FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Zilberman-Peled, B Appelbaum, L Vallone, D Foulkes, NS Anava, S Anzulovich, A Coon, SL Klein, DC Falcon, J Ron, B Gothilf, Y AF Zilberman-Peled, B. Appelbaum, L. Vallone, D. Foulkes, N. S. Anava, S. Anzulovich, A. Coon, S. L. Klein, D. C. Falcon, J. Ron, B. Gothilf, Y. TI Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the pineal gland of the gilthead seabream SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE melatonin; AANAT; OTX5; BMAL; CLOCK ID SEROTONIN-N-ACETYLTRANSFERASE; PHOTORECEPTOR CONSERVED ELEMENTS; MELATONIN SYNTHESIS ENZYMES; MESSENGER-RNA; CIRCADIAN CLOCK; SPARUS-AURATA; E-BOX; PROTEASOMAL PROTEOLYSIS; MOLECULAR ANALYSIS; TELEOST FISH AB Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT) is considered the key enzyme in the generation of circulating melatonin rhythms; the rate of melatonin production is determined by AANAT activity. In all the examined species, AANAT activity is regulated at the post-translational level and, to a variable degree, also at the transcriptional level. Here, the transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream (Sparus aurata) was investigated. Real-time polymerase chain reaction quantification of aanat2 mRNA levels in the pineal gland collected throughout the 24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the amplitude was reduced, but the daily rhythmic expression pattern was maintained under constant illumination, indicating a circadian clock-controlled regulation of seabream aanat2. DNA constructs were prepared in which green fluorescent protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo transient expression analyses in zebrafish embryos indicated that these promoters contain the necessary elements to drive enhanced expression in the pineal gland. In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock-controlled circadian rhythm of luciferase activity, characteristic for an E-box-driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5). Promoter sequence analyses revealed the presence of the photoreceptor conserved element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5 that have been previously associated with pineal-specific and rhythmic gene expression). These results suggest that seabream aanat2 is a clock-controlled gene that is regulated by conserved mechanisms. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. San Luis Univ, Fac Chem Biochem & Pharm, Dept Biochem & Biol Sci, San Luis, Argentina. NICHHD, NIH, Bethesda, MD 20892 USA. CNRS, Lab Arago, Banyuls sur Mer, France. Univ Paris 06, Banyuls sur Mer, France. Israel Oceanog & Limnol Res, Elat, Israel. RP Gothilf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. EM yoavg@tauex.tau.ac.il RI FALCON, Jack/I-5302-2013; Foulkes, Nicholas/K-7003-2013 OI FALCON, Jack/0000-0002-7572-6581; NR 47 TC 14 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 2007 VL 19 IS 1 BP 46 EP 53 DI 10.1111/j.1365-2826.2006.01501.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 116WZ UT WOS:000242835800006 PM 17184485 ER PT J AU Erie, EA Shim, H Smith, AL Lin, X Keyvanfar, K Xie, CS Chen, JC Cai, HB AF Erie, Elizabeth A. Shim, Hoon Smith, Aleah L. Lin, Xian Keyvanfar, Keyvan Xie, Chengsong Chen, Jichun Cai, Huaibin TI Mice deficient in the ALS2 gene exhibit lymphopenia and abnormal hematopietic function SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE amyotrophic lateral sclerosis (ALS); ALS2; ALS2 knockout mice; lymphopenia; hematopoietic stem and progenitor cells; cytokine-stimulated proliferation ID NUCLEOTIDE EXCHANGE FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOSOME TRAFFICKING; ALS2-DEFICIENT MICE; GTPASE; RAB5; RHO; DEGENERATION; RAC2 AB One form of juvenile onset autosomal recessive amyotrophic lateral sclerosis (ALS2) has been linked to the dysfunction of the ALS2 gene. The ALS2 gene is expressed in lymphoblasts, however, whether ALS2-deficiency affects periphery blood is unclear. Here we report that ALS2 knockout (ALS2(-/-)) mice developed peripheral lymphopenia but had higher proportions of hematopoietic stem and progenitor cells in which the stem cell factor-induced cell proliferation was up-regulated. Our findings reveal a novel function of the ALS2 gene in the lymphopoicsis and hernatopoiesis, suggesting that the immune system is involved in the pathogenesis of ALS2. (c) 2006 Elsevier B.V. All rights reserved. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC Room 3E-5132,10 Ctr Dr, Bethesda, MD 20892 USA. EM chenji@nhlbi.nih.gov; caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU NIA NIH HHS [Z01 AG000959-02] NR 24 TC 5 Z9 5 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2007 VL 182 IS 1-2 BP 226 EP 231 DI 10.1016/j.jneuroim.2006.10.019 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 132SJ UT WOS:000243962200025 PM 17156857 ER PT J AU Ding, L Hikosaka, O AF Ding, Long Hikosaka, Okihide TI Temporal development of asymmetric reward-induced bias in macaques SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MONKEY CAUDATE-NUCLEUS; SUPERIOR COLLICULUS; PREFRONTAL CORTEX; REACTION-TIME; FOREPERIOD DURATION; EXPECTED REWARD; BASAL GANGLIA; EYE FIELDS; ATTENTION; NEURONS AB Time and expected outcome are two ubiquitous factors contributing to decision-making. However, it is unclear how they interact to influence motor responses. When two differential reward outcomes are expected at the end of a waiting period, behavioral bias is consistently induced, manifested as shorter latencies for motor responses associated with the preferred reward. To examine how this bias develops in time during the waiting period, we manipulated the duration of the waiting period in an asymmetric reward saccade task in monkeys. We found that the bias increases with the duration of waiting period. Surprisingly, the bias resulted from gradual suppression of saccades to nonpreferred targets rather than from facilitation of saccades to preferred targets. These results have important implications on the neural correlates of reward-induced bias. C1 NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. RP Ding, L (reprint author), NEI, Lab Sensorimotor Res, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM dingl@nei.nih.gov FU Intramural NIH HHS NR 34 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2007 VL 97 IS 1 BP 57 EP 61 DI 10.1152/jn.00902.2006 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 126RO UT WOS:000243532900007 PM 17021019 ER PT J AU Uittenbogaard, M Martinka, DL Johnson, PF Vinson, C Chiaramello, A AF Uittenbogaard, Martine Martinka, Debra L. Johnson, Peter F. Vinson, Charles Chiaramello, Anne TI 5 ' UTR of the neurogenic bHLH Nex1/MARH-2/NeuroD6 gene is regulated by two distinct promoters through CRE and C/EBP binding sites SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neuronal differentiation; bHLH transcription factor; C/EBP; CREB; NeuroD family ID HELIX PROTEINS NEX; DNA-BINDING; PAIRED DOMAIN; PC12 CELLS; TRANSCRIPTION FACTORS; GAP-43 GENE; GLIAL FATE; DIFFERENTIATION; BETA; EXPRESSION AB Expression of the bHLH transcription factor Nex1/ MATH-2/NeuroD6, a member of the NeuroD subfamily, parallels overt neuronal differentiation and synaptogenesis during brain development. Our previous studies have shown that Nex1 is a critical effector of the NGF pathway and promotes neuronal differentiation and survival of PC12 cells in the absence of growth factors. In this study, we investigated the transcriptional regulation of the Nex1 gene during NGF-induced neuronal differentiation. We found that Nex1 expression is under the control of two conserved promoters, Nex1-P1 and Nex1-P2, located in two distinct non-coding exons. Both promoters are TATA-less with multiple transcription start sites, and are activated on NGF or cAMP exposure. Luciferase-reporter assays showed that the Nex1-P2 promoter activity is stronger than the Nex1-P1 promoter activity, which supports the previously reported differential expression levels of Nex1 transcripts throughout brain development. Using a combination of DNasel footprinting, EMSA assays, and site-directed mutagenesis, we identified the essential regulatory elements within the first 2 kb of the Nex1 5'UTR. The Nex1-P1 promoter is mainly regulated by a conserved CRE element, whereas the Nex1-P2 promoter is under the control of a conserved C/EBP binding site. Overexpression of wild-type C/EBP beta resulted in increased Nex1-P2 promoter activity in NGF-differentiated PC12 cells. The fact that Nex1 is a target gene of C/EBP beta provides new insight into the C/EBP transcriptional cascade known to promote neurogenesis, while repressing gliogenesis. (c) 2006 Wiley-Liss, Inc. C1 George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Neurosci Program, Washington, DC 20037 USA. NCI, Frederick Canc Res & Dev Ctr, Canc Res Ctr, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. RP Chiaramello, A (reprint author), George Washington Univ, Med Ctr, Dept Anat & Cell Biol, 2300 I St NW, Washington, DC 20037 USA. EM anaaec@gwumc.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NICHD NIH HHS [P30 HD040677, P30 HD40677]; NINDS NIH HHS [R01 NS041391, R01 NS041391-04, R01 NS041391-04S1, R01-NS 041391] NR 41 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2007 VL 85 IS 1 BP 1 EP 18 DI 10.1002/jnr.21093 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 127QQ UT WOS:000243601800001 PM 17075921 ER PT J AU Major, EO Schwartz, L Monaco, MC AF Major, Eugene O. Schwartz, Lynnae Monaco, Maria Chiara TI Lineage directed differentiation of human brain derived progenitor cells alters JC Virus and HIV-1 fate of infection: Implications of neuropathogenesis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 8th International Symposium on Neurovirology CY OCT 30-NOV 02, 2007 CL San Diego, CA SP NIMH, NINDS, NIDA, Biogen Idec, Dept Microbiol & Immunol, Drexel Univ Coll Med, Inst Mol Med & Infect Dis, Temple Univ Sch Med, Dept Neurosci, Sbarro Inst Canc Res & Mol Med, Journal NeuroVirol C1 [Major, Eugene O.; Schwartz, Lynnae; Monaco, Maria Chiara] NINDS, NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2007 VL 13 SU 1 BP 26 EP 27 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 228SX UT WOS:000250754000045 ER PT J AU Grant, CW Oh, U Yao, K Yamano, Y Jacobson, S AF Grant, Christian W. Oh, Unsong Yao, Karen Yamano, Yoshihisa Jacobson, Steven TI Dysregulation of TGF-beta signaling in virus-induced neurologic disease: implications for the function of both regulatory and effector T cells SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 8th International Symposium on Neurovirology CY OCT 30-NOV 02, 2007 CL San Diego, CA SP NIMH, NINDS, NIDA, Biogen Idec, Dept Microbiol & Immunol, Drexel Univ Coll Med, Inst Mol Med & Infect Dis, Temple Univ Sch Med, Dept Neurosci, Sbarro Inst Canc Res & Mol Med, Journal NeuroVirol C1 [Grant, Christian W.; Oh, Unsong; Yao, Karen; Jacobson, Steven] NIH, NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. [Yamano, Yoshihisa] City Hosp, Dept Neurol, Kagoshima, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2007 VL 13 SU 1 BP 82 EP 82 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 228SX UT WOS:000250754000150 ER PT J AU Ellis, RJ Joseph, J de Almeida, SM AF Ellis, Ronald J. Joseph, Jeymohan de Almeida, Segio Montiero TI NeuroAIDS in Brazil SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE HIV; clade; subtype; neuroAIDS ID IMMUNODEFICIENCY-VIRUS TYPE-1; SUBTYPE-C; RESISTANCE; INHIBITORS AB Brazil has the largest number of HIV cases of any single country in Latin America - over 600,000. Recently, investigators have begun to characterize the extent of neurological morbidity due to HIV in this country. During 2005 and 2006, the U. S. National Institute of Mental Health cosponsored two meetings of experts aimed at summarizing existing knowledge of HIV and its neurological complications in Brazil. Topics addressed ranged from clinical neurobehavioral aspects to molecular biology. Experts attending the meeting considered fruitful directions for future research. C1 Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Univ Calif San Diego, HIV Neurobehav Res Ctr, San Diego, CA 92103 USA. NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. Univ Fed Parana, Neurol Unit, BR-80060000 Curitiba, Parana, Brazil. RP Ellis, RJ (reprint author), Univ Calif San Diego, Dept Neurosci, 150 W Washington St,2nd Floor, San Diego, CA 92103 USA. EM roellis@UCSD.edu RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X NR 7 TC 2 Z9 3 U1 0 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. PY 2007 VL 13 IS 2 BP 89 EP 96 DI 10.1080/13550280601132074 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 171VP UT WOS:000246763800001 PM 17505977 ER PT J AU Schwartz, L Civitello, L Dunn-Pirio, A Ryschkewitsch, S Berry, E Cavert, W Kinzel, N Lawrence, DMP Hazra, R Major, EO AF Schwartz, Lynnae Civitello, Lucy Dunn-Pirio, Anastasie Ryschkewitsch, Samantha Berry, Elizabeth Cavert, Winston Kinzel, Nikilyn Lawrence, Diane M. P. Hazra, Rohan Major, Eugene O. TI Evidence of human immunodeficiency virus type 1 infection of nestin-positive neural progenitors in archival pediatric brain tissue SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE neural progenitors; gag; nestin; laser microdissection; pediatric neuroAIDS ID CENTRAL-NERVOUS-SYSTEM; TYRAMIDE SIGNAL AMPLIFICATION; LASER CAPTURE MICRODISSECTION; CHEMOKINE RECEPTORS; HIV-1 INFECTION; HIV-1-ASSOCIATED DEMENTIA; PRECURSOR CELLS; GLIAL-CELLS; ASTROCYTES; EXPRESSION AB Human immunodeficiency virus type 1 (HIV-1) central nervous system (CNS) infection in children is associated with impaired brain growth and neurodevelopmental delays. Neural progenitors are critical for neurogenesis. Human multipotential neural progenitors grown in culture are permissive for HIV-1 infection, but it is not known if infection of these cells occurs in vivo. Brain tissue from pre-highly active antiretroviral therapy (HAART) era pediatric acquired immunodeficiency syndrome (AIDS) patients was examined for evidence of HIV-1 infection of nestin-positive neural progenitors by in situ hybridization; or after laser microdissection harvest, DNA extraction, and polymerase chain reaction (PCR). HIV-1 or viral DNA was identified in nestin-positive cells in four of seven HIV-1-infected children, suggesting in vivo infection of neural progenitors. C1 NIH, Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. Univ Maryland, Coll Chem & Life Sci, College Pk, MD USA. Hampshire Coll, Sch Nat Sci, Amherst, MA USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN USA. Mayo Grad Sch, Rochester, MN USA. NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Schwartz, L (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM schwartl@ninds.nih.gov FU Intramural NIH HHS NR 58 TC 30 Z9 31 U1 0 U2 2 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. PY 2007 VL 13 IS 3 BP 274 EP 283 DI 10.1080/13550280701344975 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 186KZ UT WOS:000247778900011 PM 17613718 ER PT J AU Shankar, LK Sullivan, DC AF Shankar, Lalitha K. Sullivan, Daniel C. TI PET/CT in cancer patient management - Commentary SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RP Shankar, LK (reprint author), NCI, Canc Imaging Program, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2007 VL 48 SU 1 BP 1S EP 1S PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 125DC UT WOS:000243420900001 PM 17204714 ER PT J AU Tokugawa, J Ravasi, L Nakayama, T Schmidt, KC Sokoloff, L AF Tokugawa, Joji Ravasi, Laura Nakayama, Toshiyuki Schmidt, Kathleen C. Sokoloff, Louis TI Operational lumped constant for FDG in normal adult male rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE lumped constant; FDG; rats ID CEREBRAL GLUCOSE-UTILIZATION; F-18 FLUORODEOXYGLUCOSE; DEOXYGLUCOSE METHOD; METABOLIC-RATE; BRAIN; HUMANS; TRANSPORT; KINETICS; INVIVO AB We determined an operational value for the lumped constant to be used in measurements of the local rate of cerebral glucose use (ICMRglc) with FDG in normal adult male rats. Methods: The standard quantitative autoradiographic method was used with 2-deoxy-D-C-14-glucose (C-14-DG) and with C-14-FDG in awake normal adult male rats. Timed arterial blood samples were drawn for 45 min after the bolus and assayed for plasma glucose and C-14 concentrations. At the end of the 45-min experimental period, the rats were killed, and their brains were removed and divided in half sagittally. One hemisphere was immediately frozen and assayed for local C-14 concentrations by quantitative autoradiography; the other was weighed, homogenized in t-octylphenoxypolyethoxyethanol solution, and assayed for C-14 concentrations in the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in each pair receiving C-14-DG and the other receiving C-14-FDG, were studied in parallel on the same day. Additional unpaired animals (n = 8) were studied with either C-14-DG or C-14-FDG but not in parallel on the same day. To calculate the ICMRglc in rats studied with C-14-FDG, the rate constants for C-14-FDG were estimated from the C-14-DG values determined for rats and the C-14-FDG/C-14-DG ratios determined for humans. In all of the rats studied with either C-14-DG or C-14-FDG, the ICMRglc was first calculated in 12 representative brain structures with the lumped constant of 0.48 previously determined for C-14-DG in rats. The ratio of the ICMRglc thus determined with C-14-FDG to that determined with C-14-DG for each structure was then multiplied by the lumped constant for C-14-DG to estimate the lumped constant for C-14-FDG. The ICMRglc and the lumped constant for FDG in the brain as a whole were similarly estimated from the tracer concentrations in the brain homogenates. Results: The mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the autoradiographic assays and the assays with brain homogenates, respectively. Conclusion: The appropriate value for the lumped constant to be used in determinations of the ICMRglc in normal adult male rat studies with F-18-FDG and small-animal PET scanners is 0.71. C1 NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Milan, Inst Radiol Sci, Milan, Italy. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM louissokoloff@mail.nih.gov NR 21 TC 10 Z9 10 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2007 VL 48 IS 1 BP 94 EP 99 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 123PC UT WOS:000243306800046 PM 17204704 ER PT J AU Sprague, DR Chin, FT Liow, JS Fujita, M Burns, HD Hargreaves, R Stubbs, JB Pike, VW Innis, RB Mozley, PD AF Sprague, David R. Chin, Frederick T. Liow, Jeih-San Fujita, Masahiro Burns, H. Donald Hargreaves, Richard Stubbs, James B. Pike, Victor W. Innis, Robert B. Mozley, P. David TI Human biodistribution and radiation dosimetry of the tachykinin NK1 antagonist radioligand [F-18]SPA-RQ: Comparison of thin-slice, bisected, and 2-dimensional planar image analysis SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE [F-18]SPA-RQ; PET dosimetry; biodistribution ID SUBSTANCE-P RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; WHOLE-BODY BIODISTRIBUTION; TRANSPORTER PROBE; ALZHEIMERS-DISEASE; NONHUMAN-PRIMATES; PET; BRAIN; IMMUNOREACTIVITY; PARKINSONS AB F-18-Labeled substance P antagonist-receptor quantifier ([F-18]SPA-RQ) [2-fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-[(2S,3S)-2-phenyi-piperidin-3-yl)amine] is a selective radioligand for in vivo quantification of tachykinin NK1 receptors with PET. The aims of this study were to estimate the radiation safety profile and relative risks of [F-18]SPA-RQ with 3 different methods of image analysis. Methods: Whole-body PET images were acquired in 7 healthy subjects after injection of 192 +/- 7 MBq (5.2 +/- 0.2 mCi) [F-18]SPA-RQ. Emission images were serially acquired at multiple time-points from 0 to 120 min and approximately 180-240 min after injection. Urine samples were collected after each imaging session and for 24 h after the last scan to measure excreted radioactivity. Horizontal tomographic images were compressed to varying degrees in the anteroposterior direction to create 3 datasets: thin-slice, bisected, and 2-dimensional (2D) planar images. Regions of interest were drawn around visually identifiable source organs to generate time-activity curves for each dataset. Residence times were determined from these curves, and doses to individual organs and the body as a whole were calculated using OLINDA/EXM 1.0. Results: The lungs, upper large intestine wall, small intestine, urinary bladder wall, kidneys, and thyroid had the highest radiation-absorbed doses. Biexponential fitting of mean bladder and urine activity showed that about 41% of injected activity was excreted via urine. Assuming a 2.4-h urine voiding interval, the calculated effective doses from thin-slice, bisected, and 2D planar images were 29.5, 29.3, and 32.3 mu Sv/MBq (109, 108, and 120 mrem/mCi), respectively. Conclusion: Insofar as effective dose is an accurate measure of radiation risk, all 3 methods of analysis provided quite similar estimates of risk to human subjects. The radiation dose was moderate and would potentially allow subjects to receive multiple PET scans in a single year. Individual organ exposures varied among the 3 methods, especially for structures asymmetrically located in an anterior or posterior position. Bisected and 2D planar images almost always provided higher organ dose estimates than thin-slice images. Thus, either the bisected or 2D planar method of analysis appears acceptable for quantifying human radiation burden, at least for radioligands with a relatively broad distribution in the body and not concentrated in a small number of radiation sensitive organs. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Merck Res Labs, West Point, PA USA. Radiat Dosimetry Syst Inc, San Francisco, CA USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 1,Room B3-11,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU Intramural NIH HHS [Z01 MH002852-01]; NIMH NIH HHS [Z01 MH002852] NR 29 TC 21 Z9 21 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2007 VL 48 IS 1 BP 100 EP 107 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 123PC UT WOS:000243306800047 PM 17204705 ER PT J AU Conley, YP Tinkle, MB AF Conley, Yvette P. Tinkle, Mindy B. TI The future of genomic nursing research SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE genomics; nursing; research; health policy ID HEALTH DISPARITIES; BIOMEDICAL-RESEARCH; RACE; DISEASE; LEADERSHIP; KNOWLEDGE; ETHNICITY; GENETICS; ERA AB Purpose: To look toward the future of genomics research and identify genomic-based resources and opportunities for nurse scientists to incorporate genomic concepts into their programs of research. Organizing Framework: Five research themes for the future, developed by the National Institute of Nursing Research in collaboration with nurse scientists, are the framework for this article: (a) changing lifestyle behaviors for better health; (b) managing the effects of chronic illness to improve health and quality of life; (c) identifying effective strategies to reduce health disparities; (d) harnessing advanced technologies to serve human needs; and (e) enhancing end-of-life experiences for patients and their families. Conclusions: Nurse scientists around the world are increasingly integrating genomics into their programs of research. Emerging international genomic initiatives, discoveries, and resources will provide rich opportunities for nurse scientists, as members of interdisciplinary teams, to address important biological, behavioral, social, and ethical questions. This evolving genomic nursing science will be necessary in practice, education, and policy in a time when rapid genomic discoveries are occurring. C1 Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. NINR, NIH, Bethesda, MD 20892 USA. RP Conley, YP (reprint author), Univ Pittsburgh, Sch Nursing, 3500 Vic St,440 Vic Bldg, Pittsburgh, PA 15261 USA. EM yconley@pitt.edu NR 37 TC 10 Z9 14 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2007 VL 39 IS 1 BP 17 EP 24 DI 10.1111/j.1547-5069.2007.00138.x PG 8 WC Nursing SC Nursing GA 139EL UT WOS:000244415000008 PM 17393961 ER PT J AU Pogribny, IP Tryndyak, VP Muskhelishvili, L Rusyn, I Ross, SA AF Pogribny, Igor P. Tryndyak, Volodymyr P. Muskhelishvili, Levan Rusyn, Ivan Ross, Sharon A. TI Methyl deficiency, alterations in global histone modifications, and carcinogenesis SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board ID C57BL/6J MALE-MICE; DNA-DAMAGE; PRENEOPLASTIC LESIONS; LYSINE METHYLATION; CHOLINE-DEFICIENT; GENE-EXPRESSION; HUMAN-DISEASE; HUMAN CANCERS; H3 LYSINE-9; RAT-LIVER AB The methyl-deficient model of endogenous hepatocarcinogenesis in rodents is unique in that dietary omission rather than the addition of chemical carcinogens leads to tumor formation. Thus, the biochemical and molecular events predisposing to cancer in this model result from chronic metabolic stress and provide an ideal model system to study progressive alterations that occur during carcinogenesis. Moreover, epigenetic alterations imposed by this diet are believed to be 1 of the main mechanisms responsible for malignant transformation of rat liver cells. In this study we examined the changes in global histone modification patterns in liver during hepatocarcinogenesis induced by methyl deficiency. Feeding animals the methyl-deficient diet (MDD) led to progressive loss of histone H4 lysine 20 trimethylation (H4K20me3), H3 lysine 9 trimethylation (H3K9me3), and histone H3 lysine 9 H3K9ac) and histone H4 lysine 16(H4K16ac) acetylation. A considerable decrease of H4K20me3 and H3K9ac was also detected in liver tumors induced by MDD. In contrast, liver tumors displayed an increase in H3K9me3 and H4K16ac. To determine the possible mechanism of alterations of histone modifications, we analyzed the expression of histone-modifying enzymes in liver during hepatocarcinogenesis. The expression of Suv4-2Oh2 and RIZ1 histone methyltransferases (HMTs) steadily decreased along with the development of liver tumors and reached its lowest level in tumor tissue, whereas the expression of Suv39-h1 HMT and histone acetyltransferase 1(HAT1) substantially increased in tumors. These results illustrate the complexity and importance of histone modification changes in the etiology of hepatocarcinogenesis induced by MDD. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. NCI, Rockville, MD 20852 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 NR 68 TC 60 Z9 63 U1 0 U2 7 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 216S EP 222S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800011 PM 17182829 ER PT J AU Schatzkin, A AF Schatzkin, Arthur TI Can biomarkers help us understand the nutritional and lifestyle factors important in cancer prognosis? SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board ID SURROGATE END-POINTS; BREAST-CANCER; POSTMENOPAUSAL WOMEN; SEX-HORMONES; RISK AB In attempting to discover the causes of cancer, investigators have recognized that biomarkers can confirm biological plausibility, enhance relative risks, and serve as surrogate endpoints in observational and intervention studies. In the arena of cancer survival, the potential value of biomarkers is increasingly appreciated. A broad range of histological, cellular, and molecular markers have been identified among persons diagnosed with cancer. Molecular and cellular markers are being used to stage disease, predict prognosis, and target therapeutic interventions. Biomarkers in survivors can also help us to understand factors that influence prognosis by both elucidating pertinent biological pathways and sharpening risk estimates. However, as in the case of incident cancer, the use of biomarkers as surrogate endpoints postdiagnosis is problematic because of the potential existence of alternative pathways to recurrence and death that bypass the surrogate endpoint. In evaluating potential surrogates, an understanding of the causal structure underlying the interrelations of exposures, surrogate, and recurrence or death is essential. Three questions can help to shed light on this structure: 7) What is the relation of the surrogate endpoint to recurrence or death? 2) What is the relation of the intervention (or exposure) to the surrogate? 3) To what extent does the surrogate endpoint mediate the relation between intervention (exposure) and recurrence or death? To address these questions, it is imperative to integrate biomarker studies into ongoing pharmacotherapeutic and lifestyle intervention studies with recurrence or mortality as explicit endpoints. C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20815 USA. RP Schatzkin, A (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20815 USA. EM schatzka@mail.nih.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 249S EP 252S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800017 PM 17182835 ER PT J AU Wright, ME Albanes, D AF Wright, Margaret E. Albanes, Demetrius TI beta-carotene, smoking, and lung cancer. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 275S EP 276S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800025 ER PT J AU Panagiotidis, M Cidlowski, JA AF Panagiotidis, Michail Cidlowski, John A. TI Inhibition of Na+/K+-ATPase by ouabain potentiates apoptosis by inducing perturbations in cell calcium homeostasis. A protective role selective for Bcl-2 SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 279S EP 279S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800034 ER PT J AU Chen, Q Lee, JH Zhang, LQ Sun, A Krishna, MC Espey, MG Pooput, C Kirk, K Choyke, P Buettner, GR Shacter, E Levine, M AF Chen, Qi Lee, Je-Hyuk Zhang, Liqun Sun, Andrew Krishna, Murali C. Espey, Michael G. Pooput, Chaya Kirk, Kenneth Choyke, Peter Buettner, Garry R. Shacter, Emily Levine, Mark TI Pharmacologic ascorbate concentrations selectively kill cancer cells: Ascorbic acid as a prodrug for ascorbate radical or H2O2 delivery to tissues SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Iowa City, IA USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 293S EP 293S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800079 ER PT J AU Wilson, RT Wang, JY Chinchilli, V Richie, J Moore, LE Albanes, D AF Wilson, Robin Taylor Wang, Jiangyue Chinchilli, Vernon Richie, John Moore, Lee E. Albanes, Demetrius TI Supplementary and dietary vitamin D intake and renal cell cancer risk SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition, and Cancer CY JUL 13-14, 2006 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int, Calif Walnut Commiss, Campbell Soup Co, Cranberry Inst, Hormel Inst, IP 6 Int Inc, Kyushu Univ, Japan Grad Sch Agr, Natl Fisheries Inst, United Soybean Board C1 Penn State Univ, Penn State Coll Med, Penn State Canc Inst, Hershey, PA 17033 USA. Penn State Univ, Penn State Coll Med, Div Biostat, Hershey, PA 17033 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2007 VL 137 IS 1 SU S BP 293S EP 293S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 123XQ UT WOS:000243330800078 ER PT J AU Pope, SK Kritchevsky, SB Morris, MC Block, G Tylavsky, FA Lee, JS Stewart, S Harris, T Rubin, SM Simonsick, EM AF Pope, S. K. Kritchevsky, S. B. Morris, M. C. Block, G. Tylavsky, F. A. Lee, J. S. Stewart, S. Harris, T. Rubin, S. M. Simonsick, E. M. CA Hlth ABC Study TI Cognitive ability is associated with suspected reporting errors on food frequency questionnaires SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE diet surveys; cognition; energy intake; African Americans ID MINI-MENTAL-STATE; REPRODUCIBILITY; VALIDITY; POPULATION; PEOPLE; WOMEN AB Objective: To examine potential for bias in reported total energy intake on a Food Frequency Questionnaire (FFQ) among older adults. Design: Longitudinal cohort study. Subjects/setting: 2,706 Community-dwelling Black and White older adults, aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Multivariate logistic regression analyses were conducted with potential errors on reported total energy intake on the Food Frequency Questionnaire (FFQ) as the outcome variable and with cognitive ability, measured by the Modified Mini Mental State Exam (3MS) as the primary independent variable. The regression model controlled for site, race, gender, age, body size, and physical activity. Separate models were fit using 3MS as a continuous variable and for multiple 3MS cutpoints. All models revealed similar findings. Results: Cognitive ability was inversely associated with potential errors in reporting total energy intake, whereby a five-point increase in 3MS scores was associated with a 14% decreased likelihood of reporting errors (Odds Ratio=0.86, 95% Confidence Interval: 0.77, 0.95), Additionally, compared to White women, White men were 2 times more likely, and Black women and Black men were 3 times more likely, to have errors in reporting total energy intake. Conclusion: This study provides evidence that for older adults, lower cognition scores are associated with increased potential errors in reporting total energy intake. Applications: Dietary reporting from older adults may be inaccurate due to cognitive deficits. A brief assessment of cognitive function may assist clinicians in dietary evaluations and recommendation and may benefit studies using FFQ data where the measure of cognitive function could be utilized to stratify data analyses and conduct sensitivity analyses. C1 Univ Arkansas Med Sci, Dept Geriatr, Coll Med, Little Rock, AR 72205 USA. Wake Forest Univ Hlth sci, Sch Med, J Paul Sticht Ctr Aging, Winston Salem, NC USA. Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Arkansas Med Sci, Coll Med & Publ Hlth, Dept Biostat, Little Rock, AR 72205 USA. NIA, Intramural Res Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NIA, Baltimore, MD 21224 USA. RP Pope, SK (reprint author), Univ Arkansas Med Sci, Dept Geriatr, Coll Med, 4301 W Markham St,Mailslot 808, Little Rock, AR 72205 USA. EM skpope@uams.edu RI Block, Gladys/E-3304-2010 FU NIA NIH HHS [K01-AG-2-0173, N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 23 TC 13 Z9 13 U1 0 U2 2 PU SERDI EDITION PI PARIS PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD JAN-FEB PY 2007 VL 11 IS 1 BP 55 EP 58 PG 4 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 149BM UT WOS:000245121600009 PM 17315081 ER PT J AU Sprince, N Park, H Zwerling, C Whitten, P Lynch, C Burmeister, L Thu, K Gillette, P Alavanja, M AF Sprince, Nancy Park, Hyesook Zwerling, Craig Whitten, Paul Lynch, Charles Burmeister, Leon Thu, Kendall Gillette, Patricia Alavanja, Michael TI Risk factors for low back injury among farmers in Iowa: A case-control study nested in the agricultural health study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE agricultural work; farmer; low back injury; risk factors ID FAMILY HEALTH; FOLLOW-UP; PAIN; WORK; PREVALENCE; DEPRESSION; OPERATORS; SYMPTOMS; INDUSTRY; ALABAMA AB The aim of this study was to assess risk factors for low back injury requiring medical advice or treatment among Iowa farmers. Although farmers are at risk for low back injury, few studies have addressed risk factors for farm work-related low back injury. We screened 6999 participants in the Iowa portion of the Agricultural Health Study to identify 49 male farmers who reported farm work-related low back injury requiring medical advice or treatment in the previous year. We compared them with 465 uninjured male farmer controls. Multivariable modeling identified four risk factors significantly associated with low back injury: age less than 45 years (OR = 3.32; 95% CI 1.75-6.20), doctor-diagnosed asthma (OR = 4.26; 95% CI 1.49-12.10), education beyond high school (OR = 2.12; 95% CI 1.13-3.90), and difficulty hearing normal conversation (even with a hearing aid, in the case of those using one) (OR = 1.98; 95% CI 1.02-3.80). Although hearing difficulty may be a general risk factor for occupational injury, asthma may be a more specific risk factor for low back injury. Future research to assess the risk factors, asthma and difficulty hearing, may be particularly important, since farmers are at increased risk for hearing loss, and farmers come into contact with many inhaled agents that can cause asthma. C1 Univ Iowa, Iowa City, IA 52242 USA. Ewha Womans Univ, Seoul, South Korea. No Illinois Univ, De Kalb, IL 60115 USA. NCI, Bethesda, MD 20892 USA. RP Sprince, N (reprint author), Univ Iowa, 100 Oakdale Campus,108 IREH, Iowa City, IA 52242 USA. EM nancy-sprince@uiowa.edu NR 41 TC 23 Z9 23 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD JAN PY 2007 VL 4 IS 1 BP 10 EP 16 DI 10.1080/15459620601067266 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 118IE UT WOS:000242934900003 PM 17162476 ER PT J AU Christenson, EM Anseth, KS van den Beucken, LJJP Chan, CK Ercan, B Jansen, JA Laurencin, CT Li, WJ Murugan, R Nair, LS Ramakrishna, S Tuan, RS Webster, TJ Mikos, AG AF Christenson, Elizabeth M. Anseth, Kristi S. van den Beucken, Leroen J. J. P. Chan, Casey K. Ercan, Batur Jansen, John A. Laurencin, Cato T. Li, Wan-Ju Murugan, Ramalingam Nair, Lakshmi S. Ramakrishna, Seeram Tuan, Rocky S. Webster, Thomas J. Mikos, Antonios G. TI Nanobiomaterial applications in orthopedics SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE biomaterials; orthopedic; tissue engineering; nanocomposites; nanofibers ID MESENCHYMAL STEM-CELLS; 3-DIMENSIONAL NANOFIBROUS SCAFFOLD; CALCIUM-PHOSPHATE COATINGS; IN-VIVO; OSTEOBLAST ADHESION; NANOPHASE CERAMICS; OCTACALCIUM PHOSPHATE; BIOLOGICAL RESPONSE; BIOMIMETIC COATINGS; ENHANCED FUNCTIONS AB Advancements in nanobiotechnology are revolutionizing our capability to understand biological intricacies and resolve biological and medical problems by developing subtle biomimetic techniques. Nanocomposites and nanostructured materials are believed to play a pivotal role in orthopedic research since bone itself is a typical example of a nanocomposite. This article reviews current strategies using nanobiomaterials to improve current orthopedic materials and examines their applications in bone tissue engineering. Preliminary investigations support the potential of nanobiomaterials in orthopedic applications; however, significant advancements are necessary to achieve clinical use. Overall, current trends in nanobiotechnology foreshadow a bright future through the use of nanobiomaterials in the orthopedic domain. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 Rice Univ, Dept Bioengn, Houston, TX 77251 USA. Univ Colorado, Dept Biol & Chem Engn, Boulder, CO 80309 USA. Radboud Univ Nijmegen, Med Ctr, Dept Periodontol & Biomat, Nijmegen, Netherlands. Natl Univ Singapore, Div Bioengn, Singapore, Singapore. Brown Univ, Div Engn & Orthopaed, Providence, RI 02912 USA. Univ Virginia, Dept Orthopaed Surg, Charlottesville, VA USA. Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. Univ Virginia, Dept Chem Engn, Charlottesville, VA USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mikos, AG (reprint author), Rice Univ, Dept Bioengn, MS142,POB 1892, Houston, TX 77251 USA. EM mikos@rice.edu RI Li, Wan-Ju/A-7002-2008; Ramalingam, Murugan/C-9827-2010; van den beucken, Jeroen/B-8790-2013; van den beucken, jeroen/G-9940-2013; Jansen, J.A./H-8055-2014; ERCAN, BATUR/A-1232-2016; van den Beucken, Jeroen/N-2910-2013 OI ERCAN, BATUR/0000-0003-1657-1142; van den Beucken, Jeroen/0000-0002-0301-1966 FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR42639, R01 AR48756, Z01 AR41113]; NIDCR NIH HHS [1 T32 DE 015355-01, R01 DE15164] NR 63 TC 184 Z9 195 U1 5 U2 54 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2007 VL 25 IS 1 BP 11 EP 22 DI 10.1002/jor.20305 PG 12 WC Orthopedics SC Orthopedics GA 118DE UT WOS:000242921500002 PM 17048259 ER PT J AU Strizzi, L Bianco, C Hrota, M Watanabe, K Mancino, M Hamada, S Raafat, A Lawson, S Ebert, AD D'Antonio, A Losito, S Nonmanno, N Salomon, DS AF Strizzi, L. Bianco, C. Hrota, M. Watanabe, K. Mancino, M. Hamada, S. Raafat, A. Lawson, S. Ebert, A. D. D'Antonio, A. Losito, S. Nonmanno, N. Salomon, D. S. TI Development of leiomyosarcoma of the uterus in MMTV-CR-I transgenic mice SO JOURNAL OF PATHOLOGY LA English DT Article DE Cripto-1; transgenic mice; uterus; sarcoma ID GLYCOGEN-SYNTHASE KINASE-3; GYNECOLOGIC-ONCOLOGY-GROUP; MAMMARY EPITHELIAL-CELLS; WNT SIGNALING PATHWAY; BETA-CATENIN; VERTEBRATE DEVELOPMENT; UTERINE SARCOMAS; STEM-CELLS; CRIPTO-1; CANCER AB Overexpression of Cripto-1 (CR-1) in FVB/N mice using the MMTV-LTR promoter results in increased mammary tumourigenesis in these female transgenic mice (MMTV-CR-1). Here, we characterize uterine tumours that developed in 15/76 (19.7%) of MMTV-CRI female nulliparous or multiparous mice during 24 months of observation compared with 0133 (0%) of FVB/N normal control mice observed during the same time period (p < 0.01). The uterine tumours collected from the MMTV-CR-1 mice were classified as leiomyosarcomas and found to express the CR-1 transgene by polymerase chain reaction analysis and immunohistochemistry. Detection by western blot analysis showed higher levels of phosphorylated (P) forms of c-src, Akt, GSK-3 beta, and dephosphorylated (DP)-beta-catenin in lysates from MMTV-CR-1 uterine leiomyosarcomas in comparison with lysates from normal control FVB/N uteri. Immunostaining showed increased nuclear localization of beta-catenin in the MMTV-CR-1 uterine leiomyosarcomas. Increased immunostaining for CR-1 was detected in 9/13 (69.2%) cases of human leiomyosarcoma compared with staining in 3115 (20%) human leiomyoma sections. Stronger immunostaining for P-src, P-Akt, P-GSK-3 beta and increased nuclear localization of beta-catenin was also seen in human leiomyosarcomas in comparison with leiomyomas. Normal human uterine smooth muscle (UtSM) cells treated with exogenous soluble rhCR-1 showed increased levels of P-src, P-Akt, P-GSK-3 beta and dephosphorylated (DP)-beta-catenin and increased proliferation (P < 0.05) and migration (p < 0.01) in comparison with untreated control UtSM cells. Inhibitors against c-src, Akt or beta-catenin, individually or in combination, significantly reduced CR-1-induced migration. These results suggest a role for CR-1 during uterine tumourigenesis either directly by activating c-sre and Akt and/or via cross-talk with the canonical Wnt signalling pathway, as suggested by the increased expression of P-GSK-3 beta, DP-beta-catenin, and increased nuclear localization of beta-catenin in human and MMTV-CR-1 mice leiomyosarcomas. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. Vivantes Humboldt Klinikum, Dept Obstet & Gynaecol, Berlin, Germany. AORN Cardorelli, Surg Pathol Unit, Naples, Italy. INT Fdn Pascale, Surg Pathol Unit, Naples, Italy. INT Fdn Pascale, Cell Biol & Preclin Models Unit, Naples, Italy. RP Salomon, DS (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37,Room 1118B, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov NR 37 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2007 VL 211 IS 1 BP 36 EP 44 DI 10.1002/path.2083 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 126AV UT WOS:000243485500005 PM 17072826 ER PT J AU Glasofer, DR Tanofsky-Kraff, M Eddy, KT Yanovski, SZ Theim, KR Mirch, MC Ghorbani, S Ranzenhofer, LM Haaga, D Yanovski, JA AF Glasofer, Deborah R. Tanofsky-Kraff, Marian Eddy, Kamryn T. Yanovski, Susan Z. Theim, Kelly R. Mirch, Margaret C. Ghorbani, Samareh Ranzenhofer, Lisa M. Haaga, David Yanovski, Jack A. TI Binge eating in overweight treatment-seeking adolescents SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adolescents; binge eating; binge eating disorder; obesity ID DISORDER EXAMINATION; COMORBID PSYCHOPATHOLOGY; COMMUNITY SAMPLE; BULIMIA-NERVOSA; RISK-FACTORS; PUBERTAL CHANGES; BODY-FAT; CHILDREN; WEIGHT; ONSET AB Objective To examine the frequency and recency of binge eating in relation to psychopathology in overweight, treatment-seeking adolescents. Methods We investigated psychological correlates of the frequency and recency of reported loss of control (LOC) eating episodes in 160 overweight (body mass index [BMI]: 40.7 +/- 8.8 kg/m(2)) adolescents. On the basis of the responses to the eating disorder examination (EDE), participants were categorized into one of four groups: full-syndrome binge eating disorder (BED); recent but infrequent binge eating (episodes within the 3 months before interview; RECENT-BINGE); remote and infrequent LOC eating (episodes occurring > 3 months before assessment; PAST-LOC), or no history of LOC episodes (NE). Results The BED group reported higher EDE scores (global, p < .01), and more negative mood and anxiety than all other groups (p's < .01). Compared with NE, RECENT-BINGE also reported more anxiety and higher EDE scores (p's < .01). Conclusions Overweight, treatment-seeking adolescents with BED are clearly distinguishable from teens without the disorder on measures of eating-related psychopathology, mood, and anxiety. RECENT-BINGE, but not PAST-LOC, is also associated with significantly greater eating-related and general psychopathology. C1 NICHD, Unit Growth & Obes, DEB, CRC,NIH, Bethesda, MD 20892 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. NIDDK, Div Nutr Res Coordinat, DHHS, NIH, Bethesda, MD 20892 USA. RP Tanofsky-Kraff, M (reprint author), NICHD, Unit Growth & Obes, DEB, CRC,NIH, 10 Ctr Dr,Room 1-3330 MSC 1103, Bethesda, MD 20892 USA. EM tanofskm@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 54 TC 104 Z9 104 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JAN-FEB PY 2007 VL 32 IS 1 BP 95 EP 105 DI 10.1093/jpepsy/jsl012 PG 11 WC Psychology, Developmental SC Psychology GA 123WR UT WOS:000243327500012 PM 16801323 ER PT J AU Higgins, RD AF Higgins, Rosemary D. TI The vascular contribution to necrotizing enterocolitis SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 NICHD, Neonatal Res Network Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Higgins, RD (reprint author), NICHD, Neonatal Res Network Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03B,MSC 7510, Bethesda, MD 20892 USA. EM higginsr@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2007 VL 150 IS 1 BP 5 EP 6 DI 10.1016/j.jpeds.2006.10.063 PG 2 WC Pediatrics SC Pediatrics GA 125OC UT WOS:000243450500002 PM 17188603 ER PT J AU Thompson, DR Obarzanek, E Franko, DL Barton, BA Morrison, J Biro, FM Daniels, SR Stregel-Moore, RH AF Thompson, Douglas R. Obarzanek, Eva Franko, Debra L. Barton, Bruce A. Morrison, John Biro, Frank M. Daniels, Stephen R. Stregel-Moore, Ruth H. TI Childhood overweight and cardiovascular disease risk factors: The National Heart, Lung, and Blood Institute Growth and Health Study SO JOURNAL OF PEDIATRICS LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; SEXUAL-MATURATION; YOUNG ADULTHOOD; US CHILDREN; OBESITY; ADOLESCENTS; PREVALENCE; ADIPOSITY AB Objective. To estimate the prevalence and incidence of overweight in African-American and Caucasian girls, and to examine associations between adolescent overweight and cardiovascular disease (CVD) risk factors. Study design. In the National Heart, Lung and Blood Institute Growth and Health Study (NGHS), annual measurements were obtained from girls followed longitudinally between age 9 or 10 and 18 years; self-reported measures were obtained at age 21 to 23 years. A total of 1166 Caucasian girls and 1213 African-American girls participated in the study. Childhood overweight as. defined by the Centers for Disease Control and Prevention (CDC) was the independent variable of primary interest. Measured outcomes included blood pressure and lipid levels. Results. Rates of overweight increased through adolescence from 7% to 10% in the Caucasian girls and from 17% to 24% in the African-American girls. The incidence of overweight was greater at age 9 to 12 than in later adolescence. Girls who were overweight during childhood were 11 to 30 times more likely to be obese in young adulthood. Overweight was significantly associated with increased percent body fat, sum of skinfolds and waist circumference measurements, and unhealthful systolic and diastolic blood pressure, high-density lipoprotein cholesterol, and triglyceride levels. Conclusion. A relationship between CVD risk factors and CDC-defined overweight is present at age 9. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. NHLBI, Bethesda, MD 20892 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA. Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. RP Thompson, DR (reprint author), Maryland Med Res Inst, Baltimore, MD 21210 USA. EM dthompson@mmri.org OI Barton, Bruce/0000-0001-7878-8895; weissman, ruth/0000-0001-6121-4641 FU NHLBI NIH HHS [R01 HL071122, HC55023-26, R01 HL071122-01, U01-HL-48941-44]; NIDDK NIH HHS [HL/DK71122, R01 DK071122, R56 DK071122]; NIMH NIH HHS [MH57897] NR 61 TC 135 Z9 142 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2007 VL 150 IS 1 BP 18 EP 25 DI 10.1016/j.jpeds.2006.09.039 PG 8 WC Pediatrics SC Pediatrics GA 125OC UT WOS:000243450500005 PM 17188606 ER PT J AU Friel, LA Romero, R Edwin, S Nien, JK Gomez, R Chaiworapongsa, T Kusanovic, JP Tolosa, JE Hassan, SS Espinoza, J AF Friel, Lara A. Romero, Roberto Edwin, Sam Nien, Jyh Kae Gomez, Ricardo Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Tolosa, Jorge E. Hassan, Sonia S. Espinoza, Jimmy TI The calcium binding protein, S100B, is increased in the amniotic fluid of women with intra-amniotic infection/inflammation and preterm labor with intact or ruptured membranes SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE chorioamnionitis; fetal inflammation; funisitis; interieukin-6; intra-amniotic infection; neonatal morbidity; parturition; preterm premature rupture of membranes ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; FULL-TERM INFANTS; GESTATIONAL-AGE; BRAIN-DAMAGE; INTRAVENTRICULAR HEMORRHAGE; EARLY IDENTIFICATION; CARDIAC-SURGERY; EARLY INDICATOR; TRAUMA PATIENTS; SEPTIC SHOCK AB Objective: S100B is produced by glia of the central and peripheral nervous systems and is considered a marker of neurologic injury in the perinatal period. Indeed, increased neonatal urine S100B concentration is associated with adverse neurological outcomes including intraventricular hemorrhage and hypoxic-ischemic encephalopathy, while elevated adult serum concentrations are associated with infectious diseases/sepsis. The objective of this study was to determine whether amniotic fluid (AF) S100B concentrations change with advancing gestational age and intra-amniotic infection (IAI). Study design: S100B concentration was measured in the AF of women in midtrimester, at term, and in pregnancies with preterm labor and intact membranes (PTL) or preterm premature rupture of membranes (PPROM), with and without IAI. Placental pathology was performed and neonatal outcomes were analyzed. Results: (1) AF S100B concentration did not change during gestation; (2) patients with IN had significantly higher AF S100B concentration than those without IAI following an episode of PTL or PPROM and; (3) neonates who had morbidity/mortality had had an elevated AF S100B concentration; however, this could be explained by the association with intra-amniotic infection/inflammation. Thus, AF S100B concentration was not an independent predictor of neonatal morbidity or fetal/neonatal death. Conclusions: An elevated concentration of AF S100B may reflect intra-amniotic infection/inflammation and not necessarily fetal neurologic damage. C1 Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, Div Intramural Res, NIH, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Wayne State Univ, Ctr Mol Med & Genet, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Hosp Dr Sotero del Rio, Ctr Perinatal Diag & Res, Santiago, Chile. Penn Hosp, Philadelphia, PA 19107 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Friel, LA (reprint author), Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, Div Intramural Res, NIH, 4 Brush S-Hutzel Womens Hosp 3990 John R, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov FU Intramural NIH HHS [Z01 HD002400-16] NR 40 TC 20 Z9 21 U1 0 U2 6 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 EI 1619-3997 J9 J PERINAT MED JI J. Perinat. Med. PY 2007 VL 35 IS 5 BP 385 EP 393 DI 10.1515/JPM.2007.101 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 208OX UT WOS:000249330200005 PM 17624933 ER PT J AU Nien, JK Mazaki-Tovi, S Romero, R Erez, O Kusanovic, JP Gotsch, F Pineles, BL Gomez, R Edwin, S Mazor, M Espinoza, J Yoon, BH Hassan, SS AF Nien, Jyh Kae Mazaki-Tovi, Shali Romero, Roberto Erez, Offer Kusanovic, Juan Pedro Gotsch, Francesca Pineles, Beth L. Gomez, Ricardo Edwin, Samuel Mazor, Moshe Espinoza, Jimmy Yoon, Bo Hyun Hassan, Sonia S. TI Adiponectin in severe preeclampsia SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE adiponectin; Doppler; obesity; preeclampsia; pregnancy; uterine artery ID HEALTHY NULLIPAROUS WOMEN; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; GESTATIONAL DIABETES-MELLITUS; ADIPOSE-SPECIFIC PROTEIN; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; PLASMA-PROTEIN; METABOLIC SYNDROME; RISK-FACTORS AB Aims: Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods: This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results: (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions: Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia. C1 [Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. [Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Edwin, Samuel; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, NIH, DHHS,Intramural Div,Perinatol Res Branch, Hutzel Womens Hosp, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, NIH, DHHS,Intramural Div,Perinatol Res Branch, Hutzel Womens Hosp, Box 4,3990 John R, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [NIH0011422970, Z01 HD002400-16] NR 104 TC 44 Z9 48 U1 0 U2 2 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2007 VL 35 IS 6 BP 503 EP 512 DI 10.1515/JPM.2007.121 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 246XT UT WOS:000252042400009 PM 17919115 ER PT J AU Nien, JK Shali, T Romero, R Kusanovic, JP Erez, O Gotsch, F Pineles, BL Friell, LA Espinoza, J Goncalves, L Santolaya, J Gomez, R Hong, JS Edwin, S Soto, E Richani, K Mazor, M Hassan, SS AF Nien, Jyh Kae Mazaki-Tovi, Shali Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Pineles, Beth L. Friell, Lara A. Espinoza, Jimmy Goncalves, Luis Santolaya, Joaquin Gomez, Ricardo Hong, Joon-Seok Edwin, Samuel Soto, Eleazar Richani, Karina Mazor, Moshe Hassan, Sonia S. TI Resistin: a hormone which induces insulin resistance is increased in normal pregnancy SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE adipokines; nomogram; obesity; pregnancy; resistin ID GESTATIONAL DIABETES-MELLITUS; PLASMA ADIPONECTIN CONCENTRATIONS; LINKED-IMMUNOSORBENT-ASSAY; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; ADIPOSE-TISSUE; METABOLIC SYNDROME; SERUM RESISTIN; TNF-ALPHA; CARBOHYDRATE-METABOLISM AB Aims: Resistin, a newly discovered adipokine, is thought to play a key role in the regulation of insulin resistance. The objectives of this study were to develop a nomogram of maternal plasma concentrations of resistin from 11 weeks of gestation to term and to determine whether resistin concentrations differ between normal and overweight pregnant women. Methods: In this cross-sectional study, plasma concentrations of resistin were determined in normal pregnant women of normal body mass index (BMI 18.5-24.9; n=261), overweight pregnant women (BMI >= 25; n=140), and non-pregnant women of normal BMI (n=40). Blood samples were collected once from each woman between the first trimester and term. Percentiles for resistin concentration were determined for five prespecified windows of gestational age. Plasma resistin concentration was determined by immunoassay. Nonparametric statistics were used for analysis. Results: The median maternal plasma concentration of resistin between 11 to 14 weeks of gestation in women of normal weight was significantly higher than non-pregnant women; the plasma concentration of resistin increased with gestational age. Conclusions: Normal pregnant women have a higher median plasma concentration of resistin than non-pregnant women and the concentration of this adipokine increases with advancing gestation. Alterations in the maternal plasma concentration of resistin during pregnancy could contribute to metabolic changes of pregnancy. C1 [Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Pineles, Beth L.; Friell, Lara A.; Espinoza, Jimmy; Goncalves, Luis; Santolaya, Joaquin; Hong, Joon-Seok; Edwin, Samuel; Soto, Eleazar; Richani, Karina; Hassan, Sonia S.] NICHD, NIH, Hutzel Womens Hosp, DHHS,Intramural Div,Perinatol Res Branch, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Friell, Lara A.; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Hutzel Womens Hosp, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), NICHD, NIH, Hutzel Womens Hosp, DHHS,Intramural Div,Perinatol Res Branch, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-16] NR 107 TC 44 Z9 44 U1 0 U2 2 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2007 VL 35 IS 6 BP 513 EP 521 DI 10.1515/JPM.2007.122 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 246XT UT WOS:000252042400010 PM 17919114 ER PT J AU Nien, JK Mazaki-Tovi, S Romero, R Erez, O Kusanovic, JP Gotsch, F Pineles, BL Gomez, R Edwin, S Mazor, M Espinoza, J Yoon, BH Hassan, SS AF Nien, Jyh Kae Mazaki-Tovi, Shali Romero, Roberto Erez, Offer Kusanovic, Juan Pedro Gotsch, Francesca Pineles, Beth L. Gomez, Ricardo Edwin, Samuel Mazor, Moshe Espinoza, Jimmy Yoon, Bo Hyun Hassan, Sonia S. TI Plasma adiponectin concentrations in non-pregnant, normal and overweight pregnant women SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE adipokines; adiponectin; nomogram; obesity; pregnancy ID GESTATIONAL DIABETES-MELLITUS; INDUCED INSULIN-RESISTANCE; ACTIVATED PROTEIN-KINASE; ADIPOSE-SPECIFIC PROTEIN; NECROSIS-FACTOR-ALPHA; METABOLIC SYNDROME; SERUM ADIPONECTIN; ANOREXIA-NERVOSA; ENDOCRINE ORGAN; TNF-ALPHA AB Aims: Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and in obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Methods: A cross-sectional study was designed to include normal pregnant (normal weight and overweight; 11-42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results: (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant differences in the median adiponectin concentration between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower plasma adiponectin concentrations than normal weight women. Conclusions: Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented, can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. C1 [Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, NIH, Hutzel Womens Hosp, DHHS,Intramural Div,Perinatol Res Branch, Detroit, MI 48201 USA. NICHD, NIH, Hutzel Womens Hosp, DHHS,Intramural Div,Perinatol Res Branch, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), NICHD, NIH, Hutzel Womens Hosp, DHHS,Intramural Div,Perinatol Res Branch, Box 4,3990 John R, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16] NR 123 TC 44 Z9 45 U1 0 U2 3 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2007 VL 35 IS 6 BP 522 EP 531 DI 10.1515/JPM.2007.123 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 246XT UT WOS:000252042400011 PM 17919116 ER PT J AU Saito, S Heller, T Liang, TJ AF Saito, Satoru Heller, Theo Liang, T. Jake TI A new in vitro model of hepatitis C virion production (The possibility to develop vaccines and drugs for HCV) SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 NIH, NIDDK, Liver Dis Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 22P EP 22P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046500040 ER PT J AU Kitazawa, T Hashiba, K Cao, J Unno, T Komori, SI Yamada, M Wess, J Taneike, T AF Kitazawa, Takio Hashiba, Kano Cao, Jinshan Unno, Toshihiro Komori, Sei-Ichi Yamada, Masahisa Wess, Jurgen Taneike, Tetsuro TI Different functional roles of M2 and M3 receptors in gastric contraction induced by carbachol and nerve stimulation SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Rakuno Gakuen Univ, Sch Vet Med, Dept Pharmacol, Hokkaido 0698501, Japan. Gifu Univ, Fac Appl Biol Sci, Pharmacol Lab, Gifu 5011193, Japan. RIKEN, Brain Sci Inst, Mol Neuropathol Grp, Neurogenet Lab, Saitama 3510198, Japan. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 67P EP 67P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046500206 ER PT J AU Ueyama, T Tatsuno, T Kawasaki, T Tsujibe, S Shirai, Y Sumimoto, H Leto, TL Saito, N AF Ueyama, Takehiko Tatsuno, Toshihiko Kawasaki, Takumi Tsujibe, Satosi Shirai, Yasuhito Sumimoto, Hideki Leto, Thomas. L. Saito, Naoaki TI A regulated adaptor function of p40phox: a head-to-tail (PX-PB1 domain) intramolecular interaction of p40phox in its resting state SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 657, Japan. Kyushu Univ, Med Inst Bioregulat, Fukuoka, Japan. NIH, NIAID, LHD, Mol Defenses Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 95P EP 95P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046500321 ER PT J AU Sakamoto, T Unno, T Matsuyama, H Kitazawa, T Taneike, T Yamada, M Jurgen, W Komori, S AF Sakamoto, Takashi Unno, Toshihiro Matsuyama, Hayato Kitazawa, Takio Taneike, Tetsuro Yamada, Masahisa Jurgen, Wess Komori, Seiichi TI Synergistic activation of receptoroperated cationic channels by M-2 and M-3 muscarinic receptors in mouse ileal smooth muscle cells. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Unity Grad Sch Vet Sci, Dept Pathol Vet Sci, Gifu 50111, Japan. Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 50111, Japan. Rakuno Gakuen Univ, Fac Vet Med, Dept Pharmacol, Ebetsu, Hokkaido 069, Japan. NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 104P EP 104P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046500356 ER PT J AU Ide, S Minami, M Uhl, GR Ishihara, K Satoh, M Sora, I Ikeda, K AF Ide, Soichiro Minami, Masabumi Uhl, George R. Ishihara, Kumatoshi Satoh, Masamichi Sora, Ichiro Ikeda, Kazutaka TI Analyses of antinociceptive effects of butorphanol in mu-opioid receptor knockout mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Hiroshima Int Univ, Fac Pharmaceut Sci, Neuropharmacol Lab, Kure 7370112, Japan. Tokyo Inst Psychiat, Div Psychibiol, Tokyo 1568585, Japan. Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sapporo, Hokkaido 0600812, Japan. NIDA, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. Yasuda Womens Univ, Hiroshima 7310153, Japan. RI Ide, Soichiro/D-5472-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 184P EP 184P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046501192 ER PT J AU Unno, T Matsuyama, H Izumi, Y Yamada, M Jurgen, W Komori, S AF Unno, Toshihiro Matsuyama, Hayato Izumi, Yusuke Yamada, Masahisa Jurgen, Wess Komori, Seiichi TI Roles of M-2 and M-3 muscarinic receptors in cholinergic nerve-induced contractions in mouse ileum studied with receptor knockout mice. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 206P EP 206P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046501278 ER PT J AU Suguro, M Unno, T Matsuyama, H Yamada, M Jurgen, W Komori, S AF Suguro, Mayuko Unno, Toshihiro Matsuyama, Hayato Yamada, Masahisa Jurgen, Wess Komori, Seiichi TI M-3 subtype of muscarinic receptor mediates the Ca2+ sensitization of the contractile elements in the longitudinal smooth muscle of mice ileum SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 50111, Japan. NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 249P EP 249P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046501451 ER PT J AU Tanahashi, Y Unno, T Matsuyama, H Yamada, M Jurgen, W Komori, S AF Tanahashi, Yasuyuki Unno, Toshihiro Matsuyama, Hayato Yamada, Masahisa Jurgen, Wess Komori, seiichi TI Roles of M(2)and M-3 muscarinic receptors in carbachol-induced suppression of voltage-gated Ca2+ channel currents in mouse ileal smooth muscle cells. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 80th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 14-16, 2007 CL Nagoya, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Unit Grad Sch Vet Sci, Dept Vet Pathol Sci, Gifu 50111, Japan. Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 50111, Japan. RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 351, Japan. NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2007 VL 103 SU 1 BP 249P EP 249P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148AI UT WOS:000245046501450 ER PT J AU Faucette, SR Zhang, TC Moore, R Sueyoshi, T Omiecinski, CJ LeCluyse, EL Negishi, M Wang, HB AF Faucette, Stephanie R. Zhang, Tong-Cun Moore, Rick Sueyoshi, Tatsuya Omiecinski, Curtis J. LeCluyse, Edward L. Negishi, Masahiko Wang, Hongbing TI Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID REPORTER GENE ASSAY; DISTAL ENHANCER MODULE; HUMAN HEPATOCYTES; CLINICAL PHARMACOKINETICS; NUCLEAR TRANSLOCATION; CYTOCHROME P4502B6; INDUCTION; CAR; EXPRESSION; CARBAMAZEPINE AB Both the human pregnane X receptor (hPXR) and constitutive androstane receptor (hCAR) are capable of regulating CYP3A4 and CYP2B6 gene expression. However, the majority of currently identified CYP3A4 and CYP2B6 inducers are confirmed activators of hPXR but not hCAR. To compare these receptors with respect to their chemical selectivities, 16 drugs known to induce CYP3A4 and/or CYP2B expression were evaluated for relative activation of hPXR versus hCAR. Because of the high basal but low chemical-induced activation of hCAR in immortalized cells, alternative methods were used to evaluate hCAR activation potential. Thirteen of the 16 compounds were classified as moderate to strong hPXR activators. In contrast, carbamazepine (CMZ), efavirenz (EFV), and nevirapine (NVP) were classified as negligible or weak hPXR activators at concentrations associated with efficacious CYP2B6 reporter or endogenous gene induction in primary human hepatocytes, suggesting potential activation of hCAR. Subsequent experiments demonstrated that these three drugs efficiently induced nuclear accumulation of in vivo-transfected enhanced yellow fluorescent protein-hCAR and significantly increased expression of a CYP2B6 reporter gene when hCAR was expressed in CAR(-/-) mice. In addition, using a recently identified, chemically responsive splice variant of hCAR (hCAR3), the hCAR activation profiles of the 16 compounds were evaluated. By combining results from the hPXR- and hCAR3-based reporter gene assays, these inducers were classified as hPXR, hCAR, or hPXR/hCAR dual activators. Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for in vitro prediction of chemical-mediated human CAR activation. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27515 USA. Natl Inst Environm & Hlth Sci, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. CellzDirect Inc, Pittsboro, NC USA. RP Wang, HB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. EM hwang@rx.umaryland.edu OI LeCluyse, Edward/0000-0002-2149-8990 FU NIDDK NIH HHS [DK061652, R01 DK061652]; NIGMS NIH HHS [R01 GM066411] NR 38 TC 172 Z9 181 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 72 EP 80 DI 10.1124/jpet.106.112136 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600009 PM 17041008 ER PT J AU O'Dell, LE Chen, SA Smith, RT Specio, SE Balster, RL Paterson, NE Markou, A Zorrilla, EP Koob, GF AF O'Dell, Laura E. Chen, Scott A. Smith, Ron T. Specio, Sheila E. Balster, Robert L. Paterson, Neil E. Markou, Athina Zorrilla, Eric P. Koob, George F. TI Extended access to nicotine self-administration leads to dependence: Circadian measures, withdrawal measures, and extinction behavior in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID UNLIMITED ACCESS; ADMINISTERED NICOTINE; RECEPTOR ANTAGONIST; CIGARETTE-SMOKING; SEEKING BEHAVIOR; MEAL PATTERNS; BODY-WEIGHT; FOOD-INTAKE; HEROIN; REINSTATEMENT AB The present study characterized nicotine intake, circadian patterns of food and water intake, precipitated somatic signs of withdrawal, and extinction of nicotine-seeking behavior in rats with 23-h access to intravenous self-administration (IVSA). Separate groups of animals were allowed access to nicotine IVSA (0.015, n = 9; 0.03, n = 14; 0.06, n = 16; mg/kg/0.1 ml infusion/s; fixed ratio 1) and trained to nosepoke for food and water 23 h/day for 40 consecutive days. Somatic signs of nicotine withdrawal were examined following saline or mecamylamine administration (1.5 mg/kg i.p.), and extinction of nicotine-seeking behavior was assessed. A dose-dependent decrease in lever responding and an increase in nicotine intake were observed, with the highest nicotine dose producing the lowest amount of lever responding and the highest amount of nicotine intake. Nicotine acutely reduced diurnal and nocturnal food intake, producing smaller and fewer meals, and an increased rate of eating. Differences in rate of nicotine intake between the light and dark phase decreased significantly, especially in rats receiving higher unit nicotine doses (0.03 and 0.06 mg/kg), along with long-term decreases in the circadian profile and amplitude of feeding. Mecamylamine precipitated robust withdrawal signs, the magnitude of which was positively correlated with the total amount of self-administered nicotine. Extinction of nicotine-seeking behavior was observed and was facilitated by removal of nicotine-associated cues. The results demonstrate that rats will self-administer nicotine to the point of producing dependence, as measured by somatic signs, resistance to extinction, and measures of food intake. C1 Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA. Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. Univ Texas, Dept Psychol, El Paso, TX 79968 USA. NIH, Lab Clin & Translat Studies, Anim Ctr, NIAAA, Poolesville, MD USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. RP Koob, GF (reprint author), Scripps Res Inst, Dept Mol & Integrat Neurosci, SP30-2400,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM gkoob@scripps.edu RI koob, george/P-8791-2016 FU NIDDK NIH HHS [DK64871] NR 51 TC 66 Z9 66 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 180 EP 193 DI 10.1124/jpet.106.105270 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600021 PM 17050784 ER PT J AU Cormaci, G Mori, T Hayashi, T Su, TP AF Cormaci, Gianfrancesco Mori, Tomohisa Hayashi, Teruo Su, Tsung-Ping TI Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: Implication for neuroplasticity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDUCED BEHAVIORAL SENSITIZATION; LIPID RAFT RECONSTITUTION; SIGMA(1) BINDING-SITES; NEUROACTIVE STEROIDS; PLACE PREFERENCE; ERK PATHWAY; PC12 CELLS; RECEPTORS; COCAINE; BRAIN AB The alpha-1 receptor (Sig-1R) can bind psychostimulants and was shown to be up-regulated in the brain of methamphetamine self-administering rats. Up-regulation of Sig-1Rs has been implicated in neuroplasticity. However, the mechanism(s) whereby Sig-1Rs are up-regulated by psychostimulants is unknown. Here, we employed a neuroblastoma cell line B-104, devoid of dopamine receptors and transporter, and examined the effects of psychostimulants as well as cAMP on the expression of Sig-1Rs in this cell line, with a specific goal to identify signal transduction pathway( s) that may regulate Sig-1R expression. Chronic treatments of B-104 cells with physiological concentrations of cocaine or methamphetamine failed to alter the expression of Sig-1Rs. N-6,2 '-O-Dibutyryl-cAMP (dB-cAMP), when used at 0.5 mM, caused a down-regulation of Sig-1Rs that could be blocked by a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide dihydrochloride (H-89). However, dB-cAMP, when used at 2 mM, caused an up-regulation of Sig-1Rs that was insensitive to the H-89 blockade but was partially blocked by an extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase inhibitor PD98059 (2 '-amino-3 '-methoxyflavone). Furthermore, 2 mM dB-cAMP induced an ERK phosphorylation lasting at least 90 min, at which time the phosphorylation caused by 0.5 mM dB-cAMP had already diminished. PD98059, applied 90 min after addition of 2 mM dB-cAMP, attenuated the Sig-1R up-regulation. Our results indicate that cAMP is bimodal in regulating Sig-1R expression: a down-regulation via PKA and an up-regulation via ERK. Results also suggest that psychostimulants may manipulate the cAMP-PKA-Sig-1R and/or the cAMP-ERK-Sig-1R pathways to achieve a neuroplasticity that favors addictive behaviors. C1 Natl Inst Drug Abuse, Cellular Pathobiol Unit, Dev & Plast Sect,Cellular Neurobiol Res Branch,In, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Su, TP (reprint author), Natl Inst Drug Abuse, Cellular Pathobiol Unit, Dev & Plast Sect,Cellular Neurobiol Res Branch,In, NIH,Dept Hlth & Human Serv, Triad Bldg,Room 3304,333 Cassel Dr, Baltimore, MD 21224 USA. EM tsu@intra.nida.nih.gov RI Hayashi, Teruo/A-9690-2008 FU Intramural NIH HHS NR 41 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 202 EP 210 DI 10.1124/jpet.106.108415 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600023 PM 17050780 ER PT J AU Tien, ES Matsui, K Moore, R Negishi, M AF Tien, Eric S. Matsui, Kenji Moore, Rick Negishi, Masahiko TI The nuclear receptor constitutively active/androstane receptor regulates type 1 deiodinase and thyroid hormone activity in the regenerating mouse liver SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANDROSTANE RECEPTOR; PARTIAL-HEPATECTOMY; X-RECEPTOR; GENE; CAR; METABOLISM; MICE; EXPRESSION; INDUCTION; PROMOTION AB We observed that the level of reverse triiodothyronine ( rT3) was significantly increased after partial hepatectomy ( PH) in both wild- type and constitutively active/ androstane receptor ( CAR) knockout ( KO) mice, and treatment with phenobarbital ( PB), a CAR activator, after PH decreased rT3 to restore its original level only in wild- type mice. On the other hand, no significant changes in the level of total T3 or free T3 in the serum were observed in either wild- type or CAR KO mice after PH or treatment with PB. Type 1 deiodinase ( D1) activity and expression were significantly reduced by PH and up- regulated by PB in a CAR- dependent manner. In addition, known T3- regulated genes [ tyrosine aminotransferase ( TAT) and basic transcription element binding protein ( BTEB)] were also significantly decreased by PH and induced by PB. Injection of rT3 into normal mice revealed that rT3 is capable of repressing the known thyroid hormone- regulated genes Tat, Bteb, and Cpt- 1 in the liver. Our results suggest that PH decreases D1 activity leading to increased rT3 level, resulting in the repression of T3 target genes. Subsequent treatment with PB decreases rT3 in a CAR-dependent manner through the up- regulation of the D1 gene. C1 [Tien, Eric S.; Matsui, Kenji; Moore, Rick; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmaceut Sect, Reprod & Dev Toxicol Lab, POB 12233,E4-07, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS NR 36 TC 24 Z9 27 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 307 EP 313 DI 10.1124/jpet.106.112706 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600036 PM 17050775 ER PT J AU Othman, AA Syed, SA Newman, AH Eddington, ND AF Othman, Ahmed A. Syed, Shariq A. Newman, Amy H. Eddington, Natalie D. TI Transport, metabolism, and in vivo population pharmacokinetics of the chloro benztropine analogs, a class of compounds extensively evaluated in animal models of drug abuse SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE UPTAKE INHIBITORS; COCAINE-ABUSE; RHESUS-MONKEYS; P-GLYCOPROTEIN; VITRO; COMBINATION; CLEARANCE; BINDING; POTENT; BRAIN AB Recently, extensive behavioral research has been conducted on the benztropine ( BZT) analogs with the goal of developing successful therapeutics for cocaine abuse. The present study was conducted to characterize the contribution of dispositional factors in mediating the behavioral differences among the chloro BZT analogs and to identify cytochrome P450 enzymes involved in their metabolism. Bidirectional transport and efflux studies of four of the chloro BZT analogs were conducted. Screening with a panel of human and rat Supersomes was performed for 4', 4"- diCl BZT. In addition, pharmacokinetic and brain distribution studies for 4'-Cl and 4', 4"-diCl BZT in Sprague-Dawley rats were conducted. The permeability of the chloro analogs ranged from 8.26 to 32.23 and from 1.37 to 21.65 x 10(-6) cm/s, whereas the efflux ratios ranged from 2.1 to 6.9 and from 3.3 to 28.4 across Madin-Darby canine kidney-multidrug resistance 1 ( MDCK - MDR1) and Caco-2 monolayers, respectively. The P-glycoprotein ( P-gp) inhibitor verapamil reduced the efflux ratios and enhanced the absorptive transport of the chloro BZT analogs. 4', 4''- diCl BZT was a substrate of human CYP2D6 and 2C19 and rat 2C11 and 3A1. The brain uptake for 4'- Cl and 4', 4"- diCl BZT was comparable and higher than previously reported for cocaine ( brain- to- plasma partition coefficient = 4.6 - 4.7 versus 2.1 for cocaine). The rank order for t(1/2) was 4', 4"- diCl BZT >> 4'- Cl BZT > cocaine and for steadystate volume of distribution was 4"- Cl BZT > 4', 4"-diCl BZT >> cocaine. In conclusion, the chloro analogs differ significantly in their clearance and duration of action, which correlates to their behavioral profiles and abuse liability. Furthermore, these results suggest that the distinctive behavioral profile of these analogs is not due to limited brain exposure. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, 20 Penn St,HSF 2, Baltimore, MD 21201 USA. EM neddingt@rx.umaryland.edu FU Intramural NIH HHS; NIDA NIH HHS [R01 DA16715-03] NR 31 TC 15 Z9 15 U1 3 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 344 EP 353 DI 10.1124/jpet.106.111245 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600040 PM 17003230 ER PT J AU Lahiri, DK Chen, DM Maloney, B Holloway, HW Yu, QS Utsuki, T Giordano, T Sambamurti, K Greig, NH AF Lahiri, Debomoy K. Chen, DeMao Maloney, Bryan Holloway, Harold W. Yu, Qian-sheng Utsuki, Tada Giordano, Tony Sambamurti, Kumar Greig, Nigel H. TI The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN MESSENGER-RNA; PRECURSOR PROTEIN; A-BETA; NEURODEGENERATIVE DISEASES; 5'-UNTRANSLATED REGION; REGULATES TRANSLATION; RESPONSIVE ELEMENT; MOLECULAR TARGETS; CEREBRAL-CORTEX; SECRETASE AB Major characteristics of Alzheimer's disease ( AD) are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid beta- peptide ( A beta), a proteolytic fragment of amyloid beta precursor protein (APP), aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop safe A beta- lowering drugs. A selective acetylcholinesterase inhibitor, phenserine, in current human trials lowers both APP and A beta. Phenserine is dose- limited in animals by its cholinergic actions; its cholinergically inactive enantiomer, posiphen (+)-[ phenserine], was assessed. In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time-dependently lowered APP and A beta levels by reducing the APP synthesis rate. This action translated to an in vivo system. Posiphen administration to mice (7.5 - 75 mg/ kg daily, 21 consecutive days) significantly decreased levels of total APP ( tissue mass- adjusted) in a dose- dependent manner. A beta(40) and A beta(42) levels were significantly lowered by posiphen ( >= 15 mg/ kg) compared with controls. The activities of alpha-, beta-, and gamma- secretases were assessed in the same brain samples, and beta- secretase activity was significantly reduced. Posiphen, like phenserine, can lower A beta via multiple mechanisms and represents an interesting drug candidate for AD treatment. C1 Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. NIA, Neurosci Lab, Sect Drug Design & Delivery, Baltimore, MD 21224 USA. Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71105 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, PR-313,791 Union Dr, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU NIA NIH HHS [AG18884, R01 AG18379] NR 44 TC 62 Z9 65 U1 2 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2007 VL 320 IS 1 BP 386 EP 396 DI 10.1124/jpet.106.112102 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119ER UT WOS:000242995600044 PM 17003227 ER PT J AU Lawrence, JJ AF Lawrence, J. Josh TI Homosynaptic and heterosynaptic modes of endocannabinoid action at hippocampal CCK plus basket cell synapses SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID INHIBITION C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Lawrence, JJ (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. EM lawrenjo@mail.nih.gov NR 7 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2007 VL 578 IS 1 BP 3 EP 4 DI 10.1113/jphysiol.2006.123802 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 123LH UT WOS:000243296900002 PM 17082227 ER PT J AU Lemaire, R Stauber, J Wisztorski, M Van Camp, C Desmons, A Deschamps, M Proess, G Rudlof, I Woods, AS Day, R Salzet, M Fournier, I AF Lemaire, R. Stauber, J. Wisztorski, M. Van Camp, C. Desmons, A. Deschamps, M. Proess, G. Rudlof, I. Woods, A. S. Day, R. Salzet, M. Fournier, I. TI Tag-mass: Specific molecular imaging of transcriptome and proteome by mass spectrometry based on photocleavable tag SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE MALDI; specific tissue imaging; Tag-Mass; photocleavage; multiplex; transcriptome; proteome ID DIRECT TISSUE-ANALYSIS; RAT-BRAIN; MALDI-TOFMS; HYBRIDIZATION; LOCALIZATION; EXPRESSION; DNA; MS AB MALDI tissue imaging of tissues has become a promising technique for tracking biomarkers while determining their location and structural characterization. We have now developed specific targeting probes ( oligonucleotides, antibodies), named Tag-Mass. This approach is based on probes modified with a photocleavable linker coupled with a tag cleaved and detected using mass spectrometry. Tag-Mass development is the key for a rapid, sensitive, and accurate approach to correlate levels of expression of different mRNA or proteins in diseases. C1 Univ Sci & Tech Lille Flandres Artois, FRE CNRS 2933, MALDI Imaging Team, Lab Neuroimmunol Annelides, F-59655 Villeneuve Dascq, France. Soc EUROGENTEC, Eurogentec Biol Dept, B-4102 Seraing, Belgium. NIDA, IRP, NIH, Baltimore, MD 21224 USA. Univ Sherbrooke, Fac Med, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada. RP Fournier, I (reprint author), Univ Sci & Tech Lille Flandres Artois, FRE CNRS 2933, MALDI Imaging Team, Lab Neuroimmunol Annelides, F-59655 Villeneuve Dascq, France. EM isabelle.fournier@univ-lille1.fr RI Michel, Salzet/A-7675-2011; FOURNIER, Isabelle/H-9195-2015; Wisztorski, Maxence/F-4380-2010 OI Michel, Salzet/0000-0003-4318-0817; FOURNIER, Isabelle/0000-0003-1096-5044; Wisztorski, Maxence/0000-0003-1320-075X FU Intramural NIH HHS [Z99 DA999999] NR 19 TC 48 Z9 48 U1 4 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PY 2007 VL 6 IS 6 BP 2057 EP 2067 DI 10.1021/pr0700044 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 173ST UT WOS:000246893500001 PM 17477556 ER PT J AU Patel, BB Li, XM Dixon, MP Blagoi, EL Seeholzer, SH Chen, YB Miller, CG He, YA Tetruashvily, M Chaudhry, AH Ke, E Xie, J Cooper, H Bellacosa, A Clapper, ML Boman, BM Zhang, T Litwin, S Ross, EA Conrad, P Crowell, JA Kopelovich, L Knudson, A Yeung, AT AF Patel, Bhavinkumar B. Li, Xin-Ming Dixon, Maketa P. Blagoi, Elena L. Seeholzer, Steven H. Chen, Yibai Miller, C. Glenn He, Yin A. Tetruashvily, Mazell Chaudhry, Anam H. Ke, Eileen Xie, Joan Cooper, Harry Bellacosa, Alfonso Clapper, Margie L. Boman, Bruce M. Zhang, Tao Litwin, Samuel Ross, Eric A. Conrad, Peggy Crowell, James A. Kopelovich, Levy Knudson, Alfred Yeung, Anthony T. TI Searchable high-resolution 2D gel proteome of the human colon crypt SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; colonic crypts; morphologically normal ID ENDOTHELIAL GROWTH-FACTOR; MASS-SPECTROMETRY; COLORECTAL-CANCER; EPITHELIAL-CELLS; GENE ONTOLOGY; C-ABL; MUCOSA; EXPRESSION; PROTEINS; RESOURCE AB We seek alterations in protein patterns at the earliest possible step on the path to cancer, namely, in cells of the target tissue from normal persons versus the corresponding normally appearing cells from persons who are heterozygous for mutation in a tumor suppressor gene that predisposes strongly to carcinoma in that tissue. To begin a systematic comparison of the proteomes of cells from normal and from neoplastic colons, we have undertaken the isolation of human colon crypts that are derived from the normal-appearing mucosa of left ( descending) colon of patients with sporadic colorectal cancer. Two-dimensional (2D) gel electrophoresis is a proteomic approach that excels in the resolution of protein isoforms. Here, we document the practicality of this approach with human samples using gels of three overlapping pH ranges. For the first time, about 800 nonredundant proteins and 900 isoforms from purified human colonic crypts were identified, permitting an assessment of the contributions of protein isoforms. These interactive, searchable, hyperlink-enabled proteome maps and gene ontology analyses will facilitate future studies to discover the earliest markers and intervention targets during progression to colon cancer. C1 Fox Chase Canc Ctr, Div Basic Sci Med Sci & Populat Sci, Philadelphia, PA 19111 USA. Thomas Jefferson Univ, Div Genet & Prevent Med, Philadelphia, PA 19107 USA. Univ Calif San Francisco, UCSF Colorectal Canc Prevent Program, San Francisco, CA 94115 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Yeung, AT (reprint author), Fox Chase Canc Ctr, Div Basic Sci Med Sci & Populat Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM AT_Yeung@fccc.edu FU NCI NIH HHS [P30CA06927, CA119242]; NIDDK NIH HHS [DK063014]; PHS HHS [N01-NC-15103] NR 46 TC 15 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PY 2007 VL 6 IS 6 BP 2232 EP 2238 DI 10.1021/pr060641e PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 173ST UT WOS:000246893500019 PM 17444668 ER PT J AU Wu, WW Wang, G Yu, MJ Knepper, MA Shen, RF AF Wu, Wells W. Wang, Guanghui Yu, Ming-Jiun Knepper, Mark A. Shen, Rong-Fong TI Identification and quantification of basic and acidic proteins using solution-based two-dimensional protein fractionation and label-free or O-18-labeling mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE basic and acidic proteins; solution-based two-dimensional protein fractionation; label-free O-18-labeling; mass spectrometry ID PROTEOMIC ANALYSIS; MAPPING METHOD; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; GEL-ELECTROPHORESIS; GENE-EXPRESSION; YEAST PROTEOME; MALDI-TOF; ION-TRAP; CHROMATOGRAPHY AB Reduction in sample complexity enables more thorough proteomic analysis using mass spectrometry (MS). A solution-based two-dimensional (2D) protein fractionation system, ProteomeLab PF 2D, has recently become available for sample fractionation and complexity reduction. PF 2D resolves proteins by isoelectric point (pI) and hydrophobicity in the first and second dimensions, respectively. It offers distinctive advantages over 2D gel electrophoresis with respects to automation of the fractionation processes and characterization of proteins having extreme pIs. Besides fractionation, PF 2D is equipped with built-in UV detectors intended for relative quantification of proteins in contrasting samples using its software tools. In this study, we utilized PF 2D for the identification of basic and acidic proteins in mammalian cells, which are generally under-characterized. In addition, mass spectrometric methods (label-free and O-18-labeling) were employed to complement protein quantification based on UV absorbance. Our studies indicate that the selection of chromatographic fractions could impact protein identification and that the UV-based quantification for contrasting complex proteomes is constrained by coelution or partial coelution of proteins. In contrast, the quantification post PF 2D chromatography based on label-free or O-18-labeling mass spectrometry provides an alternative platform for basic/acidic protein identification and quantification. With the use of HCT116 colon carcinoma cells, a total of 305 basic and 183 acidic proteins was identified. Quantitative proteomics revealed that 17 of these proteins were differentially expressed in HCT116 p53-/- cells. C1 NIH, NHLBI, Proteom Core Facil, Bethesda, MD 20892 USA. NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Shen, RF (reprint author), NIH, NHLBI, Bldg 10,Rm 8C103C,10 Ctr Dr, Bethesda, MD 20892 USA. EM shenr@nhlbi.nih.gov OI YU, MING-JIUN/0000-0003-0393-4696 FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 38 TC 21 Z9 21 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PY 2007 VL 6 IS 7 BP 2447 EP 2459 DI 10.1021/pr060621c PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 186QD UT WOS:000247792300004 PM 17506541 ER PT J AU Marques-Deak, AH Lotufo, F Dominguez, WV Solis, AC Kurcgant, D Sato, F Ross, JM Prado, EBA AF Marques-Deak, A. H. Lotufo Neto, F. Dominguez, W. V. Solis, A. C. Kurcgant, D. Sato, F. Ross, J. M. Prado, E. B. A. TI Cytokine profiles in women with different subtypes of major depressive disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; major depressive disorder; stress; cortisol; hypothalamic-pituitary-adrenal axis; cytokines ID NECROSIS-FACTOR-ALPHA; PLASMA-LEVELS; MULTIPLE-SCLEROSIS; IMMUNE; NEUROTRANSMISSION; ANTIDEPRESSANTS; ENDOCRINE; DYSTHYMIA; PATTERNS; CORTISOL AB Background: Depression has been associated with activation of the immune system. Some studies have shown increased levels of pro-inflammatory cytokines in patients with major depressive disorder (MDD), but conflicting results also have been described. Methods: Forty-six unmedicated women with MDD were classified in subgroups (melancholic vs. non-melancholic; acute vs. chronic; severe vs. moderate, and episodic vs. recurrent presentations) and compared with 41 healthy controls. Evaluations of serum IL-1 beta, IL-6, IFN-gamma and cortisol were performed on both groups. Patients were evaluated prior and after antidepressant treatment. Results: The sub-classification of depression did not predict differences in cytokine levels. Patients currently depressed had similar levels of cytokines and cortisol as healthy controls. After remission of the symptoms, patients with MDD evolved with enhancement of cytokine levels, but no differences were observed in cortisol levels. Limitations: In patient treatment, two different classes of antidepressants were applied. The dexamethasone/CRH test was not performed to evaluate the HPA axis. Conclusions: Out-patient women diagnosed with MDD exhibited normal levels of both cortisol and cytokines before treatment, yet demonstrated an increase in cytokines after antidepressant treatment. In some patients with MDD, the presence of acute stress due to hospitalization may indeed contribute and justify the usual finding of higher levels in both cortisol and cytokines. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Dept Stomatol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Dept Nephrol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. RP Marques-Deak, AH (reprint author), NIMH, 5625 Fischer Lane,Room 4N13,MSC-9401, Rockville, MD 20852 USA. EM deaka@mail.nih.gov RI Ross, Jaime/A-6893-2012; Solis, Ana Cristina/G-2708-2012; Lotufo-Neto, Francisco/D-3982-2014; OI , Ana Cristina/0000-0003-1746-4912 NR 38 TC 60 Z9 61 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN-FEB PY 2007 VL 41 IS 1-2 BP 152 EP 159 DI 10.1016/j.jpsychires.2005.11.003 PG 8 WC Psychiatry SC Psychiatry GA 115BO UT WOS:000242709800019 PM 16375926 ER PT J AU Beckjord, E Compas, BE AF Beckjord, Ellen Compas, Bruce E. TI Sexual quality of life in women with newly diagnosed breast cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE breast cancer; chemotherapy; sexual quality of life; physical quality of life ID SURVIVORS; DYSFUNCTION; OUTCOMES; HEALTH; CHEMOTHERAPY; ADJUSTMENT; TAMOXIFEN; SURGERY; IMPACT AB Sexual quality of life (QOL) is a significant concern for breast cancer survivors.-This study investigated sexual quality of life in a sample of 191 newly diagnosed breast cancer patients. Sixty percent of the sample indicated disruption in their sexual quality of life. Sexual QOL during treatment was significantly more disrupted among women who received chemotherapy, were younger, had higher stage of disease, reported more depressive symptoms near time of diagnosis, and underwent a total mastectomy. Hierarchical linear regression was used to model sexual QOL and feelings of sexual attractiveness. Worse physical quality of life, chemotherapy, and depressive symptoms near time of diagnosis were associated with worse sexual QOL during treatment. An interaction between chemotherapy status and type Of Surgery, for feelings of sexual attractiveness, suggested that chemotherapy affected sexual attractiveness only among women who underwent a lumpectomy. These results add to growing evidence that sexual QOL is a multidimensional construct with aspects differentially affected by variables related to cancer survivorship. C1 DCCPS, Canc Prevent Fellowship Program, NCI, DHHS,NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37203 USA. Univ Vermont, Burlington, VT 05405 USA. RP Beckjord, E (reprint author), DCCPS, Canc Prevent Fellowship Program, NCI, DHHS,NIH, 6130 Execut Blvd,4051A,MSC 7365, Bethesda, MD 20892 USA. EM beckjore@mail.nih.gov FU NCI NIH HHS [R01 CA67936] NR 30 TC 19 Z9 22 U1 1 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2007 VL 25 IS 2 BP 19 EP 36 DI 10.1300/8077v2502_02 PG 18 WC Psychology, Social SC Psychology GA 181CV UT WOS:000247415400002 PM 17613483 ER PT J AU Wiener, LS Steffen-Smith, E Fry, T Wayne, AS AF Wiener, Lori S. Steffen-Smith, Emilie Fry, Terry Wayne, Alan S. TI Hematopoietic stem cell donation in children: A review of the sibling donor experience SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Review DE hematopoietic stem cell transplantation; bone marrow and peripheral blood stem cell transplantation; pediatric sibling donors; psychosocial adjustment ID BONE-MARROW-TRANSPLANTATION; PEDIATRIC CANCER-PATIENTS; QUALITY-OF-LIFE; PERIPHERAL-BLOOD; ALLOGENEIC TRANSPLANTATION; PSYCHOLOGICAL ADJUSTMENT; PSYCHOSOCIAL-ASPECTS; G-CSF; COLLECTION; RISKS AB Hematopoietic Stein Cell Transplant (HSCT) represents the second most frequent major organ transplant In the United States. Compared with other family members, siblings are more likely to be immunologically matched with the recipient and therefore are often the most suitable donors. Due to a dearth of information on the positive and adverse effects of HSCT on pediatric sibling donors, we sought to examine available data. Eight Published reports assessing the pediatric sibling donor experience were identified in the literature. Studies were predominately small (n < 44.) and cross-sectional. Results suggest a range of psychological distress responses with higher distress in pediatric donor than non-donor siblings. Recommendations include future longitudinal research on sibling donor psychosocial adjustment, identification of sibling donors at high risk for maladaptive responses. and development of educational and psychosocial interventions for this overlooked pediatric population. C1 NCI, Pediat Psychol Support & Res Program, SE Pediat Clin 1, Bethesda, MD 20892 USA. NCI, Hematol Dis Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wiener, LS (reprint author), NCI, Pediat Psychol Support & Res Program, SE Pediat Clin 1, 9000 Rockville Pike Bldg 10,Room 6466, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov; steffene@mail.nih.gov; fryt@mail.nih.gov; waynea@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 47 TC 21 Z9 21 U1 1 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2007 VL 25 IS 1 BP 45 EP 66 DI 10.1300/J077v25n01_03 PG 22 WC Psychology, Social SC Psychology GA 155VT UT WOS:000245607300003 PM 17360315 ER PT J AU Simons-Morton, B AF Simons-Morton, Bruce TI Parent involvement in novice teen driving: Rationale, evidence of effects, and potential for enhancing graduated driver licensing effectiveness SO JOURNAL OF SAFETY RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Novice Teen Driving, GDL and Beyond CY FEB 05-07, 2007 CL Tucson, AZ SP Natl Safety Council DE graduated driver licensing; teen driving; motor-vehicles; youths; delayed licensure ID MOTOR-VEHICLE CRASHES; CHECKPOINTS PROGRAM; 16-YEAR-OLD DRIVERS; BRIEF INTERVENTION; LEARNER DRIVERS; RISK; RESTRICTIONS; EXPERIENCE; PASSENGERS; EDUCATION AB Motor-vehicle crash rates are highly elevated immediately after licensure and then decline gradually over a period of years. Young age, risk taking, and inexperience contribute to the problem, but inexperience is particularly important early on. Driving is like other complex, skilled behaviors in which subtle improvements in perception and judgment develop gradually over a period of years. After all, safe driving is more a matter of attention and perception than physical management of the vehicle. Inexperience is particularly linked to driving performance and safety outcomes under certain driving conditions, with driving at night and with teen passengers as the most important cases. Surprisingly, driving outcomes do not appear to be affected by the pre-license training or supervised practice driving. Given the limits of training, safety effects can best be achieved by countermeasures that delay licensure or limit novice teen driving under high risk driving conditions while novices gain experience and develop safety competence. The two complementary approaches of Graduated Driver Licensing policies and parent management have been shown to provide safety effects by limiting the driving conditions of novice teenagers. (C) 2007 National Safety Council and Elsevier Ltd. All rights reserved. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z01 HD001707-09, Z99 HD999999] NR 74 TC 37 Z9 37 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4375 J9 J SAFETY RES JI J. Saf. Res. PY 2007 VL 38 IS 2 BP 193 EP 202 DI 10.1016/j.jsr.2007.02.007 PG 10 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 172QO UT WOS:000246819200011 PM 17478190 ER PT J AU Mahoney, S Zarate, C AF Mahoney, Sheila Zarate, Carlos, Jr. TI Persistent sexual arousal syndrome: A case report and review of the literature SO JOURNAL OF SEX & MARITAL THERAPY LA English DT Article ID DYSFUNCTION; PRIAPISM; WOMEN; HYPERSEXUALITY; DEPRESSION; PREVALENCE; FLUOXETINE; QUETIAPINE; TRAZODONE; BUPROPION AB This article describes a case of persistent sexual arousal syndrome (PSAS) seen by the Gynecology Consult Service of the National Institutes of Health. This syndrome was first described in 2001 and is characterized by excessive and unrelenting sexual arousal in the absence of desire. PSAS has only recently come to the attention of the health care community, and its prevalence in the population is not completely known. It is important to report cases of this syndrome in order to help clarify its prevalence, etiology, and prognosis and to determine possible methods of treatment. C1 NICHD, RBMB, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Mahoney, S (reprint author), NICHD, RBMB, NIH, Bldg 10 CRC E,Rm 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM mahoneys@mail.nih.gov FU Intramural NIH HHS NR 29 TC 22 Z9 23 U1 1 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 0092-623X J9 J SEX MARITAL THER JI J. Sex Marital Ther. PD JAN-FEB PY 2007 VL 33 IS 1 BP 65 EP 71 DI 10.1080/00926230600998532 PG 7 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 126PG UT WOS:000243526200007 PM 17162489 ER PT J AU Orme, AM Yao, H Etzkorn, LH AF Orme, Anthony M. Yao, Haining Etzkorn, Letha H. TI Indicating ontology data quality, stability, and completeness throughout ontology evolution SO JOURNAL OF SOFTWARE MAINTENANCE AND EVOLUTION-RESEARCH AND PRACTICE LA English DT Article DE ontology completeness metrics; ontology stability metrics; ontology complexity metrics; ontology cohesion metrics ID OBJECT-ORIENTED METRICS; VALIDATION; SYSTEM; SUITE AB Many application areas today make use of ontologies. With the advent of semantic Web technologies, ontology based systems have become widespread. Developing an ontology is part of the necessary early development of an ontology-based system. Since the validity and quality of the ontology data directly affects the validity and quality of the system using the ontology, evolution of the ontology data directly affects the evolution and/or maintenance of the ontology-based systems that depend on and employ the ontology data. Our research examines the quality, completeness, and stability of ontology data as ontologies evolve. We propose a metrics suite, based on standard software quality concepts, to measure the complexity and cohesion of ontology data. First we theoretically validate our metrics. Then we examine empirically whether our metrics determine ontology data quality, by comparing them to human evaluator ratings. We conclude that several of our metrics successfully determine ontology complexity or cohesion. Finally, we examine, over evolving ontology data, whether our metrics determine ontology completeness and stability. We determine that various metrics reflect different kinds of changes. Our experiments indicate our metrics' measure ontology stability and completeness; however, interpretation of specific metrics values and the interaction of different metrics requires further study. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Athens State Univ, Athens, AL 35611 USA. NIH, Natl Lib Med, Bethesda, MD 20894 USA. Univ Alabama, Huntsville, AL 35899 USA. RP Orme, AM (reprint author), Athens State Univ, Athens, AL 35611 USA. EM tony.orme@athens.edu NR 24 TC 13 Z9 14 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1532-060X EI 2047-7481 J9 J SOFTW MAINT EVOL-R JI J. Softw. Maint. Evol.-Res. Pract. PD JAN-FEB PY 2007 VL 19 IS 1 BP 49 EP 75 DI 10.1002/smr.341 PG 27 WC Computer Science, Software Engineering SC Computer Science GA 141NP UT WOS:000244585900003 ER PT J AU Heymann, JB Belnap, DM AF Heymann, J. Bernard Belnap, David M. TI Bsoft: Image processing and molecular modeling for electron microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE single particle analysis; tomography; three-dimensional image reconstruction; distributed processing; image processing workflow ID HERPES-SIMPLEX-VIRUS; 3-DIMENSIONAL RECONSTRUCTION; CRYOELECTRON MICROSCOPY; BIOLOGICAL MACROMOLECULES; DATABASE; CRYOTOMOGRAPHY; MICROGRAPHS; ORIENTATIONS; INFORMATION; HANDEDNESS AB Bsoft is a software package written for image processing of electron micrographs, interpretation of reconstructions, molecular modeling, and general image processing. The code is modularized to allow for rapid testing and deployment of new processing algorithms, while also providing sufficient infrastructure to deal with many file formats and parametric data. The design is deliberately open to allow interchange of information with other image and Molecular processing software through a standard parameter file (Currently a text-based encoding Of parameters in the STAR Format) and its support of multiple image and molecular formats. It also allows shell scripting of processes and allows subtasks to be distributed across multiple computers for Concurrent processing. Bsoft has undergone many modifications and advancements since its initial release [Heymann, J.B., 2001. Bsoft: image and Molecular processing in electron microscopy. J. StrUCt. Biol. 133, 156-169]. Much of the emphasis is oil single particle analysis and tomography, and sufficient functionality is available in the package to support most needed operations for these techniques. The key graphical user interface is the program bshow, which displays an image and is used for many interactive purposes Such as fitting the contrast transfer function or picking particles. Bsoft also offers various tools to manipulate atomic structures and to refine the fit of a known molecular structure to a density in a reconstruction. Published by Elsevier Inc. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. RP Heymann, JB (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM Bernard_Heymann@nih.gov RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 NR 40 TC 231 Z9 232 U1 2 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2007 VL 157 IS 1 BP 3 EP 18 DI 10.1016/j.jsb.2006.06.006 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 124SV UT WOS:000243391100002 PM 17011211 ER PT J AU Dawson, DA Grant, BF Chou, SP Stinson, FS AF Dawson, Deborah A. Grant, Bridget F. Chou, S. Patricia Stinson, Frederick S. TI The impact of partner alcohol problems on women's physical and mental health SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID USE DISORDER CRITERIA; DRUG-USE; EMERGENCY-DEPARTMENT; POPULATION SAMPLE; SUBSTANCE USE; RISK-FACTORS; AUDADIS-ADR; US COUPLES; VIOLENCE; ABUSE AB Objective: The purpose of this study was to examine the association between partner alcohol problems and selected physical and mental health outcomes among married or cohabiting women, before and after adjusting for potential confounders, and to compare these associations with those reflecting the impact of the women's own alcohol-use disorders (AUDs). Method: This analysis is based on data from the Wave 1 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of U.S. adults 18 years of age and older. The analytic sample consisted of 11,683 married or cohabiting women. Classification of their own AUDs was based on self-report of symptoms operationalizing the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for alcohol abuse or dependence. Current partner alcohol problems were identified by the women after an explanation that recapitulated the essence of these criteria. Physical health measures included criminal victimization of any type, injury, emergency-department and hospital visits, self-reported fair or poor health, and Short Form-12 Health Survey Questionnaire, Version 2 (SF- 12v2). -based physical quality of life. Mental health measures included DSM-IV mood and anxiety disorders, number of past-year stressors, and SF- 12v2-based mental/psychological quality of life. All measures refer to the 12 months immediately preceding the interview. Associations were tested using bivariate and multivariate logistic and linear regression models. Results: At the bivariate level, women whose partners had alcohol problems were more likely to experience victimization, injury, mood disorders, anxiety disorders, and being in fair or poor health than women whose partners did not have alcohol problems (odds ratio [OR]: 1.7-4.5). They also experienced more life stressors and had lower mental/psychological quality-of-life scores. All but one of these differences remained significant after adjusting for potential confounders, which included the significantly greater rates of substance use and AUDs among women whose partners had alcohol problems. Although the magnitudes of the ORs decreased after adjustment (adjusted OR [AOR]: 2.1-3.4), they generally exceeded the AORs associated with the women's own AUDs. Conclusions: Partner alcohol problems pose diverse health threats for women that go beyond their well-documented association with domestic violence. Mood, anxiety, stress, general health, and quality-of-life problems should be addressed by groups that provide couples' treatment or counseling to female partners of alcoholics. C1 NIAAA, Div Intramural Clin & Biol Res, NIH, LEB, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Div Intramural Clin & Biol Res, NIH, LEB, Room 3071,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@gmail.nih.gov FU Intramural NIH HHS NR 71 TC 45 Z9 45 U1 3 U2 11 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JAN PY 2007 VL 68 IS 1 BP 66 EP 75 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 199RJ UT WOS:000248712600009 PM 17149519 ER PT J AU Dinc, S Ozbirecikli, B Kuru, B Gulcelik, MA Ustun, H Alagol, H Oz, M AF Dinc, Soykan Ozbirecikli, Bulent Kuru, Bekir Gulcelik, Mehmet Ali Ustun, Huseyin Alagol, Haluk Oz, Murat TI Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE granulocyte-macrophage colony stimulating factor; dimethylhydrazine; colon cancer; free radicals; nitric oxide ID INHIBITS TUMOR-GROWTH; NITRIC-OXIDE; GM-CSF; COLORECTAL-CANCER; HYDRAZINE DERIVATIVES; CHRONIC INFLAMMATION; ANTITUMOR IMMUNITY; ANTIOXIDANT STATUS; REACTIVE OXYGEN; FACTOR AUGMENTS AB Background and Objectives: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. Methods: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 mu g/kg GM-CSF (n = 30), and DMH +12 mu g/kg (n = 30) GM-CSF. Results: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 812, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GMCSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). Conclusions: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects. C1 NIDA, DHHS, Intamural Res Program, Cellular Neurobiol Sect, Baltimore, MD 21224 USA. Oncol Training & Res Hosp, Dept Gen Surg, Ankara, Turkey. Ankara Training & Res Hosp, Dept Pathol, Ankara, Turkey. RP Oz, M (reprint author), NIDA, DHHS, Intamural Res Program, Cellular Neurobiol Sect, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 51 TC 1 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JAN 1 PY 2007 VL 95 IS 1 BP 12 EP 21 DI 10.1002/jso.20540 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 126ND UT WOS:000243518700006 PM 17192887 ER PT J AU Chumbler, NR Mkanta, WN Richardson, LC Harris, L Darkins, A Kobb, R Ryan, P AF Chumbler, Neale R. Mkanta, William N. Richardson, Lisa C. Harris, Linda Darkins, Adam Kobb, Rita Ryan, Patricia TI Remote patient-provider communication and quality of life: empirical test of a dialogic model of cancer care SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID FUNCTIONAL ASSESSMENT; FACT-G; SCALE; PILOT; COORDINATION; TECHNOLOGY; VALIDATION; DISTRESS AB We examined the feasibility of a Cancer Care Dialogues Model, with daily telehealth interactions between patients at home and their care coordinator, who acted as an adjunct to the oncologist. The patient and the care coordinator used a home messaging device, connected via the ordinary telephone network. Thirty-four patients with a new diagnosis of cancer and whose treatment plan included chemotherapy taken at a single clinic were enrolled and followed for six months. The home messaging device collected information daily on common symptoms associated with chemotherapy. On average, the patients had the home messaging device for 120 days (range 30-180). The mean cooperation rate was 84% (range 4-100). No variables were significantly associated with patient cooperation in the dialogues over time. The health-related quality of life (HRQL) mean score at baseline was 73.9 (SD 15.4), and the mean score at six months was 78.4 (SD 14.5). After adjusting for demographic and clinical factors, there was a 6.5-point increase in HRQL score between the baseline and end of treatment, which represented an important clinical difference. Management of nervousness/worry over time through cancer care dialogues is important in maintaining HRQL and can be assisted by remote home messaging. C1 N Florida S Georgia Vet Hlth Syst, VA HSR&D RR&D, Rehabil Outcomes Res Ctr 151B, Gainesville, FL 32608 USA. Univ Florida, Dept Hlth Serv Res Management & Policy, Gainesville, FL USA. Ctr Dis Control, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. Dept Vet Affairs, Vet Hlth Adm, Off Care Coordinat, Washington, DC USA. RP Chumbler, NR (reprint author), N Florida S Georgia Vet Hlth Syst, VA HSR&D RR&D, Rehabil Outcomes Res Ctr 151B, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM Neale.Chumbler@med.va.gov NR 21 TC 8 Z9 8 U1 1 U2 7 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2007 VL 13 IS 1 BP 20 EP 25 DI 10.1258/135763307779701112 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 135WC UT WOS:000244183600005 PM 17288654 ER PT J AU Kong, HH Cowen, EW Azad, NS Dahut, W Gutierrez, M Turner, ML AF Kong, Heidi H. Cowen, Edward W. Azad, Nilofer S. Dahut, William Gutierrez, Martin Turner, Maria L. TI Keratoacanthomas associated with sorafenib therapy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. OI Kong, Heidi/0000-0003-4424-064X FU Intramural NIH HHS [Z99 CA999999] NR 3 TC 60 Z9 62 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2007 VL 56 IS 1 BP 171 EP 172 DI 10.1016/j.jaad.2006.10.032 PG 2 WC Dermatology SC Dermatology GA 124AL UT WOS:000243339100032 PM 17190642 ER PT J AU Baum, BJ AF Baum, Bruce J. TI Inadequate training in the biological sciences and medicine for rental students - An impending crisis for denistry SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material ID DENTISTRY; THERAPY; CONNECTION; TRENDS C1 Natl Inst Dent & Craniofacial Res, Gene Transfer Sect, Gene Therapy & Therapeut Branch, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Transfer Sect, Gene Therapy & Therapeut Branch, NIH,US Dept Hlth & Human Serv, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS NR 27 TC 24 Z9 25 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2007 VL 138 IS 1 BP 16 EP + PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 127PI UT WOS:000243598400002 PM 17197393 ER PT J AU Lang, I Guralnik, J Wallace, RB Melzer, D AF Lang, Iain Guralnik, Jack Wallace, Robert B. Melzer, David TI What level of alcohol consumption is hazardous for older people? Functioning and mortality in US and English national cohorts SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE moderate drinking; alcohol consumption; functioning; mortality ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; DRINKING; METAANALYSIS; ADULTS; COMORBIDITY; DISABILITY; EXCLUSION; PATTERN AB OBJECTIVES: To estimate disability plus mortality risks in older people according to level of alcohol intake. DESIGN: Two population-based cohort studies. SETTING: The Health and Retirement Study (United States) and the English Longitudinal Study of Aging (England). PARTICIPANTS: Thirteen thousand three hundred thirty-three individuals aged 65 and older followed for 4 to 5 years. MEASUREMENTS: Difficulties with activities of daily living (ADLs), instrumental activities of daily living (IADLs), poor cognitive function, and mortality. RESULTS: One-tenth (10.8%) of U.S. men, 28.6% of English men, 2.9% of U.S. women, and 10.3% of English women drank more than the U.S. National Institute on Alcohol Abuse and Alcoholism recommended limit for people aged 65 and older. Odds ratios (ORs) of disability, or disability plus mortality, in subjects drinking an average of more than one to two drinks per day were similar to ORs in subjects drinking an average of more than none to one drink per day. For example, those drinking more than one to two drinks per day at baseline had an OR of 1.0 (95% confidence interval (CI)=0.8-1.2) for ADL problems, 0.7 (95% CI=0.6-1.0) for IADL problems, and 0.8 (95% CI=0.6-1.1) for poor cognitive function. Findings were robust across alternative models. The shape of the relationship between alcohol consumption and risk of disability was similar in men and women. CONCLUSION: Functioning and mortality outcomes in older people with alcohol intakes above U.S. recommended levels for the old but within recommendations for younger adults are not poor. More empirical evidence of net benefit is needed to support screening and intervention efforts in community-living older people with no specific contraindications who drink more than one to two drinks per day. C1 Peninisula Med Sch, Epidemiol & Publ Hlth Grp, Exeter EX2 5DW, Devon, England. NIA, Epidemiol & Demog Sect, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. RP Melzer, D (reprint author), Peninisula Med Sch, Epidemiol & Publ Hlth Grp, Rd & E Hosp Site,Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk RI Lang, Iain/B-8255-2008; OI Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS; NIA NIH HHS [R03-AG022912-01, U01 AG009740] NR 49 TC 62 Z9 63 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2007 VL 55 IS 1 BP 49 EP 57 DI 10.1111/j.1532-5415.2006.01007.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 126IV UT WOS:000243507500007 PM 17233685 ER PT J AU Shumway-Cook, A Guralnik, JM Phillips, CL Coppin, AK Ciol, MA Bandinelli, S Ferrucci, L AF Shumway-Cook, Anne Guralnik, Jack M. Phillips, Caroline L. Coppin, Antonia K. Ciol, Marcia A. Bandinelli, Stefania Ferrucci, Luigi TI Age-associated declines in complex walking task performance: The Walking InCHIANTI Toolkit SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mobility; aging; performance-based measures ID LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; COMMUNITY MOBILITY; SUBSEQUENT DISABILITY; FALLS; GAIT; BALANCE; YOUNG; RISK; PREDICTORS AB OBJECTIVES: To describe a set of complex walking tasks (CWTs) that can be used to evaluate mobility and to characterize age- and sex-specific performance on these tests. DESIGN: A population-based study of persons living in the Chianti geographic area (Tuscany, Italy). SETTING: Community. PARTICIPANTS: One thousand two hundred twenty-seven persons (aged 20-95) selected from the city registries of Greve and Bagno a Ripoli (Tuscany, Italy). MEASUREMENTS: Gait velocity (m/s) was measured during 13 walking tests (Walking InCHIANTI Toolkit (WIT)) used to examine walking ability under a range of conditions and distances. Other measures included performance on the Short Physical Performance Battery and self-reported health and functional status, including disability in activities of daily living. RESULTS: Age-associated differences on the WIT were reflected in the number of older adults unable to complete CWTs and a decrease in gait velocity. For all tasks, decrements in walking speed with increasing age were significantly larger at aged 65 and older. Performance on CWTs was highly variable and could not be explained by usual gait speed measured under low-challenge conditions alone. CONCLUSION: CWTs may provide important insight into mobility function, particularly in persons with normal or near-normal usual gait speed. Further research is needed to elucidate the specific physiological mechanisms that contribute to declining performance on CWT with increasing age. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Geriatr Rehabil Unit, Florence, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Shumway-Cook, A (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. EM ashumway@u.washington.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413]; NIMHD NIH HHS [R01 MD009164] NR 34 TC 83 Z9 84 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2007 VL 55 IS 1 BP 58 EP 65 DI 10.1111/j.1532-5415.2006.00962.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 126IV UT WOS:000243507500008 PM 17233686 ER PT J AU Rhoades, DA Welty, TK Wang, WY Yeh, F Devereux, RB Fabsitz, RR Lee, ET Howard, BV AF Rhoades, Dorothy A. Welty, Thomas K. Wang, Wenyu Yeh, Fawn Devereux, Richard B. Fabsitz, Richard R. Lee, Elisa T. Howard, Barbara V. TI Aging and the prevalence of cardiovascular disease risk factors in older American Indians: The Strong Heart Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cardiovascular disease risk factors; epidemiology; Indians; North American; aging; cholesterol; diabetes mellitus; hypertension; smoking; longitudinal study; cohort study ID ALL-CAUSE; EPIDEMIOLOGIC TRANSITION; INSULIN-RESISTANCE; SMOKING-CESSATION; DIABETES TRENDS; ALASKA NATIVES; LIPID LEVELS; WOMEN; POPULATION; MORTALITY AB OBJECTIVES: To describe longitudinal changes in the prevalence of major cardiovascular disease (CVD) risk factors in aging American Indians. DESIGN: Population-based ongoing epidemiological study. SETTING: The Strong Heart Study is a study of CVD and its risk factors. Standardized examinations were repeated in 1993 to 1995 and again in 1997 to 1999. PARTICIPANTS: A diverse cohort of 4,549 American Indians aged 45 to 74 at the initial examinations in 1989 to 1991. MEASUREMENTS: Changes in the prevalence of hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), current smoking, and type 2 diabetes mellitus. RESULTS: The prevalence of hypertension rose rapidly and steadily with aging. A nonsignificant decrease in LDL-C was seen in men, and men and women initially had rapid increases in the prevalence of low HDL-C. The prevalence of smoking decreased, but the prevalence of diabetes mellitus continued to rise for men and women. CONCLUSION: Overall, unfavorable changes in CVD risk factors were seen in the aging participants and will likely be reflected in worsening morbidity and mortality. C1 Univ Colorado, Hlth Sci Ctr, Native Elder Res Ctr, Denver, CO 80202 USA. Grp Hlth Permanente, Seattle, WA USA. Missouri Breaks Res Inc, Timber Lake, SD USA. Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Cornell Univ, Cornell Med Ctr, New York Hosp, Ithaca, NY 14853 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Medstar Res Inst, Washington, DC USA. RP Rhoades, DA (reprint author), 4034 30th Ave W, Seattle, WA 98199 USA. EM drhoades@myuw.net FU AHRQ HHS [P01 HS10854]; NHLBI NIH HHS [U01-HL41642, U01-HL41654, U01-HL41652, 1 R01 HL-67031]; NIA NIH HHS [1P30 AG/NE15292] NR 48 TC 29 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2007 VL 55 IS 1 BP 87 EP 94 DI 10.1111/j.1532-5415.2006.01018.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 126IV UT WOS:000243507500012 PM 17233690 ER PT J AU Jackson, SN Wang, HYJ Woods, AS AF Jackson, Shelley N. Wang, Hay-Yan J. Woods, Amina S. TI In situ structural characterization of glycerophospholipids and sulfatides in brain tissue using MALDI-MS/MS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; TANDEM MASS-SPECTROMETRY; EARLY ALZHEIMERS-DISEASE; FAST-ATOM-BOMBARDMENT; ELECTROSPRAY-IONIZATION; FRAGMENTATION PROCESSES; CHARGE-REMOTE; PHOSPHOLIPIDS; LIPIDOMICS; PHOSPHATIDYLETHANOLAMINE AB Lipids are major structural components of biomembranes. Negatively charged species such as phosphatidylinositol, phosphatidylserine, sulfatides, and the zwitterionic phosphatidylethanolamines are major components of the cytoplasmic surface of the cellular membrane lipid bilayer and play a key role in several receptors signaling functions. Lipids are not just involved in metabolic and neurological diseases; negatively charged lipids in particular play crucial roles in physiological events such as signal transduction, receptors, and enzymatic activation, as well as storage and release of therapeutic drugs and toxic chemicals in the body. Due to the importance of their role in signaling, the field of lipidomics has rapidly expanded in recent years. In the present study, direct probing of tissue slices with negative ion mode matrix assisted laser desorption/ionization mass spectrometry was employed to profile the distribution of lipids in the brain. In total, 32 lipid species consisting of phosphatidylethanolamines, phosphatidylglycerol, phosphatidylinositols, phosphatidylserines, and sulfatides were assigned. To confirm the structure of lipid species, MALDI-MS/MS analysis was conducted. Product-ion spectra obtained in negative ion mode allow for the assignment of the head groups and the fatty acid chains for the lipid species. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS NR 38 TC 81 Z9 82 U1 5 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JAN PY 2007 VL 18 IS 1 BP 17 EP 26 DI 10.1016/j.jasms.2006.08.015 PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 129EV UT WOS:000243712200003 PM 17005416 ER PT J AU Kamijo, Y Hora, K Nakajima, T Kono, K Takahashi, K Ito, Y Higuchi, M Kiyosawa, K Shigematsu, H Gonzalez, FJ Aoyama, T AF Kamijo, Yuji Hora, Kazuhiko Nakajima, Tarnie Kono, Keiichi Takahashi, Kyoko Ito, Yuki Higuchi, Makoto Kiyosawa, Kendo Shigematsu, Hidekazu Gonzalez, Frank J. Aoyama, Toshifumi TI Peroxisome proliferator-activated receptor alpha protects against glomerulonephritis induced by long-term exposure to the plasticizer di-(2-ethylhexyl)phthalate SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE GENE; PPAR-ALPHA; DI(2-ETHYLHEXYL) PHTHALATE; METABOLIZING ENZYMES; LIPID-PEROXIDATION; OXIDATIVE STRESS; MESANGIAL CELLS; MICE LACKING; EXPRESSION; DISEASE AB Safety concerns about di-(2-ethylhexyl)phthalate (DEHP), a plasticizer and a probable endocrine disruptor, have attracted considerable public attention, but there are few studies about long-term exposure to DEHP. DEHP toxicity is thought to involve peroxisome proliferator-activated receptor a (PPAR alpha), but this contention remains controversial. For investigation of the long-term toxicity of DEHP and determination of whether PPAR alpha mediates toxicity, wild-type and PPAR alpha-null mice were fed a diet that contained 0.05 or 0.01% DEHP for 22 mo. PPAR alpha-null mice that were exposed to DEHP exhibited prominent immune complex glomerulortephritis, most likely related to elevated glomerular oxidative stress. Elevated NADPH oxidase, low antioxidant enzymes, and absence of the PPAR alpha-dependent anti-inflammatory effects that normally antagonize the NF kappa B signaling pathway accompanied the glomerulonephritis in PPAR alpha-null mice. The results reported here indicate that PPAR alpha protects against the nephrotoxic effects of long-term exposure to DEHP. C1 Shinshu Univ, Sch Med, Dept Metab Regulat, Inst Aging & Adaptat, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Internal Med, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Pathol, Matsumoto, Nagano 3908621, Japan. Nagoya Univ, Dept Occupat & Environm Med, Grad Sch Med, Nagoya, Aichi, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Kamijo, Y (reprint author), Shinshu Univ, Sch Med, Dept Metab Regulat, Inst Aging & Adaptat, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM yujibeat@hsp.md.shinshu-u.ac.jp RI Ito, Yuki/C-3698-2008 NR 46 TC 22 Z9 23 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2007 VL 18 IS 1 BP 176 EP 188 DI 10.1681/ASN.2006060597 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 126TG UT WOS:000243537800021 PM 17135395 ER PT J AU Fried, LF Biggs, ML Shlipak, MG Seliger, S Kestenbaum, B Stehman-Breen, C Sarnak, M Siscovick, D Harris, T Cauley, J Newman, AB Robbins, J AF Fried, Linda F. Biggs, Mary Louise Shlipak, Michael G. Seliger, Stephen Kestenbaum, Bryan Stehman-Breen, Catherine Sarnak, Mark Siscovick, David Harris, Tamara Cauley, Jane Newman, Anne B. Robbins, John TI Association of kidney function with incident hip fracture in older adults SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CYSTATIN-C; CARDIOVASCULAR HEALTH; SERUM CREATININE; ELDERLY PERSONS; RENAL-DISEASE; RISK; HOMOCYSTEINE; OSTEOPOROSIS; FAILURE AB Kidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95% Cl 1.01, 1.33) but not in men (HR 1.14; 95% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk. C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Div Geriatr, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA. Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. Univ Washington, Sch Med, Div Nephrol, Seattle, WA USA. Amgen Inc, Thousand Oaks, CA USA. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. RP Fried, LF (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Univ Dr C,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM linda.fried@med.va.gov RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086] NR 25 TC 90 Z9 90 U1 1 U2 7 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2007 VL 18 IS 1 BP 282 EP 286 DI 10.1681/ASN.2006050546 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 126TG UT WOS:000243537800031 PM 17167115 ER PT J AU Olney, CA Warner, DG Reyna, G Wood, FB Siegel, ER AF Olney, Cynthia A. Warner, Debra G. Reyna, Greysi Wood, Fred B. Siegel, Elliot R. TI MedlinePlus and the challenge of low health literacy: findings from the Colonias project SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID CHRONIC DISEASE; MEXICO BORDER; CARE AB Objective: To explore the potential of a community-based health information outreach project to overcome problems associated with health literacy in low-income Hispanic communities along the Texas-Mexico border. Methods: Using a train-the-trainer approach, community outreach workers known as promotoras were trained by a health information outreach team to search English and Spanish versions of MedlinePlus. These 15 proinotoras submitted written examples on a weekly basis of the topics they helped residents explore on MedlinePlus and the ways in which the residents used the information. These weekly reports, along with verbal interviews with promotoras and others in the communities, allowed development of a database of 161 incidents ("stories") demonstrating how community residents used MedlinePlus. These stories were thematically analyzed to explore how the program benefited participants. Results: The database of stories included examples of community residents becoming better informed about their illnesses, resolving to visit doctors, making decisions about recommended treatments, reducing their anxiety about health conditions, committing to healthy or preventive behavior, and assisting family members. Conclusion: With the help of paraprofessionals like promotoras, community-based health information outreach projects may improve the ability of community residents to understand their health conditions and to participate actively in their health care. C1 CO Evaluat Consulting LLC, Greensboro, NC 27404 USA. Univ Texas, Hlth Sci Ctr, Reg Acad Hlth Ctr, Harlingen, TX 78550 USA. Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. RP Olney, CA (reprint author), CO Evaluat Consulting LLC, POB 4891, Greensboro, NC 27404 USA. EM olneyc@triad.rr.com; dwarner3@Rgv.rr.com; reynag@uthscsa.edu; fredwood@mail.nih.gov; siegel@nlm.nih.gov FU NLM NIH HHS [N0-1-LM-1-3515] NR 25 TC 12 Z9 14 U1 2 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2007 VL 95 IS 1 BP 31 EP 39 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA 129ML UT WOS:000243733500006 PM 17252064 ER PT J AU Joubert, DJ Lee, TP AF Joubert, Douglas J. Lee, Tamera P. TI Empowering your institution through assessment SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID LIBRARIES; OUTCOMES AB Objectives: The objectives of this study are to describe the process of linking Association of Academic Health Sciences Libraries (AAHSL) data with 2002 LibQUAL+ data and to address four analytical questions created by the AAHSL Task Force on Quality Assessment that relate both to user satisfaction and to services provided by AAHSL libraries. Methods: For the thirty-five AAHSL libraries that participated in the 2002 LibQUAL+ survey, nested-effect of variance was analyzed using a linear mixed model. Using the Pearson correlation coefficient, this study explored four questions about the effect of user demographics on perceived levels of satisfaction with library services. Results: The supposition that library user satisfaction may differ according to library institutional reporting structure was unsupported. Regarding effect on mean overall satisfaction, size of library staff is not significant (P = 0.860), number of constituents is slightly significant (P = 0.027), and ratio of staff to constituents has a moderate and significant effect (P = 0.004). Conclusions: From a demographic perspective, the 2002 LibQUAL+ survey represents the largest cross section of AAHSL libraries. Increased understanding of how qualitative assessment can supplement quantitative data supports evidence-based decision-making and practice. It also could promote changes in data collection and usage. C1 NIH, Bethesda, MD 20906 USA. Med Coll Georgia, Augusta, GA 30912 USA. RP Joubert, DJ (reprint author), NIH, Lib Bldg 10 Room 1L09A, Bethesda, MD 20906 USA. EM joubertd@ors.od.nih.gov; tlee@mail.mcg.edu OI Joubert, Douglas/0000-0003-4090-5587 NR 16 TC 5 Z9 5 U1 0 U2 1 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2007 VL 95 IS 1 BP 46 EP 53 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA 129ML UT WOS:000243733500008 PM 17252066 ER PT J AU Miller, N AF Miller, Naomi TI Analysis of user messages to MedlinePlus.gov SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID HEALTH INFORMATION; WEB SITES; INTERNET; QUALITY; READABILITY; CONSUMERS C1 Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA. RP Miller, N (reprint author), Natl Lib Med, Publ Serv Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM naomi_miller@nlm.nih.gov NR 16 TC 3 Z9 3 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2007 VL 95 IS 1 BP 81 EP 83 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA 129ML UT WOS:000243733500013 PM 17252071 ER PT J AU Qin, J Zhang, B AF Qin, Jing Zhang, Biao TI Empirical-likelihood-based inference in missing response problems and its application in observational studies SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE auxiliary information; average treatment effect; biased sampling; causal inference; empirical likelihood; missing data; observational studies; propensity score; survey sampling ID BIASED SAMPLING MODELS; PROPENSITY SCORE; NONPARAMETRIC-ESTIMATION; AUXILIARY INFORMATION; DISTRIBUTIONS AB The problem of missing response data is ubiquitous in medical and social science studies. In the case of responses that are missing at random (depending on some covariate information), analyses focused only on the complete data may lead to biased results. Various debias methods have been extensively studied in the literature, particularly the weighting method that was motivated by Horvitz and Thompson's estimators. To improve efficiency, Robins, Rotnitzky and Zhao proposed augmented estimating equations based on corrected complete-case analyses. A nice feature of the augmented method is its 'double robustness', i.e. the estimator that is derived from the augmented method is asymptotically unbiased if either the underlying missing data mechanism or the underlying regression function is correctly specified. Furthermore, the augmented estimator can achieve full efficiency if both the missing data mechanism and the regression function are correctly specified. In general, however, it is very difficult to specify the regression function correctly, especially when the dimension of covariates is high- this is the so-called curse of dimensionality problem. The augmented estimator has much lower efficiency if the 'working regression model' is not close to the true regression model. In this paper, the empirical likelihood method is employed to seek a constrained empirical likelihood estimation of mean response with the assumption that responses are missing at random. The empirical-likelihood-based estimators enjoy the double-robustness property. Moreover, it is possible that the empirical-likelihood-based inference can produce asymptotically unbiased and efficient estimators even if the true regression function is not completely known. Simulation results indicate that the empirical-likelihood-based estimators are very robust to a misspecification of the propensity score and dominate other competitors in the sense of having smaller mean-square errors. Methods that are developed in this paper have a nice application in observational causal inferences. The propensity score is used to adjust for differences in pretreatment variables in the estimation of average treatment effects. C1 Univ Toledo, Dept Math, Toledo, OH 43606 USA. NIAID, Bethesda, MD 20892 USA. RP Zhang, B (reprint author), Univ Toledo, Dept Math, Toledo, OH 43606 USA. EM bzhang@utnet.utoledo.edu NR 37 TC 46 Z9 49 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2007 VL 69 BP 101 EP 122 PN 1 PG 22 WC Statistics & Probability SC Mathematics GA 125YO UT WOS:000243479600006 ER PT J AU Chatterjee, N Chen, YH AF Chatterjee, Nilanjan Chen, Yi-Hau TI Maximum likelihood inference on a mixed conditionally and marginally specified regression model for genetic epidemiologic studies with two-phase sampling SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE case-control studies; gene-environment interaction; missing data; outcome-dependent sampling; semiparametric methods ID 2-STAGE CASE-CONTROL; LOGISTIC-REGRESSION; COVARIATE DATA; EXPOSURE; DISEASE; INDEPENDENCE; INFORMATION; DESIGN; RISK AB Two-phase stratified sampling designs can reduce the cost of genetic epidemiologic studies by limiting expensive ascertainments of genetic and environmental exposure to an efficiently selected subsample (phase II) of the main study (phase I). Family history and some covariate information, which may be cheaply gathered for all subjects at phase I, can be used for sampling of informative subjects at phase II. We develop alternative maximum likelihood methods for analysis of data from such studies by using a novel regression model that permits the estimation of 'marginal' risk parameters that are associated with the genetic and environmental covariates of interest, while simultaneously characterizing the 'conditional' risk of the disease associated with family history after adjusting for the other covariates. The methods and appropriate asymptotic theories are developed with and without an assumption of gene-environment independence, allowing the distribution of the environmental factors to remain non-parametric. The performance of the alternative methods and of sampling strategies is studied by using simulated data involving rare and common genetic variants. An application of the methods proposed is illustrated by using a case-control study of colorectal adenoma embedded within the prostate, lung, colorectal and ovarian cancer screening trial. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Acad Sinica, Taipei 115, Taiwan. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov NR 28 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2007 VL 69 BP 123 EP 142 DI 10.1111/j.1467-9868.2007.00580.x PN 2 PG 20 WC Statistics & Probability SC Mathematics GA 141RR UT WOS:000244596900001 ER PT J AU Dunson, DB Pillai, N Park, JH AF Dunson, David B. Pillai, Natesh Park, Ju-Hyun TI Bayesian density regression SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE conditional density function; Dirichlet process; generalized Polya um; local smoothing; mixture model; monparametric Bayes method ID DIRICHLET PROCESSES; NONPARAMETRIC PROBLEMS; MIXTURES; MODELS; DISTRIBUTIONS; INFERENCE; PRIORS AB The paper considers Bayesian methods for density regression, allowing a random probability distribution to change flexibly with multiple predictors. The conditional response distribution is expressed as a non-parametric mixture of regression models, with the mixture distribution changing with predictors. A class of weighted mixture of Dirichlet process priors is proposed for the uncountable collection of mixture distributions. It is shown that this specification results in a generalized Polya urn scheme, which incorporates weights that are dependent on the distance between subjects' predictor values. To allow local dependence in the mixture distributions, we propose a kernel-based weighting scheme. A Gibbs sampling algorithm is developed for posterior computation. The methods are illustrated by using simulated data examples and an epidemiologic application. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. RP Dunson, DB (reprint author), NIEHS, POB 12233,MD A3-03, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 34 TC 89 Z9 89 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2007 VL 69 BP 163 EP 183 DI 10.1111/j.1467-9868.2007.00582.x PN 2 PG 21 WC Statistics & Probability SC Mathematics GA 141RR UT WOS:000244596900003 ER PT J AU Li, Y Tiwari, RC Guha, S AF Li, Yi Tiwari, Ram C. Guha, Subharup TI Mixture cure survival models with dependent censoring SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Archimedean copula model; asymptotic normality; consistency; cure model; dependent censoring; latency distribution; martingale processes; testing cure fraction ID COPULA AB The paper is motivated by cure detection among the prostate cancer patients in the National Institutes of Health surveillance epidemiology and end results programme, wherein the main end point (e.g. deaths from prostate cancer) and the censoring causes (e.g. deaths from heart diseases) may be dependent. Although many researchers have studied the mixture survival model to analyse survival data with non-negligible cure fractions, none has studied the mixture cure model in the presence of dependent censoring. To account for such dependence, we propose a more general cure model that allows for dependent censoring. We derive the cure models from the perspective of competing risks and model the dependence between the censoring time and the survival time by using a class of Archimedean copula models. Within this framework, we consider the parameter estimation, the cure detection and the two-sample comparison of latency distributions in the presence of dependent censoring when a proportion of patients is deemed cured. Large sample results by using martingale theory are obtained. We examine the finite sample performance of the proposed methods via simulation and apply them to analyse the surveillance epidemiology and end results prostate cancer data. C1 Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Harvard Sch Publ Hlth, Dept Biostat, LW211,44 Binney St, Boston, MA 02115 USA. EM yili@jimmy.harvard.edu NR 25 TC 11 Z9 12 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2007 VL 69 BP 285 EP 306 DI 10.1111/j.1467-9868.2007.00589.x PN 3 PG 22 WC Statistics & Probability SC Mathematics GA 171CW UT WOS:000246713500001 ER PT J AU Baker, SG Frangakis, C Lindeman, KS AF Baker, Stuart G. Frangakis, Constantine Lindeman, Karen S. TI Estimating efficacy in a proposed randomized trial with initial and later non-compliance SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE causal inference; potential outcomes; principal stratification ID CAUSAL INFERENCE; CLINICAL-TRIAL; MEAN MODELS; DESIGN; LABOR AB A controversial topic in obstetrics is the effect of walking on the probability of Caesarean section among women in labour. A major reason for the controversy is the presence of non-compliance that complicates the estimation of efficacy, the effect of treatment received on outcome. The intent-to-treat method does not estimate efficacy, and estimates of efficacy that are based directly on treatment received may be biased because they are not protected by randomization. However, when non-compliance occurs immediately after randomization, the use of a potential outcomes model with reasonable assumptions has made it possible to estimate efficacy and still to retain the benefits of randomization to avoid selection bias. In this obstetrics application, non-compliance occurs initially and later in one arm. Consequently some parameters cannot be uniquely estimated without making strong assumptions. This difficulty is circumvented by a new study design involving an additional randomization group and a novel potential outcomes model (principal stratification). C1 NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Baker, SG (reprint author), NCI, NIH, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 20 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2007 VL 56 BP 211 EP 221 DI 10.1111/j.1467-9876.2007.00574.x PN 2 PG 11 WC Statistics & Probability SC Mathematics GA 149PR UT WOS:000245159600006 ER PT J AU Peddada, S Haseman, J AF Peddada, Shyamal Haseman, Joe TI Tests for a simple tree order restriction with application to dose-response studies - Response SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Letter C1 Natl Inst Environm Hlth Sci, Natl Inst Hlth, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Peddada, S (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2007 VL 56 BP 494 EP 495 DI 10.1111/j.1467-9876.2007.00589_2.x PN 4 PG 3 WC Statistics & Probability SC Mathematics GA 209YI UT WOS:000249423500009 ER PT J AU Francischetti, IMB Seydel, KB Monteiro, RQ Whitten, RO Erexson, CR Noronha, ALL Ostera, GR Kamiza, SB Molyneux, ME Ward, JM Taylor, TE AF Francischetti, I. M. B. Seydel, K. B. Monteiro, R. Q. Whitten, R. O. Erexson, C. R. Noronha, A. L. L. Ostera, G. R. Kamiza, S. B. Molyneux, M. E. Ward, J. M. Taylor, T. E. TI Plasmodium falciparum-infected erythrocytes induce tissue factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE endothelial cell; malaria; Plasmodium falciparum; platelets; prothrombinase; tissue factor ID INTERCELLULAR-ADHESION MOLECULE-1; HUMAN CEREBRAL MALARIA; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FACTOR-XA; CLINICAL SEVERITY; MALAWIAN CHILDREN; ESCHERICHIA-COLI; AFRICAN CHILDREN; ACTIVATION AB Background: Plasmodium falciparum malaria infects 300-500 million people every year, causing 1-2 million deaths annually. Evidence of a coagulation disorder, activation of endothelial cells (EC) and increase in inflammatory cytokines are often present in malaria. Objectives: We have asked whether interaction of parasitized red blood cells (pRBC) with EC induces tissue factor (TF) expression in vitro and in vivo. The role of phosphatidylserine-containing pRBC to support the assembly of blood coagulation complexes was also investigated. Results: We demonstrate that mature forms of pRBC induce functional expression of TF by EC in vitro with productive assembly of the extrinsic Xnase complex and initiation of the coagulation cascade. Late-stage pRBC also support the prothrombinase and intrinsic Xnase complex formation in vitro, and may function as activated platelets in the amplification phase of the blood coagulation. Notably, post-mortem brain sections obtained from P. falciparum-infected children who died from cerebral malaria and other causes display a consistent staining for TF in the EC. Conclusions: These findings place TF expression by endothelium and the amplification of the coagulation cascade by pRBC and/or activated platelets as potentially critical steps in the pathogenesis of malaria. Furthermore, it may allow investigators to test other therapeutic alternatives targeting TF or modulators of EC function in the treatment of malaria and/or its complications. C1 NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. CellNetix Pathol, Olympia, WA USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. Fundacao Oswaldo Cruz, Lab Imunoparasitol, Salvador, BA, Brazil. NIAID, Biochem & Biophys Parasitol Sect, LMVR, NIH, Bethesda, MD USA. Coll Med, Blantyre Malaria Project, Blantyre, Malawi. Coll Med, Dept Histopathol, Blantyre, Malawi. Coll Med, Malawi Liverpool Wellcome Trust Programme, Blantyre, Malawi. Sch Trop Med, Liverpool, Merseyside, England. Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA. RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-28, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov RI Monteiro, Robson/B-8007-2014 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999]; NIAID NIH HHS [R01 AI034969, R01 AI 34969]; Wellcome Trust [058390] NR 76 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2007 VL 5 IS 1 BP 155 EP 165 DI 10.1111/j.1538-7836.2006.02232.x PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 116WP UT WOS:000242834800023 PM 17002660 ER PT J AU Steinmaus, C Moore, LE Shipp, M Kalman, D Rey, OA Biggs, ML Hopenhayn, C Bates, MN Zheng, SC Wiencke, JK Smith, AH AF Steinmaus, Craig Moore, Lee E. Shipp, Miriam Kalman, David Rey, Omar A. Biggs, Mary L. Hopenhayn, Claudia Bates, Michael N. Zheng, Shichun Wiencke, John K. Smith, Allan H. TI Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; BLADDER-CANCER RISK; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; DRINKING-WATER; LUNG-CANCER; SKIN-CANCER; MONOMETHYLARSONOUS ACID; THIOREDOXIN REDUCTASE; METHYLATED ARSENICALS; C677T POLYMORPHISM AB Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer. C1 Univ Calif Berkeley, Sch Publ Hlth, Arsen Hlth Effects Res Program, Berkeley, CA 94720 USA. California Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Catolica Cordoba, Fac Med, Cordoba, Argentina. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. RP Smith, AH (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Arsen Hlth Effects Res Program, 140 Warren Hall, Berkeley, CA 94720 USA. EM ahsmith@berkeley.edu RI Smith, Allan/F-9249-2011 FU NIEHS NIH HHS [K23 ES11133, P42 ES04705] NR 105 TC 55 Z9 60 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD JAN 1 PY 2007 VL 70 IS 2 BP 159 EP 170 DI 10.1080/15287390600755240 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 148TN UT WOS:000245097600009 PM 17365577 ER PT J AU Ferguson, LJC Lebetkin, EH Lih, FB Tomer, KB Parkinson, HD Borghoff, SJ Burka, LT AF Ferguson, Ling-Jen Chen Lebetkin, Edward H. Lih, Fred B. Tomer, Kenneth B. Parkinson, Horace D. Borghoff, Susan J. Burka, Leo T. TI C-14-labeled pulegone and metabolites binding to alpha 2u-globulin in kidneys of male F-344 rats SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID MONOTERPENE KETONE; MENTHOFURAN; (R)-(+)-PULEGONE; HEPATOTOXICITY; R-(+)-PULEGONE; MOUSE; OIL; NEPHROTOXICITY; PEPPERMINT; PROTEINS AB Pulegone is a major constituent of pennyroyal oil and a minor component of peppermint oil. Pulegone is biotransformed to menthofuran and menthones ( diastereomeric menthone and isomenthone) in pennyroyal and peppermint as well as in rodents. Pulegone and menthofuran are hepatotoxic to rodents, and menthones are less toxic. The metabolism and disposition of pulegone and menthofuran were previously studied in rodents, and higher concentrations of pulegone- and menthofuran-derived radioactivity were observed in male than female rat kidney. One explanation is the association of pulegone and metabolites with a male rat-specific protein, alpha 2u-globulin. To test this hypothesis, male and female rats were dosed orally with C-14-labeled pulegone (80 mg/kg, 120 mu Ci/kg) or menthofuran (60 mg/kg, 120 mu Ci/kg) or menthones (80 mg/kg, 120 mu Ci/ kg) in corn oil, and the kidney cytosol was prepared 24 h after dosing. An equilibrium dialysis experiment showed that in all three studies the radioactivity was associated with kidney cytosol proteins of male but not female rats. The chemicals present in the male rat kidney cytosol after dialysis were extracted with dichloromethane and characterized by high-performance liquid chromatography (HPLC) and gas chromatography/ mass spectrometry (GC-MS). All parent compounds were detected, and the metabolites characterized included piperitone from pulegone or menthones treatment, menthones and possibly 8-hydroxymenthones from pulegone treatment, and mintlactones (diastereomeric mintlactone and isomintlactone) and 7a-hydroxy-mintlactone from menthofuran treatment. Analysis of the male rat kidney cytosol by a gel filtration column demonstrated that the retention was due to reversible binding of these chemicals with the male rat-specific protein alpha 2u-globulin. However, binding of pulegone and/or metabolites to alpha 2u-globulin did not produce accumulation of this protein in the kidney. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC USA. RP Ferguson, LJC (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrestr Dr SE, Albuquerque, NM 87108 USA. EM ljferguson@lrri.org RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 24 TC 3 Z9 3 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2007 VL 70 IS 17 BP 1416 EP 1423 DI 10.1080/15287390701382720 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206OI UT WOS:000249192400002 PM 17687727 ER PT J AU Wallenborn, JG Schladweiler, MC Nyska, A Johnson, JA Thomas, R Jaskot, RH Richards, JH Ledbetter, AD Kodavanti, UP AF Wallenborn, J. Grace Schladweiler, Mette C. Nyska, Abraham Johnson, Jo Anne Thomas, Ronald Jaskot, Richard H. Richards, Judy H. Ledbetter, Allen D. Kodavanti, Urmila P. TI Cardiopulmonary responses of Wistar kyoto, spontaneously hypertensive, and stroke-prone spontaneously hypertensive rats to particulate matter (PM) exposure SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID OIL FLY-ASH; NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; COMBUSTION-DERIVED PARTICLES; AMBIENT AIR-POLLUTION; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; PULMONARY RESPONSES; MODEL; APOPTOSIS; DAMAGE AB Humans with underlying cardiovascular disease, including stroke, are more susceptible to ambient particulate matter ( PM)induced morbidity and mortality. We hypothesized that stroke-prone spontaneously hypertensive rats (SHRSP) would be more susceptible than healthy Wistar Kyoto (WKY) rats to PM-induced cardiac oxidative stress and pulmonary injury. We further postulated that PM-induced injury would be greater in SHRSP than in spontaneously hypertensive rats (SHR) based on the greater disease severity in SHRSP than SHR. First, male WKY and SHRSP were intratracheally ( IT) instilled with saline or 1.11, 3.33, or 8.33 mg/kg of oil combustion PM and responses were analyzed 4 or 24 h later. Second, SHR and SHRSP were IT instilled with saline or 3.33 or 8.33 mg/kg of the same PM and responses were analyzed 24 h later. Pulmonary injury and inflammation were assessed in bronchoalveolar lavage fluid (BALF) and cardiac markers in cytosolic and mitochondrial fractions. BALF neutrophilic inflammatory response was induced similarly in all strains following PM exposure. BALF protein leakage, gamma-glutamyl transferase, and N-acetylglucosaminidase activities, but not lactate dehydrogenase activity, were exacerbated in SHRSP compared to WKY or SHR. Pulmonary cytosolic and cardiac mitochondrial ferritin levels decreased, and cardiac cytosolic superoxide dismutase (SOD) activity increased in SHRSP only. Pulmonary SOD activity decreased in WKY and SHRSP. Cardiac mitochondrial isocitrate dehydrogenase (ICDH) activity decreased in PM-exposed WKY and SHR; control levels were lower in SHRSP than SHR or WKY. In summary, strain-related differences exist in pulmonary protein leakage and oxidative stress markers. PM-induced changes in cardiac oxidative stress sensitive enzymes are small, and appear only slightly exacerbated in SHRSP compared to WKY or SHR. Multiple biological markers may be differentially affected by PM in genetic models of cardiovascular diseases. Preexisting cardiovascular disease may influence susceptibility to PM pulmonary and cardiac health effects in a disease-specific manner. C1 US EPA, Pulm Toxicol Branch, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab,ORD, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. RP Kodavanti, UP (reprint author), US EPA, Pulm Toxicol Branch, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab,ORD, MD B143-01, Res Triangle Pk, NC 27711 USA. EM kodavanti.urmila@epa.gov NR 59 TC 13 Z9 14 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2007 VL 70 IS 22 BP 1912 EP 1922 DI 10.1080/15287390701551233 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 236IS UT WOS:000251297200004 PM 17966062 ER PT J AU Krewski, D Yokel, RA Nieboer, E Borchelt, D Cohen, J Harry, J Kacew, S Lindsay, J Mahfouz, AM Rondeau, V AF Krewski, Daniel Yokel, Robert A. Nieboer, Evert Borchelt, David Cohen, Joshua Harry, Jean Kacew, Sam Lindsay, Joan Mahfouz, Amal M. Rondeau, Virginie TI Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review DE aluminium; aluminium oxide; aluminium hydroxide; speciation; human health; neurotoxicity; exposure; toxicokinetics; toxicology; epidemiology; Alzheimer's disease; risk assessment ID CHRONIC-RENAL-FAILURE; AMYOTROPHIC-LATERAL-SCLEROSIS; ACCELERATOR MASS-SPECTROMETRY; CENTRAL-NERVOUS-SYSTEM; ATOMIC-ABSORPTION-SPECTROMETRY; NEUTRON-ACTIVATION ANALYSIS; BLOOD-BRAIN-BARRIER; PORPHYRIA-CUTANEA-TARDA; REDUCTION PLANT WORKERS; TANGLE-BEARING NEURONS C1 [Krewski, Daniel; Kacew, Sam] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk & Assessment, Inst Populat Hlth, Ottawa, ON K1N 6N5, Canada. [Krewski, Daniel] Univ Ottawa, Fac Med, Dept Epidemiol & Community Hlth, Ottawa, ON, Canada. [Yokel, Robert A.] Univ Kentucky, Med Ctr, Coll Pharm, Lexington, KY 40506 USA. [Yokel, Robert A.] Univ Kentucky, Med Ctr, Grad Ctr Toxicol, Lexington, KY 40506 USA. [Nieboer, Evert] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada. [Nieboer, Evert] Univ Tromso, Inst Community Med, N-9001 Tromso, Norway. [Borchelt, David] Univ Florida, McKnight Brain Inst, Dept Neurosci, SanteFe Hlth Alzheimers Dis Res Ctr, Gainesville, FL 32611 USA. [Cohen, Joshua] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Harry, Jean] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. [Kacew, Sam] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. [Lindsay, Joan] Publ Hlth Agcy Canada, Surveillance Div, Aging Related Dis Sect, Ottawa, ON, Canada. [Mahfouz, Amal M.] US EPA, Washington, DC 20460 USA. [Rondeau, Virginie] Univ Victor Segalen Bordeaux 2, INSERM, Biostat E0338, Bordeaux, France. RP Krewski, D (reprint author), Univ Ottawa, McLaughlin Ctr Populat Hlth Risk & Assessment, Inst Populat Hlth, Room 320,1 Stewart St, Ottawa, ON K1N 6N5, Canada. EM cphra@uottawa.ca RI rondeau, virginie/E-4192-2014; OI rondeau, virginie/0000-0001-7109-4831; Cohen, Joshua/0000-0003-1737-0991 FU Intramural NIH HHS [Z99 ES999999] NR 1515 TC 168 Z9 177 U1 4 U2 72 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1093-7404 EI 1521-6950 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PY 2007 VL 10 SU 1 BP 1 EP 269 DI 10.1080/10937400701597766 PG 269 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 242UK UT WOS:000251751500001 PM 18085482 ER PT J AU Vira, M Linehan, WM AF Vira, Manish Linehan, W. Marston TI Expanding the morphological and molecular genetic phenotype of kidney cancer SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Vira, M (reprint author), NCI, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2007 VL 177 IS 1 BP 10 EP 11 DI 10.1016/j.juro.2006.10.011 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 116ZV UT WOS:000242843200002 PM 17161990 ER PT J AU Wood, BJ Locklin, JK Viswanathan, A Kruecker, J Haernmerich, D Cebral, J Sofer, A Cheng, R McCreedy, E Cleary, K McAuliffe, MJ Glossop, N Yanof, J AF Wood, Bradford J. Locklin, Julia K. Viswanathan, Anand Kruecker, Jochen Haemmerich, Dieter Cebral, Juan Sofer, Ariela Cheng, Ruida McCreedy, Evan Cleary, Kevin McAuliffe, Matthew J. Glossop, Neil Yanof, Jeff TI Technologies for guidance of radiofrequency ablation in the multimodality interventional suite of the future SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 28-DEC 03, 2004 CL Chicago, IL SP Radiol Soc N Amer ID FINITE-ELEMENT AB Several new image-guidance tools and devices are being prototyped, investigated, and compared. These tools are introduced and include prototype software for image registration and fusion, thermal modeling, electromagnetic tracking, semiautomated robotic needle guidance, and multimodality imaging. The integration of treatment planning with computed tomography robot systems or electromagnetic needle-tip tracking allows for seamless, iterative, "see-and-treat," patient-specific tumor ablation. Such automation, navigation, and visualization tools could eventually optimize radiofrequency ablation and other needle-based ablation procedures and decrease variability among operators, thus facilitating the translation of novel image-guided therapies. Much of this new technology is in use or will be available to the interventional radiologist in the near future, and this brief introduction will hopefully encourage research in this emerging area. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Philips Res N Amer, Briarcliff Manor, NY 10510 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA. George Mason Univ, Syst Engn & Operat Res Dept, Fairfax, VA 22030 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Imaging Sci & Informat Syst Ctr, Dept Radiol, Washington, DC 20007 USA. Traxtal Technol, Toronto, ON M5V 2J1, Canada. Philips Med Syst, CT Clin Sci, Cleveland, OH 44143 USA. RP Locklin, JK (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM locklinj@cc.nih.gov OI Viswanathan, Anand/0000-0003-3810-6217; Haemmerich, Dieter/0000-0003-1127-7024 FU Intramural NIH HHS [Z99 CL999999]; NCRR NIH HHS [C06 RR018823] NR 14 TC 72 Z9 79 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2007 VL 18 IS 1 BP 9 EP 24 DI 10.1016/j.jvir.2006.10.013 PN 1 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 137NL UT WOS:000244299200003 PM 17296700 ER PT J AU Wassef, M Upchurch, GR Kuivaniemi, H Thompson, RW Tilson, MD AF Wassef, Momtaz Upchurch, Gilbert R., Jr. Kuivaniemi, Helena Thompson, Robert W. Tilson, M. D., III TI Challenges and opportunities in abdominal aortic aneurysm research SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID WALL STRESS; ATHEROSCLEROTIC PLAQUE; GENETIC-HETEROGENEITY; MARFAN-SYNDROME; RUPTURE RISK; MICE; DOXYCYCLINE; REPAIR; INACTIVATION; SURVEILLANCE AB Abdominal Aortic Aneurysms (AAAs) are associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Basic research studies have led to a better understanding of aneurysm disease over the past two decades. There has also been a growing appreciation that fundamental knowledge regarding the process of aneurysmal degeneration is still somewhat limited. Opportunities in research include: 1) the investigation of potential new mechanism-based pharmacologic interventions; 2) identify the genetic basis for an inherited predisposition; 3) develop and refine noninvasive approaches for the early detection; 4) examine potential novel surgical approaches and design new biomaterials; and 5) initiate and promote awareness programs for diagnosis and treatment of aortic aneurysms. The optimal approach to addressing these issues will require integrative, multidisciplinary research programs that involve basic scientists working in concert with vascular and cardiothoracic surgeons, as well as other clinical specialists with expertise in vascular disease. