LA English DT Article DE corneal endothelial cells; cell culture; corneal organ culture; keratoplasty; transplantation ID POSTERIOR LAMELLAR KERATOPLASTY; RECIPIENTS IN-VITRO; LARGE T-ANTIGEN; GROWTH-FACTORS; VIII COLLAGEN; CELLS; EXPRESSION; CULTURE; PROLIFERATION; PROTEINS AB Purpose. To investigate the feasibility of transplanting untransformed human corneal endothelial cells as a treatment strategy and possible alternative for penetrating keratoplasty by growing donor cells in culture and then transplanting them to denuded. Descemet's membrane of recipient corneas. Methods. Corneas from adult donors (50-80 years old) were obtained from eye banks. To grow corneal endothelial cells, Descemet's membrane with associated cells was dissected from the stroma. Endothelial cells were released by ethylenediaminetetraacetic acid treatment, grown in medium containing multiple growth factors, and identified as being of endothelial origin by morphology and by reverse-transcription polymerase chain reaction for keratin 12 and collagen type VIII. In transplantation experiments, cultured cells were seeded onto denuded Descemet's membrane of a second donor cornea at 5 x 10(5) cells/mL. The recipient cornea was incubated in organ culture for as long as 2 weeks. The morphology and ultrastructure of the endothelium were evaluated 7 and 14 days after transplantation by transmission electron microscopy, and by immunolocalization of zonula occludins-1 (ZO-1). Endothelial cell density was calculated in transplants by counting ZO-1-stained cells. Results. Corneal endothelial cells cultured from adult donors consistently grew well in culture medium. Cells were identified as corneal endothelium by characteristic morphology and messenger RNA expression. Morphologic and ultrastructural studies of corneas containing transplanted endothelial cells demonstrated that with time there was an increase in endothelial cell-Descemet's membrane adhesion, in the extent of cell-cell contacts and lateral interdigitation, and in formation of a single cell layer. ZO-1 staining revealed tight junction formation similar to that of corneas in vivo. Mean endothelial cell density in transplanted corneas was 1,895 cells/mm(2) (range 1,503-2,159 cells/mm(2)). Conclusion. Untransformed adult human corneal endothelial cells can be efficiently and consistently cultured and transplanted onto denuded Descemet's membrane. Transplanted cells in organ culture exhibit morphologic characteristics and cell densities similar to corneal endothelial cells in vivo. These results provide evidence for the feasibility of developing methods for in vivo transplantation of untransformed corneal endothelial cells cultured from adult donor tissue. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Natl Yang Ming Univ, Vet Gen Hosp, Dept Ophthalmol, Taipei 112, Taiwan. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Joyce, NC (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [NE1 EY05767] NR 42 TC 101 Z9 117 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD OCT PY 2001 VL 20 IS 7 BP 731 EP 737 DI 10.1097/00003226-200110000-00012 PG 7 WC Ophthalmology SC Ophthalmology GA 493KG UT WOS:000172221300012 PM 11588426 ER PT J AU Alston, TA AF Alston, TA TI Chicken soup for the stomach SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE erythromycin; gastric motility; motilin; nutrition; stomach; vomiting ID ERYTHROMYCIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 13 TC 0 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2001 VL 29 IS 10 BP 2033 EP 2034 DI 10.1097/00003246-200110000-00037 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 485JN UT WOS:000171751400037 PM 11588484 ER PT J AU Wilson, SB Byrne, MC AF Wilson, SB Byrne, MC TI Gene expression in NKT cells: defining a functionally distinct CD1d-restricted T cell subset SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID DEPENDENT DIABETES-MELLITUS; OLIGONUCLEOTIDE ARRAYS; DENDRITIC CELLS; IL-4 PRODUCTION; HELPER-CELLS; ALPHA-CHAIN; MICE; LYMPHOCYTES; CD4(+); MOUSE AB Since their discovery as cells bearing both TCRs and NK cell receptors, NKT cells have been intensively studied as a possible bridge between innate and adaptive immunity. Although their involvement in a wide variety of immune responses and in disease states have been well documented, molecular details of this functionality have been lacking. Recently, transcriptional profiling using microarrays has been applied to these cells, pinpointing gene-expression differences between this regulatory T cell subset and conventional T cells, and providing a framework for subset-specific therapeutic intervention in clinical settings. C1 Dana Farber Canc Inst, Canc Immunol & AIDS Dept, Dana 1416, Boston, MA 02115 USA. Wyeth Res Corp, Inst Genet, Cambridge, MA 02140 USA. RP Wilson, SB (reprint author), Dana Farber Canc Inst, Canc Immunol & AIDS Dept, Dana 1416, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI 45051] NR 50 TC 26 Z9 27 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2001 VL 13 IS 5 BP 555 EP 561 DI 10.1016/S0952-7915(00)00258-2 PG 7 WC Immunology SC Immunology GA 469BC UT WOS:000170791800008 PM 11544003 ER PT J AU Auchincloss, H AF Auchincloss, H TI Transplantation new technologies for old questions - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material 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, Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2001 VL 13 IS 5 BP 563 EP 565 DI 10.1016/S0952-7915(00)00259-4 PG 3 WC Immunology SC Immunology GA 469BC UT WOS:000170791800009 ER PT J AU Baid, S Saidman, SL Tolkoff-Rubin, N Williams, WW Delmonico, FL Cosimi, AB Pascual, M AF Baid, S Saidman, SL Tolkoff-Rubin, N Williams, WW Delmonico, FL Cosimi, AB Pascual, M TI Managing the highly sensitized transplant recipient and B cell tolerance SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RENAL-ALLOGRAFT REJECTION; ACUTE HUMORAL REJECTION; PATHOLOGICAL FEATURES; KIDNEY-TRANSPLANTATION; HYPERACUTE REJECTION; GRAFT-SURVIVAL; ANTIBODY; RESCUE; ORGAN; PREVENTION AB The detection of anti-donor-HLA antibodies in a renal allograft recipient's serum, either at the time of or after transplantation, is usually associated with specific antibody-mediated clinical syndromes. These can be divided temporally into three categories: hyperacute rejection, acute humoral rejection and chronic humoral rejection. With the identification of new immunosuppressive drug combinations, more-effective control of alloantibody production has been recently achieved in humans. Thus, prevention and/or treatment of antibody-mediated allograft injury are now possible. Ultimately, the induction of mixed hematopoietic chimerism may allow us to overcome the problem of allosensitization and accept an allograft without chronic immunosuppression. C1 Massachusetts Gen Hosp, Renal Unit, Histocompatibil Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Histocompatabil Lab, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Histocompatibil Lab, 55 Fruit St, Boston, MA 02114 USA. NR 47 TC 29 Z9 29 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2001 VL 13 IS 5 BP 577 EP 581 DI 10.1016/S0952-7915(00)00262-4 PG 5 WC Immunology SC Immunology GA 469BC UT WOS:000170791800012 PM 11544007 ER PT J AU Moore, KJ Fitzgerald, ML Freeman, MW AF Moore, KJ Fitzgerald, ML Freeman, MW TI Peroxisome proliferator-activated receptors in macrophage biology: friend or foe? SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; GAMMA PPAR-GAMMA; IN-VITRO; OXIDIZED LDL; CYCLOPENTENONE PROSTAGLANDINS; CHOLESTEROL EFFLUX; EXPRESSION; INHIBIT; TROGLITAZONE; DISEASE AB Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear hormone receptor, with a well-established role in adipogenesis and glucose metabolism. Over the past 3 years several laboratories have reported that this protein can influence macrophage responses to a variety of inflammatory stimuli. The effect of PPAR-gamma activation on macrophage lipid uptake, cholesterol efflux, and cytokine production have all recently been examined in several in-vitro culture systems. In addition, PPAR-gamma ligands have been shown to influence atherosclerotic lesion formation in murine models of that disease. This review attempts to summarize and critically evaluate that work and its implications for the use of PPAR-gamma activators in understanding and treating the pathogenetic processes that contribute to atherosclerotic plaque formation. Curr Opin Lipidol 12:519-527,, (C) 2001 Lippincott Williams & Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. NR 45 TC 42 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 2001 VL 12 IS 5 BP 519 EP 527 DI 10.1097/00041433-200110000-00007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 481FJ UT WOS:000171509000007 PM 11561171 ER PT J AU Tena, G Asai, T Chiu, WL Sheen, J AF Tena, G Asai, T Chiu, WL Sheen, J TI Plant mitogen-activated protein kinase signaling cascades SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Review ID MAP KINASE; ARABIDOPSIS-THALIANA; NEGATIVE REGULATOR; RESISTANCE GENE; TOBACCO CELLS; PATHWAYS; PHOSPHATASE; ELICITOR; AUXIN; PHOSPHORYLATION AB Mitogen-activated protein kinase (MAPK) cascades have emerged as a universal signal transduction mechanism that connects diverse receptors/sensors to cellular and nuclear responses in eukaryotes. Recent studies in plants indicate that MAPK cascades are vital to fundamental physiological functions involved in hormonal responses, cell cycle regulation, abiotic stress signaling, and defense mechanisms. New findings have revealed the complexity and redundancy of the signaling components, the antagonistic nature of distinct pathways, and the use of both positive and negative regulatory mechanisms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Tena, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Wellman 11,50 Blossom St, Boston, MA 02114 USA. NR 49 TC 266 Z9 306 U1 3 U2 34 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD OCT PY 2001 VL 4 IS 5 BP 392 EP 400 DI 10.1016/S1369-5266(00)00191-6 PG 9 WC Plant Sciences SC Plant Sciences GA 466ZN UT WOS:000170676200004 PM 11597496 ER PT J AU Halban, PA Kahn, SE Lernmark, A Rhodes, CJ AF Halban, PA Kahn, SE Lernmark, A Rhodes, CJ TI Gene and cell-replacement therapy in the treatment of type 1 diabetes - How high must the standards be set? SO DIABETES LA English DT Article ID PANCREATIC BETA-CELL; GLUCOSE-TOLERANCE; INSULIN-SECRETION; GRANULE BIOGENESIS; HUMAN PROINSULIN; NORMAL MEN; NOD MOUSE; EXPRESSION; MELLITUS; STIMULATION AB Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The beta -cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faithfully mimicked in surrogate cells. In particular, insulin is normally secreted in a well-regulated fashion in rapid response to the metabolic needs of the individual and most specifically (but not exclusively) to changes in circulating levels of glucose. Such regulated secretion will be indispensable in order to avoid both hyper- and hypoglycemic episodes and depends on the ability of cells to store insulin in secretory granules before exocytosis in response to physiological stimuli. Furthermore, any newly created insulin-secreting cell will have to be able to adapt to alterations in insulin requirements that accompany changes with exercise, body weight, and aging. Fine tuning of insulin secretion over the longer term will also be important to avoid "clinical shifting" that could be caused by over-insulinization, including increased adiposity and cardiovascular disease. Finally, it will be necessary to ensure that newly created or implanted (surrogate) beta -cells are protected in some way from recognition by the immune system and in particular from autoimmune destruction. C1 Univ Geneva, Med Ctr, Louis Jeantet Res Labs, Geneva, Switzerland. Univ Washington, Dept Med, Robert H Williams Lab, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Pacific NW Res Inst, Seattle, WA USA. RP Halban, PA (reprint author), Ctr Med Univ Geneva, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. OI Kahn, Steven/0000-0001-7307-9002 FU NIAID NIH HHS [AI42380]; NIDDK NIH HHS [DK353004, DK02654, DK26190, DK47919, DK50610, DK50703, DK55267] NR 70 TC 73 Z9 77 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2001 VL 50 IS 10 BP 2181 EP 2191 DI 10.2337/diabetes.50.10.2181 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 477KR UT WOS:000171283200001 PM 11574396 ER PT J AU Moore, A Bonner-Weir, S Weissleder, R AF Moore, A Bonner-Weir, S Weissleder, R TI Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes SO DIABETES LA English DT Article ID MAGNETIC-RESONANCE MICROSCOPY; BLOOD-FLOW; IRON-OXIDE; ANTIGEN EXPRESSION; FUNCTIONAL-STATE; ISLET VOLUME; BB RAT; PANCREAS; AUTOANTIGEN; IDENTIFICATION AB Pancreatic beta -cell mass (BCM) is a major determinant of the quantity of insulin that can be secreted. BCM is markedly reduced in type 1 diabetes because of selective autoimmune destruction of beta -cells. Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical information; thus, the development of noninvasive means of BCM measurement could be important in intervention therapy. The goal of this study was to develop such noninvasive methods for measuring BCM featuring target-specific imaging probes and to investigate whether this technique is feasible, accurate, and predictive of BCM in normal and diabetic states. Using a beta -cell-specific monoclonal antibody IC2, modified with a radioisotope chelator for nuclear imaging, we showed that highly specific binding and accumulation to beta -cells occurs after intravenous administration of the probe, with virtually no binding to exocrine pancreas or stromal tissues. Furthermore, we observed a direct correlation between accumulation of the probe with BCM in diabetic and normal animals. Nuclear imaging of the animals that received an injection of the radioactive probe showed major difference in signal intensity between normal and diabetic pancreases. The results front this study set the route for further development of imaging probes for measuring BCM that would aid in diagnosis and treatment of diabetic patients in the clinic. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Moore, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Room 5419,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R21 DK5811] NR 36 TC 76 Z9 84 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2001 VL 50 IS 10 BP 2231 EP 2236 DI 10.2337/diabetes.50.10.2231 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 477KR UT WOS:000171283200008 PM 11574403 ER PT J AU Conigrave, KM Hu, BF Camargo, CA Stampfer, MJ Willett, WC Rimm, EB AF Conigrave, KM Hu, BF Camargo, CA Stampfer, MJ Willett, WC Rimm, EB TI A prospective study of drinking patterns in relation to risk of type 2 diabetes among men SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; ALCOHOL-CONSUMPTION; INSULIN SENSITIVITY; BLOOD-PRESSURE; CIGARETTE-SMOKING; MELLITUS; ETHANOL; POPULATION; QUESTIONNAIRE; HYPOGLYCEMIA AB Using data from a 12-year prospective study, we determined the importance of the pattern of alcohol consumption as a risk factor for type 2 diabetes in a cohort of 46,892 U.S. male health professionals who completed biennial postal questionnaires. Overall, 1,571 new cases of type 2 diabetes were documented. Compared with zero alcohol consumption, consumption of 15-29 g/day of alcohol was associated with a 36% lower risk of diabetes (RR = 0.64; 95% CI 0.53-0.77). This inverse association between moderate consumption and diabetes remained if light drinkers rather than abstainers were used as the reference group (RR = 0.60, CI 0.50-0.73). There were few heavy drinkers, but the inverse association persisted to those drinking greater than or equal to 50 g/day of alcohol (RR = 0.60, Cl 0.43-0.84). Frequency of consumption was inversely associated with diabetes. Consumption of alcohol on at least 5 days/week provided the greatest protection, even when less than one drink per drinking day was consumed (RR = 0.48, Cl 0.27-0.86). Compared with infrequent drinkers, for each additional day per week that alcohol was consumed, risk was reduced by 7% (95% Cl 3-10%) after controlling for average daily consumption. There were similar and independent inverse associations for beer, liquor, and white wine. Our findings suggested that frequent alcohol consumption conveys the greatest protection against type 2 diabetes, even if the level of consumption per drinking day is low. Beverage choice did not alter risk. C1 Royal Prince Alfred Hosp, Drug & Alcohol Dept, Sydney, NSW, Australia. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Univ Sydney, Dept Publ Hlth & Community Med, Sydney, NSW 2006, Australia. Univ Sydney, Dept Med Psychol, Sydney, NSW 2006, Australia. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Conigrave, KM (reprint author), Royal Prince Alfred Hosp, Drug & Alcohol Dept, Missenden Rd, Camperdown, NSW 2050, Australia. OI Conigrave, Katherine/0000-0002-6428-1441 FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL-03533, HL35464]; NIAAA NIH HHS [AAIII81] NR 52 TC 137 Z9 143 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2001 VL 50 IS 10 BP 2390 EP 2395 DI 10.2337/diabetes.50.10.2390 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 477KR UT WOS:000171283200029 PM 11574424 ER PT J AU Nathan, DM AF Nathan, DM CA Diabet Control Complications Trial TI Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the diabetes control and complications trial SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR-DISEASE; ENERGY-EXPENDITURE; INSULIN THERAPY; ADIPOSE-TISSUE; GAIN; TESTS; DCCT; THERMOGENESIS; PARTICIPANTS; POPULATION AB OBJECTIVE - To examine the differential effects of intensive and conventional diabetes therapy on weight gain and body composition in adults With type 1 diabetes. RESEARCH DESIGN AND METHODS - Between 1982 and 1989,1,246 adults (aged 18-39 years) in the Diabetes Control and Complications Trial were randomly assigned to either conventional therapy (1-2 injections of insulin per day) or intensive therapy (multiple daily injections or continuous subcutaneous infusion With frequent blood-glucose testing). Height and weight were measured at baseline and at annual Visits for an average of 6 years (range 3-9). Body Composition was assessed cross-sectionally with bioelectrical impedance analysis during 1992, at which time waist and hip circumferences were measured. RESULTS - Intensively treated patients gained an average of 4.75 kg more than their conventionally treated counterparts (P < 0.0001). This represented excess increases in BMI of 1.5 kg/m(2) among men and 1.8 kg/m(2) among women. Growth-curve analysis showed that weight gain was most rapid during the first year of therapy. Intensive therapy patients were also more likely to become overweight (BMI greater than or equal to 27.8 kg/m(2) for men, greater than or equal to 27.3 kg/m(2) for women) or experience major weight gain (BMI increased greater than or equal to5 kg/m(2)). Waist-to-hip ratios, however, did not differ between treatment groups, Major weight gain was associated with higher percentages of body fat and greater fat-free mass, but among patients without major weight gain, those receiving intensive therapy had greater fat-free mass with no difference in adiposity. CONCLUSIONS - Intensive therapy for type I diabetes produces substantial excess weight gain compared with conventional therapy. However, the additional weight appears to include lean tissue as well as fat. C1 Massachusetts Gen Hosp, Diabet Univ Bulfinch 408, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Diabet Univ Bulfinch 408, Boston, MA 02114 USA. EM nathan@gcrc.mgh.harvard.edu RI Zinman, Bernard/E-7266-2013 NR 40 TC 84 Z9 88 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2001 VL 24 IS 10 BP 1711 EP 1721 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 478AW UT WOS:000171321600003 ER PT J AU Larme, AC Pugh, JA AF Larme, AC Pugh, JA TI Evidence-based guidelines meet the real world - The case of diabetes care SO DIABETES CARE LA English DT Article ID UNITED-STATES; MELLITUS; MANAGEMENT; PHYSICIAN; PATIENT; ORGANIZATION; EXPERIENCE; ATTITUDES; BARRIERS; SYSTEM AB OBJECTIVE - Improving diabetes care in the U.S. is critical because diabetes rates are increasing dramatically, particularly among minority and low-income populations. Although evidence-based practice guidelines for diabetes have been widely disseminated, many physicians fail to implement them. The objective of this study was to explore what happens to diabetes practice guidelines in real-world clinical settings. RESEARCH DESIGN AND METHODS - A qualitative research design was used. Open-ended semistructured interviews lasting 1-2 h were conducted with 32 key informants (physicians, certified diabetes educators, researchers, and agency personnel) selected for their knowledge of diabetes care in South Texas, an area with a high diabetes prevalence and a large proportion of minority and low-income patients. RESULTS - Health professionals stress that contextual factors are more important barriers to optimal diabetes care than physician knowledge and attitudes. Barriers exist at multiple levels and are interrelated in a complex manner. Examples include the following: time constraints and practice economics in the private practice setting; the need to maintain referral relationships and maldistribution of professionals in the practice community; low awareness and low socioeconomic status among patients; and lack of access for low-income patients, low reimbursement, and insufficient focus on prevention in the U.S. health care system. CONCLUSIONS - Contextual barriers must be addressed in order for diabetes practice guidelines to be implemented in real-world clinical practice. Suggested changes include an increased focus on prevention, improvements in health care delivery for chronic diseases, and increased attention to the special needs of minority and low-income populations. C1 Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78229 USA. Dept Vet Affairs Med Ctr, Res & Dev Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Larme, AC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, 7703 Floyd Curl Dr,Mail Code 7795, San Antonio, TX 78229 USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [HS07397] NR 27 TC 39 Z9 40 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2001 VL 24 IS 10 BP 1728 EP 1733 DI 10.2337/diacare.24.10.1728 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 478AW UT WOS:000171321600005 PM 11574433 ER PT J AU Malecki, MT Klupa, T Frey, J Cyganek, K Galicka-Stankowska, D Wanic, K Sieradzki, J AF Malecki, MT Klupa, T Frey, J Cyganek, K Galicka-Stankowska, D Wanic, K Sieradzki, J TI Identification of a new mutation in the hepatocyte nuclear factor-1 alpha gene in a Polish family with early-onset Type 2 diabetes mellitus SO DIABETES NUTRITION & METABOLISM LA English DT Article DE diabetes; MODY; genetics; hepatocyte nuclear factor-1 alpha; mutation ID YOUNG; HNF-1-ALPHA; MODY AB Recently, several genes associated with early-onset, autosomal dominant Type 2 diabetes (MODY) have been identified. Mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene seem to account for a substantial proportion of this type of diabetes in several populations. However, it is still of interest to estimate the frequency of HNF-1 alpha mutations in various ethnic groups. The aim of our study was to determine the contribution of the HNF-1 alpha gene to the development of MODY in a Polish population. We selected 15 families with MODY for this project. The 10 exons and promoter region of the gene were screened for sequence differences by direct sequencing of probands DNA. We detected 7 previously described polymorphisms that were not associated with diabetes. However, one sequence difference, a deletion of a cytosine in codon 225 in exon 3 (designated S225fdelC), was a new mutation resulting in a frame shift and synthesis of a nonsense peptide from amino acid 225 to 232 followed by the stop codon. Thus, the S225fdelC mutation effectively caused the loss of a part of the DNA binding domain and the entire transactivation domain. This mutation was present in 4 affected members of the family. They developed diabetes at an early age (mean age at diagnosis 23 yr) and were characterized by severely impaired insulin secretion. In addition, one family member who was not a carrier of the S225fdelC mutation was diagnosed with diabetes. Thus, he represents an example of phenocopy. In conclusion, we have identified a new HNF-1 alpha variant that represents the first MODY mutation described in a Polish population. MODY3 mutations, including those in the exon 4 "hot spot", do not appear to be a very common cause of MODY in the Polish population. (C) 2001, Editrice Kurtis. C1 Jagiellonian Univ, Dept Metab Dis, Coll Med, PL-31501 Krakow, Poland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Sieradzki, J (reprint author), Jagiellonian Univ, Dept Metab Dis, Coll Med, 15 Kopernika St, PL-31501 Krakow, Poland. NR 15 TC 2 Z9 2 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-3402 J9 DIABETES NUTR METAB JI Diabetes Nutr. Metab. PD OCT PY 2001 VL 14 IS 5 BP 288 EP 291 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 501XR UT WOS:000172711800008 PM 11806470 ER PT J AU Gragnoli, C Cockburn, BN Chiaramonte, F Gorini, A Marietti, G Marozzi, G Signorini, AM AF Gragnoli, C Cockburn, BN Chiaramonte, F Gorini, A Marietti, G Marozzi, G Signorini, AM TI Early-onset Type II diabetes mellitus in Italian families due to mutations in the genes encoding hepatic nuclear factor 1 alpha and glucokinase SO DIABETOLOGIA LA English DT Article DE Type II diabetes mellitus; genetics; hepatocyte nuclear factor-1 alpha; hepatocyte nuclear factor-4 alpha; glucokinase; MODY; Italian; mutation; polymorphism ID FACTOR-1-ALPHA GENE; YOUNG MODY3; HEPATOCYTE; IDENTIFICATION; PROMOTER AB Aims/hypothesis. Maturity-onset-diabetes of the young (MODY) is caused by mutations in at least five different genes. Our aim was to determine the prevalence of the most common MODY genes in Italian families with early-onset Type II (non-insulin-dependent) diabetes mellitus. Methods. We screened 28 Italian early-onset Type II diabetic families (diagnosis < 35 years) for mutations in the hepatic nuclear factor-4 alpha, (MODY1), glucokinase (MODY2) and hepatic nuclear factor-la (MODY3). Both strands of exons, flanking introns and minimal promoter regions of the above-mentioned genes were amplified using polymerase chain reaction and were sequenced directly. Results. We identified four different mutations, three of which are not described, (W113X, G42P43fsCC --> A, H514R) and four new polymorphisms (G184G, T513T, IVS3-nt47delG, IVS1- nt53C --> G) in the hepatic nuclear factor-1 alpha gene, two new potential mutations (G44S, IVS4nt + 7C --> T) and three new polymorphisms (promoter-nt84C --> G, IVS9 + nt8C --> T, IVS9 + nt49G --> A) in the glucokinase gene, and a new polymorphism (IVS1c-nt11T --> G) in the hepatic nuclear factor-4 alpha gene. Conclusion/interpretation. Mutations in the hepatic nuclear factor-1 alpha and glucokinase are associated with Type II diabetes in 14% and 7% of Italian families, respectively. Our findings provide an impetus for screening Italian MODY and early-non Type II diabetic families for mutations in the above mentioned genes to identify relatives at risk who could benefit from primary prevention care. C1 Univ Chicago, Howard Hughes Med Inst, Dept Biochem & Mol Biol & Med, Chicago, IL 60637 USA. Santo Spirito Hosp, Rome, Italy. Univ Studies, Diabet Unit, Siena, Italy. Univ Cattolica Sacro Cuore, Childrens Inst, Rome, Italy. RP Gragnoli, C (reprint author), Massachusetts Gen Hosp, WEL 320,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-20595, DK-44840] NR 10 TC 31 Z9 35 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2001 VL 44 IS 10 BP 1326 EP 1329 DI 10.1007/s001250100644 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 486RT UT WOS:000171831300015 PM 11692182 ER PT J AU Bostic, JQ Rustuccia, C Schlozman, SC AF Bostic, JQ Rustuccia, C Schlozman, SC TI The suicidal student SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Tufts Univ, Medford, MA 02155 USA. Pembroke Hill Sch, Kansas City, MO USA. RP Bostic, JQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD OCT PY 2001 VL 59 IS 2 BP 81 EP 82 PG 2 WC Education & Educational Research SC Education & Educational Research GA 499DG UT WOS:000172555300017 ER PT J AU Teixeira, J Maheswaran, S Donahoe, PK AF Teixeira, J Maheswaran, S Donahoe, PK TI Mullerian inhibiting substance: An instructive developmental hormone with diagnostic and possible therapeutic applications SO ENDOCRINE REVIEWS LA English DT Review ID NF-KAPPA-B; RIBONUCLEIC-ACID EXPRESSION; NUCLEAR RECEPTOR SF-1; HUMAN OVARIAN-CANCER; ADRENAL HYPOPLASIA CONGENITA; FOLLICLE-STIMULATING-HORMONE; TRANSCRIPTION FACTOR GATA-4; STEROIDOGENIC FACTOR-I; GRANULOSA-CELL TUMORS; RAT SERTOLI-CELLS AB Dr. Alfred Jost pioneered the field of reproductive endocrinology with his seminal observation that two hormones produced by the testes are required for the male embryo to develop a normal internal reproductive tract. T induces the Wolffian ducts to differentiate into epididymides, vasa deferens, and seminal vesicles. Mullerian inhibiting substance (MIS) causes regression of the Mullerian ducts, which in its absence would normally develop into the Fallopian tubes, uterus, and upper vagina as is observed in female embryos. This review will summarize our current understanding of molecular mechanisms underlying the function of AUS both as a fetal gonadal hormone that causes Mullerian duct regression and as an adult hormone, the roles for which are currently being investigated, i.e., inhibition of steroidogenesis, germ cell development, and cancer. We will also address the regulation of MIS expression as one of the first genes expressed after the commitment of the bipotential gonads to differentiate into testes under the influence of SRY, the gene on the sex-determining region of the Y chromosome. We will discuss what is known regarding MIS signal transduction, which as with other members of the TGF beta family of growth and differentiation factors, occurs through a heteromeric complex of single transmembrane serine/threonine kinase receptors to effect downstream signaling events, including Smad, nuclear factor-kappaB, beta -catenin, and p16 activation. Finally, we will assess the clinical relevance of studying MIS in patients with persistent Mullerian duct syndrome and our efforts to determine the therapeutic value of MIS for patients with ovarian and other MIS receptor-expressing cancers. C1 Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, J (reprint author), WRN1024,32 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu FU NCI NIH HHS [R29CA-79459, R01CA-17393, R29 CA079459, R29 CA079459-02]; NICHD NIH HHS [R01HD-32112, U54HD-28138] NR 203 TC 193 Z9 206 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2001 VL 22 IS 5 BP 657 EP 674 DI 10.1210/er.22.5.657 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 481AT UT WOS:000171496700005 PM 11588147 ER PT J AU Tsaih, SW Korrick, S Schwartz, J Lee, MLT Amarasiriwardena, C Aro, A Sparrow, D Hu, H AF Tsaih, SW Korrick, S Schwartz, J Lee, MLT Amarasiriwardena, C Aro, A Sparrow, D Hu, H TI Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: The normative aging study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood; bone; environmental exposure; K-X-ray fluorescence; lead; N-telopeptides; urine ID LINKED N-TELOPEPTIDES; BLOOD LEAD; OCCUPATIONAL EXPOSURE; POSTMENOPAUSAL WOMEN; ISOTOPE-DILUTION; ASCORBIC-ACID; HUMAN PLASMA; I COLLAGEN; PREGNANCY; SKELETON AB Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring crosslinked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead greater than or equal to 0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead greater than or equal to 0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Normat Aging Study, Dept Vet Affairs, Outpatient Clin, Boston, MA USA. RP Tsaih, SW (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR 02635]; NIEHS NIH HHS [R01-ES05257, P42-ES05947, ES 03918, ES 08074, ES 00002, ES 05947] NR 44 TC 31 Z9 31 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2001 VL 109 IS 10 BP 995 EP 999 DI 10.2307/3454952 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800018 PM 11675263 ER PT J AU Long, CM Suh, HH Kobzik, L Catalano, PJ Ning, YY Koutrakis, P AF Long, CM Suh, HH Kobzik, L Catalano, PJ Ning, YY Koutrakis, P TI A pilot investigation of the relative toxicity of indoor and outdoor fine particles: In vitro effects of endotoxin and other particulate properties SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE alveolar macrophage; cytokines; endotoxin; fine particles; indoor air pollution; PM2.5; toxicity; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; RAT ALVEOLAR MACROPHAGES; AIRWAY EPITHELIAL-CELLS; CYTOKINE PRODUCTION; ORGANIC AEROSOL; AIRBORNE PARTICLES; PERSONAL EXPOSURE; UNITED-STATES; FACTOR-ALPHA; IN-VITRO AB dIn this study we assessed the in vitro toxicity of 14 paired indoor and outdoor PM2.5 Samples (particulate matter less than or equal to 2.5 mum in aerodynamic diameter) collected in 9 Boston-area homes. Samples were collected as part of a large indoor particle characterization study that included the simultaneous measurement of indoor and outdoor PM2.5, particle size distributions, and compositional data (e.g., elemental/organic carbon, endotoxin, etc.). Bioassays were conducted using rat alveolar macrophages (AMs), and tumor necrosis factor (TNF) was measured to assess particle-induced proinflammatory responses. Additional experiments were also conducted in which Ams were primed with lipopolysaccharides (LPS) to simulate preexisting pulmonary inflammation such as that which might exist in sick and elderly individuals. Significant TNF production above that of negative controls was observed for AMs exposed to either indoor or outdoor PM2.5. TNF releases were further amplified for primed AMs, suggesting that preexisting inflammation can potentially exacerbate the toxicity of not only outdoor PM2.5 (as shown by previous studies) but also indoor PM2.5. In addition, indoor particle TNF production was found to be significantly higher than outdoor particle TNF production in unprimed AMs, both before and after normalization for endotoxin concentrations. Our results suggest that indoor-generated particles may be more bioactive than ambient particles. Endotoxin was demonstrated to mediate proinflammatory responses for both indoor and outdoor PM2.5, but study findings suggest the presence of other proinflammatory components of fine particles, particularly for indoor-generated particles. Given these study findings and the fact that people spend 85-90% of their time indoors, future studies are needed to address the toxicity of indoor particles. C1 Gradient Corp, Cambridge, MA 02142 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Long, CM (reprint author), Gradient Corp, 238 Main St, Cambridge, MA 02142 USA. NR 53 TC 84 Z9 87 U1 4 U2 17 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2001 VL 109 IS 10 BP 1019 EP 1026 DI 10.2307/3454956 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800022 PM 11689347 ER PT J AU Sarnat, JA Schwartz, J Catalano, PJ Suh, HH AF Sarnat, JA Schwartz, J Catalano, PJ Suh, HH TI Gaseous pollutants in particulate matter epidemiology: Confounders or surrogates? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; carbon monoxide; confounding; exposure error; personal exposure; PM2.5; nitrogen dioxide; ozone; sulfur dioxide ID AIR-POLLUTION; PERSONAL EXPOSURE; PARTICLES; OUTDOOR; INDOOR; OZONE; ASSOCIATION; CALIFORNIA; BALTIMORE; MORTALITY AB Air pollution epidemiologic studies use ambient pollutant concentrations as surrogates of personal exposure. Strong correlations among numerous ambient pollutant concentrations, however, have made it difficult to determine the relative contribution of each pollutant to a given health outcome and have led to criticism that health effect estimates for particulate matter may be biased due to confounding. In the current study we used data collected from a multipollutant exposure study conducted in Baltimore, Maryland, during both the summer and winter to address the potential for confounding further. Twenty-four-hour personal exposures and corresponding ambient concentrations to fine particulate matter (PM2.5), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide were measured for 56 subjects. Results from correlation and regression analyses showed that personal PM(2.)5 and gaseous air pollutant exposures were generally not correlated, as only 9 of the 178 individual-specific pairwise correlations were significant. Similarly, ambient concentrations were not associated with their corresponding personal exposures for any of the pollutants, except for PM2.5, which had significant associations during both seasons (p < 0.0001). Ambient gaseous concentrations were, however, strongly associated with personal PM2.5 exposures. The strongest associations were shown between ambient O-3 and personal PM2.5 (p < 0.0001 during both seasons). These results indicate that ambient PM2.5 concentrations are suitable surrogates for personal PM2.5 exposures and that ambient gaseous concentrations are surrogates, as opposed to confounders, of PM2.5. These findings suggest that the use of multiple pollutant models in epidemiologic studies of PM2.5 may not be suitable and that health effects attributed to the ambient gases may actually be a result of exposures to PM2.5. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Sarnat, JA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Rm 1308, Boston, MA 02115 USA. NR 28 TC 123 Z9 132 U1 0 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2001 VL 109 IS 10 BP 1053 EP 1061 DI 10.2307/3454961 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800027 PM 11675271 ER PT J AU Marino, M Chiovato, L Lisi, S Pinchera, A McCluskey, RT AF Marino, M Chiovato, L Lisi, S Pinchera, A McCluskey, RT TI Phosphoinositide 3-kinase inhibits megalin-mediated transcytosis of thyroglobulin across thyroid epithelial cells at a post-sorting level SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID RECEPTOR GENE FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; ENDOPLASMIC-RETICULUM; NONDIPLOID KARYOTYPE; ENDOCYTIC RECEPTOR; HEYMANN NEPHRITIS; HORMONE RELEASE; FOLLICLE CELLS; GP330; WORTMANNIN AB Background: Phosphoinositide 3-kinase (PI3-K) is implicated in various cellular processes involving signaling, including intracellular trafficking. PI3-K has been shown to play a part in both receptor- and non-receptor-mediated transcytosis across cultured kidney cells and undifferentiated thyroid cells. Objective: To investigate the role of PI3-K in transcytosis of thyroglobulin (Tg) across differentiated cultured Fisher rat thyroid cells (FRTL-5 cells)-a process known to be mediated by megalin, a member of the low-density lipoprotein receptor family. Design: We studied the effect of the microbial product wortmannin, a specific inhibitor of PI3-K, on transcytosis of Tg across FRTL-5 cells. Methods: Transcytosis experiments were performed using FRTL-5 cells cultured as tight layers on filters in the upper chamber of dual chambered devices, with megalin expression exclusively on the upper cell surface. Tg was added to the upper chamber and cells were incubated at 37 degreesC. Transcytosed Tg was measured in fluids collected from the lower chamber. To study the role of PI3-K, cells were pre-incubated with wortmannin. Results: Pre-incubation of FRTL-5 cells with wortmannin did not affect Tg binding and uptake, but resulted in a considerable increase in Tg transcytosis (by 40-75%, depending on the concentration of wortmannin), suggesting that PI3-K exerts an inhibitory effect on Tg transcytosis. In experiments in which a monoclonal antibody against megalin was used to reduce Tg transcytosis, pre-incubation with wortmannin did not increase Tg transcytosis from its reduced levels, indicating that PI3-K is involved in the megalin-mediated pathway. Wortmannin did not affect the extent of release of tri-iodothyronine from exogenously added Tg by FRTL-5 cells, which was used as a measure of Tg degradation in the lysosomal pathway, indicating that the effect of PI3-K on transcytosis occurs after diversion of Tg from the lysosomal pathway. Conclusions: PI3-K exerts an inhibitory role on megalin-mediated Tg transcytosis across cultured thyroid cells. PI3-K action takes place at a post-sorting level, after Tg bypassing of the lysosomal pathway. C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. FU PHS HHS [46301] NR 38 TC 3 Z9 3 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD OCT PY 2001 VL 145 IS 4 BP 477 EP 483 DI 10.1530/eje.0.1450477 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479TA UT WOS:000171418600018 PM 11581008 ER PT J AU Mulroy, T Sen, J AF Mulroy, T Sen, J TI p38 MAP kinase activity modulates alpha beta T cell development SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 7th Human Leukocyte Differentiation Antigen Workshop (HLDA7) CY 2000 CL HARROGATE, ENGLAND DE thymus; pre-T cell receptor; signal transduction; p38 MAP kinase ID ACTIVATED PROTEIN-KINASE; SIGNALING PATHWAYS; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; SELECTIVE ACTIVATION; IMMATURE THYMOCYTES; TYROSINE KINASES; MICE LACKING; PROLIFERATION; SLP-76 AB Reciprocal interactions between bone marrow derived precursor cells and the thymic environment lead to the generation of the complete repertoire of diverse and functional T cells. We have previously shown that p38 MAP kinase is activated in response to intrathymic signals in thymocytes. In this report we provide evidence that p38 MAP kinase activity is essential for pre-TCR-mediated transition of thymocytes; from the CD4(-) CD8(-) to the CD4(+) CD8(+) stage of development. In the absence of p38 MAP kinase activity differentiation of ap T cells, but not gamma delta T cells, was blocked. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Sen, J (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74404] NR 36 TC 13 Z9 18 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2001 VL 31 IS 10 BP 3056 EP 3063 DI 10.1002/1521-4141(2001010)31:10<3056::AID-IMMU3056>3.0.CO;2-B PG 8 WC Immunology SC Immunology GA 485WA UT WOS:000171785400025 PM 11592082 ER PT J AU Zweemer, RP Verheijen, RHM Coebergh, JWW Jacobs, IJ van Diest, PJ Gille, JJP Skates, S Menko, FH Ten Kate, LP Kenemans, P AF Zweemer, RP Verheijen, RHM Coebergh, JWW Jacobs, IJ van Diest, PJ Gille, JJP Skates, S Menko, FH Ten Kate, LP Kenemans, P TI Survival analysis in familial ovarian cancer, a case control study SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE ovarian cancer; hereditary; survival; BRCA1; BRCA2 ID DEOXYRIBONUCLEIC-ACID PLOIDY; GERMLINE MUTATIONS; PROGNOSTIC FACTORS; BRCA2 GENE; STAGE-III; BREAST; CARCINOMA; NETHERLANDS; PACLITAXEL; FEATURES AB Objective: familial ovarian cancer patients have been found to differ from sporadic cases, clinically as well as in the molecular make-up of the tumour. Here, a case control study is performed to analyse potential differences in survival. Study design: 31 families with a strong history of ovarian and/or breast cancer presenting to a family cancer clinic 44 ovarian cancer patients were included. Each patient was matched for age and stage with controls from a cancer registry. Survival rates and the effect of several prognostic factors were analysed. Results: median survival in the study group differed significantly from controls. A survival benefit for familial cases was maintained up to 5 years after diagnosis. Long-term survival was equally poor in both groups. Conclusion: the difference in survival between familial ovarian cancer cases and matched controls may reflect differences in biological behaviour. This may have important implications for the management and prevention of familial ovarian cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Vrije Univ Amsterdam, Med Ctr, Dept Obstet & Gynaecol, Amsterdam, Netherlands. Comprehens Canc Ctr S, Eindhoven, Netherlands. Erasmus Univ, Rotterdam, Netherlands. St Bartholomews Hosp, Gynaecol Canc Res Unit, London, England. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Clin & Human Genet, Amsterdam, Netherlands. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Verheijen, RHM (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Obstet & Gynaecol, Amsterdam, Netherlands. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 29 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD OCT PY 2001 VL 98 IS 2 BP 219 EP 223 DI 10.1016/S0301-2115(01)00318-9 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 485TC UT WOS:000171779000012 PM 11574135 ER PT J AU Royall, DR Rauch, R Roman, GC Cordes, JA Polk, MJ AF Royall, DR Rauch, R Roman, GC Cordes, JA Polk, MJ TI Frontal MRI findings associated with impairment oh the executive interview (EXIT25) SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; BEDSIDE ASSESSMENT; QUALITATIVE EVALUATION; DIAGNOSTIC-CRITERIA; VASCULAR DEMENTIA; ELDERLY SUBJECTS; SCHIZOPHRENIA; DYSFUNCTION AB We examined the association between the Executive Interview (EXIT25), a bedside measure of executive control, and regional magnetic resonance imaging (MR[) pathology among 52 consecutive geriatric patients presenting to a university dementia assessment clinic, Left frontal (p <.002), left medial (p <.03), right frontal (p <.02), and right medial (p <.02) cortical lesions significantly worsened EXIT25 scores, even after adjusting for age, global cognitive impairment (our the Mini-Mental State Examination), and the severity of cortical dementia on the Qualitative Evaluation of Dementia [QED]. The EXIT25's associations with right hemisphere lesions did not persist after adjusting for left frontal lesions. Left posterior lesions did not significantly affect the EXIT25. Similarly, left frontal circuit pathology worsened EXIT25 scores (p <.05). Pathology in left anterior subcortical structures showed a trend (p =.052). EXIT25 scores were not affected by right subcortical pathology, nor by pathology in either hippocampus. We conclude that the EXIT25 is specifically affected by frontal system MRI lesions, particularly on the left. This conclusion is consistent with earlier functional neuroimaging studies associating EXIT25 performance with left mesiofrontal perfusion. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Dept Pharmacol, San Antonio, TX USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Syst, Dept Med Neurol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Syst, Dept Psychiat, San Antonio, TX 78284 USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 55 TC 26 Z9 26 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD OCT-DEC PY 2001 VL 27 IS 4 BP 293 EP 308 DI 10.1080/03610730109342350 PG 16 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 486ZH UT WOS:000171848900001 PM 11681194 ER PT J AU Layne, MD Patel, A Chen, YH Rebel, VI Carvajal, IM Pellacani, A Ith, B Zhao, DZ Schreiber, BM Yet, SF Lee, ME Storch, J Perrella, MA AF Layne, MD Patel, A Chen, YH Rebel, VI Carvajal, IM Pellacani, A Ith, B Zhao, DZ Schreiber, BM Yet, SF Lee, ME Storch, J Perrella, MA TI Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice SO FASEB JOURNAL LA English DT Article DE atheroma; inflammatory cytokines; chemokines ID COLONY-STIMULATING FACTOR; E-DEFICIENT MICE; APOLIPOPROTEIN-E; AP2(-/-) MICE; CELLS; ARTERIOSCLEROSIS; CHEMOKINES; RECEPTOR; DISEASE; LESIONS AB Atherosclerosis is an inflammatory disease process associated with elevated levels of plasma cholesterol, especially low-density lipoproteins. The latter become trapped within the arterial wall and are oxidized and taken up by macrophages to form foam cells. This process is an initiating event for atherosclerosis. Fatty acid binding proteins (FABP) are involved in fatty acid metabolism and cellular lipid transport, and adipocyte FABP (aP2) is also expressed in macrophages. We recently generated mice lacking both apolipoprotein (Apo) E and aP2 (ApoE(-/-) aP2(-/-)) and found that these mice, compared with ApoE(-/-) mice, developed markedly smaller atherosclerotic lesions that contained fewer macrophages. Here we investigated the mechanism(s) responsible for this prevention of atherosclerotic lesion formation. Bone marrow transplantations were performed in ApoE(-/-) mice, receiving cells from either ApoE(-/-) or ApoE(-/-) aP2(-/-) mice. The lack of aP2 in donor marrow cells led to the development of smaller (5.5-fold) atherosclerotic lesions in the recipient mice. No differences were found in plasma cholesterol, glucose, or insulin levels between recipients of bone marrow cells from ApoE(-/-) or ApoE(-/-) aP2(-/-) mice. However, the expression of chemoattractant and inflammatory cytokines was decreased in macrophages from ApoE(-/-) aP2(-/-) mice compared with ApoE(-/-) mice, which may contribute to the decrease in atherosclerotic lesion formation. Taken together, we demonstrate the importance of macrophage aP2 in the development of atherosclerotic lesions. C1 Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Program Dev Cardiovasc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Perrella, MA (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care, 75 Francis St, Boston, MA 02115 USA. EM mperrella@rics.bwh.harvard.edu RI Yet, Shaw-Fang/B-1067-2010; OI Layne, Matthew/0000-0003-0007-4870; Yet, Shaw-Fang/0000-0001-9097-3962; Storch, Judith/0000-0001-5482-1777; Schreiber, Barbara/0000-0001-8560-4249 FU NIDDK NIH HHS [R01 DK038389] NR 32 TC 45 Z9 50 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2001 VL 15 IS 12 BP 2733 EP + DI 10.1096/fj.01-0374fje PG 19 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 488DM UT WOS:000171920400013 PM 11606480 ER PT J AU Madry, H Zurakowski, D Trippel, SB AF Madry, H Zurakowski, D Trippel, SB TI Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation SO GENE THERAPY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Orthopedic-Research-Society CY MAR 12-15, 2000 CL ORLANDO, FLORIDA SP Orthoped Res Soc DE cartilage; chondrocytes; IGF-I; gene transfer; cell transplantation ID MEDIATED GENE-TRANSFER; PLATE CHONDROCYTES; CARTILAGE; INTERLEUKIN-1; AUTOCRINE; ARTHRITIS; SYNOVIUM; DEFECTS; REPAIR; CELLS AB Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage, Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein. Transplantation of transfected articular chondrocytes on to the surface of articular cartilage explants led to the formation of a new tissue layer on the cartilage explant surface. The new tissue was characterized by the presence of type II collagen and proteoglycan and by the absence of type I collagen, consistent with hyaline-like cartilage, The tissue formed by the chondrocytes expressing IGF-I was thicker and contained more cells than controls transfected with an expression plasmid vector containing the Escherichia coli (E. coli) beta -galactosidase (lacZ) gene. Transplantation of articular chondrocytes that overexpress human IGF-I also increased DNA synthesis and the synthesis of glycosaminoglycans by the underlying explant cartilage chondrocytes. These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg,Orthopaed Res Labs, Cambridge, MA 02138 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Biostat, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Trippel, SB (reprint author), Indiana Univ, Dept Orthopaed Surg, 541 Clin Dr,Suite 600, Indianapolis, IN 46202 USA. FU NIAMS NIH HHS [AR 31068, AR 45749] NR 25 TC 86 Z9 92 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2001 VL 8 IS 19 BP 1443 EP 1449 DI 10.1038/sj.gt.3301535 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 476GC UT WOS:000171217000001 PM 11593356 ER PT J AU Ferrantelli, F Xu, WD Hofmann-Lehmann, R Li, PL Cavacini, L Posner, M Katinger, H Stiegler, G McClure, H Ruprecht, RM AF Ferrantelli, F Xu, WD Hofmann-Lehmann, R Li, PL Cavacini, L Posner, M Katinger, H Stiegler, G McClure, H Ruprecht, RM TI The correlates of protective immunity against HIV as determined by passive immunization with human neutralizing monoclonal antibodies in primates SO GENE THERAPY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Inst Appl Microbiol, Vienna, Austria. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RI Hofmann-Lehmann, Regina/C-6528-2009; Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2001 VL 8 SU 1 BP S2 EP S2 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 476KC UT WOS:000171224500006 ER PT J AU Martuza, RL AF Martuza, RL TI Conditionally replicating herpes simplex viral vectors for cancer therapy. SO GENE THERAPY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2001 VL 8 SU 1 BP S5 EP S5 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 476KC UT WOS:000171224500020 ER PT J AU Rabkin, SD Martuza, R Toda, M Todo, T AF Rabkin, SD Martuza, R Toda, M Todo, T TI Defective vector replication-competent helper HSV combinations for cancer therapy SO GENE THERAPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA 02129 USA. RI rabkin, samuel/C-2443-2012; Toda, Masahiro/L-2268-2013 OI rabkin, samuel/0000-0003-2344-2795; NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2001 VL 8 SU 1 BP S11 EP S11 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 476KC UT WOS:000171224500042 ER PT J AU Qian, Y Fritzsch, B Shirasawa, S Chen, CL Choi, YJ Ma, QF AF Qian, Y Fritzsch, B Shirasawa, S Chen, CL Choi, YJ Ma, QF TI Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3 SO GENES & DEVELOPMENT LA English DT Article DE noradrenergic; sensory neurons; respiratory control; RnX; Phox2b; Mash1 ID HOMEOBOX GENE PHOX2B; NERVOUS-SYSTEM; DEVELOPMENTAL EXPRESSION; PREBOTZINGER COMPLEX; RESPIRATORY CONTROL; NEURAL CREST; BHLH PROTEIN; HOX11 GENE; MICE; GANGLIA AB Brainstem visceral sensory and (nor)adrenergic neurons play crucial roles in modulating cardiovascular and respiratory functions. The origins and formation of these neurons are poorly understood. Here we show that these two classes of neurons are derived from Mash1-positive precursor cells, and can be prospectively identified by combinatorial expression of two homeobox genes, Rnx and Phox2 (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from respiratory failure. Here we show that Rnx function is required for formation of first-order relay visceral sensory neurons in the brainstem. In addition, as in Phox2b-deficient mice, the development of most (nor)adrenergic centers is compromised in Rnx mutants. We also provide genetic evidence to show that Rnx and Phox2 proteins may function independently to specify the (nor)adrenergic phenotype. Out studies reveal a surprising ontogenetic relationship between relay visceral sensory and (nor)adrenergic neurons, and suggest that it may be a common theme in the developing nervous system that the same set of transcriptional regulators is associated with formation of multiple components within a neuronal network. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. Int Med Ctr Japan, Dept Pathol, Tokyo 1628655, Japan. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. OI Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [2 P01 DC 0015, T32 DC000015]; NIDCR NIH HHS [1 R01 DE13843-01, R01 DE013843] NR 56 TC 85 Z9 88 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2001 VL 15 IS 19 BP 2533 EP 2545 DI 10.1101/gad.921501 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 480UW UT WOS:000171482000006 PM 11581159 ER PT J AU Yahata, T Shao, WL Endoh, H Hur, JY Coser, KR Sun, HP Ueda, Y Kato, S Isselbacher, KJ Brown, M Shioda, T AF Yahata, T Shao, WL Endoh, H Hur, JY Coser, KR Sun, HP Ueda, Y Kato, S Isselbacher, KJ Brown, M Shioda, T TI Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein SO GENES & DEVELOPMENT LA English DT Article DE CITED protein; CBP/p300; estrogen receptor; nuclear receptor; transcriptional coactivator; transforming growth factor-alpha ID MELANOCYTE-SPECIFIC GENE; BREAST-CANCER CELLS; GROWTH-FACTOR-ALPHA; NUCLEAR-PROTEIN; RECEPTOR-ALPHA; TGF-ALPHA; EXPRESSION; MSG1; ACTIVATION; MRG1 AB CITED1, a CBP/p300.binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-alpha (ER alpha) and ER beta in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ER alpha in an estrogen-dependent manner through its transactivating domain, and this binding activity was separable from its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing the estrogen-dependent interaction between p300 and ER alpha. The estrogen-induced expression of the transforming growth factor-alpha (TGF-alpha) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrogen-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that endogenous CITED1 is recruited to the chromosomal TGF-alpha promoter in MCF-7 cells in an estrogen-dependent manner but not to the pS2 promoter. These results suggest that CITED1 may play roles in regulation of estrogen sensitivity in a gene-specific manner. C1 Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Yamanouchi Pharmaceut, Mol Med Labs, Tsukuba, Ibaraki 305, Japan. Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 113, Japan. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [R01 CA082230, R01-CA57374, R01-CA82230] NR 41 TC 73 Z9 82 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2001 VL 15 IS 19 BP 2598 EP 2612 DI 10.1101/gad.906301 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 480UW UT WOS:000171482000011 PM 11581164 ER PT J AU Serluca, FC Sidow, A Mably, JD Fishman, MC AF Serluca, FC Sidow, A Mably, JD Fishman, MC TI Partitioning of tissue expression accompanies multiple duplications of the Na plus /K+ ATPase alpha subunit gene SO GENOME RESEARCH LA English DT Article ID VERTEBRATE GENOME EVOLUTION; NA,K-ATPASE BETA-SUBUNIT; MOLECULAR-CLONING; EXTRACELLULAR DOMAIN; ZEBRAFISH GENOME; NA+/K+-ATPASE; SODIUM-PUMP; MAP; IDENTIFICATION; NA+,K+-ATPASE AB Vertebrate genomes contain multiple copies of related genes that arose through gene duplication. In the past it has been proposed that these duplicated genes were retained because of acquisition of novel beneficial functions. A more recent model, the duplication-degeneration-complementation hypothesis (DDC), posits that the functions of a single gene may become separately allocated among the duplicated genes, rendering both duplicates essential. Thus far, empirical evidence for this model has been limited to the engrailed and sox family of developmental regulators, and it has been unclear whether it may also apply to ubiquitously expressed genes with essential functions for cell survival. Here we describe the cloning of three zebrafish a subunits of the Na(+),K(+)-ATPase and a comprehensive evolutionary analysis of this gene family. The predicted amino acid sequences are extremely well conserved among vertebrates. The evolutionary relationships and the map positions of these genes and of other a-like sequences indicate that both tandem and ploidy duplications contributed to the expansion of this gene family in the teleost lineage. The duplications are accompanied by acquisition of clear functional specialization, consistent with the DDC model of genome evolution. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dev Biol Lab, Boston, MA USA. Massachusetts Gen Hosp, Dev Biol Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02119 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01HL63206]; NIDDK NIH HHS [R01DK55383] NR 38 TC 31 Z9 31 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2001 VL 11 IS 10 BP 1625 EP 1631 DI 10.1101/gr.192001 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 480HM UT WOS:000171456000004 PM 11591639 ER PT J AU Tornatore, J Lewis, M Narayan, S Sherman, C Bremer, K Hepburn, K AF Tornatore, J Lewis, M Narayan, S Sherman, C Bremer, K Hepburn, K TI Two perspectives on caring for a spouse with dementia: More work or an affirmation of the relationship? SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98108 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Metropolitan State Univ, St Paul, MN 55106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400146 ER PT J AU Villa, VM Harada, N AF Villa, VM Harada, N TI The aging Vietnam veteran: Evidence of health vulnerabilities SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Publ Hlth, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 46 EP 46 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400165 ER PT J AU Morgan, K Greco, MA Shiromani, P Yalla, S Sullivan, M AF Morgan, K Greco, MA Shiromani, P Yalla, S Sullivan, M TI Evidence of orexins in the urinary bladder SO GERONTOLOGIST LA English DT Meeting Abstract C1 Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 88 EP 88 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400309 ER PT J AU Ruckdeschel, K Van Haitsma, K AF Ruckdeschel, K Van Haitsma, K TI A workshop for nursing home staff: Recognizing and responding to their own and residents' emotions SO GERONTOLOGIST LA English DT Meeting Abstract C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Philadelphia Geriatr Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 196 EP 197 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400695 ER PT J AU Hazuda, HP Gerety, MB Lee, S Mulrow, CD Lichtenstein, MJ AF Hazuda, HP Gerety, MB Lee, S Mulrow, CD Lichtenstein, MJ TI The ADAPT: A new measure of subclinical disability (SCD) SO GERONTOLOGIST LA English DT Meeting Abstract 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 GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 257 EP 257 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400912 ER PT J AU Plowman, JL Siddle, J Fox, AR AF Plowman, JL Siddle, J Fox, AR TI The mobile geriatric unit (MGU): A GRECC demonstration project SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 333 EP 334 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401187 ER PT J AU Fink, DJ AF Fink, DJ TI Stroke update: Current therapy and prospects for the future SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15240 USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 348 EP 348 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401240 ER PT J AU Hedrick, SC AF Hedrick, SC TI Outcomes of Medicaid funded community residential care in Washington State SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 361 EP 361 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401284 ER PT J AU Kier, FJ Molinari, V Kunik, ME AF Kier, FJ Molinari, V Kunik, ME TI Obtaining age-related mental health competency: What is needed? SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 381 EP 382 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401361 ER PT J AU Spiro, MJ Spiro, RG AF Spiro, MJ Spiro, RG TI Release of polymannose oligosaccharides from vesicular stomatitis virus G protein during endoplasmic reticulum-associated degradation SO GLYCOBIOLOGY LA English DT Article DE vesicular stomatitis virus G protein; endoplasmic reticulum-associated degradation; polymannose oligosaccharide release; endomannosidase; castanospermine ID N-LINKED OLIGOSACCHARIDES; NEWLY SYNTHESIZED GLYCOPROTEINS; ALPHA-D-MANNOSIDASE; RAT-LIVER GOLGI; QUALITY-CONTROL; GLYCOPEPTIDE EXPORT; HEPG2 CELLS; INTERMEDIATE COMPARTMENT; MOLECULAR CHAPERONE; SECRETORY PATHWAY AB To further explore the localization of the N-deglycosylation involved in the endoplasmic reticulum (ER)-associated quality control system we studied HepG2 cells infected with vesicular stomatitis virus (VSV) and its ts045 mutant, as in this system oligosaccharide release can be attributed solely to the VSV glycoprotein (G protein). We utilized the restricted intracellular migration of the mutant protein as well as dithiothreitol (DTT), low temperature, and a castanospermine (CST)-imposed glucosidase blockade to determine in which intracellular compartment deglycosylation takes place. Degradation of the VSV ts045 G protein was considerably greater at the nonpermissive than at the permissive temperature; this was reflected by a substantial increase in polymannose oligosaccharide release. Under both conditions these oligosaccharides were predominantly in the characteristic cytosolic form, which terminates in a single N-acetylglucosamine (OS-GlcNAc(1)); this was also the case in the presence of DTT, which retains the G protein completely in the ER. However when cells infected with the VSV mutant were examined at 15 degreesC or exposed to CST, both of which represent conditions that impair ER-to-cytosol transport, the released oligosaccharides were almost exclusively (>95%) in the vesicular OS-GlcNAC(2) form; glucosidase blockade had a similar effect on the wld-type virus. Addition of puromycin to glucosidase-inhibited cells resulted in a pronounced reduction (>90%) in oligosaccharide release, which reflected a comparable impairment in glycoprotein biosynthesis and indicated that the OS-GlcNAc(2) components originated from protein degradation rather than hydrolysis of oligosaccharide lipids. Our findings are consistent with N-deglycosylation of the VSV G protein in the ER and the subsequent transport of the released oligosaccharides to the cytosol where OS-GlcNAc(2) to OS-GlcNAc(1) conversion by an endo-beta -N-acetylglucosaminidase takes place. Studies with the ts045 G protein at the nonpermissive temperature permitted us to determine that it can be processed by Golgi endomannosidase although remaining endo H sensitive, supporting the concept that it recycles between the ER and cis-Golgi compartments. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 17477] NR 52 TC 18 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 BP 803 EP 811 DI 10.1093/glycob/11.10.803 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800003 PM 11588156 ER PT J AU Ohtsuka, Y Lee, J Stamm, DS Sanderson, IR AF Ohtsuka, Y Lee, J Stamm, DS Sanderson, IR TI MIP-2 secreted by epithelial cells increases neutrophil and lymphocyte recruitment in the mouse intestine SO GUT LA English DT Article DE chemokines; epithelial cells; intestinal mucosa; leucocyte recruitment; transgenic mouse ID MACROPHAGE INFLAMMATORY PROTEIN-2; C-X-C; BINDING-PROTEIN; TRANSGENIC MICE; BOWEL-DISEASE; REGULATED EXPRESSION; LAMINA PROPRIA; MESSENGER-RNA; IN-VITRO; INTERLEUKIN-8 AB Background-Invasion of the intestinal mucosa by leucocytes is a characteristic of intestinal inflammation but the role of the epithelium in orchestrating this recruitment has not been examined in vivo. Cultured intestinal epithelial cells secrete a wide variety of chemokines, often in response to agents present in the intestinal lumen. Macrophage inflammatory protein 2 (MIP-2) is a chemokine that attracts neutrophils, and its secretion from intestinal epithelial cells is enhanced by inflammatory stimuli such as interleukin 1 beta. We hypothesised that the production of MIP-2 by epithelial cells would increase leucocyte migration into the intestine. Aim-To study the effects of a chemokine secreted from intestinal epithelial cells in vivo. Methods-MIP-2 was expressed in the mouse intestinal epithelium using an epithelial cell specific promoter from the gene encoding the intestinal fatty acid binding protein. The intestines of these transgenic mice were then analysed. Results-Epithelial cells from transgenic mice expressed MIP-2 but wild-type mice did not. Neutrophil recruitment, examined by myeloperoxidase (MPO) staining and total MPO activity per unit weight of intestine, was significantly increased in transgenic mice in both the small intestine and proximal colon, and this was blocked by anti-MIP-2 antibody treatment. Both intraepithelial and lamina propria lymphocytes were also increased in transgenic mice. They showed chemotactic activity to MIP-2 in the Boyden chambers and expressed MIP-2 receptor (CXCR-2) mRNA confirmed by reverse transcription-polymerase chain reaction. Conclusion-These experiments are the first to show a functional role for epithelial chemokines in vivo and reveal an unexpected role for the neutrophil chemokine MIP-2 in controlling mucosal lymphocyte migration. C1 St Bartholomews & Royal London Sch Med & Dent, Dept Adult & Paediat Gastroenterol, London EC1A 7BE, England. Massachusetts Gen Hosp, Dev Gastroenterol Lab, Harvard Clin Nutr Res Ctr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. RP Sanderson, IR (reprint author), St Bartholomews & Royal London Sch Med & Dent, Dept Adult & Paediat Gastroenterol, Suite 31,Dominion House,59 Bartholomew Close, London EC1A 7BE, England. FU NIAID NIH HHS [AI43472]; NIDDK NIH HHS [DK40561, DK43351, DK47753] NR 33 TC 73 Z9 76 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2001 VL 49 IS 4 BP 526 EP 533 DI 10.1136/gut.49.4.526 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476LT UT WOS:000171229100014 PM 11559650 ER PT J AU Linnan, LA Sorensen, G Colditz, G Klar, N Emmons, KM AF Linnan, LA Sorensen, G Colditz, G Klar, N Emmons, KM TI Using theory to understand the multiple determinants of low participation in worksite health promotion programs SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID PHYSICAL-ACTIVITY INTERVENTIONS; CARDIOVASCULAR RISK REDUCTION; SMOKING CESSATION PROGRAM; WORKPLACE HEALTH; EMPLOYEE PARTICIPATION; ORGANIZATIONAL-FACTORS; WELLNESS PROGRAM; PERSPECTIVE; FITNESS; TRIAL AB Low participation at the employee or worksite level limits the potential public health impact of worksite-based interventions. Ecological models suggest that multiple levels of influence operate to determine participation patterns in worksite health promotion programs. Most investigations into the determinants of low participation study the intrapersonal, interpersonal, and institutional influences on employee participation. Community- and policy-level influences have not received attention, nor has consideration been given to worksite-level participation issues. The purpose of this article is to discuss one macrosocial theoretical perspective-political economy of health-that may guide practitioners and researchers interested in addressing the community- and policy-level determinants of participation in worksite health promotion programs. The authors argue that using theory to investigate the full spectrum of determinants offers a more complete range of intervention and research options for maximizing employee and worksite levels of participation. C1 Univ N Carolina, Sch Publ Hlth Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Linnan, LA (reprint author), Univ N Carolina, Sch Publ Hlth Hlth Behav & Hlth Educ, CB 7440, Chapel Hill, NC 27599 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 85 TC 72 Z9 72 U1 2 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2001 VL 28 IS 5 BP 591 EP 607 DI 10.1177/109019810102800506 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475FR UT WOS:000171152100005 PM 11575688 ER PT J AU Kieran, MW Billett, A AF Kieran, MW Billett, A TI Antiangiogenesis therapy - Current and future agents SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE-KINASE; MATRIX METALLOPROTEINASE INHIBITOR; BLOOD-VESSEL FORMATION; TUMOR ANGIOGENESIS; IN-VIVO; PHASE-I; PANCREATIC-CANCER; MULTIPLE-MYELOMA; KAPOSIS-SARCOMA AB Approaches to cancer therapy for most tumors in adults and children have changed little in 50 years: surgery, radiation, and chemotherapy are standard for many solid tumors, When the concept of angiogenesis in cancer biology was introduced in the 1970s, there was little recognition of the therapeutic potential of attacking a tumor's blood supply. Advances in understanding the molecular processes that regulate tumor blood supply and novel agents that can interfere with them have generated a great deal of scientific interest and excitement. This article reviews the current understanding of angiogenesis and its role in cancer then discusses new therapeutic options in animals and humans, with a focus on pediatric tumors and the potential for treating them. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Oncol Inpatient Unit, Boston, MA USA. Harvard Univ, Med Sch, Boston, MA USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 116 TC 15 Z9 21 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2001 VL 15 IS 5 BP 835 EP + DI 10.1016/S0889-8588(05)70254-9 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 505JG UT WOS:000172909200004 PM 11765376 ER PT J AU Fisher, DE AF Fisher, DE TI Pathways of apoptosis and the modulation of cell death in cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID NECROSIS-FACTOR RECEPTOR; NF-KAPPA-B; C-MYC PROTEIN; P53 TUMOR-SUPPRESSOR; BCL-X-L; DOMAIN-CONTAINING PROTEIN; MYELOID-LEUKEMIA CELLS; DNA-BINDING DOMAIN; CYTOCHROME-C; IN-VIVO AB Although cell death once was viewed exclusively as the disordered, chaotic outcome of metabolic catastrophe, apoptosis now is recognized as a highly ordered, evolutionarily conserved, and genetically selected program that is essential for normal development. The death receptor pathway of apoptosis, cytotoxic T cells, prolife survival signals, Bcl-2 family of regulators, p53 and regulated cell death in cancer, and oncogenes are reviewed. Future prospects in this arena also are discussed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol & Oncol, Boston, MA USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, D630,44 Binney St, Boston, MA 02115 USA. NR 226 TC 18 Z9 19 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2001 VL 15 IS 5 BP 931 EP + DI 10.1016/S0889-8588(05)70258-6 PG 27 WC Oncology; Hematology SC Oncology; Hematology GA 505JG UT WOS:000172909200008 PM 11765380 ER PT J AU Ochoa, ER Campo-Ruiz, V Lauwers, GY Gonzalez, S AF Ochoa, ER Campo-Ruiz, V Lauwers, GY Gonzalez, S TI Near-infrared confocal reflectance microscopy of the human liver. A pilot study. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 68 BP 190A EP 190A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700068 ER PT J AU Huang, L Fowler, N Mehal, WZ Schmidt, E Crispe, N Koziel, MJ AF Huang, L Fowler, N Mehal, WZ Schmidt, E Crispe, N Koziel, MJ TI Hepatocytes expressing HCV structural proteins enhance apoptosis of activated T cells in vivo. SO HEPATOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Yale Univ, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 314 BP 252A EP 252A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700315 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Does diabetes increase the risk of acute hepatic failure?. SO HEPATOLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 491 BP 295A EP 295A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700485 ER PT J AU Heathcote, EJ Jeffers, L Perrillo, R Wright, T Sherman, M Gilson, R Shakil, AO Namini, H James, C Ho, V Fry, J Brosgart, CL AF Heathcote, EJ Jeffers, L Perrillo, R Wright, T Sherman, M Gilson, R Shakil, AO Namini, H James, C Ho, V Fry, J Brosgart, CL TI Serum HBV DNA suppression and seroconversion following long-term adefovir dipivoxil therapy in chronic hepatitis B patients. SO HEPATOLOGY LA English DT Meeting Abstract C1 Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Univ Miami, Miami, FL 33152 USA. Ochsner Clin N 8, New Orleans, LA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Toronto Gen Hosp, Toronto, ON, Canada. Mortimer Market Ctr, London, England. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Gilead Sci Inc, Foster City, CA 94404 USA. RI Gilson, Richard/C-5123-2009 NR 0 TC 6 Z9 7 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 575 BP 316A EP 316A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700569 ER PT J AU Sandberg, JA Rossi, SJ Gordon, GS Turik, MA Braun, DK Aitchison, R Babcock, SA Hansen, B Wright, T Blatt, LM AF Sandberg, JA Rossi, SJ Gordon, GS Turik, MA Braun, DK Aitchison, R Babcock, SA Hansen, B Wright, T Blatt, LM TI Safety analysis of a phase I study of HEPTAZYME (TM), a nuclease resistant ribozyme targeting hepatitis C (HCV) RNA. SO HEPATOLOGY LA English DT Meeting Abstract C1 Ribozyme Pharmaceut Inc, Boulder, CO USA. San Francisco VAMC, San Francisco, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 646 BP 333A EP 333A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700640 ER PT J AU Hampel, H Rabeneck, L El-Serag, HB AF Hampel, H Rabeneck, L El-Serag, HB TI "Extrahepatic" disorders associated with hepatitis C infection: A case-control study. SO HEPATOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 681 BP 342A EP 342A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700674 ER PT J AU He, WP Contreras, AM Hiasa, Y Schmidt, EV Chung, RT AF He, WP Contreras, AM Hiasa, Y Schmidt, EV Chung, RT TI Interferon exerts dose-dependent selective inhibitory effects on HCV internal ribosome entry site-mediated translation in a novel replication system. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 742 BP 357A EP 357A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700736 ER PT J AU Bilello, JP Delaney, WE Boyce, FM Isom, HC AF Bilello, JP Delaney, WE Boyce, FM Isom, HC TI Baculovirus entry into nondividing hepatocytes is enhanced by transient disruption of intercellular junctions. SO HEPATOLOGY LA English DT Meeting Abstract C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. Gilead Sci, Foster City, CA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 834 BP 380A EP 380A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700827 ER PT J AU Hiasa, Y Kamegaya, Y Contreras, AM He, WP Schmidt, EV Chung, RT AF Hiasa, Y Kamegaya, Y Contreras, AM He, WP Schmidt, EV Chung, RT TI PKR levels are increased in hepatitis C virus-related hepatocellular carcinoma. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 878 BP 391A EP 391A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700871 ER PT J AU Abraczinskas, DR Pascual, M Contreras, AM Feng, S Ko, D Baid, S Ookubo, R Schoenfeld, D Cosimi, AB Chung, RT AF Abraczinskas, DR Pascual, M Contreras, AM Feng, S Ko, D Baid, S Ookubo, R Schoenfeld, D Cosimi, AB Chung, RT TI Low-dose steroid induction with tacrolimus-mycophenolate mofetil is associated with increased risk of HCV allograft hepatitis in liver transplant recipients with HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Faulkner Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 950 BP 409A EP 409A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700943 ER PT J AU Contreras, AM He, WP Hiasa, Y Leonetti, RM Schmidt, EV Chung, RT AF Contreras, AM He, WP Hiasa, Y Leonetti, RM Schmidt, EV Chung, RT TI Quasispecies generation in a novel HCV RNA replication system is region-specific and increased by addition of ribavirin. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 963 BP 413A EP 413A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700956 ER PT J AU Bini, E Brau, N Ho, S Johnson, D Rossi, SJ Jeffers, L Wright, T AF Bini, E Brau, N Ho, S Johnson, D Rossi, SJ Jeffers, L Wright, T TI Current HCV therapies do not meet the needs of the majority of US veterans. SO HEPATOLOGY LA English DT Meeting Abstract C1 New York Harbor VAMC, New York, NY USA. Bronx VAMC, Bronx, NY USA. Minneapolis VAMC, Minneapolis, MN USA. Bay Pines VAMC, Bay Pines, FL USA. San Francisco VAMC, San Francisco, CA USA. Miami VAMC, Miami, FL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 991 BP 420A EP 420A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700983 ER PT J AU Jackson, TE Brown-Ausberger, T Hillgren, K Rossi, SJ Wright, T Blatt, L Turik, M Sandberg, JA AF Jackson, TE Brown-Ausberger, T Hillgren, K Rossi, SJ Wright, T Blatt, L Turik, M Sandberg, JA TI Pharmacokinetic analysis of a phase I study of HEPTAZYME (TM) in patients with HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Ribozyme Pharmaceut Inc, Westminster, CO USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. San Francisco VAMC, San Francisco, CA USA. Ribozyme Pharmaceut Inc, Boulder, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 994 BP 420A EP 420A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700986 ER PT J AU Lauer, GM Nguyen, TN Day, CL Klenerman, P Chung, RT Walker, BD AF Lauer, GM Nguyen, TN Day, CL Klenerman, P Chung, RT Walker, BD TI Comprehensive analysis of the HCV-specific CD8+T cell response in individuals with chronic or resolved HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. John Radcliffe Hosp, Oxford OX3 9DU, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1039 BP 432A EP 432A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701031 ER PT J AU Sevigny, J Dranoff, JA Braun, N Lemmens, R Kruglov, E Csizmadia, E Smith, RN Zimmermann, H Kirley, T Robson, SC AF Sevigny, J Dranoff, JA Braun, N Lemmens, R Kruglov, E Csizmadia, E Smith, RN Zimmermann, H Kirley, T Robson, SC TI Identification and characterization of membrane-associated hepatic NTP diphosphohydrolases. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Frankfurt, Inst Zool, Biozentrum, AK NCh, D-6000 Frankfurt, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Cincinnati, Cincinnati, OH USA. RI Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1118 BP 451A EP 451A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701110 ER PT J AU Sugimoto, K Stadanlick, J Brensinger, C Rensman, B Chang, KM AF Sugimoto, K Stadanlick, J Brensinger, C Rensman, B Chang, KM TI Effect of host ethnicity and viral genotype in immnopathogenesis of chronic hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract 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 W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1232 BP 480A EP 480A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701224 ER PT J AU Day, CL Lauer, GM Nguyen, TN Chung, RT Walker, BD AF Day, CL Lauer, GM Nguyen, TN Chung, RT Walker, BD TI Breadth and specificity of CD4+T cells in resolved hepatitis C virus infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1250 BP 484A EP 484A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701241 ER PT J AU Brau, N Bini, EJ Aytaman, A Finch, DA Stancic, S AF Brau, N Bini, EJ Aytaman, A Finch, DA Stancic, S TI Migraine headaches during treatment with oral ribavirin in combination therapy for chronic hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. VA New York Harbor HCS, New York, NY USA. VA New York Harbor HCS, Brooklyn, NY USA. VA Hudson Valley HCS, Montrose, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1694 BP 595A EP 595A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701685 ER PT J AU Brau, N Xiao, PY Finch, DA Lieber, CS AF Brau, N Xiao, PY Finch, DA Lieber, CS TI Interferon dose increase for early (week 12) non-responders to interferon alfa-2b+ribavirin therapy for chronic hepatitis C does not lead to a viral response at 48 weeks. SO HEPATOLOGY LA English DT Meeting Abstract C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1703 BP 598A EP 598A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701694 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Tissue and molecular events in human conjunctival scarring in ocular cicatricial pemphigoid SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE ocular cicatricial pemphigoid; conjunctiva; fibrosis; collagen; transforming growth factor-beta 1; heat shock protein 47 ID COLLAGEN-BINDING HEAT-SHOCK-PROTEIN-47; MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; GROWTH-FACTOR PDGF; SYSTEMIC-SCLEROSIS; BASEMENT-MEMBRANE; SCLERODERMA FIBROBLASTS; PULMONARY FIBROSIS; MESSENGER-RNA; INTERSTITIAL FIBROSIS; EXTRACELLULAR-MATRIX AB Detailed histomorphometric analysis of human conjunctival biopsy specimens has convincingly demonstrated that tissue remodeling of the extracellular matrix (ECM) is an essential and dynamic process associated with conjunctival scarring in ocular cicatricial pemphigoid (OCP). The conjunctival scarring often eventually results in impaired vision and/or blindness. The molecular mechanisms of conjunctival scarring are not completely understood. Accumulating evidence indicates that the early phase of conjunctival fibrosis is linked with an immuno-inflammatory process mediated by cytokines released by activated conjunctival cells and/or by infiltrating cells. Fibrogenic cytokines secreted by inflammatory cells and fibroblasts might actively be involved in remodeling of the matrix within the conjunctival stroma, possibly by regulating the altered metabolism of matrix proteins. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. NR 114 TC 20 Z9 20 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 2001 VL 16 IS 4 BP 1203 EP 1212 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 482BA UT WOS:000171553900024 PM 11642740 ER PT J AU Bonmassar, G Hadjikhani, N Ives, JR Hinton, D Belliveau, JW AF Bonmassar, G Hadjikhani, N Ives, JR Hinton, D Belliveau, JW TI Influence of EEG electrodes on the BOLD fMRI signal SO HUMAN BRAIN MAPPING LA English DT Article DE electroencephalography; functional magnetic resonance imaging; MRI; MRI artifacts; magnetic susceptibility; eddy currents; chemical shifts ID HUMAN VISUAL-CORTEX; MAGNETIC-RESONANCE SPECTROSCOPY; FUNCTIONAL MRI; EPILEPSY; LOCALIZATION; STIMULATION; ACTIVATION; CONTRAST; PATIENT; AREAS AB Measurement of the EEG during fMRI scanning can give rise to image distortions due to magnetic susceptibility, eddy currents or chemical shift artifacts caused by certain types of EEG electrodes, cream, leads, or amplifiers. Two different creams were tested using MRS and T2* measurements, and we found that the one with higher water content was superior. This study introduces an index that quantifies the influence of EEG equipment on the BOLD fMRI signal. This index can also be used more generally to measure the changes in the fMRI signal due to the presence of any type of device inside (or outside) of the field of view (e.g., with fMRI and diffuse optical tomography, infrared imaging, transcranial magnetic stimulation, ultrasound imaging, etc.). Quantitative noise measurements are hampered by the normal variability of functional activation within the same subject and by the different slice profiles obtained when inserting a subject multiple times inside a MR imaging system. Our measurements account for these problems by using a matched filtering of cortical surface maps of functional activations. The results demonstrate that the BOLD signal is not influenced by the presence of EEG electrodes when using a properly constructed MRI compatible recording cap. C1 Massachusetts Gen Hosp, A Martinos Ctr, Charlestown, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Bonmassar, G (reprint author), Massachusetts Gen Hosp, A Martinos Ctr, Bldg 149 13th St, Charlestown, MA 02139 USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NCRR NIH HHS [P41RR14075]; NINDS NIH HHS [R01 NS37462] NR 38 TC 47 Z9 48 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2001 VL 14 IS 2 BP 108 EP 115 DI 10.1002/hbm.1045 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 478CJ UT WOS:000171325100004 PM 11500994 ER PT J AU Boumil, RM Lee, JT AF Boumil, RM Lee, JT TI Forty years of decoding the silence in X-chromosome inactivation SO HUMAN MOLECULAR GENETICS LA English DT Review ID DNA METHYLTRANSFERASE GENE; XIST GENE; HISTONE MACROH2A1; MOUSE EMBRYOS; IMMUNODEFICIENCY SYNDROME; REPEAT HYPOTHESIS; FEMALE MAMMALS; LINKED GENES; EXPRESSION; RNA AB In 1961, Mary Lyon first put forth the hypothesis that one X chromosome is inactivated in each cell of the female mammal. As we enter the new millennium and complete 40 years of study, the field of X-inactivation is rich with ideas and many contrasting viewpoints. This review will focus on the random form of X-inactivation and present the latest views on its mechanism. Much attention has been focused on the genetic parsing of X-chromosome counting, choice, silencing and maintenance. It is now known that counting is functionally distinct from choice and that initiation and establishment of silencing are distinct from maintenance. Since Xist's seminal discovery 10 years ago, significant progress has been made towards understanding its function. Required only for initiation and establishment, Xist must act within a narrow developmental window, but its precise mode of action remains elusive. The ongoing search for Xist RNA-binding factors and effector proteins for silencing has led to members of the macroH2A family of histone variants. Finally, the recent discovery of Tsix implicates regulation of Xist expression by an antisense mechanism. Required for choice but not counting, Tsix blocks Xist RNA accumulation and hence blocks initiation of silencing on the future active X. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Mol Biol, Howard Hughes Med Inst,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Mol Biol, Howard Hughes Med Inst,Dept Genet, Boston, MA 02114 USA. NR 79 TC 112 Z9 119 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2001 VL 10 IS 20 BP 2225 EP 2232 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 486AG UT WOS:000171795300007 PM 11673405 ER PT J AU Grompe, M D'Andrea, A AF Grompe, M D'Andrea, A TI Fanconi anemia and DNA repair SO HUMAN MOLECULAR GENETICS LA English DT Review ID INTERSTRAND CROSS-LINKS; COMPLEMENTATION GROUP-A; GROUP-C PROTEIN; NUCLEAR-COMPLEX; CELL-CYCLE; G2 PHASE; HEMATOLOGIC ABNORMALITIES; CHROMOSOMAL-ABERRATIONS; HEMATOPOIETIC-CELLS; APOPTOTIC RESPONSES AB Fanconi anemia (FA) is an autosomal recessive disorder caused by defects in at least eight distinct genes FANCA, B, C, D1, D2, E, F and G. The clinical phenotype of all FA complementation groups is similar and is characterized by progressive bone marrow failure, cancer proneness and typical birth defects. The principal cellular phenotype is hypersensitivity to DNA damage, particularly interstrand DNA crosslinks. The FA proteins constitute a multiprotein pathway whose precise biochemical function(s) remain unknown. Five of the FA proteins (FANCA, C, E, F and G) interact in a nuclear complex upstream of FANCD2. FANCB and FANCD1 have not yet been cloned, but it is likely that FANCB is part of the nuclear complex and that FANCD1 acts downstream of FANCD2. The FA nuclear complex regulates the mono-ubiquitination of FANCD2 in response to DNA damage, resulting in targeting of this protein into nuclear foci. These foci also contain BRCA1 and other DNA damage response proteins. In male meiosis, FANCD2 also co-localizes with BRCA1 at synaptonemal complexes. Together, these data suggest that the FA pathway functions primarily as a DNA damage response system, although its exact role (direct involvement in DNA repair versus indirect, facilitating role) has not yet been defined. C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Grompe, M (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, 3181 SW Sam Jackson Pk,Rd L103, Portland, OR 97201 USA. FU NHLBI NIH HHS [1PO1HL48546, R01HL52725] NR 100 TC 101 Z9 103 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2001 VL 10 IS 20 BP 2253 EP 2259 DI 10.1093/hmg/10.20.2253 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 486AG UT WOS:000171795300010 PM 11673408 ER PT J AU Perkins, RB Hall, JE Martin, KA AF Perkins, RB Hall, JE Martin, KA TI Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea SO HUMAN REPRODUCTION LA English DT Article DE aetiology; hypothalamic amenorrhoea; neuro-endocrine; recovery ID GONADOTROPIN-RELEASING-HORMONE; LUTEINIZING-HORMONE; ANOREXIA-NERVOSA; YOUNG-WOMEN; WEIGHT-LOSS; SECRETION; BLOCKADE; CYCLE; IRREGULARITIES; ABERRATIONS AB BACKGROUND: Hypothalamic amenorrhoea (HA) is a syndrome associated with infertility and osteopenia in reproductive-age women. METHODS: To understand better the natural history of this disorder, 28 women participated in a retrospective, questionnaire-based analysis to elucidate factors associated with spontaneous recovery. RESULTS: 54% of subjects developed HA related to an eating disorder, 21% related to stress +/- weight loss, and 25% without obvious contributing factors (idiopathic). HA associated with a clear precipitant had a better prognosis than idiopathic HA (71 versus 29% recovery; P < 0.05). Reversal of the inciting factor appeared necessary but not sufficient for recovery (83% recovery if factor reversed). Normal menarche occurred in 61% of subjects, oligomenorrhoea in 32%, and primary amenorrhoea in 7%. Oligomenorrhoea and normal menarche showed a trend toward better prognosis than primary amenorrhoea (NS). Compared with controls, 46% of HA patients had decreased frequency of LH pulses, 7% decreased amplitude, 18% decreases in both frequency and amplitude, 18% absent pulses, and 11% normal-appearing pulses. Pulse pattern at baseline did not predict recovery. CONCLUSIONS: The aetiology of HA at the time of presentation predicts subsequent recovery of menstrual function. In stress, weight loss, or eating disorder-related HA, rates of recovery exceeded 80% when precipitating factors were reversed. Idiopathic HA may represent a different disorder as recovery rates were < 30%. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Martin, KA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St BHX 5, Boston, MA 02114 USA. NR 47 TC 32 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD OCT PY 2001 VL 16 IS 10 BP 2198 EP 2205 DI 10.1093/humrep/16.10.2198 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 480BY UT WOS:000171442600031 PM 11574516 ER PT J AU Wall, C Weinberg, MS Schmidt, PB Krebs, DE AF Wall, C Weinberg, MS Schmidt, PB Krebs, DE TI Balance prosthesis based on micromechanical sensors using vibrotactile feedback of tilt SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE accelerometer; balance; gyroscope; micromechanical; neuroprosthesis; postural contral; prosthesis; vestibular AB A prototype balance prosthesis has been made using miniature, high-performance inertial sensors to measure lateral head tilt and vibrotactile elements mounted on the body to display head tilt to the user. The device has been used to study the feasibility of providing artificial feedback of head tilt to reduce postural sway during quiet standing using six healthy subjects. Two vibrotactile display schemes were used: one in which the individual vibrating elements, called tactors, were placed on the shoulders (shoulder tactors); another in which columns of tactors were placed on the right and left sides of the trunk (side tactors). Root-mean-square head-tilt angle (Tilt) and center of pressure displacement (Sway) were measured for normal subjects standing in a semi-tandem Romberg position with eyes closed, under four conditions: no balance aids; shoulder tactors; side tactors; and light touch. Compared with no balance aids, the side tactors significantly reduced Tilt (35%) and Sway (33%). Shoulder tactors also significantly reduced Tilt (44%) and Sway (17%). Compared with tactors, light touch resulted in less Sway, but more Tilt. The results suggest that healthy normal subjects can reduce their lateral postural sway using head tilt information as provided by a vibrotactile display. Thus, further testing with balance-impaired subjects is now warranted. C1 Draper Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Cambridge, MA 02139 USA. MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Biomot Lab, Cambridge, MA 02139 USA. RP Weinberg, MS (reprint author), Draper Lab, 555 Tech Sq,Mail Stop 37, Cambridge, MA 02139 USA. FU NIA NIH HHS [R01 AG11255] NR 23 TC 74 Z9 75 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2001 VL 48 IS 10 BP 1153 EP 1161 DI 10.1109/10.951518 PG 9 WC Engineering, Biomedical SC Engineering GA 473ZT UT WOS:000171080300011 PM 11585039 ER PT J AU Li, XP Su, M West, CA He, CF Swanson, SJ Secomb, TW Mentzer, SJ AF Li, XP Su, M West, CA He, CF Swanson, SJ Secomb, TW Mentzer, SJ TI Effect of shear stress on efferent lymph-derived lymphocytes in contact with activated endothelial monolayers SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE shear stress; adhesion; lymphocyte; endothelial cells; image analysis ID LUNG MICROVASCULAR ENDOTHELIUM; CELL-ADHESION; FLOW; SELECTIN; MEMBRANE; IDENTIFICATION; ARREST AB Lymphocyte interactions with endothelial cells in microcirculation are an important regulatory step in the delivery of lymphocytes to peripheral sites of inflammation. In normal circumstances, the predicted wall shear stress in small venules range from 10 to 100 dyn/cm(2). Attempts to measure the adhesion of lymphocytes under physiologic conditions have produced variable results, suggesting the importance of studying biologically relevant migratory lymphocytes. To quantify the effect of shear stress on these migratory lymphocytes, we used lymphocytes obtained front sheep efferent lymph ducts. defined as migratory cells, to perfuse sheep endothelial monolayers under conditions of flow. Quantitative cytomorphometry was used to distinguish cells in contact with the endothelial monolayers front cells in the flow stream. As expected, migratory cells in contact with the normal endothelial monolayer demonstrated flow velocities less than the velocity of cells in the adjacent flow stream. The How velocities of these efferent lymphocytes were independent of cell size. To model the inflammatory microcirculation, lymphocytes were perfused over sequential endothelial monolayers to directly compare the velocity of cells in contact with cytokine-activated and unactivated control monolayers. The tumor necrosis factor and interleukin-l-activated endothelial monolayers marginally decreased cell velocities at 1.2 dyn/cm(2) (3.6%), but significantly reduced cell velocities 0.3 dyn/cm(2) (27.4%; P < 0.05). Similarly, the fraction of statically adherent lymphocytes decreased as shear stress increased to 1.2 dyn/cm(2). These results suggest that typical wall shear stress in small venules, of the order of 20 dyn/cm(2), are too high to permit adhesion and transmigration of migratory lymphocytes. Additional mechanisms must be present in vivo to facilitate lymphocyte transmigration in the inflammatory microcirculation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Surg Res Labs,Lab Immunophysiol, Boston, MA 02115 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. RP Mentzer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Surg Res Labs,Lab Immunophysiol, 44 Binney St,Room G09 JFB, Boston, MA 02115 USA. OI Secomb, Timothy/0000-0002-0176-5502 FU NHLBI NIH HHS [HL47078] NR 33 TC 14 Z9 14 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 2001 VL 37 IS 9 BP 599 EP 605 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 489NK UT WOS:000171997600010 PM 11710437 ER PT J AU Sha, DD Sutton, JP AF Sha, DD Sutton, JP TI Towards automated enhancement, segmentation and classification of digital brain images using networks of networks SO INFORMATION SCIENCES LA English DT Article DE neural networks; image enhancement; automated image segmentation; automated image classification; hierarchical networks; dynamic clustering; pattern recognition ID NEURAL NETWORKS; MODEL; MRI AB An adaptive image processing algorithm (IEEE Trans. Neural Networks 8 (1997) 169), based on biological principles, is extended and applied to enhance, segment and classify digital brain images acquired using magnetic resonance imaging (MRI). The algorithm is based on the network of networks (NoN) neural computing theory (World Cong. Neural Networks 1 (1995) 561). The initial algorithm, developed by Guan and Sutton (GS), uses vector connections among model neurons to delineate regions of pixels that have dynamic boundaries, corresponding to critical features of images. The boundaries subdivide large regions into smaller regions, where the smaller regions operate as gradient descent networks to enhance local aspects of blurred images. In this report, the authors develop and test two new algorithms that build upon the success of the GS algorithm. The first algorithm, termed the segmentation-variance (Sv) algorithm, maps pixels into discrete groups using a segmentation function of the local variance. Boundaries formed at the transition zones among groups are subsequently tuned to automatically delineate brain regions of interest. This is demonstrated using MRI scans of the human brain. In a second algorithm, pixel groupings formed using the SV algorithm are consolidated into larger groups to generate histograms. Dynamic maps and histograms capture features of object relationships and are used to classify structures. The resultant algorithm is called the dynamic segmentation and classification (DSC) algorithm. It is tested on MRI scans of four geometric patterns under various noise conditions. The SV and DSC algorithms illustrate proof of principal concepts in the evolution towards automated segmentation and classification of digital brain images. (C) 2001 Elsevier Science Inc. All rights reserved. C1 MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Univ, Charlestown, MA 02129 USA. RP Sutton, JP (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 23 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0020-0255 J9 INFORM SCIENCES JI Inf. Sci. PD OCT PY 2001 VL 138 IS 1-4 BP 45 EP 77 DI 10.1016/S0020-0255(01)00130-X PG 33 WC Computer Science, Information Systems SC Computer Science GA 459RM UT WOS:000170265100004 ER PT J AU Eisenstein, EM Eisenstein, D Smith, JC AF Eisenstein, EM Eisenstein, D Smith, JC TI The evolutionary significance of habituation and sensitization across phylogeny: A behavioral homeostasis model SO INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Article DE habituation; sensitization; evolution; learning; behavior; homeostasis; behavioral homeostasis; sensoristasis ID WITHDRAWAL REFLEX; DISHABITUATION; APLYSIA AB The phenomenon of habituation may be interpreted as a process that has evolved for filtering out iterative stimuli of little present relevance. That habituation is seen in aneural as well as neural organisms throughout phylogeny with remarkably similar characteristics suggests that its role is an important one in animal survival. If habituation is to be viewed as a process to filter out iterative stimuli that have no significant consequences. then how is sensitization to be viewed? One way of viewing these two behavioral changes, i.e. habituation and sensitization, is that they are homeostatic processes which optimize an organism's likelihood of detecting and assessing the significance of a stimulus in a new iterative series or a change in it. If one views the level of initial responsiveness to a new stimulus as a function of an organism's threshold just prior to stimulus occurrence, then "high responders" (i.e. those who initially react more strongly) are assumed to have a lower threshold for detecting and assessing the significance of this stimulus than are the "low responders" (i.e. those who initially react more weakly). Thus, high-responders would initially receive more sensory input and progressively decrease their responsiveness to a non-threatening stimulus (habituation). Likewise, initial low-responders would receive less sensory input followed by a decreased threshold and an increased response to the next stimulus occurrence (sensitization). The level of responsiveness achieved in both habituaters and sensitizers, as an asymptote is approached, is a balance between being too sensitive to an unimportant stimulus (and possibly missing other significant stimuli) and being too insensitive, and missing a change in the relevance of the present stimulus. These response changes can be taken as indices of the organism's mechanisms for achieving an appropriate threshold level to an iterative stimulus in order to accurately assess its present significance and then eventually to asymptote at an optimal stable response level. This approach toward an asymptote is a behavioral homeostatic process that reflects the accumulated significance of the iterative stimulus at each occurrence. The purpose of adding "behavioral" to the term "homeostasis" is to extend the usual meaning of the concept from primarily internal processes to also include (a) iterative external stimulation, (b) the organism's initial threshold to the initial stimulus as well as (c) the behavior which results from it. Since we are discussing organisms that range from intact, single-celled protozoa to intact mammals, as well as surgically simplified preparations, the terms stimulus, response and behavior will be used broadly. While other investigators have focused on specific cellular mechanisms underlying habituation and sensitization in a given organism, this paper focuses on the adaptive significance of these two behavioral processes viewed across phylogeny. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Fed Bur Invest, Los Angeles, CA USA. RP Eisenstein, EM (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Res & Dev 695-151, Los Angeles, CA 90073 USA. NR 39 TC 15 Z9 16 U1 0 U2 5 PU TRANSACTION PERIOD CONSORTIUM PI PISCATAWAY PA RUTGERS UNIV, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA SN 1053-881X J9 INTEGR PHYS BEH SCI JI Integr. Physiol. Behav. Sci. PD OCT-DEC PY 2001 VL 36 IS 4 BP 251 EP 265 DI 10.1007/BF02688794 PG 15 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 548DT UT WOS:000175373900001 ER PT J AU Mistry, R Rosansky, J McGuire, J McDermott, C Jarvik, L AF Mistry, R Rosansky, J McGuire, J McDermott, C Jarvik, L CA UPBEAT Collaborative Grp TI Social isolation predicts re-hospitalization in a group of older American veterans enrolled in the UPBEAT Program SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE elderly; older; veteran; social; networks; support; isolations; health; service; utilization ID HEALTH-SERVICES; SUPPORT; READMISSION; POPULATION; SCHIZOPHRENIA; MORTALITY; DISTRESS; IMPACT; ADULTS; MODEL AB Objectives Does social isolation predict re-hospitalization in a group of older men enrolled in Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT), a mental health care-coordination project at nine Veterans Affairs Healthcare Centers nationwide? Methods The current study examined 123 UPBEAT patients located at West Los Angeles, whose ratings were available on the Lubben Social Network Scale (LSNS), the SF-36 scale, the Cumulative Illness Rating Scale (CIRS) and the Mental Health Index (MHI-38) Depression and Anxiety subscales. Within one year of enrollment, 55% of patients were re-hospitalized. Odds of re-hospitalization were calculated using two logistic regression models. Social isolation risk (LSNS) and demographic covariates were included. In addition, Model I contained depression and anxiety measures (MHI-38) and physician-rated medical burden (CIRS), while in Model 2, patient-perceived physical (PCS) and mental health (MCS) subscales from the SF-36 were included. Results The group of patients who were socially isolated or at high or moderate risk for isolation, were 4-5 times more likely to be re-hospitalized within the year, than low isolation risk patients. In both Models I (chi-square = 19.86; p = 0.031) and 2 (chi-square = 26.42; p = 0.002) demographic characteristics were not significant predictors of re-hospitalization, but social isolation risk was a significant predictor (Model 1: odds ratio (OR) = 5.31; 95% confidence intervals (Cl) = 1.81-15.53; and Model 2: OR = 3.86; 95% CI = 1.39-10.73). In addition, MHI-Anxiety was a significant predictor (OR = 1.22; 95% Cl = 1.05-1.43) in Model I and in Model 2, patient-perceived physical health significantly predicted re-hospitalization (OR = 0.91; 95% CI = 0.86-0.96). Conclusion When controlling for other covariates, social isolation, physical health and mental health were significant risk factors for re-hospitalization. These findings underline the importance of assessing and addressing lack of social support, along with other factors, in the health care of older male veterans. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr 116S, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Community Hlth Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Policy & Social Sci Res, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Mistry, R (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr 116S, Mail Code 116 S,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 40 TC 35 Z9 35 U1 2 U2 14 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2001 VL 16 IS 10 BP 950 EP 959 DI 10.1002/gps.447 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 486ZE UT WOS:000171848600004 PM 11607938 ER PT J AU Vonderheide, RH Butler, MO Liu, JF Battle, TE Hirano, N Gribben, JG Frank, DA Schultze, JL Nadler, LM AF Vonderheide, RH Butler, MO Liu, JF Battle, TE Hirano, N Gribben, JG Frank, DA Schultze, JL Nadler, LM TI CD40 activation of carcinoma cells increases expression of adhesion and major histocompatibility molecules but fails to induce either CD80/CD86 expression or T cell alloreactivity SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CD40; carcinoma; costimulation; tumor immunity ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN DENDRITIC CELLS; B-CELLS; IN-VIVO; ANTITUMOR IMMUNITY; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; PROTEIN-KINASE; LIGAND; PROLIFERATION AB A major obstacle for the development of cancer immunotherapy is the poor capacity of most tumor cells to present antigen. It has previously been shown that ligation of CD40 on the surface of malignant B cells results in the induction of efficient antigen presentation primarily because of upregulated expression of MHC, costimulatory, and adhesion molecules. Ongoing clinical trials are testing the impact of CD40 ligation as immunotherapy for B cell malignancies. Because CD40 is also widely expressed in carcinomas, we studied whether CD40 activation of these cells using soluble recombinant trimeric human CD40 ligand (srhCD40L) can also induce T cell responses. Here, we show that carcinoma cells upregulate expression of CD54 and MHC molecules following in vitro exposure to srhCD40L but do not upregulate CD80 or CD86. CD40-activated carcinoma cells failed to trigger mixed lymphocyte reactions, in sharp contrast to CD40-activated lymphoma cells for which CD40 activation, as expected, resulted in increased expression of MHC, adhesion, and costimulatory molecules, and generated brisk allogeneic lymphocyte reactions. Retroviral-mediated expression of CD80 in carcinoma cells, with or without CD40 activation, triggered mixed lymphocyte reactions, provided cells were treated with IFN-gamma. Thus, the cell surface phenotype induced on carcinoma cells followina CD40 activation is not fully capable of inducing T cell proliferation; however, these results support ongoing efforts to exploit costimulation in clinical efforts aimed at increasing carcinoma immunogenicity. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vonderheide, RH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [P01-CA-66996, 1K08 CA-84050, 1K08 CA-87720, CA-79547, CA-81534] NR 44 TC 11 Z9 11 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2001 VL 19 IS 4 BP 791 EP 798 PG 8 WC Oncology SC Oncology GA 474YV UT WOS:000171135600020 PM 11562757 ER PT J AU Barker, FG Simmons, ML Chang, SM Prados, MD Larson, DA Sneed, PK Wara, WM Berger, MS Chen, PC Israel, MA Aldape, KD AF Barker, FG Simmons, ML Chang, SM Prados, MD Larson, DA Sneed, PK Wara, WM Berger, MS Chen, PC Israel, MA Aldape, KD TI EGFR overexpression and radiation response in glioblastoma multiforme SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 22-26, 2000 CL BOSTON, MASSACHUSETTS SP Amer Soc Therapeut Radiol & Oncol DE epidermal growth factor receptor; p53; glioblastoma multiforme; radiosensitivity ID EPIDERMAL-GROWTH-FACTOR; FACTOR-RECEPTOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; MAMMARY-CARCINOMA CELLS; HUMAN-BRAIN-TUMORS; P53 EXPRESSION; PROGNOSTIC-SIGNIFICANCE; ASTROCYTIC TUMORS; LABELING INDEX; HUMAN GLIOMAS AB Purpose: Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment. Methods and Materials: Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53-immunoreactivity, and p53 exon 5-8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis. Results: Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.46). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (> 50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age. Conclusion: The observed relative radioresistance of some GMs is associated with overexpression of EGFR. (C) 2001 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Neurooncol Serv, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Cox 315,32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA 09291, CA 13525] NR 81 TC 165 Z9 173 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2001 VL 51 IS 2 BP 410 EP 418 DI 10.1016/S0360-3016(01)01609-1 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 474ZR UT WOS:000171137600017 PM 11567815 ER PT J AU Reni, M Ferreri, AJM Guha-Thakurta, N Blay, JY Dell'Oro, S Biron, P Hochberg, FH AF Reni, M Ferreri, AJM Guha-Thakurta, N Blay, JY Dell'Oro, S Biron, P Hochberg, FH TI Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE primary brain lymphomas; consolidation radiotherapy; high-dose methotrexate; intrathecal chemotherapy; non-Hodgkin's lymphoma ID NON-HODGKINS-LYMPHOMA; PRIMARY CNS LYMPHOMA; RADIATION-THERAPY; NEUROLOGIC TOXICITY; INITIAL TREATMENT; CHEMOTHERAPY; SURVIVAL; MANAGEMENT; TRIAL; NEUROTOXICITY AB Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (greater than or equal to1 g/m(2)) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose (<3 g/m(2) vs. greater than or equal to3 g/m(2)), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose (< 40 Gy vs. greater than or equal to 40 Gy) was assessed in 70 irradiated complete responders. Results: No difference in overall survival (OS) was detected between mono-CHT and combination CHT (p = 0.38). MTX greater than or equal to3 g/m(2) (P = 0.04), thiotepa (p = 0.03), and intrathecal CHT (p = 0.03) improved the OS, and nitrosoureas (p = 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX greater than or equal to3 g/m(2), only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of greater than or equal to 40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX greater than or equal to3 g/m(2) seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders. (C) 2001 Elsevier Science Inc. C1 San Raffaele H Sci Inst, Dept Radiochemtherapy, I-20132 Milan, Italy. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Ctr Leon Berard, Unite Cytokines & Canc, F-69373 Lyon, France. RP Reni, M (reprint author), San Raffaele H Sci Inst, Dept Radiochemtherapy, Via Olgettina 60, I-20132 Milan, Italy. RI Ferreri, Andres Jose Maria/A-6662-2013; Reni, Michele/J-8296-2016; Blay, Jean-Yves/N-3966-2016 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Reni, Michele/0000-0002-6463-0293; Blay, Jean-Yves/0000-0001-7190-120X NR 44 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2001 VL 51 IS 2 BP 419 EP 425 DI 10.1016/S0360-3016(01)01639-X PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 474ZR UT WOS:000171137600018 PM 11567816 ER PT J AU Nguyen, QD Uy, HS Merchant, A Medina, CA Baltatzis, S Zhao, TZ Zhao, ZS Cantor, H Foster, CS AF Nguyen, QD Uy, HS Merchant, A Medina, CA Baltatzis, S Zhao, TZ Zhao, ZS Cantor, H Foster, CS TI Effect of Fas and Fas ligand deficiency in resistance of C57BL/6 mice to HSV-1 keratitis and chorioretinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HERPES-SIMPLEX VIRUS; ANTERIOR-CHAMBER INOCULATION; INTRACAMERAL INOCULATION; TYPE-1 RETINITIS; IMMUNE-RESPONSES; DISEASE PATTERNS; T-CELLS; LYMPHOCYTES; EXPRESSION; INFECTION AB PURPOSE. To investigate the effect of Fas and Fas ligand (FasL) deficiency on the development of herpes stromal keratitis and on the von Szily model of herpes retinitis in C57BL/6 mice, which are ordinarily resistant to development of both of these herpetic diseases. METHODS. Anterior chamber inoculation of the right eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both eyes of each mouse were enucleated on postinoculation day 15 and processed for histopathologic examination. HSV-1 was inoculated into one cornea of other mice, and the severity of stromal keratitis was scored. RESULTS. Contralateral destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23); ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20 for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL deficient; 0/12 or 0/28) or B6.MRL.1pr (Fas deficient; 0/11 or 0/34) mice (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory cells in the contralateral retina but not destructive chorioretinitis was observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRI.1pr mice, Few inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and three lpr mice. CONCLUSIONS Immune dysregulation secondary to deficiency in Fas or FasL system does not influence the resistance of the C57BL/6 mice to develop herpes simplex keratitis or destructive herpes simplex chorioretinitis. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 34 TC 2 Z9 2 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2001 VL 42 IS 11 BP 2505 EP 2509 PG 5 WC Ophthalmology SC Ophthalmology GA 479ZA UT WOS:000171433300012 PM 11581190 ER PT J AU Lin, HC Chang, JH Jain, S Gabison, EE Kure, T Kato, T Fukai, N Azar, DT AF Lin, HC Chang, JH Jain, S Gabison, EE Kure, T Kato, T Fukai, N Azar, DT TI Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a 28-kDa fragment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BASEMENT-MEMBRANE ZONES; LEWIS-LUNG-CARCINOMA; MATRIX METALLOPROTEINASES; ANGIOGENESIS INHIBITOR; TUMOR-GROWTH; GELATINASE-B; ANGIOSTATIN; ENDOSTATIN; EXPRESSION; PROTEOLYSIS AB PURPOSE. To localize endostatin and Collagen type XVIII in human corneas and to characterize the enzymatic action of matrix metalloproteinases (MMPs) in the cleavage of Collagen type XVIII and generation of endostatin in the cornea. METHODS. Anti-endostatin and anti-hinge antibodies were generated using peptide fragments corresponding to the endostatin region and the adjacent nonendostatin hinge region of Collagen XVIII noncollagenous (NC)1 domain, respectively. Confocal immunostaining was performed to localize Collagen XVIII in human corneas. SV40-immortalized corneal epithelial cells were immunoprecipitated and incubated with active MMP-1, -2, -3, -7, or -9, and Western blot analysis was performed to study Collagen XVIII cleavage. Incubation with MMP-7 was performed at various concentrations (0, 2, 4, and 6 mug/ml) and time intervals (0, 1, 5, and 12 hours). Purified recombinant NC I fragment of Collagen XVIII was also digested with MMP-7, and the cleavage product was sequenced. RESULTS. Collagen XVIII was immunolocalized to the human corneal epithelium, epithelial basement membrane, and Descemet membrane. Western blot analysis demonstrated a 180- to 200-kDa band corresponding to Collagen XVIII. MMP-7 (but not MMP-1, -2, -3, and -9) cleaved corneal epithelium- derived collagen XVIII to generate a 28-kDa endostatin-spanning fragment in a time- and concentration-dependent fashion. MMP-7 cleaved purified recombinant 34-kDa NCl fragment of Collagen XVIII in the hinge region to generate a 28-kDa fragment. CONCLUSIONS. Collagen XVIII is present in human cornea. MMP-7 cleaves the Collagen XVIII NCI domain to generate a 28-kDa fragment in the cornea. C1 Harvard Univ, External Dis & Refract Surg Serv, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Azar, DT (reprint author), Harvard Univ, External Dis & Refract Surg Serv, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Sch Med, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 39 TC 97 Z9 102 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2001 VL 42 IS 11 BP 2517 EP 2524 PG 8 WC Ophthalmology SC Ophthalmology GA 479ZA UT WOS:000171433300014 PM 11581192 ER PT J AU Ellis, DZ Nathanson, JA Rabe, J Sweadner, KJ AF Ellis, DZ Nathanson, JA Rabe, J Sweadner, KJ TI Carbachol and nitric oxide inhibition of Na,K-ATPase activity in bovine ciliary processes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ADENOSINE TRIPHOSPHATASE-ACTIVITY; DEPENDENT PROTEIN-KINASE; NA+-K+-ATPASE; REGULATED PHOSPHOPROTEIN; EPITHELIAL-CELLS; CHOROID-PLEXUS; AQUEOUS-HUMOR; HUMAN EYE; SODIUM; RABBIT AB PURPOSE. Nitric oxide (NO) donors and cholinergic agents decrease intraocular pressure, in part because they induce a decrease in aqueous humor production. Because Na,K-adenosine triphosphatase (ATPase) is involved in aqueous humor formation, this study was conducted to investigate the hypothesis that NO and cholinomimetics regulate its activity in bovine ciliary processes. METHODS. Bovine tissue slices were incubated with agonists and antagonists in a physiological buffer in vitro. Na,K-ATPase activity was determined by assaying hydrolysis of adenosine triphosphate (ATP) in suspended permeabilized tissue slices. RESULTS. Carbachol-induced inhibition of Na,K-ATPase activity correlated with increases in cGMP. This inhibition was abolished by the muscarinic blocker atropine, the NO inhibitor N-w-nitro-L-arginine (L-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Sodium nitroprusside (SNP) mimicked the actions of carbachol. The SNP-induced decrease in Na,K-ATPase activity correlated with an increase in cGMP and was also abolished by ODQ. Both 8-bromo (Br)-cGMP and okadaic acid also inhibited Na,K-ATPase activity. CONCLUSIONS. Carbachol-induccd inhibition of Na,K-ATPase activity involves muscarinic receptor activation. That SNP mimics and L-NAME reverses carbachol's effect on Na,K-ATPase activity suggests that the actions of carbachol are mediated by NO. Carbachol's and SNP's effects on Na,K-ATPase activity involved soluble guanylate cyclase and cGMP. Inhibition of Na,K-ATPase activity by 8-Br-cGMP and okadaic acid indicates that protein phosphorylation events may mediate SNP-induced inhibition of Na,K-ATPase activity. C1 Massachusetts Gen Hosp, Ctr Neurosci, Cambridge, MA 02139 USA. RP Ellis, DZ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, 149-6118,149 13th St, Cambridge, MA 02139 USA. FU NEI NIH HHS [R01-EY05077]; NINDS NIH HHS [R01-NS27653] NR 41 TC 30 Z9 34 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2001 VL 42 IS 11 BP 2625 EP 2631 PG 7 WC Ophthalmology SC Ophthalmology GA 479ZA UT WOS:000171433300031 PM 11581209 ER PT J AU Rahman, MU AF Rahman, MU TI Failure to recognize CPPD disease as a cause of fever/mental status change: Why does this happen? SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Editorial Material ID DIHYDRATE DEPOSITION DISEASE; MONOSODIUM URATE MONOHYDRATE; PHYSICAL DIAGNOSIS; LIGAMENTUM-FLAVUM; NECK PAIN; PYROPHOSPHATE; PSEUDOGOUT; CARTILAGE; CRYSTALS; FEVER C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Rahman, MU (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2001 VL 7 IS 5 BP 288 EP 290 DI 10.1097/00124743-200110000-00005 PG 3 WC Rheumatology SC Rheumatology GA 484ED UT WOS:000171676500003 PM 17039157 ER PT J AU Stone, VE Hogan, JW Schuman, P Rompalo, AM Howard, AA Korkontzelou, C Smith, DK AF Stone, VE Hogan, JW Schuman, P Rompalo, AM Howard, AA Korkontzelou, C Smith, DK TI Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: Survey of women in the HER study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; antiretroviral therapy; complexity; women; HIV/AIDS ID MEDICATION; THERAPY; INFECTION; HIV/AIDS; DISEASE AB Background: Research regarding treatment adherence in chronic diseases,. such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS. Objective: To examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past I and 3 days). Methods: Cross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study. Results: Seventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education, Conclusions: Self-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Med Unit, Boston, MA 02114 USA. Brown Univ, Sch Med, Ctr Stat Sci, Providence, RI 02912 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Johns Hopkins Sch Med, Baltimore, MD USA. Albert Einstein Coll Med, New York, NY USA. US Ctr Dis Control & Prevent, Atlanta, GA USA. RP Stone, VE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. RI Hogan, Joseph/J-4579-2014 FU NIAID NIH HHS [P30 AI 42853]; PHS HHS [U64/CCU106795] NR 37 TC 149 Z9 155 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD OCT 1 PY 2001 VL 28 IS 2 BP 124 EP 131 DI 10.1097/00126334-200110010-00003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 480NK UT WOS:000171467600003 PM 11588505 ER PT J AU Yyldyz, A Sachs, GS AF Yyldyz, A Sachs, GS TI Administration of antidepressants - Single versus split dosing: a meta-analysis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE antidepressants; meta-analysis; dosing schedule; adaptation; compliance ID DOSAGE REGIMENS; DEPRESSION; TRAZODONE; FREQUENCY AB Objective: To evaluate the literature comparing antidepressant effects of multiple daily dosing versus single daily dosing of antidepressants. Method: Studies comparing efficacy of single versus multiple daily dosing of antidepressants were reviewed. Data from the clinical trials meeting our inclusion criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant efficacy of single versus multiple daily dosing overall and separately for the short. intermediate, and long half life antidepressant agent subgroups. Results: The review process identified 22 studies comparing the therapeutic effect of antidepressants according to their dosing schedules. Although most studies used antidepressant medications with short half-lives, none found a significant difference in therapeutic efficacy. Furthermore. the improvement rates in depression scores in between the two groups were almost identical (SDD versus MDD). Conclusion: This meta-analytic approach found no advantage for multiple daily dosing and suggests that sustained therapeutic serum levels are not necessary for achievement of therapeutic activity. Antidepressant benefit may simply require a limited duration of exposure above the threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated with depression sufficiently to achieve an adaptive therapeutic response. Moreover, a single daily dosing regimen offers the potential advantages of simplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. Dokuz Eylul Sch Med, Dept Psychiat, Izmir, Turkey. RP Yyldyz, A (reprint author), 170 Sok,Guller Apt 8-8, TR-35360 Izmir, Turkey. NR 37 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2001 VL 66 IS 2-3 BP 199 EP 206 DI 10.1016/S0165-0327(00)00307-4 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 484PC UT WOS:000171697900012 PM 11578673 ER PT J AU Perell, KL Gregor, RJ Scremin, AME AF Perell, KL Gregor, RJ Scremin, AME TI Muscle-strength and gait-speed changes after bicycle exercise in participants with unilateral CVA SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE cerebrovascular accident; bicycling; muscle strength ID ELECTROMYOGRAPHIC TEMPORAL ANALYSIS; STROKE; REHABILITATION; HEMIPARESIS; LOCOMOTION; VELOCITY AB The purpose of this study was to determine the effect of bicycle exercise on knee-muscle strength and gait speed in 8 male participants with cerebrovascular accident (CVA). Isokinetic knee-extensor and -flexor strength were measured in both concentric- and eccentric-contraction modes. Fifty-foot walking tests were used for gait speed. After only 4 weeks of stationary recumbent cycling (12 sessions), participants improved eccentric muscle strength of the knee extensors, bilaterally. Walking-speed improvements approached but did not achieve significance with training. Improvement in concentric muscle strength of the knee extensors was observed in the involved limb, although most participants demonstrated a nonsignificant increase in muscle strength in the contralateral limb, as well. No improvements were demonstrated in the knee-flexor muscles. Thus. bicycle exercise serves to improve knee-extensor strength. In addition, these strength improvements might have implications for better control of walking in terms of bilateral improvement of eccentric muscle strength. C1 VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Phys Med & Rehabil, Dept Med, Los Angeles, CA USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA USA. Georgia Inst Technol, Dept Hlth & Performance Sci, Atlanta, GA 30332 USA. RP Perell, KL (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. NR 24 TC 4 Z9 4 U1 1 U2 3 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD OCT PY 2001 VL 9 IS 4 BP 386 EP 397 PG 12 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 482UU UT WOS:000171596300004 ER PT J AU Xie, AL Skatrud, JB Puleo, DS Morgan, BJ AF Xie, AL Skatrud, JB Puleo, DS Morgan, BJ TI Exposure to hypoxia produces long-lasting sympathetic activation in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sympathetic nervous system; chemical stimuli ID OBSTRUCTIVE SLEEP-APNEA; RAT BRAIN-STEM; ROSTRAL VENTROLATERAL MEDULLA; CHRONIC EPISODIC HYPOXIA; SYSTEMIC BLOOD-PRESSURE; BODY NEGATIVE-PRESSURE; NERVE ACTIVITY; CARDIOVASCULAR-RESPONSES; VENTILATORY RESPONSE; C-FOS AB The relative contributions of hypoxia and hypercapnia. in causing persistent sympathoexcitation after exposure to the combined stimuli were assessed in nine healthy human subjects during wakefulness. Subjects were exposed to 20 min of isocapnic hypoxia (arterial O-2 saturation, 77-87%) and 20 min of normoxic hypercapnia (end-tidal PCO2, +5.3-8.6 Torr above eupnea) in random order on 2 separate days. The intensities of the chemical stimuli were manipulated in such a way that the two exposures increased sympathetic burst frequency by the same amount (hypoxia: 167 +/- 29% of baseline; hypercapnia: 171 +/- 23% of baseline). Minute ventilation increased to the same extent during the first 5 min of the exposures (hypoxia: +4.4 +/- 1.5 l/min; hypercapnia: +5.8 +/- 1.7 l/min) but declined with continued exposure to hypoxia and increased progressively during exposure to hypercapnia. Sympathetic activity returned to baseline soon after cessation of the hypercapnic stimulus. In contrast, sympathetic activity remained above baseline after withdrawal of the hypoxic stimulus, even though blood gases had normalized and ventilation returned to baseline levels. Consequently, during the recovery period, sympathetic burst frequency was higher in the hypoxia vs. the hypercapnia trial (166 +/- 21 vs. 104 +/- 15% of baseline in the last 5 min of a 20-min recovery period). We conclude that both hypoxia and hypercapnia cause substantial increases in sympathetic outflow to skeletal muscle. Hypercapnia-evoked sympathetic activation is short-lived, whereas hypoxia-induced sympathetic activation outlasts the chemical stimulus. C1 William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI 53705 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 49 TC 134 Z9 140 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 OCT PY 2001 VL 91 IS 4 BP 1555 EP 1562 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 474VV UT WOS:000171128300009 PM 11568136 ER PT J AU Conhaim, RL Watson, KE Lai-Fook, SJ Harms, BA AF Conhaim, RL Watson, KE Lai-Fook, SJ Harms, BA TI Transport properties of alveolar epithelium measured by molecular hetastarch absorption in isolated rat lungs SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE pulmonary edema; lung fluid balance; epithelial transport; epithelial permeability ID UNANESTHETIZED SHEEP; CLEARANCE; LIQUID; PROTEIN; PRESSURE; ALBUMIN AB To evaluate the transport properties of the alveolar epithelium, we instilled hetastarch (Het; 6%, 10 ml, 1 - 1 X 10(4) kDa) into the trachea of isolated rat lungs and then measured the molecular distribution of Het that entered the lung perfusate from the air space over 6 h. Het transport was driven by either diffusion or an oncotic gradient. Perfusate Het had a unique, bimodal molecular weight distribution, consisting of a narrow low-molecular-weight peak at 10-15 kDa (range, 5-46 kDa) and a broad high-molecular-weight band (range 46-2,000 kDa; highest at 288 kDa). We modeled the low-molecular-weight transport as (passive) restricted diffusion or osmotic flow through a small-pore system and the high-molecular-weight transport as passive transport through a large-pore system. The equivalent small-pore radius was 5.0 mn, with a distribution of 150 pores per alveolus. The equivalent large-pore radius was 17.0 nm, with a distribution of one pore per seven alveoli. The small-pore fluid conductivity (2 X 10(-5) ml.h(-1).cm(-2).mmHg(-1)) was 10-fold larger than that of the large-pore conductivity. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Surg, Madison, WI 53792 USA. Univ Kentucky, Ctr Biomed Engn, Lexington, KY 40506 USA. RP Conhaim, RL (reprint author), Univ Wisconsin, Sch Med, Dept Surg, Clin Sci Ctr H4 710, 600 Highland Ave, Madison, WI 53792 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 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 OCT PY 2001 VL 91 IS 4 BP 1730 EP 1740 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 474VV UT WOS:000171128300030 PM 11568157 ER PT J AU Behairy, Y Meldrum, RD Harris, WH AF Behairy, Y Meldrum, RD Harris, WH TI Hybrid revision total hip arthroplasty - A 7-year follow-up study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; hybrid revision; results ID REPLACEMENT AB The hybrid method for fixation of total hip arthroplasty (THA) has shown excellent results during the first decade in primary operations. To investigate its role in revision surgery, data on 48 revision THAs in 45 patients that met the inclusion criteria were gathered prospectively, using HGP cementless acetabular components and precoated cemented femoral components inserted with so-called second generation femoral cementing technique in each case. For the 48 hips during an average follow-up period of 7.4 years, no acetabular components was loose or had pelvic lysis. One acetabular component was revised for recurrent dislocation; I of 48 femoral components was revised for aseptic loosening and I for periprosthetic fracture. Three additional femoral stems (6%) were loose. In this small series, the hybrid concept for revision of failed nonseptic THAs has shown excellent results. C1 Massachusetts Gen Hosp, Orthapaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthapaed Biomech & Biomat Lab, GRJ 1126,55 Fruit St, Boston, MA 02114 USA. NR 38 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2001 VL 16 IS 7 BP 829 EP 837 DI 10.1054/arth.2001.24950 PG 9 WC Orthopedics SC Orthopedics GA 482LF UT WOS:000171577100003 PM 11607897 ER PT J AU Park, SY Kelminson, KL Lee, AK Zhang, P Warner, RE Rehkopf, DH Calderwood, SB Koehler, JE AF Park, SY Kelminson, KL Lee, AK Zhang, P Warner, RE Rehkopf, DH Calderwood, SB Koehler, JE TI Identification, characterization, and functional analysis of a gene encoding the ferric uptake regulation protein in Bartonella species SO JOURNAL OF BACTERIOLOGY LA English DT Article ID VIBRIO-CHOLERAE FUR; ESCHERICHIA-COLI; BACILLARY ANGIOMATOSIS; PSEUDOMONAS-AERUGINOSA; CLONING; IRON; VIRULENCE; HENSELAE; MUTAGENESIS; SEQUENCE AB Environmental iron concentrations coordinately regulate transcription of genes involved in iron acquisition and virulence via the ferric uptake regulation (fur) system. We identified and sequenced the fur gene and flanking regions of three Bartonella species. The most notable difference between Bartonella Fur and other Fur proteins was a substantially higher predicted isoelectric point. No promoter activity or Fur autoregulation was detected using a gfp reporter gene fused to the 204 nucleotides immediately upstream of the Bartonella fur gene. Bartonella henselae fur gene expression complemented a Vibrio cholerae fur mutant. C1 Univ Calif San Francisco, Div Infect Dis, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Infect Dis, Dept Med, San Francisco, CA 94143 USA. Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Koehler, JE (reprint author), Univ Calif San Francisco, Div Infect Dis, Dept Pediat, 521 Parnassus Ave,Room C-443, San Francisco, CA 94143 USA. NR 35 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2001 VL 183 IS 19 BP 5751 EP 5755 DI 10.1128/JB.183.19.5751-5755.2001 PG 5 WC Microbiology SC Microbiology GA 471ZQ UT WOS:000170958900035 PM 11544240 ER PT J AU Park, BH Saxer, C Srinivas, SM Nelson, JS de Boer, JF AF Park, BH Saxer, C Srinivas, SM Nelson, JS de Boer, JF TI In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE burn depth; polarization; fiber optics; coherent optical systems ID BIOLOGICAL TISSUE; LASER-DOPPLER AB We report the first application of high-speed fiber-based polarization sensitive optical coherence tomography (PS-OCT) to image burned tissue in vivo. Thermal injury denatures collagen in skin and PS-OCT can measure the reduction in collagen birefringence using depth resolved changes in the polarization state of light propagated in, and reflected from, the tissue. Stokes vectors were calculated for each point in a scan and birefringence relative to incident polarization determined using four incident polarization states. Using a high-speed fiber-based PS-OCT system on rat skin burned for varying periods of time, a correlation between birefringence and actual burn depth determined by histological analysis was established. In conclusion, PS-OCT has potential use for noninvasive assessment of burn depth. (C) 2001 Society of Photo-Optical Instrumentation Engineers. C1 Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Univ Calif Irvine, Beckman Laser Inst & Med Clin, 1002 Hlth Sci Rd E, Irvine, CA 92612 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NIGMS NIH HHS [GM 58785] NR 17 TC 177 Z9 180 U1 4 U2 28 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 OCT PY 2001 VL 6 IS 4 BP 474 EP 479 DI 10.1117/1.1413208 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 505DF UT WOS:000172895700013 PM 11728208 ER PT J AU Choi, SJ Kurihara, N Oba, Y Roodman, GD AF Choi, SJ Kurihara, N Oba, Y Roodman, GD TI Osteoclast inhibitory peptide 2 inhibits osteoclast formation via its C-terminal fragment SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoclast inhibitory peptide 2; osteoclasts; inhibitors; legumain; receptors ID ASPARAGINYL ENDOPEPTIDASE LEGUMAIN; BONE-RESORPTION; IDENTIFICATION; EXPRESSION; CLONING; EFFICIENCY; RECEPTOR AB Osteoclast inhibitory peptide 2 (OIP-2) is a novel autocrine/paracrine factor produced by osteoclasts (OCLs) that inhibits bone resorption and OCL formation in vitro and in vivo. It is identical to the asparaginyl endopeptidase legumain. During maturation of OIP-2, a signal peptide and a 17-kDa C-terminal fragment (CTF) are cleaved to produce the mature enzyme. To determine if enzyme activity is required for inhibition of OCL formation or if only the CTF is responsible for these effects, we synthesized His-tagged complementary DNA (cDNA) constructs for the CTF of OIP-2, the proform of OIP-2, and the "mature enzyme" form of OIP-2. The proform or the CTF portion of OIP-2 inhibited OCL formation in a dose-dependent manner in murine bone marrow cultures stimulated with 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. The mature form of OIP-2, which was enzymatically active, did not inhibit OCL formation. In addition, OIP-2 inhibited OCL formation in cultures of highly purified human OCL precursor cells or RAW264.7 cells stimulated with 10 ng/ml of receptor activator of NF-kappaB (RANK) ligand. Binding studies with His-tagged OIP-2 showed expression of a putative OIP-2 receptor on RAW264.7 cells treated with RANK ligand for 4 days and human marrow cultures treated with 1,25(OH)(2)D-3 for 3 weeks. These data show that the CTF of OIP-2, rather than the mature enzyme, mediates the inhibitory effects of OIP-2 through a putative receptor on OCL precursors. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Roodman, GD (reprint author), Univ Pittsburgh, E1152 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA. NR 18 TC 21 Z9 22 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 OCT PY 2001 VL 16 IS 10 BP 1804 EP 1811 DI 10.1359/jbmr.2001.16.10.1804 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475BP UT WOS:000171142000010 PM 11585344 ER PT J AU Alston, TA AF Alston, TA TI PaO2 exceeding the barometric pressure: An explosive situation? SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE deep hypothermic circulators arrest; hyperoxia; pH-stat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiothorac Anesthesia Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiothorac Anesthesia Grp, Dept Anesthesia & Crit Care, Fruit St, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2001 VL 15 IS 5 BP 655 EP 655 DI 10.1053/jcan.2001.26553 PG 1 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 483TP UT WOS:000171652200024 PM 11688012 ER PT J AU Johnson, JD Harissi-Dagher, M Pineda, R Yoo, S Azar, DT AF Johnson, JD Harissi-Dagher, M Pineda, R Yoo, S Azar, DT TI Diffuse lamellar keratitis: Incidence, associations, outcomes, and a new classification system SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; INTERFACE KERATITIS; LASER; COMPLICATIONS; MANAGEMENT AB Purpose: To evaluate the incidence, associations, and visual outcomes in patients with diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK). Setting. University-based refractive surgery center, Boston, Massachusetts, USA. Methods: This retrospective review comprised 2711 eyes that had LASIK between September 1996 and September 1999. All eyes that developed DLK after LASIK were included. They were divided into type I DLK (center sparing) or type II DLK (center involved) and then subdivided into A (sporadic-DLK not diagnosed in other patients treated on the same day) or B (cluster - other patients identified with DLK). Type IA corresponded to center sparing, sporadic; type IB, center sparing, cluster; type IIA, center involved, sporadic; and type IIB, center involved, cluster. The main outcome measures were incidence of DLK after LASIK, time to diagnosis, time to resolution, and changes in best spectacle-corrected visual acuity (BSCVA). Unpaired t tests were used for statistical analyses. Results: Thirty-six eyes (1.3%) developed DLK. Type I occurred in 58.3% of cases (type IA, n = 18; type IB, n = 3) and type II, in 41.7% (type IIA, n = 10; type IIB, n = 5). The mean time to diagnosis was not statistically significantly different between type I (1.8 days) and type II (1.1 days), Fourteen eyes (38.9%) developed DLK after an epithelial defect, representing an odds ratio of 13 times. The association with an epithelial defect was statistically significantly greater with type I (11/21 eyes, 52.4%) than with type II (3/15 eyes, 20.0%; P = .05). The mean time to resolution was 3.5 days in type I (type IA = 3.6 days; type IB = 2.7 days). This was significantly shorter than in type II, which had a mean time to resolution of 12.1 days (type IIA = 9.3 days; type IIB = 10.2 days) (P = .001). Loss of 2 or more lines of BSCVA occurred in 2 of 5 patients with type IIB and in no patients with types IA, IB, or IIA. Conclusions: Epithelial defects after LASIK increased the risk of DLK occurrence, especially type I. Type II DLK was associated with a prolonged time to resolution and carried a significantly higher risk of BSCVA loss than type I. (C) 2001 ASCRS and ESCRS. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA 02114 USA. Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 58 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 2001 VL 27 IS 10 BP 1560 EP 1566 DI 10.1016/S0886-3350(01)00958-0 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 485WF UT WOS:000171785900014 PM 11687352 ER PT J AU Shekelle, PG Park, RE Kahan, JP Leape, LL Kamberg, CJ Bernstein, SJ AF Shekelle, PG Park, RE Kahan, JP Leape, LL Kamberg, CJ Bernstein, SJ TI Sensitivity and specificity of the RAND/UCLA Appropriateness Method to identify the overuse and underuse of coronary revascularization and hysterectomy SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE quality of health care; sensitivity and specificity; coronary revascularization; hysterectomy ID NEW-YORK-STATE; BYPASS GRAFT-SURGERY; CAROTID ENDARTERECTOMY; MEDICAL PROCEDURES; ANGIOGRAPHY; CARE; VALIDITY; CRITERIA; DISEASE; RISK AB There is no empirical evidence on the sensitivity and specificity of methods to identify the possible overuse and underuse of medical procedures. To estimate the sensitivity and specificity of the RAND/UCLA Appropriateness Method. Parallel three-way replication of the RAND/UCLA Appropriateness Method for each of two procedures, coronary revascularization and hysterectomy. Maximum likelihood estimates of the sensitivity and specificity of the method for each procedure. These values were then used to re-calculate past estimates of overuse and underuse, correcting for the error rate in the appropriateness method. The sensitivity of detecting overuse of coronary revascularization was 68% (95% confidence interval 60-76%) and the specificity was 99% (98-100%). The corresponding values for hysterectomy were 89% (85-94%) and 86% (83-89%). The sensitivity and specificity of detecting the underuse of coronary revascularization were 94% (92-95%) and 97% (96-98%), respectively. Past applications of the appropriateness method have overestimated the prevalence of the over-use of hysterectomy, underestimated the prevalence of the overuse of the coronary revascularization. and provided true estimates of the underuse of revascularization. The sensitivity and specificity of the RAND/UCLA Appropriateness Method vary according to the procedure assessed and appear to estimate the underuse of procedures more accurately than their overuse. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90066 USA. RAND, Santa Monica, CA 90401 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Hlth Management, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Policy, Ann Arbor, MI 48109 USA. Ann Arbor VA Healthcare Syst, Ann Arbor, MI 48105 USA. RP Shekelle, PG (reprint author), 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU AHRQ HHS [HS07185-02] NR 31 TC 42 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2001 VL 54 IS 10 BP 1004 EP 1010 DI 10.1016/S0895-4356(01)00365-1 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 473MJ UT WOS:000171047800006 PM 11576811 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, KW TI Mechanisms for the induction of autoimmunity by infectious agents SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESISTANT LYME ARTHRITIS; CD8 T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GUILLAIN-BARRE-SYNDROME; MYELIN BASIC-PROTEIN; MOLECULAR MIMICRY; BORRELIA-BURGDORFERI; INFLAMMATORY DISEASE; PREVENTS DEVELOPMENT; REACTIVE ARTHRITIS C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1410,44 Binney St, Boston, MA 02115 USA. NR 48 TC 207 Z9 215 U1 1 U2 10 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 OCT PY 2001 VL 108 IS 8 BP 1097 EP 1104 DI 10.1172/JCI14235 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 483BU UT WOS:000171614500002 PM 11602615 ER PT J AU Zhou, GC Myers, R Li, Y Chen, YL Shen, XL Fenyk-Melody, J Wu, M Ventre, J Doebber, T Fujii, N Musi, N Hirshman, MF Goodyear, LJ Moller, DE AF Zhou, GC Myers, R Li, Y Chen, YL Shen, XL Fenyk-Melody, J Wu, M Ventre, J Doebber, T Fujii, N Musi, N Hirshman, MF Goodyear, LJ Moller, DE TI Role of AMP-activated protein kinase in mechanism of metformin action SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACETYL-COA CARBOXYLASE; GLUCOSE-TRANSPORT; INSULIN-RESISTANCE; RESPIRATORY-CHAIN; RAT-LIVER; MUSCLE; MITOCHONDRIAL; EXPRESSION; HEPATOCYTES; INHIBITION AB Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity, is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using, a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders. C1 Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA. Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA. Merck Res Labs, Dept Comparat Med, Rahway, NJ 07065 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zhou, GC (reprint author), Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 37 TC 2604 Z9 2686 U1 33 U2 237 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 OCT PY 2001 VL 108 IS 8 BP 1167 EP 1174 DI 10.1172/JCI13505 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 483BU UT WOS:000171614500011 PM 11602624 ER PT J AU Guerra, C Navarro, P Valverde, AM Arribas, M Bruning, J Kozak, LP Kahn, CR Benito, M AF Guerra, C Navarro, P Valverde, AM Arribas, M Bruning, J Kozak, LP Kahn, CR Benito, M TI Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR MECHANISMS; TARGETED DISRUPTION; MICE; IRS-2; GENE; MELLITUS; GLUCOSE; MUSCLE AB Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insulin receptors in brown adipocytes show an age-dependent loss of interscapular brown fat but increased expression of uncoupling protein-1 and -2. In parallel, these mice develop an insulin-secretion defect resulting in a progressive glucose intolerance, without insulin resistance. This model provides direct evidence for not only a role for the insulin receptors in brown fat adipogenesis, the data also suggest a novel role of brown adipose tissue in the regulation of insulin secretion and glucose homeostasis. C1 Univ Complutense Madrid, Fac Farm, Dept Bioquim & Biol Mol, Madrid 28040, Spain. Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Benito, M (reprint author), Univ Complutense Madrid, Fac Farm, Dept Bioquim & Biol Mol, Madrid 28040, Spain. FU NIDDK NIH HHS [DK-3320] NR 33 TC 112 Z9 118 U1 0 U2 7 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 OCT PY 2001 VL 108 IS 8 BP 1205 EP 1213 DI 10.1172/JCI13103 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 483BU UT WOS:000171614500015 PM 11602628 ER PT J AU Swenson, JM Spargo, J Tenover, FC Ferraro, MJ AF Swenson, JM Spargo, J Tenover, FC Ferraro, MJ TI Optimal inoculation methods and quality control for the NCCLS oxacillin agar screen test for detection of oxacillin resistance in Staphylococcus aureus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID METHICILLIN RESISTANCE; MECA GENE; SUSCEPTIBILITY; EXPRESSION; VITEK AB To define more precisely the inoculation methods to be used in the oxacillin screen test for Staphylococcus aureus, we tested agar screen plates prepared in house with 6 mug of oxacillin/ml and 4% NaCl using the four different inoculation methods that would most likely be used by clinical laboratories. The organisms selected for testing were 19 heteroresistant mecA-producing strains and 41 non-mecA-producing strains for which oxacillin MICs were near the susceptible breakpoint. The inoculation method that was preferred by all four readers and that resulted in the best combination of sensitivity and specificity was a 1-mul loopful of a 0.5 McFarland suspension. A second objective of the study was to then use this method to inoculate plates from five different manufacturers of commercially prepared media. Although all commercial media performed with acceptable sensitivity compared to the reference lot, one of the commercial lots demonstrated a lack of specificity. Those lots of oxacillin screen medium that fail to grow heteroresistant strains can be detected by using S. aureus ATCC 43300 as a positive control in the test and by using transmitted light to carefully examine the plates for any growth. However, lack of specificity with commercial lots may be difficult to detect using any of the current quality control organisms. C1 Ctr Dis Control & Prevent, Nosocomial Pathogens Lab Branch, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Dept Microbiol, Boston, MA 02114 USA. RP Swenson, JM (reprint author), CDC, Mailstop G08,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 20 TC 22 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2001 VL 39 IS 10 BP 3781 EP 3784 DI 10.1128/JCM.39.10.3781-3784.2001 PG 4 WC Microbiology SC Microbiology GA 479AW UT WOS:000171382600068 PM 11574618 ER PT J AU Serino, G Rosling, B Ramberg, P Socransky, SS Lindhe, J AF Serino, G Rosling, B Ramberg, P Socransky, SS Lindhe, J TI Initial outcome and long-term effect of surgical and non-surgical treatment of advanced periodontal disease SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE access surgery; advanced periodontitis; clinical trial; scaling; root planing; maintenance ID PROBING ATTACHMENT LOSS; 4 MODALITIES; THERAPY; DEPTH; SURGERY; POCKETS; PLAQUE; ACCESS; TEETH; LEVEL AB Aim: A clinical trial was performed to determine (i) the initial outcome of nonsurgical and surgical access treatment in subjects with advanced periodontal disease and (ii) the incidence of recurrent disease during 12 years of maintenance following active therapy. Material and Methods: Each of the 64 subjects included in the trial showed signs of (i) generalized gingival inflammation, (ii) had a minimum of 12 non-molar teeth with deep pockets (greater than or equal to6 mm) and with greater than or equal to6 nun alveolar bone loss. They were randomly assigned to 2 treatment groups; one surgical (SU) and one non-surgical (SRP). Following a baseline examination, all patients were given a detailed case presentation which included oral hygiene instruction. The subjects in SU received surgical access therapy, while in SRP non-surgical treatment was provided. After this basic therapy, all subjects were enrolled in a maintenance care program and were provided with meticulous supportive periodontal therapy (SPT) 3-4 times per year, Sites that at a recall appointment bled on gentle probing and had a PPD value of greater than or equal to5 mm were exposed to renewed subgingival instrumentation. Comprehensive re-examinations were performed after 1, 3, 5 and 13 years of SPT. If a subject between annual examinations exhibited marked disease progression (i.e., additional PAL loss of greater than or equal to2 mm at greater than or equal to4 teeth). he/she was exited from the study and given additional treatment. Results: It was observed that (i) surgical therapy (SU) was more effective than non-surgical scaling and root planing (SRP) in reducing the overall mean probing pocket depth and in eliminating deep pockets, (ii) more SRP-treated subjects exhibited signs of advanced disease progression in the 1-3 year period following active therapy than SU-treated subjects. Conclusion: In subjects with advanced periodontal disease, surgical therapy provides better short and long-term periodontal pocket reduction and may lead to fewer subjects requiring additional adjunctive therapy. C1 Univ Gothenburg, Fac Odontol, Dept Periodontol, SE-40530 Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. RP Serino, G (reprint author), Univ Gothenburg, Fac Odontol, Dept Periodontol, Box 450, SE-40530 Gothenburg, Sweden. FU NIDCR NIH HHS [DE-12861] NR 27 TC 43 Z9 49 U1 1 U2 14 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2001 VL 28 IS 10 BP 910 EP 916 DI 10.1034/j.1600-051x.2001.028010910.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 469WB UT WOS:000170838100003 PM 11686808 ER PT J AU Haffajee, AD Thompson, M Torresyap, G Guerrero, D Socransky, SS AF Haffajee, AD Thompson, M Torresyap, G Guerrero, D Socransky, SS TI Efficacy of manual and powered toothbrushes (I). Effect on clinical parameters SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal disease; gingivitis; plaque; toothbrushing; powered toothbrushing; manual toothbrushing ID OSCILLATING/ROTATING ELECTRIC TOOTHBRUSH; SUPRAGINGIVAL PLAQUE CONTROL; NON-SURGICAL TREATMENT; PERIODONTAL-DISEASE; BACTERIAL-COLONIZATION; BARRIER MATERIAL; GINGIVITIS; REGENERATION; MAINTENANCE; REMOVER AB Background/aim: The purpose of the present investigation was to compare manual (Crest Complete) and powered toothbrushing (Braun Oral-B 3D Plaque Remover) for their ability to affect clinical parameters of periodontal diseases. Methods: 48 periodontal maintenance subjects completed this single-blind 6-month longitudinal study. Subjects had a minimum of 20 natural teeth excluding third molars and > 10% of sites (approximately 17 sites) with pocket depth greater than or equal to4 mm and/or > 10% sites with attachment level >4 mm. At baseline, subjects received full mouth clinical measurements (168 sites) to determine mean Plaque Index, Gingival Index, pocket depth and attachment level and % of sites exhibiting BOP. Subjects were then randomly assigned to one of two groups. The control group (N=26) used a manual toothbrush while the test group (N=22) used a powered toothbrush, Subjects received instruction in oral hygiene and used their assigned toothbrush twice daily according to instruction. Follow-up clinical assessments were performed at 3 and 6 months. Significance of differences in clinical measures over time was determined using the Quade test and between brushing groups at each time point using the Mann-Whitney test. Results: Mean pocket depth, mean plaque index and % of sites exhibiting BOP showed significant reductions from baseline to 3 and 6 months in both groups. Mean probing attachment level and mean Gingival Index were significantly reduced in the powered brushing group only. There was a significant positive correlation between plaque reduction and reduction in other clinical parameters in both brushing groups. The majority of subjects showed improvements in clinical parameters at 6 months, although a greater proportion of subjects in the powered group showed a reduction in Plaque Index (77% versus 65%) and in % sites exhibiting BOP (82% versus 69%). Mean pocket depth and mean attachment level showed significantly greater reductions between baseline and 6 months in lingual and mandibular areas in the powered group. Conclusions: Both manual and powered toothbrushes reduced pocket depth, plaque index and BOP, The powered toothbrush significantly reduced mean gingival index and probing attachment level. The greatest benefit of the powered brush was at mandibular and lingual surfaces. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. NR 35 TC 22 Z9 22 U1 4 U2 16 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2001 VL 28 IS 10 BP 937 EP 946 DI 10.1034/j.1600-051x.2001.028010937.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 469WB UT WOS:000170838100007 PM 11686812 ER PT J AU Haffajee, AD Smith, C Torresyap, G Thompson, M Guerrero, D Socransky, SS AF Haffajee, AD Smith, C Torresyap, G Thompson, M Guerrero, D Socransky, SS TI Efficacy of manual and powered toothbrushes (II). Effect on microbiological parameters SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal disease; bacteria; plaque; DNA probes; powered toothbrushing; manual toothbrushing ID DNA AB Background/aim: The purpose of the present investigation was to determine the effect of self-performed supragingival plaque removal using either manual (Crest Complete) or power (Braun 3D Plaque Remover) toothbrushing on supra and subgingival plaque composition. Methods: 47 periodontal maintenance subjects completed this single-blind 6 month longitudinal study. At baseline, samples of supra and separately subgingival plaque were taken from the mesial aspect of each tooth in each subject using sterile curettes and individually analyzed for their content of 18 bacterial taxa using checkerboard DNA-DNA hybridization. After random assignment to groups receiving either a manual (n=25) or power toothbrush (n=22), subjects received instruction in oral hygiene and used their assigned toothbrush 2X daily for 6 months. Clinical monitoring and microbiological sampling were repeated at 3 and 6 months. Significant differences in microbiological measures over time were sought using the Quade test and between brushing groups at each time point using the Mann-Whitney test. Results: Mean total counts were significantly reduced for supra- and subgingival plaque samples in the manual group and subgingival samples in the powered brushing group. Actinomyces naeslundii and Actinomyces israelii/gerencseriae were the most numerous organisms detected at baseline and showed the greatest reductions in counts in both brushing groups. Streptococcus constellatus/intermedius was significantly reduced in both groups, while Streptococcus mitis/oralis/sanguis was significantly reduced in the manual toothbrushing group. Mean counts of species were more markedly altered in subgingival plaque. Major reductions occurred in both groups for A. naeslundii, A, israeliilgerencseriae, Peptostreptococcus micros, Veillonella parvula, Prevotella intermedia/nigrescens, S. mitis/oralis/sanguis and S. constellatus/intermedius. All taxa examined were reduced in prevalence (% of sites colonized) in the subgingival plaque samples for both brushing groups. The reductions in prevalence were greater for A. naeslundii, S. constellatus/intermedius, V. parvula, A. israeliilgerencseriae, S. mitis/oratis/sanguis, P. micros, Streptococcus mutans and P. intermedia/nigrescens. Mean prevalence was decreased more for Porphyromonas gingivalis, Campylobacter rectus/showae, Treponema denticola and Bacteroides forsythus in supragingival plaque than subgingival plaque. Conclusions: The major finding was the effect of supragingival plaque removal on the composition of the subgingival microbiota. Counts and prevalence of most taxa examined were markedly decreased in both toothbrushing groups. This reduction should translate to a decreased risk of periodontal disease initiation or recurrence. Further, the decreased prevalence of periodontal pathogens in supragingival plaque lowers potential reservoirs of these species. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. NR 8 TC 27 Z9 30 U1 4 U2 10 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2001 VL 28 IS 10 BP 947 EP 954 DI 10.1034/j.1600-051x.2001.028010947.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 469WB UT WOS:000170838100008 PM 11686813 ER PT J AU Caroff, SN Campbell, EC Havey, J Sullivan, KA Mann, SC Gallop, R AF Caroff, SN Campbell, EC Havey, J Sullivan, KA Mann, SC Gallop, R TI Treatment of tardive dyskinesia with donepezil: A pilot study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting on Psychiatric Services CY OCT 25-29, 2000 CL PHILADELPHIA, PENNSYLVANIA ID CHOLINERGIC NEURONS AB Background: Tardive dyskinesia (TD) remains a significant clinical problem for which there is no uniformly effective treatment. Earlier trials with acetylcholine precursors may have been disappointing because of underlying damage to striatal cholinergic neurons in patients with TD. In contrast, new cholinesterase inhibitors, developed for the treatment of dementia, may improve TD by directly increasing cholinergic synaptic transmission. Method. We conducted an 8-week open-label trial of donepezil in the treatment of TD. Ten patients with schizophrenia or schizoaffective disorder who received stable doses of antipsychotics and met DSM-IV criteria for TD were treated with donepezil, 5 to 10 mg/day, for 6 weeks after a 2-week baseline period. Changes in total Abnormal Involuntary Movement Scale (AIMS) scores measured every 2 weeks were assessed for significance. Patients were also assessed using the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Barnes Akathisia Scale, and the Simpson-Angus Scale. Results: Total AIMS scores decreased significantly (p = .0009), with no changes in other measures. Nine patients showed a positive response. Improvement was greatest in orofacial and upper extremity movements. No significant interactions were noted between the total AIMS scores and age (p > .29), duration of TD (p > .38), or duration of antipsychotic treatment (p > .14). Conclusion. Donepezil appeared to be effective in suppressing TD in this pilot study. However, placebo-controlled, double-blind studies are necessary before donepezil can be recommended as a treatment for TD. C1 Univ Penn, Sch Med, Dept Vet Affairs Med Ctr, Philadelphia, PA USA. RP Caroff, SN (reprint author), Behav Hlth Serv, VA Med Ctr, 7 E 116A,Univ Ave, Philadelphia, PA 19104 USA. NR 31 TC 24 Z9 24 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2001 VL 62 IS 10 BP 772 EP 775 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 494LN UT WOS:000172284200004 PM 11816865 ER PT J AU Thase, ME Nierenberg, AA Keller, MB Panagides, J AF Thase, ME Nierenberg, AA Keller, MB Panagides, J CA Relapse Prevention Study Grp TI Efficacy of mirtazapine for prevention of depressive relapse: A placebo-controlled double-blind trial of recently remitted high-risk patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID LONG-TERM TREATMENT; COGNITIVE THERAPY; MAJOR DEPRESSION; DISORDER AB Background: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to I year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. Method: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. Results: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a new-onset adverse event. Conclusion: Continuation-phase therapy with mirtazapine is effective and well tolerated. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Dept Psychiat, Butler Hosp, Providence, RI USA. Organon Inc, W Orange, NJ USA. RP Thase, ME (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU NIMH NIH HHS [U01 MH061590] NR 24 TC 50 Z9 54 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 PD OCT PY 2001 VL 62 IS 10 BP 782 EP 788 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 494LN UT WOS:000172284200006 PM 11816867 ER PT J AU Goff, DC Leahy, L Berman, I Posever, T Herz, L Leon, AC Johnson, SA Lynch, G AF Goff, DC Leahy, L Berman, I Posever, T Herz, L Leon, AC Johnson, SA Lynch, G TI A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID GLUTAMATE RECEPTORS; EXPRESSION; HIPPOCAMPUS; BINDING; MEMORY; RATS AB CX516, a positive modulator of the glutamatergic alpha -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other "ampakines" hold promise for the treatment of schizophrenia. C1 Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. Cortex Pharmaceut, Irvine, CA USA. Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY USA. Vet Affairs Med Ctr, Bedford, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Lemmuel Shattuck Hosp, Boston, MA USA. Taunton State Hosp, Taunton, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 17 TC 151 Z9 153 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2001 VL 21 IS 5 BP 484 EP 487 DI 10.1097/00004714-200110000-00005 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 478HT UT WOS:000171341500005 PM 11593073 ER PT J AU Vaananen, A Srinivas, R Parikka, M Palosaari, H Bartlett, JD Iwata, K Grenman, R Stenman, UH Sorsa, T Salo, T AF Vaananen, A Srinivas, R Parikka, M Palosaari, H Bartlett, JD Iwata, K Grenman, R Stenman, UH Sorsa, T Salo, T TI Expression and regulation of MMP-20 in human tongue carcinoma cells SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE matrix metalloproteinases; enamelysin; tongue carcinoma; trypsin-2 ID MATRIX METALLOPROTEINASES; ENAMELYSIN MMP-20; MESSENGER-RNA; COLLAGENASE; ACTIVATION; LINES; IDENTIFICATION; KERATINOCYTES; TETRACYCLINES; SPECIFICITY AB Human matrix metal loproteinase-20 (MMP-20, enamelysin) fragments the enamel-specific protein amelogenin and has been shown to be synthesized exclusively by odontoblasts and ameloblasts and in certain odontogenic tumors. Here we demonstrate, for the first time, the expression of MMP-20 mRNA and protein in two carcinoma cell lines originating from the tongue. Treatment of the SCC-25 and HSC-3 cells with phorbol 12-myristate 13-acetate (10 nmol/L) up-regulated MMP-20 mRNA and protein expression by up to 1.6-fold, but transforming growth factor beta (10 ng/mL) had no effect. The latent proform of recombinant (r) human MMP-20 was converted by tumor-related trypsin-2. Activated rMMP-20 did not degrade type I or type II collagen, but efficiently hydrolyzed fibronectin, type IV collagen, laminin-1 and -5, tenascin-C, and beta-casein. This implies that MMP-20 not only participates in dental matrix remodeling but is also present in tongue carcinoma cells. C1 Oulu Univ, Inst Dent, Dept Diagnost & Oral Med, FIN-90014 Oulu, Finland. Univ Helsinki, Fac Med, Helsinki, Finland. Forsyth Inst, Dept Biomineralizat, Boston, MA USA. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA USA. Fuji Chem Ind Co Ltd, Dept Biopharmaceut, Takaoka, Toyama, Japan. Turku Univ Hosp, Dept Otolaryngol, FIN-20520 Turku, Finland. Univ Helsinki Hosp, Dept Clin Chem, Helsinki, Finland. Oulu Univ Hosp, Oulu, Finland. RP Salo, T (reprint author), Oulu Univ, Inst Dent, Dept Diagnost & Oral Med, POB 5281, FIN-90014 Oulu, Finland. RI Parikka, Mataleena/D-4364-2014 FU NIDCR NIH HHS [R29 DE012098] NR 29 TC 29 Z9 31 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2001 VL 80 IS 10 BP 1884 EP 1889 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 536CZ UT WOS:000174684300005 PM 11706946 ER PT J AU Brown, DFM Nadel, ES AF Brown, DFM Nadel, ES TI Wide complex tachycardia SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PARKINSON-WHITE-SYNDROME; NATURAL-HISTORY; POPULATION C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2001 VL 21 IS 3 BP 271 EP 274 DI 10.1016/S0736-4679(01)00390-0 PG 4 WC Emergency Medicine SC Emergency Medicine GA 484CL UT WOS:000171672600008 PM 11604282 ER PT J AU Sasada, T Ghendler, Y Neveu, JM Lane, WS Reinherz, EL AF Sasada, T Ghendler, Y Neveu, JM Lane, WS Reinherz, EL TI A naturally processed mitochondrial self-peptide in complex with thymic MHC molecules functions as a selecting ligand for a viral-specific T cell receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE positive selection; thymocyte development; CTL; naturally processed peptides; TAP-1(-/-) ID CLASS-I MOLECULES; POSITIVE SELECTION; NEGATIVE SELECTION; ANTIGEN; THYMOCYTES; BINDING; RECOGNITION; LYMPHOCYTES; REPERTOIRE; MICE AB Peptide fragments of self-proteins bound to major histocompatibility complex molecules within the thymus are important for positively selecting T Cell receptor (TCR)-bearing CD4(+)CD8(+) double positive (DP) thymocytes for further maturation. The relationship between naturally processed thymic self-peptides and TCR-specific cognate peptides is unknown. Here we employ HPLC purification of peptides released from H-2K(b) molecules of the C57BL/6 thymus in conjunction with mass spectrometry (MS) and functional profiling to identify a naturally processed K-b-bound peptide positively selecting the N15 TCR specific for the vesicular stomatitis virus octapeptide (VSV8) bound to K-b. The selecting peptide was identified in 1 of 80 HPLC fractions and shown by tandem MS (MS/MS) sequencing to correspond to residues 68-75 of the MLRQ subunit of the widely expressed mitochondrial NADH ubiquinone oxidoreductase (NUbO(68-75)), Of note, the peptide differs at six of its eight residues from the cognate peptide VSV8 and functions as a weak agonist for mature CD8 single positive (SP) N15 T cells, with activity 10,000-fold less than VSV8. In N15 transgenic (tg) recombinase activating gene 2(-/-) transporter associated with antigen processing 1(-/-) fetal thymic organ culture, NUbO(68-75) induces phenotypic and functional differentiation of N15 TCR bearing CD8 SP thymocytes. Failure of NUbO(68-75) to support differentiation of a second K-b-restricted TCR indicates that its inductive effects are not general. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immunol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Immunol Lab, Boston, MA 02115 USA. Harvard Univ, Microchem & Proteom Anal Facil, Cambridge, MA 02138 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45022, R01 AI045022, R21 AI045022, R56 AI045022] NR 44 TC 26 Z9 26 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 2001 VL 194 IS 7 BP 883 EP 891 DI 10.1084/jem.194.7.883 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484CD UT WOS:000171671900003 PM 11581311 ER PT J AU Weninger, W Crowley, MA Manjunath, N von Andrian, UH AF Weninger, W Crowley, MA Manjunath, N von Andrian, UH TI Migratory properties of naive, effector, and memory CD8(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE lymphocyte homing; lymph node; chemokines; adhesion molecules; inflammation ID HIGH ENDOTHELIAL VENULES; SELECTIN-DEFICIENT MICE; PERIPHERAL LYMPH-NODES; RECEPTOR EXPRESSION; P-SELECTIN; IN-VIVO; MEDIATED CYTOTOXICITY; MOLECULAR MECHANISMS; T-HELPER-2 CELLS; IMMUNE-RESPONSES AB It has been proposed that two different antigen-experienced T cell subsets may be distinguishable by their preferential ability to home to lymphoid organs (central memory cells) or non-lymphoid tissues (effector memory/effector cells). We have shown recently that murine antigen-primed CD8(+) T cells cultured in interleukin (IL)-15 (CD8(IL-15)) resemble central memory cells in phenotype and function. In contrast, primed CD8(+) T cells cultured in IL-2 (CD8(IL-2)) become cytotoxic effector cells. Here, the migratory behavior of these two subsets was investigated. Naive, CD8(IL-15) cells and, to a lesser degree, CD8(IL-2) cells localized to T cell areas in the but only naive and CD8(IL-15) cells horned to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of peripheral LNs revealed that CD8(IL-15) cells, but not CD8(IL-2) cells, rolled and arrested in high endothelial venules (HEVs). Migration of CD8(IL-15) cells to LNs depended on L-selectin and required chemokines that bind CC chemokine receptor (CCR)7. Both antigen-experienced populations, but not naive T cells, responded to inflammatory chemokines and accumulated at sites of inflammation. However, CD8(IL-2) cells were 12 times more efficient in migrating to inflamed peritoneum than CD8(IL-15) cells. Furthermore, CD8(IL-15) cells proliferated rapidly upon reencounter with antigen at sites of inflammation. Thus, central memory-like CD8(IL-15) cells home avidly to lymphoid organs and moderately to sites of inflammation, where they mediate rapid recall responses, whereas CD8(IL-2) effector T cells accumulate in inflamed tissues, but are excluded from most lymphoid organs. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL48675, HL54936, HL56949, P01 HL048675, P01 HL056949, R01 HL054936] NR 63 TC 352 Z9 361 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 2001 VL 194 IS 7 BP 953 EP 966 DI 10.1084/jem.194.7.953 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484CD UT WOS:000171671900009 PM 11581317 ER PT J AU von Boehmer, H AF von Boehmer, H TI Coming to grips with Notch SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID T-CELL DEVELOPMENT; NF-KAPPA-B; LYMPHOID PRECURSORS; FATE; DIFFERENTIATION; RECEPTOR; THYMUS; MICE; INACTIVATION; ACTIVATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 20 TC 17 Z9 17 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 2001 VL 194 IS 7 BP F43 EP F46 DI 10.1084/jem.194.7.F43 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484CD UT WOS:000171671900001 PM 11581323 ER PT J AU Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS AF Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS CA Chronic Prostatitis Collaborative TI Quality of life is impaired in men with chronic prostatitis - The chronic prostatitis collaborative research network SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Urological-Association CY APR 29-MAY 04, 2000 CL ATLANTA, GEORGIA SP Amer Urol Assoc DE prostatitis; health-related quality of life ID CHRONIC NONBACTERIAL PROSTATITIS; CHRONIC ABACTERIAL PROSTATITIS; PELVIC PAIN SYNDROME; HEALTH-STATUS; OF-LIFE; SICKNESS IMPACT; SYMPTOMS; VALIDATION; DIAGNOSIS AB OBJECTIVE: Health-related quality of life (HRQOL) Impairment may be a central component of chronic prostatitis for men afflicted with this condition. Our objective was to examine HRQOL, and factors associated with HRQOL, using both general and condition-specific instruments. DESIGN: Chronic Prostatitis Cohort (CPC) study. SETTING: Six clinical research centers across the United States and Canada. PARTICIPANTS: Two hundred seventy-eight men with chronic prostatitis. MEASUREMENTS AND MAIN RESULTS: The Short Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS), and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were measures used. CPC subjects' MCS scores (44.0 +/- 9.8) were lower than those observed in the most severe subgroups of patients with congestive heart failure and diabetes mellitus, and PCS scores (46.4 +/- 9.5) were worse than those among the general U.S. male population. Decreasing scores were seen in both domains with worsening symptom severity (P <.01). History of psychiatric disease and younger age were strongly associated with worse MCS scores, whereas history of rheumatologic disease was associated with worse PCS scores. Predictors of more severe NIH-CPSI scores included lower educational level and lower income; history of rheumatic disease was associated with higher scores. CONCLUSIONS: Men with chronic prostatitis experience impairment in the mental and physical domains of general HRQOL, as well as condition-specific HRQOL. To optimize the care of men with this condition, clinicians should consider administering HRQOL Instruments to their patients to better understand the impact of the condition on patients' lives. C1 Massachusetts Gen Hosp, Gen Med Unit, Med Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Urol Surg, Dept Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Inst Hlth Serv & Hlth Policy Studies, Chicago, IL USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. RI Landis, J. Richard/A-9330-2010 NR 35 TC 86 Z9 88 U1 0 U2 1 PU BLACKWELL SCIENCE 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 OCT PY 2001 VL 16 IS 10 BP 656 EP 662 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 485RV UT WOS:000171773400002 ER PT J AU Fairchild, DG McLoughlin, KS Gharib, S Horsky, J Portnow, M Richter, J Gagliano, N Bates, DW AF Fairchild, DG McLoughlin, KS Gharib, S Horsky, J Portnow, M Richter, J Gagliano, N Bates, DW TI Productivity, quality, and patient satisfaction - Comparison of part-time and full-time primary care physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE productivity; quality of care; patient satisfaction; part-time physicians; women in medicine ID ACADEMIC MEDICINE; WOMEN PHYSICIANS; OUTCOMES; SPECIALTY; FUTURE AB CONTEXT. Although few data are available, many believe that part-time primary care physicians (PCPs) are less productive and provide lower quality care than full-time PCPs. Some insurers exclude part-time PCPs from their provider networks. OBJECTIVE: To compare productivity, quality of preventive care, patient satisfaction, and risk-adjusted resource utilization of part-time and full-time PCPs. DESIGN. Retrospective cohort study. SETTING: Boston. PARTICIPANTS: PCPs affiliated with 2 academic outpatient primary care networks. MEASUREMENTS: PCP productivity, patient satisfaction, resource utilization, and compliance with screening guidelines. RESULTS: Part-time PCP productivity was greater than that of full-time PCPs (2.1 work relative value units (RVUs)/bookable clinical hour versus 1.3 work RVUs/bookable clinical hour, P <.01). A similar proportion of part-time PCPs (80%) and full-time PCPs (75%) met targets for mammography, Pap smears, and cholesterol screening (P =.67). After adjusting for clinical case mix, practice location, gender, board certification status, and years In practice, resource utilization of part-time PCPs ($138 [95% confidence Interval (CI), $108 to $167]) was similar to that of full-time PCPs ($139 [95% CI, $108 to $170], P =.92). Patient satisfaction was similar for part-time and full-time PCPs. CONCLUSIONS: In these academic primary care practices, rates of patient satisfaction, compliance with screening guidelines, and resource utilization were similar for part-time PCPs compared to full-time PCPs. Productivity per clinical hour was markedly higher for part-time PCPs. Despite study limitations, these data suggest that academic part-time PCPs are at least as efficient as full-time PCPs and that the quality of their work is similar. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Brigham & Womens Phys Hosp Org, Boston, MA 02115 USA. Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fairchild, DG (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 30 Z9 30 U1 2 U2 6 PU BLACKWELL SCIENCE 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 OCT PY 2001 VL 16 IS 10 BP 663 EP 667 DI 10.1111/j.1525-1497.2001.01111.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 485RV UT WOS:000171773400003 PM 11679033 ER PT J AU Saha, S Bindman, AB AF Saha, S Bindman, AB TI The mirage of available health care for the uninsured SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; MANAGED CARE; PHYSICIANS C1 Oregon Hlth Sci Univ, Dept Med, Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97201 USA. Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Div Gen Internal Med,Primary Care Res Ctr, San Francisco, CA USA. RP Saha, S (reprint author), Oregon Hlth Sci Univ, Dept Med, Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97201 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE 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 OCT PY 2001 VL 16 IS 10 BP 714 EP 716 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 485RV UT WOS:000171773400011 PM 11679041 ER PT J AU Arcasoy, SM Hersh, C Christie, JD Zisman, D Pochettino, A Rosengard, BR Blumenthal, NP Palevsky, HL Bavaria, JE Kotloff, RM AF Arcasoy, SM Hersh, C Christie, JD Zisman, D Pochettino, A Rosengard, BR Blumenthal, NP Palevsky, HL Bavaria, JE Kotloff, RM TI Bronchogenic carcinoma complicating lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID CARDIAC TRANSPLANTATION; HEART-TRANSPLANTATION; CANCER; MALIGNANCIES; RISK AB Background: Malignancy is a well-recognized complication of solid-organ transplantation. Although a variety of malignancies have been reported in lung transplant recipients, a paucity of information exists regarding the incidence and clinical course of bronchogenic carcinoma in this patient population. Methods: We conducted a retrospective cohort study of our lung transplant experience at the University of Pennsylvania., Results: We identified 6 patients with bronchogenic carcinoma detected at the, time of, or developing after, transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients with lung cancer had a history of smoking, with an average of 79 +/- 39 pack-years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had idiopathic pulmonary fibrosis. Lung cancers were all of non-small-cell histology and first developed in native lungs. Three patients had bronchogenic carcinoma at the time of surgery. The remaining 3 patients were diagnosed between 280 and 1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid course suggestive of an infectious process. The land 2-year survival rates after diagnosis were 33% and 17%, respectively. Conclusion: Lung transplant recipients are at risk for harboring or developing bronchogenic carcinoma in their native lungs. Rapid progression to locally advanced or metastatic disease commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should be considered in the differential diagnosis of pleuroparenchymal processes involving the native lung. C1 Univ Penn, Med Ctr, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Arcasoy, SM (reprint author), Hosp Univ Penn, Pulm Allergy & Crit Care Div, 832 W Gates,3600 Spruce St, Philadelphia, PA 19104 USA. NR 26 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD OCT PY 2001 VL 20 IS 10 BP 1044 EP 1053 DI 10.1016/S1053-2498(01)00301-1 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 480XG UT WOS:000171488200002 PM 11595559 ER PT J AU Lee, SP Ko, CW AF Lee, SP Ko, CW TI Pronucleating proteins in bile - a myth? SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID CHOLESTEROL C1 Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lee, SP (reprint author), Univ Washington, Dept Med, POB 358280,111GI-A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2001 VL 35 IS 4 BP 525 EP 526 DI 10.1016/S0168-8278(01)00209-4 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 484RW UT WOS:000171704200014 PM 11682039 ER PT J AU Dodd, CH Hsu, HC Chu, WJ Yang, PG Zhang, HG Mountz, JD Zinn, K Forder, J Josephson, L Weissleder, R Mountz, JM Mountz, JD AF Dodd, CH Hsu, HC Chu, WJ Yang, PG Zhang, HG Mountz, JD Zinn, K Forder, J Josephson, L Weissleder, R Mountz, JM Mountz, JD TI Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE rodent; T lymphocytes; cell trafficking; MRI, superparamagnetic iron oxide; homing; in vivo animal models ID TAT PROTEIN; IN-VIVO; ADHESION MOLECULES; HIGH-RESOLUTION; APOPTOSIS; ACTIVATION; EXPRESSION; MICE; LYMPHOCYTES; ANTIGEN AB The present study analyzed the feasibility of using magnetic resonance imaging (MRI) to monitor T-cell homing in vivo after loading T cells with superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC-CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3 (0.1 mug/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation-induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1 (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 X 10(7)) were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec system. Homing of T cells into the spleen was observed by a decrease in MRI signal intensity within I It after the transfer, which remained decreased for 2-24 h after transfer. These homing data were confirmed by FACS analysis and biodistribution analysis using I-125-CLIO-Tat. Thus, T cells can be efficiently loaded with FITC-CLIO-Tat without interfering with their normal activation and AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T cells can be monitored in vivo over time by MRI. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Radiol, Ctr Nucl Imaging Res, Birmingham, AL 35294 USA. Univ Alabama, Dept Radiol, Div Nucl Med, Birmingham, AL 35294 USA. Birmingham Vet Adm Med Ctr, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Rheumatol, 701 S 19th St,473 Lyons Harrison Res Bldg, Birmingham, AL 35294 USA. OI Zinn, Kurt/0000-0001-7463-4741 FU NCI NIH HHS [CA 20408]; NIA NIH HHS [R01 AG11653-6A2]; NIAID NIH HHS [R01 AI42900, R01 AI46990]; NIAMS NIH HHS [N01-AR-6-2224] NR 50 TC 163 Z9 175 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 1 PY 2001 VL 256 IS 1-2 BP 89 EP 105 DI 10.1016/S0022-1759(01)00433-1 PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 469WR UT WOS:000170839500009 PM 11516758 ER PT J AU Fors, BP Goodarzi, K von Andrian, UH AF Fors, BP Goodarzi, K von Andrian, UH TI L-selectin shedding is independent of its subsurface structures and topographic distribution SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NODE HOMING RECEPTOR; PROTEIN-KINASE-C; MEMBRANE-PROXIMAL CLEAVAGE; SOLUBLE L-SELECTIN; CELL-SURFACE; DOWN-REGULATION; IN-VITRO; ADHESION MOLECULE; HUMAN NEUTROPHILS; CROSS-LINKING AB L-selectin (CD62L), a lectin-like adhesion molecule, mediates lymphocyte homing and leukocyte accumulation at sites of inflammation. Its transmembrane (TM) and intracellular (IC) domains confer clustering of L-selectin on microvilli of resting leukocytes, which is important for L-selectin function. Following activation of protein kinase C (PKC) or calmodulin inhibition, the wild-type (WT) protein is rapidly cleaved in its membrane-proximal ectodomain. To examine whether L-selectin topography or TM/IC domains are involved in this shedding process, we used stable transfectants expressing WT L-selectin (on microvilli) or chimeric molecules consisting of the L-selectin ectodomain linked to the TM/IC domains of CD44 (excluded from microvilli) or CD31 (randomly distributed). PKC activation by PMA altered the cells' surface morphology, but did not induce a redistribution of L-selectin ectodomains. All cell lines shed ectodomains upon PMA activation in a dose-dependent fashion and with similar kinetics. Calmodulin inhibition by trifluoperazine induced shedding in both WT and chimera transfectants. At high trifluoperazine concentrations, shedding of WT L-selectin was significantly more pronounced than that of chimeric molecules. Regardless of the activating stimulus, shedding was blocked by a hydroxamate-based metalloprotease inhibitor, suggesting that ectodomain downregulation occurred through proteolytic cleavage by identical protease(s). These results show that the recognition site(s) for PKC-induced L-selectin shedding is exclusively contained within the ectodomain; the nature of subsurface structures and surface topography are irrelevant. Shedding induced by calmodulin inhibition has two components: one requires the L-selectin TM/IC domain, and the other is independent of it. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL54936, R01 HL48675]; NIAID NIH HHS [R01 AI072252] NR 73 TC 15 Z9 16 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2001 VL 167 IS 7 BP 3642 EP 3651 PG 10 WC Immunology SC Immunology GA 496JH UT WOS:000172392100015 PM 11564777 ER PT J AU Andoh, A Kinoshita, K Rosenberg, I Podolsky, DK AF Andoh, A Kinoshita, K Rosenberg, I Podolsky, DK TI Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MESSENGER-RNA STABILITY; FACTOR GENE-EXPRESSION; GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; CROHNS-DISEASE; C3; TRANSCRIPTION; DEPOSITION; BLOOD; IDENTIFICATION AB Mucosal damage induces a massive influx of serum complement components into the lumen. The epithelium produces a number of factors that can potentially ameliorate injury including intestinal trefoil factor (ITF), a small protease-resistant peptide produced and secreted onto the mucosal surface by goblet cells, and decay-accelerating factor (DAF), a protein produced by columnar epithelium which protects the host tissue from autologous complement injury. However, coordination of these intrinsic defensive products has not been delineated. DAF protein and mRNA expression were evaluated by immunoblotting and Northern blotting, respectively. NF-kappaB-DNA binding activity and DAF promoter activity were assessed by an electrophoretic gel mobility shift assay and a reporter gene luciferase assay, respectively. ITF induced a dose- and time-dependent increase in DAF protein and mRNA expression in human (HT-29 and T84) and rat (IEC-6) intestinal epithelial cells. In differentiated T84 cells grown on cell culture inserts, basolateral stimulation with ITF strongly enhanced DAF expression, but apical stimulation had no effects. The C3 deposition induced by complement activation was significantly blocked by the treatment with ITF. In HT-29 cells, ITF increased the stability of DAF mRNA. ITF also enhanced the promoter activity of the DAF gene via NF-kappaB motif and induced activation of NF-kappaB-DNA binding activity. ITF promotes protection of epithelial cells from complement activation via up-regulation of DAF expression, contributing to a robust mucosal defense. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK46906, P30 DK43351] NR 42 TC 34 Z9 37 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2001 VL 167 IS 7 BP 3887 EP 3893 PG 7 WC Immunology SC Immunology GA 496JH UT WOS:000172392100044 PM 11564806 ER PT J AU Ali Tahir, SM Cheng, O Shaulov, A Koezuka, Y Bubley, GJ Wilson, SB Balk, SP Exley, MA AF Ali Tahir, SM Cheng, O Shaulov, A Koezuka, Y Bubley, GJ Wilson, SB Balk, SP Exley, MA TI Loss of IFN-gamma production by invariant NK T cells in advanced cancer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-E PRODUCTION; INNATE IMMUNE-SYSTEM; ALPHA-GALACTOSYLCERAMIDE; CUTTING EDGE; SELECTIVE REDUCTION; ANTIGEN RECEPTOR; DENDRITIC CELLS; MICE; RECOGNITION; ACTIVATION AB Invariant NK T cells express certain NK cell receptors and an invariant TCR alpha chain specific for the MHC class I-like CD1d protein. These invariant NK T cells can regulate diverse immune responses in mice, including antitumor responses, through mechanisms including rapid production of IL-4 and IFN-gamma, but their physiological functions remain uncertain. Invariant NK T cells were markedly decreased in peripheral blood from advanced prostate cancer patients, and their ex vivo expansion with a CD1d-presented lipid Ag (alpha -galactosylceramide) was diminished compared with healthy donors. Invariant NK T cells from healthy donors produced high levels of both IFN-gamma and IL-4. In contrast, whereas invariant NK T cells from prostate cancer patients also produced IL-4, they had diminished IFN-gamma production and a striking decrease in their IFN-gamma :IL-4 ratio. The IFN-gamma deficit was specific to the invariant NK T cells, as bulk T cells from prostate cancer patients produced normal levels of IFN-gamma and IL-4. These findings support an immunoregulatory function for invariant NK T cells in humans mediated by differential production of Th1 vs Th2 cytokines. They further indicate that antitumor responses may be suppressed by the marked Th2 bias of invariant NK T cells in advanced cancer patients. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Kirin Brewery Co Ltd, Pharmaceut Res Lab, Gunma, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Harvard Inst Med Bldg,Room 1050,330 Brookline Ave, Boston, MA 02215 USA. NR 45 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2001 VL 167 IS 7 BP 4046 EP 4050 PG 5 WC Immunology SC Immunology GA 496JH UT WOS:000172392100063 ER PT J AU Vemulapalli, RK Cantey, JR Steed, LL Knapp, TL Thielman, NM AF Vemulapalli, RK Cantey, JR Steed, LL Knapp, TL Thielman, NM TI Emergence of resistance to clarithromycin during treatment of disseminated cutaneous Mycobacterium chelonae infection: Case report and literature review SO JOURNAL OF INFECTION LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Infectious-Diseases-Society-of-America CY NOV 18-21, 1999 CL PHILADELPHIA, PENNSYLVANIA SP Infect Dis Soc Amer ID STERNAL WOUND INFECTIONS; FORTUITUM COMPLEX; ORGANISMS; SUSCEPTIBILITY; ENDOCARDITIS; SUBGROUPS; DIALYSIS; KANSASII; AIDS; SKIN AB Results of in vitro susceptibility studies and one clinical trial have led to recommendations of clarithromycin monotherapy for the treatment of disseminated cutaneous Mycobacterium chelonae infections. We describe the case of a 65-year-old woman, immunocompromised by the use of chronic steroid therapy, who developed disseminated cutaneous infection with M. chelonae and failed clarithromycin monotherapy due to the development of drug resistance. In the relapse isolate we document the presence of a single point mutation at position 2058 in the gene coding for 23S rRNA peptidyltransferase regions, a mutation previously implicated in the development of resistance to clarithromycin. Two susceptible control isolates lacked the mutation. Three additional reports in the literature of patients developing recurrent skin lesions with clarithromycin-resistant M. chelonae following initial response to monotherapy are summarized. We demonstrate that clarithromycin monotherapy in patients with disseminated cutaneous infections can lead to clarithromycin resistance and therapeutic failure associated with a single point mutation at position 2058 of 23S rRNA. (C) 2001 The British Infection Society. C1 Med Univ S Carolina, Dept Med, Div Infect Dis, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Dermatol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Thielman, NM (reprint author), Duke Univ, Med Ctr, Div Infect Dis & Internal Hlth, Box 3281,Room 0376,Orange Zone,Duke S, Durham, NC 27710 USA. NR 29 TC 38 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD OCT PY 2001 VL 43 IS 3 BP 163 EP 168 DI 10.1053/jinf.2001.0880 PG 6 WC Infectious Diseases SC Infectious Diseases GA 492YQ UT WOS:000172195500001 PM 11798252 ER PT J AU Palframan, RT Jung, S Cheng, G Weninger, W Luo, Y Dorf, M Littman, DR Rollins, BJ Zweerink, H Rot, A von Andrian, UH AF Palframan, RT Jung, S Cheng, G Weninger, W Luo, Y Dorf, M Littman, DR Rollins, BJ Zweerink, H Rot, A von Andrian, UH TI Inflammatory chemokine transport and presentation in HEV: A remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Ctr Blood Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2001 VL 117 IS 4 MA 002 BP 1003 EP 1003 PG 1 WC Dermatology SC Dermatology GA 486YT UT WOS:000171847500037 ER PT J AU Panini, SR Yang, L Rusinol, AE Sinensky, MS Bonventre, JV Leslie, CC AF Panini, SR Yang, L Rusinol, AE Sinensky, MS Bonventre, JV Leslie, CC TI Arachidonate metabolism and the signaling pathway of induction of apoptosis by oxidized LDL/oxysterol SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonic acid; calcium; cPLA(2); eicosanoids ID CYTOSOLIC PHOSPHOLIPASE A(2); LOW-DENSITY-LIPOPROTEIN; TUMOR-NECROSIS-FACTOR; OXYSTEROL-INDUCED APOPTOSIS; ACTIVATED PROTEIN-KINASE; HUMAN ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; ACID RELEASE; 5,8,11,14-EICOSATETRAYNOIC ACID; ATHEROSCLEROTIC PLAQUES AB Owing at least in part to oxysterol components that can induce apoptosis, oxidized LDL (oxLDL) is cytotoxic to mammalian cells with receptors that can internalize it. Vascular cells possess such receptors, and it appears that the apoptotic response of vascular cells to the oxysterols borne by oxLDL is an important part of the atherogenic effects of oxLDL. Thus, an analysis of the signaling pathway of apoptotic induction by oxysterols is of value in understanding the development of atherosclerotic plaque. In a prior study, we demonstrated an induction of calcium ion flux into cells treated with 25-hydroxycholesterol (25-OHC) and showed that this response is essential for 25-OHC-induced apoptosis. One possible signal transduction pathway initiated by calcium ion fluxes is the activation of cytosolic phospholipase A(2) (cPLA(2)). In the current study, we demonstrate that activation of cPLA(2) does occur in both macrophages and fibroblasts treated with 25-OHC or oxLDL. Activation is evidenced by 25-OHC-induced relocalization of cPLA(2) to the nuclear envelope and arachidonic acid release. jlr Loss of cPLA(2) activity, either through genetic knockout in mice, or by treatment with a cPLA(2) inhibitor, results in an attenuation of arachidonic acid release as well as of the apoptotic response to oxLDL in peritonea] macrophages or to 25-OHC in cultured fibroblast and macrophage cell lines. C1 E Tennessee State Univ, James H Quillen Coll Med, Dept Biochem & Mol Biol, Johnson City, TN 37614 USA. Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Med Serv, Cambridge, MA 02129 USA. Natl Jewish Med & Res Ctr, Cell Biol Program, Dept Pediat, Denver, CO 80206 USA. RP Sinensky, MS (reprint author), E Tennessee State Univ, James H Quillen Coll Med, Dept Biochem & Mol Biol, Ross Dr,Bldg 11, Johnson City, TN 37614 USA. FU NHLBI NIH HHS [HL 34303, HL 61378]; NIDDK NIH HHS [DK 39773, DK 38542]; NINDS NIH HHS [NS 10828] NR 52 TC 80 Z9 81 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2001 VL 42 IS 10 BP 1678 EP 1686 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486DL UT WOS:000171803100019 PM 11590225 ER PT J AU Sisodia, SS Tanzi, RE AF Sisodia, SS Tanzi, RE TI Special issue: Alzheimer's disease - Guest Editor's Introduction SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Editorial Material C1 Univ Chicago, Ctr Mol Neurobiol, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Cambridge, MA 02129 USA. RP Sisodia, SS (reprint author), Univ Chicago, Ctr Mol Neurobiol, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 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. PD OCT PY 2001 VL 17 IS 2 BP 99 EP 99 DI 10.1385/JMN:17:2:99 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 492EE UT WOS:000172154800001 ER PT J AU Bertram, L Tanzi, RE AF Bertram, L Tanzi, RE TI Dancing in the dark? The status of late-onset Alzheimer's disease genetics SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE genetics; presenilin; genome; amyloid; Alzheimer's ID LIPOPROTEIN RECEPTOR GENE; APOLIPOPROTEIN-E GENOTYPE; AMYLOID BETA-PROTEIN; ALPHA-2-MACROGLOBULIN GENE; MISSENSE MUTATIONS; NO ASSOCIATION; VLDL RECEPTOR; APOE GENOTYPE; LRP GENE; POLYMORPHISM AB Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. Recent estimates suggest that possibly over 70% of the genetic variance for the disease remains unaccounted for by apolipoprotein E (APOE) and the three known early-onset AD genes (APP, PSEN1, PSEN2). Specifically, one recent segregation analysis predicted the existence of up to four additional susceptibility genes having a similar or greater effect than APOE. However, most of the nearly three dozen putative AD loci proposed to date have only been inconsistently replicated in follow up analyses and more studies are necessary to distinguish false-positive findings from genuine signals. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk-profiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. In this review, we will present a brief overview of analytic tools in complex disease genetics, as well as a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on chromosomes 12, 10, and 9. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 72 TC 20 Z9 23 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. PD OCT PY 2001 VL 17 IS 2 BP 127 EP 136 DI 10.1385/JMN:17:2:127 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 492EE UT WOS:000172154800004 PM 11816786 ER PT J AU Schaefer, PW Gonzalez, RG Hunter, G Wang, B Koroshetz, WJ Schwamm, LH AF Schaefer, PW Gonzalez, RG Hunter, G Wang, B Koroshetz, WJ Schwamm, LH TI Diagnostic value of apparent diffusion coefficient hyperintensity in selected patients with acute neurologic deficits SO JOURNAL OF NEUROIMAGING LA English DT Article DE apparent diffusion coefficient; diffusion-weighted imaging; vasogenic edema; stroke ID BLOOD-BRAIN-BARRIER; REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; HYPERTENSIVE ENCEPHALOPATHY; VENOUS THROMBOSIS; CEREBRAL-ISCHEMIA; ACUTE STROKE; MR; EDEMA; CYCLOSPORINE; DISRUPTION AB Background and Purpose. A pattern of decreased intensity on apparent diffusion coefficient (ADC) maps is useful in the early detection of ischemic brain injury. Less information exists with regard to patients with acute neurologic deficits in whom there is abnormal conventional magnetic resonance imaging (MRI) and increased ADC intensity. Methods. The authors identified 13 patients with acute neurologic deficits who underwent diffusion MRI and had calculated ADC maps demonstrating hyperintensity in regions characterized by computed tomography hypodensity and MRI T2 hyperintensity. The initial and follow-up imaging characteristics and clinical syndromes were recorded. Results. Clinical syndromes included hypertensive encephalopathy, posterior leukoencephalopathy, hyperperfusion following carotid endarterectomy, venous sinus thrombosis, HIV encephalopathy, and brain tumor. Diffusion-weighted imaging (DWI) was hyperintense in 3 of 13 patients, isointense in 4 of 13 patients, heterogeneous in 3 of 13 patients, and hypointense in 3 of 13 patients. The ADC values in these regions were significantly higher than those in control regions (P < .0001). At early follow-up, MRI abnormalities resolved completely in 3 of 13 patients and partially in 9 of 13 patients. MRI abnormalities were unchanged in 1 patient. Conclusions. In the evaluation of patients with acute neurologic deficits, ADC hyperintensity may identify a subset of patients with vasogenic edema of nonischemic etiology. Frequently, these conditions are potentially reversible if appropriately managed. DWI and conventional images alone are not sufficient to identify these neurologic conditions. C1 Massachusetts Gen Hosp, Dept Neurol VBK 915, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol VBK 915, Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 35 TC 23 Z9 24 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2001 VL 11 IS 4 BP 369 EP 380 PG 12 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 477RQ UT WOS:000171298400004 PM 11677876 ER PT J AU Greer, DM Buonanno, FS AF Greer, DM Buonanno, FS TI Cerebral infarction in conjunction with patent foramen ovale and May-Thurner syndrome SO JOURNAL OF NEUROIMAGING LA English DT Article DE stroke; May-Thurner; patent foramen ovale; iliac compression ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; STROKE AB Stroke patients with paradoxical embolus mandate a search for deep venous thrombosis (DVT) in the lower extremities. Iliac vein compression, or May-Thurner syndrome, places certain patients at risk for development of DVT. The authors present 3 stroke patients with patent foramen ovals and paradoxical cerebral embolism, with demonstrated iliac vein compression as the presumed source of their embolus. May-Thurner syndrome should be considered a potential source of clot, as definitive therapy of this disorder Gan be curative. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Buonanno, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802,32 Fruit St, Boston, MA 02114 USA. NR 13 TC 12 Z9 12 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2001 VL 11 IS 4 BP 432 EP 434 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 477RQ UT WOS:000171298400013 PM 11677885 ER PT J AU Irizarry, MC Hyman, BT AF Irizarry, MC Hyman, BT TI Alzheimer disease therapeutics SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid beta protein; cholinesterase inhibitors; estrogen; inflammation; neurofibrillary tangles; Tau ID RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL; ESTROGEN-REPLACEMENT THERAPY; AMYLOID PRECURSOR PROTEIN; DOUBLE-BLIND; APOLIPOPROTEIN-E; MOUSE MODEL; CHOLINERGIC NEURONS; SENILE DEMENTIA; NUCLEUS BASALIS AB Alzheimer disease (AD) is characterized pathologically by cholinergic deficits, amyloid plaques, neurofibrillary tangles, gliosis, and neuronal and synaptic loss. The primary therapeutic approach that has arisen from the pathological analysis of AD brain has been cholinergic augmentation by cholinesterase inhibitors, which modestly improve cognitive function. Research on the underlying pathophysiological dysfunction have focussed on AD-specific processes such as amyloid precursor protein, tau, and cerebral apolipoprotein E metabolism, and more general neurodegenerative processes such as inflammation, oxidation, excitotoxicity, and apoptosis. Rational neuroprotective approaches have led to recent trials of estrogen, antioxidant and anti-inflammatory medications in AD, and to the: development of anti-amyloid strategies for delaying progression or preventing development of AD. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Alzheimer Dis Res Unit, Boston, MA 02114 USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Ctr Aging Genet & Neurodegenerat, Alzheimer Dis Res Unit, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG00793] NR 70 TC 37 Z9 40 U1 0 U2 5 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 OCT PY 2001 VL 60 IS 10 BP 923 EP 928 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 478KC UT WOS:000171344600001 PM 11589422 ER PT J AU Zaidi, AU McDonough, JS Klocke, BJ Latham, CB Korsmeyer, SJ Flavell, RA Schmidt, RE Roth, KA AF Zaidi, AU McDonough, JS Klocke, BJ Latham, CB Korsmeyer, SJ Flavell, RA Schmidt, RE Roth, KA TI Chloroquine-induced neuronal cell death is p53 and Bcl-2 family-dependent but caspase-independent SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; autophagy; caspase-3; lysosome; telencephalon ID MITOCHONDRIAL PERMEABILITY TRANSITION; X-DEFICIENT MICE; ALZHEIMERS-DISEASE; PROTEIN-DEGRADATION; CATHEPSIN-D; HUNTINGTIN EXPRESSION; LYSOSOMAL SYSTEM; UP-REGULATION; IN-VITRO; APOPTOSIS AB Chloroquine is a lysosomotropic agent that causes marked changes in intracellular protein processing and trafficking and extensive autophagic vacuole formation. Chloroquine may be cytotoxic and has been used as a model of lysosomal-dependent cell death. Recent studies indicate that autophagic cell death may involve Bcl-2 family members and share some features with caspase-dependent apoptotic death. To determine the molecular pathway of chloroquine-induced neuronal cell death, we examined the effects of chloroquine on primary telencephalic neuronal cultures derived from mice with targeted gene disruptions in p53, and various caspase and bcl-2 family members. In wild-type neurons, chloroquine produced concentration- and time-dependent accumulation of autophagosomes, caspase-3 activation, and cell death. Cell death was inhibited by 3-methyladenine, an inhibitor of autophagic vacuole formation, but not by Boc-Asp-FMK (BAF), a broad caspase inhibitor. Targeted gene disruptions of b53 and bax inhibited and bcl-x potentiated chloroquine-induced neuron death. Caspase-9- and caspase-3-deficient neurons were not protected from chloroquine cytotoxicity. These studies indicate that chloroquine activates a regulated cell death pathway that partially overlaps with the apoptotic cascade. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, Div Neuropathol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Howard Hughes Med Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunol Sect, New Haven, CT 06510 USA. RP Roth, KA (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, Div Neuropathol, 660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA. OI Roth, Kevin/0000-0002-0643-995X FU NIA NIH HHS [AG16945]; NINDS NIH HHS [NS35107] NR 62 TC 60 Z9 61 U1 0 U2 4 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 OCT PY 2001 VL 60 IS 10 BP 937 EP 945 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 478KC UT WOS:000171344600003 PM 11589424 ER PT J AU Frank, LM Brown, EN Wilson, MA AF Frank, LM Brown, EN Wilson, MA TI A comparison of the firing properties of putative excitatory and inhibitory neurons from CA1 and the entorhinal cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID HIPPOCAMPAL PLACE CELLS; THETA FIELD POTENTIALS; SINGLE UNIT-ACTIVITY; FREELY-MOVING RATS; BEHAVING RAT; WORKING-MEMORY; PARIETAL CORTEX; PYRAMIDAL CELLS; PHASE-RELATIONS; INTERNEURONS AB The superficial layers of the entorhinal cortex (EC) provide the majority of the neocortical input to the hippocampus, and the deep layers of the EC receive the majority of neocortically bound hippocampal outputs. To characterize information transmission through the hippocampal and EC circuitry, we recorded simultaneously from neurons in the superficial EC, the CA1 region of hippocampus, and the deep EC while rodents ran for food reward in two environments. Spike waveform analysis allowed us to classify units as fast-spiking (FS) putative inhibitory cells or putative excitatory (PE) cells. PE and FS units' firing were often strongly correlated at short time scales, suggesting the presence a monosynaptic connection from the PE to FS units. EC PE units, unlike those found in CA1, showed little or no tendency to fire in bursts. We also found that the firing of FS and PE units from all regions was modulated by the similar to8 Hz theta rhythm, although the firing of deep EC FS units tended to be less strongly modulated than that of the other types of units. When we examined the spatial specificity of FS units, we determined that FS units in all three regions showed low specificity. At the same time, retrospective coding, in which firing rates were related to past position, was present in FS units from all three regions and deep EC FS units often fired in a "path equivalent" manner in that they were active in physically different, but behaviorally related positions both within and across environments. Our results suggest that while the firing of FS units from CAI and the EC show similarly low levels of position specificity, FS units from each region differ from one another in that they mirrored the associated PE units in terms of their tendency to show more complex positional firing properties like retrospective coding and path equivalence. C1 MIT, RIKEN MIT Neurosci Res Ctr, Ctr Learning & Memory, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Sch Med, Boston, MA 02114 USA. RP Wilson, MA (reprint author), MIT, RIKEN MIT Neurosci Res Ctr, Ctr Learning & Memory, E18-370,45 Carleton St, Cambridge, MA 02139 USA. OI Frank, Loren/0000-0002-1752-5677 FU NIMH NIH HHS [P50 MH058880, R01 MH059733, MH-59733, MH-61637, MH-58880, K02 MH061637] NR 57 TC 105 Z9 105 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2001 VL 86 IS 4 BP 2029 EP 2040 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 482EN UT WOS:000171562000043 PM 11600659 ER PT J AU Asahi, M Wang, XY Mori, T Sumii, T Jung, JC Moskowitz, MA Fini, ME Lo, EH AF Asahi, M Wang, XY Mori, T Sumii, T Jung, JC Moskowitz, MA Fini, ME Lo, EH TI Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stroke; extracellular proteolysis; blood-brain barrier; myelin; neuroprotection; mouse ID CENTRAL-NERVOUS-SYSTEM; TRANSIENT ISCHEMIA; ENDOTHELIAL-CELLS; SERINE PROTEASES; NEURONAL DEATH; KEY REGULATOR; EXPRESSION; INHIBITION; DAMAGE; RAT AB Deleterious processes of extracellular proteolysis may contribute to the progression of tissue damage after acute brain injury. We recently showed that matrix metalloproteinase-9 (MMP-9) knock-out mice were protected against ischemic, and traumatic brain! injury. In this study, we examined the mechanisms involved! by focusing. on relevant MMP-9 substrates in blood-brain barrier, matrix, and white matter. MMP-9 knock-out and wild-type mice were subjected to transient focal ischemia. MMP-9 levels increased after ischemia in wild-type brain, with expression primarily present in vascular endothelium. Western blots showed that the blood-brain: barrier-associated protein and MMP-9 substrate zonae occludens-1 was degraded after ischemia, but this was reduced in knock-out mice. There were no detectable changes in another blood-brain barrier-associated protein, occludin. Correspondingly, blood-brain barrier disruption assessed via Evans Blue, leakage was significantly attenuated in MMP-9 knock-out mice compared with wild types. In white matter, ischemic degradation: of the MMP-9 substrate myelin basic protein was significantly reduced in knock-out mice compared with wild types, whereas there was no degradation of other myelin proteins that are not MMP substrates (proteolipid protein and DM20). There were no detectable changes in the ubiquitous structural protein actin or the extracellular matrix protein laminin. Finally, 24 hr lesion volumes were significantly reduced in knock-out mice compared with wild types. These data demonstrate that the protective effects of MMP-9 gene knock-out after transient focal ischemia may be mediated by reduced proteolytic degradation of critical blood-brain barrier and white matter components. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02139 USA. Tufts Univ, New England Eye Ctr, Vis Res Labs, Boston, MA 02111 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E 149 2322, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02139 USA. RI Moskowitz, Michael/D-9916-2011 FU NEI NIH HHS [R01-EY12651]; NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS38731, R01-NS40529] NR 55 TC 609 Z9 657 U1 2 U2 28 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 2001 VL 21 IS 19 BP 7724 EP 7732 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 475GL UT WOS:000171154000034 PM 11567062 ER PT J AU Kim, BT Raghavendra, VL Sailor, KA Bowen, KK Dempsey, RJ AF Kim, BT Raghavendra, VL Sailor, KA Bowen, KK Dempsey, RJ TI Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after traumatic brain injury in rats SO JOURNAL OF NEUROSURGERY LA English DT Article DE glial cell line-derived neurotrophic factor; neuron death; neuroprotection; traumatic brain injury; rat ID CONTROLLED CORTICAL IMPACT; NERVE GROWTH-FACTOR; BARRIER BREAKDOWN; HEAD-INJURY; DEATH; EXPRESSION; ASTROCYTES; RECEPTOR; GDNF; ISCHEMIA AB Object. The purpose of this study was to evaluate whether glial cell line-derived neurotrophic factor (GDNF) can protect against hippocampal neuronal death after traumatic brain injury (TBI). Methods. Male Sprague-Dawley rats were subjected to moderate TBI with a controlled cortical impact device while in a state of halothane-induced anesthesia. Then, GDNF or artificial cerebrospinal fluid ([aCSF]; vehicle) was infused into the frontal horn of the left lateral ventricle. In eight brain-injured and eight sham-operated rats, GDNF was infused continuously for 7 days (200 ng/day intracerebroventricularly at a rate of 8.35 ng/0.5 mul/hour). An equal volume of vehicle was infused at the same rate into the remaining eight brain-injured and eight sham-operated rats. Seven days postinjury, all rats were killed. Their brains were sectioned and stained with cresyl violet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3 regions with the aid of microscopy. A parallel set of sections from each brain was subjected to immunoreaction with antibodies against glial fibrillary acidic protein (GFAP; astroglia marker). In the aCSF-treated group, TBI resulted in a significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 regions (68%, p < 0.05) compared with the sham-operated control animals. Compared with control rats infused with aCSF, GDNF infusion significantly decreased the TBI-induced neuronal loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, P < 0.05). There was no difference in the number of GFAP-positive astroglial cells in the GDNF-infused rats in the TBI and sham-operated groups compared with the respective vehicle-treated groups. Conclusions. The authors found that GDNF treatment following TBI is neuroprotective. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Soonchunhyang Univ Hosp, Dept Neurosurg, Seoul, South Korea. RP Dempsey, RJ (reprint author), Univ Wisconsin, Dept Neurol Surg, H4-336 CSC,600 Highland Ave, Madison, WI 53792 USA. NR 32 TC 48 Z9 53 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2001 VL 95 IS 4 BP 674 EP 679 DI 10.3171/jns.2001.95.4.0674 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 478NQ UT WOS:000171352600017 PM 11596962 ER PT J AU Mata, M Zhang, MD Hu, XP Fink, DJ AF Mata, M Zhang, MD Hu, XP Fink, DJ TI HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons, of the rat peripheral nervous system SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE herpesvirus 1; receptor; nectin; neurons ID HERPES-SIMPLEX VIRUS; RECEPTOR-RELATED PROTEIN-1; POLIOVIRUS RECEPTOR; GLYCOPROTEIN-C; TYPE-1; ENTRY; CELLS; MEMBER; DOMAIN; BIND AB The entry of herpes simplex virus (HSV)-1 into cells is a complex process mediated in part by the binding of the HSV glycoprotein D (gD) to a specific cellular receptor identified as HveC, or nectin-1. We examined the distribution of HveC in sensory and motor neurons of the peripheral nervous system (PNS) by immunocytochemistry. HveC is expressed at high levels in sensory neurons of dorsal root ganglion and their peripheral axons, at lower levels in motor neurons of spinal cord, and without detectable expression in motor nerve terminals at the neuromuscular junction. These results have implications regarding the tropism of HSV to specific neuronal populations, and for the construction of HSV-based vectors for the peripheral nervous system. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biochem, Pittsburgh, PA 15213 USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fink, DJ (reprint author), S-520 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 14 TC 41 Z9 44 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2001 VL 7 IS 5 BP 476 EP 480 DI 10.1080/135502801753170336 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 485LL UT WOS:000171755800010 PM 11582520 ER PT J AU Kling, DE Narra, V Islam, S Kinane, TB Alessandrini, A Ercolani, L Donahoe, PK Schnitzer, JJ AF Kling, DE Narra, V Islam, S Kinane, TB Alessandrini, A Ercolani, L Donahoe, PK Schnitzer, JJ TI Decreased mitogen activated protein kinase activities in congenital diaphragmatic hernia-associated pulmonary hypoplasia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT Experimental Biology 99 Meeting CY APR 17-21, 1999 CL WASHINGTON, D.C. DE congenital diaphragmatic hernia; mitogen activated protein kinase; lung; fetal; nitrofen; extracellular regulated kinase ID LUNG HYPOPLASIA; GROWTH-FACTOR; FETAL SHEEP; RATS; IMMATURITY; RECEPTOR; GLUCOCORTICOIDS; PHOSPHATASE-1; INHIBITION; EXPRESSION AB Background/Purpose: The mechanisms that cause pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) currently are unknown. The authors proposed that the reduced size and immaturity of these lungs may be associated with differences in the levels of mitogen activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2). Methods: ERK-1 activities were measured using immune-complex kinase assays on fetal whole-lung lysates obtained from both nitrofen and olive oil-treated (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activities were estimated by semiquantitative Western blot analysis, using an antibody specific for the diphosphorylated (dp-ERK, activated) forms of the enzymes. Results: ERK-1 activities, measured using immune-complex kinase assays, were reduced in CDH lungs compared with olive oil-treated controls (P < .02). In addition, dp-ERK-1 and dp-ERK-2 levels were found to be reduced in CDH lungs compared with controls (dp-ERK-1, P = .003; dp-ERK-2, P = .04), whereas ERK-1 and ERK-2 protein levels were unchanged. Conclusions: The lower values of ERK-1 activity and reduced amounts of dp-ERK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with CDH. The observed reduction in ERK-1 and ERK-2 activities implicates attenuated cell signaling upstream of the ERK-1 and -2 enzymes. Copyright (C) 2001 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Pediat Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. RP Schnitzer, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Pediat Surg Serv, 55 Fruit St,WN 11, Boston, MA 02114 USA. FU NHLBI NIH HHS [1R01HL62615] NR 34 TC 5 Z9 5 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD OCT PY 2001 VL 36 IS 10 BP 1490 EP 1496 DI 10.1053/jpsu.2001.27029 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 478AD UT WOS:000171320000004 PM 11584394 ER PT J AU Jones, MD Boat, TF Stockman, JA Clark, EB Minaga-Miya, K Gilchrist, GS Colletti, R Winter, HS AF Jones, MD Boat, TF Stockman, JA Clark, EB Minaga-Miya, K Gilchrist, GS Colletti, R Winter, HS TI Federation of Pediatric Organizations subspecialty forum SO JOURNAL OF PEDIATRICS LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. Amer Board Pediat Inc, Chapel Hill, NC USA. Childrens Med & Res Ctr, Cincinnati, OH USA. Childrens Hosp, Denver, CO 80218 USA. Univ Colorado, Sch Med, Boulder, CO 80309 USA. RP Jones, MD (reprint author), FOPO, 111 Silver Cedar Court, Chapel Hill, NC 27514 USA. NR 5 TC 7 Z9 7 U1 0 U2 1 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 OCT PY 2001 VL 139 IS 4 BP 487 EP 493 DI 10.1067/mpd.2001.118840 PG 7 WC Pediatrics SC Pediatrics GA 484MZ UT WOS:000171695300005 PM 11598593 ER PT J AU Blais, MA Otto, MW Zucker, BG McNally, RJ Schmidt, NB Fava, M Pollack, MH AF Blais, MA Otto, MW Zucker, BG McNally, RJ Schmidt, NB Fava, M Pollack, MH TI The anxiety sensitivity index: Item analysis and suggestions for refinement SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID CARBON-DIOXIDE CHALLENGE; BREATH-HOLDING DURATION; PANIC ATTACKS; PSYCHOMETRIC PROPERTIES; SUFFOCATION FEAR; TRAIT ANXIETY; DEPRESSION; PREDICTORS; SCALE; PATHOGENESIS AB Anxiety sensitivity is the fear of anxiety-related sensations, and is measured by the 16-item Anxiety Sensitivity Index (ASI; Reiss, Peterson, Gursky, & McNally, 1986). Despite the popularity and utility of the ASI in research, a number of studies have provided evidence for the inadequacy of several items, and item-to-scale correlations for the ASI have not been published. In this study, a converging set of analyses to evaluate the item adequacy and factor structure of the ASI was used. The results of these multiple analyses converged nicely suggesting that Items 1, 5, 7, 8, and 13 should be considered for removal from the instrument. The impact of removing these problematic items from the scale was explored through the reanalysis of data from 3 previously published studies that compared the original ASI with the new 11-item version (the ASI minus the 5 problematic items). The results of these analyses suggest that the 2 scales function comparably in many respects but that the new version maybe a more precise measure of anxiety sensitivity. The 11-item ASI appears to tap 2 primary aspects of anxiety sensitivity: fears of somatic sensations of anxiety and fears of loss of mental control. Suggestions for further development of the ASI are offered. C1 Massachusetts Gen Hosp, Inpatient Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 54 TC 59 Z9 60 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD OCT PY 2001 VL 77 IS 2 BP 272 EP 294 DI 10.1207/S15327752JPA7702_10 PG 23 WC Psychology, Clinical; Psychology, Social SC Psychology GA 484BW UT WOS:000171671200009 PM 11693859 ER PT J AU Chang, LT Suh, HH Wolfson, JM Misra, K Allen, GA Catalano, PJ Koutrakis, P AF Chang, LT Suh, HH Wolfson, JM Misra, K Allen, GA Catalano, PJ Koutrakis, P TI Laboratory and field evaluation of measurement methods for one-hour exposures to O-3, PM2.5, and CO SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID CARBON-MONOXIDE EXPOSURES; CONGESTIVE-HEART-FAILURE; AMBIENT AIR-POLLUTION; ACTIVE OZONE SAMPLER; PASSIVE SAMPLER; HOSPITAL ADMISSIONS; PERSONAL EXPOSURES; PRESCHOOL-CHILDREN; METHOD PERFORMANCE; EMISSION RATES AB While researchers have linked acute (less than 12-hr) ambient O-3, PM2.5, and CO concentrations to a variety of adverse health effects, few studies have characterized short-term exposures to these air pollutants, in part due to the lack of sensitive, accurate, and precise sampling technologies. In this paper, we present results from the laboratory and field evaluation of several new (or modified) samplers used in the "roll-around" system (RAS), which was developed to measure 1-hr O-3, PM2.5, and CO exposures simultaneously. All the field evaluation data were collected during two sampling seasons: the summer of 1998 and the winter of 1999. To measure 1-hr O-3 exposures, a new active O-3 sampler was developed that uses two nitrite-coated filters to measure O-3 concentrations. Laboratory chamber tests found that the active O-3 sampler performed extremely well, with a collection efficiency of 0.96 that did not vary with temperature or relative humidity (RH). In field collocation comparisons with a reference UV photometric monitor, the active O-3 sampler had an effective collection efficiency ranging between 0.92 and 0.96 and a precision for 1-hr measurements ranging between 4 and 6 parts per billion (ppb). The limits of detection (LOD) of this method were 9 ppb-hr for the chamber tests and similar to 16 ppb-hr for the field comparison tests. PM2.5 and CO concentrations were measured using modified continuous monitors-the DustTrak and the Langan, respectively. A size-selective inlet and a Nafion dryer were placed upstream of the DustTrak inlet to remove particles with aerodynamic diameters greater than 2.5 mum and to dry particles prior to the measurements, respectively. During the field validation tests, the DustTrak consistently reported higher PM2.5 concentrations than those obtained by the collocated 12-hr PM2.5 PEM samples, by approximately a factor of 2. After the DustTrak response was corrected (correction factor of 2.07 in the summer and 2.02 in the winter), measurements obtained using these methods agreed well with R-2 values of 0.87 in the summer and 0.81 in the winter. The results showed that the DustTrak can be used along with integrated measurements to measure the temporal and spatial variation in PM2.5 exposures. Finally, during the field validation tests, CO concentrations measured using the Langan were strongly correlated with those obtained using the reference method when the CO levels were above the LOD of the instrument [similar to1 part per million (ppm)]. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Chang, LT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 68 TC 33 Z9 33 U1 1 U2 9 PU AIR & WASTE MANAGEMENT ASSOC PI PITTSBURGH PA ONE GATEWAY CENTER, THIRD FL, PITTSBURGH, PA 15222 USA SN 1047-3289 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PD OCT PY 2001 VL 51 IS 10 BP 1414 EP 1422 PG 9 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA 482WC UT WOS:000171599400008 PM 11686245 ER PT J AU Stoddard, FJ Saxe, G AF Stoddard, FJ Saxe, G TI Ten-year research review of physical injuries SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE pediatric injury; pain; stress; burns; psychiatric treatment ID POSTTRAUMATIC-STRESS-DISORDER; SPINAL-CORD INJURY; ADOLESCENT SUICIDE; CHILD MALTREATMENT; PEDIATRIC AMPUTEES; SOCIAL-INTERACTION; VITAL-STATISTICS; TRAUMATIC INJURY; SUBSTANCE-ABUSE; YOUNG-ADULTS AB Objective: To review the past 10 years of research relevant to psychiatry on injuries in children and adolescents. Method: A literature search of databases for "wounds and injuries, excluding head injuries," was done with Medline and PsycINFO, yielding 589 and 299 citations, respectively. Further searching identified additional studies. Results: Progress is occurring in prevention, pain management, acute care, psychiatric treatment, and outcomes, The emotional and behavioral effects of injuries contribute to morbidity and mortality. Psychiatric assessment, crisis intervention, psychotherapy, psychopharmacological treatment, and interventions for families are now priorities. Research offers new interventions for pain, delirium, posttraumatic stress disorder, depression, prior maltreatment, substance abuse, disruptive behavior, and end-of-life care. High-risk subgroups are infants, adolescents, maltreated children, suicide attempters, and substance abusers. Staff training improves quality of care and reduces staff stress. Conclusions: Despite the high priority that injuries receive in pediatric research and treatment, psychiatric aspects are neglected. There is a need for assessment and for planning of psychotherapeutic, psychopharmacological, and multimodal treatments, based on severity of injury, comorbid psychopathology, bodily location(s), and prognosis. Psychiatric collaboration with emergency, trauma, and rehabilitation teams enhances medical care. Research should focus on alleviating pain, early psychiatric case identification, and treatment of children, adolescents, and their families, to prevent further injuries and reduce disability. C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. RP Stoddard, FJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, SBH 6,Fruit St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01-MH57370] NR 176 TC 57 Z9 59 U1 5 U2 13 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 OCT PY 2001 VL 40 IS 10 BP 1128 EP 1145 DI 10.1097/00004583-200110000-00007 PG 18 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 475XM UT WOS:000171195200006 PM 11589526 ER PT J AU Cook, EH Wagner, KD March, JS Biederman, J Landau, P Wolkow, R Messig, M AF Cook, EH Wagner, KD March, JS Biederman, J Landau, P Wolkow, R Messig, M TI Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE sertraline; obsessive-compulsive disorder ID CONTROLLED TRIAL; PLACEBO; CLOMIPRAMINE; MULTICENTER; SCALE; EPIDEMIOLOGY; OUTPATIENTS; RELIABILITY; VALIDITY AB Objective: To evaluate the safety and effectiveness of sertraline in the long-term treatment of pediatric obsessive-compulsive disorder (OCD). Method: Children (6-12 years; n = 72) and adolescents (13-18 years n = 65) with DSM-III-R-defined OCD who had completed a 12-week, double-blind, placebo-controlled sertraline study were given open-label sertraline 50 to 200 mg/day in this 52-week extension study Concomitant psychotherapy was allowed during the extension study. Outcome was evaluated by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), National Institute of Mental Health Global Obsessive-Compulsive Scale, and Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores. Results: Significant improvement (p < .0001) was demonstrated on all four outcome parameters on an intent-to-treat analysis for the overall study population (n = 132), as well as the child and the adolescent samples. At endpoint, 72% of children and 61 % of adolescents met response criteria (25% decrease in CY-BOCS and a CGI-I score of 1 or 2). Significant (p < .05) improvements were also demonstrated from the extension study baseline to endpoint on all outcome parameters in those patients who received sertraline during the 12-week, double-blind acute study. Long-term sertraline treatment was well tolerated, and there were no discontinuations; due to changes in vital signs, laboratory values, or electrocardiograms. Conclusion: Sertraline (50-200 mg/day) was effective and generally well tolerated in the treatment of childhood and adolescent OCD for up to 52 weeks. Improvement was seen with continued treatment. C1 Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Texas, Med Branch, Div Child & Adolescent Psychiat, Galveston, TX 77550 USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Dept Psychiat, Pediat Pharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Pfizer Inc, New York, NY USA. RP Cook, EH (reprint author), Univ Chicago, Dept Psychiat, MC 3077,5841 S Maryland Ave, Chicago, IL 60637 USA. NR 30 TC 78 Z9 78 U1 2 U2 6 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 OCT PY 2001 VL 40 IS 10 BP 1175 EP 1181 DI 10.1097/00004583-200110000-00011 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 475XM UT WOS:000171195200010 PM 11589530 ER PT J AU Sultzer, DL Gray, KF Gunay, I Wheatley, MV Mahler, ME AF Sultzer, DL Gray, KF Gunay, I Wheatley, MV Mahler, ME TI Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; dementia; agitation; treatment; trazodone ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE PATIENTS; PLACEBO-CONTROLLED TRIAL; AGGRESSIVE-BEHAVIOR; DOUBLE-BLIND; PHARMACOLOGICAL TREATMENT; DISRUPTIVE BEHAVIORS; AGITATION; DISTURBANCES; SEROTONIN AB OBJECTIVES: Several previous studies have examined the effects of pharmacological interventions for agitated behavior in patients with dementia. However, the choice of medication in clinical practice continues to be directed largely by local pharmacotherapy culture rather than empirical treatment guidelines. We examined the relationship between behavioral improvement and co-occurring delusions and mood symptoms in patients with dementia who were treated with haloperidol, an antipsychotic medication, or trazodone, a serotonergic antidepressant. DESIGN: Randomized, double-blind, parallel-group, 9-week treatment trial. SETTING: Inpatient geropsychiatry unit. PARTICIPANTS: Twenty-eight patients with dementia and agitated or aggressive behaviors. INTERVENTION: Haloperidol 1 to 5 mg/day or trazodone 50 to 250 mg/day. MEASUREMENTS: Cohen-Mansfield Agitation Inventory (CMAI), Hamilton Depression Rating Scale (Ham-D), and delusional thoughts subscale and hallucinations subscale of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). RESULTS: CMAI scores improved in each treatment group over the 9 weeks of treatment (P < .001 in each group). Within the haloperidol treatment group, CMAI improvement was not associated with baseline delusional thoughts score or with change in delusional thoughts score over the course of treatment. Within the trazodone treatment group, CMAI improvement was associated with baseline score on total Ham-D (r = -0.60, P = .02), Ham-D items measuring Subjective mood symptoms (r = -0.50, P = .07), and Ham-D items measuring neurovegetative signs (r = -0.49, P = .08). CMAI improvement was also associated with improvement in Ham-D total score over the course of treatment (r = 0.62, P = .02). CONCLUSIONS: Mild depressive symptoms in patients with dementia and agitated behavior are associated with greater behavioral improvement by trazodone-treated patients. In contrast, the presence of delusions in concert with behavioral disturbance does not necessarily predict greater behavioral improvement with haloperidol treatment than in subjects without signs of psychosis. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Texas, SW Med Sch, Dept Psychiat, Dallas, TX 75230 USA. VA N Texas Healthcare Syst, Dallas, TX USA. RP Sultzer, DL (reprint author), W Los Angeles VA Healthcare Ctr, 3 South,116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH56031, MH00910] NR 57 TC 26 Z9 28 U1 2 U2 4 PU BLACKWELL SCIENCE 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 OCT PY 2001 VL 49 IS 10 BP 1294 EP 1300 DI 10.1046/j.1532-5415.2001.49256.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 482VL UT WOS:000171597900004 PM 11890487 ER PT J AU Ellis, FH Xu, XJ Kulke, MH LoCicero, J Loda, M AF Ellis, FH Xu, XJ Kulke, MH LoCicero, J Loda, M TI Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID KINASE INHIBITOR P27; BARRETTS-ESOPHAGUS; ADENOCARCINOMA; P27(KIP1); CANCER; EXPRESSION; HYPERPLASIA; RATS AB Objective: In a previous study, we showed that experimentally induced gastroduodenal-esophageal reflux in mice treated with a carcinogen can result in Barrett esophagus and Barrett-associated adenocarcinoma. Since we have shown that most Barrett-associated adenocarcinomas in human beings have lost the tumor suppressor gene p27, we sought to determine whether cancer would be more likely to develop in p27 knockout mice than in p27 heterozygous or p27 wild type mice. Methods: Three groups of mice were treated by esophagojejunostomy resulting in gastroduodenal-esophageal reflux and by a carcinogen (N-methyl-N-benzylnitrosamine): group 1 (50 wild type), group II (45 p27 heterozygous), and group III (50 p27 knockout). The mice were killed 18 to 20 weeks after operation and studied macroscopically and histopathologically. Results: Barrett esophagus developed in 7 (14%) mice in group 1, 4 (8.9%) mice in group II, and 13 (26%) mice in group III. Cancers developed in 30 (60%) mice in group I, 31 (68%) mice in group II, and 43 (86%) mice in group III. Ten percent of the cancers in group I were adenocarcinomas, as were 16.1% in group II, and 23.3% in group III. The difference between rates of Barrett esophagus in groups I and II compared with group III was statistically significant (P =.035), as was true of the cancer rates (P =.006). The percentage of cancers that were adenocarcinomas was highest in group III, but not significantly different from groups I and II. Conclusions: This experimental mouse model of Barrett esophagus and Barrett-associated adenocarcinoma is similar to what occurs in human beings and may be useful in developing methods to inhibit malignant transformation of Barrett esophagus. C1 Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ellis, FH (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, West Campus,110 Francis St,Suite 2A, Boston, MA 02215 USA. FU NCI NIH HHS [5R01CA81755-03] NR 22 TC 16 Z9 16 U1 0 U2 0 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 OCT PY 2001 VL 122 IS 4 BP 809 EP 814 DI 10.1067/mtc.2001.116471 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 481XG UT WOS:000171545300027 PM 11581618 ER PT J AU Savarese, VW Suvak, MK King, LA King, DW AF Savarese, VW Suvak, MK King, LA King, DW TI Relationships among alcohol use, hyperarousal, and marital abuse and violence in Vietnam veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE drinking frequency; drinking quantity; hyperarousal; marital violence ID POSTTRAUMATIC-STRESS-DISORDER; MISSISSIPPI PTSD SCALE; COMBAT VETERANS; CIVILIAN VERSION; NATIONAL SAMPLE; DIRECTIONS; AGGRESSION; VARIABLES; VALIDITY; IMAGERY AB Alcohol use (frequency and quantity) and the hyperarousal feature of PTSD were examined in relation to male-perpetrated marital abuse and violence using data from 376 couples who participated in the National Vietnam Veterans Readjustment Study. Veteran's self-reported hyperarousal was significantly associated with partner's report of physical violence and psychological abuse toward her. Differential relationships were found between veteran's self-reported drinking frequency and drinking quantity and the outcomes; of the two components, only the average quantity consumed per occasion was independently related to husband-to-wife violence. Moreover, a complex interaction emerged between hyperarousal and the two dimensions of alcohol consumption in predicting violence, with the relationship between hyperarousal and violence varying as a function of both drinking frequency and drinking quantity. C1 VA Boston Healthcare Syst 116B 3, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP King, LA (reprint author), VA Boston Healthcare Syst 116B 3, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 54 TC 88 Z9 88 U1 2 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2001 VL 14 IS 4 BP 717 EP 732 DI 10.1023/A:1013038021175 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 505QP UT WOS:000172927300007 PM 11776419 ER PT J AU Collins, TC Johnson, M Daley, J Henderson, WG Khuri, SF Gordon, HS AF Collins, TC Johnson, M Daley, J Henderson, WG Khuri, SF Gordon, HS TI Preoperative risk factors for 30-day mortality after elective surgery for vascular disease in Department of Veterans Affairs hospitals: Is race important? SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SURGICAL CARE; ARTERIAL-DISEASE; QUALITY; ADJUSTMENT; MORBIDITY; ISCHEMIA; INDEX; LIMB AB Purpose. Racial variation in health care outcomes is an important topic. Risk-adjustment models have not been developed for elective abdominal aortic aneurysm repair (AAA), lower extremity bypass revascularization (LEB), or lower extremity amputation (AMP). Earlier studies examining racial variation in mortality and morbidity from AAA, LEB, or AMP were limited to administrative data. This study determined risk factors for mortality after surgery for vascular disease and determined whether race is an important risk factor. Methods. Data in this prospective observational study were obtained from the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program. Detailed demographic and clinical data were collected prospectively from patients' medical records by trained nurse reviewers. Eligible patients were those 18 years and older who underwent elective AAA, LEB, or AMP at one of 44 VA medical centers performing both vascular and cardiac surgery (phase I; October 1991 to December 1993) and at one of these 44 or 79 additional VA medical centers performing vascular but not cardiac surgery (phase II; January 1994 to August 1995). The independent association of several preoperative factors with the 30-day postoperative mortality rate was examined with stepwise logistic regression analysis for AAA, LEB, and AMP. Models were developed in the combined 44 VA medical centers and validated in the 79 VA medical centers. The independent association of race with the 30-day postoperative mortality rate was examined after controlling for important preoperative risk factors for each operation. Results. More than 10,000 surgical operations were examined, and 5, 3, and 10 independent preoperative predictors of 30-day mortality rate were identified for AAA, LEB, and AMP, respectively. The observed mortality rate for patients undergoing AAA was higher (7.2% vs 3.2%; P =.02) in African American patients than in white patients in the 44 VA medical centers, although the differences were not significant in LEB and AMP or at the additional 79 hospitals. After important preoperative risk factors were controlled, there was no difference in 30-day mortality rates between African American patients and white patients. Conclusion: We identified several important preoperative risk factors for 30-day mortality rate in three vascular operations. From the results of this study, race was determined not to be an independent predictor of mortality. C1 Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Partners Hlth Care Syst, Inst Hlth Policy,Ctr Hlth Syst Design & Evaluat, Boston, MA USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. Hines VA Cooperat Studies Program, Hines, IL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Collins, TC (reprint author), Dept Vet Affairs, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 35 TC 38 Z9 39 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2001 VL 34 IS 4 BP 634 EP 640 DI 10.1067/mva.2001.117329 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 489YK UT WOS:000172020400012 PM 11668317 ER PT J AU Yutan, E Glickerman, DJ Caps, MT Hatsukami, T Harley, JD Kohler, TR Davies, MG AF Yutan, E Glickerman, DJ Caps, MT Hatsukami, T Harley, JD Kohler, TR Davies, MG TI Percutaneous transluminal revascularization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System experience SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the Western-Vascular-Society CY SEP 17-19, 1999 CL LAKE TAHOE, CALIFORNIA SP Western Vasc Soc ID RENOVASCULAR DISEASE; BALLOON ANGIOPLASTY; FOLLOW-UP; HYPERTENSION; MANAGEMENT; RECONSTRUCTION; SURVIVAL AB Purpose: The safety and efficacy of percutaneous transluminal intervention for renal artery stenosis is improving. This study evaluates the immediate and long-term anatomic and functional outcomes of percutaneous transluminal angioplasty and stenting for atherosclerotic renal artery stenosis in a Veterans Affairs population. Methods. We performed a retrospective analysis of records from patients who underwent renal artery angioplasty with or without stenting at the Veterans Affairs Puget Sound Health Care System between January 1990 and June 1999. Indications for intervention included hypertension (78%) and rising serum creatinine (78%). Seventy-six patients (74 men, average age of 67 years, range 42-83 years) underwent 88 attempted interventions. Seventy-two percent of contralateral kidneys had significant disease (47% had a >60% stenosis; 16% were nonfunctioning or absent). Results. Of the 88 planned interventions, 86 were successfully performed with placement of 46 stents (52%). Technical success (defined by <30% residual stenosis) was achieved in 78 vessels (89%). The procedure-related complication rate was 5%. Patient mortality by life table analysis was 49% at 5 years. Assisted primary patency rate at 5 years was 100%. Primary and secondary restenosis rates were 37%8% and 31%+/-8% at 5 years, respectively. Sixty-eight percent of patients treated for hypertension demonstrated clinical benefit (improved or cured hypertension). This clinical benefit was maintained in 52% of the patients at 5 years, as measured by life table analysis. Serum creatinine was lowered or maintained in 88% of the patients, but this clinical benefit was only maintained in 25% of patients at 5 years. Conclusions. Transluminal intervention for clinically symptomatic atherosclerotic renal artery stenosis is technically successful and safe. There are excellent assisted-patency and low restenosis rates. There is immediate clinical benefit for most patients, as evidenced by improved control of hypertension and preservation of renal function. However, within 5 years the benefit is not maintained for either hypertension (50%) or renal function (20%). Therefore, although technically successful, functional outcomes after endoluminal intervention are not maintained in the long term. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Sect Vasc Surg & Intervent Radiol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Sect Surg Perioperat Care, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Diagnost Serv, Seattle, WA USA. RP Davies, MG (reprint author), Univ Rochester, Med Ctr, Dept Surg, Ctr Vasc Dis,Div Vasc Surg, 601 Elmwood Ave,Box SURG, Rochester, NY 14642 USA. NR 22 TC 32 Z9 32 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2001 VL 34 IS 4 BP 685 EP 693 DI 10.1067/mva.2001.117886 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 489YK UT WOS:000172020400020 PM 11668325 ER PT J AU Gjoerup, O Zaveri, D Roberts, TM AF Gjoerup, O Zaveri, D Roberts, TM TI Induction of p53-independent apoptosis by simian virus 40 small t antigen SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN-VIRUS-40 LARGE-T; PROTEIN PHOSPHATASE 2A; SV40 SMALL-T; CELL-CYCLE REGULATION; POLYOMAVIRUS SMALL-T; SMALL TUMOR-ANTIGEN; ADENOVIRUS E4ORF4 PROTEIN; INHIBITOR OKADAIC ACID; VIRAL-DNA REPLICATION; NF-KAPPA-B AB Simian virus 40 small t antigen (st) is required for optimal transformation and replication properties of the virus. We find that in certain cell types, such as the human osteosarcoma cell line U2OS, st is capable of inducing apoptosis, as evidenced by a fragmented nuclear morphology and positive terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining of transfected cells. The cell death can be p53 independent, since it also occurs in p53-deficient H1299 cells. Genetic analysis indicates that two specific mutants affect apoptosis induction. One of these (C103S) has been frequently used as a PP2A binding mutant. The second mutant (TR4) lacks the final four amino acids of st, which have been reported to be unimportant for PP2A binding in vitro. However, TR4 unexpectedly fails to bind PP2A in vivo. Furthermore, a long-term colony assay reveals a potent colony inhibition upon st expression, and the behavior of st mutants in this assay reflects the relative frequency of nuclear fragmentation observed in transfections using the same mutants. Notably, either Bcl-2 coexpression or broad caspase inhibitor treatment could restore normal nuclear morphology. Finally, fluorescence-activated cell sorting analysis suggests a correlation between the ability of st to modulate cell cycle progression and apoptosis. Taken together, these observations underscore that st does not always promote proliferation but may, depending on conditions and cell type, effect a cell death response. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NCI NIH HHS [CA30002, P01 CA050661, P01-CA50661, R01 CA030002, R37 CA030002] NR 88 TC 30 Z9 30 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 OCT PY 2001 VL 75 IS 19 BP 9142 EP 9155 DI 10.1128/JVI.75.19.9142-9155.2001 PG 14 WC Virology SC Virology GA 470XX UT WOS:000170898600028 PM 11533178 ER PT J AU Norris, PJ Sumaroka, M Brander, C Moffett, HF Boswell, SL Nguyen, T Sykulev, Y Walker, BD Rosenberg, ES AF Norris, PJ Sumaroka, M Brander, C Moffett, HF Boswell, SL Nguyen, T Sykulev, Y Walker, BD Rosenberg, ES TI Multiple effector functions mediated by human immunodeficiency virus-specific CD4(+) T-cell clones SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; GP160 SUBUNIT VACCINE; MHC CLASS-II; HLA CLASS-I; ANTIRETROVIRAL TREATMENT; TYPE-1 INFECTION; IMMUNE-RESPONSES; LYTIC PATHWAYS; CYCLOPHILIN-A; LYMPHOCYTES-T AB Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4(+) T-cell clones specific for Gag from HIV-1-infected persons with vigorous Gag-specific responses detectable in peripheral blood mononuclear cells. Multiple peptides containing T helper epitopes were identified, including a minimal peptide, VHAGPIAG (amino acids 218 to 226), in the cyclophilin binding domain of Gag. Peptide recognition by all clones examined induced cell proliferation, gamma interferon (IFN-gamma) secretion, and cytolytic activity. Cytolysis was abrogated by concanamycin A and EGTA but not brefeldin A or anti-Fas antibody, implying a perforin-mediated mechanism of cell lysis. Additionally, serine esterase release into the extracellular medium, a marker for cytolytic granules, was demonstrated in an antigen-specific, dose-dependent fashion. These data indicate that T helper cells can target multiple regions of the p24 Gag protein and suggest that cytolytic activity may be a component of the antiviral effect of these cells. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. Fenway Community Hlth Ctr, Boston, MA 02115 USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, GRJ 504,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI040873, K08 AI001698-01A1, K08 AI001698, AI01541, R21 AI040873, AI01698-01, AI40873] NR 57 TC 57 Z9 58 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 OCT PY 2001 VL 75 IS 20 BP 9771 EP 9779 DI 10.1128/JVI.75.20.9771-9779.2001 PG 9 WC Virology SC Virology GA 474JG UT WOS:000171102900024 PM 11559810 ER PT J AU Bourcier, KD Lim, DG Ding, YH Smith, KJ Wucherpfennig, K Hafler, DA AF Bourcier, KD Lim, DG Ding, YH Smith, KJ Wucherpfennig, K Hafler, DA TI Conserved CDR3 regions in T-cell receptor (TCR) CD8(+) T cells that recognize the Tax11-19/HLA-A*0201 complex in a subject infected with human T-Cell leukemia virus type 1: Relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure SO JOURNAL OF VIROLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; ANTIGENIC PEPTIDE; NEUROLOGICAL DISEASE; CLONAL EXPANSION; LYMPHOCYTES; REPERTOIRE; TETRAMERS; EPITOPE; IMPRINT; ALTER AB We investigated the T-cell receptor (TCR) repertoire of CD8(+) T cells that recognize the Tax11-19 immunodominant epitope of Tax protein expressed by human T-cell leukemia virus (HTLV-1) that is implicated in the disease HTLV-1-associated myelopathy (HAM/TSP). A panel of Tax11-19-reactive CD8(+) T-cell clones was generated by single-cell cloning of Tax11-19/HLA-A*0201 tetramer-positive peripheral blood lymphocytes from an HTLV-1-infected individual. The analyses of TCR usage revealed that the combination of diverse TCR alpha and beta chains could be used for the recognition of Tax11-19 but the major population of T-cell clones (15 of 24 clones) expressed the TCR V beta 13S1 and V alpha 17 chain. We found striking similarities in CDR3 regions of TCR alpha and beta chains between our major group of CD8(+) T-cell clones and those originating from different subjects as previously reported, including TCRs with resolved crystal structures. A 3-amino-acid sequence (PG-G) in the CDR3 region of the V beta chain was conserved among all the Tax11-19-reactive T-cell clones expressing V beta 13S1 and V alpha 17 chains. Conserved amino acids in the CDR3 region do not directly contact the Tax11-19 peptide, as corroborated by the crystal structure of B7-TCR, a TCR that is almost identical to VB13S1 clones isolated in this study. Analysis of fine peptide specificity using altered peptide ligands (APL) of Tax11-19 revealed a similar recognition pattern among this panel of T-cell clones. These data suggest that the PG-G amino acids in the CDR3 beta loop provide a structural framework necessary for the maintenance of the tertiary TCR structure. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Lab Mol Immunol, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Bourcier, KD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Lab Mol Immunol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIAID NIH HHS [P01AI39671, P01 AI039671]; NINDS NIH HHS [1NS2424710, P01NS38037, P01 NS038037] NR 27 TC 21 Z9 22 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 OCT PY 2001 VL 75 IS 20 BP 9836 EP 9843 DI 10.1128/JVI.75.20.9836-9843.2001 PG 8 WC Virology SC Virology GA 474JG UT WOS:000171102900031 PM 11559817 ER PT J AU Bilello, JP Delaney, WE Boyce, FM Isom, HC AF Bilello, JP Delaney, WE Boyce, FM Isom, HC TI Transient disruption of intercellular junctions enables baculovirus entry into nondividing hepatocytes SO JOURNAL OF VIROLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; PRIMARY RAT HEPATOCYTES; LONG-TERM CULTURE; HEPATITIS-B VIRUS; MAMMALIAN-CELLS; HIGHLY EFFICIENT; RECOMBINANT BACULOVIRUS; ADHERENS JUNCTIONS; AIRWAY EPITHELIA; TIGHT JUNCTIONS AB Baculovirus infection has extended the capabilities for transfection of exogenous genes into a variety of mammalian cell types. Because rat hepatocytes plated on collagen-coated dishes and maintained in dimethyl sulfoxide (DMSO)-supplemented chemically defined medium are an excellent model system for studying liver function in vitro, we investigated the ability of baculoviruses to infect and deliver exogenous genes to cells in this culture system. Efficient delivery to hepatocytes in short-term culture becomes restricted to peripheral cells, or "edge" cells, as the hepatocytes acquire intercellular junctions and form islands with time in culture. This barrier to baculovirus entry can be overcome, and the percentage of internal cells within the hepatocyte islands that are infected with the baculovirus can be increased more than 100-fold, when cells are subjected to transient calcium depletion before and during infection. These findings suggest that at least in some cell types, such as hepatocytes, baculovirus entry may require contact with the basolateral surface. We conclude from this study that recombinant baculovirus infection following transient depletion of extracellular calcium results in delivery of exogenous genes to at least 75% of hepatocytes in long-term DMSO culture, thereby making it possible for the first time to carry out gain-of-function and loss-of-function studies in this cell system. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pathol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Cell & Mol Biol Grad Program, Hershey, PA 17033 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. RP Isom, HC (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, 500 Univ Dr,POB 850, Hershey, PA 17033 USA. FU NCI NIH HHS [CA23931, CA73045, R01 CA023931]; NIDDK NIH HHS [DK49088, DK54482, R01 DK054482, DK53430] NR 52 TC 21 Z9 23 U1 1 U2 1 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 OCT PY 2001 VL 75 IS 20 BP 9857 EP 9871 DI 10.1128/JVI.75.20.9857-9871.2001 PG 15 WC Virology SC Virology GA 474JG UT WOS:000171102900033 PM 11559819 ER PT J AU Casserly, LF Chow, N Ali, S Gottlieb, DJ Epstein, LJ Kaufman, JS AF Casserly, LF Chow, N Ali, S Gottlieb, DJ Epstein, LJ Kaufman, JS TI Proteinuria in obstructive sleep apnea SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Nephrology CY OCT 11-13, 2000 CL TORONTO, CANADA SP Amer Soc Nephrol DE polysomnography; obesity; nephrotic range proteinuria; hypopnea; urine protein; sleep study ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; URINARY ALBUMIN EXCRETION; ESSENTIAL-HYPERTENSION; MASSIVE OBESITY; RISK FACTOR; NEPHROTIC SYNDROME; MICROALBUMINURIA; ASSOCIATION; HEMODYNAMICS; POPULATION AB Background. Previous studies have reported an association between obstructive sleep apnea (OSA) and proteinuria, but are limited in their ability to assess proteinuria accurately, to adjust for confounders such as obesity, or to exclude confidently underlying renal disease in patients with OSA and nephrotic-range proteinuria. Methods. The spot urine protein/creatinine ratio was measured in a prospective consecutive series of 148 patients referred for polysomnography who were not diabetic and had not been treated previously for OSA. The urine protein/creatinine ratio was compared across four levels of OSA severity, based on the frequency of apneas and hypopneas per hour: <5 (absent). 5 to 14.9 (mild). 15 to 29.9 (moderate), and greater than or equal to 30 (severe). Results. The median level of urine protein/creatinine ratio in all categories of OSA was <0.2 (range 0.03 to 0.69: median 0.06 in patients with normal apnea hypopnea index. 0.06, 0.07, 0.07 in patients with mild, moderate. and severe OSA. respectively). Eight subjects had a urine protein/creatinine ratio greater than 0.2. Univariate analysis showed a significant association between urine protein/creatinine ratio and older age (P < 0.0001). hypertension (P < 0.0001), coronary artery disease (P = 0.003). and arousal index (P = 0.003). Body mass index (P = 0.16). estimated creatinine clearance (P = 0.17) and apnea hypopnea index (P = 0.13) were not associated with the urine protein/creatinine ratio. In multiple regression analysis. only age and hypertension were independent positive predictors of the urine protein/creatinine ratio (P < 0.0001, R-2 = 0.17). Conclusion. Clinically significant proteinuria is uncommon in sleep apnea. Nephrotic range proteinuria should not be ascribed to sleep apnea and deserves a thorough renal evaluation. C1 Boston Univ, Sch Med, Evans Mem Dept Med, Renal Unit, Boston, MA 02118 USA. VA Boston Healthcare Syst, Res Serv, Boston, MA USA. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Casserly, LF (reprint author), EBRC 5th Floor,Renal Sect,650 Albany St, Boston, MA 02118 USA. NR 48 TC 33 Z9 35 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2001 VL 60 IS 4 BP 1484 EP 1489 DI 10.1046/j.1523-1755.2001.00952.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 474VF UT WOS:000171127000029 PM 11576363 ER PT J AU Johansen, KL Chertow, GM da Silva, M Carey, S Painter, P AF Johansen, KL Chertow, GM da Silva, M Carey, S Painter, P TI Determinants of physical performance in ambulatory patients on hemodialysis SO KIDNEY INTERNATIONAL LA English DT Article DE chronic renal failure. gait speed; serum albumin; dialysis dose; nutrition and dialysis; physical function ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; EXERCISE CAPACITY; GAIT SPEED; MAINTENANCE DIALYSIS; RENAL-FAILURE; STRENGTH; ADULTS; ANEMIA; TIME AB Background. Physical performance measures, particularly gait speed, have been useful as predictors of loss of independence. institutionalization, and mortality in older nonuremic individuals. Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis, nor have the determinants of gait speed in the dialysis population been studied. Methods. We performed a cross-sectional analysis to determine whether demographic, clinical, or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units. Three physical performance measures were examined, including gait speed, time to climb stairs. and time to rise from a chair five times in succession. Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following candidate predictor variables: age, gender, body mass index. dialysis vintage, Kt/V, albumin. blood urea nitrogen, creatinine, hematocrit, lean body mass, phase angle, ferritin, and the following comorbidities: hypertension, diabetes mellitus. coronary artery disease, peripheral vascular disease. and cerebrovascular disease. Results. Subjects included 31 men and 15 women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of similar age). Results of multivariable regression showed that age, albumin, and Kt/V were important determinants of gait speed in this population. Overall, the model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001). Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables. except that comorbidity was more important than age for stair climbing. The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance. Conclusions. Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age, serum albumin, and dialysis dose. Prospective studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis. C1 San Francisco VA Med Ctr, Div Nephrol 111J, San Francisco, CA 94121 USA. Moffitt Long Hosp, San Francisco, CA USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Div Nephrol 111J, 4150 Clement St, San Francisco, CA 94121 USA. FU NCRR NIH HHS [RR-00083] NR 33 TC 63 Z9 64 U1 1 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2001 VL 60 IS 4 BP 1586 EP 1591 DI 10.1046/j.1523-1755.2001.00972.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 474VF UT WOS:000171127000043 PM 11576377 ER PT J AU Pena, CS Saini, S Baron, RL Hamm, BA Morana, G Caudana, R Giovagnoni, A Villa, A Carriero, A Mathieu, D Bourne, MW Kirchin, MA Pirovano, G Spinazzi, A AF Pena, CS Saini, S Baron, RL Hamm, BA Morana, G Caudana, R Giovagnoni, A Villa, A Carriero, A Mathieu, D Bourne, MW Kirchin, MA Pirovano, G Spinazzi, A TI Detection of malignant primary hepatic neoplasms with gadobenate dimeglumine (Gd-BOPTA) enhanced T1-weighted hepatocyte phase MR imaging: Results of off-site blinded review in a phase-II multicenter trial SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE liver neoplasms, MR; liver neoplasms, diagnosis; magnetic resonance (MR), contrast media ID HEPATOCELLULAR-CARCINOMA; MN-DPDP; LIVER; CT; VOLUNTEERS; CIRRHOSIS; EFFICACY; LESIONS AB Objective: To investigate the efficacy of gadobenate dimeglumine (Gd-BOPTA) enhanced MR imaging for the detection of liver lesions in patients with primary malignant hepatic neoplasms. Materials and Methods: Thirty-one patients with histologically proven primary 4 malignancy of the liver were evaluated before and after administration of Gd-BOPTA at dose 0.05 or 0.10 mmol/kg. T1-weighted spin echo (T1W-SE) and gradient echo (T1W-GRE) images were evaluated for lesion number, location, size and confidence by three off-site independent reviewers and the findings were compared to reference standard imaging (intraoperative ultrasound, computed tomography during arterial portography or lipiodol computed tomography). Results were analyzed for significance using a two-sided McNemar's test. Results: More lesions were identified on Gd-BOPTA enhanced images than on unenhanced images and there was no significant difference in lesion detection between either concentration. The largest benefit was in detection of lesions under 1 cm in size (7 to 21, 9 to 15, 16 to 18 for reviewers A, B, C respectively). In 68% of the patients with more than one lesion, Gd-BOPTA increased the number of lesions detected. Conclusion: Liver MR imaging after Gd-BOPTA increases the detection of liver lesions in patients with primary malignant hepatic neoplasm. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. Humboldt Univ, Charite Hosp, Charite, Dept Radiol, D-10098 Berlin, Germany. Univ Verona, Policlin Borgo Roma, Ist Radiol, I-37134 Verona, Italy. Univ Modena, Dipartimento Sci Med Oncol & Radiol, I-41100 Modena, Italy. Policlin San Matteo, Ist Radiol, I-27100 Pavia, Italy. Osped Santissima Annunziata, Ist Sci Radiol & Formaz Imagine, I-66100 Chieti, Italy. Hop Henri Mondor, Serv Radiol, F-94010 Creteil, France. Univ Wales Hosp, Dept Diagnost Radiol, Cardiff CF4 4XW, S Glam, Wales. Bracco SpA, Med & Regulatory Affairs, I-20134 Milan, Italy. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 32 Fruit St, Boston, MA 02114 USA. NR 20 TC 8 Z9 10 U1 0 U2 1 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 OCT-DEC PY 2001 VL 2 IS 4 BP 210 EP 215 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 510UR UT WOS:000173226100005 PM 11754328 ER PT J AU Tsuzuki, Y Carreira, CM Bockhorn, M Xu, L Jain, RK Fukumura, D AF Tsuzuki, Y Carreira, CM Bockhorn, M Xu, L Jain, RK Fukumura, D TI Pancreas microenvironment promotes VEGF expression and tumor growth: Novel window models for pancreatic tumor angiogenesis and microcirculation SO LABORATORY INVESTIGATION LA English DT Article ID HUMAN ADENOCARCINOMA LS174T; EXOCRINE PANCREAS; SCID MICE; CANCER; METASTASIS; VESSELS; PERMEABILITY; PROGRESSION; ENDOTHELIUM; MODULATION AB Pancreatic cancer has a poor prognosis, and treatment strategies based on preclinical research have not succeeded in significantly extending patient survival. This failure likely stems from the general lack of information on pancreatic tumor physiology, attributable to the difficulties in developing relevant, orthotopic models that accurately reflect pancreatic cancer in the clinic. To overcome this limitation, we developed abdominal wall windows suitable for intravital microscopy that allowed us to monitor angiogenesis and microvascular function noninvasively during tumor growth in vivo. We used two complementary tumor models in mice: orthotopic (human ductal pancreatic adenocarcinoma, PANC-1, grown in the pancreas), and ectopic (PANC-1 grown in the abdominal wall). We found that orthotopic PANC-1 tumors grew faster than the ectopic tumors and exhibited metastatic spread in the late stage similar to advanced pancreatic cancer in the clinic. Orthotopic PANC-1 tumors expressed vascular endothelial growth factor (VEGF)(121) and VEGF(165), contained higher levels of tumor cell-derived VEGF protein, and maintained vascular density and hyperpermeability during exponential tumor growth. Orthotopic PANC-1 tumors showed lower leukocyte-endothelial interactions in the early stage of growth. In addition, both VEGF(121) and VEGF(165) promoted the growth of PANC-1 cells in vitro. Finally, Anti-VEGF neutralizing antibody inhibited angiogenesis and tumor growth of PANC-1 tumors in both sites. We conclude that the orthotopic pancreas microenvironment enhances VEGF expression, which stimulates growth of PANC-1 tumors (compared with ectopic tumors). The mechanism is autocrine and/or paracrine and also is involved in the maintenance of blood vessels. This comparative system of orthotopic and ectopic pancreatic cancer will provide the rigorous understanding of pancreatic tumor pathophysiology needed for development of novel therapeutic strategies. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,COX-7, Boston, MA 02114 USA. FU NCI NIH HHS [P01-CA90124] NR 50 TC 70 Z9 70 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2001 VL 81 IS 10 BP 1439 EP 1451 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 485CE UT WOS:000171735300012 PM 11598156 ER PT J AU Zeitels, SM Jarboe, J Franco, RA AF Zeitels, SM Jarboe, J Franco, RA TI Phonosurgical reconstruction of early glottic cancer SO LARYNGOSCOPE LA English DT Article DE vocal cord; glottic; cancer; phonosurgery; laryngoplasty ID VOCAL FOLD; THYROPLASTY; CARCINOMA; SURGERY C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2001 VL 111 IS 10 BP 1862 EP 1865 DI 10.1097/00005537-200110000-00036 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 479UX UT WOS:000171422900036 PM 11801959 ER PT J AU Dodge, JE Munson, C List, AF AF Dodge, JE Munson, C List, AF TI KG-1 and KG-1a model the p15 in acute myeloid CpG island methylation observed leukemia patients SO LEUKEMIA RESEARCH LA English DT Article DE 5-methylcytosine; acute myeloid leukemia; p15; p16; KG-1; KG-1a ID ACUTE MYELOGENOUS LEUKEMIA; CELL-CYCLE CONTROL; DNA METHYLATION; P15(INK4B); EXPRESSION; LINE; PROMOTER; PROTEIN; GENES; HYPERMETHYLATION AB p15 and p16 are tumor suppressor genes that have 5 ' CpG islands and both are subject to hypermethylation associated with their transcriptional inactivation in hematological malignancies. In this study, we used sodium bisulfite sequencing to obtain a complete map of the 5-methylcytosine status of 80 CpGs covering similar to 900 bp in the 5 ' p15 CpG island, and 53 CpGs covering similar to 700 bp in the 5 ' p 16 CpG island in the hematopoietic cell lines HL60, KG-1, and KG-1a, two normal human bone marrow samples (NBM), and eight cytosine arabinoside (ara-C)-resistant adult acute myeloid leukemia (AML) patients. We found methylation of the p15 CpG island in 75% of the AML cases studied spread throughout the 5 ' region analyzed but only minimal methylation of p15 in NBM. Further, the p16 CpG island was not aberrantly methylated in NBM or the eight AML patients studied. Two distinct modes of p15 methylation in AML were identified, variegated and complete. Interestingly, KG-1 and KG-1a model the methylation of p15 observed in AML, where KG-1 methylation is variegated and KG-1 a methylation is complete. Both KG-1 and KG-la had no detectable p15 mRNA or protein. These results demonstrate that rather than continuous increases in p15 methylation, surprisingly two punctuated modes of aberrant p15 methylation, variegated and complete, were observed in vitro and in vivo. Thus aberrant methylation of tumor suppressor genes is not a binary switch but in the case of p15 occurs in two independent and stable states. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Arizona, Arizona Canc Ctr, Dept Pharmacol & Toxicol, Tucson, AZ 85724 USA. RP Dodge, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NCI NIH HHS [3P30 CA 23074-19] NR 37 TC 23 Z9 23 U1 2 U2 3 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 OCT PY 2001 VL 25 IS 10 BP 917 EP 925 DI 10.1016/S0145-2126(01)00053-4 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 477GW UT WOS:000171276000013 PM 11532526 ER PT J AU Sasaki, H Chen, LB Auclair, D Moriyama, S Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y AF Sasaki, H Chen, LB Auclair, D Moriyama, S Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y TI Overexpression of Hrad17 gene in non-small cell lung cancers correlated with lymph node metastasis SO LUNG CANCER LA English DT Article DE Hrad17; lymph node metastasis; lung cancer; prognosis ID SCHIZOSACCHAROMYCES-POMBE RAD17; SACCHAROMYCES-CEREVISIAE; CHECKPOINT GENE; HUMAN HOMOLOGS; IDENTIFICATION; REGION; MOUSE AB We used palindromic PCR-driven cDNA differential display technique to identify and isolate a gene, human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, from colon cancer tissues. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in non-small cell lung cancer (NSCLC). We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with NSCLC who had undergone surgery. Expression of Hrad17 messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 non-small cell lung carcinomas and adjacent histologically normal lung samples from patients for whom follow up data were available. Hrad17 transcripts were detected in 26 (25.5%) of the tumor samples, although some of the paired normal lung samples showed weak expression. There was no relationship between Hrad17 gene expression and age, gender or T-status. About 13 of 31 (41.9%) NSCLC patients with Hrad17 overexpressions were node positive, on the other hand, 13 of 76 (18.3%) cases without Hrad17 overexpressions were node positive. Thus the expression of Hrad17 mRNA correlated with lymph node metastasis (P=0.0231) from NSCLC. Hrad17 protein was highly expressed at the advancing margin of the tumor of lung cancer tissue but not within the normal lung tissue by immunohistochemistry. Thus the expression of Hrad17 might correlate with more advanced NSCLC. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan. NR 22 TC 7 Z9 13 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 OCT PY 2001 VL 34 IS 1 BP 47 EP 52 DI 10.1016/S0169-5002(01)00223-9 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 484HN UT WOS:000171684300006 PM 11557112 ER PT J AU Guo, ZM Yang, H Hamilton, ML VanRemmen, H Richardson, A AF Guo, ZM Yang, H Hamilton, ML VanRemmen, H Richardson, A TI Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE mouse aorta; antioxidant enzyme; oxidative DNA damage; comet assay ID NUCLEOTIDE EXCISION-REPAIR; DIETARY RESTRICTION; CALORIC RESTRICTION; WISTAR RATS; ELECTROCHEMICAL DETECTION; LIPID-PEROXIDATION; PROTEIN OXIDATION; DEPENDENT CHANGES; DIFFERENT TISSUES; FREE-RADICALS AB In this study, DNA damage in mouse aortic cells was measured using the comet assay. The tail moment of the comet assay in aortic cells obtained from 26-month-old mice fed ad libitum (O) was significantly increased as compared to 6-month-old mice fed ad libitum (Y-AL) after the cells were incubated with formamidopyrimidine-DNA glycosylase (Fpg), which specifically recognizes oxidized purines, endonuclease III (Endo III), which specifically recognizes oxidized pyrimidines, or the combination of Endo III and Fpg. The tail moment in aortic cells obtained from 26-month-old mice fed a food-restricted diet (O-FR) was significantly reduced as compared to O-AL mice after the cells were incubated with the combination of Endo III and Fpg. These results indicate that oxidative DNA lesions, i.e. the Endo III- and Fpg-sensitive sites, increase with age in mouse aortic cells and that FR attenuates the age-related increase in oxidative DNA damage. To determine if the changes in oxidative DNA damage in mouse aortic cells are related to the antioxidant status in these cells, we measured the activities of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, extracellular-SOD, catalase and glutathione peroxidase-1 in the mouse aorta, We observed that the activities of all antioxidant enzymes studied were significantly increased with age and that FR attenuated the age-related increase. These data indicate that the age-related increase and FR-induced decrease in oxidative DNA damage, i.e. the Endo III- and Fpg-sensitive sites, in mouse aortic cells is not due to alteration of the antioxidant defense system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Audie L Morphy Div, San Antonio, TX 78229 USA. RP Guo, ZM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG14674, AG13319] NR 60 TC 42 Z9 43 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT PY 2001 VL 122 IS 15 BP 1771 EP 1786 DI 10.1016/S0047-6374(01)00298-6 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 479BY UT WOS:000171385100009 PM 11557279 ER PT J AU Cohen, JG Dryja, TP Davis, KB Diller, LR Li, FP AF Cohen, JG Dryja, TP Davis, KB Diller, LR Li, FP TI RB1 genetic testing as a clinical service: A follow-up study SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE genetic testing; retinoblastoma; RB1; late effects ID FAMILIAL ADENOMATOUS POLYPOSIS; NONPOLYPOSIS COLON-CANCER; SUSCEPTIBILITY GENE; RETINOBLASTOMA GENE; HEREDITARY RETINOBLASTOMA; COLORECTAL-CANCER; BREAST-CANCER; MUTATIONS; IDENTIFICATION; RISK AB Background Genetic testing for inherited predisposition to diverse cancers has recently become available as a clinical service. We conducted a follow-up study of the initial series of US families who underwent RBI genetic testing to evaluate long-term effects of the service. Procedure. We enrolled 52 of 71 eligible families who responded to a follow-up study questionnaire administered 3-10 years after receipt of their RBI results. Each family had one proband with unilateral, non-familial retinoblastoma, which is associated with a 12% pre-test probability of hereditary retinoblastoma. RBI testing identified germline RBI mutations in five patients, lowered the carrier probability to 2% in 21 patients, and did not substantially modify the carrier probability in the remaining 26. Results. Diverse medical specialists offered and arranged for RBI testing, and their recommendation was the most influential factor in the decision to be tested, Pre-test counseling was provided by ophthalmologists (30), oncologists (11), and geneticists and genetic counselors (11). Most respondents, regardless of test result, were satisfied and perceived gains from their genetic testing, Based on small numbers, families with reduced likelihood of hereditary retinoblastoma reported more positive outcomes. Parents of RBI carriers were more likely to seek medical services, worry, and decide against having more children. Conclusions. This study demonstrates the feasibility of follow-up studies of families who had genetic testing. Results from Our small series suggest that genetic information and counseling are important components of RBI clinical genetic testing, and long-term adverse effects of testing are uncommon. Med Pediatr Oncol 2001;37:372-378. (C) 2001 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. UCL, London, England. RP Li, FP (reprint author), Dana Farber Canc Inst, Smith 201,44 Binney St, Boston, MA 02115 USA. EM frederick_li@dfci.harvard.edu FU NCI NIH HHS [5P30 CA 06516] NR 28 TC 11 Z9 12 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD OCT PY 2001 VL 37 IS 4 BP 372 EP 378 DI 10.1002/mpo.1213 PG 7 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 480YK UT WOS:000171490600004 PM 11568901 ER PT J AU Clark, JA Talcott, JA AF Clark, JA Talcott, JA TI Symptom indexes to assess outcomes of treatment for early prostate cancer SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Association-for-Health-Services-Research CY JUN 25-27, 2000 CL LOS ANGELES, CALIFORNIA SP Assoc Hlth Serv Res DE prostate cancer; quality of life; treatment outcomes ID QUALITY-OF-LIFE; SPARING RADICAL PROSTATECTOMY; RADIATION-THERAPY; SEXUAL FUNCTION; HEALTH-STATUS; URINARY; INCONTINENCE; RADIOTHERAPY; MEN; IMPOTENCE AB BACKGROUND. Patients' perceptions of treatment outcomes are important in the management of early prostate cancer, but few studies have offered reliable and responsive measures to assess the likely side effects of the most common treatments. OBJECTIVE. To develop indexes of urinary, bowel, and sexual function, and related distress. RESEARCH DESIGN. Prospective cohort study of the outcomes of treatment for early prostate cancer, with self-administered questionnaires completed before treatment, and 3 and 12 months afterward. Hypothesized indexes, based on a clinical model of pathophysiological side effects of treatment, were defined and evaluated with respect to reliability and validity. SUBJECTS. Patients (n = 184) undergoing radical prostatectomy or external beam radiotherapy for early prostate cancer. MEASURES. Urinary and bowel items pertained to frequency or intensity of symptoms of dysfunction; parallel items assessed symptom-related distress. Sexual dysfunction items assessed the quality of erections, orgasm, and ejaculation; distress was assessed by 2 items adapted from the MOS Sexual Problems (MOS-SP) scale. HRQoL was assessed by the SF-36 and Profile of Mood States. RESULTS. Symptom and symptom-related distress indexes for urinary incontinence, urinary obstruction/irritation, bowel dysfunction, and sexual dysfunction were defined. Symptom and distress indexes in each domain were highly correlated. Responsiveness was substantial and varied by treatment in ways consistent with clinical experience. The indexes accounted for significant proportions of the variance in HRQoL measures. CONCLUSIONS. These indexes may be used in monitoring outcomes of treatment for early prostate cancer. C1 Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Ctr Outcomes Res, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Clark, JA (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. FU AHRQ HHS [HS06824] NR 45 TC 69 Z9 69 U1 0 U2 2 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 OCT PY 2001 VL 39 IS 10 BP 1118 EP 1130 DI 10.1097/00005650-200110000-00009 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 477KT UT WOS:000171283300009 PM 11567174 ER PT J AU Earles, JE Hartung, GH Dickert, JM Moriyama, HH Coll, KJ Aiello, LM Jackson, R Polonsky, W AF Earles, JE Hartung, GH Dickert, JM Moriyama, HH Coll, KJ Aiello, LM Jackson, R Polonsky, W TI Interdisciplinary treatment of diabetes mellitus in a military treatment facility SO MILITARY MEDICINE LA English DT Article ID INSULIN SENSITIVITY; PHYSICAL-ACTIVITY; EXERCISE; MEN AB The American Diabetes Association emphasizes interdisciplinary management as the standard of care for patients with diabetes. Many times, however, interdisciplinary means various health care professionals treating a patient but not necessarily interacting with each other regarding the patient's care. Recently, Tripler Army Medical Center replicated the Joslin Diabetes Center's diabetes outpatient intensive treatment program as part of a Joslin Diabetes Center/Department of Defense/Veteran's Administration research collaboration. Tripler Army Medical Center named this interdisciplinary program Holopono, which is Hawaiian for success. Holopono is a team of health care professionals providing integrated care and education to a group of diabetes patients over 3.5 days. Individual care management, aided by an Internet-based tele-medicine system, then continues for 1 year after entry into the program. This article describes the Holopono program, the role of each team member, and how the team functions together to provide comprehensive diabetes care. C1 Tripler Army Med Ctr, Dept Psychol, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Dept Med, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Nutr Care Div, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Joslin Vis Network Coordinator, Honolulu, HI 96859 USA. Branch Med Clin Makalapa, Dept Internal Med, Honolulu, HI 96860 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Earles, JE (reprint author), Tripler Army Med Ctr, Dept Psychol, Honolulu, HI 96859 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2001 VL 166 IS 10 BP 848 EP 852 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 653DG UT WOS:000181419500008 PM 11603233 ER PT J AU Keel, SB Jaffe, KA Nielsen, P Rosenberg, AE AF Keel, SB Jaffe, KA Nielsen, P Rosenberg, AE TI Orthopaedic implant-related sarcoma: A study of twelve cases SO MODERN PATHOLOGY LA English DT Article DE prosthetic implant; sarcoma ID MALIGNANT FIBROUS HISTIOCYTOMA; TOTAL HIP-REPLACEMENT; SITE; ASSOCIATION; ARTHROPLASTY; LYMPHOMA; FIXATION; PLATE; TIBIA; BONE AB Sarcoma developing in association with a metallic orthopaedic prosthesis or hardware is an uncommon, but well recognized complication. We review 12 cases of sarcomas arising in bone or soft tissue at the site of orthopaedic hardware or a prosthetic joint. Nine patients were male, and three were female. Their ages ranged from 18 to 85 (mean 55) years at the time of diagnosis of the malignancy. Five patients had undergone hip arthroplasty for degenerative joint disease, four had been treated with intramedullary nail placement for fracture, two had staples placed for fixation of osteotomy, and one had hardware placed for fracture fixation followed years later by a hip arthroplasty. The time interval between the placement of hardware and diagnosis of sarcoma was known In 11 cases and ranged from 2.5 to 33 (mean 11) years. The patients presented with pain, swelling, or loosening of hardware and were found to have a destructive bone or soft tissue mass on radiography. Two sarcomas were located primarily in the soft tissue and 10 in bone. Seven patients developed osteosarcoma, four malignant fibrous histiocytoma, and one a malignant peripheral nerve sheath tumor. All sarcomas were high grade. Three patients had metastatic disease at the time of diagnosis. Follow-up was available on eight patients: five patients died of disease 2 months to 8 years (mean 26 months) after diagnosis; two patients died without evidence of disease 7 and 30 months after diagnosis; and one patient is alive and free of disease 8 years after diagnosis. Sarcomas that occur adjacent to orthopaedic prostheses or hardware are of varied types, but are usually osteosarcoma. or malignant fibrous histiocytoma. They behave aggressively and frequently metastasize. Clinically, they should be distinguished from non-neoplastic reactions associated with implants, such as infection and a reaction to prosthetic wear debris. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ Alabama, Med Ctr, Dept Orthopaed Surg, Birmingham, AL 35294 USA. RP Rosenberg, AE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. NR 45 TC 61 Z9 61 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2001 VL 14 IS 10 BP 969 EP 977 DI 10.1038/modpathol.3880420 PG 9 WC Pathology SC Pathology GA 481UU UT WOS:000171539500007 PM 11598166 ER PT J AU Chen, HM Engelman, A AF Chen, HM Engelman, A TI Asymmetric processing of human immunodeficiency virus type 1 cDNA in vivo: Implications for functional end coupling during the chemical steps of DNA transposition SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETROVIRAL DNA; V(D)J RECOMBINATION; PREINTEGRATION COMPLEXES; TN10 TRANSPOSITION; STRAND CLEAVAGE; MU-TRANSPOSASE; IN-VIVO; INTEGRATION; INVITRO; PROTEIN AB Retroviral integration, like all forms of DNA transposition, proceeds through a series of DNA cutting and joining reactions. During transposition, the 3 ' ends of linear transposon or donor DNA are joined to the 5 ' phosphates of a double-stranded cut in target DNA. Single-end transposition must be avoided in vivo because such aberrant DNA products would be unstable and the transposon would therefore risk being lost from the cell. To avoid suicidal single-end integration, transposons link the activity of their transposase protein to the combined functionalities of both donor DNA ends. Although previous work suggested that this critical coupling between transposase activity and DNA ends occurred before the initial hydrolysis step of retroviral integration, work in the related Tn10 and V(D)J recombination systems had shown that end coupling regulated transposase activity after the initial hydrolysis step of DNA transposition. Here, we show that integrase efficiently hydrolyzed just the wild-type end of two different single-end mutants of human immunodeficiency virus type I in vivo, which, in contrast to previous results, proves that two functional DNA ends are not required to activate integrase's initial hydrolysis activity. Furthermore, despite containing bound protein at their processed DNA ends, these mutant viruses did not efficiently integrate their singly cleaved wild-type end into target DNA in vitro. By comparing our results to those of related DNA recombination systems, we propose the universal model that end coupling regulates transposase activity after the first chemical step of DNA transposition. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394, R01 AI039394, R37 AI039394] NR 42 TC 35 Z9 36 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 OCT PY 2001 VL 21 IS 20 BP 6758 EP 6767 DI 10.1128/MCB.21.20.6758-6767.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474NC UT WOS:000171112500005 PM 11564861 ER PT J AU Alberta, JA Park, SK Mora, J Yuk, DI Pawlitzky, I Iannarelli, P Vartanian, T Stiles, CD Rowitch, DH AF Alberta, JA Park, SK Mora, J Yuk, DI Pawlitzky, I Iannarelli, P Vartanian, T Stiles, CD Rowitch, DH TI Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MOTOR-NEURON INDUCTION; ZONE PROGENITOR CELLS; SPINAL-CORD; FLOOR PLATE; VENTRICULAR ZONE; PRECURSOR CELL; STEM-CELLS; EXPRESSION; LINEAGE AB Oligodendrocyte precursor development in the embryonic spinal cord is thought to be regulated by the secreted signal, Sonic hedgehog (Shh). Such precursors can be identified by the expression of Olig genes, encoding basic helix-loop-helix factors, in the spinal cord and brain. However, the signaling pathways that govern oligodendrocyte precursor (OLP) development in the rostral central nervous system are poorly understood. Here, we show that Shh is required for oligodendrocyte development in the mouse forebrain and spinal cord, and that Shh proteins are both necessary and sufficient for OLP production in cortical neuroepithelial cultures. Moreover, adenovirus-mediated Olig1 ectopic expression can promote OLP formation independent of Shh activity. Our results demonstrate essential functions for Shh during early phases of oligodendrocyte development in the mammalian central nervous system. They further suggest that a key role of Shh signaling is activation of Olig genes. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24296, HD01182]; NINDS NIH HHS [NS4051, NS02028, NS38475] NR 44 TC 68 Z9 71 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD OCT PY 2001 VL 18 IS 4 BP 434 EP 441 DI 10.1006/mcne.2001.1026 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 487PX UT WOS:000171885400007 PM 11640898 ER PT J AU Hitchcock, AL Krebber, H Frietze, S Lin, A Latterich, M Silver, PA AF Hitchcock, AL Krebber, H Frietze, S Lin, A Latterich, M Silver, PA TI The conserved Np14 protein complex mediates proteasome-dependent membrane-bound transcription factor activation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FATTY-ACID DESATURASE; SACCHAROMYCES-CEREVISIAE PROTEASOME; ENDOPLASMIC-RETICULUM; 26S PROTEASOME; CELL-CYCLE; REGULATED PROTEOLYSIS; GAMMA-SECRETASE; ER DEGRADATION; OLE1 GENE; YEAST AB Proteolytic activation of membrane-bound transcription factors has emerged as an important mechanism for the regulation of gene expression. Two membrane-bound transcription factors regulated in this manner are the Saccharomyces cerevisiae proteins Mga2p and Spt23p, which direct transcription of the Delta9-fatty acid desaturase gene OLE1. We now show that a membrane-associated complex containing the highly conserved Np14p, Ufd1p, and Cdc48p proteins mediates the proteasome-regulated cleavage of Mga2p and Spt23p. Mutations in NPL4, UFD1, and CDC48 cause a block in Mga2p and Spt23p processing, with concomitant loss of OLE1 expression. Taken together, our data indicate that the Np14 complex may serve to target the proteasome to the ubiquitinated endoplasmic reticulum. membrane-bound proteins Mga2p and Spt23p. Given the recent finding that NPL4 is allelic to the ERAD gene HRD4, we further propose that this NPL4 function extends to all endoplasmic reticulum-membrane-associated targets of the proteasome. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Salk Inst Biol Studies, La Jolla, CA 92037 USA. RP Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu NR 70 TC 119 Z9 125 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2001 VL 12 IS 10 BP 3226 EP 3241 PG 16 WC Cell Biology SC Cell Biology GA 481VC UT WOS:000171540300026 PM 11598205 ER PT J AU Weilbaecher, KN Motyckova, G Huber, WE Takemoto, CM Hemesath, TJ Xu, Y Hershey, CL Dowland, NR Wells, AG Fisher, DE AF Weilbaecher, KN Motyckova, G Huber, WE Takemoto, CM Hemesath, TJ Xu, Y Hershey, CL Dowland, NR Wells, AG Fisher, DE TI Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice SO MOLECULAR CELL LA English DT Article ID COLONY-STIMULATING FACTOR; HELIX-LOOP-HELIX; MICROPHTHALMIA TRANSCRIPTION FACTOR; OP OP MOUSE; BONE-RESORPTION; FACTOR-I; OSTEOPETROTIC MOUSE; TARGETED DISRUPTION; GROWTH-FACTOR; FACTOR GENE AB Osteoclasts are multinucleated hematopoietic cells essential for bone resorption. Macrophage colony-stimulating factor (M-CSF) is critical for osteoclast development and function, although its nuclear targets in osteoclasts are largely unknown. Miff and TFE3 are two closely related helix-loop-helix (HLH) transcription factors previously implicated in osteoclast development and function. We demonstrate that cultured Mitf(mi/mi) osteoclasts are immature, mononuclear, express low levels of TRAP, and fail to mature upon M-CSF stimulation. In addition, M-CSF induces phosphorylation of Miff and TFE3 via a conserved MAPK consensus site, thereby triggering their recruitment of the coactivator p300. Furthermore, an unphosphorylatable mutant at the MAPK consensus serine is specifically deficient in formation of multinucleated osteoclasts, mimicking the defect in Mitf(mi/mi) mice. These results identify a signaling pathway that appears to coordinate cytokine signaling with the expression of genes vital to osteoclast development. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. Johns Hopkins Univ, Div Pediat Hematol, Baltimore, MD 21205 USA. Decode Genet, IS-110 Reykjavik, Iceland. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. FU NIA NIH HHS [K08 AG00852]; NIAMS NIH HHS [R01 AR45662] NR 52 TC 95 Z9 96 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT PY 2001 VL 8 IS 4 BP 749 EP 758 DI 10.1016/S1097-2765(01)00360-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 487ZE UT WOS:000171908900007 PM 11684011 ER PT J AU Guo, SS Sawicki, MP AF Guo, SS Sawicki, MP TI Molecular and genetic mechanism of tumorigenesis in Multiple Endocrine Neoplasia type-1 SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENE; FAMILIAL ISOLATED HYPERPARATHYROIDISM; ZOLLINGER-ELLISON-SYNDROME; SPORADIC PITUITARY-TUMORS; NONFAMILIAL PRIMARY HYPERPARATHYROIDISM; JUND-ACTIVATED TRANSCRIPTION; MEN1 GENE; PARATHYROID TUMORS; NEUROENDOCRINE TUMORS; GERMLINE MUTATIONS AB Multiple endocrine neoplasia type 1 (MEN1) is a rare but informative syndrome for endocrine tumorigenesis. Since its isolation, several groups have begun to determine the role of menin, the protein product of MEN1, in sporadic endocrine tumors as well as tumors of the MEN1 syndrome. Mutations of menin have been reported in more than 400 families and tumors, most of which are truncating mutations, thus supporting the function of menin as a tumor suppressor. The exact function of menin is unknown, but overexpression of menin inhibits proliferation of Ras-transformed NIH3T3 cells. Since menin interacts with proteins from both the TGF beta and AP-1 signaling pathways, perhaps its tumor suppressor function is related to these key cell growth pathways. In this review we will discuss the various clinical manifestations of MEN1 syndrome, potential mechanisms of MEW tumorigenesis, and mutations associated with MEN and sporadic endocrine tumors. C1 W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Sawicki, MP (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 131 TC 59 Z9 63 U1 0 U2 0 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 OCT PY 2001 VL 15 IS 10 BP 1653 EP 1664 DI 10.1210/me.15.10.1653 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 477DL UT WOS:000171267800001 PM 11579199 ER EF