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48202 USA. Washington Univ, Sch Med, Dept Surg Radiol & Cell Biol & Physiol, St Louis, MO 63130 USA. St Lukes Roosevelt Hosp, Dept Surg, New York, NY 10025 USA. RP Upchurch, GR (reprint author), Univ Michigan, Med Ctr, Div Vasc Surg, 1500 E Med Ctr Dr,TC2210 N, Ann Arbor, MI 48109 USA. EM riversu@umich.cdu OI Kuivaniemi, Helena/0000-0001-5753-8766 NR 46 TC 36 Z9 37 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2007 VL 45 IS 1 BP 192 EP 198 DI 10.1016/j.jvs.2006.09.004 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 125PK UT WOS:000243454100041 PM 17210410 ER PT J AU Wencker, M Sausse, C Derse, D Gazzolo, L Dodon, MD AF Wencker, Melanie Sausse, Celine Derse, David Gazzolo, Louis Dodon, Madeleine Due TI Human T-cell leukemia virus type 1 tax protein down-regulates pre-T-cell receptor alpha gene transcription in human immature thymocytes SO JOURNAL OF VIROLOGY LA English DT Article ID LOOP-HELIX PROTEINS; KIX DOMAIN; BINDING PROTEINS; TRANSGENIC MICE; CD34(+) CELLS; IN-VITRO; E-BOX; EXPRESSION; CBP/P300; RECRUITMENT AB The human pre-T-cell receptor alpha (TCR alpha; pT alpha) gene encodes a polypeptide which associates with the TCRP chain and CD3 molecules to form the pre-TCR complex. The surface expression of the pre-TCR is pTa dependent, and signaling through this complex triggers an early alpha beta T-cell developmental checkpoint inside the thymus, known as beta-selection. E2A transcription factors, which are involved at multiple stages of T-cell development, regulate the transcription of the pTa gene. Here we show that the regulatory protein Tax of the human T-cell leukemia virus type 1 (HTLV-1) efficiently suppresses the E47-mediated activation of the pT alpha promoter. Furthermore, we report that in Tax lentivirally transduced human MOLT-4 T cells, which constitutively express the pT alpha gene, the amount of pT alpha transcripts decreases. Such a decrease is not observed in MOLT-4 cells transduced by a vector encoding the Tax mutant K88A, which is unable to interact with p300. These data underline that Tax inhibits pT alpha transcription by recruiting this coactivator. Finally, we show that the expression of Tax in human immature thymocytes results in a decrease of pT alpha gene transcription but does not modify the level of E47 transcripts. These observations indicate that Tax, by silencing E proteins, down-regulates pT alpha gene transcription during early thymocyte development. They further provide evidence that Tax can interfere with an important checkpoint during T-cell differentiation in the thymus. C1 Ecole Normale Super Lyon, U758, INSERM, IFR 128, F-69364 Lyon 07, France. NCI, HIV Drug Resistance Program, Canc Res Ctr, Frederick, MD 21702 USA. RP Dodon, MD (reprint author), Ecole Normale Super Lyon, U758, INSERM, IFR 128, 46 Allee Italie, F-69364 Lyon 07, France. EM madeleine.duc.dodon@ens-lyon.fr RI Wencker, Melanie/M-3849-2014; Duc-Dodon, Madeleine/I-6580-2016; OI Wencker, Melanie/0000-0003-4200-0079 NR 47 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 1 BP 301 EP 308 DI 10.1128/JVI.00766-06 PG 8 WC Virology SC Virology GA 118RE UT WOS:000242958600028 PM 17050604 ER PT J AU Aulicino, PC Holmes, EC Rocco, C Mangano, A Sen, L AF Aulicino, Paula C. Holmes, Edward C. Rocco, Carlos Mangano, Andrea Sen, Luisa TI Extremely rapid spread of human immunodeficiency virus type 1 BF recombinants in Argentina SO JOURNAL OF VIROLOGY LA English DT Article ID SEQUENCE ALIGNMENT; TRANSMISSION; SUBTYPE AB The epidemic of human immunodeficiency virus type 1 (HIV-1) in Argentina is distinctive in that many infections are caused by subtype BF recombinant viruses. To determine their demographic history, we estimated the evolutionary rate, mode of population growth, and age of genetic diversity among 40 BF vpu sequences. This revealed one of the highest substitution rates reported for HIV-1, at 10.793 x 10(-3) substitutions per site per year, and a very rapid rate of population growth, with an initial mean epidemic doubling time of 3.72 months. This rapid population growth is compatible with an elevated fitness for subtype BF compared to that for "pure" B and F viruses. C1 Hosp Pediat JP Garrahan, CONICET, Lab Biol Celular & Retrovirus, RA-1245 Buenos Aires, DF, Argentina. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Sen, L (reprint author), Hosp Pediat JP Garrahan, CONICET, Lab Biol Celular & Retrovirus, Combate Pozos 1881, RA-1245 Buenos Aires, DF, Argentina. EM lsen@garrahan.gov.ar OI Holmes, Edward/0000-0001-9596-3552 NR 17 TC 26 Z9 26 U1 0 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 JAN PY 2007 VL 81 IS 1 BP 427 EP 429 DI 10.1128/JVI.01403-06 PG 3 WC Virology SC Virology GA 118RE UT WOS:000242958600041 PM 17050594 ER PT J AU Thio, CL Astemborski, J Bashirova, A Mosbruger, T Greer, S Witt, MD Goedert, JJ Hilgartner, M Majeske, A O'Brien, SJ Thomas, DL Carrington, M AF Thio, Chloe L. Astemborski, Jacquie Bashirova, Arman Mosbruger, Timothy Greer, Spencer Witt, Mallory D. Goedert, James J. Hilgartner, Margaret Majeske, Audrey O'Brien, Stephen J. Thomas, David L. Carrington, Mary TI Genetic protection against hepatitis B virus conferred by CCR5 Delta 32: Evidence that CCR5 contributes to viral persistence SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CCR5; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; IMMUNE-RESPONSE; PROMOTER POLYMORPHISM; DISEASE PROGRESSION; AIDS; MICE; TUBERCULOSIS; HEMOPHILIA AB Recovery from acute hepatitis B virus (HBV) infection requires a broad, vigorous T-cell response, which is enhanced in mice when chemokine receptor 5 (CCR5) is missing. To test the hypothesis that production of a nonfunctional CCR5 (CCR5 Delta 32 [a functionally null allele containing a 32-bp deletion]) increases the likelihood of recovery from hepatitis B in humans, we studied 526 persons from three cohorts in which one person with HBV persistence was matched to two persons who recovered from an HBV infection. Recovery or persistence was determined prior to availability of lamivudine. We determined genotypes for CCR5 Delta 32 and for polymorphisms in the CCR5 promoter and in coding regions of the neighboring genes, chemokine receptor 2 (CCR2) and chemokine receptor-like 2 (CCRL2). Allele and haplotype frequencies were compared among the 190 persons with viral recovery and the 336 with persistence by use of conditional logistic regression. CCR5 Delta 32 reduced the risk of developing a persistent HBV infection by nearly half (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.83; P = 0.006). This association was virtually identical in persons with and without a concomitant human immunodeficiency virus infection. Of the nine individuals who were homozygous for the deletion, eight recovered from infection (OR, 0.25; 95% CI, 0.03 to 1.99; P = 0.19). None of the other neighboring polymorphisms examined were associated with HBV outcome. These data demonstrate a protective effect of CCR5 Delta 32 in recovery from an HBV infection, provide genetic epidemiological evidence for a role of CCR5 in the immune response to HBV, and suggest a potential therapeutic treatment for patients persistently infected with HBV. C1 NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Harbor UCLA, Los Angeles Biomed Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. New York Presbyterian Hosp, Cornell Med Ctr, Dept Pediat, New York, NY USA. RP Carrington, M (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [5-MO1-RR-00722, M01 RR000059, M01 RR000071, M01 RR000722, M01 RR002558, MO1-RR00059, MO1-RR00071, MO1-RR02558, MO1-RR06020]; NIAID NIH HHS [U01 AI035039, U01 AI035040, U01 AI035041, U01 AI035042, U01 AI035043, U01 AI037613, U01 AI037984, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35042, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984]; NICHD NIH HHS [N01-HD-4-3200, R01-HD-4-1224]; NIDA NIH HHS [DA00441, K08 DA000441] NR 39 TC 42 Z9 47 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 2 BP 441 EP 445 DI 10.1128/JVI.01897-06 PG 5 WC Virology SC Virology GA 124EK UT WOS:000243350100001 PM 17079285 ER PT J AU Belov, GA Altan-Bonnet, N Kovtunovych, G Jackson, CL Lippincott-Schwartz, J Ehrenfeld, E AF Belov, George A. Altan-Bonnet, Nihal Kovtunovych, Gennadiy Jackson, Catherine L. Lippincott-Schwartz, Jennifer Ehrenfeld, Ellie TI Hijacking components of the cellular secretory pathway for replication of poliovirus RNA SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; POLY(RC) BINDING-PROTEIN; ADP-RIBOSYLATION FACTOR; BREFELDIN-A; IN-VITRO; MEMBRANE ASSOCIATION; 3A PROTEIN; COPI COAT; CELLS; ARF AB Infection of cells with poliovirus induces a massive intracellular membrane reorganization to form vesicle-like structures where viral RNA replication occurs. The mechanism of membrane remodeling remains unknown, although some observations have implicated components of the cellular secretory and/or autophagy pathways. Recently, we showed that some members of the Arf family of small GTPases, which control secretory trafficking, became membrane-bound after the synthesis of poliovirus proteins in vitro and associated with newly formed membranous RNA replication complexes in infected cells. The recruitment of Arfs to specific target membranes is mediated by a group of guanine nucleotide exchange factors (GEFs) that recycle Arf from its inactive, GDP-bound state to an active GTP-bound form. Here we show that two different viral proteins independently recruit different Arf GEFs (GBF1 and BIG1/2) to the new structures that support virus replication. Intracellular Arf-GTP levels increase similar to 4-fold during poliovirus infection. The requirement for these GEFs explains the sensitivity of virus growth to brefeldin A, which can be rescued by the overexpression of GBF1. The recruitment of Arf to membranes via specific GEFs by poliovirus proteins provides an important clue toward identifying cellular pathways utilized by the virus to form its membranous replication complex. C1 NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Ehrenfeld, E (reprint author), NIAID, NIH, 50 S Dr Rm 6120, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Belov, George/B-4625-2008; Jackson, Catherine/A-3421-2013 OI Belov, George/0000-0002-0892-1731; Jackson, Catherine/0000-0002-0843-145X FU Intramural NIH HHS NR 46 TC 97 Z9 102 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 2 BP 558 EP 567 DI 10.1128/JVI.01820-06 PG 10 WC Virology SC Virology GA 124EK UT WOS:000243350100014 PM 17079330 ER PT J AU Lisco, A Grivel, JC Biancotto, A Vanpouille, C Origgi, F Malnati, MS Schols, D Lusso, P Margolis, LB AF Lisco, Andrea Grivel, Jean-Charles Biancotto, Angelique Vanpouille, Christophe Origgi, Francesco Malnati, Mauro S. Schols, Dominique Lusso, Paolo Margolis, Leonid B. TI Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-HERPESVIRUS 7; EX-VIVO; CXCR4-TROPIC HIV-1; T-CELLS; INHIBITION; INFECTION; DNA; HISTOCULTURES AB Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HRV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HfV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Ist Sci San Raffaele, Univ Human Virol, DIBIT, Milan, Italy. Univ Cagliari, Dept Med Sci, Sch Med, Cagliari, Italy. Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. RP Lusso, P (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D58,9000 Rockville Pike, Bethesda, MD 20892 USA. EM paolo.lusso@hsr.it; margolis@healix.nih.gov NR 24 TC 34 Z9 36 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 2 BP 708 EP 717 DI 10.1128/JVI.01367-06 PG 10 WC Virology SC Virology GA 124EK UT WOS:000243350100028 PM 17065205 ER PT J AU Nishimura, Y Igarashi, T Buckler-White, A Buckler, C Imamichi, H Goeken, RM Lee, WR Lafont, BAP Byrum, R Lane, HC Hirsch, VM Martin, MA AF Nishimura, Yoshiaki Igarashi, Tatsuhiko Buckler-White, Alicia Buckler, Charles Imamichi, Hiromi Goeken, Robert M. Lee, Wendy R. Lafont, Bernard A. P. Byrum, Russ Lane, H. Clifford Hirsch, Vanessa M. Martin, Malcolm A. TI Loss of naive cells accompanies memory CD4(+) T-cell depletion during long-term progression to AIDS in simian immunodeficiency virus-infected macaques SO JOURNAL OF VIROLOGY LA English DT Article ID END-STAGE DISEASE; RHESUS-MONKEYS; HIV-INFECTION; GASTROINTESTINAL-TRACT; IN-VIVO; MARROW-TRANSPLANTATION; VIRAL REPLICATION; PERIPHERAL-BLOOD; TYPE-1 INFECTION; NATURAL-HISTORY AB Human immunodeficiency virus and simian immunodeficiency virus (SfV) induce a slow progressive disease, characterized by the massive loss of memory CD4(+) T cells during the acute infection followed by a recovery phase in which virus replication is partially controlled. However, because the initial injury is so severe and virus production persists, the immune system eventually collapses and a symptomatic fatal disease invariably occurs. We have assessed CD4(+) T-cell dynamics and disease progression in 12 SIV-infected rhesus monkeys for nearly 2 years. Three macaques exhibiting a rapid progressor phenotype experienced rapid and irreversible loss of memory, but not naive, CD4(+) T lymphocytes from peripheral blood and secondary lymphoid tissues and died within the first 6 months of virus inoculation. In contrast, SIV-infected conventional progressor animals sustained marked but incomplete depletions of memory CD4(+) T cells and continuous activation/proliferation of this T-lymphocyte subset. This was associated with a profound loss of naive CD4(+) T cells from peripheral blood and secondary lymphoid tissues, which declined at rates that correlated with disease progression. These data suggest that the persistent loss of memory CD4(+) T cells, which are being eliminated by direct virus killing and activation-induced cell death, requires the continuous differentiation of naive into memory CD4(+) T cells. This unrelenting replenishment process eventually leads to the exhaustion of the naive CD4(+) T-cell pool and the development of disease. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. Bioqual, Rockville, MD 20850 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM malm@nih.gov RI Lafont, Bernard/B-7236-2014 NR 50 TC 41 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2007 VL 81 IS 2 BP 893 EP 902 DI 10.1128/JVI.01635-06 PG 10 WC Virology SC Virology GA 124EK UT WOS:000243350100045 PM 17093193 ER PT J AU Melendi, GA Hoffman, SJ Karron, RA Irusta, PM Laham, FR Humbles, A Schofield, B Pan, CH Rabold, R Thumar, B Thumar, A Gerard, NP Mitzner, W Barnum, SR Gerard, C Kleeberger, SR Polack, FP AF Melendi, Guillermina A. Hoffman, Scott J. Karron, Ruth A. Irusta, Pablo M. Laham, Federico R. Humbles, Alison Schofield, Brian Pan, Chien-Hsiung Rabold, Richard Thumar, Bhagvanji Thumar, Adeep Gerard, Norma P. Mitzner, Wayne Barnum, Scott R. Gerard, Craig Kleeberger, Steven R. Polack, Fernando P. TI C5 modulates airway hyperreactivity and pulmonary eosinophilia during enhanced respiratory syncytial virus disease by decreasing C3a receptor expression SO JOURNAL OF VIROLOGY LA English DT Article ID FORMALIN-INACTIVATED RSV; COMPLEMENT ANAPHYLATOXIN C3A; IMMUNIZED BALB/C MICE; ALLERGIC-ASTHMA; T-CELLS; EFFECTOR PHASE; G-GLYCOPROTEIN; MURINE MODEL; INFECTION; VACCINE AB Enhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes. Mice with a targeted disruption of complement component C5 affected by the enhanced disease displayed enhanced airway reactivity, lung eosinophilia, and mucus production compared to wild-type mice and C5-deficient mice reconstituted with C5. C3aR expression in bronchial epithelial and smooth muscle cells in the lungs of C5-deficient mice was enhanced compared to that in wild-type and reconstituted rodents. Treatment of C5-deficient mice with a C3aR antagonist significantly attenuated airway reactivity, eosinophilia, and mucus production. These results indicate that C5 plays a crucial role in modulating the enhanced-disease phenotype, by affecting expression of C3aR in the lungs. These findings reveal a novel autoregulatory mechanism for the complement cascade that affects the innate and adaptive immune responses. C1 Johns Hopkins Univ, Bloombergt Sch Publ Hlth, Dept Pediat, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloombergt Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloombergt Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloombergt Sch Publ Hlth, Dept Environm Hlth, Baltimore, MD 21205 USA. INFANT Fdn, Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Univ Alabama, Dept Microbiol, Birmingham, AL USA. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Georgetown Univ, Dept Human Sci, Washington, DC USA. RP Polack, FP (reprint author), Johns Hopkins Univ, Bloombergt Sch Publ Hlth, Dept Pediat, Sch Med, 615 N Wolfe St,E5202, Baltimore, MD 21205 USA. EM fpolack@jhsph.edu RI Pan, Chien-Hsiung/E-3857-2010 FU Intramural NIH HHS; NIAID NIH HHS [R21 AI054952, R01 AI054952, AI-054952] NR 46 TC 18 Z9 18 U1 0 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 JAN PY 2007 VL 81 IS 2 BP 991 EP 999 DI 10.1128/JVI.01783-06 PG 9 WC Virology SC Virology GA 124EK UT WOS:000243350100054 PM 17079327 ER PT J AU Hartge, P Berg, CD AF Hartge, Patricia Berg, Christine D. TI Improving uptake of cancer screening in women SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Early Detect Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. RP Hartge, P (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8090, Rockville, MD 20852 USA. EM hartgep@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN-FEB PY 2007 VL 16 IS 1 BP 66 EP 67 DI 10.1089/jwh.2006.E071 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 140SH UT WOS:000244526500008 PM 17324098 ER PT J AU Frayling, TM Rafiq, S Murray, A Hurst, AJ Weedon, MN Henley, W Bandinelli, S Corsi, AM Ferrucci, L Guralnik, JM Wallace, RB Melzer, D AF Frayling, Timothy M. Rafiq, Sajjad Murray, Anna Hurst, Alison J. Weedon, Michael N. Henley, William Bandinelli, Stefania Corsi, Anna-Maria Ferrucci, Luigi Guralnik, Jack M. Wallace, Robert B. Melzer, David TI An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; MENDELIAN RANDOMIZATION; GENETIC-DETERMINANTS; INFLAMMATION; IL-18; LONGEVITY; DISEASE; CENTENARIANS; STATE; TWINS AB Background. The proinflammatory cytokine interleukin-18 (IL-18) is associated with major disabling conditions, although whether as byproduct or driver is unclear. The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown. Methods. We used 1671 participants aged 65-80 years from two studies: the InCHIANTI study and wave 6 of the Iowa-Established Populations for Epidemiological Study of the Elderly (EPESE). We tested three common polymorphisms against IL- 18 concentration and measures of functioning. Results. In the InCHIANTI study, a I standard deviation increase in serum IL- 18 concentrations was associated with an increased chance of being in the 20% of slowest walkers (odds ratio 1.45; 95% confidence interval, 1. 17-1.80; p =.0007) and 20% of those with poorest function based on the Short Physical Performance Battery Score (odds ratio 1.52; 95% confidence interval, 1.22-1.89; p =.000 16) in age sex adjusted logistic regression models. There was no association with Activities of Daily Living (p =.26) or Mini-Mental State Examination score (p =.66). The C allele of the IL-18 polymorphism rs5744256 reduced serum concentrations of IL- 18 by 39 pmol/mL per allele (p =.00001). The rs5744256 single nucleotide polymorphism was also associated with shorter walk times in InCHIANTI (n = 662, p =.016) and Iowa-EPESE (n = 995, p =.026). In pooled ranked models rs5744256 was also associated with higher SPPB scores (n = 167 1, p =.019). Instead of adjusting for confounders in the IL-18 walk time association, we used rs5744256 in a Mendelian randomization analysis: The association remained in instrumental variable models (p =.021). Conclusion. IL-18 concentrations are associated with physical function in 65- to 80-year-olds. A polymorphism in the IL-18 gene alters IL-18 concentrations and is associated with an improvement in walk speed. IL-18 may play an active role in age-related functional impairment, but these findings need independent replication. C1 Peninsula Med Sch, Exeter EX1 2LU, Devon, England. Univ Plymouth, Dept Stat, Plymouth PL4 8AA, Devon, England. Italian Natl Res Council Aging, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Univ Florence, IOT, Florence, Italy. Univ Florence, Dept Med & Surg Crit Care, Florence, Italy. Natl Inst Aging, Longitudinal Studies Sect, Clin Res Branch, Ctr Gerontol Res, Baltimore, MD USA. Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Frayling, TM (reprint author), Peninsula Med Sch, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM tim.frayling@pms.ac.uk OI Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413, R01 AG024233, R01 AG24233-01]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 29 TC 34 Z9 35 U1 1 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2007 VL 62 IS 1 BP 73 EP 78 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 178KS UT WOS:000247220200011 PM 17301041 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word form OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2007 VL 36 IS 1 BP 17 EP 17 DI 10.1038/laban0107-17 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 159KB UT WOS:000245863400005 PM 17183336 ER PT J AU Chalela, JA Kidwell, CS Nentwich, LM Luby, M Butman, JA Demchuk, AM Hill, MD Patronas, N Latour, L Warach, S AF Chalela, Julio A. Kidwell, Chelsea S. Nentwich, Lauren M. Luby, Marie Butman, John A. Demchuk, Andrew M. Hill, Michael D. Patronas, Nicholas Latour, Lawrence Warach, Steven TI Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison SO LANCET LA English DT Article ID DIFFUSION-WEIGHTED MR; INTRACEREBRAL HEMORRHAGE; ISCHEMIC-STROKE; SYMPTOM ONSET; CT; BRAIN; INFARCTION; DIAGNOSIS; VARIABILITY; ACCURACY AB Background Although the use of magnetic resonance imaging (MRI) for the diagnosis of acute stroke is increasing, this method has not proved more effective than computed tomography (CT) in the emergency setting. We aimed to prospectively compare CT and MRI for emergency diagnosis of acute stroke. Methods We did a single-centre, prospective, blind comparison of non-contrast CT and MRI (with diffusion-weighted and susceptibility weighted images) in a consecutive series of patients referred for emergency assessment of suspected acute stroke. Scans were independently interpreted by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. Results 356 patients, 217 of whom had a final clinical diagnosis of acute stroke, were assessed. MRI detected acute stroke (ischaemic or haemorrhagic), acute ischaemic stroke, and chronic haemorrhage more frequently than did CT (p<0.0001, for all comparisons). MRI was similar to CT for the detection of acute intracranial haemorrhage. MRI detected acute ischaemic stroke in 164 of 356 patients (46%; 95% CI 41-51%), compared with CT in 35 of 356 patients (10%; 7-14%). In the subset of patients scanned within 3 h of symptom onset, MRI detected acute ischaemic stroke in 41 of 90 patients (46%; 35-56%); CT in 6 of 90 (7%; 3-14%). Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78-88%) and CT of 26% (56 of 217; 20-32%) for the diagnosis of any acute stroke. Interpretation MRI is better than CT for detection of acute ischaemia, and can detect acute and chronic haemorrhage; therefore it should be the preferred test for accurate diagnosis of patients with suspected acute stroke. Because our patient sample encompassed the range of disease that is likely to be encountered in emergency cases of suspected stroke, our results are directly applicable to clinical practice. C1 NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Georgetown Univ, Washington Hosp Ctr, Washington, DC USA. Boston Med Ctr, Boston, MA USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Warach, S (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, NIH, 10 Ctr Dr,Rm B1D733,MSC 1063, Bethesda, MD 20892 USA. EM warachs@ninds.nih.gov RI Butman, John/A-2694-2008; Demchuk, Andrew/E-1103-2012; OI Demchuk, Andrew/0000-0002-4930-7789; Hill, Michael/0000-0002-6269-1543; Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS002975-07] NR 28 TC 425 Z9 444 U1 2 U2 27 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN-FEB PY 2007 VL 369 IS 9558 BP 293 EP 298 DI 10.1016/S0140-6736(07)60151-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 131ZR UT WOS:000243912000033 PM 17258669 ER PT J AU Schunemann, HJ Hill, SR Kakad, M Bellamy, R Uyeki, TM Hayden, FG Yazdanpanah, Y Beigel, J Chotpitayasunondh, T Del Mar, C Farrar, J Hien, TT Ozbay, B Sugaya, N Fukuda, K Shindo, N Stockman, L Vist, GE Croisier, A Nagjdaliyev, A Roth, C Thomson, G Zucker, H Oxman, AD AF Schunemann, Holger J. Hill, Suzanne R. Kakad, Meetali Bellamy, Richard Uyeki, Timothy M. Hayden, Frederick G. Yazdanpanah, Yazdan Beigel, John Chotpitayasunondh, Tawee Del Mar, Chris Farrar, Jeremy Hien, Tran Tinh Ozbay, Bulent Sugaya, Norio Fukuda, Keiji Shindo, Nikki Stockman, Lauren Vist, Gunn E. Croisier, Alice Nagjdaliyev, Azim Roth, Cathy Thomson, Gail Zucker, Howard Oxman, Andrew D. TI WHO rapid advice guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus SO LANCET INFECTIOUS DISEASES LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; OSELTAMIVIR TREATMENT; PANDEMIC INFLUENZA; HEALTHY-ADULTS; SAFETY; ZANAMIVIR; EFFICACY; RECOMMENDATIONS; PROPHYLAXIS; AMANTADINE AB Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely. C1 Italian Natl Canc Inst, INFORMA Unit, Dept Epidemiol, Ist Regina Elena, I-00161 Rome, Italy. WHO, Hlth Technol & Pharmaceut, CH-1211 Geneva, Switzerland. Norwegian Knowledge Ctr Hlth Serv, Oslo, Norway. James Cook Univ Hosp, Dept Infect & Travel Med, Middlesbrough, Cleveland, England. Bond Univ, Fac Med & Hlth Sci, Gold Coast, Qld, Australia. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Resp & Enter Viruses Branch, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Influenza Div, Atlanta, GA USA. Univ Oxford, Clin Res Unit, Oxford OX1 2JD, England. Hosp Trop Dis, Ho Chi Minh City, Vietnam. Serv Univ Malad Infect, Fac Med Lille, CH Tourcoing, Tourcoing, France. NIH, Ctr Clin, Bethesda, MD 20892 USA. Queen Sirikit Natl Inst Child Hlth, MOPH, Bangkok, Thailand. Children Clin Hosp, Baku, Azerbaijan. Yuzunzu Yil Univ Van, Van, Turkey. Keio Univ, Fac Med, Keiyu Hosp, Dept Pediat, Kanagawa, Japan. WHO, Global Influenza Programme, CSR Off Alert & Response & Emerging & Dangerous P, CH-1211 Geneva, Switzerland. RP Schunemann, HJ (reprint author), Italian Natl Canc Inst, INFORMA Unit, Dept Epidemiol, Ist Regina Elena, I-00161 Rome, Italy. EM Schuneh@mcmaster.ca RI Del Mar, Christopher/B-1136-2008; Beigel, John/A-7111-2009 OI Del Mar, Christopher/0000-0003-3821-8163; NR 36 TC 111 Z9 124 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2007 VL 7 IS 1 BP 21 EP 31 DI 10.1016/S1473-3099(06)70684-3 PG 11 WC Infectious Diseases SC Infectious Diseases GA 123DO UT WOS:000243276700027 PM 17182341 ER PT J AU Singleton, A AF Singleton, Andy TI Lifeline SO LANCET NEUROLOGY LA English DT Editorial Material C1 NIA, Genet Mol Lab, Bethesda, MD 20892 USA. RP Singleton, A (reprint author), NIA, Genet Mol Lab, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2007 VL 6 IS 1 BP 25 EP 25 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 119UI UT WOS:000243039000015 ER PT J AU Litton, P AF Litton, Paul TI The insignificance of choice and Wallace's normative approach to responsibility SO LAW AND PHILOSOPHY LA English DT Article C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Litton, P (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Rm 1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM littonp@mail.hih.gov NR 11 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-5249 J9 LAW PHILOS JI Law Philos. PD JAN PY 2007 VL 26 IS 1 BP 67 EP 93 DI 10.1007/s10982-006-0001-0 PG 27 WC Ethics; Law SC Social Sciences - Other Topics; Government & Law GA 089WR UT WOS:000240913100003 ER PT J AU Hoffman, AF Oz, M Yang, RQ Lichtman, AH Lupica, CR AF Hoffman, Alexander F. Oz, Murat Yang, Ruiqin Lichtman, Aron H. Lupica, Carl R. TI Opposing actions of chronic Delta 9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation SO LEARNING & MEMORY LA English DT Article ID RAT-BRAIN; SYNAPTIC-TRANSMISSION; ENDOGENOUS CANNABINOIDS; WORKING-MEMORY; SPATIAL MEMORY; CB1 RECEPTORS; MARIJUANA USE; CA1 NEURONS; IN-VIVO; INHIBITION AB Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long- term potentiation (LTP), a potential substrate for learning and memory, the consequences of prolonged exposure to Delta(9)-THC for hippocampal function are poorly understood. Rats were injected with Delta(9)-THC (10 mg/ kg, i. p., q. d.) for 1, 3, or 7 d, and electrophysiological recordings were performed in hippocampal slices 1d after the final injection. At this time, Delta(9)-THC was undetectable in hippocampus using liquid chromatography-mass spectrometry (LC-MS). Hippocampal LTP generated using high- frequency (HFS) or theta burst stimulation was not observed in brain slices from the 7-d Delta(9)-THC-treated animals. Delta(9)-THC also blocked HFS- LTP after 3 d, but not 1 d of treatment. The complete blockade of LTP persisted for 3 d after the last Delta(9)-THC injection, and full reversal of the LTP deficit was not observed up to 14 d following Delta(9)-THC withdrawal. The cannabinoid antagonist AM251 (2 mg/kg), administered before each Delta(9)-THC injection prevented the blockade of LTP, and 7-d treatment with AM251 alone significantly increased the level of LTP. Chronic Delta(9)-THC also produced tolerance to the inhibition of synaptic GABA, but not glutamate release by the agonist WIN55,212-2. These data define consequences of repeated Delta(9)-THC exposure for synaptic plasticity in the hippocampus that may help explain memory impairments in humans following chronic marijuana use. C1 Natl Inst Drug Abuse, US Dept Hlth & Human Serv, NIH,Electrophysiol Res Unit, Intramural Res Program,Cellular Neurobiol Branch, Baltimore, MD 21224 USA. Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Lupica, CR (reprint author), Natl Inst Drug Abuse, US Dept Hlth & Human Serv, NIH,Electrophysiol Res Unit, Intramural Res Program,Cellular Neurobiol Branch, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov RI Oz, Murat/E-2148-2012; Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 FU Intramural NIH HHS; NIDA NIH HHS [P50 DA005274, P50-DA005274, R01 DA015683, R01-DA015683] NR 78 TC 76 Z9 82 U1 5 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD JAN-FEB PY 2007 VL 14 IS 1-2 BP 63 EP 74 DI 10.1101/lm.439007 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 143JF UT WOS:000244716200008 PM 17202425 ER PT J AU Ise, T Nagata, S Kreitman, RJ Wilson, WH Wayne, AS Stetler-Stevenson, M Bishop, MR Scheinberg, DA Rassenti, L Kipps, TJ Kyle, RA Jelinek, DF Pastan, I AF Ise, T. Nagata, S. Kreitman, R. J. Wilson, W. H. Wayne, A. S. Stetler-Stevenson, M. Bishop, M. R. Scheinberg, D. A. Rassenti, L. Kipps, T. J. Kyle, R. A. Jelinek, D. F. Pastan, I. TI Elevation of soluble CD307 (IRTA2/FcRH5) protein in the blood and expression on malignant cells of patients with multiple myeloma, chronic lymphocytic leukemia, and mantle cell lymphoma SO LEUKEMIA LA English DT Article DE immunotherapy; immunomodulation; cancer diagnosis; monoclonal antibodies ID FC-RECEPTOR HOMOLOGS; B-CELLS; FAMILY; CLASSIFICATION; ANTIBODIES AB CD307 is a differentiation antigen expressed in B-lineage cells. One soluble and two membrane-bound forms have been predicted and an enzyme-linked immunosorbent assay ( ELISA) for soluble CD307 established. Our goal was to determine if CD307 is expressed on the surface of cells from patients with multiple myeloma ( MM), chronic lymphocytic leukemia ( CLL), mantle cell lymphoma ( MCL) and other B-cell malignancies and if soluble CD307 levels are elevated in the blood of patients with these B-cell malignancies. Cells and blood were collected from patients. Expression of CD307 was measured by flow cytometry and blood levels of soluble CD307 by ELISA. High soluble CD307 levels were detected in 21/43 ( 49%) of patients with MM, 36/46 ( 78%) with CLL and 9/24 ( 38%) with MCL. Soluble CD307 levels correlated with plasma cell percentages in bone marrow aspirates in MM and total white blood cells in CLL. CD307 on the cell membrane was detected by flow cytometry in 8/8 MM, 23/29 CLL and 4/5 MCL samples. Because CD307 is present on malignant cells from patients with MM, CLL and MCL, CD307 may be a useful therapeutic target for the treatment of these diseases. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Ctr Expt Therapeut, New York, NY 10021 USA. Univ Calif San Diego, Moores Canc Ctr, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. Mayo Clin, Coll Med, Genomics Res Ctr, Lab Med & Pathol, Rochester, MN USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS NR 25 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2007 VL 21 IS 1 BP 169 EP 174 DI 10.1038/sj.leu.2404445 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 118IA UT WOS:000242934500025 PM 17051241 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, Kieron Wilson, Wyndham H. TI Angioimmunoblastic T-cell lymphoma: Immune modulation as a therapeutic strategy SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID VIRUS-INFECTION; HELPER-CELLS; LYMPHADENOPATHY C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunleavk@mail.nih.org; wilsonw@mail.nih.gov NR 15 TC 8 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 3 BP 449 EP 451 DI 10.1080/10428190701245138 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 148WM UT WOS:000245108100004 PM 17454581 ER PT J AU Sabaawy, HE Sandoval, C Guo, QX Yin, CH Kulangara, A Lee, J Wormser, G Jayabose, S Pine, SR AF Sabaawy, Hatem E. Sandoval, Claudio Guo, Qianxu Yin, Changhong Kulangara, Anita Lee, Jooyun Wormser, Gary Jayabose, Somasundaram Pine, Sharon R. TI Lymphoproliferative clonal origin of AIDS-related non-Hodgkin's lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Letter ID EPSTEIN-BARR-VIRUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; B-CELL; NUCLEOTIDE-SEQUENCE; GENE; PCR C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Maria Fareri Childrens Hosp, Dept Pediat, Valhalla, NY USA. New York Med Coll, Westchester Med Ctr, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. RP Pine, SR (reprint author), NCI, Human Carcinogenesis Lab, 37 Convent Dr, Bethesda, MD 20892 USA. EM pines@mail.nih.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 4 BP 812 EP 815 DI 10.1080/10428190601173109 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 165PY UT WOS:000246318900028 PM 17454643 ER PT J AU Dunleavy, K Staudt, LM Wilson, WH AF Dunleavy, Kieron Staudt, Louis M. Wilson, Wyndham H. TI The BCL-2 biomarker in the era of molecular diagnosis of diffuse large B-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; ELDERLY-PATIENTS; R-CHOP; CHEMOTHERAPY; RITUXIMAB; SURVIVAL; DLBCL C1 NCI, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 17 TC 1 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 6 BP 1061 EP 1063 DI 10.1080/10428190701420467 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 186LB UT WOS:000247779100003 PM 17577765 ER PT J AU Morris, JC Janik, JE AF Morris, John C. Janik, John E. TI Therapeutic immunotoxins for lymphoid malignancies: The end of the beginning SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID ANTI-CD30 IMMUNOTOXIN; CYTOTOXIC ACTIVITY; ANTIBODY; HODGKINS C1 NCI, Ctr Canc Res, Mark O Hatfield Clin Res Ctr, Metab Branch, Bethesda, MD 20892 USA. RP Morris, JC (reprint author), NCI, Ctr Canc Res, Mark O Hatfield Clin Res Ctr, Metab Branch, Room 4-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov NR 12 TC 1 Z9 1 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 6 BP 1067 EP 1069 DI 10.1080/10428190701344949 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 186LB UT WOS:000247779100005 PM 17577767 ER PT J AU Noel, D Djouad, F Bouffi, C Mrugala, D Jorgensen, C AF Noel, Daniele Djouad, Farida Bouffi, Carine Mrugala, Dominique Jorgensen, Christian TI Multipotent mesenchymal stromal cells and immune tolerance SO LEUKEMIA & LYMPHOMA LA English DT Review DE mesenchymal stem cell; immunosuppression; characterization ID HEMATOPOIETIC STEM-CELLS; ANTIGEN-PRESENTING CELL; PROLIFERATION IN-VITRO; VERSUS-HOST-DISEASE; ACTIVATED T-CELLS; EX-VIVO EXPANSION; BONE-MARROW; INTERFERON-GAMMA; PROGENITOR CELLS; DENDRITIC CELLS AB Multipotent mesenchymal stromal cells or mesenchymal stem cells ( MSC) are isolated mainly from bone marrow and adipose tissue but are identified in other tissues such as synovium, periosteum or placenta. They are characterised by their property to adhere to plastic, their phenotype and their ability to differentiate into three lineages ( chondrocytes, osteoblasts and adipocytes). More recently, these cells were shown to escape immune recognition and inhibit immune responses. MSC may modulate the function of the major immune cell populations, including antigen-presenting cells, T cells, B cells and natural killer cells. The aim of this review is to focus on the molecular mechanisms, still poorly understood, which are responsible of the immunosuppressive effects mediated by the MSC. Finally, the data obtained from in vivo experimentation in various animal models as well as potential therapeutic applications will be presented. C1 INSERM, U844, Montpellier, France. Univ Montpellier 1, UFR Med, Montpellier, France. Hop St Eloi, Unite Therapie Cellulaire & Genique, Montpellier, France. NIH, Cartilage Biol & Orthopaed Branch, Bethesda, MD USA. Hop Lapeyronie, Serv Immunol Rhumatol, Montpellier, France. RP Noel, D (reprint author), INSERM, CHU St Eloi, U844, 80 Ave Augustin Fliche, F-34091 Montpellier, France. EM noel@montp.inserm.fr RI Noel, Daniele/E-5719-2016; OI Djouad, Farida/0000-0001-8248-6822 NR 56 TC 69 Z9 75 U1 1 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 7 BP 1283 EP 1289 DI 10.1080/10428190701361869 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 186LD UT WOS:000247779300007 PM 17613755 ER PT J AU Herishanu, Y Wiestner, A AF Herishanu, Yair Wiestner, Adrian TI Prognostic factors for risk-adapted therapy in chronic lymphocytic leukemia - The search continues SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID GENE-EXPRESSION; FLUDARABINE; ABERRATIONS C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bld 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnera@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 8 BP 1468 EP 1469 DI 10.1080/10428190701534473 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 199UO UT WOS:000248720900004 PM 17701575 ER PT J AU Bishu, S Quigley, JM Schmitz, J Bishu, SR Stemm, RA Olsasky, SM Paknikar, S Holdeman, KH Armitage, JO Hankins, JH AF Bishu, S. Quigley, J. M. Schmitz, J. Bishu, S. R. Stemm, R. A. Olsasky, S. M. Paknikar, S. Holdeman, K. H. Armitage, J. O. Hankins, J. H. TI F-18-fluoro-deoxy-glucose positron emission tomography in the assessment of peripheral T-cell lymphomas SO LEUKEMIA & LYMPHOMA LA English DT Article DE PET; diagnostic accuracy; PTCL ID NON-HODGKINS-LYMPHOMA; FDG-PET; F-18 FLUORODEOXYGLUCOSE; COMPUTED-TOMOGRAPHY; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; CT; CLASSIFICATION; CHEMOTHERAPY AB F-18-fluoro-deoxy-glucose positron emission tomography (PET) is highly sensitive and specific in the imaging of B- cell lymphomas. In contrast, its utility in the diagnostic evaluation of T-cell lymphomas is less defined. In this article, we present our finding utilizing PET in peripheral T-cell lymphomas (PTCL). A retrospective review of patients who underwent PET examinations at our institution produced 24 PET examinations among patients with PTCL. A lesion-based analysis was undertaken to evaluate the diagnostic accuracy of PET in PTCL. PET findings were compared with a standard of reference and sensitivity, specificity, positive and negative predictive values were calculated. PET had an overall sensitivity of 86% and specificity of 100%. PET had high sensitivity (95%) at nodal and non-cutaneous extra-nodal sites and poor sensitivity ( 3%) at cutaneous sites. The mean SUV of abnormal foci in anaplastic large cell lymphoma was 11 mg/ ml (range: 3 - 40), and PTCL- unclassified was 8 mg/ ml (range: 1 - 23). C1 NIMH, Natl Inst Hlth, Bethesda, MD USA. Univ Nebraska, Med Ctr, Coll Med, Omaha, NE USA. Creighton Univ, Med Ctr, Coll Med, Omaha, NE USA. No Univ, Med Ctr, Dept Pathol, Omaha, NE USA. Creighton Univ, Med Ctr, Dept Radiol, Div Nucl Med, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Radiol, Div Nucl Med, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Dept Med, Sect Hematol & Oncol, Omaha, NE 68105 USA. RP Bishu, S (reprint author), 5225 Pooks Hill Rd,1207-S, Bethesda, MD 20814 USA. EM bishus@mail.nih.gov NR 30 TC 31 Z9 31 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 8 BP 1531 EP 1538 DI 10.1080/10428190701344915 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 199UO UT WOS:000248720900013 PM 17701584 ER PT J AU Bishu, S Quigley, JM Bishu, SR Olsasky, SM Stem, RA Shostrom, VK Holdeman, KP Paknikar, S Armitage, JO Hankins, JH AF Bishu, Shrinivas Quigley, Joanna M. Bishu, Shreenath R. Olsasky, Sarah M. Stem, Richard A. Shostrom, Valerie K. Holdeman, Karen P. Paknikar, Subash Armitage, James O. Hankins, Jordan H. TI Predictive value and diagnostic accuracy of F-18-fluoro-deoxy-glucose positron emission tomography treated grade 1 and 2 follicular lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE follicular lymphoma grade 1; follicular lymphoma grade 2; PET; staging; therapeutic assessment ID NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; FDG-PET; RESPONSE ASSESSMENT; STAGE-I; THERAPY; CRITERIA; DISEASE; CHEMOTHERAPY; EXPERIENCE AB F-18-fluoro-deoxy-glucose positron emission tomography (PET) is a powerful tool for the imaging of aggressive B-cell lymphomas. In contrast, there is relatively little data on PET in follicular lymphoma grade 1 (FL-1) and grade 2 (FL-2). In this manuscript, we present our findings utilizing PET in treated FL-1 and FL-2. A retrospective review of patients who underwent PET examinations at our institution produced 95 PET examinations among 31 patients with FL-1 and FL-2. PET was obtained at initial staging, mid-induction and post-treatment. Results were compared with clinical follow-up. PET had high sensitivity (95%) and specificity (88%) for lesion detection in treated FL-1 and FL-2. Abnormal foci in FL-1 and FL-2 had similar intensities. Post-induction PET positive patients had shorter mean progression free survivals compared with PET negative patients (p-value <= 0.001), post-salvage PET positive trended toward shorter mean response duration compared with negative patients (p-value: 0.09). Our results indicate that PET is accurate in the diagnostic assessment of treated FL-1 and FL-2 and, post- treatment PET positive patients are likely to relapse prior to PET negative patients. C1 NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Coll Med, Lincoln, NE 68583 USA. NW Univ, Dept Pathol, Evanston, IL 60208 USA. Univ Nebraska, Med Ctr, Coll Publ Hlth, Lincoln, NE 68583 USA. Univ Nebraska, Dept Radiol, Div Nucl Med, Lincoln, NE 68583 USA. Creighton Univ, Med Ctr, Dept Radiol, Div Nucl Med, Omaha, NE 68178 USA. Univ Nebraska, Med Ctr, Dept Med, Sect Oncol & Hematol, Lincoln, NE 68583 USA. RP Bishu, S (reprint author), 5225 Pooks Hill Rd,1207-S, Bethesda, MD 20814 USA. EM bishus@mail.nih.gov NR 35 TC 35 Z9 37 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 8 BP 1548 EP 1555 DI 10.1080/10428190701422059 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 199UO UT WOS:000248720900015 PM 17701586 ER PT J AU Wang, S AF Wang, Sophia TI Publishing on genes and lymphoma in the era of "big science'' SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID NON-HODGKIN-LYMPHOMA; RISK C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wang, S (reprint author), 6120 Execut Blvd,Room 5104, Rockville, MD 20852 USA. EM wangso@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2007 VL 48 IS 11 BP 2091 EP 2092 DI 10.1080/10428190701684526 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 229XE UT WOS:000250839100003 PM 17990173 ER PT J AU Silver, RT Bennett, JM Goldman, JM Spivak, JL Tefferi, A AF Silver, R. T. Bennett, J. M. Goldman, J. M. Spivak, J. L. Tefferi, A. TI The Third International Congress on Myeloproliferative and Myelodysplastic Syndromes SO LEUKEMIA RESEARCH LA English DT Article DE myelodysplastic syndrome; JAK2; myeloproliferative; leukemia AB This meeting was convened by Richard T. Silver and co-chaired by Jerry L. Spivak. It was held from 27 to 29 October 2005 in Washington, DC. Thirty-one invited speakers from seven different countries participated in the conference, which was attended by more than 300 individuals from 23 countries. As in previous years, a clinical symposium for patients, held the day before the symposium, was sponsored by the Cancer Research and Treatment Fund, Inc., New York, NY 10021. This meeting report provides a summary of the five sessions prepared and highlighted by one of the session chairs. In addition to the formal presentations on the biology, clinical aspects and management of these diverse marrow stem cell disorders, there was considerable interest generated because of the availability of several new agents that have been recently approved. A special luncheon satellite symposium was devoted to the dramatic changes in the therapeutic options for the myelodysplastic syndromes, sponsored by MGI Pharma, Inc. The keynote address was presented by Dr. George Q. Daley from Harvard Medical School and the Children's Hospital Medical Center. He reviewed the molecular steps in the formation of the Philadelphia chromosome and some of the newly described mutations leading to resistance to chemotherapy (see Section 4). (c) 2006 Elsevier Ltd. All rights reserved. C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Mayo Clin, Coll Med, Rochester, MN USA. RP Silver, RT (reprint author), Cornell Univ, Weill Med Coll, 1300 York Ave Box 581, New York, NY 10021 USA. EM rtsilve@med.cornell.edu NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2007 VL 31 IS 1 BP 11 EP 17 DI 10.1016/j.leukres.2006.02.023 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 116JF UT WOS:000242797900004 PM 16620972 ER PT S AU Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ AF Schoenbaum, Geoffrey Gottfried, Jay A. Murray, Elisabeth A. Ramus, Seth J. BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Preface SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci C1 [Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Gottfried, Jay A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Murray, Elisabeth A.] NIMH, Bethesda, MD 20892 USA. [Ramus, Seth J.] Bowdoin Coll, Brunswick, ME 04011 USA. RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP XI EP XIII DI 10.1196/annals.1401.040 PG 3 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300001 PM 18156507 ER PT S AU Murray, EA Izquierdo, A AF Murray, Elisabeth A. Izquierdo, Alicia BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Orbitofrontal cortex and amygdala contributions to affect and action in primates SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci DE reward; emotion; inferotemporal cortex; stimulus-reward association ID ORBITAL PREFRONTAL CORTEX; MONKEYS MACACA-MULATTA; INFANT RHESUS-MONKEYS; MACAQUE MONKEYS; BASOLATERAL AMYGDALA; DEFENSIVE BEHAVIORS; EMOTIONAL RESPONSES; UNILATERAL LESIONS; VOLUNTARY MOVEMENT; NEUROTOXIC LESIONS AB The amygdala and orbitofrontal cortex (OFC) work together as part of the neural circuitry guiding goal-directed behavior. This chapter explores the way in which the amygdala and OFC contribute to emotion and reward processing in macaque monkeys, taking into account recent methodological and conceptual advances. Although direct functional interaction of the amygdala and OFC is necessary for some types of stimulus-reward associations, it is not necessary for others. Both regions contribute to the expression of defensive responses to a potential predator. Contrary to the prevailing view, the amygdala and OFC make distinct contributions to emotional responses and reward processing. C1 [Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Izquierdo, Alicia] Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA. RP Murray, EA (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, 49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov; murraye@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 FU Intramural NIH HHS NR 73 TC 72 Z9 72 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP 273 EP 296 DI 10.1196/annals.1401.021 PG 24 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300017 PM 17846154 ER PT S AU Simmons, JM Ravel, S Shidara, M Richmond, BJ AF Simmons, Janine M. Ravel, Sabrina Shidara, Munetaka Richmond, Barry J. BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum: Guiding actions toward rewards SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci DE motivation; limbic system; basal ganglia; electrophysiology ID BASAL GANGLIA; PREFRONTAL CORTEX; MOTIVATIONAL SIGNIFICANCE; AMYGDALOID PROJECTIONS; CORTICAL PROJECTIONS; BASOLATERAL AMYGDALA; PRIMATE STRIATUM; NEURAL RESPONSES; FRONTAL-CORTEX; ANTICIPATION AB We have investigated how neuronal activity in the orbitofrontal-ventral striatal circuit is related to reward-directed behavior by comparing activity in these two regions during a visually guided reward schedule task. When a set of visual cues provides information about reward contingency, that is, about whether or not a trial will be rewarded, significant subpopulations of neurons in both orbitofrontal cortex and ventral striatum encode this information. Orbitofrontal and ventral striatal neurons also differentiate between rewarding and non-rewarding trial outcomes, whether or not those outcomes were predicted. The size of the neuronal subpopulation encoding reward contingency is twice as large in orbitofrontal cortex (50% of neurons) as in ventral striatum (26%). Reward-contingency-dependent activity also appears earlier during a trial in orbitofrontal cortex than in ventral striatum. The peak reward-contingency representation in orbitofrontal cortex (31% of neurons), occurs during the wait period, a period of high anticipation prior to any action. The peak ventral striatal representation of reward contingency (18%) occurs during the go period, a time of action. We speculate that signals from orbitofrontal cortex bias ventral striatal activity, and that a flow of reward-contingency information from orbitofrontal cortex to ventral striatum serves to guide actions toward rewards. C1 [Simmons, Janine M.; Ravel, Sabrina; Richmond, Barry J.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. [Shidara, Munetaka] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. RP Simmons, JM (reprint author), NIMH, Neuropsychol Lab, Room 1B80,Bldg 49, Bethesda, MD 20892 USA. EM simmonsj@mail.nih.gov NR 61 TC 18 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP 376 EP 394 DI 10.1196/annals.1401.028 PG 19 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300022 PM 17872398 ER PT S AU Blair, RJR AF Blair, R. J. R. BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Dysfunctions of medial and lateral orbitofrontal cortex in psychopathy SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci DE psychopathy; orbitofrontal cortex; amygdala ID VENTROMEDIAL PREFRONTAL CORTEX; CALLOUS-UNEMOTIONAL TRAITS; ANTERIOR CINGULATE CORTEX; BILATERAL AMYGDALA LESIONS; RESPONSE-REVERSAL; DECISION-MAKING; RHESUS-MONKEYS; HUMAN BRAIN; CONDUCT PROBLEMS; CRIMINAL PSYCHOPATHS AB Psychopathy is a developmental disorder marked by emotional hypo-responsiveness and an increased risk for instrumental and reactive aggression. In this paper, it will be argued that the developmental origins of psychopathy do not lie in orbitofrontal cortex (OFC) dysfunction. This is because the key functional impairments seen in psychopathy are associated with amygdala damage, not with OFC damage. However, it will be argued that the role played by the integrated functioning of the amygdala and medial OFC in stimulus-reinforcement learning and decision making is disrupted in psychopathy. Impaired learning of stimulus-reinforcement associations and representation of reinforcement expectations are thought to underlie the impairments in socialization and appropriate decision making seen in psychopathy. It is suggested that the impairment in the role of medial OFC in prediction error signaling and the detection of contingency change may underlie the impairments in flexible behavioral change seen in psychopathy. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Room 206,15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 127 TC 44 Z9 45 U1 9 U2 44 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP 461 EP 479 DI 10.1196/annals.1401.017 PG 19 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300028 PM 17698995 ER PT S AU Drevets, WC AF Drevets, Wayne C. BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Orbitofrontal cortex function and structure in depression SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci DE major depressive disorder; bipolar disorder; anterior cingulate cortex; PET; MRI ID MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; MAGNETIC-RESONANCE SPECTROSCOPY; AMINOBUTYRIC-ACID LEVELS; SEVERE MENTAL-ILLNESS; GLIAL-CELL DENSITY; MOOD-DISORDERS; BIPOLAR DISORDER; MAJOR DEPRESSION AB The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression. C1 NIMH MIB, Mood & Anxiety Program, NIH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RP Drevets, WC (reprint author), NIMH MIB, Mood & Anxiety Program, NIH, Sect Neuroimaging Mood & Anxiety Disorders, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM drevetsw@intra.nimh.nih.gov NR 142 TC 166 Z9 171 U1 5 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP 499 EP 527 DI 10.1196/annals.1401.029 PG 29 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300030 PM 17872395 ER PT S AU Resnick, SM Lamar, M Driscoll, I AF Resnick, Susan M. Lamar, Melissa Driscoll, Ira BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes SO LINKING AFFECT TO ACTION: CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Linking Affect to Action - Critical Contributions of the Orbitofrontal Cortex CY MAR 11-14, 2007 CL New York, NY SP New York Acad Sci DE orbitofrontal cortex; aging; cognition; MRI; longitudinal studies ID IMMEDIATE VISUAL MEMORY; OLDER-ADULTS; RECOGNITION MEMORY; ALZHEIMER-DISEASE; AGING BRAIN; IMPAIRMENT; LESIONS; SAMPLE; TASKS; RATS AB Cross-sectional and longitudinal findings from the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study indicate that the orbitofrontal cortex (OFC) is among those regions vulnerable to age-associated tissue loss in older adults without dementia. Neuropathologic and recent in vivo amyloid imaging studies indicate that the OFC is also among the earliest neocortical regions to show deposition of amyloid plaques in aging and Alzheimer's disease. We performed behavioral and imaging studies to investigate age effects on specific aspects of OFC function. We compared performance in young (age 20-40) and old (age 60 and older) adults on cognitive tasks selected for differential sensitivity to OFC versus dorsolateral prefrontal cortex (DLPFC). Overall, greater age differences were seen in the OFC tasks compared to DLPFC tasks, with Delayed Match and Non-Match to Sample tasks showing the greatest effect size among OFC tasks and Self-Ordered Pointing Task showing the greatest effect size among DLPFC tasks. A functional magnetic resonance imaging study was conducted in parallel to probe the neural underpinnings of age differences in OFC function using the Delayed Match and Non-Match to Sample paradigm. Young but not old adults showed the expected OFC activation. Older compared with young adults showed greater activation in association with successful performance for several posterior regions, perhaps indicating compensation in the face of OFC deficits. Together, these findings indicate a vulnerability of the OFC to age-related decline in brain structure and function. Future studies using new in vivo imaging probes will help determine whether neuropathologic changes underlie the structural and functional changes. C1 [Resnick, Susan M.; Driscoll, Ira] NIA, LPC, NIH, Gerontol Res Ctr,Intramural Res Program, Baltimore, MD 21224 USA. [Lamar, Melissa] Kings Coll London, Inst Psychiat, London SE5 8AH, England. RP Resnick, SM (reprint author), NIA, LPC, NIH, Gerontol Res Ctr,Intramural Res Program, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM susan.resnick@nih.gov FU Intramural NIH HHS [Z01 AG000191-11] NR 39 TC 35 Z9 36 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-683-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1121 BP 562 EP 575 DI 10.1196/annals.1401.027 PG 14 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychiatry SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BHD18 UT WOS:000252265300033 PM 17846159 ER PT S AU Maceyka, M Milstien, S Spiegel, S AF Maceyka, Michael Milstien, Sheldon Spiegel, Sarah BE Brown, HA TI Measurement of mammalian sphingosine-1-phosphate phosphohydrolase activity In Vitro and In Vivo SO LIPIDOMICS AND BIOACTIVE LIPIDS: LIPIDS AND CELL SIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID LIPID PHOSPHATE PHOSPHATASES; SPHINGOSINE 1-PHOSPHATE; SACCHAROMYCES-CEREVISIAE; SPHINGOLIPID METABOLISM; CERAMIDE SYNTHESIS; KEY REGULATOR; CELL-DEATH; KINASE; GROWTH; RECEPTORS AB Sphingolipid metabolites have emerged as key players in diverse processes including cell migration, growth, and apoptosis. Ceramide and sphingosine typically inhibit cell growth and induce apoptosis, while sphingosine-1-phosphate (S1P) promotes cell growth, inhibits apoptosis, and induces cell migration. Thus, enzymes that regulate the levels of these sphingolipid metabolites are of critical importance to understanding cell fate. There are two known mammalian isoforms of S1P phosphohydrolases (SPP1 and SPP2) that reversibly degrade S1P to sphingosine. This chapter discusses the importance of SPPs and describes assays that can be used to measure the activity of these two specific SIP phosphohydrolases in cells and cell lysates. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23284 USA. NIMH, NIH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Maceyka, M (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23284 USA. RI Maceyka, Michael/B-9277-2008 FU Intramural NIH HHS; NIGMS NIH HHS [R37 GM043880] NR 42 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373965-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 434 BP 243 EP 256 DI 10.1016/S0076-6879(07)34013-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGX42 UT WOS:000251128300013 PM 17954251 ER PT S AU Mitra, P Payne, SG Milstien, S Spiegel, S AF Mitra, Poulami Payne, Shawn G. Milstien, Sheldon Spiegel, Sarah BE Brown, HA TI A rapid and sensitive method to measure secretion of sphingosine-1-phosphate SO LIPIDOMICS AND BIOACTIVE LIPIDS: LIPIDS AND CELL SIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID SPHINGOSINE 1-PHOSPHATE; MAST-CELLS; RECEPTORS; KINASE; DEGRANULATION; TRANSPORTER; CHEMOTAXIS; PLATELETS; MOTILITY; PROTEIN AB The serum-borne, bioactive sphingolipid mediator, sphingosine-1-phosphate (S1p), regulates numerous important physiological and pathological processes, mainly acting through specific cell surface G-protein-coupled receptors. Although many mammalian cells can produce S1P, there is little information as to how it is secreted to reach its receptors. Progress in elucidating this mechanism has been hampered by the difficulty of measuring very low levels of Sip. This chapter describes a simple, rapid method to measure Sip export from cells. It also discusses the current knowledge of how Sip is exported out of cells and its physiological significance. C1 Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Sch Med, Richmond, VA 23298 USA. NIMH, NIH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Mitra, P (reprint author), Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Sch Med, Richmond, VA 23298 USA. FU Intramural NIH HHS; NIGMS NIH HHS [R 37 GM043880] NR 21 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373965-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 434 BP 257 EP 264 DI 10.1016/S0076-6879(07)34014-7 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGX42 UT WOS:000251128300014 PM 17954252 ER PT J AU Terrault, NA Shiffman, ML Lok, ASF Saab, S Tong, L Brown, RS Everson, GT Reddy, KR Fair, JH Kulik, LM Pruett, TL Seeff, LB AF Terrault, Norah A. Shiffman, Mitchell L. Lok, Anna S. F. Saab, Sammy Tong, Lan Brown, Robert S., Jr. Everson, Gregory T. Reddy, K. Rajender Fair, Jeffrey H. Kulik, Laura M. Pruett, Timothy L. Seeff, Leonard B. CA A2ALL Study Grp TI Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation SO LIVER TRANSPLANTATION LA English DT Article ID FIBROSIS PROGRESSION; UNITED-STATES; SEVERITY; RECURRENCE; CIRRHOSIS; SURVIVAL; GENOTYPE; PATIENT; DISEASE; SYSTEM AB In this retrospective study of hepatitis C virus (HCV)-infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT <= 20) compared to later cases (LDLT > 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT > 20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT > 20, and LDLT <= 20 were 80%, 79% and 55%, with similar results conditional on survival to 90 days (84%, 87% and 68%, respectively). Predictors of graft loss beyond 90 days included LDLT _-20 vs. DDLT (hazard ratio [HR] = 2.1, P = 0.04), pretransplant hepatocellular carcinoma (HCC) (HR = 2.21, P = 0.03) and model for end-stage liver disease (MELD) at transplantation (HR = 1.24, P = 0.04). In conclusion, 3-year graft and patient survival in HCV-infected recipients of DDLT and LDLT > 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation. C1 Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. Virginia Commonwealth Univ, Med Ctr, Dept Med, Div Gastroenterol, Richmond, VA USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Columbia Univ, Med Ctr, Dept Med, New York, NY USA. Univ Colorado, Dept Med, Div Gastroenterol, Denver, CO USA. Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. Northwestern Univ, Dept Med, Div Gastroenterol, Chicago, IL 60611 USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. NIDDK, NIH, Bethesda, MD USA. RP Terrault, NA (reprint author), Data Coordinating Ctr, A2ALL Study, 315 W Huron St,Suite 240, Ann Arbor, MI 48103 USA. EM o2all-dcc@umich.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NIDDK NIH HHS [U01 DK062444-01, U01 DK062444, U01 DK062467, U01 DK062483, U01 DK062484, U01 DK062494, U01 DK062496, U01 DK062498, U01 DK062505, U01 DK062531, U01 DK062536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK62536] NR 21 TC 66 Z9 67 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JAN PY 2007 VL 13 IS 1 BP 122 EP 129 DI 10.1002/lt.20995 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 121VC UT WOS:000243184100017 PM 17192908 ER PT J AU Romanowska, M Kikawa, KD Fields, JR Maciag, A North, SL Shiao, YH Kasprzak, KS Anderson, LM AF Romanowska, Malgorzata Kikawa, Keith D. Fields, Janet R. Maciag, Anna North, S. Lynn Shiao, Yih-Horng Kasprzak, Kazimierz S. Anderson, Lucy M. TI Effects of selenium supplementation on expression of glutathione peroxidase isoforms in cultured human lung adenocarcinoma cell lines SO LUNG CANCER LA English DT Article DE lung adenocarcinoma cells; lung epithelial cells; glutathione peroxidase; selenium ID MESSENGER-RNA; NUTRITIONAL PREVENTION; CANCER PREVENTION; ENZYME-ACTIVITIES; OXIDATIVE STRESS; DIETARY SELENIUM; RAT-LIVER; MECHANISM; TRIAL; CHEMOPREVENTION AB Selenium is an essential nutrient, a component of several anti-oxidant enzymes, and a possible factor in cancer risk, including lung cancer. We determined the subtoxic range of selenium concentration (as sodium setenite) required to increase and maintain the expression of anti-oxidant selenoproteins gluthathione peroxidases GPX1 and GPX4 at a constant level in cultures of human lung adenocarcinoma cell lines (H460, H1703 and H1944) and in HPL1D, a non-transformed lung epithelial cell line. Selenium dose-dependently increased GPX1 protein expression 1.8-fold in HPL1D cells and similar to 40-fold in H460 and H1944 cancer cells, with maximum effects at 20-40 nM. GPX4 protein was also increased, but more so in HPL1D (five-fold) than in H460 or H1944 cells (two- to three-fold). GPX1 mRNA showed similar patterns but differences of lesser magnitude. GPX1 protein and activity level was not consistently detectable in H1703 cells, with or without Se supplementation; its mRNA was present but very low. GPX4 protein level was also tow in H1703 cells, but was markedly increased by selenium supplementation (48-fold). These results confirm a rote for selenium in risk of lung cancer and the independent regulation of GPX1 and GPX4. Characterization of individual tumors with regard to GPX1 and GPX4 tevels and regulation might be useful for interpretation of clinical studies on effects of selenium in lung cancer risk. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Romanowska, M (reprint author), Natl Canc Inst, Comparat Carcinogenesis Lab, Bldg 538, Frederick, MD 21702 USA. EM mromanowska@ncifcrf.gov FU Intramural NIH HHS NR 44 TC 19 Z9 21 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JAN PY 2007 VL 55 IS 1 BP 35 EP 42 DI 10.1016/j.lungcan.2006.09.007 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 134SB UT WOS:000244103200004 PM 17052796 ER PT J AU Tsurutani, J Steinberg, SM Ballas, M Robertson, M LoPiccolo, J Soda, H Kohno, S Egilsson, V Dennis, PA AF Tsurutani, Junji Steinberg, Seth M. Ballas, Marc Robertson, Matthew LoPiccolo, Jaclyn Soda, Hiroshi Kohno, Shigeru Egilsson, Valgardur Dennis, Phillip A. TI Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma SO LUNG CANCER LA English DT Article DE bronchioloalveolar carcinoma; prognostic factor; NSCLC; akt; smoking ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; TREATED PATIENTS; PATHWAY; GEFITINIB; PTEN; CHEMOTHERAPY; RESISTANCE; PHOSPHORYLATION AB Purpose: Lung cancer is the leading cause of cancer related mortality in the world. Bronchiotoalveotar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKls). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and At activation in patients with BAC. Methods: Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. At activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and Log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results: Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. At activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that mate gender (HR 2.24, 95% CI, 1.07-4.71, p=0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p=0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p=0.013) were associated with a worse prognosis. Conclusions: Mate gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients. Published by Elsevier Ireland Ltd. C1 NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, Canc Res Ctr, Bethesda, MD 20889 USA. Natl Univ Hosp Reykjavik, Dept Pathol, IS-101 Reykjavik, Iceland. Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528501, Japan. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Canc Res Ctr, Navy Med Oncol,Bldg 8,Room 5101,8901 Wisconsin Av, Bethesda, MD 20889 USA. EM pdennis@nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010292-07] NR 35 TC 25 Z9 27 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JAN PY 2007 VL 55 IS 1 BP 115 EP 121 DI 10.1016/j.lungcan.2006.09.026 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 134SB UT WOS:000244103200015 PM 17097759 ER PT J AU James, JA Kim-Howard, XR Bruner, BF Jonsson, MK McClain, MT Arbuckle, MT Walker, C Dennis, GJ Merrill, JT Harley, JB AF James, J. A. Kim-Howard, X. R. Bruner, B. F. Jonsson, M. K. McClain, M. T. Arbuckle, M. T. Walker, C. Dennis, G. J. Merrill, J. T. Harley, J. B. TI Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus SO LUPUS LA English DT Article DE hydroxychloroquine; SLE; systemic lupus erythematosus; therapy ID CONNECTIVE-TISSUE DISEASE; REVISED CRITERIA; LONG-TERM; FOLLOW-UP; ANTIBODIES; COHORT; AUTOANTIBODIES; CLASSIFICATION; EXACERBATIONS; ANTIMALARIALS AB Systemic lupus erythematosus (SLE) is a clinically diverse, complex autoimmune disease which may present with coincident onset of many criteria or slow, gradual symptom accrual. Early intervention has been postulated to delay or prevent the development of more serious sequelae. One option for treatment in this setting is hydroxychloroquine. Using 130 US military personnel who later met ACR SLE criteria, a retrospective study of onset, development and progression of SLE with and without pre-classification hydroxychloroquine (n = 26) use was performed. Patients treated with hydroxychloroquine prior to diagnosis had a longer (Wilcoxon signed rank test, P = 0.018) time between the onset of the first clinical symptom and SLE classification (median: 1.08 versus 0.29 years). Patients treated with prednisone before diagnosis also more slowly satisfied the classification criteria (Wilcoxon signed rank test, P = 0.011). The difference in median times between patients who received NSAIDs before diagnosis, as opposed to those who did not, was not different (P = 0.19). Patients treated with hydroxychloroquine also had a lower rate of autoantibody accumulation and a decreased number of autoantibody specificities at and after diagnosis. These findings are consistent with early hydroxychloroquine use being associated with delayed SLE onset. A prospective, blinded trial testing the capacity of hydroxychloroquine to delay or prevent SLE in high risk populations is warranted. C1 Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma Hlth Sci, Dept Med, Oklahoma City, OK 73104 USA. Univ Oklahoma Hlth Sci, Dept Pathol, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Univ Bergen, Broegelmann Res Lab, N-5020 Bergen, Norway. Walter Reed Army Med Ctr, Dept Rheumatol, Washington, DC 20307 USA. NIAMSD, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Oklahoma City, OK 73104 USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthritis & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM jamesj@omrf.ouhsc.edu FU NCRR NIH HHS [RR15577, RR20143]; NIAID NIH HHS [AI31584, AI50350, AI62629]; NIAMS NIH HHS [AR45084, AR45451, AR48045, AR48980, AR49084, P30 AR053483]; PHS HHS [ARC24717, ARC49084] NR 21 TC 59 Z9 62 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2007 VL 16 IS 6 BP 401 EP 409 DI 10.1177/0961203307078579 PG 9 WC Rheumatology SC Rheumatology GA 196GZ UT WOS:000248471000003 PM 17664230 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, Ferenc Basser, Peter J. Hecht, Anne-Marie Geissler, Erik TI Comparative study of scattering and osmotic properties of synthetic and biopolymer gels SO MACROMOLECULAR SYMPOSIA LA English DT Proceedings Paper CT 18th Polymer-Networks-Group Meeting CY SEP 03-07, 2006 CL Sheffield, ENGLAND SP Polymer Networks Grp DE anomalous X-ray scattering; biopolymers; gels; ion distribution; small-angle neutron scattering ID PHYSIOLOGICAL SALT-SOLUTIONS; NETWORKS; SWOLLEN AB The effect of monovalent/divalent cation exchange on the structure and osmotic properties of chemically cross-linked polyacrylate and DNA gels swollen in near physiological salt solutions has been investigated. Both systems exhibit a reversible volume phase transition in the presence of calcium ions. The small-angle neutron scattering spectra of these gels display qualitatively similar features. At low values of q surface scattering is observed, while in the intermediate q range the signal is characteristic of scattering from rod-like elements. At high values of q the scattering intensity is governed by the local (short-range) geometry of the polymer chains. The competition between monovalent and divalent cations has been studied by anomalous small-angle X-ray scattering (ASAXS). The ASAXS results reveal that the local concentration of the divalent counter-ions in the vicinity of the polymer chains significantly exceeds that of the monovalent counter-ions. C1 NICHHD, Natl Inst Hlth, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, St Martin Dheres, France. RP Horkay, F (reprint author), NICHHD, Natl Inst Hlth, Sect Tissue Biophys & Biomimet, 13 S Dr, Bethesda, MD 20892 USA. NR 24 TC 7 Z9 7 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PY 2007 VL 256 BP 80 EP 87 DI 10.1002/masy.200751009 PG 8 WC Polymer Science SC Polymer Science GA 233GJ UT WOS:000251078100010 ER PT J AU Sampath, S Raval, AN Lederman, RJ McVeigh, ER AF Sampath, Smita Raval, Amish N. Lederman, Robert J. McVeigh, Elliot R. TI High-resolution 3D arteriography of chronic total peripheral occlusions using a T-1-W turbo spin-echo sequence with inner-volume Imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE atherosclerosis; turbo spin-echo; plaque; magnetic resonance imaging; peripheral vascular disease; angiography; interventional ID ATHEROSCLEROTIC CAROTID PLAQUE; BLOOD MR-ANGIOGRAPHY; ARTERIAL-DISEASE; CONTRAST AGENT; EX-VIVO; QUANTIFICATION; THROMBOSIS; SYSTEM; WALL AB Percutaneous revascularization of peripheral artery chronic total occlusion (CTO) is challenging under X-ray guidance without direct image feedback, due to poor visualization of the obstructed segment and underappreciation of vessel tortuosity. Operators are required to steer interventional devices relatively "blindly," and therefore procedural failure or perforation may occur. Alternatively, MRI may allow complete visualization of both patent and occluded arterial segments. We designed and implemented a 3D high-resolution, T-1-weighted (T-1-W) turbo spin-echo (TSE) MRI sequence with inner-volume (IV) imaging to enable detailed peripheral artery CTO imaging. Using this sequence, high-resolution volumes of interest (VOIs) around the vessel were achieved within 5-10 min. This imaging approach may be used for rapid pre- and postprocedural evaluations, and as a 3D roadmap that can be overlaid during real-time X-, MR-, or XMR-guided catheterization. Experiments were successfully performed on a carotid CTO model in swine ex vivo, and in peripheral arteries in normal volunteers and patients in vivo. Delineation of the vascular architecture, including contrast differences between the patent and occluded artery segments, and lesion morphology heterogeneity were visualized. C1 NHLBI, Cardiac Energet Lab, Div Intramural Res, NIH,DHHS, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Sampath, S (reprint author), NHLBI, Cardiac Energet Lab, Div Intramural Res, NIH,DHHS, Bldg 10,Rm B1D-416 MSC 1061, Bethesda, MD 20892 USA. EM sampaths@mail.nih.gov OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [NIH0012028025, Z01 HL004609-04, Z01 HL005062-05] NR 30 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2007 VL 57 IS 1 BP 40 EP 49 DI 10.1002/mrm.21098 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 126TR UT WOS:000243538900006 PM 17152076 ER PT J AU Chang, LC Koay, CG Pierpaoli, C Basser, PJ AF Chang, Lin-Ching Koay, Cheng Guan Pierpaoli, Carlo Basser, Peter J. TI Variance of estimated DTI-derived parameters via first-order perturbation methods SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DTI; variance; uncertainty; perturbation; error propagation ID DIFFUSION TENSOR MRI; ACQUISITION SCHEMES; MULTIPLE-SCLEROSIS; WATER DIFFUSION; ANISOTROPY; NOISE; TRACTOGRAPHY; MATTER; UNCERTAINTY; ORIENTATION AB In typical applications of diffusion tensor imaging (DTI), DT-derived quantities are used to make a diagnostic, therapeutic, or scientific determination. In such cases it is essential to characterize the variability of these tensor-derived quantities. Parametric and empirical methods have been proposed to estimate the variance of the estimated DT, and quantities derived from it. However, the former method cannot be generalized since a parametric distribution cannot be found for all DT-derived quantities. Although powerful empirical methods, such as the bootstrap, are available, they require oversampling of the diffusion-weighted imaging (DWI) data. Statistical perturbation methods represent a hybrid between parametric and empirical approaches, and can overcome the primary limitations of both methods. In this study we used a first-order perturbation method to obtain analytic expressions for the variance of DT-derived quantities, such as the trace, fractional anisotropy (FA), eigenvalues, and eigenvectors, for a given experimental design. We performed Monte Carlo (MC) simulations of DTI experiments to test and validate these formulae, and to determine their range of applicability for different experimental design parameters, including the signal-to-noise ratio (SNR), diffusion gradient sampling scheme, and number of DWI acquisitions. This information should be useful for designing DTI studies and assessing the quality of inferences drawn from them. C1 NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bethesda, MD 20892 USA. RP Chang, LC (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bldg 13,Room 3W16,13 S Dr, Bethesda, MD 20892 USA. EM changlin@nih.gov RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 FU Intramural NIH HHS NR 38 TC 33 Z9 33 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2007 VL 57 IS 1 BP 141 EP 149 DI 10.1002/mrm.21111 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 126TR UT WOS:000243538900016 PM 17191228 ER PT J AU Murray, PR AF Murray, Patrick R. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Introduction to the Ninth Edition of the Manual of Clinical Microbiology SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Editorial Material; Book Chapter C1 NCI, Ctr Clin, Bethesda, MD 20892 USA. RP Murray, PR (reprint author), NCI, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 3 EP 3 PG 1 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500002 ER PT J AU Murray, PR AF Murray, Patrick R. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Manual of CLINICAL MICROBIOLOGY Preface SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Editorial Material; Book Chapter C1 NCI, Ctr Clin, Bethesda, MD 20892 USA. RP Murray, PR (reprint author), NCI, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP XXV EP XXV PG 1 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500001 ER PT J AU Conville, PS Witebsky, FG AF Conville, Patricia S. Witebsky, Frank G. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Nocardia, Rhodococcus, Gordonia, Actinomadura, Streptomyces, and Other Aerobic Actinomycetes SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Article; Book Chapter ID RIBOSOMAL-RNA GENE; HUMAN-IMMUNODEFICIENCY-VIRUS; RESTRICTION-ENDONUCLEASE ANALYSIS; CATHETER-RELATED BACTEREMIA; CENTRAL VENOUS CATHETER; OF-THE-LITERATURE; PERFORMANCE LIQUID-CHROMATOGRAPHY; SEQUENCE-BASED IDENTIFICATION; HEART-TRANSPLANT RECIPIENTS; FIELD GEL-ELECTROPHORESIS C1 [Conville, Patricia S.; Witebsky, Frank G.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C-385,10 Ctr Dr MSC 1508, Bethesda, MD 20892 USA. NR 275 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 515 EP 542 PG 28 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500036 ER PT J AU Major, EO Ryschkewitsch, C Valsamakis, A Hou, JA AF Major, Eugene O. Ryschkewitsch, Caroline Valsamakis, Alexandra Hou, Jean BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Human Polyomaviruses SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Article; Book Chapter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; POLYMERASE-CHAIN-REACTION; RENAL-TRANSPLANT RECIPIENTS; JC VIRUS-DNA; REAL-TIME PCR; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW-TRANSPLANTATION; HUMORAL IMMUNE-RESPONSE; BK-VIRUS; CEREBROSPINAL-FLUID C1 [Major, Eugene O.; Ryschkewitsch, Caroline; Hou, Jean] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. [Valsamakis, Alexandra] Johns Hopkins Med, Dept Pathol, Baltimore, MD 21287 USA. RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, 10 Ctr Dr,MSC 1296,Bldg 10,Room 3B14A, Bethesda, MD 20892 USA. NR 117 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 1612 EP 1621 PG 10 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500108 ER PT J AU Shea, YR AF Shea, Yvonne R. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Algorithms for Detection and Identification of Fungi SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Article; Book Chapter ID LATEX AGGLUTINATION-TEST; ARABINITOL/L-ARABINITOL RATIO; BRONCHOALVEOLAR LAVAGE FLUID; LINKED-IMMUNOSORBENT-ASSAY; REAL-TIME PCR; CRYPTOCOCCAL CAPSULAR POLYSACCHARIDE; GALACTOMANNAN ENZYME-IMMUNOASSAY; BETA-D-GLUCAN; INVASIVE ASPERGILLOSIS; CEREBROSPINAL-FLUID C1 NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shea, YR (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C325,10 Ctr Dr, Bethesda, MD 20892 USA. NR 96 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 1745 EP 1761 PG 17 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500119 ER PT J AU McPherson, T Nutman, TB AF McPherson, Tess Nutman, Thomas B. BE Baron, EJ Jorgensen, JH Landry, ML Pfaller, MA TI Filarial Nematodes SO MANUAL OF CLINICAL MICROBIOLOGY, 9TH ED LA English DT Article; Book Chapter ID LOA-LOA INFECTION; BANCROFTIAN FILARIASIS; WUCHERERIA-BANCROFTI; ONCHOCERCA-VOLVULUS; LYMPHATIC FILARIASIS; DOUBLE-BLIND; ACUTE DERMATOLYMPHANGIOADENITIS; NONENDEMIC POPULATIONS; CLINICAL PRESENTATION; IVERMECTIN TREATMENT C1 [McPherson, Tess; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP McPherson, T (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 59 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-371-0 PY 2007 BP 2156 EP 2165 PG 10 WC Microbiology SC Microbiology GA BOY07 UT WOS:000278004500146 ER PT J AU Bohr, VA AF Bohr, Vilhelm A. TI Functional genomics of aging III - Editorial SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material C1 GRC, NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), GRC, NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2007 VL 128 IS 1 BP 2 EP 2 DI 10.1016/j.mad.2006.12.002 PG 1 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 137OK UT WOS:000244301700001 ER PT J AU Kusumoto, R Muftuoglu, M Bohr, VA AF Kusumoto, Rika Muftuoglu, Meltem Bohr, Vilhelm A. TI The role of WRN in DNA repair is affected by post-translational modifications SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 3rd International Conference on Functional Genomics of Ageing CY MAR 29-APR 01, 2006 CL Palermo, ITALY DE acetylation; base excision repair; non-homologous end-joining; phosphorylation; post-translational modifications; Werner syndrome ID WERNER-SYNDROME PROTEIN; BASE EXCISION-REPAIR; STRAND-ANNEALING ACTIVITIES; SYNDROME GENE-PRODUCT; ABL TYROSINE KINASE; FUNCTIONAL INTERACTION; HELICASE ACTIVITY; LIGASE-IV; EXONUCLEASE ACTIVITY; REPLICATION ARREST AB Werner syndrome (WS) is an autosomal recessive progeroid disease characterized by genomic instability. WRN gene encodes one of the RecQ helicase family proteins, WRN, which has ATPase, helicase, exonuclease and single stranded DNA annealing activities. There is accumulating evidence suggesting that WRN contributes to the maintenance of genomic integrity through its involvement in DNA repair, replication and recombination. The role of WRN in these pathways can be modulated by its post-translational modifications in response to DNA damage. Here, we review the functional consequences of post-translational modifications on WRN as well as specific DNA repair pathways where WRN is involved and discuss how these modifications affect DNA repair pathways. Published by Elsevier Ireland Ltd. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov FU Intramural NIH HHS NR 78 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2007 VL 128 IS 1 BP 50 EP 57 DI 10.1016/j.mad.2006.11.010 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 137OK UT WOS:000244301700011 PM 17116323 ER PT J AU Hasebe, T Hartman, R Fu, LZ Amano, T Shi, YB AF Hasebe, Takashi Hartman, Rebecca Fu, Liezhen Amano, Tosikazu Shi, Yun-Bo TI Evidence for a cooperative role of gelatinase A and membrane type-1 matrix metalloproteinase during Xenopus laevis development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE matrix metalloproteinase (MMP)-2 (gelatinase A; GelA); MMP-14 (membrane type 1-MMP; MT1-MMP); Xenopus laevis; development ID INDUCED TAIL RESORPTION; HORMONE RESPONSE GENES; EXTRACELLULAR-MATRIX; AMPHIBIAN METAMORPHOSIS; EXPRESSION PATTERN; FROG METAMORPHOSIS; TADPOLE TAIL; STROMELYSIN-3; APOPTOSIS; ACTIVATION AB Matrix metalloproteinases (MMPs) are a large family of extracellular or membrane-bound proteases. Their ability to cleave extracellular matrix (ECM) proteins has implicated a role in ECM remodeling to affect cell fate and behavior during development and in pathogenesis. We have shown previously that membrane-type 1 (MT-1)-MMP is coexpressed temporally and spatially with the MMP gelatinase A (GelA) in all cell types of the intestine and tail where GelA is expressed during Xenopus laevis metamorphosis, suggesting a cooperative role of these MMPs in development. Here, we show that Xenopus GelA and MT1-MMP interact with each other in vivo and that overexpression of MT1-MMP and GelA together in Xenopus embryos leads to the activation of pro-GelA. We further show that both MMPs are expressed during Xenopus embryogenesis, although MT1-MMP gene is expressed earlier than the GelA gene. To investigate whether the embryonic MMPs play a role in development, we have studied whether precocious expression of these MMPs alters development. Our results show that overexpression of both MMPs causes developmental abnormalities and embryonic death by a mechanism that requires the catalytic activity of the MMPs. More importantly, we show that coexpression of wild type MT1-MMP and GelA leads to a cooperative effect on embryonic development and that this cooperative effect is abolished when the catalytic activity of either MMP is eliminated through a point mutation in the catalytic domain. Thus, our studies support a cooperative role of these MMPs in embryonic development, likely through the activation of pro-GelA by MT1-MMP. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Nippon Med Coll, Dept Biol, Nakahara Ku, Kawasaki, Kanagawa 2110063, Japan. RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM Shi@helix.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD001901-10] NR 67 TC 21 Z9 22 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN PY 2007 VL 124 IS 1 BP 11 EP 22 DI 10.1016/j.mod.2006.09.001 PG 12 WC Developmental Biology SC Developmental Biology GA 128TI UT WOS:000243681200002 PM 17055228 ER PT S AU Ricci, AJ Kachar, B AF Ricci, Anthony J. Kachar, Bechara BE Hamill, OP TI Hair cell mechanotransduction: The dynamic interplay between structure and function SO MECHANOSENSITIVE ION CHANNELS, PT B SE Current Topics in Membranes LA English DT Review; Book Chapter ID MECHANO-ELECTRICAL TRANSDUCTION; DEVELOPING INNER-EAR; MYOSIN I-BETA; MECHANOELECTRICAL-TRANSDUCTION; BULLFROGS SACCULUS; TIP LINKS; SPONTANEOUS OSCILLATION; BUNDLE STIFFNESS; FAST ADAPTATION; INTERNAL EAR C1 Stanford Univ, Dept Otolaryngol, Stanford, CA 94305 USA. Natl Inst Deafness & Commun Disorders, Sect Struct Biol, Bethesda, MD 20892 USA. RP Ricci, AJ (reprint author), Stanford Univ, Dept Otolaryngol, Stanford, CA 94305 USA. NR 159 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-153359-5 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2007 VL 59 BP 339 EP 374 DI 10.1063/S1063-5823(06)59012-X PG 36 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BGE60 UT WOS:000246336800012 PM 25168142 ER PT J AU Persky, S Blascovich, J AF Persky, Susan Blascovich, Jim TI Immersive virtual environments versus traditional platforms: Effects of violent and nonviolent video game play SO MEDIA PSYCHOLOGY LA English DT Article ID AGGRESSIVE-BEHAVIOR; PHYSIOLOGICAL AROUSAL; SEX-DIFFERENCES; THOUGHTS; PERSONALITY; TECHNOLOGY; PSYCHOLOGY; HOSTILITY; COGNITION; EXPOSURE AB An experiment focused on the effects of platform (desktop computer, immersive virtual environment; IVE), content (violent, nonviolent), and player gender on video game play outcomes. Results revealed an interaction such that participants reported higher levels of aggressive feelings when playing a violent video game in an IVE compared to violent game play on a desktop platform or nonviolent game play on either platform. Physiological results supported these findings. No gender effects were found, nor did platform intensify any effects for nonviolent game play. The findings suggest that the intensifying effects of IVEs for game play and aggression are content specific and provide further evidence that attention to playing platform is crucial in understanding violent video game effects. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Persky, S (reprint author), NHGRI, NIH, 31 Ctr Dr,Room B1B54D, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov NR 45 TC 19 Z9 19 U1 6 U2 13 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1521-3269 J9 MEDIA PSYCHOL JI Media Psychol. PY 2007 VL 10 IS 1 BP 135 EP 156 PG 22 WC Communication; Film, Radio, Television; Psychology, Applied SC Communication; Film, Radio & Television; Psychology GA 187QQ UT WOS:000247863500007 ER PT J AU Becker, KG AF Becker, Kevin G. TI Autism, asthma, inflammation, and the hygiene hypothesis SO MEDICAL HYPOTHESES LA English DT Editorial Material ID PERVASIVE DEVELOPMENTAL DISORDERS; SINGLE-NUCLEOTIDE POLYMORPHISMS; HEPATOCYTE GROWTH-FACTOR; SPECTRUM DISORDERS; HEAD CIRCUMFERENCE; CHILDHOOD ASTHMA; RISING INCIDENCE; SIBSHIP SIZE; RISK-FACTORS; BIRTH-ORDER AB Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIH, NIA, TRIAD Technol Ctr, Gene Express & Genom Unit,RRB, Baltimore, MD 21224 USA. RP Becker, KG (reprint author), NIH, NIA, TRIAD Technol Ctr, Gene Express & Genom Unit,RRB, Room 208,333 Cassell Dr, Baltimore, MD 21224 USA. EM beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS [Z99 AG999999] NR 118 TC 43 Z9 51 U1 0 U2 15 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2007 VL 69 IS 4 BP 731 EP 740 DI 10.1016/j.mehy.2007.02.019 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210TH UT WOS:000249478000004 PM 17412520 ER PT S AU Krieger, A Csoma, C Iordachita, LI Guion, P Singh, AK Fichtinger, G Whitcomb, LL AF Krieger, Axel Csoma, Csaba Iordachita, Lulian I. Guion, Peter Singh, Anurag K. Fichtinger, Gabor Whitcomb, Louis L. BE Ayache, N Ourdelin, S Maeder, A TI Design and preliminary accuracy studies of an MRI-Guided, transrectal prostate intervention system SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION- MICCAI 2007, PT 2, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 10th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2007) CY OCT 29-NOV 02, 2007 CL Brisbane, AUSTRALIA ID 1.5 T; CANCER; BIOPSY AB This paper reports a novel system for magnetic resonance imaging (MRI) guided transrectal prostate interventions, such as needle biopsy, fiducial marker placement, and therapy delivery. The system utilizes a hybrid tracking method, comprised of passive fiducial tracking for initial registration and subsequent incremental motion measurement along the degrees of freedom using fiber-optical encoders and mechanical scales. Targeting accuracy of the system is evaluated in prostate phantom experiments. Achieved targeting accuracy and procedure times were found to compare favorably with existing systems using passive and active tracking methods. Moreover, the portable design of the system using only standard MRI image sequences and minimal custom scanner interfacing allows the system to be easily used on different MRI scanners. C1 [Krieger, Axel; Csoma, Csaba; Iordachita, Lulian I.; Fichtinger, Gabor; Whitcomb, Louis L.] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. [Guion, Peter; Singh, Anurag K.] NCI, NIH, DHHS, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Krieger, A (reprint author), Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. RI Iordachita, Iulian/A-3507-2010 OI Iordachita, Iulian/0000-0002-2510-9008 FU NIH [1R01EB002963]; NSF [EEC-9731748] FX The authors gratefully acknowledge support under grants NIH 1R01EB002963 and NSF EEC-9731748. NR 11 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-75758-0 J9 LECT NOTES COMPUT SC PY 2007 VL 4792 BP 59 EP + PG 3 WC Computer Science, Theory & Methods; Robotics; Neurosciences; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Robotics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGW25 UT WOS:000250917700008 ER PT S AU Huang, A Li, J Summers, RM Petrick, N Hara, AK AF Huang, Adam Li, Jiang Summers, Ronald M. Petrick, Nicholas Hara, Amy K. BE Giger, ML Karssemeijer, N TI Using pareto fronts to evaluate polyp detection algorithms for CT colonography - art. no. 651407 SO Medical Imaging 2007: Computer-Aided Diagnosis, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE CT colonography; virtual colonoscopy; computer-aided diagnosis; polyp detection; Pareto front AB We evaluate and improve an existing curvature-based region growing algorithm for colonic polyp detection for our CT colonography (CTC) computer-aided detection (CAD) system by using Pareto fronts. The performance of a polyp detection algorithm involves two conflicting objectives, minimizing both false negative (FN) and false positive (FP) detection rates. This problem does not produce a single optimal solution but a set of solutions known as a Pareto front. Any solution in a Pareto front can only outperform other solutions in one of the two competing objectives. Using evolutionary algorithms to find the Pareto fronts for multi-objective optimization problems has been common practice for years. However, they are rarely investigated in any CTC CAD system because the computation cost is inherently expensive. To circumvent this problem, we have developed a parallel program implemented on a Linux cluster environment. A data set of 56 CTC colon surfaces with 87 proven positive detections of polyps sized 4 to 60 mm is used to evaluate an existing one-step, and derive a new two-step region growing algorithm. We use a popular algorithm, the Strength Pareto Evolutionary Algorithm (SPEA2), to find the Pareto fronts. The performance differences are evaluated using a statistical approach. The new algorithm outperforms the old one in 81.6% of the sampled Pareto fronts from 20 simulations. When operated at a suitable sensitivity level such as 90.8% (79/87) or 88.5% (77/87), the FP rate is decreased by 24.4% or 45.8% respectively. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Huang, A (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6632-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6514 BP 51407 EP 51407 AR 651407 DI 10.1117/12.709426 PN 1-2 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI25 UT WOS:000247298700006 ER PT S AU Gavrielides, MA Petrick, N Myers, KJ AF Gavrielides, Marios A. Petrick, Nicholas Myers, Kyle J. BE Giger, ML Karssemeijer, N TI Automated alignment of serial thoracic scans using home structure descriptors - art. no. 65143C SO Medical Imaging 2007: Computer-Aided Diagnosis, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm AB In this manuscript we present an automated algorithm for the alignment of thoracic scans using descriptors of bone structures. Bone structures were utilized because they are expected to be less susceptible to sources of errors such as patient positioning and breath hold. The algorithm employed the positioning of ribs relative to the spinal cord along with a description of the scapula. The spinal cord centroid was detected by extracting local maxima of the distance transform followed by point tracing along consecutive slices. Ribs were segmented using adaptive thresholding followed by the watershed algorithm to detach ribs from the vertebra, and by imposing requirements of rib proximity to the lung border. The angles formed between the spinal cord centroid and segmented rib centroids were used to describe rib positioning. Additionally, the length of the scapula was extracted in each slice. A cost function incorporating the difference of features from rib positioning and scapula length between two slices was derived and used to match slices. The method was evaluated on a set of 12 pairs of full and partial CT scans acquired on the same day. Evaluation was based on whether the slices showing a nodule at its maximum diameter in each scan were matched. Full-to-partial and partial-tofull alignment were performed. Results showed that the proposed metric matched nodule slices within an average distance of 1.08 and 1.17 slices from the target for full-to-partial and partial-to-full alignment respectively. These preliminary results are encouraging for using this method as a first step in an overall process of temporally analyzing CT lung nodules. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Gavrielides, MA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6632-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6514 BP C5143 EP C5143 AR 65143C DI 10.1117/12.711506 PN 1-2 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI25 UT WOS:000247298700117 ER PT S AU Yao, JH Li, J Summers, R AF Yao, Jianhua Li, Jiang Summers, Ronald BE Giger, ML Karssemeijer, N TI Collaborative classifiers in CT colonography CAD - art. no. 65142H SO Medical Imaging 2007: Computer-Aided Diagnosis, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE CAD; SVM; collaborative classifier; CT colonography ID CLASSIFICATION; SYSTEM AB Multiple classifiers working collaboratively can usually achieve better performance than any single classifier working independently. Our CT colonography computer-aided detection (CAD) system uses support vector machines (SVM) as the classifier. In this paper, we developed and evaluated two schemes to collaboratively apply multiple SVMs in the same CAD system. One is to put the classifiers in a sequence (SVM sequence) and apply them one after another; the other is to put the classifiers in a committee (SVM committee) and use the committee decision for the classification. We compared the sequence order (best-first, worst-first and random) in the SVM sequence and two decision functions in the SVM committee (majority vote and sum probability). The experiments were conducted on 786 CTC datasets, with 63 polyp detections. We used 10-fold cross validation to generate the FROC curves, and conducted 100 bootstraps to evaluate the performance variation. The result showed that collaborative classifiers performed much better than individual classifiers. The SVM sequence had slightly better accuracy than the SVM committee but also had bigger performance variation. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6632-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6514 BP H5142 EP H5142 AR 65142H DI 10.1117/12.708318 PN 1-2 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI25 UT WOS:000247298700087 ER PT S AU Lamy, J Summers, RM AF Lamy, Julien Summers, Ronald M. BE Giger, ML Karssemeijer, N TI Intra-patient colon surface registration based on taeniae coli SO MEDICAL IMAGING 2007: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE computer assisted diagnostic; registration; colon; tenia ID CT COLONOGRAPHY; SUPINE AB CT colonography, a prevalent tool to diagnose colon cancer in its early stages, is often limited by bad distention, or retained fluids, which will cause segments of the colon to be impossible to process by CAD tools. By scanning patients in both prone and supine positions, collapsed segments and retained fluids will not be in the same place in both images, increasing the length of the colon that can be processed correctly. In order to fully use these two scans, they must be registered, so that a lesion identified on one of them can be mapped to the other, thus increasing sensitivity and specificity of CAD tools. The surface of the colon is however large (more than half a million vertices on our images), and has no canonical shape, which makes atlases and other widely used registration algorithms non optimal. We present in this paper a fast method to register the colon surface between prone and supine scans using landmarks present on the colon, the teniae coli. Our method is composed of three steps. First, we regrister the body, based on manually placed landmarks. Then we register the three tenize coli, and, from this registration, we compute a deformation field for each vertex of the colon surface. We tested our method on 5 cases, by measuring the RMS error after body registration, quantifying the intrisic movement of the colon, and after colon surface registration. The RMS error was reduced from 1.8 cm to 0.49 cm, a reduction of 71%. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Lamy, J (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM lamyj@cc.nih.gov; rms@nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6632-7 J9 PROC SPIE PY 2007 VL 6514 AR 65140C DI 10.1117/12.709780 PN 1-2 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI25 UT WOS:000247298700011 ER PT S AU Gallas, BD Pennello, GA AF Gallas, Brandon D. Pennello, Gene A. BE Jiang, Y Sahiner, B TI Pooling MRMC forced-choice data - art. no. 651506 SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE multi-reader; multi-case; MRMC; variance; percent correct; sensitivity; specificity; pooling ID OPERATING CHARACTERISTIC ANALYSIS; MULTIREADER; VARIANCE AB There are at least two sources of variance when estimating the performance of an imaging device: the doctors (readers) and the patients (cases). These sources of variability generate variances and covariances in the observer study data that can be addressed with multi-reader, multi-case (MRMC) variance analysis. Frequently, a fully-crossed study design is used to collect the data; every reader reads every case. For imaging devices used during in vivo procedures, however, a fully-crossed design is infeasible. Instead, each patient is diagnosed by only one doctor, a doctor-patient study design. Here we investigate percent correct (PC) under this doctor-patient study design. From a probabilistic foundation, we present the bias and variance of two statistics: pooled PC and reader-averaged PC. We also present variance estimates of these statistics and compare them to naive estimates. Finally, we run simulations to assess the statistics and the variance estimates. The two PC statistics have the same means but different variances. The variances depend on how patients are distributed among the readers and the amount of reader variability. Regarding the variance estimates, the MRMC estimates are unbiased, whereas the naive estimates bracket the true variance and can be extremely biased. C1 NIBIB, CRDH, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Gallas, BD (reprint author), NIBIB, CRDH, Lab Assessment Med Imaging Syst, 127210 Twinbrook Pkwy, Rockville, MD 20852 USA. OI Gallas, Brandon/0000-0001-7332-1620 NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP 51506 EP 51506 AR 651506 DI 10.1117/12.709628 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600005 ER PT S AU Paquerault, S Wade, DI Petrick, N Myers, KJ Samuelson, FW AF Paquerault, Sophie Wade, Darin I. Petrick, Nicholas Myers, Kyle J. Samuelson, Frank W. BE Jiang, Y Sahiner, B TI Observer evaluation of computer-aided detection: Second reader versus concurrent reader scenario - art. no. 65151N SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE computer-aided detection; CAD second reader; CAD concurrent reader; multiple readers multiple cases (MRMC) study; free-response receiver operating characteristic; bootstrap ID BREAST-CANCER DETECTION; SCREENING MAMMOGRAPHY; DETECTION SYSTEM; PERFORMANCE; DIAGNOSIS; PROGRAM AB We are comparing the performance of computer-aided detection (CAD) used as a second reader to concurrent-use CAD. We have designed a multi-reader multi-case (MRMC) observer study using fixed-size mammographic background images with fixed intensity Gaussian signals added in two experiments. A CAD system was developed to automatically detect these signals. The two experiments utilized signals of different contrast levels to assess the impact of CAD when the standalone CAD sensitivity was superior (low contrast) or equivalent (high contrast) to the average reader in the study. Seven readers participated in the study and were asked to review 100 images, identify signal locations, and rate each on a 100-point scale. A rating of 50 was used as a cutpoint and provided a binary classification of each candidate. Readers read the case set using CAD in both the second-reader and concurrent-reader scenarios. Results from the different signal intensities and reading paradigms were analyzed using the area under the Free-response Receiver Operating Characteristics curves. Sensitivity and the average number of FPs/image were also determined. The results showed that CAD, either used as a second reader or as a concurrent reader, can increase reader sensitivity but with an increase in FPs. The study demonstrated that readers may benefit from concurrent CAD when CAD standalone performance outperforms average reader sensitivity. However, this trend was not observed when CAD performance was equivalent to the sensitivity of the average reader. C1 US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. RP Paquerault, S (reprint author), US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP N5151 EP N5151 AR 65151N DI 10.1117/12.707778 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600054 ER PT S AU Park, S Badano, A Callas, BD Myers, KJ AF Park, Subok Badano, Aldo Callas, Brandon D. Myers, Kyle J. BE Jiang, Y Sahiner, B TI A contrast-sensitive channelized-Hotelling observer to predict human performance in a detection task using lumpy backgrounds and Gaussian signals - art. no. 65150V SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE anthropomorphic model observer; human contrast sensitivity; channelized-Hotelling observer; lumpy backgrounds ID MODEL AB Previously, a non-prewhitening matched filter (NPWMF) incorporating a model for the contrast sensitivity of the human visual system was introduced for modeling human performance in detection tasks with different viewing angles and white-noise backgrounds by Badano et al. But NPWMF observers do not perform well detection tasks involving complex backgrounds since they do not account for random backgrounds. A channelized-Hotelling observer (CHO) using difference-of-Gaussians (DOG) channels has been shown to track human performance well 14 in detection tasks using lumpy backgrounds. 2 In this work, a CHO with DOG channels, incorporating the model of the human contrast sensitivity, was developed similarly. We call this new observer a contrast-sensitive CHO (CS-CHO). The Barten model was the basis of our human contrast sensitivity model. A scalar was multiplied to the Barten model and varied to control the thresholding effect of the contrast sensitivity on luminance-valued images and hence the performance-prediction ability of the CS-CHO. The performance of the CS-CHO was compared to the average human performance from the psychophysical study by Park et al., where the task was to detect a known Gaussian signal in non-Gaussian distributed lumpy backgrounds. Six different signal-intensity values were used in this study. We chose the free parameter of our model to match the mean human performance in the detection experiment at the strongest signal intensity. Then we compared the model to the human at five different signal-intensity values in order to see if the performance of the CS-CHO matched human performance. Our results indicate that the CS-CHO with the chosen scalar for the contrast sensitivity predicts human performance closely as a function of signal intensity. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. OI badano, aldo/0000-0003-3712-6670 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP V5150 EP V5150 AR 65150V DI 10.1117/12.708582 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600028 ER PT S AU Liang, H Park, S Gallas, BD Badano, A AF Liang, Hongye Park, Subok Gallas, Brandon D. Badano, Aldo BE Jiang, Y Sahiner, B TI Effect of slow display on stack-mode reading of volumetric image datasets using an anthropomorphic observer - art. no. 65150W SO Medical Imaging 2007: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm ID NOISE AB Active-matrix liquid crystal displays (LCDs) are becoming widely used in medical imaging applications. With the increasing volume of CT images to be interpreted per day, the ability of showing a fast sequence of images in stack mode is preferable for a medical display. Slow temporal response of LCD display can compromise the image quality/fidelity when the images are browsed in a fast sequence. In this paper, we report on the effect of the LCD response time at different image browsing speeds based on the performance of a contrast-sensitive channelized-Hotelling observer. A correlated stack of simulated cluster lumpy background images with a signal present in some of the images was used. The effect of different browsing speeds is calculated with LCD temporal response measurements established in our previous work. The image set is then analyzed by the model observer, which has been shown to predict human detection performance in non-Gaussian lumpy backgrounds. This allows us to quantify the effect of slow temporal response of medical liquid crystal displays on the performance of the anthropomorphic observer. Slow temporal response of the display device greatly affects the lesion contrast and observer performance. This methodology, after validation with human observers, could be used to set limits for the rendering speed of large volumetric image datasets (from CT, MR, or tomosynthesis) read in stack-mode. C1 US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Liang, H (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6633-4 J9 P SOC PHOTO-OPT INS PY 2007 VL 6515 BP W5150 EP W5150 AR 65150W DI 10.1117/12.708993 PG 8 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ28 UT WOS:000247398600029 ER PT S AU Tan, S Yao, JH Ward, MM Yao, L Summers, RM AF Tan, Sovira Yao, Jianhua Ward, Michael M. Yao, Lawrence Summers, Ronald M. BE Pluim, JPW Reinhardt, JM TI Level sets on non-planar manifolds for ridge detection on isosurfaces - art. no. 651230 SO Medical Imaging 2007: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE ridgeline detection; level set; triangular mesh; manifolds; isosurfaces ID ACTIVE CONTOURS AB We describe an algorithm for evolving a level set on a non-planar manifold like the isosurface of a 3D object. The surface is represented by a triangular mesh and the feature that guides our level set via a speed function is its curvature. We overcome the difficulty of computing the gradient and curvature of the level set distance function on a non-planar, non-Cartesian mesh by performing the calculations locally in neighborhoods small enough to be considered planar. Moreover we use a least squares estimation of derivatives to replace finite differences and achieve better accuracy. The algorithm was motivated by our need to detect the ridge lines of vertebral bodies. The advantage of using level sets is that they are capable of producing a continuous ridge line despite noise and gaps in the ridge. We tested our algorithm on 40 vertebral bodies (80 ridge lines). 76 ridge lines showed no noticeable mistakes. The same set of parameters was used. For the remaining 4, we had to change the parameters of the speed function sigmoid to correct small under- or over-segmenting. To further test our algorithm we designed a synthetic surface with large curvature and to which we added noise and a ridge. The level set was able to evolve on the surface and stop at the ridge. Tests on synthetic cylinders with a ground truth ridge and to which we added noise indicate that the level set has good accuracy. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6512 BP 51230 EP 51230 AR 651230 DI 10.1117/12.708217 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500105 ER PT S AU Banh, DPT Kyprianou, IS Paquerault, S Myers, KJ AF Banh, Diem Phuc T. Kyprianou, Iacovos S. Paquerault, Sophie Myers, Kyle J. BE Pluim, JPW Reinhardt, JM TI Morphology-based three-dimensional segmentation of coronary artery tree from CTA scans - art. no. 65122I SO Medical Imaging 2007: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE coronary; 3D segmentation; cardiac CT scans; heart modeling AB We developed an algorithm based on a rule-based threshold framework to segment the coronary arteries from angiographic computed tomography (CTA) data. Computerized segmentation of the coronary arteries is a challenging gprocedure due to the presence of diverse anatomical structures surrounding the heart on cardiac CTA data. The proposed algorithm incorporates various levels of image processing and organ information including region, connectivity and morphology operations. It consists of three successive stages. The first stage involves the extraction of the three-dimensional scaffold of the heart envelope. This stage is semiautomatic requiring a reader to review the CTA scans and manually select points along the heart envelope in slices. These points are further processed using a surface spline-fitting technique to automatically generate the heart envelope. The second stage consists of segmenting the left heart chambers and coronary arteries using grayscale threshold, size and connectivity criteria. This is followed by applying morphology operations to further detach the left and right coronary arteries from the aorta. In the final stage, the 3D vessel tree is reconstructed and labeled using an Isolated Connected Threshold technique. The algorithm was developed and tested on a patient coronary artery CTA that was graciously shared by the Department of Radiology of the Massachusetts General Hospital. The test showed that our method constantly segmented the vessels above 79% of the maximum gray-level and automatically extracted 55 of the 58 coronary segments that can be seen on the CTA scan by a reader. These results are an encouraging step toward our objective of generating high resolution models of the male and female heart that will be subsequently used as phantoms for medical imaging system optimization studies. C1 US FDA, NIBIB, Lab Assessment Med Imaging Syst, CDRH, Rockville, MD 20857 USA. RP Banh, DPT (reprint author), US FDA, NIBIB, Lab Assessment Med Imaging Syst, CDRH, HFZ-140,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6512 BP I5122 EP I5122 AR 65122I DI 10.1117/12.710122 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500087 ER PT S AU Monzon, A Hemler, PF Nalls, M Manini, T Clark, BC Harris, TB McAuliffe, MJ AF Monzon, A. Hemler, P. F. Nalls, M. Manini, T. Clark, B. C. Harris, T. B. McAuliffe, M. J. BE Pluim, JPW Reinhardt, JM TI Segmentation of magnetic resonance images of the thighs for a new National Institutes of Health initiative - art. no. 65123L SO Medical Imaging 2007: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE magnetic resonance images; segmentation; mathematical morphology; validation; quantification AB This paper describes a new system for semi-automatically segmenting the background, subcutaneous fat, interstitial fat, muscle, bone, and bone marrow from magnetic resonance images (MRI's) of volunteers for a new osteoarthritis study. Our system first creates separate right and left thigh images from a single MR image containing both legs. The subcutaneous fat boundary is very difficult to detect in these images and is therefore interactively defined with a single boundary. The volume within the boundary is then automatically processed with a series of clustering and morphological operations designed to identify and classify the different tissue types required for this study. Once the tissues have been identified, the volume of each tissue is determined. and a single, false colored, segmented image results. We quantitatively compare the segmentation in three different ways. In our first method we simply compare the tissue volumes of the resulting segmentations performed independently on both the left and right thigh. A second quantification method compares our results temporally with three image sets of the same volunteer made one month apart including a month of leg disuse. Our final quantification methodology compares the volumes of different tissues detected with our system to the results of a manual segmentation performed by a trained expert. The segmented image results of four different volunteers using images acquired at three different times suggests that the system described in this paper provides more consistent results than the manually segmented set. Furthermore, measurements of the left and right thigh and temporal results for both segmentation methods follow the anticipated trend of increasing fat and decreasing muscle over the period of disuse. C1 NIH, Bethesda, MD 20892 USA. RP Monzon, A (reprint author), NIH, 35 Convent Dr,MSC 3726, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6512 BP L5123 EP L5123 AR 65123L DI 10.1117/12.708269 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500126 ER PT S AU Freidlin, RZ Komlosh, ME Loew, MH Basser, PJ AF Freidlin, Raisa Z. Komlosh, Michal E. Loew, Murray H. Basser, Peter J. BE Pluim, JPW Reinhardt, JM TI Parsimonious model selection for tissue classification: A DTI study of zebrafish - art. no. 65122T SO Medical Imaging 2007: Image Processing, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE DTI; diffusion tensor; MRI; hierarchical; parsimonious; model selection ID VERTEBRATE GENOME EVOLUTION; DIFFUSION TENSOR; MAGNETIC-RESONANCE; FIBER ORIENTATION; MR-IMAGES; IN-VIVO AB One aim of this work is to investigate the feasibility of using a hierarchy of models to describe diffusion tensor MRI data. Parsimonious model selection criteria are used to choose among different models of diffusion within tissue. Second, based on this information, we assess whether we can perform simultaneous tissue segmentation and classification. The proposed hierarchical framework used for parsimonious model selection is based on the F-test, adapted from Snedecor. Diffusion Magnetic Resonance Microscopy (MRM) provides near-microscopic resolution without relying on a sample's optical transparency for image formation. Diffusion MRM is a noninvasive imagring technique for quantitative analysis of intrinsic features of tissues. Thus, we propose using Diffusion MRM to characterize normal tissue structure in adult zebrafish, and possibly subtle anatomical or structural differences between normals and knockouts. Both numerical phantoms and diffusion weighted image (DWI) data obtained from adult zebrafish are used to test this model selection framework. C1 NIH, TAIS, CBEL, DCB,CIT, Bethesda, MD 20892 USA. RP Freidlin, RZ (reprint author), NIH, TAIS, CBEL, DCB,CIT, Bldg 10, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6512 BP T5122 EP T5122 AR 65122T DI 10.1117/12.708312 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500098 ER PT S AU Xue, ZY Antani, S Long, LR Jeronimo, J Thoma, GR AF Xue, Zhiyun Antani, Sameer Long, L. Rodney Jeronimo, Jose Thoma, George R. BE Pluim, JPW Reinhardt, JM TI Comparative performance analysis of cervix ROI extraction and specular reflection removal algorithms for uterine cervix image analysis SO MEDICAL IMAGING 2007: IMAGE PROCESSING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE technology assessment; performance evaluation; computer aided diagnosis; uterine cervix cancer AB Cervicography is a technique for visual screening of uterine cervix images for cervical cancer. One of our research goals is the automated detection in these images of acetowhite (AW) lesions, which are sometimes correlated with cervical cancer. These lesions are characterized by the whitening of regions along the squamocolumnar junction on the cervix when treated with 5% acetic acid. Image preprocessing is required prior to invoking AW detection algorithms on cervicographic images for two reasons: (1) to remove Specular Reflections (SR) caused by camera flash, and (2) to isolate the cervix region-of-interest (ROI) from image regions that are irrelevant to the analysis. These image regions may contain medical instruments, film markup, or other non-cervix anatomy or regions, such as vaginal walls. We have qualitatively and quantitatively evaluated the performance of alternative preprocessing algorithms on a test set of 120 images. For cervix ROI detection, all approaches use a common feature set, but with varying combinations of feature weights, normalization, and clustering methods. For SR detection, while one approach uses a Gaussian Mixture Model on an intensity/saturation feature set, a second approach uses Otsu thresholding on a top-hat transformed input image. Empirical results are analyzed to derive conclusions on the performance of each approach. C1 NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 9 TC 0 Z9 0 U1 2 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6630-3 J9 PROC SPIE PY 2007 VL 6512 AR 65124I DI 10.1117/12.709588 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGE24 UT WOS:000246288500157 ER PT S AU Badal, A Kyprianou, I Badano, A Sempau, J Myers, KJ AF Badal, Andreu Kyprianou, Iacovos Badano, Aldo Sempau, Josep Myers, Kyle J. BE Hsieh, J Flynn, MJ TI Monte Carlo package for simulating radiographic images of realistic anthropomorphic phantoms described.Fby triangle meshes SO Medical Imaging 2007: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE Monte Carlo simulation; PENELOPE; NCAT; angiography; computer-aided design; computer graphics ID PHOTON TRANSPORT; PENELOPE; CODE AB X-ray imaging system optimization increases the benefit-to-cost ratio by reducing the radiation dose to the patient while maximizing image quality. We present a new simulation tool for the generation of realistic medical x-ray images for assessment and optimization of complete imaging systems. The Monte Carlo code simulates radiation transport physics using the subroutine package PENELOPE, which accurately simulates the transport of electrons and photons within the typical medical imaging energy range. The new code implements a novel object-oriented geometry package that allows simulations with homogeneous objects of arbitrary shapes described by triangle meshes. The flexibility of this code, which uses the industry standard PLY input-file format, allows the use of detailed anatomical models developed using computer-aided design tools applied to segmented CT and MRI data. The use of triangle meshes highly simplifies the ray-tracing algorithm without reducing the generality of the code, since most surface models can be tessellated into triangles while retaining their geometric details. Our algorithm incorporates an octree spatial data structure to sort the triangles and accelerate the simulation, reaching execution speeds comparable to the original quadric geometry model of PENELOPE. Coronary angiograms were simulated using a tessellated version of the NURBS-based Cardiac-Torso (NCAT) phantom: The phantom models 330 objects, comprised in total of 5 million triangles. The dose received by each organ and the contribution of the different scattering processes to the final image were studied in detail. C1 US FDA, CDRH NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Badal, A (reprint author), US FDA, CDRH NIBIB, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20852 USA. RI Sempau, Josep/J-7834-2013 OI Sempau, Josep/0000-0002-2754-7685 NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 P SOC PHOTO-OPT INS PY 2007 VL 6510 BP U339 EP U350 DI 10.1117/12.707934 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100034 ER PT S AU Freed, M Kupinski, MA Furenlid, LR Barrett, HH AF Freed, Melanie Kupinski, Matthew A. Furenlid, Lars R. Barrett, Harrison H. BE Hsieh, J Flynn, MJ TI A prototype instrument for adaptive SPECT imaging SO Medical Imaging 2007: Physics of Medical Imaging, Pts 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE SPECT; imaging; instrumentation; adaptive AB We have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the object for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented along with recommendations for system improvements. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Tucson, AZ USA. RP Freed, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, NIBIB CDRH Lab Assessment Med Imaging Syst, Tucson, AZ USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 P SOC PHOTO-OPT INS PY 2007 VL 6510 BP U302 EP U313 DI 10.1117/12.708818 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100030 ER PT S AU Kyprianou, IS Badano, A Gallas, BD Myers, KJ AF Kyprianou, Iacovos S. Badano, Aldo Gallas, Brandon D. Myers, Kyle J. BE Hsieh, J Flynn, MJ TI A method to estimate the point response function of digital x-ray detectors from edge measurements SO MEDICAL IMAGING 2007: PHYSICS OF MEDICAL IMAGING, PTS 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE point response function; edge; pinhole; MTF; Monte Carlo; PENELOPE; MANTIS ID MODULATION TRANSFER-FUNCTION; IMAGING DETECTORS; MTF; RADIOGRAPHY; SYSTEMS AB Currently, the most accurate measurement of the detector point response can be performed with the pinhole method. The small size of the pinhole however, severely reduces the x-ray intensity output, requiring multiple long exposures, something that can potentially reduce the x-ray tube life-cycle. Even though deriving the 1D Line Response Function (LRF) of the detector using the edge method is much more efficient, the measurement process introduces a convolution with a line, in addition to the common pixel sampling, effectively broadening the LRE. We propose a practical method to recover the detector point response function by removing the effects of the line and the pixel from a set of Edge Response Function (ERF) measurements. We use the imaging equation to study the effects of the edge, line and pixel measurements, and derive an analytical formula for the recovered detector point response function based on a gaussian mixture model. The method allows for limited recovery of asymmetries in the detector response function. We verify the method with pinhole and edge measurements of a digital flat panel detector. Monte Carlo simulations are also performed, using the MANTIS x-ray and optical photon and electron' transport simulation package, for comparison. We show that the standard LRF underestimates the detector performance when compared with the recovered response. Our simulation results suggest that both the edge and pinhole methods for estimating the detector response have limitations in that they cannot completely capture rotational asymmetries or other morphological details smaller than the detector pixel size. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20857 USA. EM iacovos.kyprianou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6628-0 J9 PROC SPIE PY 2007 VL 6510 DI 10.1117/12.709517 PN 1-3 PG 12 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI21 UT WOS:000247292100010 ER PT S AU Chen, S Ross, TJ Chuang, KS Stein, EA Yang, YH Zhan, W AF Chen, Sharon Ross, Thomas J. Chuang, Keh-Shih Stein, Elliot A. Yang, Yihong Zhan, Wang BE Manduca, A Hu, XP TI Dimensionality estimation for group fMRI data reduction at multiple levels - art. no. 651116 SO Medical Imaging 2007: Physiology, Function, and Structure from Medical Images SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE autoregressive (AR); data reduction; dimensionality; group fMRI; independent component analysis (ICA); principle component analysis (PCA); resting state ID INDEPENDENT COMPONENT ANALYSIS AB Current techniques substantially overestimate the dimensionality of group fMRI data, and this problem worsens when principle component analysis (PCA) based data reductions are applied at multiple levels. In this paper, the mechanism of the overestimation is investigated, and a new method is developed for more reliable dimensionality estimation for group fMRI data at multiple levels. Simulation suggests that small variation of the signal components within a group is a major cause of dimensionality overestimation. To obtain an improved estimation, appropriate colored noise is added into the group fMRI data in order to blur the signal component variations. The noise parameters are estimated from the original fMRI data, and the improved dimensionality is determined by applying a first-order autoregressive (AR(1)) noise fitting technique to the PCA spectrum. The proposed method was tested on group resting-state fMRI datasets acquired from 14 normal human subjects in 5 different sessions. The PCA-based data reductions were performed at 3 levels in either "individual-session-subject" or "individual-subject-session" order. Results indicate that the proposed method significantly reduces the dimensionality overestimation for multiple level data reductions. Consistency of the estimated dimensionalities is observed with different group orders of the data reduction. C1 NIH, Natl Inst Drug Abuse, Baltimore, MD 21224 USA. RP Zhan, W (reprint author), NIH, Natl Inst Drug Abuse, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Ross, Thomas/0000-0002-7745-3572 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6629-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6511 BP 51116 EP 51116 AR 651116 DI 10.1117/12.710046 PN 1-2 PG 10 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ23 UT WOS:000247397500037 ER PT S AU Van Uitert, RL Summers, RM AF Van Uitert, Robert L. Summers, Ronald M. BE Manduca, A Hu, XP TI Colonic wall thickness using level sets for CT virtual Colonoscopy visual assessment and polyp detection - art. no. 65110S SO Medical Imaging 2007: Physiology, Function, and Structure from Medical Images SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE CT; colon; 3D reconstruction; colon cancer; image processing; computer-aided detection ID COLONOGRAPHY AB The detection of polyps in virtual colonoscopy is an active area of research. One of the critical elements in detecting cancerous polyps using virtual colonoscopy, especially in conjunction with computer-aided detection, is the accurate segmentation of the colon wall. The large CT attenuation difference between the lumen and inner, mucosal layer of the colon wall makes the segmentation of the lumen easily performed by traditional threshold segmentation techniques. However, determining the location of the colon outer wall is often difficult due to the low contrast difference between the colon wall's outer serosal layer and the fat surrounding the colon. We have developed an automatic, level set based method to determine from a CT colonography scan the location of the colon inner boundary and the colon outer wall boundary. From the location of the inner and outer colon wall boundaries, the wall thickness throughout the colon can be computed. Color mapping of the wall thickness on the colon surface allows for easy visual determination of potential regions of interest. Since the colon wall tends to be thicker at polyp locations, potential polyps also can be detected automatically at sites of increased colon wall thickness. This method was validated on several CT colonography scans containing optical colonoscopy-proven polyps. The method accurately determined thicker colonic wall regions in areas where polyps are present in the ground truth datasets and detected the polyps at a false positive rate between 44.4% and 82.8% lower than a state-of-the-art curvature-based method for initial polyp detection. C1 Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Van Uitert, RL (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6629-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6511 BP S5110 EP S5110 AR 65110S DI 10.1117/12.708572 PN 1-2 PG 7 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ23 UT WOS:000247397500023 ER PT S AU Campbell, SR Summers, RM AF Campbell, Shannon R. Summers, Ronald M. BE Manduca, A Hu, XP TI Analysis of kernel method for surface curvature estimation SO MEDICAL IMAGING 2007: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE virtual endoscopy; virtual colonoscopy; computer aided diagnosis; curvature estimation ID COMPUTER-ASSISTED DETECTION; AIDED DIAGNOSIS; CT COLONOGRAPHY; COLONIC POLYPS; DETECTOR; IMAGES AB Surface curvature estimation is a common component of CT colonography computer-aided polyp detection algorithms. A commonly used method to compute such curvatures employs convolution kernels. We have observed situations where the kernel method produces inaccurate results that could lead to undesirable false negative and false positive polyp diagnoses. In this paper, we numerically examine this method of curvature estimation. We propose optimal choices for smoothing parameters intrinsic to the method. The proposed smoothing parameters achieve more accurate and reliable curvatures compared to those reported in the literature. Our results include responses of the system with respect to Gaussian smoothing and Gaussian noise, results on the accuracy of the curvature estimation as a function of the distance from the true surface, and examples of specific topologies of the colonic surface for which the kernel method yields inaccurate responses. C1 Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Campbell, SR (reprint author), Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM kuzershan@yahoo.com NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6629-7 J9 PROC SPIE PY 2007 VL 6511 AR 65112I DI 10.1117/12.708285 PN 1-2 PG 10 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ23 UT WOS:000247397500081 ER PT S AU Jabour, P Huang, A Summers, RM AF Jabour, Paul Huang, Adam Summers, Ronald M. BE Manduca, A Hu, XP TI Using the teniae coli as a registration tool in CT Colonography SO MEDICAL IMAGING 2007: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE CT colonography; virtual colonoscopy; computer-aided diagnosis; polyp detection; registration; teniae coli ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; SUPINE; SCREEN AB We have found greater difficulty achieving desirable sensitivities and specificities with our computer-aided detection (CAD) system on polyps sized 6-9 mm. Missed polyps in our ground truth CAD training datasets could be one possible cause. Most CT colonography (CTC) protocols require supine and prone scans therefore the number of polyps visible to a radiologist in at least one scan may increase. However, registration of a specific polyp visible in both scans can prove difficult without a uniform coordinate system. Using a teniae coli registration tool we hypothesized we could register and find a statistically significant number of 6-9 mm polyps believed to be not findable in one scan subsequently reducing error in the training data and enabling better training of our CAD system. Database queries yielded 20 polyps initially believed to be not findable in one scan. The teniae coli navigation and registration system allowed us to identify 30% (6/20) of the polyps as matches with confidence in both scans (rating 1) and 10% (2/20) of the polyps with a potential match with some uncertainty (rating 2). No convincing match was found for 60% (12/20) of polyps (rating 3). We conclude that this teniae coli registration tool is an effective means of identifying and reducing ground truth data errors in 6-9 mm polyps initially believed not findable in one scan. The use of this tool has the potential to improve the performance of a CAD system on the more difficult 6-9 mm polyps. C1 Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Jabour, P (reprint author), Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM rms@nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6629-7 J9 PROC SPIE PY 2007 VL 6511 AR 65110U DI 10.1117/12.710707 PN 1-2 PG 7 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BGJ23 UT WOS:000247397500025 ER PT S AU Guttman, MA McVeigh, ER AF Guttman, Michael A. McVeigh, Elliot R. BE Cleary, KR Miga, MI TI New methods for image guidance and visualization for cardiac procedures - art. no. 65090S SO Medical Imaging 2007: Visualization and Image-Guided Procedures, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm ID RADIOFREQUENCY ABLATION LESIONS; INVASIVE VALVE OPERATIONS; PERCUTANEOUS HEART-VALVE; MESENCHYMAL STEM-CELLS; REAL-TIME; CATHETER-TRACKING; MR FLUOROSCOPY; STEADY-STATE; SWINE; REPLACEMENT AB Interventional cardiac MRI has been undergoing rapid development because of the availability of MRI compatible interventional catheters, and the increased performance of the MRI systems. Intravascular techniques do not require an open access scanner, and hence higher imaging performance during procedures can be achieved. Now, with the availability of a short, relatively open cylindrical bore scanner high imaging performance is also available to guide direct surgical procedures. C1 NHLBI, Dept Hlth & Human Serv, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Guttman, MA (reprint author), NHLBI, Dept Hlth & Human Serv, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6627-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6509 BP S5090 EP S5090 AR 65090S DI 10.1117/12.718223 PN 1-2 PG 9 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI23 UT WOS:000247294800027 ER PT S AU Kyprianou, IS Badal, A Badano, A Banh, D Freed, M Myers, KJ Thompson, L AF Kyprianou, Iacovos S. Badal, Andreu Badano, Aldo Banh, Diemphuc Freed, Melanie Myers, Kyle J. Thompson, Laura BE Cleary, KR Miga, MI TI Monte Carlo simulated coronary angiograms of realistic anatomy and pathology models SO MEDICAL IMAGING 2007: VISUALIZATION AND IMAGE-GUIDED PROCEDURES, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2007 Conference CY FEB 18-20, 2007 CL San Diego, CA SP SPIE, Amer Assoc Physicists, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE angiography; coronary; phantom; Monte; Carlo; PENELOPE; NURBS; NCAT ID RAY IMAGE INTENSIFIER; MICROANGIOGRAPHIC SYSTEM; SCATTER AB We have constructed a fourth generation anthropomorphic phantom which, in addition to the realistic description of the human anatomy, includes a coronary artery disease model. A watertight version of the NURBS-based Cardiac-Torso (NCAT) phantom was generated by converting the individual NURBS surfaces of each organ into closed, manifold and non-self-intersecting tessellated surfaces. The resulting 330 surfaces of the phantom organs and tissues are now comprised of similar to 5 x 10(6) triangles whose size depends on the individual organ surface normals. A database of the elemental composition of each organ was generated, and material properties such as density and scattering cross-sections were defined using PENELOPE. A 300 pm resolution model of a heart with 55 coronary vessel segments was constructed by fitting smooth triangular meshes to a high resolution cardiac CT scan we have segmented, and was consequently registered inside the torso model. A coronary artery disease model that uses hemodynamic properties such as blood viscosity and resistivity was used to randomly place plaque within the artery tree. To generate x-ray images of the aforementioned phantom, our group has developed an efficient Monte Carlo radiation transport code based on the subroutine package PENELOPE, which employs an octree spatial data-structure that stores and traverses the phantom triangles. X-ray angiography images were generated under realistic imaging conditions (90 kVp, 10 degrees W anode spectra with 3 mm Al filtration, similar to 5 x 10(11) x-ray source photons, and 10% per volume iodine contrast in the coronaries). The images will be used in an optimization algorithm to select the optimal technique parameters for a variety of imaging tasks. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RP Kyprianou, IS (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Parkway, Rockville, MD 20857 USA. EM iacovos.kyprianou@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 24 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6627-3 J9 PROC SPIE PY 2007 VL 6509 AR 65090O DI 10.1117/12.709553 PN 1-2 PG 11 WC Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI23 UT WOS:000247294800023 ER PT J AU Pendrak, ML Rodrigues, RG Roberts, DD AF Pendrak, Michael L. Rodrigues, Rui G. Roberts, David D. TI Induction of a high affinity fibronectin receptor in Candida albicans by caspofungin: requirements for beta (1,6) glucans and the developmental regulator HbrIp SO MEDICAL MYCOLOGY LA English DT Article DE Candida albicans; high affinity fibronectin receptor; caspofungin ID EXTRACELLULAR-MATRIX PROTEINS; CELL-WALL; SACCHAROMYCES-CEREVISIAE; MOLECULAR-ORGANIZATION; BACTERIAL ADHERENCE; PLASMA FIBRONECTIN; BINDING DOMAIN; NIKKOMYCIN-Z; GENE; HEMOGLOBIN AB Candida albicans expresses at least two biochemically distinct fibronectin receptors. Hemoglobin induces expression of a low affinity receptor recognizing the fibronectin cell-binding domain, whereas growth in complex media induces a high affinity receptor recognizing the collagen-binding domain. We now show that sub-inhibitory concentrations of caspofungin and nikkomycin Z, but not fluconazole, induce the high affinity fibronectin receptor in a dose-dependent manner. Macromolecular complexes mechanically sheared from caspofungin-treated cells retained high affinity fibronectin binding that was sensitive to protease, disulfide reduction, and beta (1,3) glucanase digestion. The high affinity fibronectin receptor was not inducible in a Kre9 mutant strain of C. albicans deficient in b (1,6) glucans. Conversely, a mutant strain lacking the fibronectin binding protein A1s5p showed no defects in induction of high or low affinity fibronectin receptors. Heterozygous mutants of a regulator of white-opaque phenotypic switching, HBR1, lacked any detectable high affinity fibronectin receptor expression in response to caspofungin, and re-introduction of the gene restored activity. Therefore, sub-inhibitory dosages of caspofungin induce a high affinity fibronectin receptor that is distinct from the known receptor Als5p and is dependent on b (1,6) glucans and HBR1. C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pendrak, ML (reprint author), NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM mpendrak@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 55 TC 4 Z9 8 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 EI 1460-2709 J9 MED MYCOL JI Med. Mycol. PY 2007 VL 45 IS 2 BP 157 EP 168 DI 10.1080/13693780601164314 PG 12 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 167VC UT WOS:000246479600006 PM 17365652 ER PT J AU Te Dorsthorst, DTA Zwaaftink, RBMG Rijs, AJMM Meletiadis, J Verweij, PE AF Te Dorsthorst, D. T. A. Zwaaftink, R. B. M. Groot Rijs, A. J. M. M. Meletiadis, J. Verweij, P. E. TI A colorimetric and spectrophotometric method for in vitro susceptibility testing of Aspergillus species against caspofungin SO MEDICAL MYCOLOGY LA English DT Article DE Aspergillus; in vitro susceptibility; caspofungin; colorimetric method; spectrophotometric readings ID FILAMENTOUS FUNGI; AMPHOTERICIN-B; ITRACONAZOLE; VORICONAZOLE; FUMIGATUS AB The in vitro susceptibility of 45 Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus isolates against caspofungin (CAS) was assessed by the CLSI reference method with spectrophotometric reading and by a colorimetric method that employed the dye MTT. Perfect agreement was found between the minimal effective concentrations (MECs) and the MIC-2 values (50% growth reduction) obtained by the MTT method. The agreement found between the MICs obtained by the CLSI and the MTT method was dependent on the MIC endpoint used, the antifungal agent tested, and the species investigated. C1 Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. Canisius Wilhelmia Hosp, Dept Med Microbiol & Infect Dis, Nijmegen, Netherlands. Univ Nijmegen, Ctr Infect Dis, Nijmegen, Netherlands. NIH, Bethesda, MD 20892 USA. RP Verweij, PE (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, PO Box 9101, NL-6500 HB Nijmegen, Netherlands. EM p.verweij@mmb.umcn.nl RI Verweij, P.E./H-8108-2014 NR 9 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2007 VL 45 IS 4 BP 351 EP 355 DI 10.1080/13693780701216485 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 193IG UT WOS:000248267100005 PM 17510858 ER PT J AU Meletiadis, J Walsh, TJ Choi, EH Pappas, PG Ennis, D Douglas, J Pankey, GA Larsen, RA Hamill, RJ Chanock, S AF Meletiadis, Joseph Walsh, Thomas J. Choi, Eun Hwa Pappas, Peter G. Ennis, David Douglas, Jeffrey Pankey, George A. Larsen, Robert A. Hamill, Richard J. Chanock, Stephen TI Study of common functional genetic polymorphisms of FCGR2A, 3A and 3B genes and the risk for cryptococcosis in HIV-uninfected patients SO MEDICAL MYCOLOGY LA English DT Article DE cryptococcosis; candidate gene association studies; genetic polymorphisms; haplotype analysis; Cryptococcus neoformans ID FC-GAMMA RECEPTORS; NEOFORMANS; DISEASE; POPULATION; SUSCEPTIBILITY; ANTIBODIES; BINDING; RIIIA; IGG AB A pilot candidate gene association study was conducted to investigate the role of three common functional genetic polymorphisms of the low-affinity Fc gamma receptors, FCGR2A (131H/R), FCGR3A (158F/V) and FCGR3B (NA1/NA2) in Cryptococcus neoformans infections in individuals not infected with HIV. The FCGR2A 131RR and FCGR3A 158VV genotypes were over-represented [OR: 1.67 (1.05-2.63) and 2.04 (1.06-4.00), respectively] whereas the FCGR3B NA2NA2 was under-represented in patients with cryptococcosis (28% vs. 40% in controls). An analysis of haplotypes showed a significant difference in distribution between cases and controls overall and in Caucasians. C1 NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. Univ So Calif, Los Angeles, CA USA. Vet Adm Med Ctr, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Chanock, S (reprint author), NIH, Ctr Adv Technol, NCI, Sect Genom Variat, 8717 Grovemont Circle, Gaithersburg, MD 20892 USA. EM sc83a@nih.gov RI Choi, Eun Hwa/J-5691-2012 FU Intramural NIH HHS NR 22 TC 12 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2007 VL 45 IS 6 BP 513 EP 518 DI 10.1080/13693780701390140 PG 6 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 213QE UT WOS:000249681400004 PM 17710620 ER PT J AU Cocco, P Dosemeci, M Rice, C AF Cocco, P. Dosemeci, M. Rice, C. TI Lung cancer among silica-exposed workers: the quest for Truth between chance and necessity SO MEDICINA DEL LAVORO LA English DT Article DE silica; silicosis; lung neoplasms; occupational health; carcinogenesis ID NESTED CASE-CONTROL; CRYPTOGENIC FIBROSING ALVEOLITIS; DIATOMACEOUS-EARTH INDUSTRY; CRYSTALLINE SILICA; EPITHELIAL-CELLS; AIRWAYS OBSTRUCTION; RESPIRATORY-DISEASE; SURFACE REACTIVITY; RESPONSE ANALYSES; NONSMOKING WOMEN AB Background: In 1997, LARC upgraded crystalline silica to a Group 1 human carcinogen. However, the LARC report itself acknowledged variations in risk depending on inherent characteristics of the crystalline silica or external factors affecting its biological activity or distribution of its polymorphs. Methods: We reviewed silica physical and physico-chemical properties and how such properties may affect its interaction with the target cells. Studies of silica, silicosis and lung cancer published from 1997 onwards are then reviewed in the search of any new advances in knowledge about silica carcinogenicity. Finally, other possible confounding factors contributing to inconsistent findings on silica, silicosis, and lung cancer are reviewed. Results: Host factors, physico-chemical characteristics of the surface of silica particles, exposure circumstances, and the mineral ore composition experimentally affect the ability of silica particles of inducing release of reactive oxygen species (ROS) and TNF-alpha by alveolar macrophages, possibly accounting for the great variation in lung cancer risk among dust exposed workers across the individual studies. Most recent epidemiological studies do not consider such complex pattern of modifying factors, and they keep replicating inconsistent findings. The hypothesis of a silicosis-mediated pathway, although more consistent from an epidemiological perspectives, and reassuring in terms of the effectiveness of current standards in preventing lung cancer risk among silica exposed workers, does not seem to explain elevated risks at low silica exposure levels. Conclusion: Future studies of lung cancer risk among workers exposed to silica-containing dust should consider measurement of ROS and TNF-alpha release by workplace dust samples as Intermediate end-points predicting lung cancer risk better than silica concentration, allowing to more effectively address preventive action. C1 [Cocco, P.] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, I-09124 Cagliari, Italy. [Dosemeci, M.] NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Rice, C.] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. RP Cocco, P (reprint author), Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Via San Giorgio 12, I-09124 Cagliari, Italy. EM coccop@pacs.unica.it NR 83 TC 15 Z9 16 U1 1 U2 4 PU MATTIOLI 1885 PI FIDENZA PA VIA CODURO 1-B, FIDENZA, 43046 PR, ITALY SN 0025-7818 J9 MED LAV JI Med. Lav. PD JAN-FEB PY 2007 VL 98 IS 1 BP 3 EP 17 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 276BH UT WOS:000254115700001 PM 17240640 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Yau, YY Smith, KP Arena, R Waclawiw, MA Leitman, SF Rosing, DR AF Shizukuda, Yukitaka Bolan, Charles D. Tripodi, Dorothy J. Yau, Yu-Ying Smith, Kevin P. Arena, Ross Waclawiw, Myron A. Leitman, Susan F. Rosing, Douglas R. TI Exercise capacity of cardiac asymptomatic hereditary hemochromatosis subjects SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE hereditary hemochromatosis; exercise capacity; metabolism; symptom limited exercise ID HEART-FAILURE; VENTILATORY EFFICIENCY; ECHOCARDIOGRAPHY; THRESHOLD; TREADMILL; INDEXES; GENE AB Purpose: The exercise capacity of cardiac asymptomatic subjects with hereditary hemochromatosis (HH) has not been well described. In this study, we tested whether the iron overload associated with HH affected exercise capacity with a case control study design. Methods: Forty-three HH and 21 normal control subjects who were New York Heart Association functional class I underwent metabolic stress testing using the Bruce protocol at the clinical center of the National Institutes of Health. Exercise capacity was assessed with minute ventilation (V-E), oxygen uptake (VO2), and carbon dioxide production (VCO2) using a breath-by-breath respiratory gas analyzer. Results: The exercise capacity of HH subjects was not statistically different from that of control subjects (exercise time 564 +/- 135 vs 673 +/- 175 s, P = 0.191; peak VO2 29.6 +/- 6.4 vs 32.5 +/- 6.7 mL(.)kg(-1.)min(-1), P = 0.109; ventilatory threshold 19.0 +/- 3.4 vs 21.0 +/- 5.0 mL(.)min(-1.)kg(-1), P = 0.099; data are for HH vs control subjects). Ventilatory efficiency was comparable between groups (V-E/VCO2 Slope 23.7 +/- 3.2 vs 23.4 +/- 4.2, P = 0.791). No significant correlation between the markers of iron levels and the markers of exercise capacity was noted. Iron depletion by 6-month phlebotomy therapy in 18 subjects who were newly diagnosed did not affect exercise testing variables (exercise time 562 +/- 119 vs 579 +/- 118 s, P = 0.691; peak VO2 29.5 +/- 3.7 vs 29.1 +/- 4.7 mL(.)kg(-1.)min(-1), P = 0.600; ventilatory threshold 18.5 +/- 2.8 vs 17.9 +/- 3.8 mL(.)kg(-1.)min(-1), P = 0.651; data are from before and after phlebotomy therapy). Abnormal ischemic electrocardiographic responses and complex arrhythmias were more frequently seen in HH subjects. Conclusions: The aerobic exercise capacity of asymptomatic HH subjects seems not to be statistically different from that of normal subjects. The iron levels do not seem to affect exercise capacity in asymptomatic HH subjects. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10-CRC,Rm 6-3142,MSC-1454,10 Ctr Dr, Bethesda, MD 20892 USA. EM shizukuy@nhlbi.nih.gov RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU Intramural NIH HHS NR 24 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2007 VL 39 IS 1 BP 3 EP 7 DI 10.1249/01.mss.0000240323.08406.f3 PG 5 WC Sport Sciences SC Sport Sciences GA 127GZ UT WOS:000243574800002 PM 17218876 ER PT J AU Pelis, K AF Pelis, Kim BE Bivins, R Pickstone, JV TI 'A Band of Lunatics down Camberwell Way': Percy Lane Oliver and Voluntary Blood Donation in Interwar Britain SO MEDICINE, MADNESS AND SOCIAL HISTORY: ESSAYS IN HONOUR OF ROY PORTER LA English DT Article; Book Chapter C1 NIH, Bethesda, MD 20892 USA. RP Pelis, K (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU PALGRAVE PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND BN 978-0-230-23535-9 PY 2007 BP 148 EP + D2 10.1057/9780230235359 PG 15 WC History SC History GA BRG50 UT WOS:000282681200013 ER PT S AU Neveol, A Pereira, S Kerdelhue, G Dahamna, B Joubert, M Darmoni, SJ AF Neveol, Aurelie Pereira, Suzanne Kerdelhue, Gaetan Dahamna, Badisse Joubert, Michel Darmoni, Stefan J. BE Kuhn, KA Warren, JR Leong, TY TI Evaluation of a Simple Method for the Automatic Assignment of MeSH Descriptors to Health Resources in a French Online Catalogue SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE abstracting and indexing/methods; algorithms; catalogs; library; information storage and retrieval/methods; evaluation study; France; medical subject headings; Natural Language Processing AB Background: The growing number of resources to be indexed it? the catalogue of online health resources in French (CISMeF) calls for curating strategies involving automatic indexing tools while maintaining the catalogue's high indexing quality standards. Objective: To develop a simple automatic tool that retrieves MeSH descriptors from documents titles. Methods: fit parallel to research on advanced indexing methods, a bag-of-words tool was developed for timely inclusion in CISMeF's maintenance system. An evaluation was carried out at? a corpus of 99 documents. The indexing sets retrieved by the automatic tool were compared to manual indexing based on the title and on the full text of resources. Results: 58% of the major main headings were retrieved by the bag-of-words algorithm and the precision on main heading retrieval was 69%. Conclusion: Bag-of-words indexing has effectively been used on selected resources to be included in CISMeF since August 2006. Meanwhile, on going work aims at improving the current version of the tool. C1 [Neveol, Aurelie] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Darmoni, SJ (reprint author), CHU Rouen, DIR, 1 Rue Germont, F-76031 Rouen, France. RI JOUBERT, Michel/A-8699-2010; Stefan, Darmoni/H-4554-2016 NR 11 TC 5 Z9 5 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 407 EP 411 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000083 PM 17911749 ER PT S AU Antani, SK Deserno, TM Long, LR Thoma, GR AF Antani, Sameer K. Deserno, Thomas M. Long, L. Rodney Thoma, George R. BE Kuhn, KA Warren, JR Leong, TY TI Geographically Distributed Complementary Content-Based Image Retrieval Systems for Biomedical Image Informatics SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE medical informatics applications; image information storage and retrieval; Internet services ID MEDICAL APPLICATIONS; FRAMEWORK; DATABASES AB There is a significant increase in the use of medical images in clinical medicine, disease research, and education. While the literature lists several successful systems for content-based image retrieval and image management methods, they have been unable to make significant inroads in routine medical informatics. This can be attributed to the following: (i) the challenging nature of medical images, (ii) need for specialized methods, specific to each image Ope and detail, (iii) lack of advances in image indexing methods, and (iv) lack of a uniform data and resource exchange framework between complementary systems. Most systems tend to focus on varying degrees of the first two items, making them very versatile in a small sampling of the variety of medical images but unable to share their strengths. This paper proposes to overcome these shortcomings by defining a data and resource exchange framework using open standards and software to develop geographically distributed toolkits. As proof-of-concept, we describe the coupling of two complementary geographically separated systems: the IRMA system at Aachen University of Technology in Germany, and the SPIRS system at the U. S. National Library of Medicine in the United States of America. C1 [Antani, Sameer K.; Deserno, Thomas M.; Long, L. Rodney; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA. RP Antani, SK (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike,MS 3824, Bethesda, MD 20894 USA. EM santani@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 FU Intramural NIH HHS NR 13 TC 2 Z9 2 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 493 EP 497 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000100 PM 17911766 ER PT S AU Fung, KW Bodenreider, O Aronson, AR Hole, WT Srinivasan, S AF Fung, Kin Wah Bodenreider, Olivier Aronson, Alan R. Hole, William T. Srinivasan, Suresh BE Kuhn, KA Warren, JR Leong, TY TI Combining Lexical and Semantic Methods of Inter-terminology Mapping Using the UMLS SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE Unified Medical Language System; controlled terminology; inter-terminology mapping AB The need for inter-terminology mapping is constantly increasing with the growth in the volume of electronically captured biomedical data and the demand to re-use the same data for secondary purposes. Using the UMLS as a knowledge base, semantically-based and lexically-based mappings were generated from SNOMED CT to ICD9CM terms and compared to a gold standard. Semantic mapping performed better than lexical mapping in terms of covers age, recall and precision. As the two mapping methods are orthogonal, the two sets, of mappings can be used to validate and enhance each other A method of combining the mappings based on the precision level of sub-categories in each method was derived. The combined method outperformed both methods, achieving coverage of 91%, recall of 43% and precision of 27%. It is also possible to customize the method of combination to optimize performance according to the task at hand. C1 [Fung, Kin Wah; Bodenreider, Olivier; Aronson, Alan R.; Hole, William T.; Srinivasan, Suresh] Natl Lib Med, Bethesda, MD USA. RP Fung, KW (reprint author), 8600 Rockville Pike,MSC 3826, Bethesda, MD 20894 USA. EM kwfung@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 9 TC 11 Z9 11 U1 0 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 605 EP 609 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000122 PM 17911788 ER PT S AU Fontelo, P Liu, F Leon, S Anne, A Ackerman, M AF Fontelo, Paul Liu, Fang Leon, Sergio Anne, Abrahamane Ackerman, Michael BE Kuhn, KA Warren, JR Leong, TY TI PICO Linguist and BabelMeSH: Development and Partial Evaluation of Evidence-based Multilanguage Search Tools for MEDLINE/PubMed SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE evidence-based medicine; multilanguage search; MeSH; MEDLINE/PubMed; PICO; UMLS AB PICO Linguist and BabelMeSH are multilanguage search tools intended for users whose native language is not English. A database of medical terms was created using concept identification equivalents of English terms to other languages. The primary sources of vocabularies were UMLS, MeSH, WHO EMRO and UMLF The search interface changes according to the language selected which allows search terms to be entered in the native language. The user can limit the search output according to the language of publication but citations retrieved are in English only Links may be provided to journals if published online. Evaluation of the French and Spanish versions using journal key words and a list of common diseases showed 77.5% and 86.5% accuracy respectively User feedback was positive. PICO Linguist and BabelMeSH could be useful and convenient tools in finding current evidence sources in the medical literature especially for non-English medical terms that may be difficult to express in English. C1 [Fontelo, Paul; Liu, Fang; Leon, Sergio; Ackerman, Michael] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Fontelo, P (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM fontelo@nlm.nih.gov NR 7 TC 2 Z9 2 U1 0 U2 1 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 817 EP 821 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000164 PM 17911830 ER PT S AU Zhang, SM Bodenreider, O AF Zhang, Songmao Bodenreider, Olivier BE Kuhn, KA Warren, JR Leong, TY TI Lessons Learned from Cross-Validating Alignments between Large Anatomical Ontologies SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE anatomy; ontology alignment; collaborative evaluation; cross-validation AB Objectives: To compare the alignments of two large anatomical ontologies (the Foundational Model of Anatomy and GALEN) produced by three ontology alignment systems (AOAS, FALCON and PRIOR) in the framework of the Ontology Alignment Evaluation Initiative during its 2006 campaign. Materials: Number of mappings identified by AOAS: 3,132, FALCON: 2,518 and PRIOR: 2,589. Methods: Three approaches to analyzing and comparing the results were utilized computing the overlap among result files, manual review of some 2, 000 mappings and structural validation. Conclusions: The generic systems FALCON and PRIOR identify many false positives and false negatives. With a stricter and domain-specific lexical similarity model, AOAS has a better precision, but is more sensitive to missing synonyms and misspellings. C1 [Zhang, Songmao] Chinese Acad Sci, Inst Math, Acad Math & Syst Sci, Beijing, Peoples R China. RP Bodenreider, O (reprint author), Natl Lib Med, 8600 Rockville Pike,MS 3841, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 9 TC 2 Z9 2 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 822 EP 826 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000165 PM 17911831 ER PT S AU Logan, RA Tse, T AF Logan, Robert A. Tse, Tony BE Kuhn, KA Warren, JR Leong, TY TI A Multidiscipline Conceptual Framework for Consumer Health Informatics SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2: BUILDING SUSTAINABLE HEALTH SYSTEMS SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE health behavior; internet; informatics; communication; information science; consumer satisfaction; evaluation studies ID COMMUNICATION; RETRIEVAL; SEEKING AB This paper presents an idealized conceptual framework for consumer health informatics research drawing from complementary disciplines: information science and health campaign research. This synthesis is designed to provide researchers with a flexible model to evaluate current research and inform future studies. Following a description of the major components, we describe a recent evaluation of consumer perceptions of a health information system, Genetics Health Reference. This study illustrates how the framework may be applied to provide some direction and insights into ongoing consumer health informatics research. While this model represents a work in progress, we present it in support of efforts to understand the multidimensional impacts of the public's access to health information. We also discuss challenges that remain to develop a better conceptual understanding of how consumers converge on health informatics services. C1 [Logan, Robert A.; Tse, Tony] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Logan, RA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 38A, Bethesda, MD 20894 USA. EM logan@nlm.nih.gov FU Intramural NIH HHS NR 17 TC 2 Z9 3 U1 1 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 1169 EP 1173 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000233 PM 17911899 ER PT S AU Sahoo, SS Zeng, K Bodenreider, O Sheth, A AF Sahoo, Satya S. Zeng, Kelly Bodenreider, Olivier Sheth, Amit BE Kuhn, KA Warren, JR Leong, TY TI From "Glycosyltransferase" to "Congenital Muscular Dystrophy": Integrating Knowledge from NCBI Entrez Gene and the Gene Ontology SO MEDINFO 2007: PROCEEDINGS OF THE 12TH WORLD CONGRESS ON HEALTH (MEDICAL) INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 12th World Congress on Health (Medical) Informatics CY AUG 20-24, 2007 CL Brisbane, AUSTRALIA SP Hlth Informat Soc Australia DE knowledge integration; Semantic Web; RDF; Entrez Gene; Gene Ontology AB Entrez Gene (EG), Online Mendelian Inheritance in Man (OMIM) and the Gene Ontology (GO) are three complementary knowledge resources that can be used to correlate genomic data with disease information. However, bridging between genotype and phenotype through these resources currently requires manual effort or the development of customized software. In this paper, we argue that integrating EG and GO provides a robust and flexible solution to this problem. We demonstrate how the Resource Description Framework (RDF) developed for the Semantic Web can be used to represent and integrate these resources and enable seamless access to them as a unified resource. We illustrate the effectiveness of our approach by answering a real-world biomedical query linking a specific molecular function, glycosyltransferase, to the disorder congenital muscular dystrophy. C1 [Sahoo, Satya S.; Sheth, Amit] Wright State Univ, Dept Comp Sci & Engn, Knoesis Ctr, Dayton, OH 45435 USA. RP Bodenreider, O (reprint author), NIH, US Natl Library Med, 8600 Rockville Pike,MS 3841, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999]; NCRR NIH HHS [5 P41 RR18502, P41 RR018502] NR 12 TC 4 Z9 4 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-58603-774-1 J9 ST HEAL T PY 2007 VL 129 BP 1260 EP 1264 PG 5 WC Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA BMF03 UT WOS:000272064000251 PM 17911917 ER PT J AU Power, ML Schulkin, J Rossouw, JE AF Power, Michael L. Schulkin, Jay Rossouw, Jacques E. TI Evolving practice patterns and attitudes toward hormone therapy of obstetrician-gynecologists SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE hormone therapy; Women's Health Initiative; survey; menopause ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; CANCER; KNOWLEDGE; BREAST AB Objective: The objective of this study was to examine the opinions and prescribing practices of obstetrician-gynecologists regarding hormone therapy (HT) and the results from the Women's Health Initiative. Design: Surveys were sent to 2,500 randomly selected American College of Obstetrics and Gynecology fellows during December 2004 to March 2005; their responses are compared with those from a survey conducted in November to December 2003. Results: Respondents remained skeptical of the combined HT results (49.1% did not find the results convincing). Compared with the 2003 survey, men were more skeptical (58.8% did not consider the findings convincing in 2004 vs 53.4% in 2003, P = 0.045), and women were somewhat less skeptical (39.5% did not consider the findings convincing in 2004 vs 45.3% in 2003, P = 0.056). There was less skepticism about the estrogen-only trial, although 4 of 10 did not find the results convincing. Men were more skeptical than women; a majority of men disagreed with the decisions to stop the trials. Physicians who completed their residency more recently were more likely to accept the trial results. Respondents reported a reduction in HT prescription practice relative to the year 2000, but 62.7% reported they did not expect their prescribing practices to change further in the near future. The proportion of respondents who considered alternative therapies to HT as viable treatment options increased between 2003 and 2004 (37.1% vs 28.1%, P < 0.001). There was strong support for the use of HT for vasomotor symptoms, vaginal dryness, and osteoporosis, but most physicians did not consider HT useful for cardiovascular disease or dementia. Conclusions: Many obstetrician-gynecologists continue to express skepticism about the results and conduct of the Women's Health Initiative trials. The survey could not determine the reasons for skepticism. C1 American Coll Obstet & Gynecol, Dept Res, Washington, DC 20024 USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. RP Power, ML (reprint author), American Coll Obstet & Gynecol, Dept Res, 409 12th St SW, Washington, DC 20024 USA. EM mpower@acog.org OI Power, Michael/0000-0002-6120-3528 FU NHLBI NIH HHS [N01-HO-34205] NR 15 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2007 VL 14 IS 1 BP 20 EP 28 DI 10.1097/01.gme.0000229571.44505.cb PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 136XG UT WOS:000244256800007 PM 17019376 ER PT J AU Schooler, C AF Schooler, Carmi BE Avison, WR McLeod, JD Pescosolido, BA TI The Changing Role(s) of Sociology (and Psychology) in the National Institute of Mental Health Intramural Research Program SO MENTAL HEALTH, SOCIAL MIRROR LA English DT Article; Book Chapter ID SCHIZOPHRENIA; ENVIRONMENT C1 NIMH, US Dept HHS, NIH, Intramural Rsearch Program,Sect Socioenvironm Stu, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, US Dept HHS, NIH, Intramural Rsearch Program,Sect Socioenvironm Stu, Bethesda, MD 20892 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-36320-2 PY 2007 BP 55 EP 63 DI 10.1007/978-0-387-36320-2_3 D2 10.1007/978-0-387-36320-2 PG 9 WC Public, Environmental & Occupational Health; Sociology SC Public, Environmental & Occupational Health; Sociology GA BKT45 UT WOS:000269177000004 ER PT J AU Petersen, DW Kawasaki, ES AF Petersen, David W. Kawasaki, Ernest S. TI Manufacturing of microarrays SO MICROARRAY TECHNOLOGY AND CANCER GNE PROFILING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID OLIGONUCLEOTIDE SYNTHESIZER AB DNA microarray technology has become a powerful tool in the arsenal of the molecular biologist. Capitalizing on high precision robotics and the wealth of DNA sequences annotated from the genomes of a large number of organisms, the manufacture of microarrays is now possible for the average academic laboratory with the funds and motivation. Microarray production requires attention to both biological and physical resources, including DNA libraries, robotics, and qualified personnel. While the fabrication of microarrays is a very labor-intensive process, production of quality microarrays individually tailored on a project-by-project basis will help researchers shed light on future scientific questions. C1 SAIC Frederick Inc, Natl Canc Inst, Microarray Facil, Gaithersburg, MD USA. RP Petersen, DW (reprint author), SAIC Frederick Inc, Natl Canc Inst, Microarray Facil, 8717 Grovemont Circle,Rm 128, Gaithersburg, MD USA. EM petersed@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 7 TC 7 Z9 7 U1 2 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 593 BP 1 EP 11 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFM46 UT WOS:000243068700001 PM 17265711 ER PT J AU Wang, E Panelli, M Marincola, FM AF Wang, Ena Panelli, Monica Marincola, Francesco M. TI Complementary techniques: RNA amplification for gene profiling analysis SO MICROARRAY TECHNOLOGY AND CANCER GNE PROFILING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID MESSENGER-RNA; EXPRESSION ANALYSIS; CDNA MICROARRAY; AMPLIFIED RNA; OLIGONUCLEOTIDE MICROARRAYS; REVERSE TRANSCRIPTION; IMMUNE RESPONSIVENESS; MOLECULAR ANALYSIS; OVARIAN-CANCER; PCR AB The study of clinical samples is often limited by the amount of material available. DNA and RNA can be amplified from small specimens and, therefore, used for high-throughput analyses. While precise estimates of the level of DNA concentration in a given specimen is rarely studied (with the exception of relatively crude analyses of gene amplification or loss in cancer specimens), it is critical to know the proportional expression of various RNA transcripts since this proportion governs cell function by modulating the expression of various proteins. In addition, accurate estimates of relative RNA expression in biological conditions portray the reaction of cells to environmental stimuli shedding light on the characteristics of the microenvironment associated with particular physiologic or pathologic conditions. For this reason, the development of technologies for high fidelity messenger RNA amplification have been focused of extreme interest in the past decade with specific aim not only of increasing the abundance of RNA available to study but to accurately maintain the proportionality of expression of various RNA species among each other within a given specimen. This chapter will discuss various approaches to proportional RNA amplification focusing on amplification of the whole transcriptome (all transcripts in a given samples) rather than individual genes. These methods are suitable for high-throughput transcriptional profiling studies. C1 NIH, Dept Transfus Med, Ctr Clin, Immunogenet Sect, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Immunogenet Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM FMarincola@cc.nih.gov NR 72 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 593 BP 39 EP 53 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFM46 UT WOS:000243068700005 PM 17265715 ER PT J AU Perez-Diez, A Morgan, A Shulzhenko, N AF Perez-Diez, Ainhoa Morgan, Andrey Shulzhenko, Natatia TI Microarrays for cancer diagnosis and classification SO MICROARRAY TECHNOLOGY AND CANCER GNE PROFILING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; LASER CAPTURE MICRODISSECTION; ACUTE MYELOID-LEUKEMIA; PROSTATE-CANCER; OVARIAN-CANCER; MOLECULAR CLASSIFICATION; BREAST-CANCER; SERUM MARKER; TUMOR; CELL AB Microarray analysis has yet to be widely accepted for diagnosis and classification of human cancers, despite the exponential increase in microarray studies reported in the literature. Among several methods available, a few refined approaches have evolved for the analysis of microarray data for cancer diagnosis. These include class comparison, class prediction and class discovery. Using as examples some of the major experimental contributions recently provided in the field of both hematological and solid tumors, we discuss the steps required to utilize microarray data to obtain general and reliable gene profiles that could be universally used in clinical laboratories. As we show, microarray technology is not only a new tool for the clinical lab but it can also improve the accuracy of the classical diagnostic techniques by suggesting novel tumor-specific markers. We then highlight the importance of publicly available microarray data and the development of their integrated analysis that may fulfill the promise that this new technology holds for cancer diagnosis and classification. C1 NIAID, Ghost Lab, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Perez-Diez, A (reprint author), NIAID, Ghost Lab, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. EM aperezdiez@niaid.nih.gov NR 42 TC 24 Z9 28 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 593 BP 74 EP 85 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFM46 UT WOS:000243068700008 PM 17265718 ER PT J AU Monsurro, V Marincola, FM AF Monsurro, Vladia Marincola, Francesco M. TI Gene profiling for the prediction of tumor response to treatment: The case of immunotherapy SO MICROARRAY TECHNOLOGY AND CANCER GNE PROFILING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; BLOOD MONONUCLEAR-CELLS; T-CELLS; IMMUNE RESPONSIVENESS; METASTATIC MELANOMA; PEPTIDE VACCINE; MESSENGER-RNA; CANCER; EXPRESSION; INTERLEUKIN-2 C1 NIH, Dept Transfus Med, Ctr Clin, Immunogenet Sect, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Immunogenet Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM FMarincola@cc.nih.gov NR 57 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 593 BP 86 EP 94 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFM46 UT WOS:000243068700009 PM 17265719 ER PT J AU He, M Rosen, J Mangiameli, D Libutti, SK AF He, Mei Rosen, Jennifer Mangiameli, David Libutti, Steven K. TI Cancer development and progression SO MICROARRAY TECHNOLOGY AND CANCER GNE PROFILING SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID LASER-CAPTURE MICRODISSECTION; TRANSCRIPTIONAL REGULATORY NETWORKS; MESSENGER-RNA AMPLIFICATION; MALIGNANT THYROID-TUMORS; IN-SITU HYBRIDIZATION; DNA COPY-NUMBER; GENE-EXPRESSION; BREAST-CANCER; MICROARRAY ANALYSIS; TISSUE MICROARRAYS AB Cancer development and progression is a complex process that involves a host of functional and genetic abnormalities. Genomic perturbations and the gene expression they lead to, can now be globally identified with the use of DNA microarray. This relatively new technology has forever changed the scale of biological investigation. The enormous amount of data generated via a single chip has led to major global studies of the cellular processes underlying malignant transformation and progression. The multiplicity of platforms from different proprietors has offered investigators flexibility in their experimental design. Additionally, there are several more recent microarrays whose designs were inspired by the nucleotide-based technology. These include protein, multi-tissue, cell, and interference RNA microarrays. Combinations of microarray and other contemporary scientific methods, such as, laser capture microdissection (LCM), comparative genomic hybridization (CGH), single nucleotide polymorphism analysis (SNP) and chromatin immunoprecipitation (ChIP), have created entirely new fields of interest in the more global quest to better define the molecular basis of malignancy. In addition to basic science applications, many clinical inquiries have been performed. These queries have shown microarray to have clinical utility in cancer diagnosis, risk stratification, and patient management. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM libutti@mail.nih.gov NR 72 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 593 BP 117 EP 133 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFM46 UT WOS:000243068700012 PM 17265722 ER PT J AU Fukutome, A Watashi, K Kawakami, N Ishikawa, H AF Fukutome, Ayako Watashi, Koichi Kawakami, Norito Ishikawa, Hirofumi TI Mathematical modeling of severe acute respiratory syndrome nosocomial transmission in Japan: The dynamics of incident cases and prevalent cases SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE SARS; nosocomial transmission; Stochastic model; simulation ID HONG-KONG; SARS TRANSMISSION; CORONAVIRUS; OUTBREAK; TORONTO; AGENT AB An outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Hong Kong in late February 2003, resulting in 8,096 cumulative cases with 774 deaths. The outbreak was amplified by nosocomial transmission in many hospitals. Using mathematical modeling, we simulated the number of new incident and prevalent cases of SARS after one infected person was admitted to a hospital (index case). The simulation was tested stochastically using the SEIR model based on previously reported Gamma distributions. We estimated the duration time until 10 beds in negative pressure rooms in Chiyoda-ku, one of the 23 wards in Tokyo, were fully occupied with SARS-infected patients. We determined the impact of an increasing number of days on the number of prevalent cases until the index case was isolated. The prevalent cases increase exponentially along with the increase of the non-isolation period of the index case, and all the beds were fully occupied if the index case was not isolated until more than 6 days. However even 2 days non-isolation period of the index case could fill up all the beds when 16% of secondary infections are transmitted outside the hospital. There is a possibility that an epidemic will occur with the isolation of the index case even at early days if the infection is transmitted outside the hospital. The simulation results revealed that it was important to recognize and isolate SARS patients as early as possible and also to prevent the transmission spreading outside the hospital to control an epidemic. C1 Okayama Univ, Grad Sch Environm Sci, Dept Human Ecol, Okayama 7008530, Japan. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008558, Japan. Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Kyoto 6068507, Japan. NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Dept Mental Hlth, Bunkyo Ku, Tokyo 1130033, Japan. RP Ishikawa, H (reprint author), Okayama Univ, Grad Sch Environm Sci, Dept Human Ecol, 3-1-1 Tsushima Naka, Okayama 7008530, Japan. EM ishikawa@ems.okayama-u.ac.jp RI ISHIKAWA, Hirofumi/B-1845-2011 NR 21 TC 4 Z9 4 U1 1 U2 3 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2007 VL 51 IS 9 BP 823 EP 832 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA 210SY UT WOS:000249477100005 PM 17895599 ER PT S AU Shiva, S Brookes, PS Darley-Usmar, VM AF Shiva, Sruti Brookes, Paul S. Darley-Usmar, Victor M. BE Pon, LA Schon, EA TI Methods for measuring the regulation of respiration by nitric oxide SO MITOCHONDRIA, 2ND EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID CYTOCHROME-C-OXIDASE; MITOCHONDRIAL RESPIRATION; ISCHEMIA-REPERFUSION; CARDIAC-HYPERTROPHY; INHIBITION; NO; OXYGEN; SENSITIVITY; CONSUMPTION; REDUCTION C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Shiva, S (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Darley-Usmar, Victor/F-7656-2010 FU NHLBI NIH HHS [HL 070610, HL 071158]; NIAAA NIH HHS [AA 13395] NR 32 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-544173-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2007 VL 80 BP 395 EP 416 DI 10.1016/S0091-679X(06)80020-8 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BGB65 UT WOS:000245920700020 PM 17445706 ER PT J AU Johnson, JE Gonzales, RA Olson, SJ Wright, PF Graham, BS AF Johnson, Joyce E. Gonzales, Ricardo A. Olson, Sandy J. Wright, Peter F. Graham, Barney S. TI The histopathology of fatal untreated human respiratory syncytial virus infection SO MODERN PATHOLOGY LA English DT Article DE bronchiolitis; pathogenesis; asthma; immune response ID T-LYMPHOCYTE SUBSETS; EPITHELIAL-CELLS; BRONCHIOLITIS; INFANTS; CHEMOKINES; CHILDHOOD; CHILDREN; DEATHS; CALVES; TRACT AB The pathology of respiratory syncytial virus (RSV) infection was evaluated 1 day after an outpatient diagnosis of RSV in a child who died in a motor vehicle accident. We then identified 11 children with bronchiolitis from the Vanderbilt University autopsy log between 1925 and 1959 who met criteria for possible RSV infection in the preintensivist era. Their tissue was re-embedded and evaluated by routine hematoxylin and eosin and PAS staining and immunostaining with RSV-specific antibodies. Tissue from three cases was immunostain-positive for RSV antigen and was examined in detail. Small bronchiole epithelium was circumferentially infected, but basal cells were spared. Both type 1 and 2 alveolar pneumocytes were also infected. Although, not possible for archival cases, tissue from the index case was evaluated by immunostaining with antibodies to define the cellular components of the inflammatory response. Inflammatory infiltrates were centered on bronchial and pulmonary arterioles and consisted of primarily CD69+ monocytes, CD3+ double-negative T cells, CD8+ T cells, and neutrophils. The neutrophil distribution was predominantly between arterioles and airways, while the mononuclear cell distribution was in both airways and lung parenchyma. Most inflammatory cells were concentrated submuscular to the airway, but many cells traversed the smooth muscle into the airway epithelium and lumen. Airway obstruction was a prominent feature in all cases attributed to epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema, and compounded by compression from hyperplastic lymphoid follicles. These findings inform our understanding of RSV pathogenesis and may facilitate the development of new approaches for prevention and treatment. C1 NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. RP Graham, BS (reprint author), NIAID, NIH, Vaccine Res Ctr, Bldg 40,Room 2502,40 Convent Dr,MSC-3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU NIAID NIH HHS [R01 AI-33933] NR 29 TC 174 Z9 177 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2007 VL 20 IS 1 BP 108 EP 119 DI 10.1038/modpathol.3800725 PG 12 WC Pathology SC Pathology GA 119IC UT WOS:000243005000014 PM 17143259 ER PT J AU Hu, CAA Donald, SP Yu, J Lin, WW Liu, ZH Steel, G Obie, C Valle, D Phang, JM AF Hu, Chien-an A. Donald, Steven P. Yu, Jian Lin, Wei-Wen Liu, Zhihe Steel, Gary Obie, Cassandra Valle, David Phang, James M. TI Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE proline oxidase; apoptosis; reactive oxygen species; mitochondria; p53; proline-P5C cycle ID COLORECTAL-CANCER CELLS; CYTOCHROME-C RELEASE; TUMOR-SUPPRESSOR P53; REACTIVE OXYGEN; P53-INDUCED GENE-6; BAX GENE; EXPRESSION; HYPERPROLINEMIA; DEFICIENCY; GENERATION AB Proline oxidase (POX), a mitochondrial inner-membrane protein, catalyzes the rate-limiting oxidation of proline to pyrroline-5-carboxylate (P5C). Previously we showed that overexpression of POX is associated with generation of reactive oxygen species (ROS) and apoptosis in POX-inducible colorectal cancer cells, DLD-1.POX. We also showed expression of mitochondrial MnSOD partially blunts POX-induced ROS generation and apoptosis. To further investigate the molecular basis of POX-induced apoptosis, we utilized the DLD-1.POX cells to show that cells overproducing POX exhibit an L-proline-dependent apoptotic response. The apoptotic effect is specific for L-proline, detectable at 0.2 mM, maximal at 1 mM, and occurs during 48-72 h following the addition of L-proline to cells with maximally induced POX. The apoptotic response is mitochondria-mediated with release of cytochrome c, activation of caspase-9, chromatin condensation/DNA fragmentation, and cell shrinkage. We conclude that in the presence of proline, high POX activity is sufficient to induce mitochondria-mediated apoptosis. C1 Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Tri Serv Gen Hosp, Dept Psychiat, Taipei, Taiwan. Natl Def Med Inst, Taipei, Taiwan. Johns Hopkins Univ, Howard Hughes Med Inst, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21218 USA. RP Valle, D (reprint author), NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, 1050 Boyles St,Bldg 538,Room 115, Frederick, MD 20895 USA. EM dvalle@jhmi.edu; phang@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [1 R01 CA106644-01, R01 CA106644]; NCRR NIH HHS [P20 RR016480] NR 36 TC 44 Z9 44 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2007 VL 295 IS 1-2 BP 85 EP 92 DI 10.1007/s11010-006-9276-6 PG 8 WC Cell Biology SC Cell Biology GA 128LQ UT WOS:000243659600011 PM 16874462 ER PT J AU Minners, J Lacerda, L Yellon, DM Opie, LH McLeod, CJ Sack, MN AF Minners, Jan Lacerda, Lydia Yellon, Derek M. Opie, Lionel H. McLeod, Christopher J. Sack, Michael N. TI Diazoxide-induced respiratory inhibition - a putative mitochondrial K-ATP channel independent mechanism of pharmacological preconditioning SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE diazoxide; 5-hydroxydecanoate; respiratory inhibition; reactive oxygen species; C2C12 cells; anoxia-reoxygenation ID SENSITIVE POTASSIUM CHANNELS; OXYGEN SPECIES GENERATION; REACTIVE OXYGEN; NITRIC-OXIDE; RAT-HEART; INDUCED CARDIOPROTECTION; UNCOUPLING PROTEIN-2; SIMULATED ISCHEMIA; HYDROGEN-PEROXIDE; OXIDATION AB The ischemic preconditioning biological phenomenon has been explored to identify putative pharmacologic agents to mimic this cytoprotective program against cellular ischemic injury. Diazoxide administration confers this cytoprotection, however, whether this is via direct activation of the putative mitochondrial K-ATP (mK(ATP)) channel which was originally proposed has been questioned. Here, we present data supporting an alternate hypothesis evoking mitochondrial respiratory inhibition rather than mK(ATP) channel activation, as a mediating event in the diazoxide-activated cytoprotective program. Mitochondrial respiration and reactive oxygen species (ROS) production was measured in digitonin-permeabilized C2C12 myotubes, allowing for the modulation of mK(ATP) conductance by changing the potassium concentration of the medium (0-130 mM). Diazoxide dose-dependently attenuated succinate-supported respiration, an effect that was independent of mK(ATP) channel conductance. Similarly, 5-hydroxydecanoate (5-HD), a putative mK(ATP) channel blocker, released diazoxide-induced respiratory inhibition independently of potassium concentration. Since diazoxide-induced cytoprotection and respiratory inhibition are both integrally linked to ROS generation we repeated above experiments following ROS generation using DCF fluorescence. Cytoprotective doses of diazoxide increased ROS generation independently of potassium concentration and 5-HD inhibited ROS production under the same conditions. Collectively these data support the hypothesis that diazoxide-mediated cytoprotection is independent of the conductance of the mK(ATP) channel and rather implicate mitochondrial respiratory inhibition-triggered ROS signaling. C1 Univ Coll Hosp & Med Sch, Hatter Inst Cardiovasc Studies, London, England. Univ Cape Town, Sch Med, Hatter Inst Cardiol Res, MRC Interuniv Cape Heart Grp, ZA-7925 Cape Town, South Africa. RP Sack, MN (reprint author), NHLBI, NIH, Bldg 10 CRC,5-3150, Bethesda, MD 20892 USA. EM SackM@nih.gov FU Wellcome Trust NR 52 TC 37 Z9 37 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2007 VL 294 IS 1-2 BP 11 EP 18 DI 10.1007/s11010-005-9066-6 PG 8 WC Cell Biology SC Cell Biology GA 127YE UT WOS:000243621500002 PM 17136444 ER PT J AU LaRonde-LeBlanc, N Santhanam, AN Baker, AR Wlodawer, A Colburn, NH AF LaRonde-LeBlanc, Nicole Santhanam, Arti N. Baker, Alyson R. Wlodawer, Alexander Colburn, Nancy H. TI Structural basis for inhibition of translation by the tumor suppressor Pdcd4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION-FACTOR 4G; MESSENGER-RNA DECAY; TRANSFORMATION SUPPRESSOR; VHS DOMAIN; BINDING; PROTEIN; EIF4A; TUMORIGENESIS; EXPRESSION; CARCINOMA AB The tumor suppressor function of Programmed Cell Death 4 (Pdcd4) is achieved through interactions between Pdcd4 and components of the translation initiation complex, namely, the RNA helicase eIF4A and the scaffolding protein eIF4G. These interactions are mediated through two MA3 domains on the Pdcd4 molecule and result in inhibition of protein synthesis. We have solved the high-resolution crystal structure of the C-terminal MA3 (cMA3) domain of Pdcd4 in several crystal forms and demonstrated its similarity to the MA3 domain of eIF4G. As predicted by the structure, the cMA3 domain competes with eIF4Gc for binding to eIF4A and surprisingly is sufficient to inhibit translation initiation. Mutations that abolish eIF4A binding negate both functions of the cMA3. Interestingly mutations in the Akt phosphorylation site influenced neither cMA3 binding to eIF4A nor its ability to inhibit translation initiation. Finally, our structural analysis reveals MA3 domains to be a novel subfamily of VHS domains. C1 NCI, Macromol Crystallog Lab, CCR, Frederick, MD 21702 USA. NCI, Lab Canc Prevent, Canc Res Ctr, Frederick, MD 21702 USA. RP LaRonde-LeBlanc, N (reprint author), NCI, Macromol Crystallog Lab, CCR, Frederick, MD 21702 USA. EM nlaronde@unnd.edu RI LaRonde-LeBlanc, Nicole/C-3399-2009 OI LaRonde-LeBlanc, Nicole/0000-0002-2778-8358 FU Intramural NIH HHS NR 33 TC 54 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2007 VL 27 IS 1 BP 147 EP 156 DI 10.1128/MCB.00867-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121CX UT WOS:000243136800012 PM 17060447 ER PT J AU Swamynathan, SK Katz, JP Kaestner, KH Ashery-Padan, R Crawford, MA Piatigorsky, J AF Swamynathan, Shivalingappa K. Katz, Jonathan P. Kaestner, Klaus H. Ashery-Padan, Ruth Crawford, Mary A. Piatigorsky, Joram TI Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KRUPPEL-LIKE FACTOR; METALLOPROTEINASE GELATINASE B; OCULAR SURFACE; TRANSCRIPTION FACTOR; KERATOCONJUNCTIVITIS SICCA; EXPRESSION; MICE; DIFFERENTIATION; EYE; AP-2-ALPHA AB The Kruppel-like transcription factor KLF4 is among the most highly expressed transcription factors in the mouse cornea (B. Norman, J. Davis, and J. Piatigorsky, Investig. Ophthalmol. Vis. Sci. 45:429-440,2004). Here, we deleted the Klf4 gene selectively in the surface ectoderm-derived structures of the eye (cornea, conjunctiva, eyelids, and lens) by mating Klf4-LoxP mice (J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky, V. W. Yang, and K. H. Kaestner, Development 129:2619-2628, 2002) with Le-Cre mice (R. Ashery-Padan, T. Marquardt, X. Zhou, and P. Gross, Genes Dev. 14:2701-2711, 2000). Klf4 conditional null (Klf4CN) embryos developed normally, and the adult mice were viable and fertile. Unlike the wild type, the Klf4CN cornea consisted of three to four epithelial cell layers; swollen, vacuolated basal epithelial and endothelial cells; and edematous stroma. The conjunctiva lacked goblet cells, and the anterior cortical lens was vacuolated in Klf4CN mice. Excessive cell sloughing resulted in fewer epithelial cell layers in spite of increased cell proliferation at the Klf4CN ocular surface. Expression of the keratin-12 and aquaporin-5 genes was downregulated, consistent with the Klf4CN corneal epithelial fragility and stromal edema, respectively. These observations provide new insights into the role of KLF4 in postnatal maturation and maintenance of the ocular surface and suggest that the Klf4CN mouse is a useful model for investigating ocular surface pathologies such as dry eye, Meesmann's dystrophy, and Steven's-Johnson syndrome. C1 NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Tel Aviv Univ, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Swamynathan, SK (reprint author), NEI, Lab Mol & Dev Biol, NIH, 7 Mem Dr,Room 129, Bethesda, MD 20892 USA. EM Swamynathans@nei.nih.gov OI Swamynathan, Shivalingappa/0000-0002-9158-1511 FU NEI NIH HHS [K22 EY 016875-01, K22 EY016875] NR 74 TC 75 Z9 80 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2007 VL 27 IS 1 BP 182 EP 194 DI 10.1128/MCB.00846-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121CX UT WOS:000243136800015 PM 17060454 ER PT J AU Xu, WP Yuan, XT Beebe, K Xiang, ZX Neckers, L AF Xu, Wanping Yuan, Xitong Beebe, Kristin Xiang, Zhexin Neckers, Len TI Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER CELLS; TYROSINE KINASE; C-SRC; FAMILY KINASES; CHAPERONE COMPLEX; PROTEIN-KINASES; IN-VIVO; PHOSPHORYLATION; ACTIVATION AB The receptor tyrosine kinase ErbB2 plays a crucial role in tumorigenesis. We showed previously that the molecular chaperone Hsp90 protects ErbB2 from proteasome-mediated degradation by binding to a short loop structure in the N-lobe of the kinase domain. Here we show that loss of Hsp90 binding correlates with enhanced ErbB2 kinase activity and its transactivating potential, concomitant with constitutively increased phosphorylation of Tyr877, located in the activation loop of the kinase domain. We show further that Tyr877 phosphorylation is mediated by Src and that it is necessary for the enhanced kinase activity of ErbB2. Finally, computer modeling of the kinase domain suggests a phosphorylation-dependent reorientation of the activation loop, denoting the importance of Tyr877 phosphorylation for ErbB2 activity. These findings suggest that Hsp90 binding to ErbB2 participates in regulation of kinase activity as well as kinase stability. C1 NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Mol Modeling, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 1-5940, Bethesda, MD 20892 USA. EM neckers@nih.gov NR 40 TC 41 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2007 VL 27 IS 1 BP 220 EP 228 DI 10.1128/MCB.00899-06 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121CX UT WOS:000243136800018 PM 17030621 ER PT J AU Ge, WW Volkening, K Leystra-Lantz, C Jaffe, H Strong, MJ AF Ge, Wei-wen Volkening, Kathryn Leystra-Lantz, Cheryl Jaffe, Howard Strong, Michael J. TI 14-3-3 protein binds to the low molecular weight neurofilament (NFL) mRNA 3 ' UTR SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE neurofilament; RNA stability; motor neuron disease; ALS ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; 3'-UNTRANSLATED REGION; DESTABILIZING ELEMENT; SELECTIVE LOSS; HEAVY GENE; STABILITY; EXPRESSION; SUBUNIT; KINASE AB We have previously reported that altered stability of low molecular weight neurofilament (NFL) mRNA in lumbar spinal cord homogenates in amyotrophic lateral sclerosis (ALS) is associated with altered expression of trans-acting 3' UTR mRNA binding proteins. We have identified two hexanucleotide motifs as the main cis elements and, using LC/MS/MS of peptide digests of NFL 3' UTR interacting proteins from human spinal cord, observed that 14-3-3 proteins interact with these motifs. 14-3-3 beta, xi, tau, gamma, and eta isoforms were found to be expressed in human spinal cord. Each isoform was expressed in vitro and shown to interact with NFL 3' UTR mRNA. Mutation of one or both motifs resulted in decreased 14-3-3 interaction, changes in predicted mRNA structure or alteration in stability of the mRNA. These data show a novel interaction for 14-3-3 with NFL mRNA, and suggests that 14-3-3 may play a role in regulating NFL mRNA stability. (c) 2006 Elsevier Inc. All rights reserved. C1 John P Robarts Res Inst, Cell Biol Res Grp, London, ON N6A 5K8, Canada. Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 5A5, Canada. NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Strong, MJ (reprint author), London Hlth Sci Ctr, Univ Campus,Room C7120,339 Windermere Rd, London, ON N6A 5A5, Canada. EM mstrong@uwo.ca RI Strong, Michael/H-9689-2012 NR 47 TC 25 Z9 25 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 JAN PY 2007 VL 34 IS 1 BP 80 EP 87 DI 10.1016/j.mcn.2006.10.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 127PG UT WOS:000243598200009 PM 17098443 ER PT J AU McNeill, DR Wilson, DM AF McNeill, Daniel R. Wilson, David M., III TI A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents SO MOLECULAR CANCER RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; HUMAN APURINIC ENDONUCLEASE; POLY(ADP-RIBOSE) POLYMERASE; ALKYLATING-AGENTS; OXIDATIVE STRESS; SITE ANALOGS; CANCER CELLS; APE1; PROTEIN AB Apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is the primary enzyme in mammals for the repair of abasic sites in DNA, as well as a variety of 3' damages that arise upon oxidation or as products of enzymatic processing. If left unrepaired, APE1 substrates can promote mutagenic and cytotoxic outcomes. We describe herein a dominant-negative form of APE1 that lacks detectable nuclease activity and binds substrate DNA with a 13-fold higher affinity than the wild-type protein. This mutant form of APE1, termed ED, possesses two amino acid substitutions at active site residues Glu(96) (changed to Gin) and Asp(210) (changed to Asn). In vitro biochemical assays reveal that ED impedes wild-type APE1 AP site incision function, presumably by binding AP-DNA and blocking normal lesion processing. Moreover, tetracycline-regulated (tet-on) expression of ED in Chinese hamster ovary cells enhances the cytotoxic effects of the laboratory DNA-damaging agents, methyl methanesulfonate (MMS; 5.4-fold) and hydrogen peroxide (1.5-fold). This MMS-induced, ED-dependent cell killing coincides with a hyperaccumulation of AP sites, implying that excessive DNA damage is the cause of cell death. Because an objective of the study was to identify a protein reagent that could be used in targeted gene therapy protocols, the effects of ED on cellular sensitivity to a number of chemotherapeutic compounds was tested. We show herein that ED expression sensitizes Chinese hamster ovary cells to the killing effects of the alkylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea (also known as carmustine) and the chain terminating nucleoside analogue dideoxycytidine (also known as zalcitabine), but not to the radiornimetic bleomycin, the nucleoside analogue beta-D-arabinofuranosylcytosine (also known as cytarabine), the topoisomerase inhibitors camptothecin and etoposide, or the cross-linking agents mitomycin C and cisplatin. Transient expression of ED in the human cancer cell line NCI-H1299 enhanced cellular sensitivity to MMS, 1,3-bis(2-chloroethyl)-1-nitrosourea, and dideoxycytidine, demonstrating the potential usefulness of this strategy in the treatment of human tumors. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU Intramural NIH HHS NR 56 TC 58 Z9 59 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2007 VL 5 IS 1 BP 61 EP 70 DI 10.1158/1541-7786.MCR-06-0329 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 131CO UT WOS:000243845800006 PM 17259346 ER PT J AU Ozpolat, B Akar, U Steiner, M Zorrilia-Calancha, I Tirado-Gomez, M Colburn, N Danilenko, M Kornblau, S Berestein, GL AF Ozpolat, Bulent Akar, Ugur Steiner, Michael Zorrilia-Calancha, Isabel Tirado-Gomez, Maribel Colburn, Nancy Danilenko, Michael Kornblau, Steven Berestein, Gabriel Lopez TI Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation human myeloid leukemia cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; INITIATION-FACTOR 4A; P70 S6 KINASE; TRANSLATION INITIATION; MESSENGER-RNA; RAR-ALPHA; NB4 CELLS; TISSUE TRANSGLUTAMINASE; PROGNOSTIC-FACTOR; GENE-EXPRESSION AB Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA)-induced granulocytic differentiation in NB4 and HL60 AML cell lines and in primary human promyelocytic leukemia (AML-M3) and CD34(+) hematopoietic progenitor cells but not in differentiation-resistant NB4.R1 and HL60R cells. Induction of PDCD4 expression was associated with nuclear translocation of PDCD4 in NB4 cells undergoing granulocytic differentiation but not in NB4.R1 cells. Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells. In contrast, PDCD4 was not up-regulated during monocytic/macrophagic differentiation induced by 1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyi-phorbol-13-acetate in NB4 cells or by ATRA in THP1 myelomonoblastic cells. Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27(KiP1) and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21(waf1/Cip1), and tissue transglutarninase (TG2). Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. In conclusion, our data suggest that PDCD4 expression contributes to ATRA-induced granulocytic but not monocytic/macrophagic differentiation. The PI3K/Akt/mTOR pathway constitutively represses PDCD4 expression in AML, and ATRA induces PDCD4 through inhibition of this pathway. C1 Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 422, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, IL-84105 Beer Sheva, Israel. NCI, Ctr Canc Res, Gene Regulat Sect, Frederick, MD 21701 USA. RP Berestein, GL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Unit 422, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM glopez@mdanderson.org RI Kornblau, Steven/A-9366-2009; DANILENKO, MICHAEL/F-2283-2012 FU NCI NIH HHS [U54 RFA CA096300] NR 71 TC 62 Z9 67 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2007 VL 5 IS 1 BP 95 EP 108 DI 10.1158/1541-7786.MCR-06-0125 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 131CO UT WOS:000243845800009 PM 17259349 ER PT J AU Sauna, ZE Ambudkar, SV AF Sauna, Zuben E. Ambudkar, Suresh V. TI About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID OCCLUDED NUCLEOTIDE CONFORMATION; REPAIR PROTEIN MUTS; MULTIDRUG-RESISTANCE; TRANSITION-STATE; DRUG-BINDING; CATALYTIC CYCLE; TRANSPORTER SUPERFAMILY; CASSETTE TRANSPORTERS; GLUTAMATE RESIDUES; STRUCTURAL BIOLOGY AB The efflux of drugs by the multidrug transporter P-glycoprotein (Pgp; ABCB1) is one of the principal means by which cancer cells evade chemotherapy and exhibit multidrug resistance. Mechanistic studies of Pgp-mediated transport, however, transcend the importance of this protein per se as they help us understand the transport pathway of the ATP-binding cassette proteins in general. The ATP-binding cassette proteins comprise one of the largest protein families, are central to cellular physiology, and constitute important drug targets. The functional unit of Pgp consists of two nucleotide-binding domains (NBD) and two transmembrane domains that are involved in the transport of drug substrates. Early studies postulated that conformational changes as a result of ATP hydrolysis were transmitted to the transmembrane domains bringing about drug transport. More recent structural and biochemical studies on the other hand suggested that ATP binds at the interface of the two NBDs and induces the formation of a closed dinner, and it has been hypothesized that this dimerization and subsequent ATP hydrolysis powers transport. Based an the mutational and biochemical work on Pgp and structural studies with isolated NBDs, we review proposed schemes for the catalytic cycle of ATP hydrolysis and the transport pathway. C1 NCI, Cell Biol Lab, Ctr Canc Res,Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res,Dept Hlth & Human Serv, NIH, Bldg 37,Room 2120,37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU Intramural NIH HHS NR 80 TC 79 Z9 83 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 13 EP 23 DI 10.1158/1535-7163.MCT-06-0155 PG 11 WC Oncology SC Oncology GA 129WC UT WOS:000243759800002 PM 17237262 ER PT J AU Duan, JM Friedman, J Nottingham, L Chen, Z Ara, G Van Waes, C AF Duan, Jianming Friedman, Jay Nottingham, Liesi Chen, Zhong Ara, Gulshan Van Waes, Carter TI Nuclear factor-kappa B p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; MULTIPLE-MYELOMA; LUNG-CANCER; CYCLIN D1; IN-VITRO; RADIATION SENSITIVITY; POTENTIATES APOPTOSIS; SODIUM-BUTYRATE; DOWN-REGULATION; PHASE-II AB Histone deacetylase inhibitors (HDI) can inhibit proliferation and enhance apoptosis in a wide range of malignancies. However, HDIs show relatively modest activity in head and neck squamous cell carcinomas (HNSCC), in which we have shown the activation of nuclear factor-KB (NF-KB; NF-KB1/RelA or p50/p65), a transcription factor that promotes expression of proliferative and antiapoptotic genes. In this study, we examined if HDIs enhance activation of NF-KB and target genes and if genetic or pharmacologic inhibition of NF-KB can sensitize HNSCC to HDIs. Limited activity of classic HDIs trichostatin A and sodium butyrate was associated with enhanced activation of NF-KB reporter activity in a panel of six HNSCC cell lines. HDIs enhanced NF-KB p50/p65 DNA binding and acetylation of the ReIA p65 subunit. Transfection of small interfering RNAs targeting p65 strongly inhibited NF-KB expression and activation, induced cell cycle arrest and cell death, and further sensitized HNSCC cells when combined with HDIs. The p65 small interfering RNA inhibited HDI-enhanced expression of several NF-KB-inducible genes implicated in oncogenesis of HNSCC, such as p21, cyclin D1, and BCL-XL. Bortezomib, an inhibitor of proteasome-dependent NF-KB activation, also increased sensitization to trichostatin A, sodium butyrate, and a novel HDI, PXD101, in vitro, and to the antitumor effects of PXD101 in bortezomib-resistant UMSCC-11A xeno-grafts. However, gastrointestinal toxicity, weight loss, and mortality of the combination were dose limiting and required parenteral fluid administration. We conclude that HDI-enhanced NF-KB activation is one of the major mechanisms of resistance of HNSCC to HDIs. The combination of HDI and proteasome inhibitor produced increased antitumor activity. Low starting dosages for clinical studies combining HDIs with proteasome inhibitors and IV fluid support may be warranted. C1 NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. CuraGen Corp, Branford, CT USA. RP Van Waes, C (reprint author), NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS NR 59 TC 63 Z9 67 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 37 EP 50 DI 10.1158/1535-7163.MCT-05-0285 PG 14 WC Oncology SC Oncology GA 129WC UT WOS:000243759800005 PM 17237265 ER PT J AU Yates, MS Tauchi, M Katsuoka, F Flanders, KC Liby, KT Honda, T Gribble, GW Johnson, DA Johnson, JA Burton, NC Guilarte, TR Yamamoto, M Sporn, MB Kensler, TW AF Yates, Melinda S. Tauchi, Masafumi Katsuoka, Fumiki Flanders, Kathleen C. Liby, Karen T. Honda, Tadashi Gribble, Gordon W. Johnson, Delinda A. Johnson, Jeffrey A. Burton, Neal C. Guilarte, Tomas R. Yamamoto, Masayuki Sporn, Michael B. Kensler, Thomas W. TI Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NITRIC-OXIDE PRODUCTION; TRANSCRIPTION FACTOR NRF2; ANTIOXIDANT RESPONSE ELEMENT; HIGHLY-ACTIVE INHIBITORS; MOUSE MACROPHAGES; SYNTHETIC OLEANANE; IN-VIVO; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; NAD(P)H-QUINONE OXIDOREDUCTASE-1; QUINONE OXIDOREDUCTASE-1 AB Synthetic triterpenoids have been developed, which are potent inducers of cytoprotective enzymes and inhibitors of inflammation, greatly improving on the weak activity of naturally occurring triterpenoids. An imidazolide triterpenoid derivative, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im or TP235), has been previously shown to potently protect against hepatic tumorigenesis, acting in part by inducing cytoprotective genes through Keap1-Nrf2-antioxidant response element (ARE) signaling. In these studies, the pharmacodynamic activity of CDDO-Im is characterized in two distinct lines of ARE reporter mice and by measuring increases in Nqo1 transcript levels as a marker of cytoprotective gene induction. Oral administration of CDDO-Im induces ARE-regulated cytoprotective genes in many tissues in the mouse, including liver, lung, kidney, intestines, brain, heart, thymus, and salivary gland. CDDO-Im induces Nqo1 RNA transcripts in some organs at doses as low as 0.3 mu moI/kg body weight (orally). A structure activity evaluation of 15 additional triterpenoids (a) confirmed the importance of Michael acceptor groups on both the A and C rings, (b) showed the requirement for a nitrile group at C-2 of the A ring, and (c) indicated that substituents at C-17 dramatically affected pharmacodynamic action in vivo. In addition to CDDO-Im, other triterpenoids, particularly the methyl ester CDDO-Me (TP155) and the dinitrile TP225, are extremely potent inducers of cytoprotective genes in mouse liver, lung, small intestine mucosa, and cerebral cortex. This pharmacodynamic characterization highlights the chemopreventive promise of several synthetic triterpenoids in multiple target organs. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Univ Tsukuba, ERATO Environm Response Project, Tsukuba, Ibaraki 305, Japan. Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 305, Japan. NCI, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Dartmouth Coll, Hanover, NH 03755 USA. Univ Wisconsin, Madison, WI USA. RP Kensler, TW (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Room E7541,615 N Wolfe St, Baltimore, MD 21205 USA. EM tkensier@jhsph.edu RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [CA78814, CA94076]; NIGMS NIH HHS [T32 GM08763] NR 50 TC 159 Z9 159 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2007 VL 6 IS 1 BP 154 EP 162 DI 10.1158/1535-7163.MCT-06-0516 PG 9 WC Oncology SC Oncology GA 129WC UT WOS:000243759800017 PM 17237276 ER PT J AU Mai, V Colbert, LH Perkins, SN Schatzkin, A Hursting, SD AF Mai, Volker Colbert, Lisa H. Perkins, Susan N. Schatzkin, Arthur Hursting, Stephen D. TI Intestinal microbiota: A potential diet-responsive prevention target in Apc(Min) mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE cancer; colorectal; microflora; nutrition ID 16S RIBOSOMAL-RNA; MOLECULAR ECOLOGICAL ANALYSIS; IN-SITU HYBRIDIZATION; LACTIC-ACID BACTERIA; HUMAN FECES; MIN MOUSE; OLIGONUCLEOTIDE PROBES; FECAL SAMPLES; MICROFLORA; CANCER AB We previously reported that two dietary regimens, calorie restriction (CR) and a high olive oil-containing diet supplemented with a freeze-dried fruit and vegetable extract (OFV), reduced the development of intestinal adenomas in Apc(Min) mice by 57% and 33%, respectively, compared to control mice fed a defined diet ad libitum. The OFV diet was designed to have a strong effect on the composition of the intestinal microbiota through its high content of fiber, which represents a major source of fermentable substrate for the gut bacteria. We hypothesized that some of the observed effects of diet on intestinal carcinogenesis might be mediated by diet-related changes in the bacterial species that thrive in the gut. Therefore, we determined by fluorescent in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) how the dietary interventions affected the composition of the intestinal microbiota, and we characterized specific microbiota changes that were associated with diet and reduced intestinal carcinogenesis. The OFV diet changed the overall composition of the intestinal microbiota, smaller changes were observed for the CR diet. Furthermore, we detected a 16S rDNA fragment associated with mice that did not develop polyps. Sequence analysis suggested that hitherto unidentified bacteria belonging to the family Lachnospiraceae (order Clostridiales) were its source. Thus, these bacteria may be an indicator of intestinal conditions associated with reduced intestinal carcinogenesis in Apc(Min) mice. (c) 2006 Wiley-Liss, Inc. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. Univ Texas, Div Nutr Sci, Austin, TX 78712 USA. RP Mai, V (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 10 S Pine St,MSTF 934-B, Baltimore, MD 21201 USA. FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 35 TC 32 Z9 32 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2007 VL 46 IS 1 BP 42 EP 48 DI 10.1002/mc.20233 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 122VA UT WOS:000243254000005 PM 16929480 ER PT J AU Manna, FA Lorman, VL Podgornik, R Zeks, B AF Manna, F. A. Lorman, V. L. Podgornik, R. Zeks, B. TI Polarity and chirality in NCP mesophases and chromatin fibers SO MOLECULAR CRYSTALS AND LIQUID CRYSTALS LA English DT Article; Proceedings Paper CT 21st International Liquid Crystal Conference CY JUL 02-07, 2006 CL Keystone, CO DE chirality; chromatin fiber; condensed mesophases; NCP; polarity ID NUCLEOSOME CORE PARTICLES; X-RAY-DIFFRACTION; HISTONE ACETYLATION; DYNAMICS AB We propose a unified mechanism of phase transitions in the high density solutions of Nucleosomal Core Particles. We demonstrate its relation with the high shape and charge anisotropy of the NCP due to the DNA wrapping around the histone protein core. Hexagonal-to-lantellar transition in the solution of NCP columnar aggregates is shown to be driven by the condensation of the periodic antiparallel polar vector field. The transition results in the polar dyadic axes correlations. Fine structure of the NCP organization is also explained, namely the correlated tilting of NCP with respect to the column axis. C1 [Manna, F. A.; Lorman, V. L.] Univ Montpellier 2, CNRS, UMR 5207, Lab Phys Math & Theor,LPTA, F-34095 Montpellier 5, France. [Podgornik, R.] Univ Ljubljana, Fac Math & Phys, Dept Phys, Ljubljana, Slovenia. [Podgornik, R.] Jozef Stefan Inst, Dept Theoret Phys, Ljubljana, Slovenia. [Podgornik, R.] NICHHD, LPSB, NIH, Bethesda, MD USA. [Zeks, B.] Univ Ljubljana, Fac Med, Inst Biophys, Ljubljana 61000, Slovenia. RP Lorman, VL (reprint author), Univ Montpellier 2, CNRS, UMR 5207, Lab Phys Math & Theor,LPTA, Pl E Bataillon, F-34095 Montpellier 5, France. EM vladimir.lorman@lpta.univ-montp2.fr RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 28 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1542-1406 J9 MOL CRYST LIQ CRYST JI Mol. Cryst. Liquid Cryst. PY 2007 VL 478 BP 839 EP + DI 10.1080/15421400701686918 PG 21 WC Crystallography SC Crystallography GA 247PD UT WOS:000252090900008 ER PT J AU White, MY Van Eyk, JE AF White, Melanie Y. Van Eyk, Jennifer E. TI Cardiovascular proteomics - Past, present, and future SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; HEAT-SHOCK PROTEINS; TROPONIN-I PROTEOLYSIS; ALPHA-B-CRYSTALLIN; BOVINE DILATED CARDIOMYOPATHY; STUNNED PORCINE MYOCARDIUM; HIGH-DENSITY-LIPOPROTEIN; TRANSGENIC MOUSE MODEL; SMOOTH-MUSCLE PROTEINS; FAILING HUMAN HEART AB With cardiovascular (CV)-related disorders accounting for the highest mortality rates in the world, affecting the quantity and quality of life of patients and creating an economic burden of prolonged therapeutic intervention, there is great significance in understanding the cellular and molecular alterations that influence the progression of these pathologies. The cellular genotype is regulated by the DNA component, whilst the cellular phenotype is influenced by the protein complement. By improving the understanding of the molecular mechanisms that influence the protein profile, the pathologies that influence the intrinsic functions of the CV system may be detected earlier or managed more efficiently. This is achievable with technologies encompassed by 'proteomics.' Proteomic investigations of CV diseases, including dilated cardiomyopathy (DCM), atherosclerosis, and ischemia/reperfusion (I/R) injury, have identified candidate proteins altered with the pathologic states, complementing past biochemical and physiologic observations. Whilst proteomics is still a relatively new discipline to be applied to the basic scientific investigation of CV diseases, it is emerging as a technique to screen for potential biomarkers in both tissues/cells and biologic fluids (biofluids), as well as to identify the targets of existing therapeutics. By enabling the separation of complex mixtures over numerous dimensions, exploiting the intrinsic properties of proteins, including charge state, molecular mass, and hydrophobicity, in addition to cellular location, the discrete alterations within the cell may be resolved. Proteomics has shown alterations to myofilament proteins including troponin I and myosin light chain, correlating with the reduction in contractility in the myocardium from DCM and I/R. The diverse cell types that coalesce to induce atherosclerotic plaque formation have been investigated both collectively and individually to elucidate the influence of the modifications to single cell types on the developing plaque as a whole. Proteomics has also been used to observe changes to biofluids occurring with these pathologies, a new potential link between basic science and clinical applications. The development of CV proteomics has helped to identify a number of possible protein candidates, and offers the potential to treat and diagnose CV disease more effectively in the future. C1 Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21224 USA. Johns Hopkins Univ, Tech Implementat & Coordinat Core, NHLBI, Proteom Ctr, Baltimore, MD USA. RP Van Eyk, JE (reprint author), Johns Hopkins Univ, Dept Med, 602 Mason F Lord Bldg,Ctr Tower,5200 Eastern Ave, Baltimore, MD 21224 USA. EM jvaneyk1@jhmi.edu FU NHLBI NIH HHS [P01 HL081427-040003, P50 HL084946, P50 HL084946-039003, P01 HL077180-040001, P01 HL077180-030001, P50 HL084946-019003, N01 HV028180, P50 HL084946-029003, P01 HL077180-020001, P01 HL081427-050003, P01 HL077180-010001, P01 HL081427-020003, P01 HL081427-030003, P01HL081427, P01 HL077180, P01 HL081427-010003, P01 HL081427, P01 HL077180-050001]; PHS HHS [N0 NV 28180] NR 136 TC 17 Z9 21 U1 0 U2 5 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2007 VL 11 IS 2 BP 83 EP 95 PG 13 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 164EP UT WOS:000246216600004 PM 17397244 ER PT J AU Wettschureck, N Lee, E Libutti, SK Offermanns, S Robey, PG Spiegel, AM AF Wettschureck, Nina Lee, Eunah Libutti, Steven K. Offermanns, Stefan Robey, Pamela G. Spiegel, Allen M. TI Parathyroid-specific double knockout of G(q) and G(11) alpha-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+-sensing receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CALCIUM RECEPTOR; MOUSE MODEL; CELLS; HYPERPARATHYROIDISM; ACCUMULATION; EXPRESSION; MICE AB Germline knockout of the extracellular Ca2+-sensing receptor (CaR) leads to a phenotype that includes severe hypercalcemia, hyperparathyroidism, relative hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal death. To investigate the role of heterotrimeric G proteins in CaR signaling, we used cre/lox technology to delete the respective alpha-subunits of G(q) and G(11) selectively in parathyroid cells. Mice that were PTH-Cre(+/-); Gnaq(flox/flox); Gna11(-/-) (PTH-G alpha(q)/G(alpha 11)-double knockouts) were viable, but showed all the features of germline knockout of the CaR except hypocalcuria. Our results demonstrate the critical role of both G(q) and G(11) in mediating inhibition of PTH secretion by extracellular Ca2+. C1 Univ Heidelberg, Pharmakol Inst, D-69120 Heidelberg, Germany. NCI, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. NCI, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Brach, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Mol Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. RP Wettschureck, N (reprint author), Univ Heidelberg, Pharmakol Inst, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. EM nina.wettschureck@pharma.uni-heidelberg.de RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 22 TC 51 Z9 51 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2007 VL 21 IS 1 BP 274 EP 280 DI 10.1210/me.2006-0110 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121AV UT WOS:000243129900020 PM 16988000 ER PT J AU El-Jaick, KB Powers, SE Bartholin, L Myers, KR Hahn, J Orioli, IM Ouspenskaia, M Lacbawan, F Roessler, E Wotton, D Muenke, M AF El-Jaick, Kenia B. Powers, Shannon E. Bartholin, Laurent Myers, Kenneth R. Hahn, Jin Orioli, Ieda M. Ouspenskaia, Maia Lacbawan, Felicitas Roessler, Erich Wotton, David Muenke, Maximilian TI Functional analysis of mutations in TGIF associated with holoprosencephaly SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE TGIF; TGIF2; corepressor; HPE; complex inheritance ID SONIC-HEDGEHOG GENE; SMAD TRANSCRIPTIONAL COREPRESSOR; SIMPLE MENDELIAN DISORDERS; BETA-INDUCED FACTOR; PREMAXILLARY AGENESIS; TERMINAL DOMAIN; CANDIDATE GENE; COMPLEX TRAITS; HIGH MYOPIA; EXPRESSION AB Holoprosencephaly (HPE) is the most common structural malformation of the forebrain and face in humans. Our current understanding of the pathogenesis of HPE attempts to integrate genetic susceptibility, evidenced by mutations in the known HPE genes, with the epigenetic influence of environmental factors. Mutations or deletions of the human TGIF gene have been associated with H PE in multiple population cohorts. Here we examine the functional effects of all previously reported mutations, and describe four additional variants. Of the eleven sequence variations in TGIF, all but four can be demonstrated to be functionally abnormal. In contrast, no potentially pathogenic sequence alterations were detected in the related gene TGIF2. These results provide further evidence of a role for TGIF in HPE and demonstrate the importance of functional analysis of putative disease-associated alleles. Published by Elsevier Inc. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22903 USA. Univ Virginia, Ctr Cell Signaling, Charlottesville, VA 22903 USA. Univ Virginia, Program Cell & Dev Biol, Charlottesville, VA 22903 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Fed Rio de Janeiro, Lab Congenital Malformat, Rio De Janeiro, Brazil. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov FU FIC NIH HHS [D43 TW005503]; NHGRI NIH HHS [Z01 HG000209-04]; NIDCR NIH HHS [DE43TW05503] NR 54 TC 32 Z9 34 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2007 VL 90 IS 1 BP 97 EP 111 DI 10.1016/j.ymgme.2006.07.011 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 125XK UT WOS:000243476600016 PM 16962354 ER PT J AU Arumugam, TV Tang, SC Mughal, MR Chan, SL Mattson, MP Basta, M AF Arumugam, T. V. Tang, S. C. Mughal, M. R. Chan, S. L. Mattson, M. P. Basta, M. TI Intravenous immunoglobulin (IVIG) ameliorates ischmia/reperfusion-induced brain injury in mice SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 22-26, 2006 CL Beijing, PEOPLES R CHINA C1 NIA, Lab Neurosci, Baltimore, MD 21224 USA. NINDS, Neuronal Excitabil Sect, Bethesda, MD 20892 USA. RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 9 BP 150 EP 151 DI 10.1016/j.molimm.2006.07.014 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400026 ER PT J AU Nardai, G Basta, M Rosivall, L Tsokos, G Szebeni, J AF Nardai, Gabor Basta, Milan Rosivall, Laszlo Tsokos, George Szebeni, Janos TI Kinetics of complement activation in patients with trauma: Association with clinical correlates SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 21st International Complement Workshop CY OCT 20-27, 2006 CL Beijing, PEOPLES R CHINA C1 Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD USA. Natl Inst Trauma, Budapest, Hungary. NINDS, Neuronal Excitabil Sect, Bethesda, MD 20892 USA. Hungarian Acad Sci, Nephrol Res Grp, Budapest, Hungary. Semmelweis Univ, Fac Med, Inst Pathophysiol, H-1085 Budapest, Hungary. Bay Nano Inst, Dept Nanomed, Miskolc, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 1-3 SI SI MA 162 BP 218 EP 218 DI 10.1016/j.molimm.2006.07.167 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 096WV UT WOS:000241408400179 ER PT J AU Dror, N Alter-Koltunoff, M Azriel, A Amariglio, N Jacob-Hirsch, J Zeligson, S Morgenstern, A Tamura, T Hauser, H Rechavi, G Ozato, K Levi, BZ AF Dror, Natalie Alter-Koltunoff, Michal Azriel, Aviva Amariglio, Ninette Jacob-Hirsch, Jasmine Zeligson, Sharon Morgenstern, Avigail Tamura, Tomohiko Hauser, Hansjoerg Rechavi, Gideon Ozato, Keiko Levi, Ben-Zion TI Identitication of IRF-8 and IRF-1 target genes in activated macrophages SO MOLECULAR IMMUNOLOGY LA English DT Article DE interferon regulatory factors (IRFs); IRF-8; IRF-1; ICSBP; macrophage activation; transcriptional regulation; CXCL16; h28; LIF; MAP4K4; MMP9; MYC; PCDH7; PML; SOCS7 ID SEQUENCE-BINDING-PROTEIN; NF-KAPPA-B; INTERFERON REGULATORY FACTORS; IMMUNE-RESPONSES; TRANSCRIPTION FACTORS; FACTOR-I; EXPRESSION; PU.1; PML; INTERLEUKIN-17 AB Interferon regulatory factor 1 (IRF-1) and IRF-8, also known as interferon consensus sequence binding protein (ICSBP), are important regulators of macrophage differentiation and function. These factors exert their activities through the formation of heterocomplexes. As such, they are coactivators of various interferon-inducible genes in macrophages. To gain better insights into the involvement of these two transcription factors in the onset of the innate immune response and to identify their regulatory network in activated macrophages, DNA microarray was employed. Changes in the expression profile were analyzed in peritoneal macrophages from wild type mice and compared to IRF-1 and IRF-8 null mice, before and following 4 h exposure to IFN-gamma and LPS. The expression pattern of 265 genes was significantly changed (up/down) in peritoneal macrophages extracted from wild type mice following treatment with IFN-gamma and LPS, while no changes in the expression levels of these genes were observed in samples of the same cell-type from both IRF-1 and IRF-8 null mice. Among these putative target genes, numerous genes are involved in macrophage activity during inflammation. The expression profile of 10 of them was further examined by quantitative RT-PCR. In addition, the promoter regions of three of the identified genes were analyzed by reporter gene assay for the ability to respond to IRF-1 and IRF-8. Together, our results suggest that both IRF- I and IRF-8 are involved in the transcriptional regulation of these genes. We therefore suggest a broader role for IRF- I and IRF-8 in macrophages differentiation and maturation, being important inflammatory mediators. (c) 2006 Elsevier Ltd. All rights reserved. C1 Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD USA. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr,Funct Genom Unit, Safra Childrens Hosp,Pediat Hematooncol Dept,Mol, IL-69978 Tel Aviv, Israel. GBF, Dept Gene Regulat & Differentiat, Braunschweig, Germany. RP Levi, BZ (reprint author), Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. EM blevi@technion.ac.il NR 53 TC 42 Z9 44 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2007 VL 44 IS 4 BP 338 EP 346 DI 10.1016/j.molimm.2006.02.026 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 097PR UT WOS:000241460900009 PM 16597464 ER PT J AU Liu, Y Sun, RH Wan, WZ Wang, JN Oppenheim, JJ Chen, L Zhang, N AF Liu, Ying Sun, Ronghua Wan, Wuzhou Wang, Jingna Oppenheim, Joost J. Chen, Lin Zhang, Ning TI The involvement of lipid rafts in epidermal growth factor-induced chemotaxis of breast cancer cells SO MOLECULAR MEMBRANE BIOLOGY LA English DT Article DE lipid rafts; cancer; metastasis; chemotaxis; EGFR ID FACTOR RECEPTOR; CHOLESTEROL DEPLETION; SIGNAL-TRANSDUCTION; CHEMOKINE RECEPTORS; MEMBRANE; LOCALIZATION; CAVEOLAE; KINASES; CYCLODEXTRIN; TURNOVER AB Metastasis is the major cause of morbidity and mortality in cancer. Recent studies reveal a role of chemotaxis in cancer cell metastasis. Epidermal growth factor receptors (EGFR) have potent chemotactic effects on human breast cancer cells. Lipid rafts, organized microdomain on plasma membranes, regulate the activation of many membrane receptors. In the current study, we investigated the role of lipid rafts in EGFR-mediated cancer cell chemotaxis. Our confocal microscopy results suggested that EGFR co-localized with GM1-positive rafts. Disrupting rafts with methyl-beta-cyclodextrin (m beta CD) inhibited EGF-induced chemotaxis of human breast cancer cells. Supplementation with cholesterol reversed the inhibitory effects. Pretreatment with mbCD also impaired directional migration of cells in an in vitro "wound healing'' assay, EGF-induced cell adhesion, actin polymerization, Akt phosphorylation and protein kinase C zeta (PKC zeta) translocation. Taken together, our study indicated that integrity of lipid rafts was critical in EGF-induced chemotaxis of human breast cancer cells. C1 Tianjin Med Univ, Canc Inst & Hosp, Tianjin 300060, Peoples R China. Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA. Peking Univ, Beijing Natl Lab Mol Sci, Beijing, Peoples R China. Peking Univ, Dept Biol Chem, Coll Chem & Mol Engn, Beijing, Peoples R China. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zhang, N (reprint author), Tianjin Med Univ, Canc Inst & Hosp, Tianjin 300060, Peoples R China. EM zhang236@oakland.edu RI Wan, Wuhzou/H-8556-2013 FU Intramural NIH HHS NR 36 TC 19 Z9 19 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0968-7688 J9 MOL MEMBR BIOL JI Mol. Membr. Biol. PY 2007 VL 24 IS 2 BP 91 EP 101 DI 10.1080/10929080600990500 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172VT UT WOS:000246833300001 PM 17453416 ER PT J AU Chattoraj, DK AF Chattoraj, Dhruba K. TI Tryptophanase in sRNA control of the Escherichia coli cell cycle SO MOLECULAR MICROBIOLOGY LA English DT Editorial Material ID PLASMID STABILITY; PROTEIN; CHECKPOINT; ARREST; DNA AB The field of gene regulation underwent a major revolution with the discovery of small non-coding RNAs (sRNAs) and the various roles they play in organisms from bacteria to man. Escherichia coli has more than 60 sRNAs that are transcribed primarily from intergenic regions. They usually target the leader region of mRNAs and prevent their translation. Protein targets are relatively rare. In this issue of Molecular Microbiology, Chant and Summers provide an example of a totally unexpected protein target. They show that dimers of plasmid ColE1 make an sRNA that interacts directly with the enzyme tryptophanase and enhances its affinity for its substrate, tryptophan. A breakdown product, indole, then arrests cell division until the dimers are resolved to monomers. The monomerization helps to prevent plasmid loss. Targeting a catabolic enzyme to buy time for recombination is an amazing example of adaptation, which illustrates the power of a selfish element (a plasmid in this case) to exploit the host cell machinery to its advantage. C1 NCI, Biochem & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM chattoraj@nih.gov NR 15 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2007 VL 63 IS 1 BP 1 EP 3 DI 10.1111/j.1365-2958.2006.05517.x PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 117XH UT WOS:000242906100001 PM 17163965 ER PT J AU Cooper, RA Lane, KD Deng, BB Mu, JB Patel, JJ Wellems, TE Su, XZ Ferdig, MT AF Cooper, Roland A. Lane, Kristin D. Deng, Bingbing Mu, Jianbing Patel, Jigar J. Wellems, Thomas E. Su, Xinzhuan Ferdig, Michael T. TI Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine SO MOLECULAR MICROBIOLOGY LA English DT Article ID ANTIMALARIAL-DRUG-RESISTANCE; MALARIA PARASITES; FERRIPROTOPORPHYRIN-IX; CINCHONA ALKALOIDS; DIGESTIVE VACUOLE; PROTEIN PFCRT; EFFLUX SYSTEM; IN-VITRO; MECHANISM; HEMATIN AB Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result in verapamil-reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane-spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of the P. falciparum 106/1(K76) parasite line, we used single-step drug selection to generate isogenic clones containing unique pfcrt point mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I and K76T) and 9 (Q352K, Q352R). The resulting changes of charge and hydropathy affected quantitative CQ susceptibility and accumulation as well as the stereospecific responses to quinine and quinidine. These results, together with a previously described S163R mutation in transmembrane domain 4, indicate that transmembrane segments 1, 4 and 9 of PfCRT provide important structural components of a substrate recognition and translocation domain. Charge-affecting mutations within these segments may affect the ability of PfCRT to bind different quinoline drugs and determine their net accumulation in the DV. C1 Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Cooper, RA (reprint author), Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. EM rcooper@odu.edu RI Ferdig, Michael/C-6627-2016; OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS; NIAID NIH HHS [AI055035, AI055601] NR 62 TC 58 Z9 62 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2007 VL 63 IS 1 BP 270 EP 282 DI 10.1111/j.1365-2958.2006.05511.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 117XH UT WOS:000242906100023 PM 17163969 ER PT J AU Brett, PJ Burtnick, MN Snyder, DS Shannon, JG Azadi, P Gherardini, FC AF Brett, Paul J. Burtnick, Mary N. Snyder, D. Scott Shannon, Jeffrey G. Azadi, Parastoo Gherardini, Frank C. TI Burkholderia mallei expresses a unique lipopolysaccharide mixture that is a potent activator of human Toll-like receptor 4 complexes SO MOLECULAR MICROBIOLOGY LA English DT Article ID CYSTIC-FIBROSIS AIRWAY; HUMAN DENDRITIC CELLS; A-SUBUNIT ANALOGS; LIPID-A; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; BACTERIAL LIPOPOLYSACCHARIDES; STRUCTURAL-CHARACTERIZATION; SALMONELLA-TYPHIMURIUM; LPS MODIFICATIONS AB Burkholderia mallei, the aetiologic agent of glanders, causes a variety of illnesses in animals and humans ranging from occult infections to acute fulminating septicaemias. To better understand the role of lipopolysaccharide (LPS) in the pathogenesis of these diseases, studies were initiated to characterize the structural and biological properties of lipid A moieties expressed by this organism. Using a combination of chemical analyses and MALDI-TOF mass spectrometry, B. mallei was shown to express a heterogeneous mixture of tetra- and penta-acylated lipid A species that were non-stoichiometrically substituted with 4-amino-4-deoxy-arabinose residues. The major penta-acylated species consisted of bisphosphorylated D-glucosamine disaccharide backbones possessing two amide linked 3-hydroxyhexadecanoic acids, two ester linked 3-hydroxytetradecanoic acids [C14:0(3-OH)] and an acyloxyacyl linked tetradecanoic acid, whereas, the major tetra-acylated species possessed all but the 3'-linked C14:0(3-OH) residues. In addition, although devoid of hexa-acylated species, B. mallei LPS was shown to be a potent activator of human Toll-like receptor 4 complexes and stimulated human macrophage-like cells (THP-1 and U-937), monocyte-derived macrophages and dendritic cells to produce high levels of TNF-alpha, IL-6 and RANTES. Based upon these results, it appears that B. mallei LPS is likely to play a significant role in the pathogenesis of human disease. C1 NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Gherardini, FC (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fgherardini@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU Intramural NIH HHS NR 71 TC 28 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2007 VL 63 IS 2 BP 379 EP 390 DI 10.1111/j.1365-2958.2006.05519.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 123ON UT WOS:000243305300006 PM 17163980 ER PT J AU Lai, YP Villaruz, AE Li, M Cha, DJ Sturdevant, DE Otto, M AF Lai, Yuping Villaruz, Amer E. Li, Min Cha, David J. Sturdevant, Daniel E. Otto, Michael TI The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci SO MOLECULAR MICROBIOLOGY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; PHENOL-SOLUBLE MODULINS; BACILLUS-SUBTILIS; SIGNAL-TRANSDUCTION; NEUTROPHIL GRANULES; VIRULENCE FACTORS; GENE-EXPRESSION; EPIDERMIDIS; AUREUS; AGR AB Antimicrobial peptides (AMPs) represent a key component of innate host defence against bacterial pathogens. Bacterial resistance mechanisms usually depend on the characteristic positive charge of AMPs. However, several human cell types also produce anionic AMPs, mechanisms of resistance to which are poorly understood. Here we demonstrate that the skin commensal and leading nosocomial pathogen Staphylococcus epidermidis senses and efficiently inactivates the anionic AMP dermcidin. Dermcidin induced differential expression of global regulatory systems, leading to increased expression of proteases with the capacity to degrade dermcidin, particularly S. epidermidis SepA. A similar induction of extracellular proteolytic activity was found in Staphylococcus aureus, suggesting a common regulatory mechanism in staphylococci. Notably, human cationic AMPs also led to the activation of global regulators, but inactivation of dermcidin by SepA was much more effective than of the tested cationic peptides. The ability to react to the unusual, anionic dermcidin with effective countermeasures likely contributes to the extraordinary success of staphylococci as colonizers and infective agents on human epithelia. Our study indicates that staphylococci can react to human AMPs by specific mechanisms of resistance and establishes a crucial role for staphylococcal proteases in the interaction with human innate host defence. C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China. NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 35 TC 69 Z9 76 U1 5 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2007 VL 63 IS 2 BP 497 EP 506 DI 10.1111/j.1365-2958.2006.05540.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 123ON UT WOS:000243305300015 PM 17176256 ER PT J AU Hummer, G AF Hummer, Gerhard TI Water, proton, and ion transport: from nanotubes to proteins SO MOLECULAR PHYSICS LA English DT Article; Proceedings Paper CT 3rd International Conference on Foundations of Molecular Modeling and Simulation (FOMMS) CY JUL 09-14, 2006 CL Blaine, WA SP Amer Inst Chem Engineers, Computat Mole Sci & Engn Forum DE protein channels; nanotubes; proteins; ion transport ID MOLECULAR-DYNAMICS SIMULATIONS; CAVITY-CREATING MUTATIONS; COARSE-GRAINED MODEL; SINGLE-FILE PORES; CARBON NANOTUBES; LIQUID WATER; MECHANOSENSITIVE CHANNEL; HYDROPHOBIC HYDRATION; CYTOCHROME P450CAM; FLUID EXPERIMENTS AB Remarkably, protein channels transporting polar substances such as water, protons, and ions are often lined by predominantly non-polar residues. The unique structural, dynamic, and thermodynamic properties of water and ions in molecular confinement help explain this puzzling observation. Computer simulations of solvated nanotubes and proteins show that weakly polar cavities can be filled by water at equilibrium, but such filling is highly sensitive to small variations in the polarity of the cavity. In the filled state, water forms wires and clusters held together by tight hydrogen bonds. Simulations on quantum energy surfaces also show that 1D water wires in hydrophobic environments facilitate rapid proton motion. The unique properties of water in weakly polar channels help explain the rapid flow of water through molecular pores, the controlled proton flow in enzymes, the gating of ion transport through membrane channels, and the function of mitochondrial proton pumps. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 94 TC 59 Z9 59 U1 5 U2 25 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PD JAN-FEB PY 2007 VL 105 IS 2-3 BP 201 EP 207 DI 10.1080/00268970601140784 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 147DU UT WOS:000244984400008 ER PT J AU Liu, SB Perera, L Pedersen, LG AF Liu, S. B. Perera, L. Pedersen, L. G. TI Binuclear manganese(II) complexes in biological systems SO MOLECULAR PHYSICS LA English DT Article DE binuclear manganese (II); DNA polymerase beta; ferromagnetic; antiferromagnetic ID DENSITY-FUNCTIONAL THEORY; TRANSITION-METAL DIMERS; CRYSTAL-STRUCTURE; MAGNETIC-PROPERTIES; ESCHERICHIA-COLI; MN(II) COMPLEXES; MN; ENERGY; APPROXIMATION; PARAMETERS AB The paper reports calculations on binuclear manganese(II) clusters related to those found in biological systems. B3LYP/6-311g(d, p) density functional theory (DFT) calculations are carried out specifically on a set of clusters that derive from the X-ray crystal structure of DNA polymerase beta [Batra, V. K. et al., Structure 14, 757-766 (2006)]. Issues investigated are: (a) the relative energy of the lowest and highest spin states (antiferromagnetic (low spin/broken symmetry = LS/BS) or ferromagnetic); (b) the Mn(II)-Mn(II) distance; (c) the effect of water versus CH3OH (a sugar analogue) as a direct Mn ligand; and (d) the effect of the kind of oxygen bridge (mono-oxygen, single-oxygen from a carboxylate or phosphate, or a two-oxygen bridge from a carboxylate), on the geometry and energy. It was found generally that the antiferromagnetic state is lower in energy, that the Mn(II)-Mn(II) distance (which varies from 2.91 to 3.57 angstrom in the series studied) is longer for ferromagnetic states than for the corresponding low spin states, that the interchange of CH3OH and water does not affect the results, and that a single (carboxylate) oxygen as bridge leads to a lower energy than a corresponding two (carboxylate) oxygen bridge, as well as to a more compact structure. C1 [Liu, S. B.] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC 27599 USA. [Perera, L.; Pedersen, L. G.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Pedersen, L. G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC 27599 USA. EM lee_pedersen@unc.edu RI Liu, Shubin/B-1502-2009; perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI Liu, Shubin/0000-0001-9331-0427; perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 NR 32 TC 12 Z9 12 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PY 2007 VL 105 IS 19-22 BP 2893 EP 2898 DI 10.1080/00268970701747199 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 242UH UT WOS:000251751200040 ER PT J AU Rao, JS Ertley, RN Lee, HJ Demar, JC Arnold, JT Rapoport, SI Bazinet, RP AF Rao, J. S. Ertley, R. N. Lee, H-J DeMar, J. C., Jr. Arnold, J. T. Rapoport, S. I. Bazinet, R. P. TI n-3 oolyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism SO MOLECULAR PSYCHIATRY LA English DT Article DE docosahexaenoic acid; BDNF; MAPK; PKA; brain; rat; bipolar disorder ID BIPOLAR AFFECTIVE-DISORDER; ACTIVATED PROTEIN-KINASE; TRANSPORTER SURFACE EXPRESSION; GENE CONFERS SUSCEPTIBILITY; FAMILY-BASED ASSOCIATION; SIGNAL-REGULATED KINASE; DOCOSAHEXAENOIC ACID; NEUROTROPHIC FACTOR; POSTMORTEM BRAIN; RESPONSE ELEMENT AB Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor ( BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein ( CREB) transcription factor activity and p38 mitogen-activated protein kinase ( MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIH, Endocrine Sect, Clin Invest Lab, Div Intramural Res,Natl Ctr Complementary & Alter, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 91 TC 169 Z9 175 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2007 VL 12 IS 1 BP 36 EP 46 DI 10.1038/sj.mp.4001888 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 119EF UT WOS:000242994300003 PM 16983391 ER PT J AU Surh, YJ Chun, KS AF Surh, Young-Joon Chun, Kyung-Soo TI Cancer chemopreventive effects of curcumin SO MOLECULAR TARGETS AND THERAPEUTIC USES OF CURCUMIN IN HEALTH AND DISEASE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID NF-KAPPA-B; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED TUMOR PROMOTION; FAMILIAL ADENOMATOUS POLYPOSIS; INHIBITS CELL-PROLIFERATION; BREAST-CARCINOMA CELLS; B16F10 MELANOMA-CELLS; NITRIC-OXIDE SYNTHASE; HUMAN PROSTATE-CANCER; I CLINICAL-TRIAL; BCL-X-L AB Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis, has emerged as a promising and pragmatic medical approach to reduce the risk of cancer. Numerous components of edible plants, collectively termed "phytochemicals" have been reported to possess substantial chemopreventive properties. Curcumin, a yellow coloring ingredient derived from Curcuma longa L. (Zingiberaceae), is one of the most extensively investigated and well-defined chemopreventive phytochemicals. Curcumin has been shown to protect against skin, oral, intestinal, and colon carcinogenesis and also to suppress angiogenesis and metastasis in a variety animal tumor models. It also inhibits the proliferation of cancer cells by arresting them in the various phases of the cell cycle and by inducing apoptosis. Moreover, curcumin has a capability to inhibit carcinogen bioactivation via suppression of specific cytochrome P450 isozymes, as well as to induce the activity or expression of phase II carcinogen detoxifying enzymes. Well-designed intervention studies are necessary to assess the chemopreventive efficacy of curcumin in normal individuals as well as high-risk groups. Sufficient data from pharmacodynamic as well as mechanistic studies are necessary to advocate clinical evaluation of curcumin for its chemopreventive potential. C1 Seoul Natl Univ, Coll Pharm, Natl Res Lab Mol Carcinogenesis & Chemoprevent, Seoul 151742, South Korea. NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Surh, YJ (reprint author), Seoul Natl Univ, Coll Pharm, Natl Res Lab Mol Carcinogenesis & Chemoprevent, Seoul 151742, South Korea. EM surh@plaza.snu.ac.kr; chunkyungsoo@yahoo.co.kr NR 132 TC 67 Z9 68 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 595 BP 149 EP 172 PG 24 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA BGH28 UT WOS:000246951600005 PM 17569209 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI From Foraging to Farming INTRODUCTION SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Editorial Material; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 1 EP 6 D2 10.1017/CBO9780511512148 PG 6 WC History SC History GA BXU88 UT WOS:000297207400002 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI LAST HUNTERS, FIRST FARMERS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 7 EP 13 DI 10.1017/CBO9780511512148.003 D2 10.1017/CBO9780511512148 PG 7 WC History SC History GA BXU88 UT WOS:000297207400003 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI A MOVABLE FEAST Ten Millennia of Food Globalization Preface SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Editorial Material; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP XIII EP + DI 10.1017/CBO9780511512148.001 D2 10.1017/CBO9780511512148 PG 48 WC History SC History GA BXU88 UT WOS:000297207400001 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI BUILDING THE BARNYARD SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 14 EP 24 DI 10.1017/CBO9780511512148.004 D2 10.1017/CBO9780511512148 PG 11 WC History SC History GA BXU88 UT WOS:000297207400004 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI PROMISCUOUS PLANTS OF THE NORTHERN FERTILE CRESCENT SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 25 EP 35 DI 10.1017/CBO9780511512148.005 D2 10.1017/CBO9780511512148 PG 11 WC History SC History GA BXU88 UT WOS:000297207400005 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI PERIPATETIC PLANTS OF EASTERN ASIA SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 36 EP 50 DI 10.1017/CBO9780511512148.006 D2 10.1017/CBO9780511512148 PG 15 WC History SC History GA BXU88 UT WOS:000297207400006 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI FECUND FRINGES OF THE NORTHERN FERTILE CRESCENT SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 51 EP 60 DI 10.1017/CBO9780511512148.007 D2 10.1017/CBO9780511512148 PG 10 WC History SC History GA BXU88 UT WOS:000297207400007 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI CONSEQUENCES OF THE NEOLITHIC SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 61 EP 69 DI 10.1017/CBO9780511512148.008 D2 10.1017/CBO9780511512148 PG 9 WC History SC History GA BXU88 UT WOS:000297207400008 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI ENTERPRISE AND EMPIRES SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 70 EP 82 DI 10.1017/CBO9780511512148.009 D2 10.1017/CBO9780511512148 PG 13 WC History SC History GA BXU88 UT WOS:000297207400009 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI FAITH AND FOODSTUFFS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 83 EP 90 DI 10.1017/CBO9780511512148.010 D2 10.1017/CBO9780511512148 PG 8 WC History SC History GA BXU88 UT WOS:000297207400010 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI EMPIRES IN THE RUBBLE OF ROME SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 91 EP 96 DI 10.1017/CBO9780511512148.011 D2 10.1017/CBO9780511512148 PG 6 WC History SC History GA BXU88 UT WOS:000297207400011 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI MEDIEVAL PROGRESS AND POVERTY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 97 EP 104 DI 10.1017/CBO9780511512148.012 D2 10.1017/CBO9780511512148 PG 8 WC History SC History GA BXU88 UT WOS:000297207400012 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI SPAIN'S NEW WORLD, THE NORTHERN HEMISPHERE SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 105 EP 112 DI 10.1017/CBO9780511512148.013 D2 10.1017/CBO9780511512148 PG 8 WC History SC History GA BXU88 UT WOS:000297207400013 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI NEW WORLD, NEW FOODS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 113 EP 126 DI 10.1017/CBO9780511512148.014 D2 10.1017/CBO9780511512148 PG 14 WC History SC History GA BXU88 UT WOS:000297207400014 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI NEW FOODS IN THE SOUTHERN NEW WORLD SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 127 EP 134 DI 10.1017/CBO9780511512148.015 D2 10.1017/CBO9780511512148 PG 8 WC History SC History GA BXU88 UT WOS:000297207400015 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI THE COLUMBIAN EXCHANGE AND THE OLD WORLDS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 135 EP 149 DI 10.1017/CBO9780511512148.016 D2 10.1017/CBO9780511512148 PG 15 WC History SC History GA BXU88 UT WOS:000297207400016 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI THE COLUMBIAN EXCHANGE AND NEW WORLDS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 150 EP 162 DI 10.1017/CBO9780511512148.017 D2 10.1017/CBO9780511512148 PG 13 WC History SC History GA BXU88 UT WOS:000297207400017 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI SUGAR AND NEW BEVERAGES SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 163 EP 183 DI 10.1017/CBO9780511512148.018 D2 10.1017/CBO9780511512148 PG 21 WC History SC History GA BXU88 UT WOS:000297207400018 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI KITCHEN HISPANIZATION SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 184 EP 190 DI 10.1017/CBO9780511512148.019 D2 10.1017/CBO9780511512148 PG 7 WC History SC History GA BXU88 UT WOS:000297207400019 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI PRODUCING PLENTY IN PARADISE SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 191 EP 201 DI 10.1017/CBO9780511512148.020 D2 10.1017/CBO9780511512148 PG 11 WC History SC History GA BXU88 UT WOS:000297207400020 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI THE FRONTIERS OF FOREIGN FOODS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 202 EP 213 DI 10.1017/CBO9780511512148.021 D2 10.1017/CBO9780511512148 PG 12 WC History SC History GA BXU88 UT WOS:000297207400021 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI CAPITALISM, COLONIALISM, AND CUISINE SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 214 EP 225 DI 10.1017/CBO9780511512148.022 D2 10.1017/CBO9780511512148 PG 12 WC History SC History GA BXU88 UT WOS:000297207400022 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI HOMEMADE FOOD HOMOGENEITY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 226 EP 237 DI 10.1017/CBO9780511512148.023 D2 10.1017/CBO9780511512148 PG 12 WC History SC History GA BXU88 UT WOS:000297207400023 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI NOTIONS OF NUTRIENTS AND NUTRIMENTS SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 238 EP 252 DI 10.1017/CBO9780511512148.024 D2 10.1017/CBO9780511512148 PG 15 WC History SC History GA BXU88 UT WOS:000297207400024 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI THE PERILS OF PLENTY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 253 EP 266 DI 10.1017/CBO9780511512148.025 D2 10.1017/CBO9780511512148 PG 14 WC History SC History GA BXU88 UT WOS:000297207400025 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI THE GLOBALIZATION OF PLENTY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 267 EP 273 DI 10.1017/CBO9780511512148.026 D2 10.1017/CBO9780511512148 PG 7 WC History SC History GA BXU88 UT WOS:000297207400026 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI FAST FOOD, A HYMN TO CELLULITE SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 274 EP 284 DI 10.1017/CBO9780511512148.027 D2 10.1017/CBO9780511512148 PG 11 WC History SC History GA BXU88 UT WOS:000297207400027 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI PARLOUS PLENTY INTO THE TWENTY-FIRST CENTURY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 285 EP 294 DI 10.1017/CBO9780511512148.028 D2 10.1017/CBO9780511512148 PG 10 WC History SC History GA BXU88 UT WOS:000297207400028 ER PT J AU Kiple, KF AF Kiple, Kenneth F. BA Kiple, KF BF Kiple, KF TI PEOPLE AND PLENTY IN THE TWENTY-FIRST CENTURY SO MOVABLE FEAST: TEN MILLENNIA OF FOOD GLOBALIZATION LA English DT Article; Book Chapter C1 [Kiple, Kenneth F.] Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. [Kiple, Kenneth F.] NIH, Bethesda, MD 20892 USA. [Kiple, Kenneth F.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kiple, KF (reprint author), Bowling Green State Univ, Dept Hist, Bowling Green, OH 43403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-79353-7 PY 2007 BP 295 EP 306 DI 10.1017/CBO9780511512148.029 D2 10.1017/CBO9780511512148 PG 12 WC History SC History GA BXU88 UT WOS:000297207400029 ER PT J AU Hanagasi, HA Lees, A Johnson, JO Singleton, A Emre, M AF Hanagasi, Hasmet Ayhan Lees, Andrew Johnson, Janel O. Singleton, Andrew Emre, Murat TI Smoking-responsive juvenile-onset parkinsonism SO MOVEMENT DISORDERS LA English DT Article DE juvenile-onset Parkinsonism; nicotine; sensitivity ID ALZHEIMERS-DISEASE; DOPAMINE TRANSPORTER; NICOTINIC RECEPTORS; COGNITIVE PERFORMANCE; TRANSDERMAL NICOTINE; BINDING-SITES; DYSTONIA; TOMOGRAPHY; DEMENTIA; NEURONS AB We describe a patient with juvenile levodopa-responsive Parkinsonism who reported a dramatic response to cigarette smoking with transient but marked improvement of motor symptoms associated with oculogyric crises and psychotic behavior. His beta-CIT single-photon emission computed tomography scan showed a complete absence of presynaptic dopaminergic nerve terminals. (C) 2006 Movement Disorder Society. C1 Istanbul Univ, Istanbul Fac Med, Dept Neurol, Behav Neurol & Movement Disorders Unit, Istanbul, Turkey. UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, London, England. NIA, Mol Genet Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Hanagasi, HA (reprint author), Istanbul Univ, Istanbul Fac Med, Dept Neurol, TR-34390 Capa, Turkey. EM hasmet@yahoo.com RI Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009 NR 34 TC 13 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2007 VL 22 IS 1 BP 115 EP 118 DI 10.1002/mds.21177 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 134HF UT WOS:000244073400018 PM 17080433 ER PT J AU Stasevich, TJ Einstein, TL AF Stasevich, T. J. Einstein, T. L. TI Analytic formulas for the orientation dependence of step stiffness and line tension: Key ingredients for numerical modeling SO MULTISCALE MODELING & SIMULATION LA English DT Article DE step stiffness; step line tension; anisotropy; numerical modeling; finite element simulation; step dynamics ID EQUILIBRIUM CRYSTAL SHAPES; SURFACE ELECTROMIGRATION; EPITAXIAL-GROWTH AB We present explicit analytic, twice-differentiable expressions for the temperature-dependent anisotropic step line tension and step stiffness for the two principal surfaces of face-centered-cubic crystals, the square {001} and the hexagonal {111}. These expressions improve on simple expressions that are valid only for low temperatures and away from singular orientations. They are well suited for implementation into numerical methods such as finite element simulation of step evolution. C1 Univ Maryland, Dept Phys, College Pk, MD 20742 USA. RP Stasevich, TJ (reprint author), NCI, Fluorescence Imaging Facil, NIH, Bethesda, MD 20892 USA. EM tim_stasevich@hotmail.com; einstein@umd.edu OI Einstein, Theodore L./0000-0001-6031-4923 NR 33 TC 11 Z9 11 U1 1 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1540-3459 J9 MULTISCALE MODEL SIM JI Multiscale Model. Simul. PY 2007 VL 6 IS 1 BP 90 EP 104 DI 10.1137/060662861 PG 15 WC Mathematics, Interdisciplinary Applications; Physics, Mathematical SC Mathematics; Physics GA 174ED UT WOS:000246923200005 ER PT J AU van Gijssel, HE Leil, TA Weinberg, WC Divi, RL Olivero, OA Poirier, MC AF van Gijssel, Hilde E. Leil, Tarek A. Weinberg, Wendy C. Divi, Rao L. Olivero, Ofelia A. Poirier, Miriam C. TI Cisplatin-DNA damage in p21(WAF1/Cip1) deficient mouse keratinocytes exposed to cisplatin SO MUTAGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DEPENDENT KINASE INHIBITOR; MALIGNANT CONVERSION; SKIN CARCINOGENESIS; HUMAN FIBROBLASTS; ADDUCT FORMATION; CELL-CYCLE; IN-VITRO; P53 LOSS; P21 AB In response to DNA damage, cell cycle arrest, apoptosis, and DNA repair are mediated by a TP53 pathway that induces p21(WAF1/Cip1). The chemotherapeutic drug cis-diamminedichloroplatinum-II (cisplatin) damages cellular DNA by forming cis-diammineplatinum-N-7-d[GpG] and cis-diammine-platinum-N-7-d[ApG] adducts. To investigate the role of p21, skin keratinocytes from p21(WAF1/Cip1) wild-type (+/+), heterozygous (+/-), and null (-/-) mice, cultured in calcium levels designed to maintain a proliferating state, were exposed to 5 mu M cisplatin continuously for 0, 8, 24, 48 and 72 h. At all time points the (+/-) cells had the fewest Pt-DNA adducts, and at 24 h mean Pt-DNA adduct levels were 541, 153 and 779 fmol adduct/mu g DNA for p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively [P < 0.05 for (+/+) versus (+/-) and (-/-) versus (+/-)]. In order to understand underlying events, we examined p21(WAF1/Cip1) messenger RNA (mRNA), cell cycle arrest, and apoptosis in these cells. At 48 h of cisplatin exposure p21(WAF1/Cip1) mRNA expression was 2-fold higher in the (+/+) cells, compared to the (+/-) cells. At 24 h, the % of cells in S-phase in cisplatin-exposed cultures, compared to unexposed cultures, was decreased by 51, 40 and 11% in p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively (P = 0.04, ANOVA). At 24, 48 and 72 h the % of cisplatin-exposed (+/+) cells in apoptosis was 9.4-10.5%, while the cisplatin-exposed (+/-) and (-/-) cells had 1.2-3.7% of cells in apoptosis. The data support the interpretation that DNA replication arrest and apoptosis do not completely explain the low levels of Pt-DNA adducts in the (+/-) cells, and suggest that p21(WAF1/Cip1) controls activity resulting in either low Pt-DNA adduct formation or enhanced Pt-DNA adduct removal. C1 NCI, Carcinogen DNA Interact Sect, NIH, Lab Cellular Carcinogenesis & Tumor Promot,CCR, Bethesda, MD 20892 USA. US FDA, CDER, Off Biotechnol Prod, Immunobiol Lab, Bethesda, MD 20892 USA. Valley City State Univ, Valley City, ND 58072 USA. Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Lab Cellular Carcinogenesis & Tumor Promot,CCR, Bldg 37,Room 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS NR 33 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2007 VL 22 IS 1 BP 49 EP 54 DI 10.1093/mutage/gel050 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 123WN UT WOS:000243327000006 PM 17158520 ER PT J AU Kolenbrander, PE Jakubovics, NS Chalmers, NI AF Kolenbrander, Paul E. Jakubovics, Nicholas S. Chalmers, Natalia I. BE Whitworth, DE TI Multispecies Interactions and Biofilm Community Development SO MYXOBACTERIA: MULTICELLULARITY AND DIFFERENTIATION LA English DT Article; Book Chapter ID CELL-CELL COMMUNICATION; QUORUM-SENSING SIGNAL; STREPTOCOCCUS-GORDONII BIOFILM; CYCLIC DIGUANYLIC ACID; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PSEUDOMONAS-AERUGINOSA; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; BACTERIAL BIOFILMS; GENE-EXPRESSION C1 [Kolenbrander, Paul E.; Jakubovics, Nicholas S.] Natl Inst Dent & Craniofacial Res, Oral Biofilm Commun Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Chalmers, Natalia I.] Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, Oral Biofilm Commun Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-420-5 PY 2007 BP 453 EP 461 PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA BOY04 UT WOS:000277999600027 ER PT B AU de Jonge, N Sougrat, R Peckys, DB Lupini, AR Pennycook, SJ AF de Jonge, Niels Sougrat, Rachid Peckys, Diana B. Lupini, Andrew R. Pennycook, Stephen J. BE VoDinh, T TI Three-Dimensional Aberration-Corrected Scanning Transmission Electron Microscopy for Biology SO NANOTECHNOLOGY IN BIOLOGY AND MEDICINE: METHODS, DEVICES, AND APPLICATIONS LA English DT Article; Book Chapter ID HIGH-RESOLUTION; DARK-FIELD; CRYOELECTRON TOMOGRAPHY; SPHERICAL-ABERRATION; SCATTERED ELECTRONS; HUMAN GENOME; Z-CONTRAST; IMAGE-RECONSTRUCTION; ANGSTROM RESOLUTION; ATOMIC-RESOLUTION AB Recent instrumental developments have enabled greatly improved resolution of scanning transmission electron microscopes (STEM) through aberration correction. An additional and previously unanticipated advantage of aberration correction is the largely improved depth sensitivity that has led to the reconstruction of a three-dimensional (3D) image from a focal series. In this chapter the potential of aberration-corrected 3D STEM to provide major improvements in the imaging capabilities for biological samples will be discussed. This chapter contains a brief overview of the various high-resolution 3D imaging techniques, a historical perspective of the development of STEM, first estimates of the dose-limited axial and lateral resolution oil biological samples and initial experiments on stained thin sections. C1 [de Jonge, Niels; Peckys, Diana B.; Lupini, Andrew R.; Pennycook, Stephen J.] Oak Ridge Natl Lab, Div Mat Sci & Engn, Oak Ridge, TN USA. [Sougrat, Rachid] Natl Inst Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. RP de Jonge, N (reprint author), Oak Ridge Natl Lab, Div Mat Sci & Engn, Oak Ridge, TN USA. NR 127 TC 2 Z9 2 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-0-8493-2949-4 PY 2007 D2 10.1201/9781420004441 PG 28 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BKN95 UT WOS:000268735400013 ER PT J AU Ainslie, KM Bachelder, EM Sharma, G Grimes, CA Pishko, MV AF Ainslie, Kristy M. Bachelder, Eric M. Sharma, Gaurav Grimes, Craig A. Pishko, Michael V. TI Macrophage cell adhesion and inflammation cytokines on magnetostrictive nanowires SO NANOTOXICOLOGY LA English DT Article DE nanomaterials; biomaterials; biocompatibility ID PROTEIN ADSORPTION; MEMBRANE MICROARCHITECTURE; SILICON SURFACES; IMPLANTS; ATTACHMENT; TITANIUM; PLASMA; ALLOY; NEOVASCULARIZATION; BIOCOMPATIBILITY AB A common problem with medical implants is the biofouling response which can detrimentally damage implants or prevent the implant from function properly. This response is characterized by a thick, frequently avascular, layer of proteins and cells over the implant. To study this problem, we have examined here the adhesion of macrophages and the subsequent expression of inflammatory cytokines on nanowire arrays. We found that the cells on the nanowires typically occupied less area and were more circular than on a flat surface of the same material as the nanowires or tissue culture polystyrene (TCPS) in both the presence and absence of fetal bovine serum. Furthermore, this difference was amplified by pre-coating the surfaces with collagen. The smaller area and circular shape indicated that the cells were not thriving on the surface. Since there was potentially a high amount of cell death on the material, and biofouling is frequently characterized as a chronic inflammation, an eighteen cytokine Luminex (R) panel was performed on the supernatant from macrophages on nanowires, control wafers, and TCPS. As a positive control for inflammation, lipopolysaccharide (LPS) was added to macrophages on TCPS to estimate the maximum inflammation response of the macrophages. Our results indicated that the nanowire structure results in the up-regulation of production in macrophages of inflammatory cytokines such as IL-1 alpha, and IFN-gamma and the down-regulation of IL-6, compared to control wafers. In addition, the nanostructure also increased the production of IL-10 which is known as an inhibitor of inflammation. Our results showed that the nanoarchitecture can disrupt cell adhesion and may lead to an inflammatory response. C1 [Ainslie, Kristy M.; Pishko, Michael V.] Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA. [Bachelder, Eric M.] NIAID, NIH, Bethesda, MD 20892 USA. [Sharma, Gaurav] Univ Nebraska, Dept Chem Engn, Lincoln, NE 68588 USA. [Sharma, Gaurav; Grimes, Craig A.; Pishko, Michael V.] Penn State Univ, Dept Mat Sci & Engn, University Pk, PA 16802 USA. [Grimes, Craig A.] Penn State Univ, Dept Elect Engn, University Pk, PA 16802 USA. [Pishko, Michael V.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA. RP Pishko, MV (reprint author), Texas A&M Univ, 3122 TAMU, College Stn, TX 77845 USA. EM mpishko@tamu.edu OI Ainslie, Kristy/0000-0002-1820-8382 NR 41 TC 5 Z9 5 U1 3 U2 10 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1743-5390 J9 NANOTOXICOLOGY JI Nanotoxicology PY 2007 VL 1 IS 4 BP 279 EP 290 DI 10.1080/17435390701781142 PG 12 WC Nanoscience & Nanotechnology; Toxicology SC Science & Technology - Other Topics; Toxicology GA 363WC UT WOS:000260296800003 ER PT J AU Kritsanida, M Magiatis, P Skaltsounis, AL Stables, JP AF Kritsanida, Marina Magiatis, Prokopios Skaltsounis, Alexios-Leandros Stables, James P. TI Phytochemical investigation and anticonvulsant activity of Paeonia parnassica radix SO NATURAL PRODUCT COMMUNICATIONS LA English DT Article DE Paeonia parnassica; anticonvulsant; paeonidanin; 4-O-methylpaeoniflorin; albiflorin ID WATER-SOLUBLE CONSTITUENTS; PEONY ROOT; MONOTERPENE GLYCOSIDES; SUFFRUTICOSA; PAEONIFLORIN; FENNEL; BARK AB Based on traditional reports of the use of plants of the genus Paeonia in the treatment of epilepsy, we have screened extracts of the roots of three Greek Paeonia species (P. parnassica, P. mascula subsp. hellenica, P. clusii subsp. clusii) for anticonvulsant activity. This led to the identification of some interesting prophylactic anticonvulsant activity of the extracts of P. parnassica. Frorn the roots of this species, seventeen compounds were subsequently isolated and identified. Amongst these, seven contained the characteristic cage-like terpenic skeleton that is found only in plants of the genus Paeonia. Two of the above products: 4-O-methylpaeoniflorin (1) and paeonidanin (2) are described for the first time as natural products. The structures of all compounds have been elucidated on the basis of their spectral data. C1 Univ Athens, Dept Pharm, Lab Pharmacognosy & Nat Prod Chem, GR-15771 Athens, Greece. NINDS, NIH, Anticonvulsent Screening Program, Ctr Neurosci, Bethesda, MD 20892 USA. RP Skaltsounis, AL (reprint author), Univ Athens, Dept Pharm, Lab Pharmacognosy & Nat Prod Chem, GR-15771 Athens, Greece. EM skaltsounis@pharm.uoa.gr RI Magiatis, Prokopios/A-2008-2008; Kritsanida, Marina/S-7499-2016 NR 27 TC 3 Z9 3 U1 0 U2 2 PU NATURAL PRODUCTS INC PI WESTERVILLE PA 7963 ANDERSON PARK LN, WESTERVILLE, OH 43081 USA SN 1934-578X J9 NAT PROD COMMUN JI Nat. Prod. Commun. PY 2007 VL 2 IS 4 BP 351 EP 356 PG 6 WC Chemistry, Medicinal; Food Science & Technology SC Pharmacology & Pharmacy; Food Science & Technology GA 203XO UT WOS:000249007500003 ER PT J AU Nishio, M Watanabe, KI Sasaki, J Taya, C Takasuga, S Iizuka, R Balla, T Yamazaki, M Watanabe, H Itoh, R Kuroda, S Horie, Y Forster, I Mak, TW Yonekawa, H Penninger, JM Kanaho, Y Suzuki, A Sasaki, T AF Nishio, Miki Watanabe, Ken-ichi Sasaki, Junko Taya, Choji Takasuga, Shunsuke Iizuka, Ryota Balla, Tamas Yamazaki, Masakazu Watanabe, Hiroshi Itoh, Reietsu Kuroda, Shoko Horie, Yasuo Forster, Irmgard Mak, Tak W. Yonekawa, Hiromichi Penninger, Josef M. Kanaho, Yasunori Suzuki, Akira Sasaki, Takehiko TI Control of cell polarity and motility by the PtdIns(3,4,5)P-3 phosphatase SHIP1 SO NATURE CELL BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; GREEN FLUORESCENT PROTEIN; PHOSPHOINOSITIDE 3-KINASES; CHEMOATTRACTANT RECEPTOR; NEUTROPHIL CHEMOTAXIS; LEUKOCYTE CHEMOTAXIS; LIPID PRODUCTS; ACTIVATION; MIGRATION; ROLES AB Proper neutrophil migration into inflammatory sites ensures host defense without tissue damage. Phosphoinositide 3-kinase (PI(3)K) and its lipid product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) regulate cell migration, but the role of PtdIns(3,4,5)P-3-degrading enzymes in this process is poorly understood. Here, we show that Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1), a PtdIns(3,4,5)P-3 phosphatase, is a key regulator of neutrophil migration. Genetic inactivation of SHIP1 led to severe defects in neutrophil polarization and motility. In contrast, loss of the PtdIns(3,4,5)P-3 phosphatase PTEN had no impact on neutrophil chemotaxis. To study PtdIns(3,4,5)P-3 metabolism in living primary cells, we generated a novel transgenic mouse (AktPH-GFP Tg) expressing a bioprobe for PtdIns(3,4,5)P-3. Time-lapse footage showed rapid, localized binding of AktPH-GFP to the leading edge membrane of chemotaxing ship1(+/+)AktPH-GFP Tg neutrophils, but only diffuse localization in ship1(-/-)AktPH-GFP Tg neutrophils. By directing where PtdIns(3,4,5)P-3 accumulates, SHIP1 governs the formation of the leading edge and polarization required for chemotaxis. C1 Akita Univ, Sch Med, Dept Pathol & Immunol, Akita 0108543, Japan. Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan. Akita Univ, Sch Med, Dept Mol Biol, Akita 0108543, Japan. Tokyo Metropolitan Inst Med Sci, Dept Lab Anim Sci, Bunkyo Ku, Tokyo 1138613, Japan. Tokyo Metropolitan Inst Med Sci, Dept Pharmacol, Bunkyo Ku, Tokyo 1138613, Japan. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Akita Univ, Sch Med, Dept Gastroenterol, Akita 0108543, Japan. Univ Dusseldorf, Inst Umweltmed Forsch, D-40225 Dusseldorf, Germany. Campbell Familly Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada. Austrian Acad Sci, Inst Mol & Biotechnol, A-1030 Vienna, Austria. RP Sasaki, T (reprint author), Akita Univ, Sch Med, Dept Pathol & Immunol, 1-1-1 Hondo, Akita 0108543, Japan. EM tsasaki@med.akita-u.ac.jp RI Penninger, Josef/I-6860-2013; Forster, Irmgard/P-8545-2016; OI Penninger, Josef/0000-0002-8194-3777; Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS NR 49 TC 181 Z9 188 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2007 VL 9 IS 1 BP 36 EP U40 DI 10.1038/ncb1515 PG 16 WC Cell Biology SC Cell Biology GA 122VL UT WOS:000243255100010 PM 17173042 ER PT J AU Gold, R Stangel, M Dalakas, MC AF Gold, Ralf Stangel, Martin Dalakas, Marinos C. TI Drug Insight: the use of intravenous immunoglobulin in neurology - therapeutic considerations and practical issues SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review ID GUILLAIN-BARRE-SYNDROME; INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; MULTIFOCAL MOTOR NEUROPATHY; RANDOMIZED CONTROLLED-TRIAL; INCLUSION-BODY MYOSITIS; STIFF-PERSON SYNDROME; AMYLOID-BETA-PEPTIDE; DOUBLE-BLIND; PLASMA-EXCHANGE; IMMUNE GLOBULIN AB Over the past few years, we have achieved increasing success in the treatment of a number of autoimmune-mediated disorders affecting nerves and muscles. This success is partly attributable to the use of high-dose polyclonal intravenous immunoglobulin (IVIg), which has dramatically changed our treatment options. On the basis of results from controlled, but non-FDA-approved, clinical trials, IVIg is now the treatment of choice for Guillain-Barre syndrome, chronic idiopathic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy; IVIg offers rescue therapy for patients with rapidly worsening myasthenia gravis, and is a second-line therapy for dermatomyositis, stiff-person syndrome, and pregnancy-associated or postpartum multiple sclerosis attacks. The ability of IVIg to treat such immunologically diverse disorders effectively, coupled with its excellent safety profile, has led clinicians to use the drug more liberally, even in diseases for which the data are weak and not evidence-based and in patients with coexisting conditions. Use of IVIg for such indications can increase the risk of complications while raising the cost of the drug. Practical issues regarding dosing and frequency of infusions generate dilemmas in clinical practice. In this article, we review the current indications for IVIg treatment, address practical issues related to the use and costs of the drug, and summarize its mechanisms of action. C1 Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-44791 Bochum, Germany. Hannover Med Sch, Dept Neurol, D-3000 Hannover, Germany. Ctr Syst Neurosci, Hannover, Germany. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD USA. George Washington Univ, Washington, DC USA. RP Gold, R (reprint author), Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, Gudrunstr 56, D-44791 Bochum, Germany. EM ralf.gold@ruhr-uni-bochum.de NR 62 TC 97 Z9 98 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD JAN PY 2007 VL 3 IS 1 BP 36 EP 44 DI 10.1038/ncpneuro0376 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 122WG UT WOS:000243257500011 PM 17205073 ER PT J AU Klein, C Grudzien, M Appaswamy, G Germeshausen, M Sandrock, I Schaffer, AA Rathinam, C Boztug, K Schwinzer, B Rezaei, N Bohn, G Melin, M Carlsson, G Fadeel, B Dahl, N Palmblad, J Henter, JI Zeidler, C Grimbacher, B Welte, K AF Klein, Christoph Grudzien, Magda Appaswamy, Giridharan Germeshausen, Manuela Sandrock, Inga Schaffer, Alejandro A. Rathinam, Chozhavendan Boztug, Kaan Schwinzer, Beate Rezaei, Nima Bohn, Georg Melin, Malin Carlsson, Goran Fadeel, Bengt Dahl, Niklas Palmblad, Jan Henter, Jan-Inge Zeidler, Cornelia Grimbacher, Bodo Welte, Karl TI HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease) SO NATURE GENETICS LA English DT Article ID COLONY-STIMULATING-FACTOR; MYELOID PROGENITOR CELLS; PROTEIN HAX-1; MITOCHONDRIA; APOPTOSIS; DEATH; NEUTROPHILS; MUTATIONS; INTERACTS; LEUKEMIA AB Autosomal recessive severe congenital neutropenia (SCN)(1) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells(2,3), yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann(1). HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction(4) and cytoskeletal control(5,6). Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells. Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development. C1 Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany. Freiburg Univ Hosp, Med Ctr, Div Rheumatol & Clin Immunol, D-79106 Freiburg, Germany. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Tehran, Iran. Univ Childrens Hosp, Dept Genet & Pathol, S-75185 Uppsala, Sweden. Karolinska Univ Hosp, Karolinska Inst, Dept Woman & Child Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden. Karolinska Inst, Inst Environm Med, Div Biochem & Toxicol, S-17177 Stockholm, Sweden. Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med, S-14186 Stockholm, Sweden. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM klein.christoph@mh-hannover.de RI Schaffer, Alejandro/F-2902-2012; Rezaei, Nima/B-4245-2008 OI Rezaei, Nima/0000-0002-3836-1827 FU Intramural NIH HHS NR 30 TC 243 Z9 252 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2007 VL 39 IS 1 BP 86 EP 92 DI 10.1038/ng1940 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 121CU UT WOS:000243136500022 PM 17187068 ER PT J AU Mu, JB Awadalla, P Duan, JH McGee, KM Keebler, J Seydel, K McVean, GAT Su, XZ AF Mu, Jianbing Awadalla, Philip Duan, Junhui McGee, Kate M. Keebler, Jon Seydel, Karl McVean, Gilean A. T. Su, Xin-zhuan TI Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome SO NATURE GENETICS LA English DT Article ID DIVERSIFYING SELECTION; GENETIC DIVERSITY; MALARIA; RECOMBINATION; POLYMORPHISMS; ERYTHROCYTES; RESISTANCE; PROTEINS; LOCUS; ASSAY AB One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets(1). However, identifying those targets in a genome in which similar to 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures(2-6), genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes (similar to 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs (similar to 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per similar to 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. Univ Oxford, Dept Stat, Oxford OX1 3TG, England. RP Awadalla, P (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pawadalla@ncsu.edu; xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 29 TC 137 Z9 138 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2007 VL 39 IS 1 BP 126 EP 130 DI 10.1038/ng1924 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 121CU UT WOS:000243136500028 PM 17159981 ER PT J AU Matzinger, P AF Matzinger, Polly TI Friendly and dangerous signals: is the tissue in control? SO NATURE IMMUNOLOGY LA English DT Editorial Material ID INTRAEPITHELIAL LYMPHOCYTES; CELLS; SELF AB In their own defense, tissues send a panoply of signals that initiate immunity and guide the choice of effector class. T(H)1-T(H)2 and T-reg is far too simple a representation of the breathtaking variety of the resulting responses. C1 NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Matzinger, P (reprint author), NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pcm@helix.nih.gov NR 11 TC 273 Z9 291 U1 3 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2007 VL 8 IS 1 BP 11 EP 13 DI 10.1038/ni0107-11 PG 3 WC Immunology SC Immunology GA 118HZ UT WOS:000242934400005 PM 17179963 ER PT J AU Liu, EH Siegel, RM Harlan, DM O'Shea, JJ AF Liu, Eric H. Siegel, Richard M. Harlan, David M. O'Shea, John J. TI T cell-directed therapies: lessons learned and future prospects SO NATURE IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; ANTI-CD4 MONOCLONAL-ANTIBODY; RELAPSING MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; RENAL-TRANSPLANTATION; ALLOGRAFT-REJECTION; CROHNS-DISEASE; CLINICAL-TRIAL; BLOCKADE; IMMUNITY AB Agents interfering with T cell function are therapeutic mainstays for various autoimmune diseases and for transplant approaches to organ failure. The understanding of T cell biology has blossomed since the development of most agents now in use. Here we discuss T cell - specific agents now in use, others recently added to the therapeutic armamentarium and promising agents being investigated in clinical and preclinical studies. In addition, we reflect on the risks and benefits involved in the testing of such agents clinically, with examples of agents that have successfully been used in the clinic and agents that failed to reach therapeutic use. C1 NIDDK, Diabet Branch, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. RP Liu, EH (reprint author), NIDDK, Diabet Branch, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU Intramural NIH HHS NR 63 TC 51 Z9 53 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2007 VL 8 IS 1 BP 25 EP 30 DI 10.1038/ni1429 PG 6 WC Immunology SC Immunology GA 118HZ UT WOS:000242934400010 PM 17179969 ER PT J AU Bohn, G Allroth, A Brandes, G Thiel, J Glocker, E Schaffer, AA Rathinam, C Taub, N Teis, D Zeidler, C Dewey, RA Geffers, R Buer, J Huber, LA Welte, K Grimbacher, B Klein, C AF Bohn, Georg Allroth, Anna Brandes, Gudrun Thiel, Jens Glocker, Erik Schaffer, Alejandro A. Rathinam, Chozhavendan Taub, Nicole Teis, David Zeidler, Cornelia Dewey, Ricardo A. Geffers, Robert Buer, Jan Huber, Lukas A. Welte, Karl Grimbacher, Bodo Klein, Christoph TI A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14 SO NATURE MEDICINE LA English DT Article ID CHEDIAK-HIGASHI-SYNDROME; SEVERE CONGENITAL NEUTROPENIA; HERMANSKY-PUDLAK-SYNDROME; COLONY-STIMULATING FACTOR; GRANULE EXOCYTOSIS; GRISCELLI-SYNDROME; HUMAN-NEUTROPHILS; PROGENITOR CELLS; LINKAGE ANALYSIS; MYELOID CELLS AB Lysosome-related organelles have versatile functions, including protein and lipid degradation, signal transduction and protein secretion. The molecular elucidation of rare congenital diseases affecting endosomal-lysosomal biogenesis has given insights into physiological functions of the innate and adaptive immune system. Here, we describe a previously unknown human primary immunodeficiency disorder and provide evidence that the endosomal adaptor protein p14, previously characterized as confining mitogen-activated protein kinase (MAPK) signaling to late endosomes, is crucial for the function of neutrophils, B cells, cytotoxic T cells and melanocytes. Combining genetic linkage studies and transcriptional profiling analysis, we identified a homozygous point mutation in the 3' untranslated region (UTR) of p14 (also known as MAPBPIP), resulting in decreased protein expression. In p14-deficient cells, the distribution of late endosomes was severely perturbed, suggesting a previously unknown role for p14 in endosomal biogenesis. These findings have implications for understanding endosomal membrane dynamics, compartmentalization of cell signal cascades, and their role in immunity. C1 Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Cell Biol, D-30625 Hannover, Germany. Univ Hosp Freiburg, Div Clin Immunol & Rheumatol, D-79106 Freiburg, Germany. Natl Inst Hlth, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Med Univ Innsbruck, Div Cell Biol, A-6020 Innsbruck, Austria. Helmholtz Ctr Infect Res, HCI, Array Facil & Mucosal Immun, D-38124 Braunschweig, Germany. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM klein.christoph@mh-hannover.de RI Schaffer, Alejandro/F-2902-2012; OI Teis, David/0000-0002-8181-0253; Huber, Lukas Alfons/0000-0003-1116-2120 FU Intramural NIH HHS NR 42 TC 107 Z9 109 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2007 VL 13 IS 1 BP 38 EP 45 DI 10.1038/nm1528 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 123NE UT WOS:000243301800034 PM 17195838 ER PT J AU Hansen, A Chen, YD Inman, JM Phan, QN Qi, ZQ Xiang, CC Palkovits, M Cherman, N Kuznetsov, SA Robey, PG Mezey, E Brownstein, MJ AF Hansen, Arne Chen, Yidong Inman, Jason M. Phan, Quang N. Qi, Zhi-Qing Xiang, Charlie C. Palkovits, Miklos Cherman, Natasha Kuznetsov, Sergei A. Robey, Pamela G. Mezey, Eva Brownstein, Michael J. TI Sensitive and specific method for detecting G protein-coupled receptor mRNAs SO NATURE METHODS LA English DT Article AB G protein-coupled receptors ( GPCRs) mediate effects of extracellular signaling molecules in all the body's cells. These receptors are encoded by scarce mRNAs; therefore, detecting their transcripts with conventional microarrays is difficult. We present a method based on multiplex PCR and array detection of amplicons to assay GPCR gene expression with as little as 1 mu g of total RNA, and using it, we profiled three human bone marrow stromal cell (BMSC) lines. (c) 2007 Nature Publishing Group C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorder & Stroke, Neurochem Lab, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Inst Genom Res, Rockville, MD 20850 USA. Craig Venter Inst, Rockville, MD 20850 USA. RP Hansen, A (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 8 TC 11 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JAN PY 2007 VL 4 IS 1 BP 35 EP 37 DI 10.1038/NMETH977 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 122KK UT WOS:000243225600014 PM 17115035 ER PT J AU Baker, CI Hutchison, TL Kanwisher, N AF Baker, Chris I. Hutchison, Tyler L. Kanwisher, Nancy TI Does the fusiform face area contain subregions highly selective for nonfaces? SO NATURE NEUROSCIENCE LA English DT Letter C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Baker, CI (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,Bldg 10,Room 4C-104,MSC1366, Bethesda, MD 20892 USA. EM bakerchris@mail.nih.gov OI Baker, Chris/0000-0001-6861-8964 NR 1 TC 49 Z9 51 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 3 EP 4 DI 10.1038/nn0107-3 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100002 PM 17189940 ER PT J AU Simmons, WK Bellgowan, PSF Martin, A AF Simmons, W. Kyle Bellgowan, Patrick S. F. Martin, Alex TI Measuring selectivity in fMRI data SO NATURE NEUROSCIENCE LA English DT Letter C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Simmons, WK (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM alexmartin@mail.nih.gov RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 NR 3 TC 25 Z9 25 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 4 EP 5 DI 10.1038/nn0107-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100003 PM 17189941 ER PT J AU Harvey, BK Hope, BT Shaham, Y AF Harvey, Brandon K. Hope, Bruce T. Shaham, Yavin TI Tolerance to opiate reward: role of midbrain IRS2-Akt pathway SO NATURE NEUROSCIENCE LA English DT Editorial Material ID HEROIN; RATS; ADDICTION; MORPHINE; VECTORS; NEURONS AB Addicts report that opiate drugs lose their rewarding effects over time, but the molecular mechanisms underlying this effect are unknown. A study now reports that tolerance to morphine reward in rats is due to downregulation of IRS2-Akt signaling in the ventral tegmental area (VTA), the cell body region of the mesolimbic dopamine reward system. C1 NIA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Harvey, BK (reprint author), NIA, Intramural Res Program, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Harvey, Brandon/A-5559-2010; Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 15 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 9 EP 10 DI 10.1038/nn0107-9 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100004 PM 17189943 ER PT J AU Lerchner, A La Camera, G Richmond, B AF Lerchner, Alexander La Camera, Giancarlo Richmond, Barry TI Knowing without doing SO NATURE NEUROSCIENCE LA English DT Editorial Material ID DORSAL STRIATUM; BASAL GANGLIA AB Is it possible to know what to do without being able to act upon this knowledge? In a recent study, Atallah et al. show clear evidence that learning a new skill and expressing it are two separate steps that can be dissociated. C1 US Natl Inst Mental Hlth, NIH, Dept Hlth & Human Serv, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Lerchner, A (reprint author), US Natl Inst Mental Hlth, NIH, Dept Hlth & Human Serv, Neuropsychol Lab, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM lerchnera@mail.nih.gov; bjr@ln.nimh.nih.gov NR 12 TC 5 Z9 5 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2007 VL 10 IS 1 BP 15 EP 17 DI 10.1038/nn0107-15 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 120PC UT WOS:000243096100008 PM 17189947 ER PT J AU Nallamsetty, S Waugh, DS AF Nallamsetty, Sreedevi Waugh, David S. TI A generic protocol for the expression and purification of recombinant proteins in Escherichia coli using a combinatorial His(6)-maltose binding protein fusion tag SO NATURE PROTOCOLS LA English DT Article ID SOLUBLE-PROTEIN; AFFINITY TAGS; SOLUBILITY; VECTORS AB We describe a generic protocol for the overproduction and purification of recombinant proteins in Escherichia coli. The strategy utilizes a dual His(6)-maltose binding protein (HisMBP) affinity tag that can be removed from the target protein by digestion of the fusion protein at a designed site by tobacco etch virus protease. The MBP moiety serves to enhance the solubility and promote the proper folding of its fusion partners, and the polyhistidine tag facilitates its purification to homogeneity. This protocol is divided into three stages, each of which takes approximately 1 week to complete: (i) construction of a HisMBP fusion vector; (ii) a pilot experiment to assess the yield and solubility of the target protein; and (iii) the large-scale production and purification of the target protein. C1 [Nallamsetty, Sreedevi; Waugh, David S.] NCI, Ctr Canc Res, Macromol Crystallography Lab, Ft Detrick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Ctr Canc Res, Macromol Crystallography Lab, PO Box B, Ft Detrick, MD 21702 USA. EM waughd@ncifcrf.gov FU Intramural NIH HHS NR 18 TC 42 Z9 46 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 2 BP 383 EP 391 DI 10.1038/nprot.2007.50 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262GX UT WOS:000253138100019 PM 17406599 ER PT J AU Ramirez, DC Gomez-Mejiba, SE Mason, RP AF Ramirez, Dario C. Gomez-Mejiba, Sandra E. Mason, Ronald P. TI Immuno-spin trapping analyses of DNA radicals SO NATURE PROTOCOLS LA English DT Article ID HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; BUTYL HYDROPEROXIDE; ELECTRON-TRANSFER; STRAND BREAKS; IN-VIVO; PROTEIN; TRAPS; DMPO; IDENTIFICATION AB Immuno-spin trapping is a highly sensitive method for detecting DNA radicals in biological systems. This technique involves three main steps: (i) in situ and real-time trapping of DNA radicals with the nitrone spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), thus forming DMPO-DNA nitrone adducts (referred to here as nitrone adducts); (ii) purification of nitrone adducts; and (iii) analysis of nitrone adducts by heterogeneous immunoassays using Abs against DMPO. In experiments, DMPO is added prior to the formation of free radicals. It diffuses easily through all cell compartments and is present when DNA free radicals are formed as a result of oxidative damage. Due to its low toxicity, DMPO can be used in cells at high enough concentrations to out-compete the normal reactions of DNA radicals, thus ensuring a high yield of DNA nitrone adducts. Because both protein and DNA nitrone adducts are formed, it is important that the DNA be pure in order to avoid misinterpretations. Depending on the model under study, this protocol can be completed in as few as 6 h. C1 [Ramirez, Dario C.; Gomez-Mejiba, Sandra E.; Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Ramirez, DC (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr,Bldg 101,MD F0-02, Res Triangle Pk, NC 27709 USA. EM ramirez1@niehs.nih.gov RI RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 FU Intramural NIH HHS; NIEHS NIH HHS [1 K99 ES015415-01, R00 ES015415, R00 ES015415-02] NR 34 TC 38 Z9 39 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 3 BP 512 EP 522 DI 10.1038/nprot.2007.5 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262GY UT WOS:000253138200008 PM 17406615 ER PT J AU Hawkins, ME AF Hawkins, Mary E. TI Synthesis, purification and sample experiment for fluorescent pteridine-containing DNA: tools for studying DNA interactive systems SO NATURE PROTOCOLS LA English DT Article ID NUCLEOTIDE ANALOG 2-AMINOPURINE; KLENOW FRAGMENT; NUCLEOSIDE ANALOGS; COMPLEX-FORMATION; GUANOSINE-ANALOG; RNA-POLYMERASE; ACTIVE-SITE; OLIGONUCLEOTIDES; BINDING; DYNAMICS AB Fluorescent nucleoside analogs provide a means to study DNA interactive systems through direct measurement of fluorescence properties. As integrated parts of DNA, these probes provide opportunities for monitoring subtle changes in DNA structure as it meets and reacts with other molecules. This protocol describes modifications to standard DNA synthesis to efficiently use smaller volumes of the probe phosphoramidite, purification of pteridine-containing sequences and a deprotection procedure specific for 6MI-containing sequences. Yields for probe incorporation in DNA synthesis are comparable to those for standard phosphoramidites. Examples of the fluorescence signals one can expect are described. Automated synthesis, which is dependent on the length of the sequence, takes about 4-5 h for a 20-mer. The deprotection of 6MI-containing sequences takes approximately 6-7 h before the standard ammonium hydroxide overnight incubation. Purification through polyacrylamide gels, electroelution and ethanol precipitation can be accomplished in 6-8 h. C1 Natl Canc Inst, NIH, Oncal Branch, Bethesda, MD 20854 USA. RP Hawkins, ME (reprint author), Natl Canc Inst, NIH, Oncal Branch, 10 Ctr Dr,CRC 1-3872, Bethesda, MD 20854 USA. EM mh100x@nih.gov NR 29 TC 12 Z9 12 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 4 BP 1013 EP 1021 DI 10.1038/nprot.2007.150 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HC UT WOS:000253138600029 PM 17446875 ER PT J AU Xu, X Keefer, LK Ziegler, RG Veenstra, TD AF Xu, Xia Keefer, Larry K. Ziegler, Regina G. Veenstra, Timothy D. TI A liquid chromatography-mass spectrometry method for the quantitative analysis of urinary endogenous estrogen metabolites SO NATURE PROTOCOLS LA English DT Article ID ELECTROSPRAY-IONIZATION; DANSYL CHLORIDE; RECEPTOR-ALPHA; BREAST-CANCER; WOMEN; ASSAY; RADIOIMMUNOASSAY; 2-HYDROXYESTRONE; DERIVATIZATION; MECHANISMS AB The ability to measure estrogen metabolites (EMs) quantitatively is important for investigating their individual roles in cancer screening, treatment and prevention, as well as in a host of other hormone-related disorders. In this protocol we describe a method that is capable of quantitating 15 distinct EMs in urine. Endogenous EMs are quantitatively measured using a liquid chromatography tandem mass spectrometry method in which the spectrometer operates in a selected reaction monitoring mode. This method is capable of quantifying estrone and its 2-, and 4- and 16 alpha-hydroxy and its 2-, 4-methoxy derivatives, and 2-hydroxyestrone-3-methyl ether; 17 beta-estradiol and its 2-hydroxy, and 2- and 4-methoxy derivates, and estriol, 16-epiestriol, 17-epiestriol, and 16-ketoestradiol. The method requires only 0.5 ml of urine and approximately 60 urine samples can be quantitatively analyzed per week. C1 [Xu, Xia; Veenstra, Timothy D.] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Ziegler, Regina G.] NCI, Epidemiol Biostat Program, Div Canc Epidemiol Genet, Bethesda, MD 20892 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. EM veenstrat@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 23 TC 48 Z9 49 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 6 BP 1350 EP 1355 DI 10.1038/nprot.2007.176 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HF UT WOS:000253138900006 PM 17545972 ER PT J AU Mukhopadhyay, P Rajesh, M Hasko, G Hawkins, BJ Madesh, M Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Hasko, Gyoergy Hawkins, Brian J. Madesh, Muniswamy Pacher, Pal TI Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy SO NATURE PROTOCOLS LA English DT Article ID NF-KAPPA-B; OXIDATIVE STRESS; FLUORESCENCE; PROBES; DEATH; HYDROETHIDINE; INHIBITION; ACTIVATION; MECHANISMS; ETHIDIUM AB Annexin V and Sytox Green are widely used markers to evaluate apoptosis in various cell types using flow cytometry and fluorescent microscopy. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated for confocal microscopy and flow cytometry. This protocol describes simultaneous measurements of mitochondrial superoxide generation with apoptotic markers (Annexin V and Sytox Green) by both flow cytometry and confocal microscopy in endothelial cell lines. The advantages of the described flow cytometry method over other cell-based techniques are the tremendous speed (1-2 h), exquisite precision and the possibility of simultaneous quantitative measurements of mitochondrial superoxide generation and apoptotic (and other) markers, with maximal preservation of cellular functions. This method combined with fluorescent microscopy may be very useful to reveal important spatial-temporal changes in mitochondrial superoxide production and execution of programmed cell death in virtually any cell type. C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Hawkins, Brian J.; Madesh, Muniswamy] Univ Penn, Inst Environm Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999]; PHS HHS [ISIORR022511-01A1] NR 29 TC 179 Z9 186 U1 1 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 9 BP 2295 EP 2301 DI 10.1038/nprot.2007.327 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HM UT WOS:000253139600027 PM 17853886 ER PT J AU Knight, ZA Feldman, ME Balla, A Balla, T Shokat, KM AF Knight, Zachary A. Feldman, Morri E. Balla, Andras Balla, Tamas Shokat, Kevan M. TI A membrane capture assay for lipid kinase activity SO NATURE PROTOCOLS LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 4-KINASE; HUMAN CANCERS; CLONING; FAMILY; CELL; RAS; INFLAMMATION; P110-ALPHA; INHIBITORS AB Phosphoinositide kinases such as PI3-kinase synthesize lipid second messengers that control diverse cellular processes. Recently, these enzymes have emerged as an important class of drug targets, and there is significant interest in discovering new lipid kinase inhibitors. We describe here a procedure for the high-throughput determination of lipid kinase inhibitor IC50 values. This assay exploits the fact that phosphoinositides, but not nucleotides such as ATP, bind irreversibly to nitrocellulose membranes. As a result, the radiolabeled lipids from a kinase assay can be isolated by spotting the crude reaction on a nitrocellulose membrane and then washing. We show that diverse phosphoinositide kinases can be assayed using this approach and outline how to perform the assay in 96-well plates. We also describe a MATLAB script that automates the data analysis. The complete procedure requires 3-4 h. C1 [Knight, Zachary A.; Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. [Feldman, Morri E.] Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94158 USA. [Balla, Andras; Balla, Tamas] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Shokat, KM (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA. EM shokat@cmp.ucsf.edu OI Knight, Zachary/0000-0001-7621-1478; Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 FU Howard Hughes Medical Institute; Intramural NIH HHS; NIGMS NIH HHS [GM08284, T32 GM008284] NR 31 TC 24 Z9 24 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 10 BP 2459 EP 2466 DI 10.1038/nprot.2007.361 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HP UT WOS:000253139900018 PM 17947987 ER PT J AU Kalueff, AV Aldridge, JW LaPorte, JL Murphy, DL Tuohimaa, P AF Kalueff, Allan V. Aldridge, J. Wayne LaPorte, Justin L. Murphy, Dennis L. Tuohimaa, Pentti TI Analyzing grooming microstructure in neurobehavioral experiments SO NATURE PROTOCOLS LA English DT Article ID COMPLEX MOVEMENT SEQUENCE; DOPAMINE D1 AGONISTS; SUPER-STEREOTYPY; ANALYSIS ALGORITHM; STRESS RESEARCH; MOUSE STRAINS; SERIAL ORDER; MICE LACKING; MUTANT MICE; BEHAVIOR AB Grooming is a commonplace, robust behavior in rodent species. It has been shown to be highly sensitive to a number of experimental factors, making it an ideal target for manipulation. The complex patterning of grooming in rodents, which usually proceeds in a cephalo-caudal direction and involves several distinct stages, can be dissected into its constituent parts and microstructures. Several grooming patterning analysis methods are described in the protocol that allow for an assessment of this behavior based on measurements of grooming activity and its sequencing. Additionally, grooming can be evaluated in reference to the regional distribution and syntax in which it occurs. Owing to the ever-increasing number of rodent models that have strong grooming phenotypes, this high-throughput in-depth analysis is becoming crucial for biomedical research. C1 [Kalueff, Allan V.; LaPorte, Justin L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Kalueff, Allan V.; Tuohimaa, Pentti] Tampere Univ, Sch Med, Dept Anat, Tampere 33014, Finland. [Aldridge, J. Wayne] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 56 TC 58 Z9 58 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 10 BP 2538 EP 2544 DI 10.1038/nprot.2007.367 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HP UT WOS:000253139900027 PM 17947996 ER PT J AU Murphy, WJ O'Brien, SJ AF Murphy, William J. O'Brien, Stephen J. TI Designing and optimizing comparative anchor primers for comparative gene mapping and phylogenetic inference SO NATURE PROTOCOLS LA English DT Article ID TAGGED SEQUENCES CATS; CANINE GENOME; RADIATION; CONSERVATION; MAMMALS; MAPS AB Here we describe protocols for designing, optimizing and implementing conserved anchor primers for use in genome mapping or phylogenetic applications, with particular emphasis on homologous gene sequences among mammals. The increasing number of whole genome sequences in public databases makes this approach applicable across a wide range of taxa. Genome sequences from representatives of two or more divergent subclades within a taxonomic group of interest are used to identify candidate local alignments (i.e., exons, exons spanning introns or conserved 5'- or 3'-untranslated regions) that contain sequences with appropriate variability for the chosen downstream application. PCR primers are designed to maximize amplification success across a broad range of taxa, and are optimized under a touchdown thermocycling protocol. Based on the initial optimization results, primers are selected for application in a diverse sampling of species, or for mapping the genome of a target species of interest. We discuss factors that have to be considered for experimental design of broad-scope phylogenetic studies. With this protocol, primers can be designed, optimized and implemented within as little as 1-2 weeks. C1 [Murphy, William J.] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. [O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. EM wmurphy@cvm.tamu.edu; obrien@ncifcrf.gov NR 18 TC 14 Z9 15 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2007 VL 2 IS 11 BP 3022 EP 3030 DI 10.1038/nprot.2007.429 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 262HQ UT WOS:000253140000042 PM 18007639 ER PT J AU Grewal, SIS Jia, ST AF Grewal, Shiv I. S. Jia, Songtao TI Heterochromatin revisited SO NATURE REVIEWS GENETICS LA English DT Review ID HISTONE H3 METHYLATION; FISSION YEAST CENTROMERE; DEPENDENT RNA-POLYMERASE; EMBRYONIC STEM-CELLS; JMJC DOMAIN PROTEIN; DOUBLE-STRANDED-RNA; NUCLEAR-ORGANIZATION; GENE-EXPRESSION; CHROMOSOME SEGREGATION; LYSINE-9 METHYLATION AB The formation of heterochromatin, which requires methylation of histone H3 at lysine 9 and the subsequent recruitment of chromodomain proteins such as heterochromatin protein HP1, serves as a model for the role of histone modifications and chromatin assembly in epigenetic control of the genome. Recent studies in Schizosaccharomyces pombe indicate that heterochromatin serves as a dynamic platform to recruit and spread a myriad of regulatory proteins across extended domains to control various chromosomal processes, including transcription, chromosome segregation and long-range chromatin interactions. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU Intramural NIH HHS NR 146 TC 674 Z9 694 U1 5 U2 74 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JAN PY 2007 VL 8 IS 1 BP 35 EP 46 DI 10.1038/nrg2008 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 118HY UT WOS:000242934300014 PM 17173056 ER PT J AU Block, ML Zecca, L Hong, JS AF Block, Michelle L. Zecca, Luigi Hong, Jau-Shyong TI Microglia-mediated neurotoxicity: uncovering the molecular mechanisms SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; NIGRAL DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE BRAINS; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; AMYOTROPHIC-LATERAL-SCLEROSIS; IMMUNODEFICIENCY-VIRUS TYPE-1; ROTENONE-INDUCED DEGENERATION; ACTIVATED PROTEIN-KINASE AB Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. Recent studies show that in response to certain environmental toxins and endogenous proteins, microglia can enter an overactivated state and release reactive oxygen species (ROS) that cause neurotoxicity. Pattern recognition receptors expressed on the microglial surface seem to be one of the primary, common pathways by which diverse toxin signals are transduced into ROS production. Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease. C1 NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. Italian Natl Res Council, Inst Biomed Technol, I-20090 Segrate, Milano, Italy. RP Block, ML (reprint author), NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. EM Block@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [K99 ES015409, K99 ES015409-01] NR 233 TC 1591 Z9 1639 U1 48 U2 270 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JAN PY 2007 VL 8 IS 1 BP 57 EP 69 DI 10.1038/nrn2038 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 119EE UT WOS:000242994200016 PM 17180163 ER PT J AU Wlodawer, A AF Wlodawer, Alexander TI Natalia Sergeevna Andreeva - 1922-2006 - Obituary SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Biographical-Item C1 NCI, Canc Res Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Canc Res Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2007 VL 14 IS 1 BP 2 EP 2 DI 10.1038/nsmb0107-2 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 124BS UT WOS:000243342600002 ER PT J AU Moon, AF Garcia-Diaz, M Bebenek, K Davis, BJ Zhong, XJ Ramsden, DA Kunkel, TA Pedersen, LC AF Moon, Andrea F. Garcia-Diaz, Miguel Bebenek, Katarzyna Davis, Bryan J. Zhong, Xuejun Ramsden, Dale A. Kunkel, Thomas A. Pedersen, Lars C. TI Structural insight into the substrate specificity of DNA Polymerase mu SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID BASE EXCISION-REPAIR; CRYSTAL-STRUCTURES; POL-MU; TERMINAL DEOXYNUCLEOTIDYLTRANSFERASE; V(D)J RECOMBINATION; LESION BYPASS; MINOR-GROOVE; LAMBDA; BETA; MECHANISM AB DNA polymerase l (Pol mu) is a family X enzyme with unique substrate specificity that contributes to its specialized role in nonhomologous DNA end joining (NHEJ). To investigate Pol mu's unusual substrate specificity, we describe the 2.4 angstrom crystal structure of the polymerase domain of murine Pol l bound to gapped DNA with a correct dNTP at the active site. This structure reveals substrate interactions with side chains in Pol mu that differ from other family X members. For example, a single amino acid substitution, H329A, has little effect on template-dependent synthesis by Pol mu from a paired primer terminus, but it reduces both template-independent and template-dependent synthesis during NHEJ of intermediates whose 3' ends lack complementary template strand nucleotides. These results provide insight into the substrate specificity and differing functions of four closely related mammalian family X DNA polymerases. C1 NIEHS, Struct Biol Lab, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, US Dept Hlth & Human Serv, 111 TW Alexander Dr,MD F3-09, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA097096, R01 CA084442] NR 46 TC 60 Z9 63 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2007 VL 14 IS 1 BP 45 EP 53 DI 10.1038/nsmb1180 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 124BS UT WOS:000243342600013 PM 17159995 ER PT J AU Tessema, E Warrier, I Lulic-Botica, M Reed, M Blumer, J Aranda, JV AF Tessema, E. Warrier, I. Lulic-Botica, M. Reed, M. Blumer, J. Aranda, J. V. TI Pharmacokinetics (PK) of intravenous azithromycin in preterm newborns SO NEONATOLOGY LA English DT Meeting Abstract C1 Childrens Hosp Michigan, PPRU, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-7800 J9 NEONATOLOGY JI Neonatology PY 2007 VL 92 IS 4 MA 33 BP 290 EP 291 PG 2 WC Pediatrics SC Pediatrics GA 227KJ UT WOS:000250655300043 ER PT J AU West, M Cybulla, M Feriozzi, S Schwarting, A Schiffmann, R Mehta, A Sunder-Plassmann, G AF West, Michael Cybulla, Markus Feriozzi, Sandro Schwarting, Andreas Schiffmann, Raphael Mehta, Atul Sunder-Plassmann, Gere CA FOS Investigators TI Renal function in patients with fabry disease on enzyme replacement therapy (ERT) SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 44th ERA-EDTA Congress CY JUN 22-24, 2007 CL Barcelona, SPAIN SP ERA-EDTA C1 Dalhousie Univ, Dept Med, Halifax, NS, Canada. Univ Hosp, Dept Nephrol, Freiberg, Germany. Belcolle Hosp, Dept Nephrourol, Viterbo, Italy. Johannes Gutenberg Univ Mainz, Dept Med, Mainz, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Royal Free Hosp, Dept Haematol, London NW3 2QG, England. Med Univ Vienna, Dept Med, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PY 2007 VL 22 SU 6 BP 13 EP 13 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 264WH UT WOS:000253320600029 ER PT J AU Topaloglu, R Tinloy, B Coskun, T Gunay-Aygun, M Jeong, A Bakkaloglu, A Besbas, N Ozen, S Kalkanoglu-Sivri, S Gahl, WA Kleta, R AF Topaloglu, Rezan Tinloy, Bradford Coskun, Turgay Gunay-Aygun, Meral Jeong, Anna Bakkaloglu, Aysin Besbas, Nesrin Ozen, Seza Kalkanoglu-Sivri, Serap Gahl, William A. Kleta, Robert TI Molecular basis of cystinosis in Turkish patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 44th ERA-EDTA Congress CY JUN 22-24, 2007 CL Barcelona, SPAIN SP ERA-EDTA C1 Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PY 2007 VL 22 SU 6 BP 30 EP 31 PG 2 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 264WH UT WOS:000253320600079 ER PT J AU Sunder-Plassmann, G Beck, M Clarke, J Linhart, A Schiffmann, R Mehta, A AF Sunder-Plassmann, Gere Beck, Michael Clarke, Joe Linhart, Ales Schiffmann, Raphael Mehta, Atul CA FOS Investigators TI Renal function in patients with Fabry disease: Data from FOS - The Fabry Outcome Survey SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 44th ERA-EDTA Congress CY JUN 22-24, 2007 CL Barcelona, SPAIN SP ERA-EDTA C1 Med Univ Vienna, Dept Med 3, Vienna, Austria. Johannes Gutenberg Univ Mainz, Dept Pediat, D-6500 Mainz, Germany. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Charles Univ Prague, Dept Internal Med 2, Prague, Czech Republic. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Royal Free Hosp, Dept Haematol, London NW3 2QG, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PY 2007 VL 22 SU 6 BP 32 EP 33 PG 2 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 264WH UT WOS:000253320600085 ER PT J AU Zink, M Meyer-Lindenberg, A AF Zink, M. Meyer-Lindenberg, A. TI Molecular neurobiology of schizophrenia SO NERVENHEILKUNDE LA German DT Review DE magnetic resonance tomography; neurobiology; neurogenetics; pathogenesis; schizophrenia ID MAGNETIC-RESONANCE-SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; CARDIO-FACIAL SYNDROME; LONG-TERM TREATMENT; AMINO-ACID OXIDASE; GENE-EXPRESSION; ANIMAL-MODELS; NMDA RECEPTOR; WHITE-MATTER; PREPULSE INHIBITION AB Nourobiological theories about the molecular pathogenesis of psychotic disorders were first developed in the Hippocratic opus "The sacred disease". Pharmacological concepts of schizophrenia were guided by observations of psychotomimetic effects of dopaminergic or anti-glutamatergic substances, whereas antidopaminergic agents were antipsychotic. In parallel, neuropathological investigations accumulated evidence in favour of a neurodevelopmental theory of schizophrenia. A set of chromosomal regions linked to increased disease risk were defined by neurogenetic studies and many candidate genes such as dysbindin, neuregulin und COMT were reported. As a tool to test molecular hypotheses, several animal models were established. Neuropsychology, structural and functional magnetic resonance tomography (fMRT) do not reach a molecular resolution. However, the impact of genetic variation on neural function can be studied using translational imaging genetics. In conclusion, the combination of several neurobiological methods improves our knowledge of the pathogenesis of schizophrenia and can facilitate the development of innovative treatment approaches. C1 Klin Psychiat & Psychotherapie, Zent Inst Seel Gesundheit, D-68072 Mannheim, Germany. NIMH, Univ Syst Neurosci Psychiat, Bethesda, MD USA. RP Zink, M (reprint author), Klin Psychiat & Psychotherapie, Zent Inst Seel Gesundheit, Postfach 122120, D-68072 Mannheim, Germany. EM mathias.zink@zi-mannheim.de NR 139 TC 0 Z9 0 U1 6 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PY 2007 VL 26 IS 10 BP 882 EP 890 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 222ZJ UT WOS:000250337200006 ER PT J AU Martin, A AF Martin, Alex BE Hart, J Kraut, MA TI Neural foundations for conceptual representations: Evidence from functional brain imaging SO NEURAL BASIS OF SEMANTIC MEMORY LA English DT Article; Book Chapter ID HUMAN VISUAL-CORTEX; CATEGORY-SPECIFIC DEFICITS; FUSIFORM FACE AREA; BIOLOGICAL MOTION; TEMPORAL CORTEX; OCCIPITOTEMPORAL CORTEX; MANIPULATABLE OBJECTS; PREFRONTAL CORTEX; SEMANTIC MEMORY; MENTAL-IMAGERY C1 NIMH, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Bldg 10,Room 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. NR 91 TC 12 Z9 14 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA BN 978-0-521-84870-1 PY 2007 BP 302 EP 330 DI 10.1017/CBO9780511544965.013 D2 10.1017/CBO9780511544965 PG 29 WC Neurosciences; Neuroimaging; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA BXO20 UT WOS:000296567900013 ER PT J AU Strozyk, D White, LR Petrovitch, H Geerlings, MI Remaley, AT Launer, LJ AF Strozyk, Dorothea White, Lon R. Petrovitch, Helen Geerlings, Mirjam I. Remaley, Alan T. Launer, Lenore J. TI Sex hormones and neuropathology in elderly men: The HAAS SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; neuritic plaques; neurofibrillary tangles; apolipoprotein E; amyloid precursor protein; cerebral amyloid angiopathy; sex hormone binding globulin; testosterone; estradiol; high density; lipoprotein cholesterol; sex hormones; neuropathology ID BETA-AMYLOID PEPTIDES; ALZHEIMERS-DISEASE; FREE TESTOSTERONE; POSTMENOPAUSAL WOMEN; ENDOGENOUS ESTRADIOL; COGNITIVE FUNCTION; VASCULAR DEMENTIA; OLDER MEN; ANDROGENS; RISK AB Experimental studies suggest 17-beta estradiol (E2) and testosterone (T) may have neuroprotective proper-ties that are associated with Alzheimer's and vascular pathology. However, there are limited studies correlating steroid hormones with autopsy findings in humans. In this community-based autopsy study of elderly men (n=232) participating in the Honolulu Asia Aging Study, we found a significant decrease of neurofibrillary tangles in the highest tertile of free serum estradiol [IRR = 0.43 (0.3-0.7)] after controlling for age at blood draw, interval from blood draw until death, ApoE allele, and socio-demographic health factors. Higher Free-T levels were associated with a twofold increased risk for micro infarcts [IRR=2.2; 95% CI (1.2-4.1)]. There was no association between sex hormones and amyloid plaques or cerebral amyloid angiopathy. This community-based autopsy study suggests that peripheral levels of sex hormones are associated with neurofibrillary tangles and micro-infarcts, but not with other neuropathologic markers of brain disease in elderly men. Published by Elsevier Inc. C1 NIA, NIH, LEDB, Bethesda, MD 20892 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, NIH, LEDB, Gateway Bldg 3C-309, Bethesda, MD 20892 USA. EM launerl@mail.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [N01-HC-0-5102]; NIA NIH HHS [N01-AG-4-2149] NR 35 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2007 VL 28 IS 1 BP 62 EP 68 DI 10.1016/j.neurobiolaging.2005.11.010 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 115ND UT WOS:000242740100008 PM 16500732 ER PT J AU Sumner, CJ Fischbeck, KH AF Sumner, Charlotte J. Fischbeck, Kenneth H. BE Gilman, S TI Spinal Muscular Atrophy SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE motor neuron; spinal muscular atrophy; survival motor neuron ID MOTOR-NEURON SMN; EXONIC SPLICING ENHANCER; VALPROIC ACID INCREASES; FULL-LENGTH SMN; MOUSE MODEL; DETERMINING GENE; SINGLE NUCLEOTIDE; IN-VITRO; SURVIVAL; PROTEIN C1 [Sumner, Charlotte J.; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Sumner, CJ (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 501 EP 511 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000045 ER PT J AU Condon, TP Balmer, CW AF Condon, Timothy P. Balmer, Curtis W. BE Gilman, S TI Neurobiology of Drug Addiction SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE addiction; impulsivity; incentive salience; motive circuit; relapse; reward ID ORBITOFRONTAL CORTEX; DECISION-MAKING; COCAINE SEEKING; IMPULSIVITY; RELAPSE; ABUSE; STRESS; ALCOHOL; REWARD; RISK C1 [Condon, Timothy P.; Balmer, Curtis W.] NIDA, JBS Int Inc, NIH, Bethesda, MD 20892 USA. RP Condon, TP (reprint author), NIDA, JBS Int Inc, NIH, Bethesda, MD 20892 USA. NR 36 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 771 EP 779 PG 9 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000072 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. BE Gilman, S TI Immunobiology of Autoimmune Inflammatory Myopathies SO NEUROBIOLOGY OF DISEASE LA English DT Article; Book Chapter DE inclusion body myositis; major histocompatibility complex class I-associated signaling pathways; polymyositis; stress response; T cell-mediated cytotoxicity ID INCLUSION-BODY MYOSITIS; ENDOPLASMIC-RETICULUM STRESS; MUSCLE; DERMATOMYOSITIS; POLYMYOSITIS; MECHANISMS; EXPRESSION C1 NINDS, NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, NIH, Neuromuscular Dis Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-046638-5 PY 2007 BP 957 EP 968 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BCO40 UT WOS:000310853000088 ER PT J AU Nadon, NL AF Nadon, Nancy L. TI Animal models in gerontology research SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID EPILEPTIC EL MICE; ENVIRONMENTAL ENRICHMENT; SURVIVAL CHARACTERISTICS; STRAIN DIFFERENCES; BROWN-NORWAY; RAT STRAINS; AGE; MOUSE; RESTRICTION; FISCHER-344 AB Animal models have paved the way for the vast majority of advances in biomedical research. Studies Oil aged animals are essential for understanding the processes Inherent in normal aging and the progression of age-related diseases. Animal models arc used to identify physiological changes with age, to identify the genetic basis of normal aging and age-associated disease and degeneration, and to test potential therapeutic interventions. This chapter will focus on rodent models and will summarize Important considerations for the use of animals in aging research in general and in modeling geriatric epilepsy. C1 NIA, Bethesda, MD 20892 USA. RP Nadon, NL (reprint author), NIA, Bethesda, MD 20892 USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 15 EP 27 DI 10.1016/S0074-7742(06)81002-0 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400002 PM 17433915 ER PT J AU Murphree, LJ Rundhaugen, LM Kelly, KM AF Murphree, Lauren J. Rundhaugen, Lynn M. Kelly, Kevin M. TI Animal models of geriatric epilepsy SO NEUROBIOLOGY OF EPILEPSY AND AGING SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID CA3 CELL GRAFTS; PENTYLENETETRAZOLE-KINDLING MODEL; INDUCED STATUS EPILEPTICUS; INDUCED MAXIMAL SEIZURE; TEMPORAL-LOBE EPILEPSY; KAINIC ACID; OLD RATS; ELECTROCONVULSIVE SHOCK; ELECTRICAL STIMULATION; MESSENGER-RNA AB Geriatric epilepsy is a significant clinical problem that has not been Studied adequately in animal models. This chapter will review the available literature with particular attention to models that have demonstrated how acute seizures and epilepsy in aged animals differ from those of younger animals. Studies include several strains of mice [e.g., El, DBA, senescence-accelerated Mouse (SAM), Cacnb4 knockout] as well as acute seizure models in common strains of aged mice. Aged rats (including Fischer 344, Wistar, and Sprague-Dawley) have been used in acute seizure, lesion, and epilepsy models. This area of research remains largely unexplored and therefore provides numerous opportunities for new investigations. C1 SRA Int Inc, Fairfax, VA 22033 USA. NINDS, NIH, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Dept Neurol, Pittsburgh, PA 15212 USA. RP Murphree, LJ (reprint author), SRA Int Inc, Fairfax, VA 22033 USA. NR 60 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 81 BP 29 EP 40 DI 10.1016/S0074-7742(06)81003-2 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BGC21 UT WOS:000245980400003 PM 17433916 ER PT S AU Kiyatkin, EA AF Kiyatkin, Eugene A. BE Sharma, HS TI Physiological and pathological brain hyperthermia SO NEUROBIOLOGY OF HYPERTHERMIA SE Progress in Brain Research LA English DT Review DE brain temperature; metabolism; cerebral blood flow; hyperthermia; arousal; sexual behavior; physical exercise; psychomotor stimulants; hot and humid environment; neural damage; neurotoxicity ID CEREBRAL-BLOOD-FLOW; LOCALIZED THERMAL-CHANGES; HEART-RATE; PROLONGED EXERCISE; BODY-TEMPERATURE; MDMA ECSTASY; IN-VITRO; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHAMPHETAMINE NEUROTOXICITY; DOPAMINERGIC NEUROTOXICITY AB While brain temperature is usually considered a stable, tightly regulated parameter, recent animal research revealed relatively large and rapid brain temperature fluctuations (similar to 3 degrees C) during various forms of naturally occurring physiological and behavioral activities. This work demonstrates that physiological brain hyperthermia has an intra-brain origin, resulting from enhanced neural metabolism and increased intra-brain heat production, and discusses its possible mechanisms and functional consequences. This work also shows that brain hyperthermia may also be induced by various drugs of abuse. While each individual drug (i.e., heroin, cocaine, meth-amphetamine, MDMA) has its own, dose-dependent effects on brain and body temperatures, these effects are strongly modulated by the individual's activity state and environmental conditions, showing dramatic alterations during the development of drug-taking behavior. While brain temperatures may also increase due to environmental overheating and diminished heat dissipation from the brain, adverse environmental conditions and physiological activation strongly potentiate thermal effects of psychomotor stimulant drugs, resulting in dangerous brain overheating. Since hyperthermia exacerbates drug-induced toxicity and is destructive to neural cells and brain functions, use of these drugs under conditions that restrict heat loss may pose a significant health risk, resulting in both acute life-threatening complications and chronic destructive CNS changes. We argue that brain temperature is an important physiological parameter, affecting various neural functions, and show the potential of brain temperature monitoring for studying alterations in metabolic neural activity under physiological and pathological conditions. Finally, we discuss brain temperature as a factor affecting various neuronal and neurochemical evaluations made in different animal preparations (in vitro slices, general anesthesia, awake, freely moving conditions) and consider a possible contribution of temperature fluctuations to behavior-related and drug-induced alterations in neuronal and neurochemical parameters. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS NR 137 TC 13 Z9 13 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-51926-9 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 162 BP 219 EP 243 DI 10.1016/S0079-6123(06)62012-8 PG 25 WC Neurosciences SC Neurosciences & Neurology GA BGY46 UT WOS:000251354900012 PM 17645922 ER PT J AU Gimenez-Llort, L Schiffmann, SN Shmidt, T Canela, L Camon, L Wassholm, M Canals, M Terasmaa, A Fernandez-Teruel, A Tobena, A Popova, E Ferre, S Agnati, L Ciruela, F Martinez, E Scheel-Kruger, J Lluis, C Franco, R Fuxe, K Bader, M AF Gimenez-Llort, Lydia Schiffmann, Serge N. Shmidt, Tanja Canela, Laia Camon, Lluisa Wassholm, Monica Canals, Meritxell Terasmaa, Anton Fernandez-Teruel, Albert Tobena, Adolf Popova, Elena Ferre, Sergi Agnati, Luigi Ciruela, Francisco Martinez, Emili Scheel-Kruger, Joergen Lluis, Carmen Franco, Rafael Fuxe, Kjell Bader, Michael TI Working memory deficits in transgenic rats overexpressing human adenosine A(2A) receptors in the brain SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE adenosine receptors; dopamine receptors; transgenic rat; memory; prefrontal cortex; heterodimerization ID LONG-TERM POTENTIATION; BIOLUMINESCENCE ENERGY-TRANSFER; AGONIST H-3 CGS-21680; DOPAMINE-D-2 RECEPTORS; PREFRONTAL CORTEX; MICE LACKING; QUANTITATIVE ASSESSMENT; CINGULATE CORTEX; BLOOD-PRESSURE; BASAL GANGLIA AB Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A(2A) receptor (A(2A)R) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A(2A)Rs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A(2A)Rs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A(2A)Rs. TGR(NSEhA(2A)) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and doparninergic function, the present results render the novel TGR(NSEhA(2A)) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A(2A)Rs or to dopaminergic preftontal dysfunction as seen in schizophrenic or Parkinson's disease patients. (c) 2006 Elsevier Inc. All rights reserved. C1 Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Autonomous Univ Barcelona, Med Psychol Unit, Dept Psychiat & Forens Med, Sch Med,Inst Neurosci, Barcelona, Spain. Univ Libre Bruxelles, Lab Neurophysiol CP601, Brussels, Belgium. CSIC, Inst Biomed Invest Barcelona, IDIBAPS, Barcelona, Catalonia, Spain. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Catalonia, Spain. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. Natl Inst Drug Abuse, Behav Neurosci Branch, NIH, Baltimore, MD USA. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. NeuroSearch AS, Dept Behav Pharmacol, Ballerup, Denmark. RP Fuxe, K (reprint author), Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. EM Kjell.Fuxe@neuro.ki.se; mbader@mdc-berlin.de RI tobena, adolf/G-1032-2010; Fernandez-Teruel, Alberto/F-9374-2011; Ferre, Sergi/K-6115-2014; MARTINEZ, EMILI/K-8009-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Terasmaa, Anton/I-3312-2015; OI Fernandez-Teruel, Alberto/0000-0001-5993-7058; Ferre, Sergi/0000-0002-1747-1779; MARTINEZ, EMILI/0000-0002-3624-6489; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Terasmaa, Anton/0000-0002-5139-1764; Tobena, Adolf/0000-0001-6137-0660; Canals, Meritxell/0000-0002-7942-5006; Bader, Michael/0000-0003-4780-4164 NR 73 TC 56 Z9 57 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD JAN PY 2007 VL 87 IS 1 BP 42 EP 56 DI 10.1016/j.nlm.2006.05.004 PG 15 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 128FK UT WOS:000243643400004 PM 16824773 ER PT J AU Kalueff, AV AF Kalueff, A. V. TI Mapping convulsants' binding to the GABA-A receptor chloride ionophore: A proposed model for channel binding sites SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE GABA-A receptors; ionophore; channel chemoconvulsants; binding sites; point mutagenesis ID GAMMA-AMINOBUTYRIC-ACID; NICOTINIC ACETYLCHOLINE-RECEPTOR; BETA-LACTAM ANTIBIOTICS; CENTRAL-NERVOUS-SYSTEM; PICROTOXIN RECEPTOR; POINT MUTATION; MULTIPLE MECHANISMS; PROTEIN MOBILITY; PENICILLIN-G; AMINO-ACID AB Gamma-aminobutyric acid (GABA) type A receptors play a key role in brain inhibitory neurotransmission, and are ligand-activated chloride channels blocked by numerous convulsant ligands. Here we summarize data on binding of picrotoxin, tetrazoles, beta-lactams, bicyclophosphates, butyrolactones and neurotoxic pesticides to GABA-A ionophore, and discuss functional and structural overlapping of their binding sites. The paper reviews data on convulsants' binding sensitivity to different point mutations in ionophore-lining second trans-membrane domains of GABA-A subunits, and maps possible location of convulsants' sites within the chloride ionophore. We also discuss data on inhibition of glycine, glutamate, serotonin (5-HT3) and N-acetylcholine receptors by GABA-A channel blockers, and examine the applicability of this model to other homologous ionotropic receptors. Positioning various convulsant-binding sites within ionophore of GABA-A receptors, this model enables a better understanding of complex architectonics of ionotropic receptors, and may be used for developing new channel-modulating drugs. Published by Elsevier Ltd. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS [, NIH0012391104]; PHS HHS [NIH0012391104] NR 117 TC 16 Z9 17 U1 0 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 JAN PY 2007 VL 50 IS 1 BP 61 EP 68 DI 10.1016/j.neuint.2006.07.004 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 128GA UT WOS:000243645000006 PM 16959376 ER PT J AU Yang, J Li, SZS Bacher, J Shen, J AF Yang, Jehoon Li, Shizhe S. Bacher, John Shen, Jun TI Quantification of cortical GABA-glutamine cycling rate using in vivo magnetic resonance signal of [2-C-13]GABA derived from glia-specific substrate [2-C-13]acetate SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE GABA neurotransmission; acetate metabolism; in vivo magnetic resonance spectroscopy ID GAMMA-VINYL GABA; AMINO-ACID-METABOLISM; C-13 NMR; HUMAN BRAIN; GABAERGIC NEUROTRANSMISSION; CEREBRAL METABOLISM; ENERGY-METABOLISM; SPECTROSCOPY; COMPARTMENTATION; ASTROCYTES AB Brain [2-C-13] gamma-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-C-13]acetate reflects the extent of the GABA-glutamine neurotransmitter cycling between GABAergic neurons and glial cells. We report, for the first time, in vivo quantification of the GABA-glutamine cycling flux. The GABA-glutamine cycling flux rate was determined to be 1.8 +/- 0.4 mu mol/(g h) (mean +/- S.D., n = 6, similar to 6% of total tricarboxylic acid cycle rate) in the neocortex of vigabatrin-treated rats. The relatively small magnitude of glial contribution to the clearance of extracellular GABA measured in this study provided in vivo evidence to support the concept of a significant neuronal reuptake of GABA, which short-circuits the GABA-glutamine cycling pathway for repletion of released neurotransmitter GABA. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIMH, Mol Imaging Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIH, Off Res Serv, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, Bldg 10,Room 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 55 TC 14 Z9 15 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 JAN PY 2007 VL 50 IS 2 BP 371 EP 378 DI 10.1016/j.neuint.2006.09.011 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 135MT UT WOS:000244158400012 PM 17056156 ER PT J AU Chandrasekaran, H Li, J Delashmit, WH Narasimha, PL Yu, CH Manry, MT AF Chandrasekaran, Hema Li, Jiang Delashmit, W. H. Narasimha, P. L. Yu, Changhua Manry, Michael T. TI Convergent design of piecewise linear neural networks SO NEUROCOMPUTING LA English DT Article DE nonlinear networks; local neural networks; piecewise linear function approximation; multilayer perceptron (MLP); generalization; conjugate gradient method ID ALGORITHM; SELECTION; BRANCH; MODEL AB Piecewise linear networks (PLNs) are attractive because they can be trained quickly and provide good performance in many nonlinear approximation problems. Most existing design algorithms for piecewise linear networks are not convergent, non-optimal, or are not designed to handle noisy data. In this paper, four algorithms are presented which attack this problem. They are: (1) a convergent design algorithm which builds the PLN one module at a time using a branch and bound technique; (2) two pruning algorithms which eliminate less useful modules from the network; and (3) a sifting algorithm which picks the best networks out of the many designed. The performance of the PLN is compared with that of the multilayer perceptron (MLP) using several benchmark data sets. Numerical results demonstrate that piecewise linear networks are adequate for many approximation problems. (c) 2006 Elsevier B.V. All rights reserved. C1 NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. Fastvdo LLC, Columbia, MD 21046 USA. Lockheed Martin Missiles & Fire Control, Dallas, TX 75265 USA. RP Li, J (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10 Room B2S231,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM hchandrasekaran@mail.arc.nasa.gov; li@wcn.uta.edu; manry@uta.edu NR 34 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JAN PY 2007 VL 70 IS 4-6 BP 1022 EP 1039 DI 10.1016/j.neucom.2006.02.021 PG 18 WC Computer Science, Artificial Intelligence SC Computer Science GA 135EU UT WOS:000244137700046 ER PT J AU Kaleem, M Zhao, A Hamshere, M Myers, AJ AF Kaleem, M. Zhao, A. Hamshere, M. Myers, A. J. TI Identification of a novel valosin-containing protein polymorphism in late-onset Alzheimer's disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; genetic association; neurodegeneration; valosin-containing protein; valosin-containing protein gene AB Background/Aims: Recently, mutations in the valosin-containing protein gene (VCP) were found to be causative for a rare form of dementia [Watts GDJ, et al.: Nat Genet 2004;36: 377-381]. This gene lies within a region on the genome that has been linked to late onset Alzheimer's disease (LOAD) [Myers A, et al.: Am J Med Genet 2002;114:233-242]. In this study, we investigated whether variation within VCP could account for the LOAD linkage peakon chromosome 9. Methods: We sequenced 188 individuals from the set of sibling pairs we had used to obtain the linkage results for chromosome 9 to look for novel polymorphisms that could explain the linkage signal. Any variant that was found was then typed in 2 additional sets of neuropathologically confirmed samples to look for associations with Alzheimer's disease. Results: We found 2 variants when we sequenced VCR One was a novel rare variant (R92H) and the other is already reported within the publicly available databases (rs10972300). Neither explained the chromosome 9 linkage signal for LOAD. Conclusions:We have found a novel rare variant within the VCP gene, but we did not find a variant that could explain the linkage signal for LOAD on chromosome 9. Copyright (c) 2007 S. Karger AG, Basel. C1 Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. Natl Inst Hlth, Neurogenet Lab, Bethesda, MD USA. Cardiff Univ, Wales Sch Med, Dept Psychol Med, Cardiff, Wales. Cardiff Univ, Wales Sch Med, Dept Biostat & Bioinformat Unit, Cardiff, Wales. RP Myers, AJ (reprint author), Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Batchelors Childrens Res Bldg,Room 609 1580 10th, Miami, FL 33136 USA. EM amyers@med.miami.edu RI Myers, Amanda/B-1796-2010 OI Myers, Amanda/0000-0002-3100-9396 FU Intramural NIH HHS; NIA NIH HHS [AG 05146, AG 05128, P50 AG 08671, P50 AG 16570]; NIMH NIH HHS [MH 60451, U01 MH 46281, U01 MH 46290, U01 MH 46373]; NINDS NIH HHS [NS 39764] NR 4 TC 12 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2007 VL 4 IS 5 BP 376 EP 381 DI 10.1159/000105158 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 195BB UT WOS:000248386400003 PM 17622780 ER PT J AU Johnson, J Paisan-Ruiz, C Lopez, G Crews, C Britton, A Malkani, R Evans, EW McInerney-Leo, A Jain, S Nussbaum, RL Foote, KD Mandel, RJ Crawley, A Reimsnider, S Fernandez, HH Okun, MS Gwinn-Hardy, K Singleton, AB AF Johnson, Janel Paisan-Ruiz, Coro Lopez, Grisel Crews, Cynthia Britton, Angela Malkani, Roniel Evans, E. Whitney McInerney-Leo, Aideen Jain, Shushant Nussbaum, Robert L. Foote, Kelly D. Mandel, Ronald J. Crawley, Anthony Reimsnider, Sharon Fernandez, Hubert H. Okun, Michael S. Gwinn-Hardy, Katrina Singleton, Andrew B. TI Comprehensive screening of a north American Parkinson's disease cohort for LRRK2 mutation SO NEURODEGENERATIVE DISEASES LA English DT Article DE LRRK2; Parkinson's disease; dardarin encoding; mutation ID GENE AB Background. Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356IIe) while two others had the common Gly2019Ser mutation. In addition, I patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2. Copyright (c) 2007 S. Karger AG, Basel. C1 NIA, Natl Inst Hlth, Porter Neurosci Res Ctr, Lab Neurogenet, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Bethesda, MD USA. Natl Inst Hlth, NHGRI, Genet Dis Res Branch, Bethesda, MD USA. Univ Calif San Francisco, Med Genet, San Francisco, CA USA. Univ Florida, Movement Disorders Ctr, Gainesville, FL USA. RP Singleton, AB (reprint author), NIA, Natl Inst Hlth, Porter Neurosci Res Ctr, Lab Neurogenet, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Paisan-Ruiz, Coro/C-2912-2009; Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; OI Okun, Michael/0000-0002-6247-9358; Gwinn, Katrina/0000-0002-8277-651X FU Intramural NIH HHS NR 13 TC 18 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2007 VL 4 IS 5 BP 386 EP 391 DI 10.1159/000105160 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 195BB UT WOS:000248386400005 PM 17622782 ER PT J AU Inzitari, M Newman, AB Yaffe, K Boudreau, R De Rekeneire, N Shorr, R Harris, TB Rosano, C AF Inzitari, Marco Newman, Anne B. Yaffe, Kristine Boudreau, Robert De Rekeneire, Nathalie Shorr, Ronald Harris, Tamara B. Rosano, Caterina CA Hlth ABC Study TI Gait speed predicts decline in attention and psychomotor speed in older adults: The health aging and body composition study SO NEUROEPIDEMIOLOGY LA English DT Article DE gait speed; attention; psychomotor speed; elderly community dwellers; cognitive decline; mobility ID COGNITIVE DECLINE; CARDIOVASCULAR HEALTH; PHYSICAL PERFORMANCE; ALZHEIMER-DISEASE; ELDERLY PERSONS; BLOOD-PRESSURE; DEMENTIA; RISK; ASSOCIATION; POPULATION AB Background/Aims: Gait speed is cross-sectionally associated with attention and psychomotor speed in older community dwellers. It is unclear if gait speed predicts decline in these cognitive domains over time. Methods: Usual gait speed (m/s) over 6 m was measured at baseline in 2,776 Health, Aging and Body Composition Study participants (mean age +/- SD 73.5 +/- 2.8 years, 53% women, 37% blacks). The Digit Symbol Substitution Test (DSST) was administered at baseline and after 5 years to assess attention and psychomotor speed. We used multivariate logistic regression models to calculate the risk of DSST 5-year decline [>1 SD from mean change (9 points)] across quartiles of gait speed, adjusting for demographics, weight, physical activity, comorbidities, depression and Modified Mini-Mental State Examination. Results: After 5 years, 389 (17.1%) participants declined in DSST. Compared to those in the highest quartile of gait speed (> 1.35 m/s), participants in the lowest quartile (<1.05 m/s) were more likely to decline in DSST independently of the considered covariates ( OR 1.74, 95% CI 1.21-2.51, adjusted p for trend across quartiles = 0.006). Conclusions: In this cohort of older community dwellers, gait speed independently predicted a decline in DSST after 5 years. Copyright (c) 2007 S. Karger AG, Basel. C1 [Inzitari, Marco; Newman, Anne B.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Newman, Anne B.; Boudreau, Robert; Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [De Rekeneire, Nathalie] Ctr Dis Control, Atlanta, GA 30333 USA. [Shorr, Ronald] Univ Florida, GRECC, NF SG Vet Hlth Syst, Gainesville, FL USA. [Shorr, Ronald] Univ Florida, Dept Aging & Geriatr, Gainesville, FL USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demography & Biometr, Bethesda, MD 20892 USA. [Inzitari, Marco] Univ Florence, Dept Crit Care Med & Surg, Unit Geriatr, Florence, Italy. RP Inzitari, M (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med, 130 N Bellefield St,Room 518, Pittsburgh, PA 15213 USA. EM inzitarim@edc.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30 AG024827] NR 32 TC 72 Z9 72 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2007 VL 29 IS 3-4 BP 156 EP 162 DI 10.1159/000111577 PG 7 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 251PG UT WOS:000252385100003 PM 18042999 ER PT J AU Baade, D Fritschi, L Freedman, DM AF Baade, P. D. Fritschi, L. Freedman, D. M. TI Mortality due to amyotrophic lateral sclerosis and Parkinson's disease among melanoma patients SO NEUROEPIDEMIOLOGY LA English DT Article DE Parkinson's disease, mortality; amyotrophic lateral sclerosis, mortality; melanoma ID MOTOR-NEURON DISEASE; MALIGNANT-MELANOMA; UNITED-STATES; LEVODOPA; DEATH; QUEENSLAND; AUSTRALIA; ACCURACY AB Recent studies in the USA and elsewhere have identified a possible association between Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and melanoma. However, empirical evidence is very limited. We conducted a study of all people diagnosed as having melanoma in Australia since 1982 (n = 127,037). The subjects, excluding those who had died within 12 months of diagnosis, were followed until 31 December 2001. We then compared their mortality risk of ALS and PD to that of the general population. There were a total of 53 ALS deaths and 129 deaths due to PD. Although the absolute risk is small, the melanoma cohort had a risk of death due to ALS 70% higher (standardised mortality ratio = 169.4, 95% CI = 127-221) than the general population, and nearly a 3-fold increased risk of dying from PD (standardised mortality ratio = 266.3, 95% CI = 222-317). These increased risks continued for long-term survivors, arguing against a surveillance effect (particularly for ALS). The consistency of these results in 2 separate populations (Australia and USA) strengthens the evidence for an association between melanoma and each of the 2 neurodegenerative diseases. Copyright (c) 2007 S. Karger AG, Basel. C1 Queensland Canc Fund, Epidemiol Unit, Viertel Ctr Res Canc Control, Spring Hill, Qld 4001, Australia. Western Australia Inst Med Res, Perth, WA, Australia. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. EM peterbaade@qldcancer.com.au RI Fritschi, Lin /K-2096-2012; OI Fritschi, Lin /0000-0002-7692-3560; Baade, Peter/0000-0001-8576-8868 NR 31 TC 9 Z9 9 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 EI 1423-0208 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2007 VL 28 IS 1 BP 16 EP 20 DI 10.1159/000097851 PG 5 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 135TH UT WOS:000244175900003 ER PT J AU Xiong, CJ Tang, YX van Belle, G Miller, JP Launer, LJ Bergmann, KR Morris, JC AF Xiong, Chengjie Tang, Yuxiao van Belle, Gerald Miller, J. Philip Launer, Lenore J. Bergmann, Kelly R. Morris, John C. TI Assessing statistical applications in publications on Alzheimer's disease SO NEUROEPIDEMIOLOGY LA English DT Article DE Alzheimer's disease; Assessment of Statistical Reporting; Survey of Statistical Designs; Survey of Statistical Methods; item-specific test-retest reliability; interrater reliability; correlational validity ID RANDOMIZED CONTROLLED TRIALS; MEDICAL JOURNALS; APOLIPOPROTEIN-E; CLINICAL-TRIALS; QUANTITATIVE MORPHOMETRY; SENILE PLAQUES; ARTICLES; QUALITY; PREVALENCE; GENE AB Background/Aims: To evaluate statistical applications in publications on Alzheimer's disease ( AD). Methods: Three instruments/checklists were developed: Assessment of Statistical Reporting (ASR; 44 items), Survey of Statistical Designs (SSD; 10 items), and Survey of Statistical Methods (SSM; 7 items). After a pilot testing on 5 AD publications, the instruments/checklists were revised and tested for reliability with a sample of 30 AD articles and for validity with another sample of 10 AD articles from MEDLINE. Results: Item-specific test-retest and interrater reliability for ASR ranged from 0.29 to 1.0 with the associated standard errors (SEs) ranging from 0.01 to 0.31. The test-retest reliability (intraclass correlation coefficient = 0.94, 95% Cl: 0.88-0.97) and the interrater reliability ( intraclass correlation coefficient = 0.84, 95% Cl: 0.69-0.92) for the overall score of ASR were high. The correlational validity of the ASR with a published checklist was also high (r = 0.74, SE = 0.24). The item-specific test-retest reliability in SSD and SSM ranged from 0.58 to 1.00 with the associated SEs ranging from 0.01 to 0.32. The item-specific interrater reliability in SSD and SSM ranged from 0.17 to 1.00 with the associated SEs ranging from 0.01 to 0.22. Conclusions: This study suggested that it was feasible to assess statistical applications in AD publications. Copyright (c) 2007 S. Karger AG, Basel C1 Washington Univ, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Alzheimers Dis Res Ctr, St Louis, MO USA. Washington Univ, Dept Pathol, St Louis, MO 63130 USA. Washington Univ, Dept Neurol & Immunol, St Louis, MO USA. Rush Inst Hlth Aging, Chicago, IL USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Xiong, CJ (reprint author), Washington Univ, Div Biostat, Campus Box 8067,, St Louis, MO 63110 USA. EM chengjie@wubios.wustl.edu RI Morris, John/A-1686-2012 FU NIA NIH HHS [K25 AG025189, P01 AG003991, P01 AG026276, P50 AG005681] NR 68 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2007 VL 28 IS 4 BP 235 EP 245 DI 10.1159/000108598 PG 11 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 214FQ UT WOS:000249721800007 PM 17878738 ER PT J AU DiMaio, S Kapur, T Cleary, K Aylward, S Kazanzides, P Vosburgh, K Ellis, R Duncan, J Farahani, K Lemke, H Peters, T Lorensen, W Gobbi, D Haller, J Clarke, L Pizer, S Taylor, R Galloway, R Fichtinger, G Hata, N Lawson, K Tempany, C Kikinis, R Jolesz, F AF DiMaio, Simon Kapur, Tina Cleary, Kevin Aylward, Stephen Kazanzides, Peter Vosburgh, Kirby Ellis, Randy Duncan, James Farahani, Keyvan Lemke, Heinz Peters, Terry Lorensen, William (Bill) Gobbi, David Haller, John Clarke, Laurence (Larry) Pizer, Stephen Taylor, Russell Galloway, Robert, Jr. Fichtinger, Gabor Hata, Nobuhiko Lawson, Kimberly Tempany, Clare Kikinis, Ron Jolesza, Ferenc TI Challenges in image-guided therapy system design SO NEUROIMAGE LA English DT Article ID REGISTRATION; NEUROSURGERY; GLIOMA AB System development for image-guided therapy (IGT), or image-guided interventions (IGI), continues to be an area of active interest across academic and industry groups. This is an emerging field that is growing rapidly: major academic institutions and medical device manufacturers have produced IGT technologies that are in routine clinical use, dozens of high-impact publications are published in well regarded journals each year, and several small companies have successfully commercialized sophisticated IGT systems. In meetings between IGT investigators over the last two years, a consensus has emerged that several key areas must be addressed collaboratively by the community to reach the next level of impact and efficiency in IGT research and development to improve patient care. These meetings culminated in a two-day workshop that brought together several academic and industrial leaders in the field today. The goals of the workshop were to identify gaps in the engineering infrastructure available to IGT researchers, develop the role of research funding agencies and the recently established US-based National Center for Image Guided Therapy (NCIGT), and ultimately to facilitate the transfer of technology among research centers that are sponsored by the National Institutes of Health (NIH). Workshop discussions spanned many of the current challenges in the development and deployment of new IGT systems. Key challenges were identified in a number of areas, including: validation standards; workflows, usecases, and application requirements; component reusability; and device interface standards. This report elaborates on these key points and proposes research challenges that are to be addressed by a joint effort between academic, industry, and NIH participants. (c) 2007 Published by Elsevier Inc. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Georgetown Univ, Washington, DC 20057 USA. Kitware Inc, Clifton Pk, NY 12065 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. CIMIT, Cambridge, MA 02139 USA. Queens Univ, Goodwin Hall, Kingston, ON, Canada. Yale Univ, New Haven, CT 06511 USA. NCI, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA 90089 USA. John P Robarts Res Inst, Imaging Res Labs, London, ON N6A 5K8, Canada. GE Global Res, Niskayuna, NY 12309 USA. NIBIB, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Vanderbilt Univ, Nashville, TN 37235 USA. RP DiMaio, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM simond@bwh.harvard.edu RI Farahani, Keyvan/G-9069-2012; Peters, Terry/K-6853-2013; Hata, Nobuhiko/L-5221-2014 OI Peters, Terry/0000-0003-1440-7488; Hata, Nobuhiko/0000-0002-6818-7700 FU NCRR NIH HHS [U41 RR019703, P41 RR013218, U41-RR019703]; NIBIB NIH HHS [P41 EB015898, U54 EB005149, U54-EB005149] NR 25 TC 15 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2007 VL 37 SU 1 BP S144 EP S151 DI 10.1016/j.neuroimage.2007.04.026 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 210CK UT WOS:000249434100015 PM 17644360 ER PT J AU Lotze, M Veit, R Anders, S Birbaumer, N AF Lotze, M. Veit, R. Anders, S. Birbaumer, N. TI Evidence for a different role of the ventral and dorsal medial prefrontal cortex for social reactive aggression: An interactive fMRI study SO NEUROIMAGE LA English DT Article DE PFC; social interaction; imaging; aggression; emotion ID FRONTAL-LOBE; NEURAL CIRCUITRY; ORBITOFRONTAL CORTEX; ANTISOCIAL-BEHAVIOR; FACIAL EXPRESSIONS; EMOTION; BRAIN; SELF; DAMAGE; IDENTIFICATION AB Interactive paradigms inducing reactive aggression are absent in the brain mapping literature. We used a competitive reaction time task to investigate brain regions involved in social interaction and reactive aggression in sixteen healthy male subjects with fMRI. Subjects were provoked by increasingly aversive stimuli and were given the opportunity to respond aggressively against their opponent by administering a stimulus as retaliation. fMRI revealed an increase of medial prefrontal cortex (mPFC) activity during retaliation. The dorsal mPFC was active when subjects had to select the intensity of the retaliation stimulus, and its activity correlated with the selected stimulus strength. In contrast, ventral mPFC was active during observing the opponent suffering but also during retaliation independent of the stimulus strength. Ventral mPFC activation, stronger in low callous subjects, correlated positively with skin conductance response during observation of the suffering opponent. In conclusion, dorsal mPFC activation seems to represent cognitive operations related to more intense social interaction processes whereas the ventral mPFC might be involved in affective processes associated with compassion to the suffering opponent. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Ernst Moritz Arndt Univ Greifswald, Dept Radiol & Neuroradiol, D-17487 Greifswald, Germany. NINDS, NIH, Human Cortical Physiol Sect, Bethesda, MD 20892 USA. RP Lotze, M (reprint author), Univ Tubingen, Inst Med Psychol & Verhaltensneurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM martin.lotze@uni-tuebingen.de RI Veit, Ralf/F-8907-2012 OI Veit, Ralf/0000-0001-9860-642X NR 55 TC 62 Z9 64 U1 11 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2007 VL 34 IS 1 BP 470 EP 478 DI 10.1016/j.neuroimage.2006.09.028 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 115LH UT WOS:000242735300047 PM 17071110 ER PT J AU Zelinka, T Petrak, O Strauch, B Holaj, R Kvasnicka, J Mazoch, J Pacak, K Widimsky, J AF Zelinka, Tomas Petrak, Ondrej Strauch, Branislav Holaj, Robert Kvasnicka, Jan Mazoch, Jiri Pacak, Karel Widimsky, Jiri, Jr. TI Elevated inflammation markers in pheochromocytoma compared to other forms of hypertension SO NEUROIMMUNOMODULATION LA English DT Article DE pheochromocytoma; inflammation; catecholamines ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; APPARENTLY HEALTHY-MEN; BLOOD-CELL COUNT; CAROTID ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; PLATELET ACTIVATION; METABOLIC SYNDROME AB Objective: To investigate the effect of long-term catecholamine excess in pheochromocytoma on leukocyte and platelet count and on proteins of acute-phase response. Methods: Fifteen subjects with pheochromocytoma, 16 with primary aldosteronism, 18 with essential hypertension and 17 healthy controls were studied. Sixteen subjects with pheochromocytoma were investigated after tumor removal. Leukocyte, neutrophil and platelet count, as well as C-reactive protein were measured in all subjects, while fibrinogen, alpha(1)-antitrypsin, alpha(2) - macroglobulin, orosomucoid, transferrin and prealbumin were only measured in subjects with pheochromocytoma, primary aldosteronism and essential hypertension. Results: Subjects with pheochromocytoma showed significantly higher leukocyte [ 7.5 +/- 0.9 10(9)/I, p < 0.001 vs. primary aldosteronism ( 5.4 +/- 0.9 10(9)/I) and healthy controls (5 +/- 0.9 10(9)/I), p = 0.04 vs. essential hypertension ( 6.3 +/- 1.6 10(9)/I)], neutrophil ( p < 0.001 vs. primary aldosteronism and healthy subjects) and platelet counts ( p ! 0.001 vs. primary aldosteronism; p = 0.01 vs. essential hypertension) compared to the other groups of subjects. Similar results were obtained for positive proteins of acute-phase response in subjects with pheochromocytoma [C-reactive protein: 0.62 +/- 0.52 mg/dl, p < 0.001 vs. healthy subjects ( 0.08 +/- 0.08 mg/dl), p = 0.001 vs. primary aldosteronism ( 0.17 +/- 0.19 mg/ dI), p = 0.04 vs. essential hypertension ( 0.31 +/- 0.26 mg/ dI); fibrinogen: p = 0.02 vs. primary aldosteronism; orosomucoid: p = 0.005 vs. primary aldosteronism; alpha(2)-macroglobulin: p = 0.009 vs. primary aldosteronism]. No significant differences were found in plasma levels of alpha(1) - antitrypsin, transferrin and prealbumin. Tumor removal led to a significant decrease in leukocyte ( p = 0.004), neutrophil ( p = 0.007) and platelet count ( p = 0.003) and also to a significant decrease in acute-phase proteins (C-reactive protein: p = 0.03, fibrinogen: p = 0.008, alpha(1)-antitrypsin: p = 0.003, orosomucoid: p = 0.04). Conclusions: Chronic catecholamine excess in pheochromocytoma is accompanied by an increase in inflammation markers which was reversed by the tumor removal. Copyright (C) 2007 S. Karger AG, Basel. C1 Gen Fac Hosp, Dept Med 3, CZ-12808 Prague 2, Czech Republic. Gen Fac Hosp, Cent Hematol Labs, Prague, Czech Republic. NIH, NICHHD, Sect Med Neuroendocrinol Reprod & Med Branch, Bethesda, MD 20892 USA. RP Zelinka, T (reprint author), Gen Fac Hosp, Dept Med 3, U Nemocnice 1, CZ-12808 Prague 2, Czech Republic. EM tzeli@lf1.cuni.cz RI Petrak, Ondrej/A-5839-2017; Strauch, Branislab/D-4274-2017; Zelinka, Tomas/D-4276-2017; Holaj, Robert/D-4241-2017 OI Petrak, Ondrej/0000-0001-8992-3562; Strauch, Branislab/0000-0001-5137-7017; Zelinka, Tomas/0000-0003-3395-8373; Holaj, Robert/0000-0002-9488-9706 FU Intramural NIH HHS NR 50 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2007 VL 14 IS 1 BP 57 EP 64 DI 10.1159/000107289 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 206SO UT WOS:000249203400009 PM 17700041 ER PT J AU Alesci, S Abu-Asab, M Perera, SM Tsokos, M Morris, JC Pacak, K AF Alesci, Salvatore Abu-Asab, Mones Perera, Shiromi M. Tsokos, Maria Morris, John C. Pacak, Karel TI Mitochondrial localization of human recombinant adenovirus: From evolution to gene therapy SO NEUROIMMUNOMODULATION LA English DT Article DE human recombinant adenovirus; mitochondria; recombinant viruses; viral gene therapy ID STEROIDOGENESIS AB Mitochondrial research has influenced concepts in anthropology, human physiology and pathophysiology. We present here direct evidence that human recombinant viruses can localize in mitochondria to disrupt their integrity. This finding, while opening new perspectives in viral gene therapy, may provide new insights into the pathogenesis, prevention and treatment of viral diseases. In addition, it may advance the current understanding of cell evolution. Copyright (c) 2008 S. Karger AG, Basel. C1 [Alesci, Salvatore] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Abu-Asab, Mones; Tsokos, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Perera, Shiromi M.; Pacak, Karel] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Alesci, S (reprint author), Wyeth Res, 500 Arcola Rd,Rm S-2323, Collegeville, PA 19426 USA. EM alescis@wyeth.com RI Morris, John/A-1686-2012; OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 6 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2007 VL 14 IS 5 BP 221 EP 223 DI 10.1159/000113065 PG 3 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 260MQ UT WOS:000253014800001 PM 18219224 ER PT J AU Liu, Y Ascoli, GA AF Liu, Yuan Ascoli, Giorgio A. TI Value added by data sharing: Long-term potentiation of neuroscience research - A commentary on the 2007 SfN Satellite Symposium on Data Sharing SO NEUROINFORMATICS LA English DT Editorial Material ID PURKINJE-CELLS; NEUROINFORMATICS; MICE C1 NINDS, NIH, Bethesda, MD 20824 USA. George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA USA. RP Liu, Y (reprint author), NINDS, NIH, Bethesda, MD 20824 USA. EM liuyuan@ninds.nih.gov; ascoli@gmu.edu FU NIA NIH HHS [AG025633]; NIDA NIH HHS [DA-HHSN271200577531C]; NINDS NIH HHS [NS39600] NR 13 TC 13 Z9 13 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PY 2007 VL 5 IS 3 BP 143 EP 145 DI 10.1007/s12021-007-0009-0 PG 3 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 223XG UT WOS:000250408500002 PM 17917124 ER PT J AU Kernich, CA AF Kernich, Catherine A. TI Shingles SO NEUROLOGIST LA English DT Editorial Material C1 Univ Hosp, Univ Hosp Med Grp, Dept Med, Cleveland, OH USA. RP Kernich, CA (reprint author), Natl Inst Aging Informat Ctr, POB 8057, Gaithersburg, MD 20898 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 1074-7931 J9 NEUROLOGIST JI Neurologist PD JAN PY 2007 VL 13 IS 1 BP 43 EP 44 DI 10.1097/01.nri.0000253099.08972.d1 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 123ML UT WOS:000243299900007 PM 17215727 ER PT J AU Lahiri, DK Alley, GM Tweedie, D Chen, DM Greig, NH AF Lahiri, Dehomoy K. Alley, George M. Tweedie, David Chen, Demao Greig, Nigel H. TI Differential effects of two hexahydropyrroloindole carbamate-based anti cholinesterase drugs on the amyloid beta protein pathway involved in Alzheimer disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE acetylcholine; aging; anticholinesterase; beta-protein; cell culture; CNS; dementia; drugs; ELISA; neuron; phenylcarbamate ID PRECURSOR PROTEIN; ACETYLCHOLINESTERASE INHIBITOR; RESPONSIVE ELEMENT; CELL-LINES; PHENSERINE; BUTYRYLCHOLINESTERASE; SECRETION; TACRINE; STRATEGIES; MELATONIN AB One of the main hallmarks of Alzheimer's disease (AD) is the brain deposition of senile plaques made up of toxic amyloid beta-peptide (AP), which is derived from a larger protein called the beta-amyloid precursor protein (APP). Both APP processing and cholinesterase activity are affected in the AD brain, but, yet, cholinesterase inhibitors (ChEI) remain the primary Food and Drug Administration approved drugs for AD within the United States. Herein, we evaluated the effects of two clinically relevant drugs on the APP pathway, which is presumably involved in AD pathogenesis. Specifically, we compared the actions of the classical ChEI physostigmine WHY) and its analog phenserine (PHE) on neuronal cell viability, on IC50 and on levels of different amyloid proteins. Interestingly, these drugs share the same chemical backbone, inhibit acetylcholinesterase with similar potency, but differentially affect APP processing. PHE treatment decreased levels of APP in the human neuroblastoma cells (p = 0.009) whereas PHY showed a similar but less-pronounced trend, which did not attain statistical significance, PHE treatment significantly decreased levels of AP in human neuroblastoma cells (p = 0.02) whereas PHY showed no significant change under the same conditions. The divergent actions of these two structurally related drugs on the amyloid pathway indicate that the mechanisms underpinning the cholinergic and the amyloid-lowering properties for this class of drugs are independent of each other. C1 Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu FU NIA NIH HHS [AG18379, AG18884] NR 35 TC 7 Z9 7 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2007 VL 9 IS 2 BP 157 EP 168 DI 10.1385/NMM:9:2:157 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 168OD UT WOS:000246533000005 PM 17627035 ER PT J AU de Maturana, RL Martin, B Millar, RP Brown, P Davidson, L Pawson, AJ Nicol, MR Mason, JI Barran, P Naor, Z Maudsley, S AF de Maturana, Rakel Lopez Martin, Bronwen Millar, Robert P. Brown, Pamela Davidson, Lindsay Pawson, Adam J. Nicol, Moira R. Mason, J. Ian Barran, Perdita Naor, Zvi Maudsley, Stuart TI GnRH-mediated DAN production regulates the transcription of the GnRH receptor in gonadotrope cells SO NEUROMOLECULAR MEDICINE LA English DT Article DE GnRH; DAN; activin; StAR; p34-ARC; receptor ID FOLLICLE-STIMULATING-HORMONE; GROWTH-FACTOR-BETA; MIDBRAIN DOPAMINERGIC-NEURONS; TUMOR-SUPPRESSIVE ACTIVITY; HUMAN ARP2/3 COMPLEX; 3Y1 RAT FIBROBLASTS; PARKINSONS-DISEASE; TGF-BETA; DIFFERENTIATION FACTOR-9; MEMBRANE MICRODOMAINS AB The primary function of gonadotropin-releasing hormone (GnRH) is the regulation of pituitary gonadotropin hormone gene transcription, biosynthesis and release. These effects are mediated through intracellular mobilization of Ca2+ and activation of PKC isoforms and MAP kinases. We show here that DAN (differential screening-selected gene aberrative in neuroblastoma) which is a secreted bone morphogenic protein (BMP) antagonist belonging to the TGF beta protein superfamily, is controlled by GnRH in murine gonadotrope cells. Acute GnRH stimulation induced a rapid, 27-fold, elevation of DAN mRNA, accompanied by an approximate 3-fold increase in the amount of mature DAN glycoprotein in the cell cytoplasm and in DAN secretion into the culture medium. Incubation of L beta T2 cells in DAN-containing medium altered the levels of a number of cellular proteins. Two of these were identified as the steroidogenic acute regulatory protein (StAR) and the actin-related protein 2/3 complex subunits 2 (p34-ARC) which are primarily involved in steroidogenesis and cytoskeleton remodelling, respectively. DAN caused an approximate 2-fold specific elevation in the cytoplasmic levels of both these proteins in L beta T2 cells. We further tested the effects of DAN on classical GnRH effects viz. gonadotropin and GnRH receptor gene expression. Co-transfection of L beta T2 cells with DAN and gonadotropin subunit promoter luciferase reporter genes had no effect on GnRH stimulation of alpha GSU and LH beta or on the additive GnRH and activin induction of FSH beta subunit transcription. However, co-transfection of DAN markedly inhibited the synergistic activation of GnRH and activin on GnRH receptor gene expression thus implicating DAN as a novel autocrine/ paracrine factor that modulates GnRH function in pituitary gonadotropes. C1 Tel Aviv Univ, Dept Biochem, IL-69975 Tel Aviv, Israel. MRC, Human Reprod Sci Unit, Ctr Human Reprod Biol, Edinburgh EH16 4SB, Midlothian, Scotland. Ardana Biosci, Edinburgh EH3 7HA, Midlothian, Scotland. Ctr Reprod Biol, Div Reprod & Dev Sci, Edinburgh EH16 4SB, Midlothian, Scotland. Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland. RP Maudsley, S (reprint author), NIA, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM maudsleyst@grc.nia.nih.gov RI Pawson, Adam/Q-5678-2016; OI Pawson, Adam/0000-0003-2280-845X; Barran, Perdita/0000-0002-7720-586X NR 84 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2007 VL 9 IS 3 BP 230 EP 248 DI 10.1007/s12017-007-8004-z PG 19 WC Neurosciences SC Neurosciences & Neurology GA 211XI UT WOS:000249556200003 ER PT J AU Haberman, F Tang, SC Arumugam, TV Hyun, DH Yu, QS Cutler, RG Guo, Z Holloway, HW Greig, NH Mattson, MP AF Haberman, Frank Tang, Sung-Chun Arumugam, Thiruma V. Hyun, Dong-Hoon Yu, Qian-Sheng Cutler, Roy G. Guo, Zhihong Holloway, Harold W. Greig, Nigel H. Mattson, Mark P. TI Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice SO NEUROMOLECULAR MEDICINE LA English DT Article DE uric acid analogues; reactive oxygen species; middle cerebral artery occlusion; permanent middle cerebral artery occlusion; oxygen and glucose deprivation ID FOCAL CEREBRAL-ISCHEMIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; NITRIC-OXIDE; HIPPOCAMPAL-NEURONS; MULTIPLE-SCLEROSIS; STROKE; DAMAGE; DYSFUNCTION; DISEASE AB Uric acid is a major antioxidant in the blood of humans that can protect cultured neurons against oxidative and metabolic insults. However, uric acid has a very low solubility which compromises its potential clinical use for neurodegenerative disorders. Here we describe the synthesis, characterization and preclinical development of neuroprotective methyl- and sulfur-containing analogs of uric acid with increased solubility. In vitro and cell culture screening identified 1,7-dimethyluric acid (mUA2) and 6,8-dithiouric acid (sUA2) as two analogs with high antioxidant and neuroprotective activities. When administered intravenously in mice, uric acid analogs mUA2 and sUA2 lessened damage to the brain and improved functional outcome in an ischemia-reperfusion mouse model of stroke. Analogs sUA2 and mUA2 were also effective in reducing damage to the cerebral cortex when administered up to 4 h after stroke onset in a permanent middle cerebral artery occlusion mouse model. These findings suggest a therapeutic potential for soluble analogs of uric acid in the treatment of stroke and related neurodegenerative conditions. C1 NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD USA. Israel Inst Biol Res, Dept Med Chem, Ness Ziona, Israel. Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, 5600 Nathan Shock dr, Baltimore, MD USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural NIH HHS NR 46 TC 23 Z9 25 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2007 VL 9 IS 4 BP 315 EP 323 DI 10.1007/s12017-007-8010-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 235LC UT WOS:000251234600004 PM 17999205 ER PT J AU Caillava, C Vandenbosch, R Kaldis, P Berthet, C Gallo, V Malgrange, B Belachew, S Evercooren, ABV AF Caillava, Celine Vandenbosch, Renaud Kaldis, Philipp Berthet, Cyril Gallo, Vittorio Malgrange, Beatrice Belachew, Shibeshih Evercooren, Anne Baron-Van TI Exploring the requirement of Cdk2 for normal white matter development and myelin repair SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Caillava, Celine; Evercooren, Anne Baron-Van] CHU Pitie Salpetriere, INSERM, UPMC, UMR546, F-75013 Paris, France. [Vandenbosch, Renaud; Malgrange, Beatrice; Belachew, Shibeshih] Ctr Cellular & Mol Neurobiol, B-4000 Liege, Belgium. [Gallo, Vittorio] Ctr Res Neurosci, Washington, DC 20010 USA. [Kaldis, Philipp; Berthet, Cyril] Natl Canc Inst, Ft Detrick, MD 21702 USA. RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S118 EP S118 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800364 ER PT J AU D'Urso, A Zambroni, D Nodari, A De Arcangelis, A Georges-Labouesse, E Wrabetz, L Feltri, ML AF D'Urso, Alessandra Zambroni, Desiree Nodari, Alessandro De Arcangelis, Adele Georges-Labouesse, Elisabeth Wrabetz, Lawrence Feltri, Maria Laura TI Which alpha integrin pairs with beta1 to form the Schwann cell receptor required for axonal sorting? SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [D'Urso, Alessandra; Zambroni, Desiree; Wrabetz, Lawrence; Feltri, Maria Laura] Ist Sci San Raffaele, I-20132 Milan, Italy. [Nodari, Alessandro] NIH, Bethesda, MD 20892 USA. [De Arcangelis, Adele; Georges-Labouesse, Elisabeth] Inst Genet & Biol Mol & Cellular, Strasbourg, France. RI De Arcangelis, Adele/M-5101-2016 OI De Arcangelis, Adele/0000-0003-1114-8441 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S150 EP S150 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800460 ER PT J AU Hutchinson, MR Coats, BD Zhang, Y Lewis, SS Sprunger, DB Baker, EM Maier, SF Rice, KC Johnson, KW Watkins, LR AF Hutchinson, M. R. Coats, B. D. Zhang, Y. Lewis, S. S. Sprunger, D. B. Baker, E. M. Maier, S. F. Rice, K. C. Johnson, K. W. Watkins, L. R. TI Opioid-induced glial activation via a non-classical opioid receptor: clinical implications & the search for the target SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Hutchinson, M. R.; Coats, B. D.; Zhang, Y.; Lewis, S. S.; Sprunger, D. B.; Baker, E. M.; Maier, S. F.; Watkins, L. R.] Univ Colorado, Ctr Neurosci, Dept Psychol, Boulder, CO 80309 USA. [Hutchinson, M. R.] Univ Adelaide, Sch Med Sci, Adelaide, SA 5005, Australia. [Rice, K. C.] NIDA, Chem Biol Res Branch, Bethesda, MD USA. [Johnson, K. W.] Avegin, Alameda, CA USA. RI Hutchinson, Mark/A-9672-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S16 EP S16 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800047 ER PT J AU Mackay, R AF Mackay, Ron TI Beneficial function of debris clearance by microglial TREM2 SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Mackay, Ron] Natl Inst Hlth, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S3 EP S4 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800009 ER PT J AU Russell, JT AF Russell, James T. TI Glial cell calcium signals measured using a genetically encoded FRET based Cameleon Calcium Indicator in Transgenic Mice SO NEURON GLIA BIOLOGY LA English DT Meeting Abstract C1 [Russell, James T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2007 VL 2 SU 1 BP S108 EP S108 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 242FB UT WOS:000251708800335 ER PT J AU Lavezzari, G Roche, KW AF Lavezzari, Gabriela Roche, Katherine W. TI Constitutive endocytosis of the metabotropic glutamate receptor mGluR7 is clathrin-independent SO NEUROPHARMACOLOGY LA English DT Article DE endocytosis; Arf6; clathrin; metabotropic glutamate receptors ID PROTEIN-COUPLED RECEPTORS; MEMBRANE; DESENSITIZATION; PATHWAY; ARF6; LOCALIZATION; EXPRESSION; PLASTICITY; COMPLEX; BINDING AB Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs) that are widely expressed throughout the brain and are involved in synaptic development, transmission, and plasticity. The endocytosis of several members of the GPCR superfamily of receptors, such as beta-adrenergic receptors, has been studied extensively. In contrast, the mechanisms regulating mGluR endocytosis and intracellular trafficking remain poorly defined. We describe here for the first time a distinct endocytic and intracellular sorting pathway utilized by mGluR7. We show that mGluR7 constitutively internalizes via a non-clathrin mediated pathway in heterologous cells and in neurons. Unlike clathrin-mediated NMDAR endocytosis, mGluR7 traffics via an Arf6-positive endosomal pathway, similar to other well-characterized proteins such as major histocompatibility complex class I (MHC 1) and the GPI-anchored protein CD59. Thus constitutive endocytosis of mGluR7 in neurons is not regulated by clathrin-dependent mechanisms, and this clathrin-independent pathway ultimately determines the amount of receptor present on the plasma membrane available to bind and respond to glutamate. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Roche, KW (reprint author), NINDS, NIH, Bldg 35,Room 2C903, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS NR 26 TC 21 Z9 22 U1 0 U2 0 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 JAN PY 2007 VL 52 IS 1 BP 100 EP 107 DI 10.1016/j.neuropharm.2006.07.011 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 128ZM UT WOS:000243698200012 PM 16890965 ER PT J AU Pelkey, KA Yuan, XQ Lavezzari, G Roche, KW McBain, CJ AF Pelkey, Kenneth A. Yuan, Xiaoqing Lavezzari, Gabriela Roche, Katherine W. McBain, Chris J. TI mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082 SO NEUROPHARMACOLOGY LA English DT Article DE mGluR7; endocytosis; internalization; allosteric; GPCR; pHluorin ID METABOTROPIC GLUTAMATE RECEPTORS; PROTEIN-KINASE-C; SYNAPTIC-TRANSMISSION; PLASMA-MEMBRANE; NERVOUS-SYSTEM; ENDOCYTOSIS; SYNAPSES; CALCIUM; DESENSITIZATION; INHIBITION AB The G-protein coupled receptor (GPCR) metabotropic glutamate receptor 7 (mGluR7) is widely expressed throughout the nervous system and is implicated in diverse physiological processes ranging from synaptic plasticity to neuroprotection. To date, unequivocally assigning specific functions to mGluR7 has been hampered by a lack of specific pharmacological tools, however, an mGluR7 specific allosteric agonist, AMN082, was recently discovered. Accumulating evidence indicates that in addition to G-protein activation, GPCRs trigger critical intracellular signalling cascades during agonist-induced internalization. Thus, to determine if AMN082 will be useful for evaluating signalling events related to mGluR7 internalization as well as receptor activation we have examined whether AMN082 induces mGluR7 endocytosis. Using an immunofluorescence assay we demonstrate that AMN082 induces robust internalization of mGluR7 overexpressed in dissociated hippocampal neurons. AMN082-induced mGluR7 internalization was resistant to inhibition by a competitive antagonist consistent with the distinct binding site of the allosteric agonist from the glutamate-binding pocket utilized by conventional orthosteric ligands. Finally, as an independent assay of receptor internalization we overexpressed N-terminal pHluorin-tagged mGluR7 in neurons, allowing live imaging of surface receptors in real time. AMN082 treatment produced a rapid loss of surface mGluR7 as indicated by decreased fluorescence confirming the ability of allosteric receptor activation to trigger mGluR7 endocytosis. Thus, AMN082 will be effective for investigating physiological processes related to both mGluR7 activation and internalization such as control of bidirectional plasticity at mossy fiber-st. lucidum interneuron synapses. (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Pelkey, KA (reprint author), NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 35,35 Lincoln Dr, Bethesda, MD 20892 USA. EM pelkeyk2@mail.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS NR 52 TC 65 Z9 66 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 JAN PY 2007 VL 52 IS 1 BP 108 EP 117 DI 10.1016/j.neuropharm.2006.07.020 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 128ZM UT WOS:000243698200013 PM 16914173 ER PT J AU Scott, HL Braud, S Bannister, NJ Isaac, JTR AF Scott, Helen L. Braud, Stephanie Bannister, Neil J. Isaac, John T. R. TI Synaptic strength at the thalamocortical input to layer IV neonatal barrel cortex is regulated by protein kinase C SO NEUROPHARMACOLOGY LA English DT Article DE long-term potentiation; development; synaptic plasticity; somatosensory cortex; glutamate; NMDA receptor ID LONG-TERM POTENTIATION; CORTICAL MAP PLASTICITY; SOMATOSENSORY CORTEX; KAINATE RECEPTORS; SENSORY DEPRIVATION; CEREBRAL-CORTEX; CRITICAL PERIOD; AMPA RECEPTORS; M-ZETA; SYNAPSES AB Long-term synaptic plasticity is an important mechanism underlying the development of cortical circuits in a number of brain regions. In barrel cortex NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) play a critical role in the development and experience-dependent plasticity of the topographical map of the rodent whiskers. However, the mechanisms underlying the induction and expression of these forms of plasticity are poorly characterised. Here we investigate the role of PKC in the regulation of synaptic strength in neonatal barrel cortex using patch-clamp recordings in brain slices. We demonstrate that PKC activity tonically maintains AMPA receptor-mediated transmission at thalamocortical synapses, and that basal transmission can be potentiated by PKC activation using postsynaptic infusion of phorbol ester. Furthermore, we show that induction of NMDAR-dependent LTP requires PKC activity. These findings demonstrate that PKC is required for the regulation of transmission at thalamocortical synapses, the major ascending sensory input to barrel cortex. Thalamocortical inputs in barrel cortex only express LTP during the first postnatal week during a critical period for experience-dependent plasticity in layer IV. Therefore, the requirement for PKC in LTP suggests an important role for this kinase in the development of the barrel cortex sensory map. (c) 2006 Elsevier Ltd. All rights reserved. C1 NINDS, Dev Synapt Plast Unit, NIH, Bethesda, MD 20892 USA. Univ Bristol, MRC, Ctr Synapt Plast, Dept Anat, Bristol BS8 1TD, Avon, England. RP Isaac, JTR (reprint author), NINDS, Dev Synapt Plast Unit, NIH, Bldg 35,Rm 3C-1002 MSC 3701,35 Convent Dr, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov RI Scott, Helen/A-6307-2009 OI Scott, Helen/0000-0003-2656-4034 FU Intramural NIH HHS; Wellcome Trust NR 51 TC 6 Z9 6 U1 0 U2 1 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 JAN PY 2007 VL 52 IS 1 BP 185 EP 192 DI 10.1016/j.neuropharm.2006.06.016 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 128ZM UT WOS:000243698200020 PM 16890249 ER PT S AU Lipsky, RH Marini, AM AF Lipsky, Robert H. Marini, Ann M. BE Slikker, W Andrew, RJ Trembly, B TI Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity SO NEUROPROTECTIVE AGENTS: EIGHTH INTERNATIONAL NEUROPROTECTION SOCIETY MEETING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th International Conference on Neuroprotective Agents CY SEP 18-20, 2006 CL Mackinac Isl, MI SP Int Neuroprotect Soc DE brain-derived neurotrophic factor; neuroplasticity; tropomyosin-related tyrosine kinase receptors ID LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE RECEPTORS; BDNF VAL66MET POLYMORPHISM; SIGNAL-REGULATED KINASE; SYNAPTIC PLASTICITY; IN-VIVO; HIPPOCAMPAL FUNCTION; ALCOHOL DEPENDENCE; TRUNCATED TRKB.T1; CELL-SURVIVAL AB Neurotrophins are critical to the development and maintenance of the mammalian central nervous system. Among them is brain-derived neurotrophic factor (BDNF), whose synthesis and release is targeted by activation of glutamate receptors. Perturbation of this process probably underlies neurodegenerative and psychiatric disorders. A naturally occurring variation in humans, in the form of a common single-nucleotide polymorphism in the pro region of the polypeptide at codon 66 (Val66 -> Met), affects processing of the pro-BDNF polypeptide and its activation-dependent release. This variant is associated with differences in the volume of the hippocampal formation and with anxiety and depression-related phenotypes. Convergent findings supporting a role for BDNF in alterations to hippocampal structure and behavior are found in a "humanized" BDNF transgenic mouse. Also, recent human genetic studies have supported a role of BDNF signaling in addictive behaviors by allele-, genotype-, and haplotype-based association of the TrkB gene, which encodes the cognate receptor for BDNF, with alcohol dependence. A better understanding of the influence of BDNF-mediated pathways in cell survival and plasticity will aid in developing new approaches to restoring normal function in disease states. C1 [Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Program Neurosci, Bethesda, MD 20814 USA. [Lipsky, Robert H.] NIAAA, NIH, Neurogenet Lab, Mol Genet Sect, Bethesda, MD USA. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, Program Neurosci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM amarini@usuhs.mil OI Lipsky, Robert/0000-0001-7753-1473 FU Intramural NIH HHS NR 83 TC 145 Z9 147 U1 4 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-685-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1122 BP 130 EP 143 DI 10.1196/annals.1403.009 PG 14 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BHD20 UT WOS:000252267100009 PM 18077569 ER PT S AU Mocchetti, I Nosheny, RL Tanda, G Ren, K Meyer, EM AF Mocchetti, Italo Nosheny, Rachel L. Tanda, Gianluigi Ren, Ke Meyer, Edwin M. BE Slikker, W Andrew, RJ Trembly, B TI Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system SO NEUROPROTECTIVE AGENTS: EIGHTH INTERNATIONAL NEUROPROTECTION SOCIETY MEETING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th International Conference on Neuroprotective Agents CY SEP 18-20, 2006 CL Mackinac Isl, MI SP Int Neuroprotect Soc DE neuronal apoptosis; BDNF; CXCR4; neuroprotection; HIV-associated dementia; dopamine; substantia nigra ID CENTRAL-NERVOUS-SYSTEM; NEURONAL CELL-DEATH; HIV DEMENTIA; IN-VIVO; TRANSGENIC MICE; DOPAMINERGIC SYSTEMS; ROTATIONAL BEHAVIOR; DEGENERATION; APOPTOSIS; CXCR4 AB Human immunodeficiency virus type 1 (HIV-1) causes neuronal degeneration and, at a late stage, creates HIV-associated dementia (HAD) and other neurological abnormalities. Therefore, the need for neuroprotective agents is great. However, therapeutic agents that reduce HIV neurotoxicity are difficult to characterize and develop because rodents are not infected by HIV. This study was undertaken to develop an animal model of HIV neurotoxicity by using the HIV-1 envelope glycoprotein 120 (gp120). Vehicle or gp120 was injected acutely in the striatum of adult rats. gp120 produced loss of nigrostriatal neurons, as shown both by histochemical analysis of brain sections for apoptosis and biochemical determination of dopamine. The neurotrophin brain-derived neurotrophic factor (BDNF) delivered by a recombinant adeno-associated viral vector prevented gp120 toxicity. This study's results support the notion that gp120 produces a widespread neurotoxicity similar to that observed in HIV-positive individuals and that BDNF may be a suitable neuroprotective agent for HAD. C1 [Mocchetti, Italo; Nosheny, Rachel L.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Tanda, Gianluigi] NIDA, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. [Ren, Ke; Meyer, Edwin M.] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL USA. RP Mocchetti, I (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, Res Bldg,3970 Reservoir Rd,NW, Washington, DC 20057 USA. EM moccheti@georgetown.edu RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 FU NINDS NIH HHS [NS040670, NS046234, NS047977] NR 45 TC 17 Z9 17 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-685-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1122 BP 144 EP 154 DI 10.1196/annals.1403.010 PG 11 WC Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BHD20 UT WOS:000252267100010 PM 18077570 ER PT J AU Einat, H Yuan, PX Szabo, ST Dogra, S Manji, HK AF Einat, Haim Yuan, Peixiong Szabo, Steven T. Dogra, Samriti Manji, Husseini K. TI Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: Implications for the development of novel therapeutics for bipolar disorder SO NEUROPSYCHOBIOLOGY LA English DT Article DE protein kinase C; affective disorders; depression; animal model; treatment; growth-associated protein of 43 kDa ID HIGH-DOSE TAMOXIFEN; DOPAMINE RELEASE; GAP-43 PHOSPHORYLATION; STRIATAL SYNAPTOSOMES; IN-VIVO; INTRACELLULAR-LOCALIZATION; REPEATED AMPHETAMINE; LOCOMOTOR-ACTIVITY; MALIGNANT GLIOMAS; GENE-EXPRESSION AB Rationale: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. Objectives: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. Methods: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. Results: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. Conclusions: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder. Copyright (c) 2007 S. Karger AG, Basel. C1 Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. NIMH, Mol Pathophysiol Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. RP Einat, H (reprint author), Univ Minnesota, Coll Pharm, 376 Kirby Pl,1208 Kirby Dr, Duluth, MN 55812 USA. EM heinat@d.umn.edu RI Einat, Haim/A-7203-2009 FU Intramural NIH HHS NR 81 TC 63 Z9 64 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2007 VL 55 IS 3-4 BP 123 EP 131 DI 10.1159/000106054 PG 9 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 214FR UT WOS:000249721900001 PM 17641532 ER PT J AU Eshel, N Nelson, EE Blair, RJ Pine, DS Ernst, M AF Eshel, Neir Nelson, Eric E. Blair, R. James Pine, Daniel S. Ernst, Monique TI Neural substrates of choice selection in adults and adolescents: Development of the ventrolateral prefrontal and anterior cingulate cortices SO NEUROPSYCHOLOGIA LA English DT Article DE reward; decision-making; cognitive control; affective regulation; conflict monitoring ID STRUCTURED CLINICAL INTERVIEW; DSM-III-R; DECISION-MAKING; ORBITOFRONTAL CORTEX; RISK-TAKING; NUCLEUS-ACCUMBENS; BOLD FMRI; BRAIN; REWARD; RESPONSES AB A heightened propensity for risk-taking and poor decision-making underlies the peak morbidity and mortality rates reported during adolescence. Delayed maturation of cortical structures during the adolescent years has been proposed as a possible explanation for this observation. Here, we test the hypothesis of adolescent delayed maturation by using fMRI during a monetary decision-making task that directly examines risk-taking behavior during choice selection. Orbitofrontal/ventrolateral prefrontal cortex (OFC/VLPFC) and dorsal anterior cingulate cortex (ACC) were examined selectively since both have been implicated in reward-related processes, cognitive control, and resolution of conflicting decisions. Group comparisons revealed greater activation in the OFC/VLPFC (BA 47) and dorsal ACC (BA 32) in adults than adolescents when making risky selections. Furthermore, reduced activity in these areas correlated with greater risk-taking performance in adolescents and in the combined group. Consistent with predictions, these results suggest that adolescents engage prefrontal regulatory structures to a lesser extent than adults when making risky economic choices. Published by Elsevier Ltd. C1 NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov RI Nelson, Eric/B-8980-2008; OI Nelson, Eric/0000-0002-3376-2453; Eshel, Neir/0000-0002-5976-2013 FU Intramural NIH HHS [Z99 MH999999] NR 76 TC 194 Z9 202 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 6 BP 1270 EP 1279 DI 10.1016/j.neuropsychologia.2006.10.004 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 149EW UT WOS:000245130900013 PM 17118409 ER PT J AU Ernst, M Maheu, FS Schroth, E Hardin, J Golan, LG Cameron, J Allen, R Holzer, S Nelson, E Pine, DS Merke, DP AF Ernst, Monique Maheu, Francoise S. Schroth, Elizabeth Hardin, Julie Golan, Liza Green Cameron, Jennifer Allen, Rachel Holzer, Stuart Nelson, Eric Pine, Daniel S. Merke, Deborah P. TI Amygdala function in adolescents with congenital adrenal hyperplasia: A model for the study of early steroid abnormalities SO NEUROPSYCHOLOGIA LA English DT Article DE development; corticosteroid; androgen; affective processing; fMRI; stress hormones ID EMOTIONAL FACIAL EXPRESSIONS; GENDER-RELATED BEHAVIOR; BRAIN ENGAGEMENT; TYPED BEHAVIOR; CHILDREN; ACTIVATION; FACES; TESTOSTERONE; GIRLS; FMRI AB Early, disruption of steroids affects the development of mammalian neural circuits underlying affective processes. In humans, patients with classic congenital adrenal hyperplasia (CAH) can serve as a natural model to study early hormonal alterations on functional brain development. CAH is characterized by congenital glucocorticoid insufficiency, leading to altered hypothalamic-pituitary-adrenal (HPA) function, and hyperandrogenism. Using fMRI, we compared fourteen adolescents with CAH to 14 healthy controls on amygdala response to a face viewing task. In response to negative facial emotions, CAH females activated the amygdala significantly more than healthy females, whereas CAH males did not differ from control males. Furthermore, females with CAH showed a similar pattern of amygdala activation to control males, suggesting virilized amygdala function in females with CAH. These findings suggest a prominent effect of early hyperandrogenism on the development and function of the amygdala in females with CAH, whereas no effects were detected in males with CAH. This study provides data that can be further tested in a model of the neurobiological mechanisms underlying early androgen organizational effects on amygdala function. Published by Elsevier Ltd. C1 NIMH, Mood & Anxiety Disorders Program, DHHS, Emot Dev & Affect Neurosci Branch,NIH, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, DHHS, Emot Dev & Affect Neurosci Branch,NIH, 15K N Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Intramural NIH HHS [Z99 MH999999] NR 53 TC 35 Z9 35 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 9 BP 2104 EP 2113 DI 10.1016/j.neuropsychologia.2007.01.019 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 172NA UT WOS:000246809800011 PM 17336344 ER PT J AU Shaw, P Lawrence, E Bramham, J Brierley, B Radbourne, C David, AS AF Shaw, P. Lawrence, E. Bramham, J. Brierley, B. Radbourne, C. David, A. S. TI A prospective study of the effects of anterior temporal lobectomy on emotion recognition and theory of mind SO NEUROPSYCHOLOGIA LA English DT Article DE emotion recognition; theory of mind; amygdala ID FRONTAL-LOBE LESIONS; MIRROR FOCUS; FUNCTIONAL CONNECTIVITY; ACQUIRED THEORY; FACIAL EMOTION; HUMAN AMYGDALA; HUMAN BRAIN; EPILEPSY; PERCEPTION; CORTEX AB Nineteen patients evaluated facial emotional expressions and performed 'theory of mind' reasoning tasks before and after a temporal lobectomy for medically intractable epilepsy, and results were compared with the performance of 19 healthy controls. Following operation, which in all cases resulted in excision of the entire amygdala, there was no change in the ability to reason about the mental states of others, in line with the suggestion that the anterior temporal lobe is not necessary for theory of mind reasoning. However, following a left anterior temporal lobectomy, patients evaluated fearful facial expressions in a more normative manner. This may reflect the excision of a 'hyper-excitable' amygdala which pre-operatively misinterprets fearful expressions as containing blends of other emotions. Alternatively the results may represent an improvement in function of the right amygdala following the excision of a noxious inhibitory epileptogenic focus on the left. The finding complements earlier demonstrations that damage to the right amygdala is associated with impaired processing of fear; amelioration of right amygdala function may conversely be associated with an improvement. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Inst Psychiat, Neuropsychol Unit, London, England. Inst Psychiat, Dept Med Psychol, Sect Cognit Neuropsychiat, London, England. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, 9000 Rockville Pike,Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov RI Shaw, Philip/A-1129-2008; David, Anthony/C-1315-2011; OI David, Anthony/0000-0003-0967-774X; Bramham, Jessica/0000-0002-6696-7500 NR 47 TC 43 Z9 46 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 12 BP 2783 EP 2790 DI 10.1016/j.neuropsychologia.2007.04.020 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 205WR UT WOS:000249145800014 PM 17568631 ER PT J AU Simmons, WK Ramjee, V Beauchamp, MS McRae, K Martin, A Barsalou, LW AF Simmons, W. Kyle Ramjee, Vimal Beauchamp, Michael S. McRae, Ken Martin, Alex Barsalou, Lawrence W. TI A common neural substrate for perceiving and knowing about color SO NEUROPSYCHOLOGIA LA English DT Article DE conceptual knowledge; fusiform gyrus; fMRI; color perception; property verification ID PERCEPTUAL SYMBOL SYSTEMS; BIOLOGICAL MOTION; MANIPULATABLE OBJECTS; SEMANTIC MEMORY; FUNCTIONAL MRI; VISUAL-CORTEX; BRAIN; KNOWLEDGE; FMRI; REPRESENTATION AB Functional neuroimaging research has demonstrated that retrieving information about object-associated colors activates the left fusiform gyrus in posterior temporal cortex. Although regions near the fusiform have previously been implicated in color perception, it remains unclear whether color knowledge retrieval actually activates the color perception system. Evidence to this effect would be particularly strong if color perception cortex was activated by color knowledge retrieval triggered strictly with linguistic stimuli. To address this question, subjects performed two tasks while undergoing fMRI. First, subjects performed a property verification task using only words to assess conceptual knowledge. On each trial, subjects verified whether a named color or motor property was true of a named object (e.g., TAXI-yellow, HAIR-combed). Next, subjects performed a color perception task. A region of the left fusiform gyrus that was highly responsive during color perception also showed greater activity for retrieving color than motor property knowledge. These data provide the first evidence for a direct overlap in the neural bases of color perception and stored information about object-associated color, and they significantly add to accumulating evidence that conceptual knowledge is grounded in the brain's modality-specific systems. (c) 2007 Elsevier Ltd. All rghts reserved. C1 NIMH, Lab Brain & Cognit, Cognit Neuropsychol Sect, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Univ Texas, Sch Med, Dept Neurobiol & Anat, Houston, TX 77225 USA. Univ Western Ontario, Dept Psychol, London, ON N6A 3K7, Canada. RP Simmons, WK (reprint author), NIMH, Lab Brain & Cognit, Cognit Neuropsychol Sect, NIH, Bldg 10,Room 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. EM simmonswkyle@mail.nih.gov RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015; OI Simmons, William/0000-0002-0399-9003; Beauchamp, Michael/0000-0002-7599-9934 FU NICHD NIH HHS [R01 HD053136, R01 HD053136-10]; NIMH NIH HHS [1F31MH070152-01, F31 MH070152, F31 MH070152-02] NR 51 TC 170 Z9 181 U1 1 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2007 VL 45 IS 12 BP 2802 EP 2810 DI 10.1016/j.neuropsychologia.2007.05.002 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 205WR UT WOS:000249145800016 PM 17575989 ER PT J AU Bolla, KI Cadet, JL AF Bolla, Karen I. Cadet, Jean L. BE Kalechstein, A van Gorp, WG TI Cocaine SO NEUROPSYCHOLOGY AND SUBSTANCE USE: STATE-OF-THE-ART AND FUTURE DIRECTIONS SE Studies on Neuropsychology Development and Cognition LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; GLUCOSE METABOLIC RATES; ORBITOFRONTAL CORTEX; DECISION-MAKING; HUMAN BRAIN; DEPENDENT PATIENTS; BINDING-SITES C1 [Bolla, Karen I.] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21218 USA. [Cadet, Jean L.] NIDA, Baltimore, MD USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21218 USA. NR 140 TC 4 Z9 4 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-83771-9 J9 STUD NEUROPSYCH DEV PY 2007 BP 111 EP 138 PG 28 WC Psychology, Biological; Substance Abuse; Neurosciences; Psychology SC Psychology; Substance Abuse; Neurosciences & Neurology GA BUX53 UT WOS:000290615100005 ER PT J AU Quarta, D Ciruela, F Patkar, K Borycz, J Solinas, M Lluis, C Franco, R Wise, RA Goldberg, SR Hope, BT Woods, AS Ferre, S AF Quarta, Davide Ciruela, Francisco Patkar, Kshitij Borycz, Janusz Solinas, Marcello Lluis, Carme Franco, Rafael Wise, Roy A. Goldberg, Steven R. Hope, Bruce T. Woods, Amina S. Ferre, Sergi TI Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE dopamine D-2 receptor; nicotinic acetylcholine receptor; autoreceptor; heteroreceptor; dopamine release; striatum ID GLUTAMATE TYPE-1-ALPHA RECEPTOR; RAT NUCLEUS-ACCUMBENS; PHARMACOLOGICAL CHARACTERIZATION; EXTRACELLULAR DOPAMINE; TRANSMITTER RELEASE; BRAIN-REGIONS; A1 ADENOSINE; IN-VIVO; SYNAPTOSOMES; MICRODIALYSIS AB In the stratum, dopamine and acetylcholine (ACh) modulate dopamine release by acting, respectively, on dopamine D-2 autoreceptors and nicotinic ACh (nACh) heteroneceptors localized on dopaminergic nerve terminals. The possibility that functional interactions exist between stratal D-2 autoreceptors and nACh receptors was studied with in vivo microdialysis in freely moving rats. Local perfusion of nicotine in the ventral striatum (shell of the nucleus accumbens) produced a marked increase in the extracellular levels of dopamine, which was completely counteracted by co-perfusion with either the non-alpha(7) nACh receptor antagonist dihydro-beta-erythroidine or the D2-3 receptor agonist quinpirole. Local perfusion of the D2-3 receptor antagonist raclopride produced an increase in the extracellular levels of dopamine, which was partially, but significantly, counteracted by coperfusion with dihydro-beta-erythroidine. These findings demonstrate a potent crosstalk between G protein-coupled receptors and ligand-gated ion channels in dopaminergic nerve terminals, with the D-2 autoreceptor modulating the efficacy of non-alpha(7) nACh receptor-mediated modulation of dopamine release. We further demonstrate physical interactions between beta(2) subunits of non-alpha(7) nicotinic acetylcholine receptors and D2 autoreceptors in co-immunoprecipitation experiments with membrane preparations from co-transfected mammalian cells and rat striatum. These results reveal that stratal non-alpha(7) nicotinic acetylcholine receptors form part of heteromeric dopamine autoreceptor complexes that modulate dopamine release. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. Univ Barcelona, Dept Biochem & Mol Biol, E-08007 Barcelona, Spain. Natl Inst Drug Abuse, Cellular Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Wise, Roy/A-6465-2012; Hope, Bruce/A-9223-2010; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Solinas, Marcello/M-3500-2016 OI Hope, Bruce/0000-0001-5804-7061; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 50 TC 41 Z9 42 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2007 VL 32 IS 1 BP 35 EP 42 DI 10.1038/sj.npp.1301103 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 117UT UT WOS:000242899500003 PM 16710311 ER PT J AU Hansson, AC Bermudez-Silvaz, FJ Hyytia, P Sanchez-Vera, I Rimondini, R de Fonseca, FR Kunos, G Sommer, WH Heilig, M AF Hansson, Anita C. Bermudez-Silvaz, Francisco J. Hyytia, Petri Sanchez-Vera, Irene Rimondini, Roberto de Fonseca, Fernando Rodriguez Kunos, George Sommer, Wolfgang H. Heilig, Markus TI Genetic impairment of frontocortical endocannabinoid degradation and high alcohol preference SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE endocannabinoids; CB1; SR141716A; FAAH; alcoholism; prefrontal cortex ID RAT PREFRONTAL CORTEX; CANNABINOID CB1 RECEPTOR; ACID AMIDE HYDROLASE; VOLUNTARY ETHANOL-CONSUMPTION; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; PROBLEM DRUG-USE; KNOCKOUT MICE; MESSENGER-RNA; BRAIN AB Endocannabinoid signaling has recently been implicated in ethanol-seeking behavior. We analyzed the expression of endocannabinoid-related genes in key brain regions of reward and dependence, and compared them between the alcohol-preferring AA (Alko Alcohol) and nonpreferring ANA (Alko Non-Alcohol) rat lines. A decreased expression of fatty acid amidohydrolase (FAAH), the main endocannabinoid-degrading enzyme, was found in prefrontal cortex (PFC) of AA rats, and was accompanied by decreased enzyme activity in this region. Binding of the endocannabinoid-cannabinoid 1 (CB1) receptor ligand (3)[H]SR141716A, and [35S]GTP gamma S incorporation stimulated by the CB1 agonist WIN 55,2 12-2 were downregulated in the same area. Together, this suggests an overactive endocannabinoid transmission in the PFC of AA animals, and a compensatory downregulation of CB1 signaling. The functional role of impaired FAAH function for alcohol self-administration was validated in two independent ways. The CB1 antagonist SR141716A potently and dose-dependently suppressed self-administration in AA rats when given systemically, or locally into the PFC, but not in the striatum. Conversely, intra-PFC injections of the competitive FAAH inhibitor URB597 increased ethanol self-administration in nonselected Wistar rats. These results show for the first time that impaired FAAH function may confer a phenotype of high voluntary alcohol intake, and point to a FAAH both as a potential susceptibility factor and a therapeutic target. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Fdn IMABIS, Malaga, Spain. Natl Publ Hlth Inst, SF-00140 Helsinki, Finland. Univ Bologna, Dept Pharmacol, I-40126 Bologna, Italy. Karolinska Inst, Dept Clin Neurosci, S-10401 Stockholm, Sweden. NIAAA, Neuroendocrinol Lab, Bethesda, MD USA. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Bldg 10,CRC,EI-5334,10 Ctr Dr MSC 1108, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Rimondini, Roberto/B-2500-2010; RODRIGUEZ DE FONSECA, FERNANDO/E-9767-2012; Bermudez-Silva, Francisco Javier/Q-6920-2016; OI Rimondini, Roberto/0000-0003-4099-513X; Bermudez-Silva, Francisco Javier/0000-0003-3133-9691; Heilig, Markus/0000-0003-2706-2482; Sommer, Wolfgang/0000-0002-5903-6521; Hyytia, Petri/0000-0002-0284-1298 NR 56 TC 76 Z9 78 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2007 VL 32 IS 1 BP 117 EP 126 DI 10.1038/sj.npp.1301034 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 117UT UT WOS:000242899500011 PM 16482090 ER PT J AU Hodgkinson, CA Goldman, D Ducci, F DeRosse, P Caycedo, DA Newman, ER Kane, JM Roy, A Malhotra, AK AF Hodgkinson, Colin A. Goldman, David Ducci, Francesca DeRosse, Pamela Caycedo, Daniel A. Newman, Emily R. Kane, John M. Roy, Alec Malhotra, Anil K. TI The FEZ I gene shows no association to schizophrenia in Caucasian or African American populations SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; schizoaffective; genetics; association; haplotype; African American ID HAPLOTYPE RECONSTRUCTION; NEURITE OUTGROWTH; BRAIN-DEVELOPMENT; DISC1; DISRUPTED-IN-SCHIZOPHRENIA-1; PROTEIN; TRANSLOCATION; EXPRESSION; DISORDER; NUDEL AB Schizophrenia is a complex psychiatric disorder with both genetic and environmental components and is thought to be in part neurodevelopmental in origin. The DISC I gene has been linked to schizophrenia in two independent Caucasian populations. The DISC I protein interacts with a variety of proteins including FEZ I, the mammalian homolog of the Caenorhabditis elegans unc-76 protein, which is involved in axonal outgrowth. Variation at the FEZ I gene has been associated with schizophrenia in a large Japanese cohort. In this study, nine SNP markers at the FEZ I locus were genotyped in two populations. A North American Caucasian cohort of 212 healthy controls, 178 schizophrenics, 79 bipolar disorder, and 58 with schizoaffective disorder, and an African American cohort of 133 healthy controls, 162 schizophrenics, and 28 with schizoaffective disorder. No association to schizophrenia, bipolar disorder or schizoaffective disorder was found for any of the nine markers typed in these populations at the allelic: or the genotypic level. Additionally no association was found in either population between specific haplotypes and any of the psychiatric disorders. Variation at the FEZ I locus does not play a significant role in the etiology of schizophrenia, bipolar disorder or schizoaffective disorder in North American Caucasian or African American populations. C1 NIAAA, Neurogenet Lab, Sect Human Neurogenet, Rockville, MD 20852 USA. Hillside Hosp, Glen Oaks, NY 11004 USA. New Jersey Hlth Syst, Psychiat Serv, Dept Vet Affairs, E Orange, NJ USA. RP Hodgkinson, CA (reprint author), NIAAA, Neurogenet Lab, Sect Human Neurogenet, 5625 Fishers Lane,Room 3S32,MSC9412, Rockville, MD 20852 USA. EM chodg@mail.nih.go RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH NIH HHS [K23MH001760] NR 34 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2007 VL 32 IS 1 BP 190 EP 196 DI 10.1038/sj.npp.1301177 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 117UT UT WOS:000242899500018 PM 16936715 ER PT J AU Finger, EC Marsh, AA Buzas, B Kamel, N Rhodes, R Vythilingham, M Pine, DS Goldman, D Blair, JR AF Finger, Elizabeth C. Marsh, Abigail A. Buzas, Beata Kamel, Niveen Rhodes, Rebecca Vythilingham, Meena Pine, Daniel S. Goldman, David Blair, James R. TI The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE tryptophan depletion; 5-HTTLPR; reward; response reversal ID PREFRONTAL SEROTONIN DEPLETION; MAJOR DEPRESSIVE DISORDER; GENETIC-VARIATION; ORBITOFRONTAL CORTEX; HEALTHY-VOLUNTEERS; HUMAN-BRAIN; EXPECTED OUTCOMES; HUMAN AMYGDALA; TRANSPORTER; ACQUISITION AB Transient reductions in serotonin levels during tryptophan depletion (TD) are thought to impair reward processing in healthy volunteers, while another facet of the serotonergic system, the serotonin transporter (5-HTTLPR) short allele polymorphism, is implicated in augmented processing of aversive stimuli. We examined the impact and interactions of TD and the serotonin promoter polymorphism genotype on reward and punishment via two forms of instrumental learning: passive avoidance and response reversal. In this study, healthy volunteers (n = 35) underwent rapid TD or control procedures and genotyping (n = 26) of the 5-HTTLPR for long and short allele variants. In the passive avoidance task, tryptophan-depleted volunteers failed to respond sufficiently to rewarded stimuli compared to the control group. Additionally, long allele homozygous individuals (n = 11) were slower to learn to avoid punished stimuli compared to short allele carriers (n = 15). TD alone did not produce measurable deficits in probabilistic response reversal errors. However, a significant drug group by genotype interaction was found indicating that in comparison to short allele carriers, tryptophan-depleted individuals homozygous for the long allele failed to appropriately use punishment. information to guide responding. These findings extend prior reports of impaired reward processing in TD to include instrumental learning. Furthermore, they demonstrate behavioral differences in responses to punishing stimuli between long allele homozygotes and short allele carriers when serotonin levels are acutely reduced. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Hammersmith Hosp, Imperial Coll, Psychiat Grp, MRC Clin Sci Ctr, London, England. RP Finger, EC (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM fngere@mail.nih.gov RI Finger, Elizabeth/B-6453-2015; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS NR 67 TC 48 Z9 49 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2007 VL 32 IS 1 BP 206 EP 215 DI 10.1038/sj.npp.1301182 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 117UT UT WOS:000242899500020 PM 16900105 ER PT J AU Grillon, C Levenson, J Pine, DS AF Grillon, Christian Levenson, Jessica Pine, Daniel S. TI A single dose of the selective serotonin reuptake inhibitor citalopram exacerbates anxiety in humans: A fear-potentiated startle study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fear; anxiety; SSRI; citalopram; startle reflex; predictability ID HEALTHY-VOLUNTEERS; CONDITIONED FEAR; BED NUCLEUS; FLUOXETINE; RESPONSES; AMYGDALA; MODELS; 5-HT; MODULATION; DEPRESSION AB Serotonin reuptake inhibitors may increase symptoms of anxiety immediately following treatment initiation. The present study examined whether acute citalopram increased fear-potentiated startle to predictable and/or unpredictable shocks in healthy subjects. Eighteen healthy subjects each received two treatments, placebo and 20 mg citalopram in a crossover design. Participants were exposed to three conditions including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Changes in aversive states were investigated using acoustic startle stimuli. Citalopram did not affect baseline startle. However, the phasic startle potentiation to the threat cue in the predictable condition was robustly increased by acute citalopram. The sustained startle potentiation in the unpredictable conditions was also increased by citalopram, but only when the drug was given during the first session. These results indicate that a single dose of citalopram is not anxiogenic in itself, but can exacerbate the expression of fear and anxiety. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM Christian.grillon@nih.gov RI Levenson, Jessica/O-5448-2015 FU Intramural NIH HHS NR 38 TC 85 Z9 86 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2007 VL 32 IS 1 BP 225 EP 231 DI 10.1038/sj.npp.1301204 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 117UT UT WOS:000242899500022 PM 16971899 ER PT J AU Millstein, RA Holmes, A AF Millstein, Rachel A. Holmes, Andrew TI Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the European-Brain-and-Behavior-Society CY SEP 24-28, 2005 CL Trinity Coll, Dublin, IRELAND SP European Brain & Behav Soc HO Trinity Coll DE gene; mouse; strain; inbred; maternal separation; early life; stress; anxiety; depression; stress; postnatal; handling ID CHILDHOOD SEXUAL-ABUSE; TAIL-SUSPENSION TEST; POSTTRAUMATIC-STRESS-DISORDER; ELEVATED PLUS-MAZE; 11 INBRED STRAINS; NULL MUTANT MICE; LIFE EVENTS; PREPULSE INHIBITION; SUICIDAL-BEHAVIOR; MAJOR DEPRESSION AB Genetic factors and early life adversity both play a major role in the etiology of mood and anxiety disorders. Previous studies have shown that postnatal maternal separation (MS) can produce lasting abnormalities in emotion-related behavior and neuroendocrine responses to stress in rodents. The present study sought to examine the effects of repeated MS in eight different inbred strains of mice (129S1/SvImJ, 129P3/J, A/J, BALB/cJ, BALB/cByJ C57BL/6J, DBA/2J, FVB/NJ). Pups were separated from their dam and littermates for 180 min/day ('MS') or 15 min/day ('handling'), or left undisturbed ('facility-reared') from postnatal days P0-P13, and tested as adults for anxiety- and depression-related behaviors. Results demonstrated no clear and consistent effects of MS or handling on behavioral phenotypes in any of the strains tested. In all strains, MS produced an increase in maternal care on reunion with pups, which may have modified MS effects. Data demonstrate that the MS procedure employed does not provide a robust model of early life stress effects on the anxiety- and depression-related behaviors in the mouse strains tested. Published by Elsevier Ltd. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov FU Intramural NIH HHS NR 115 TC 172 Z9 173 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 1 BP 3 EP 17 DI 10.1016/j.neubiorev.2006.05.003 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 130YI UT WOS:000243834500002 PM 16950513 ER PT J AU Calhoun, F Warren, K AF Calhoun, Faye Warren, Kenneth TI Fetal alcohol syndrome: Historical perspectives SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE fetal alcohol syndrome; diagnosis ID SPECTRUM; MOTHERS AB Fetal alcohol syndrome (FAS), the most severe manifestation of the adverse effects of alcohol on foetal development, was first described in the French medical literature by Lemoine et al. in 1968 [Les Gfants des parents alcholiques: anomalies observes a propos de 127 cas (The children of alchoholic parents: anomalies observed in 127 cases). Quert in Medicine 8, 476-482]. Five years later, Jones et al., 1973. Pattern of malformation in offspring of chronic alcholic mothers. Lancet 1, 1129-1267] were the first to delineate systematically the association between maternal alcohol abuse and a specific pattern of birth defects and to provide diagnostic criteria for this condition. Several diagnostic systems have since been developed with a view to capturing the wide spectrum of physical and behavioral anomalies resulting from prenatal alcohol exposure. The purpose of the current paper is to outline the evolution of FAS as a medical diagnosis. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAAA, NIH, Bethesda, MD USA. RP Calhoun, F (reprint author), NIAAA, NIH, Bethesda, MD USA. EM fcalhoun@willco.niaaa.nih.gov NR 25 TC 29 Z9 31 U1 3 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 2 BP 168 EP 171 DI 10.1016/j.neubiorev.2006.06.023 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 143YU UT WOS:000244763100002 PM 17224346 ER PT J AU Macri, S Spinelli, S Adriani, W Higley, JD Laviola, G AF Macri, Simone Spinelli, Simona Adriani, Walter Higley, James Dee Laviola, Giovanni TI Early adversity and alcohol availability persistently modify serotonin and hypothalamic-pituitary-adrenal-axis metabolism and related behavior: What experimental research on rodents and primates can tell us SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE animal models; postnatal manipulations; rodents; primates; fetal alcohol syndrome (FAS); serotonin; HPA-axis; developmental plasticity ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; TRANSPORTER GENE VARIATION; PRENATAL ETHANOL EXPOSURE; MATERNAL-CARE; NONHUMAN-PRIMATES; IN-UTERO; ENVIRONMENTAL CONTRIBUTIONS; CORTICOSTERONE SECRETION; PSYCHOLOGICAL VARIABLES AB Early experiences have profound influences on individual developmental trajectories. For example alcohol exposure during central nervous system development relates to a number of pathological consequences in adulthood. An increased risk of developing psychiatric disorders, like major depression and impulse-control-related pathologies is associated with alcohol exposure during fetal life and/or during adolescence. Additionally, adverse life experiences occurring early in development may exacerbate these consequences, while impinging on the same neural systems affected by precocious alcohol exposure. Conversely, a protective and/or stimulating environment may mitigate these alcohol-related negative outcomes. Experimental research in animal models constitutes a primary source of information in understanding both functional and dysfunctional human adaptations to these events. In this review, a selection of rodent and primate studies shows that developmental ethanol exposure on the one hand, and environmental treatments aimed at modifying the mother-offspring interaction on the other hand, independently modulate similar neuro-endocrine systems. In particular, we discuss the effects that the above-mentioned independent variables exert on the hypothalamic-pituitary-adrenal (HPA)-axis and on brain serotonergic pathways. Experimental evidence indicates that pathological adaptations of these systems are valuable predictors of human neuro-behavioral abnormalities like depression, impaired impulse control and alcohol abuse. Finally, a working hypothesis is proposed, which combines primate and rodent studies aimed: (i) at studying functional and pathological individual development following early ethanol consumption, and (ii) at heading towards a better definition of potential intervention strategies. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, I-00161 Rome, Italy. NIAAA, Lab Clin & Translat Studies, NIH, Anim Ctr, Poolesville, MD USA. RP Laviola, G (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM laviola@iss.it RI Laviola, Giovanni/K-4392-2016; OI Laviola, Giovanni/0000-0003-0388-0835; Macri, Simone/0000-0003-2946-4784 NR 97 TC 19 Z9 20 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 2 BP 172 EP 180 DI 10.1016/j.neubiorev.2006.06.026 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 143YU UT WOS:000244763100003 PM 16956661 ER PT J AU Martin-Soelch, C Linthicum, J Ernst, M AF Martin-Soelch, C. Linthicum, J. Ernst, M. TI Appetitive conditioning: Neural bases and implications for psychopathology SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE functional imaging; cognition; learning; reward; amygdala; orbitofrontal cortex; anterior cingulate; striatum; eating disorders; depression ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; BASOLATERAL AMYGDALA COMPLEX; TEMPORAL DIFFERENCE MODELS; ETHANOL-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS CORE; CHRONIC MILD STRESS; ORBITOFRONTAL CORTEX; VENTRAL STRIATUM; NEURONAL-ACTIVITY AB Appetitive conditioning is the process through which new rewards are learned and acquire their motivational salience. Although it has the same evolutionary survival significance as aversive conditioning, appetitive conditioning has rarely been studied in humans. This gap may be explained by the difficulty to find in humans suitable appetitive stimuli that can elicit physiological responses similar to those elicited by aversive stimuli. To help remedy this gap, we review the literature on conditioning, with emphasis on appetitive conditioning. This review comprises three parts. First, we examine the different forms of conditioning. Second, we review the neural basis of appetitive conditioning, particularly from a functional neuroimaging perspective. And third, we demonstrate how perturbations in processes involved in appetitive conditioning can contribute to implicated psychopathologies and suggest neurobiological. models underlying these pathologies. The ultimate goal of this review is to stimulate new avenues of research that have direct links to molecular biology, and thus could prove to be invaluable to progress in the understanding and treatment of psychiatric disabilities. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. RP Ernst, M (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD USA. EM ernstm@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 136 TC 64 Z9 66 U1 9 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 3 BP 426 EP 440 DI 10.1016/j.neubiorev.2006.11.002 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 165OZ UT WOS:000246316100009 PM 17210179 ER PT J AU Rowe, MK Wiest, C Chuang, DM AF Rowe, Michael K. Wiest, Charlotte Chuang, De-Maw TI GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE animal models; anti-depressant; anti-mania; bipolar disorder; GSK-3; lithium; valproate ID GLYCOGEN-SYNTHASE KINASE-3; FORCED SWIM TEST; SUBGENUAL PREFRONTAL CORTEX; DEPENDENT PROTEIN-KINASE; DNA-BINDING ACTIVITY; VALPROIC ACID; SIGNALING PATHWAYS; MOOD DISORDERS; FRONTAL-CORTEX; BETA-CATENIN AB Bipolar disorder is a serious psychiatric condition that has been treated for over 50 years with lithium. Lithium is a well established glycogen synthase kinase-3 (GSK-3) inhibitor, suggesting that manipulating GSK-3 may have therapeutic value in treating bipolar disorder. GSK-3 is regulated by a wide variety of mechanisms including phosphorylation, binding with protein complexes, phosphorylation state of its substrates, cellular localization and autoregulation, thus providing a wide number of potential therapeutic mechanisms. Mounting evidence suggests that GSK-3 regulation can be used to manage bipolar disorder symptoms. Although GSK-3 mutations have not been detected amongst the general bipolar population, they have been correlated with females with bipolar 11 and most of the drugs used for successful bipolar disorder treatment regulate GSK-3. These drugs produce a weak anti-depressant-like and a strong anti-mania-like effect in a wide range of animal models tested, mirroring their utility in treating bipolar disorder symptoms. Taken together, the evidence suggests that targeting GSK-3 may be a means to control the symptoms of bipolar disorder. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIMH, Mol Neurobiol Sect, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Mood & Anxiety Disorders Program, Bldg 10,Room 4C206,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 117 TC 98 Z9 102 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 6 BP 920 EP 931 DI 10.1016/j.neubiorev.2007.03.002 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 216LI UT WOS:000249879100010 PM 17499358 ER PT J AU O'Donnell, KC Gould, TD AF O'Donnell, Kelley C. Gould, Todd D. TI The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE mood stabilizer; antidepressant; animal model; endophenotype; bipolar disorder; manic-depressive illness; mania; depression; rat; mouse ID FORCED-SWIMMING TEST; INDUCED STATUS EPILEPTICUS; OPEN-FIELD ACTIVITY; EMERGING EXPERIMENTAL THERAPEUTICS; ADJUNCTIVE ALCOHOL-CONSUMPTION; INTRACRANIAL SELF-STIMULATION; INDUCED LOCOMOTOR STIMULATION; CONDITIONED PLACE PREFERENCE; RECEPTOR SUPER-SENSITIVITY; GLYCOGEN-SYNTHASE KINASE-3 AB For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIMH, NIH HHS, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Gould, TD (reprint author), NIMH, NIH HHS, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bldg 35,Rm 1C-912,35 Convent Dr, Bethesda, MD 20892 USA. EM gouldt@mail.nih.gov FU Intramural NIH HHS [NIH0010875152]; PHS HHS [NIH0010875152] NR 281 TC 69 Z9 70 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2007 VL 31 IS 6 BP 932 EP 962 DI 10.1016/j.neubiorev.2007.04.002 PG 31 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 216LI UT WOS:000249879100011 PM 17532044 ER PT J AU Matsuki, T Pramatarova, A Howell, BW AF Matsuki, Tohru Pramatarova, Albena Howell, Brian W. TI Crk is required for Reelin-mediated hippocampal dendrite outgrowth SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S202 EP S202 DI 10.1016/j.neures.2007.06.916 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272801200 ER PT J AU Matsumoto, M Hikosaka, O AF Matsumoto, Masayuki Hikosaka, Okihide TI Role of the primate lateral habenula in negative motivational control of behavior SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NIH, NEI, Sensorimotor Res Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S60 EP S60 DI 10.1016/j.neures.2007.06.350 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272800347 ER PT J AU Matsumoto, N Hasegawa, RP AF Matsumoto, Narihisa Hasegawa, Ryohei P. TI Prediction of multi-dimensional decision-making based on the single-trial activities of a population of prefrontal neurons SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 AIST, Neurosci Res Inst, Tsukuba, Ibaraki, Japan. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S161 EP S161 DI 10.1016/j.neures.2007.06.665 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272800949 ER PT J AU Mizuhiki, T Richmond, BJ Shidara, M AF Mizuhiki, Takashi Richmond, Barry J. Shidara, Munetaka TI Differences between single neuronal responses in anterior and posterior insula during multi-trial reward schedules SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. AIST, Neurosci Res Inst, Tsukuba, Ibaraki, Japan. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S170 EP S170 DI 10.1016/j.neures.2007.06.719 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272801003 ER PT J AU Nakazawa, K Jinde, S Cravens, CJ Belforte, JE AF Nakazawa, Kazutoshi Jinde, Seiichiro Cravens, Catherine J. Belforte, Juan E. TI Characterization of dentate mossy cell-restricted NMDA receptor knockout mice SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2007 VL 58 SU 1 BP S14 EP S14 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 207TA UT WOS:000249272800076 ER PT J AU Meldrum, BS Rogawski, MA AF Meldrum, Brian S. Rogawski, Michael A. TI Molecular targets for antiepileptic drug development SO NEUROTHERAPEUTICS LA English DT Review DE epilepsy; channelopathy; antiepileptic drug; sodiumchannel; calcium channel; potassium channel; GABA receptor; glutamate receptor; GABA transporter; glutamate transporter; gap junction ID METHYL-D-ASPARTATE; METABOTROPIC GLUTAMATE RECEPTORS; UNION-OF-PHARMACOLOGY; GAMMA-AMINOBUTYRIC-ACID; TEMPORAL-LOBE EPILEPSY; CENTRAL-NERVOUS-SYSTEM; GATED SODIUM-CHANNELS; P/Q-TYPE CA2+; IDIOPATHIC GENERALIZED EPILEPSY; JUVENILE MYOCLONIC EPILEPSY AB This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs ( AEDs). Marketed AEDs predominantly target voltage-gated cation channels ( the alpha subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, alpha 2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABA(A) receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA(B) and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation ( HCN) channel subunits, responsible for hyperpolarization-activated current I-h; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABA(A) receptor isoforms responsible for tonic ( extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. C1 Kings Coll London, Sch Med, Ctr Neurosci, Div Biomed & Hlth Sci, London WC2R 2LS, England. NIH, NINDS, Epilepsy Res Sect, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS002877-13] NR 431 TC 232 Z9 254 U1 7 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2007 VL 4 IS 1 BP 18 EP 61 DI 10.1016/j.nurt.2006.11.010 PG 44 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 214JX UT WOS:000249734900005 PM 17199015 ER PT J AU Roecklein, BA Sacks, HJ Mortko, H Stables, J AF Roecklein, Bryan A. Sacks, Harry J. Mortko, Henry Stables, James TI Fluorofelbamate SO NEUROTHERAPEUTICS LA English DT Article DE carbamates; fluorofelbamate; felbamate; felbatol; dicarbamates; anticonvulsant; metabolism; atropaldehyde; glutathione ID PARTIAL-ONSET SEIZURES; FELBAMATE MONOTHERAPY; CONTROLLED TRIAL; METABOLITES AB The incidence of refractory seizures has remained at 30-40%, even with the approval of nine new anticonvulsants over the past 12 years. In attempts to reduce seizure frequency and severity, physicians routinely resort to combining two or more anticonvulsants, ideally with different mechanisms of action. These combinatorial therapies are difficult to administer for both patient and caregiver and often result in tolerability issues. Hence, a broad spectrum anticonvulsant, with multiple mechanisms of action, that is well tolerated, would provide physicians with an important option in their armamentarium to control seizures. Felbamate initially fit this profile and was demonstrated to effectively control both partial and generalized seizures in clinical studies supporting registration.(1-5) Unfortunately, unanticipated idiosyncratic toxicity was observed after approval and the drug is now relegated to second or third line therapy, depending on patient history and seizure type. Epileptologists still prescribe this drug for refractory seizures, and a recent communication indicates that 35,000 to 46,000 new patients have tried Felbatol ( MedPointe Pharmaceuticals, Somerset, NJ) since 1995.(6) The continued utilization of Felbatol, in light of its risk: benefit issues, highlights the need for new efficacious therapeutic options. Fluorofelbamate ( MedPointe Pharmaceuticals), a phase I drug candidate, was designed to retain the broad spectrum multimechanistic activity of felbamate, with a modified metabolism that has demonstrated, in vitro, to avoid the production of the reactive metabolite believed to cause the idiosyncratic toxicity. This drug candidate is one of several carbamates either in development or currently on the market for treatment of seizures and other CNS disorders. C1 MedPointe Pharmaceut, Somerset, NJ 08873 USA. NIH, NINDS, Bethesda, MD 20892 USA. RP Roecklein, BA (reprint author), MedPointe Pharmaceut, 265 Davidson Ave, Somerset, NJ 08873 USA. EM BRoecklein@medpointpharma.com NR 9 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2007 VL 4 IS 1 BP 97 EP 101 DI 10.1016/j.nurt.2006.11.015 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 214JX UT WOS:000249734900011 PM 17199021 ER PT J AU Witt, ED AF Witt, Ellen D. TI Puberty, honnones, and sex differences in alcohol abuse and dependence SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Review DE sex differences; alcohol drinking; pubertal hormones ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; ESTROGEN-RECEPTOR-BETA; DORSAL RAPHE NUCLEUS; MONKEYS MACACA-FASCICULARIS; CENTRAL AMYGDALOID NUCLEUS; STRIATAL DOPAMINE RELEASE; NONHUMAN PRIMATE MODEL; MENSTRUAL-CYCLE PHASE AB Sex differences in patterns of drinking and rates of alcohol abuse and dependence begin to emerge during the transition from late puberty to young adulthood. Increases in pubertal hormones, including gonadal and stress hormones, are a prominent developmental feature of adolescence and could contribute to the progression of sex differences in alcohol drinking patterns during puberty. This paper reviews experimental and correlational studies of gonadal and stress-related hormone changes and their effects on alcohol drinking and other associated actions of alcohol. Mechanisms are suggested by which reproductive hormones and stress-related hormones may modulate neural circuits within the brain reward system to produce sex differences in alcohol drinking patterns and vulnerability to alcohol abuse and dependence which become apparent during the late pubertal period. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Div Neurosci & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Witt, ED (reprint author), NIAAA, Div Neurosci & Behav, NIH, Dept Hlth & Human Serv, 5635 Fishers Lane Room 2055,MSC 9304, Bethesda, MD 20892 USA. EM ewitt@mail.nih.gov NR 222 TC 61 Z9 61 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2007 VL 29 IS 1 BP 81 EP 95 DI 10.1016/j.ntt.2006.10.013 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 144IZ UT WOS:000244791000011 PM 17174531 ER PT J AU Burgio, K AF Burgio, K. TI Combining behavior and drug therapy to improve drug withdrawal in the treatment of urge incontinence: A randomized trial SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 37th Annual Meeting of the International-Continence-Society CY AUG 20-24, 2007 CL Rotterdam, NETHERLANDS SP Int Continence Soc ID URINARY-INCONTINENCE C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NIDDKD, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 5 MA 21 BP 629 EP 630 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 197DM UT WOS:000248534000022 ER PT J AU Nygaard, I Kreder, K Mueller, E Brubaker, L Goode, P Visco, A Weber, AM Cundiff, G Wei, J AF Nygaard, Ingrid Kreder, Karl Mueller, Elizabeth Brubaker, Linda Goode, Patricia Visco, Anthony Weber, Anne M. Cundiff, Geoff Wei, John CA Pelvic Floor Disorders Network TI Does urethral competence affect urodynamic voiding parameters in women with prolapse? SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE obstruction; pelvic organ prolapse; urodynamics; voiding ID PELVIC ORGAN PROLAPSE; VAGINAL VAULT PROLAPSE; UTEROVAGINAL PROLAPSE; URINARY-INCONTINENCE; STRESS-INCONTINENCE; CONTINENT WOMEN; COLPOSUSPENSION; PREVALENCE; REPAIR AB Aims: To (1) compare voiding parameters and (2) correlate symptoms and urodynamic findings in women with pelvic organ prolapse (POP) and varying degrees of urethral competence. Methods: We compared three groups of women with stages II-IV POP. Groups 1 and 2 were symptomatically stress continent women participating in the Colpopexy and Urinary Reduction Efforts (CARE) trial; during prolapse reduction before sacrocolpopexy, Group I (n = 67) did not have and Group 2 (n 84) had urodynamic stress incontinence (USI) during prolapse reduction. Group 3 participants (n = 74), recruited specifically for this study, had stress urinary incontinence (SUI) symptoms and planned sacrocolpopexy. Participants completed standardized uroflowmetry, pressure voiding studies, and validated symptom questionnaires. Results: Subjects' median age was 61 years, median parity 3 and 87% had stage III or IV POP. Four-teen percent of women in Group 3 demonstrated USI without, and 70% with, prolapse reduction. Women in Groups 2 and 3 had more detrusor overactivity (DO) than Group 1 (17 and 24% vs. 6%, P = 0.02) and detrusor overactivity incontinence (DOI) (15 and 8% vs. 0%, P = 0.004). Based on the Blaivis-Groutz nomogram, 60% of all women were obstructed. Post-void residual volume (PVR), peak flow rate, detrusor pressure at peak flow, voiding mechanisms, voiding patterns, obstruction and urinary retention did not differ among groups. Women in Group 3 had higher irritative and obstructive symptom scores than Group 1 or 2; neither score differed by presence of DO nor obstruction, respectively. Conclusion: Women with POP have significant rates of urodynamic obstruction and retention, independent of their continence status. Symptoms of obstruction and retention correlate poorly with urodynamic findings. C1 Univ Utah, Dept Obstet & Gynecol, Coll Med, Salt Lake City, UT 84132 USA. Univ Iowa, Dept Urol, Carver Coll Med, Iowa City, IA USA. Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Alabama, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. NICHHD, Bethesda, MD USA. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V5Z 1M9, Canada. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. RP Nygaard, I (reprint author), Univ Utah, Dept Obstet & Gynecol, Coll Med, 30 North 1900 East,Room 2B 242, Salt Lake City, UT 84132 USA. EM Ingrid.nygaard@hsc.utah.edu OI Mueller, Elizabeth R./0000-0003-3069-4069 FU NICHD NIH HHS [U10 HD41269, U10 HD41248, U10 HD41268, U01 HD41249, U10 HD041261, U10 HD41267, U10 HD41263, U10 HD41250, U10 HD41261] NR 18 TC 5 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2007 VL 26 IS 7 BP 1030 EP 1035 DI 10.1002/nau.20436 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 227BV UT WOS:000250633100015 PM 17638306 ER PT B AU Kruth, HS Buono, C Waldo, SW Li, Y AF Kruth, H. S. Buono, C. Waldo, S. W. Li, Y. BE Lewis, BS Halon, DA Flugelman, MY TI Macrophage foam cell formation mediated by receptor-independent macropinocytosis of LDL SO NEW HORIZONS IN CORONARY ARTERY DISEASE LA English DT Proceedings Paper CT 7th International Congress on Coronary Artery Disease CY OCT 07-10, 2007 CL Venice, ITALY ID LOW-DENSITY-LIPOPROTEIN; LIVER-X RECEPTORS; CHOLESTEROL ACCUMULATION; ATHEROSCLEROSIS; MICE; LIGAND; CD36 AB Macrophage cholesterol accumulation is an important process in the development of atherosclerotic plaques. Previously, researchers believed that only incubation of macrophages with LDL modified, for example, by oxidation could result in cholesterol accumulation. In recent research, we reported that human monocyte-derived macrophages show receptor-independent fluid-phase uptake of native (unmodified) LDL. This uptake is mediated by macropinocytosis. During macropinocytosis, macrophages take up large amounts of fluid and LDL contained in the fluid resulting in massive macrophage cholesterol accumulation. This mechanism of LDL uptake and cholesterol accumulation does not depend on cell receptors or LDL modification. Monocyte-derived macrophages differentiated in the presence of M-CSF show constitutive macropinocytosis of LDL, while monocyte-derived macrophages differentiated with GM-CSF show PMA-activated macropinocytosis of LDL. Interestingly, treatment of M-CSF differentiated macrophages with LXR agonists substantially decreases macrophage macropinocytosis of LDL helping to explain the anti-atherosclerosis activity of LXR agonists. In conclusion, our findings direct attention to macrophage fluid-phase macropinocytosis as a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. C1 [Kruth, H. S.; Buono, C.; Waldo, S. W.; Li, Y.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-401-8 PY 2007 BP 109 EP 113 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHB05 UT WOS:000252017900019 ER PT J AU Mabry, PL Tooze, JA Moser, RP Augustson, EM Malcolm, RJ Benowitz, NL AF Mabry, Patricia L. Tooze, Janet A. Moser, Richard P. Augustson, Erik M. Malcolm, Robert J. Benowitz, Neal L. TI Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: Results from a pilot study with African American men SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTE-SMOKING; TOBACCO DEPENDENCE; PARTICULATE MATTER; SEX-DIFFERENCES; ORAL-MUCOSA; SMOKERS; REPLACEMENT; CESSATION; METABOLISM; BLOOD AB Nicotine intake via smoking is highly variable. Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms. A pilot study was undertaken to collect data on these relationships and to assess the feasibility of the methods needed for this type of research, including a sophisticated statistical modeling technique (a two-part mixed-effects model with correlated random effects that accounts for clumping at zero). Because nicotine metabolism varies by gender and race, the sample was homogeneous with respect to these characteristics. In a within-subjects study, 27 African American adult male smokers carried a computerized cigarette dispenser for 1 week, capturing the time each cigarette was smoked. Subjects then entered an inpatient setting for 1 day of scheduled smoking (matched to data from the cigarette dispenser to create an ecologically valid schedule) and 4 days of ad libitum nicotine nasal spray use, while tobacco abstinent. Eight times per day, at 2-hour intervals, blood was drawn and ratings of cigarette cravings and withdrawal symptoms were obtained. On average, subjects used less than half of the manufacturer's recommended minimum daily dose of nicotine nasal spray. Large differences in nicotine and cotinine levels were observed between individuals. When predicting nicotine, cotinine, withdrawal, and cravings, we observed significant interactions between route of nicotine intake and a variety of independent variables. C1 SAIC Frederick Inc, Bethesda, MD USA. NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Mabry, PL (reprint author), NIH, Off Behav & Social Sci Res, Off Director, 31 Ctr Dr,Bldg 31,Room B1-C19,MSC 2027, Bethesda, MD 20892 USA. EM mabryp@od.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 53 TC 5 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2007 VL 9 IS 1 BP 65 EP 82 DI 10.1080/14622200601078327 PG 18 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 135GO UT WOS:000244142300008 PM 17365738 ER PT J AU Schroeder, JR Moolchan, ET AF Schroeder, Jennifer R. Moolchan, Eric T. TI Ethnic differences among adolescents seeking smoking cessation treatment: A structural analysis of responses on the Fagerstrom Test for Nicotine Dependence SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKERS; MOTIVATION; METABOLISM; RISK AB Features of tobacco dependence vary by ethnicity, which could be partially due to measurement bias inherent in instruments that assess nicotine dependence. This study compared responses on the Fagerstrom Test for Nicotine Dependence (FTND) by African American adolescents (n = 478) with those of White adolescents (n = 661) seeking smoking cessation treatment. We conducted item-by-item comparisons by ethnicity for the six questions composing the FTND and confirmatory factor analyses and multiple indicators-multiple causes (MIMIC) modeling to test the hypothesis of measurement invariance of the FTND by ethnicity. Study participants (N = 1,139) were daily smokers of average age 15.4 years (SD = 1.3); 42.0% were African American and 61.5% female. White adolescents' pattern of responses to the FTND indicated a greater degree of dependence; these differences were statistically significant for five of the six items. The FTND exhibited a unidimensional structure with similar factor loadings in both White and African American adolescents. However, MIMIC modeling indicated differential reporting for three out of six items, suggesting that the FTND may not measure nicotine dependence equivalently for White and African American youth. C1 NIDA, IRP, Baltimore, MD 21224 USA. RP Schroeder, JR (reprint author), NIDA, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jschroed@intra.nida.nih.gov FU Intramural NIH HHS NR 27 TC 10 Z9 10 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2007 VL 9 IS 1 BP 137 EP 145 DI 10.1080/14622200601078400 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 135GO UT WOS:000244142300015 PM 17365744 ER PT J AU Melikian, AA Djordjevic, MV Hosey, J Zhang, J Chen, SQ Zang, E Muscat, J Stellman, SD AF Melikian, Assieh A. Djordjevic, Mirjana V. Hosey, James Zhang, Jie Chen, Shuquan Zang, Edith Muscat, Joshua Stellman, Steven D. TI Gender differences relative to smoking behavior and emissions of toxins from mainstream cigarette smoke SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID LUNG-CANCER RISK; N-NITROSAMINES; HISTOLOGIC TYPE; FEMALE SMOKERS; TAR CIGARETTES; TOBACCO-SMOKE; NICOTINE; WOMEN; MEN; CHROMATOGRAPHY AB This study examined whether gender differences exist in the exposure to select mainstream cigarette smoke toxins as a result of differences in smoking behavior or type of cigarettes smoked among 129 female and 128 male smokers. Smoking topography data indicated that, compared with men, women took smaller puffs ( 37.6 ml/puff vs. 45.8 ml/puff; p=.5.0001) of shorter duration ( 1.33 s/puff vs. 1.48s/ puff; p=.002) but drew more puffs per cigarette ( 13.5 vs. 12.0; p=.001) and left longer butts ( 36.3 mm or 40.2% of cigarette length vs. 34.3 mm or 39.2% of cigarette length; p=.01). These trends were similar in both African Americans and European Americans. The emissions of select toxins per cigarette, as determined by mimicking human smoking behaviors were greater among the male smokers than the female smokers and correlated significantly with delivered smoke volume per cigarette. The geometric means of emissions of nicotine from cigarettes were 1.92 mg/cigarette ( 95% CI=1.80-2.05) for women versus 2.20 ( 95% CI=2.04-2.37) for men ( p=.005). Cigarettes smoked by women yielded 139.5 ng/ cigarette of 4-( methylnitrosamino)-1-( 3-pyridyl)-1- butanone ( NNK; 95% CI=128.8-151.0), compared with 170.3 ng/cigarette ( 95% CI=156.3-185.6) for men ( p=.0007); benzo( a) pyrene ( BaP) emissions were 18.0 ng/ cigarette ( 95% CI=17.0-19.0) for women and 20.5 ng/ cigarette ( 95% CI=18.8-22.3) for men ( p=.01). The gender differences with regard to cigarette smoke yields of toxins were more profound in European Americans than in African Americans. On average, African American men's smoking habits produced the highest emissions of select toxins from cigarettes, and European American female smokers had the lowest exposure to carcinogens and toxins. Several studies have suggested that women may be more susceptible than men to the ill effects of carcinogens in tobacco and tobacco smoke, whereas other studies have not found differences in lung cancer risk between men and women. The present study suggests that gender differences in exposure to tobacco smoke cannot account for a higher rate of lung cancer in female smokers compared with male smokers. C1 NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA. NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. Amer Hlth Fdn Canc Ctr, Valhalla, NY USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. RP Melikian, AA (reprint author), NYU, Sch Med, Dept Environm Med, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. EM melikian@env.med.nyu.edu FU NCI NIH HHS [CA17613, CA70972, CA68384] NR 38 TC 29 Z9 29 U1 1 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 3 BP 377 EP 387 DI 10.1080/14622200701188836 PG 11 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 158JG UT WOS:000245787200007 PM 17365769 ER PT J AU Berlin, I Gasior, MJ Moolchan, ET AF Berlin, Ivan Gasior, Maria J. Moolchan, Eric T. TI Sex-based and hormonal contraception effects on the metabolism of nicotine among adolescent tobacco-dependent smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID DISPOSITION KINETICS; 1ST CIGARETTE; SMOKING; TRANS-3'-HYDROXYCOTININE; COTININE; CYP2A6; RATIO; TIME AB Variations in nicotine metabolism influence smoking patterns. Differences between sexes or related to sex hormones may affect nicotine metabolism. Because smoking initiation starts during adolescence, observations gathered from adolescent smokers might broaden our understanding of such sex-based differences. We tested the hypothesis that nicotine metabolism-as indexed primarily by the ratio of trans-3'-hydroxycotinine ( 3HC) to cotinine-is more rapid among adolescent girl smokers compared with boys and that regular use of hormonal contraceptives influences nicotine and cotinine metabolism. We also hypothesized that more rapid nicotine metabolism is associated with higher nicotine dependence as indexed by smoking frequency and morning urgency. Plasma samples of nicotine, cotinine, and 3HC concentrations were obtained from 120 adolescents ( 36 boys). Plasma nicotine and cotinine concentrations were similar in boys and girls. Median plasma 3HC concentrations were 44.45 ng/ml for girls versus 35.74 ng/ml for boys ( p=.025), and median plasma 3HC-cotinine ratios were significantly higher in girls than in boys ( 0.317 vs. 0.253, p=.025). After stratifying girls into two groups based on use versus nonuse of hormonal contraception, plasma 3HC-cotinine ratios in girls using hormonal contraception ( 0.47) were substantially higher ( p<.0001) than in boys ( 0.25) and were significantly higher than in girls not using hormonal contraception ( 0.28). Controlling for cigarettes smoked per day, ethnicity, and age did not modify these results. Although plasma nicotine, cotinine, or 3HC concentrations were significantly lower in less dependent adolescent smokers, nicotine and cotinine metabolite ratios were similar. This study showed that hormonal contraception in adolescent girls may accelerate cotinine metabolism, an effect likely related to induction of cytochrome P450 2A6 and independent of ethnicity and cigarette consumption. Prospective controlled studies are needed to further evaluate the role of hormonal contraception in patterns of adolescent smoking and nicotine metabolism. C1 Univ Paris 06, Grp Hosp Pitie Salpetriere, Serv Pharmacol, F-75013 Paris, France. INSERM, U677, F-75654 Paris 13, France. Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Berlin, I (reprint author), Univ Paris 06, Grp Hosp Pitie Salpetriere, Serv Pharmacol, 47 Blvd Hop, F-75013 Paris, France. EM ivan.berlin@psl.aphp.fr FU Intramural NIH HHS NR 28 TC 19 Z9 19 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 4 BP 493 EP 498 DI 10.1080/14622200701243193 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 158JH UT WOS:000245787300008 PM 17454704 ER PT J AU Weber, D Wolff, LS Orleans, T Mockenhaupt, RE Massett, HA Vose, KK AF Weber, Deanne Wolff, Lisa S. Orleans, Tracy Mockenhaupt, Robin E. Massett, Holly A. Vose, Kathryn Kahler TI Smokers' attitudes and behaviors related to consumer demand for cessation counseling in the medical care setting SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING-CESSATION; PATIENTS PERCEPTIONS; PHYSICIAN ADVICE; QUIT SMOKING AB This study describes a new segmentation strategy exploring smokers' interest levels in counseling in the medical care setting in order to understand how public health communications can be designed to increase consumer demand for cessation services within this population. A subsample of 431 smokers from a large, nationally representative mail survey was analyzed and categorized into three cessation-demand groups: Low demand (LD), medium demand (MD), and high demand ( HD). HD smokers were most likely to be heavy smokers, to make quitting a high priority, and to have self-efficacy in quitting. MD and LD smokers were less likely than HD smokers to have been told to quit smoking by a health care provider in the past or to believe that counseling is effective. The first step in the regression analysis revealed that age, cigarettes smoked per month, whether smokers were currently trying to quit, and whether they were ever told to quit smoking by their health care provider accounted for 21% of the variance in smokers' interest in smoking cessation counseling, F( 4, 234)=16.49, p<.001. When additional variables on attitudes toward smoking and quitting and perceived effectiveness of receiving counseling in the medical care setting were added to the model, an additional 11% of the variance in smokers' interest in cessation counseling was explained, F(12, 234)=10.07, p<.001. Results suggest that by categorizing smokers by interest level in cessation counseling, we emerge with three distinct portraits of smokers who might be activated in different ways to increase consumer demand for cessation counseling. C1 Porter Novelli, Washington, DC 20006 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. NCI, Rockville, MD USA. RP Weber, D (reprint author), Porter Novelli, 1909 K St,NW,4th Floor, Washington, DC 20006 USA. EM deanne.weber@porternovelli.com NR 22 TC 11 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 5 BP 571 EP 580 DI 10.1080/14622200701189024 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 167UE UT WOS:000246477200006 PM 17454713 ER PT J AU England, LJ Grauman, A Qian, C Wilkins, DG Schisterman, EF Yu, KF Levine, RJ AF England, Lucinda J. Grauman, Alyssa Qian, Cong Wilkins, Diana G. Schisterman, Enrique F. Yu, Kai F. Levine, Richard J. TI Misclassification of maternal smoking status and its effects on an epidemiologic study of pregnancy outcomes SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTE-SMOKING; BIRTH-WEIGHT; COTININE LEVELS; PREECLAMPSIA; CESSATION; HEALTH; WOMEN; RISK; PATTERNS; EXPOSURE AB Reliance on self-reported smoking status among pregnant women can result in exposure misclassification. We used data from the Calcium for Preeclampsia Prevention trial, a randomized study of nulliparous women conducted from 1992 to 1995, to characterize tobacco exposure misclassification among women who reported at study enrollment that they had quit smoking. Urinary cotinine concentration was used to validate quit status, and factors associated with exposure misclassification and the effects of misclassification on associations between smoking and pregnancy outcomes were evaluated using logistic regression. Of 4,289 women enrolled, 508 were self-reported smokers and 771 were self-reported quitters. Of 737 self-reported quitters with a valid cotinine measurement, 21.6% had evidence of active smoking and were reclassified as smokers. Women who reported having quit smoking during pregnancy were more likely to be reclassified than women who reported quitting before pregnancy (p <.001). Among smokers, factors independently associated with misclassification of smoking status included fewer cigarettes smoked per day and fewer years smoked. After reclassification the odds ratio for a small-for-gestationalage birth among smokers decreased by 14%, and the smoking-related reduction in birth weight decreased by 15%. Effects of misclassification on the association with hypertensive disorders of pregnancy were present but less dramatic. In conclusion, use of self-reported smoking status collected at the time of study enrollment resulted in the introduction of bias into our study of smoking and pregnancy outcomes. The potential for this type of bias should be considered when conducting and interpreting epidemiologic studies of smoking and pregnancy outcomes. C1 Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. RP England, LJ (reprint author), 4770 Buford Highway NE,MS K-23, Atlanta, GA 30341 USA. EM lbe9@cdc.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 25 TC 63 Z9 63 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 10 BP 1005 EP 1013 DI 10.1080/14622200701491255 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 225KU UT WOS:000250517600004 PM 17852766 ER PT J AU Ponder, P Jefferson, AM Backinger, C Grana, R AF Ponder, Paris Jefferson, Anne-Marie Backinger, Cathy Grana, Rachel TI Tobacco-related research funding at the national cancer institute: Portfolio analysis, fiscal year 2003 SO NICOTINE & TOBACCO RESEARCH LA English DT Article AB A variety of methods is used to classify research conducted or funded by the National Institutes of Health (NIH). We undertook this analysis to delineate research funded by the National Cancer Institute (NCI) that specifically addresses a tobacco-related research question. Intramural projects, extramural grants, and contracts were coded according to eight categories based on information in the abstracts. One category, "research area,'' classified projects by the primary study outcome. A total of 318 projects met our inclusion criterion of addressing a tobacco-related research question. As a result, our estimate of about US$107 million in tobacco research during the 2003 fiscal year is different from what is officially reported by NCI. The greatest proportion of tobacco research dollars was devoted to policy research (20%, n=47) and research on the determinants of tobacco use (19%, n=36). The greatest number of studies focused on investigating the consequences of tobacco use (32%, n=105). A substantial number of projects addressed a tobacco-related question specifically about women (n=45) or a racial/ethnic group (n=99) and used cigarettes as the primary tobacco product (n=277). These findings elucidate key areas for future tobacco control research and may help to determine future funding priorities at NCI and in the research community at large. Although tobacco causes nearly 30% of all cancer deaths, NCI spent 2.3% of its total fiscal year 2003 budget on tobacco-related research funding. C1 DB Consulting Grp Inc, Silver Spring, MD USA. Univ W Georgia, Dept Psychol, Carrollton, GA USA. Natl Canc Inst, Div Canc Control & Populat Sci, Behav Res Program, Tobacco Control Res Branch, Bethesda, MD USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Ponder, P (reprint author), Execut Plaza N 4040,6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. EM pponder@cdc.gov NR 4 TC 4 Z9 4 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PY 2007 VL 9 IS 10 BP 1053 EP 1057 DI 10.1080/14622200701591609 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 225KU UT WOS:000250517600010 PM 17943621 ER PT S AU Dezfulian, C Gladwin, MT Shiva, S AF Dezfulian, Cameron Gladwin, Mark T. Shiva, Sruti BE Tota, B Trimmer, B TI Nitrite is a vascular store of NO which mediates hypoxic signaling and protects against ischemia/reperfusion injury SO NITRIC OXIDE SE Advances in Experimental Biology LA English DT Article; Book Chapter DE nitrite; nitric oxide; ischemia; reperfusion; hypoxia ID K-ATP CHANNELS; REGIONAL BLOOD-FLOW; MYOCARDIAL-ISCHEMIA; INHALED NO; S-NITROSOHEMOGLOBIN; REPERFUSION INJURY; HUMAN CIRCULATION; RELAXING FACTOR; OXIDE SYNTHASE; COMPLEX-I AB The circulating anion nitrite, once thought to be a physiologically inert by-product of nitric oxide (NO) oxidation, has been proposed to be a vascular storage form of bioactive NO. Nitrite is reduced to bioactive NO along a physiological oxygen and pH gradient by its reaction with deoxygenated hemoglobin and other hemoproteins. Through this mechanism, nitrite plays a role in hypoxic vasodilation and is capable of inhibiting mitochondrial respiration during hypoxia. Accumulating data demonstrate that nitrite is a potent mediator of cytoprotection after ischemia/reperfusion (I/R) injury in several organs, including the heart, liver, and brain. However, the mechanisms of nitrite-dependent cytoprotection remain unknown. In this article, we review the role of nitrite as a hypoxic source of NO and discuss the potential mechanisms of nitrite-mediated cytoprotection from I/R injury. C1 [Dezfulian, Cameron; Gladwin, Mark T.; Shiva, Sruti] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Dezfulian, Cameron; Gladwin, Mark T.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Dezfulian, Cameron] Johns Hopkins Univ Hosp, Div Pediat Anesthesia & Crit Care Med, Baltimore, MD 21287 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mgladwin@mail.nih.gov OI Dezfulian, Cameron/0000-0002-4486-0446 NR 57 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER NORTH HOLLAND PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1872-2423 BN 978-0-08-054620-9 J9 ADV EXP BIOL PY 2007 VL 1 BP 213 EP 227 DI 10.1016/S1872-2423(07)01010-1 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA BCU83 UT WOS:000311536600011 ER PT J AU Glynn, S Boersma, B Martin, D Howe, T Ridnour, L Wink, D Yi, M Stephens, R Yfantis, H Ambs, S AF Glynn, S. Boersma, B. Martin, D. Howe, T. Ridnour, L. Wink, D. Yi, M. Stephens, R. Yfantis, H. Ambs, S. TI iNOS expression is associated with basal-like breast cancer phenotype and predicts poor survival in ERneg breast cancer SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [Glynn, S.; Boersma, B.; Martin, D.; Howe, T.; Ridnour, L.; Wink, D.; Yi, M.; Stephens, R.; Yfantis, H.; Ambs, S.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RI Boersma, Brenda/A-9270-2009; Glynn, Sharon/D-7136-2013 OI Boersma, Brenda/0000-0002-8992-2735; Glynn, Sharon/0000-0003-1459-2580 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S17 EP S17 DI 10.1016/j.niox.2007.09.038 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000032 ER PT J AU Hussain, SP Curtis, CH AF Hussain, S. P. Curtis, C. H. TI Inflammation and cancer: Influence of nitric oxide SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [Hussain, S. P.; Curtis, C. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S12 EP S12 DI 10.1016/j.niox.2007.09.017 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000013 ER PT J AU MacDonald, CJ Sienkiewicz, P Bass, SE Wink, DD Yeh, GC AF MacDonald, C. J. Sienkiewicz, P. Bass, S. E. Wink, D. D. Yeh, G. C. TI NO-aspirin 2 modulates carcinogen activation and detoxification enzyme expression in human HepG2 and LS180 cells SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [MacDonald, C. J.; Sienkiewicz, P.; Bass, S. E.; Wink, D. D.; Yeh, G. C.] NCI, NCI Frederick, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S18 EP S18 DI 10.1016/j.niox.2007.09.041 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000035 ER PT J AU Pluta, R Glasker, S Vortmeyer, AO Dejam, A Lonser, RR Schatlo, B AF Pluta, R. Glaesker, S. Vortmeyer, A. O. Dejam, A. Lonser, R. R. Schatlo, B. TI The nitric oxide pathway in ens hemangioblastomas SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [Pluta, R.; Glaesker, S.; Vortmeyer, A. O.; Dejam, A.; Lonser, R. R.; Schatlo, B.] NIH, NINDS, SNB, Bethesda, MD USA. RP Pluta, R (reprint author), NIH, NINDS, SNB, 10 Ctr Dr, Bethesda, MD USA. RI SCHATLO, Bawarjan/F-4285-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S26 EP S26 DI 10.1016/j.niox.2007.09.072 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000065 ER PT J AU Wink, D Ridnour, L Isenberg, J Roberts, D Thomas, D AF Wink, D. Ridnour, L. Isenberg, J. Roberts, D. Thomas, D. TI Discrete concentrations of NO determine pro and antitumor responses SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 1st International Conference on Nitric Oxide and Cancer CY NOV 26-28, 2007 CL Paris, FRANCE C1 [Wink, D.; Ridnour, L.; Isenberg, J.; Roberts, D.; Thomas, D.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2007 VL 17 SU 1 BP S9 EP S9 DI 10.1016/j.niox.2007.09.006 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229WD UT WOS:000250836000002 ER PT S AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, Alexander M. Bezrukov, Sergey M. BE Bezrukov, SM TI Surprising features of particle dynamics in channel-facilitated transport - art. no. 66020F SO Noise and Fluctuations in Biological, Biophysical, and Biomedical Systems SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Noise and Fluctuations in Biological, Biophysical, and Biomedical Systems CY MAY 21-23, 2007 CL Florence, ITALY SP SPIE, European Opt Soc, SIOF, SPIE Europe DE diffusion; Smoluchowski equation; membrane transport ID ESCHERICHIA-COLI; SUGAR-TRANSPORT; OUTER-MEMBRANE; MALTOPORIN; PROTEIN; TRANSLOCATION; TIME; LAMB; ATP AB We analyze the consequences of interactions between the pore and the translocating molecule within the framework of a continuous diffusion model using the Smoluchowski equation with the radiation boundary conditions. We describe the solute-pore interaction in terms of the potential of mean force. Several of our analytical findings are quite counter-intuitive. Three of the examples to be discussed here are: (i) "Sticking" to the channel slows down translocation (a particle spends more time in the channel) but increases the flux; (ii) If the potential well modeling the particle-channel interaction occupies only a part of the channel length, the average translocation time is non-monotonic in the width of the potential well, first increasing and then decreasing; (iii) At a finite potential bias applied to the channel, the mean "up-hill" and "downhill" particle translocation times (and their distributions) are identical. C1 NICHHD, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), NICHHD, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6739-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6602 BP F6020 EP F6020 AR 66020F DI 10.1117/12.724711 PG 9 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology SC Biophysics; Engineering; Mathematical & Computational Biology GA BGT41 UT WOS:000250406300009 ER PT S AU Nossal, R AF Nossal, Ralph BE Bezrukov, SM TI Stochastic trigger for clathrin-coated vesicle biogenesis - art. no. 66020J SO Noise and Fluctuations in Biological, Biophysical, and Biomedical Systems SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Noise and Fluctuations in Biological, Biophysical, and Biomedical Systems CY MAY 21-23, 2007 CL Florence, ITALY SP SPIE, European Opt Soc, SIOF, SPIE Europe DE endocytosis; clathrin coated vesicles; phosphoinositides; fluctuations ID PHOSPHOTRANSFERASE SYSTEM; THRESHOLD FLUCTUATIONS; MEMBRANE CURVATURE; PLASMA-MEMBRANE; PITS; ACTIVATION; CELL; PHOSPHORYLATION; BISTABILITY; PROTEINS AB Kinetic aspects of receptor-mediated endocytosis are identified, particularly as relating to the stochastic formation and released of clathrin coated vesicles at the plasma membrane. We discuss how one might account for the coordinated steps of this process, including receptor activation, association with adaptor proteins, coat formation, and the role of phosphoinosotide metabolism as a regulatory mechanism. In anticipation of building a detailed mathematical theory, we discuss an earlier treatment of the way threshold fluctuations affect the firing probability of nerve axons (H. Lecar, and R. Nossal, Biophys. J. 11, pp. 1048--1067, 1971), in which equations were analyzed by distinguishing different time-scales to identify pertinent kinetic variables. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6739-3 J9 P SOC PHOTO-OPT INS PY 2007 VL 6602 BP J6020 EP J6020 AR 66020J DI 10.1117/12.729597 PG 12 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology SC Biophysics; Engineering; Mathematical & Computational Biology GA BGT41 UT WOS:000250406300013 ER PT J AU Rausch, JW Le Grice, SFJ AF Rausch, Jason W. Le Grice, Stuart F. J. TI Purine analog substitution of the HIV-1 polypurine tract primer defines regions controlling initiation of plus-strand DNA synthesis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TRANSCRIPTASE RNASE-H; TYPE-1 REVERSE-TRANSCRIPTASE; SEQUENCE FEATURES IMPORTANT; A-TRACT; CLEAVAGE SPECIFICITY; RNA/DNA HYBRIDS; REPLICATION; MUTATIONS AB Despite extensive study, the mechanism by which retroviral reverse transciptases (RTs) specifically utilize polypurine tract (PPT) RNA for initiation of plus-strand DNA synthesis remains unclear. Three sequence motifs within or adjacent to the purine-rich elements are highly conserved, namely, a rU:dA tract region immediately 5' to the PPT, an rA:dT-rich sequence constituting the upstream portion of the PPT and a downstream rG:dC tract. Using an in vitro HIV-1 model system, we determined that the former two elements define the 5' terminus of the (+)-strand primer, whereas the rG:dC tract serves as the primary determinant of initiation specificity. Subsequent analysis demonstrated that G -> A or A -> G substitution at PPT positions -2, -4 and +1 (relative to the scissile phosphate) substantially reduces (+)-strand priming. We explored this observation further using PPT substrates substituted with a variety of nucleoside analogs [inosine (I), purine riboside (PR), 2-aminopurine (2-AP), 2,6-diaminopurine (2,6-DAP), isoguanine (iG)], or one of the naturally occurring bases at these positions. Our results demonstrate that for PPT positions -2 or +1, substituting position 2 of the purine was an important determinant of cleavage specificity. In addition, cleavage specificity was greatly affected by substituting -4G with an analog containing a 6-NH2 moiety. C1 NCI, RT Biochem Sect, Resistance Mechanisms Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, Resistance Mechanisms Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov FU Intramural NIH HHS NR 47 TC 13 Z9 14 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 IS 1 BP 256 EP 268 DI 10.1093/nar/gkl909 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130NH UT WOS:000243805800032 PM 17164285 ER PT J AU Yan, J Kim, YS Yang, XP Albers, M Koegl, M Jetten, AM AF Yan, Jun Kim, Yong-Sik Yang, Xiao-Ping Albers, Michael Koegl, Manfred Jetten, Anton M. TI Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEASOME-DEPENDENT DEGRADATION; TESTIS-ASSOCIATED RECEPTOR; BINDING DOMAINS; MOLECULAR-BASIS; ER-ALPHA; TRANSCRIPTION; PROTEIN; COACTIVATOR; UBIQUITYLATION; COREPRESSOR AB In this study, we demonstrate that receptor-associated protein 80 (RAP80) interacts with estrogen receptor alpha (ER alpha) in an agonist-dependent manner. The interaction is specific for ER alpha as ERP and several other nuclear receptors tested did not interact with RAP80. Interaction between RAP80 and ER alpha was supported by mammalian two-hybrid, GST pull-down, and co-immunoprecipitation analyses. The hinge/ligand-binding domain of ER alpha is sufficient for interaction with RAP80. RAP80 overexpression reduces ER alpha polyubiquitination, increases the level of ER alpha protein, and enhances ER alpha-mediated transactivation. Knockdown of endogenous RAP80 expression by small-interfering RNA (siRNA) reduced ER alpha protein level and the E2-dependent induction of pS2. In this study, we also demonstrate that RAP80 contains two functional ubiquitin-interaction motifs (UlMs) that are able to bind ubiquitin and to direct monoubiquitination of RAP80. Deletion of these UlMs does not affect the ability of RAP80 to interact with ER alpha, but eliminates the effects of RAP80 on ER alpha polyubiquitination, the level of ER alpha protein, and ER alpha-mediated transcription. These data indicate that the UIMs in RAP80 are critical for the function of RAP80. Our study identifies ER alpha as a new RAP80- interacting protein and suggests that RAP80 may be an important modulator of ER alpha activity. C1 NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Phenex Pharmaceut AG, D-67056 Ludwigshafen, Germany. RZPD German Resource Ctr Genome Res, D-69120 Heidelberg, Germany. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 56 TC 24 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2007 VL 35 IS 5 BP 1673 EP 1686 DI 10.1093/nar/gkl1112 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 166IA UT WOS:000246371200026 PM 17311814 ER PT J AU Nakanishi, S Prasad, R Wilson, SH Smerdon, M AF Nakanishi, Shima Prasad, Rajendra Wilson, Samuel H. Smerdon, Michael TI Different structural states in oligonucleosomes are required for early versus late steps of base excision repair SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-BETA; NUCLEOSOMAL DNA; HISTONE H2AX; REMODELING FACTOR; CHROMATIN FIBER; NICKED DNA; IN-VIVO; MECHANISM; DAMAGE; GLYCOSYLASE AB Chromatin in eukaryotic cells is folded into higher order structures of folded nucleosome filaments, and DNA damage occurs at all levels of this structural hierarchy. However, little is known about the impact of higher order folding on DNA repair enzymes. We examined the catalytic activities of purified human base excision repair (BER) enzymes on uracil-containing oligonucleosome arrays, which are folded primarily into 30nm structures when incubated in repair reaction buffers. The catalytic activities of uracil DNA glycosylase (UDG) and apyrimidinic/apurinic endonuclease (APE) digest G:U mismatches to completion in the folded oligonucleosomes without requiring significant disruption. In contrast, DNA polymerase P (Pol P) synthesis is inhibited in a major fraction (similar to 80%) of the oligonucleosome array, suggesting that single strand nicks in linker DNA are far more accessible to Pol P in highly folded oligonucleosomes. Importantly, this barrier in folded oligonucleosomes is removed by purified chromatin remodeling complexes. Both ISW1 and ISW2 from yeast significantly enhance Poll P accessibility to the refractory nicked sites in oligonucleosomes. These results indicate that the initial steps of BER (UDG and APE) act efficiently on highly folded oligonucleosome arrays, and chromatin remodeling may be required for the latter steps of BER in intact chromatin. C1 Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Smerdon, M (reprint author), Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. EM smerdon@wsu.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES02614, R01 ES002614, R37 ES002614] NR 51 TC 30 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2007 VL 35 IS 13 BP 4313 EP 4321 DI 10.1093/nar/gkm436 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209LS UT WOS:000249390600008 PM 17576692 ER PT J AU Antony, S Marchand, C Stephen, AG Thibaut, L Agama, KK Fisher, RJ Pommier, Y AF Antony, Smitha Marchand, Christophe Stephen, Andrew G. Thibaut, Laurent Agama, Keli K. Fisher, Robert J. Pommier, Yves TI Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID I COVALENT COMPLEXES; TOPOISOMERASE-I; MINOR-GROOVE; SPINOCEREBELLAR ATAXIA; CRYSTAL-STRUCTURE; HUMAN-CELLS; REPAIR; BINDING; ENZYME; DAMAGE AB By enzymatically hydrolyzing the terminal phosphodiester bond at the 3'-ends of DNA breaks, tyrosyl-DNA phosphodiesterase (Tdp1) repairs topoisomerase-DNA covalent complexes and processes the DNA ends for DNA repair. To identify novel Tdp1 inhibitors, we developed a high-throughput assay that uses electrochemiluminescent (ECL) substrates. Subsequent to screening of 1981 compounds from the 'diversity set' of the NCl-Developmental Therapeutics Program, here we report that furamidine inhibits Tdp1 at low micromolar concentrations. Inhibition of Tdp1 by furamidine is effective both with single- and double-stranded substrates but is slightly stronger with the duplex DNA. Surface plasmon resonance studies show that furamidine binds both single-and double-stranded DNA, though more weakly with the single-stranded substrate DNA. Thus, the inhibition of Tdp1 activity could in part be due to the binding of furamidine to DNA. However, the inhibition of Tdp1 by furamidine is independent of the substrate DNA sequence. The kinetics of Tdp1 inhibition by furamidine was influenced by the drug to enzyme ratio and duration of the reaction. Comparison with related dications shows that furamidine inhibits Tdp1 more effectively than berenil, while pentamidine was inactive. Thus, furamidine represents the most potent Tdp1 inhibitor reported to date. C1 NCI, NIH, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. SAIC Frederick Inc, Protein Chem Lab, Adv Technol Program, Ft Detrick, MD 21702 USA. RP Antony, S (reprint author), NCI, NIH, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM antonys@mail.nih.gov RI Fisher, Robert/B-1431-2009; Marchand, Christophe/D-8559-2016 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 44 TC 42 Z9 44 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2007 VL 35 IS 13 BP 4474 EP 4484 DI 10.1093/nar/gkm463 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209LS UT WOS:000249390600022 PM 17576665 ER PT J AU Barrett, T Troup, DB Wilhite, SE Ledoux, P Rudnev, D Evangelista, C Kim, IF Soboleva, A Tomashevsky, M Edgar, R AF Barrett, Tanya Troup, Dennis B. Wilhite, Stephen E. Ledoux, Pierre Rudnev, Dmitry Evangelista, Carlos Kim, Irene F. Soboleva, Alexandra Tomashevsky, Maxim Edgar, Ron TI NCBI GEO: mining tens of millions of expression profiles - database and tools update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; MICROARRAY DATA; INTEGRATION; INFORMATION; STANDARDS AB The Gene Expression Omnibus (GEO) repository at the National Center for Biotechnology Information (NCBI) archives and freely disseminates microarray and other forms of high-throughput data generated by the scientific community. The database has a minimum information about a microarray experiment (MIAME)-compliant infrastructure that captures fully annotated raw and processed data. Several data deposit options and formats are supported, including web forms, spreadsheets, XML and Simple Omnibus Format in Text (SOFT). In addition to data storage, a collection of user-friendly web-based interfaces and applications are available to help users effectively explore, visualize and download the thousands of experiments and tens of millions of gene expression patterns stored in GEO. This paper provides a summary of the GEO database structure and user facilities, and describes recent enhancements to database design, performance, submission format options, data query and retrieval utilities. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. EM barrett@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 16 TC 664 Z9 686 U1 3 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D760 EP D765 DI 10.1093/nar/gkl887 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600150 PM 17099226 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Wheeler, David L. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage (www.ncbi.nlm.nih.gov). C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov NR 12 TC 253 Z9 264 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D21 EP D25 DI 10.1093/nar/gkl986 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600006 PM 17202161 ER PT J AU Cui, WW Taub, DD Gardner, K AF Cui, Wenwu Taub, Dennis D. Gardner, Kevin TI qPrimerDepot: a primer database for quantitative real time PCR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROBE DATABASE; QUANTIFICATION; RTPRIMERDB; SEQUENCES; PROTEIN; UPDATE; TOOL AB Gene expression studies employing high throughput real time PCR methods require finding uniform conditions for optimal amplification of multiple targets, often a daunting task. We developed a primer database, qPrimerDepot, which provides optimized primers for all human and mouse RefSeq genes. These primers are designed to amplify desired templates under unified annealing temperature. For most intron-bearing genes, primers flank one of the largest introns thus minimizing background noise due to genomic DNA contamination. The qPrimerDepot database can be accessed at http://primerdepot.nci.nih.gov/ and http://mouseprimerdepot.nci.nih.gov/. C1 Natl Inst Hlth, Adv Technol Ctr, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. RP Gardner, K (reprint author), Natl Inst Hlth, Adv Technol Ctr, Lab Receptor Biol & Gene Express, Room 134C,8717 Grovemont Circle, Bethesda, MD 20892 USA. EM gardnerk@mail.nih.gov FU Intramural NIH HHS NR 15 TC 81 Z9 82 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D805 EP D809 DI 10.1093/nar/gkl767 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600157 PM 17068075 ER PT J AU D'Souza, M Glass, EM Syed, MH Zhang, Y Rodriguez, A Maltsev, N Galperin, MY AF D'Souza, Mark Glass, Elizabeth M. Syed, Mustafa H. Zhang, Yi Rodriguez, Alexis Maltsev, Natalia Galperin, Michael Y. TI Sentra: a database of signal transduction proteins for comparative genome analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INCREASED COVERAGE; BACTERIA; DOMAINS; PROKARYOTES; DIVERSITY; PATHWAYS; KINASES; SYSTEM; LIGHT AB Sentra (http://compbio.mcs.anl.gov/sentra), a database of signal transduction proteins encoded in completely sequenced prokaryotic genomes, has been updated to reflect recent advances in understanding signal transduction events on a whole-genome scale. Sentra consists of two principal components, a manually curated list of signal transduction proteins in 202 completely sequenced prokaryotic genomes and an automatically generated listing of predicted signaling proteins in 235 sequenced genomes that are awaiting manual curation. In addition to two-component histidine kinases and response regulators, the database now lists manually curated Ser/Thr/Tyr protein kinases and protein phosphatases, as well as adenylate and diguanylate cyclases and c-di-GMP phosphodiesterases, as defined in several recent reviews. All entries in Sentra are extensively annotated with relevant information from public databases (e.g. UniProt, KEGG, PDB and NCBI). Sentra's infrastructure was redesigned to support interactive cross-genome comparisons of signal transduction capabilities of prokaryotic organisms from a taxonomic and phenotypic perspective and in the framework of signal transduction pathways from KEGG. Sentra leverages the PUMA2 system to support interactive analysis and annotation of signal transduction proteins by the users. C1 Argonne Natl Lab, Div Math & Comp Sci, Computat Biol Grp, Argonne, IL 60439 USA. Univ Chicago, Comp Inst, Chicago, IL 60637 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP D'Souza, M (reprint author), Argonne Natl Lab, Div Math & Comp Sci, Computat Biol Grp, 9700 S Cass Ave, Argonne, IL 60439 USA. EM dsouza@mcs.anl.gov; galperin@ncbi.nlm.nih.gov RI Syed, Mustafa/A-5252-2011; Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999]; NIAID NIH HHS [1-U54-AI-057153, U54 AI057153]; PHS HHS [266200400042C] NR 25 TC 17 Z9 18 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D271 EP D273 DI 10.1093/nar/gkl949 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600056 PM 17135204 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI The Molecular Biology Database Collection: 2007 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN FAMILIES DATABASE; SUPPLEMENT TREMBL; DATA-BANK; PFAM; INFORMATION AB The NAR online Molecular Biology Database Collection is a public resource that contains links to the databases described in this issue of Nucleic Acids Research, previous NAR database issues, as well as a selection of other molecular biology databases that are freely available on the web and might be useful to the molecular biologist. The 2007 update includes 968 databases, 110 more than the previous one. Many databases that have been described in earlier issues of NAR come with updated summaries, which reflect recent progress and, in some instances, an expanded scope of these databases. The complete database list and summaries are available online on the Nucleic Acids Research web site http://nar.oxfordjournals.org/. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 15 TC 42 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D3 EP D4 DI 10.1093/nar/gkl1008 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600002 PM 17148484 ER PT J AU Kazakov, AE Cipriano, MJ Novichkov, PS Minovitsky, S Vinogradov, DV Arkin, A Mironov, AA Gelfand, MS Dubchak, I AF Kazakov, Alexei E. Cipriano, Michael J. Novichkov, Pavel S. Minovitsky, Simon Vinogradov, Dmitry V. Arkin, Adam Mironov, Andrey A. Gelfand, Mikhail S. Dubchak, Inna TI RegTransBase - a database of regulatory sequences and interactions in a wide range of prokaryotic genomes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PREDICTION; PROTEINS; SYSTEM; SITE AB RegTransBase is a manually curated database of regulatory interactions in prokaryotes that captures the knowledge in public scientific literature using a controlled vocabulary. Although several databases describing interactions between regulatory proteins and their binding sites are already being maintained, they either focus mostly on the model organisms Escherichia coli and Bacillus subtilis or are entirely computationally derived. RegTransBase describes a large number of regulatory interactions reported in many organisms and contains the following types of experimental data: the activation or repression of transcription by an identified direct regulator, determining the transcriptional regulatory function of a protein (or RNA) directly binding to DNA (RNA), mapping or prediction of a binding site for a regulatory protein and characterization of regulatory mutations. Currently, RegTransBase content is derived from about 3000 relevant articles describing over 7000 experiments in relation to 128 microbes. It contains data on the regulation of about 7500 genes and evidence for 6500 interactions with 650 regulators. RegTransBase also contains manually created position weight matrices (PWM) that can be used to identify candidate regulatory sites in over 60 species. RegTransBase is available at http://regtransbase.lbl.gov. C1 RAS, Inst Problems Informat Transmiss, Moscow 127994, Russia. Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Calif Berkeley, Dept Bioengn, Albany, CA 94710 USA. Virtual Inst Microbial Stress & Survival, Albany, CA 94710 USA. Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119992, Russia. State Res Ctr GosNIIGenet, Moscow 117545, Russia. Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA. RP Gelfand, MS (reprint author), RAS, Inst Problems Informat Transmiss, Bolshoi Karetny Pereulok 19, Moscow 127994, Russia. EM gelfand@iitp.ru; ildubchak@Ibl.gov RI Arkin, Adam/A-6751-2008; Mironov, Andrey/C-8024-2012; Gelfand, Mikhail/F-3425-2012 OI Arkin, Adam/0000-0002-4999-2931; NR 19 TC 62 Z9 62 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D407 EP D412 DI 10.1093/nar/gkl865 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600084 PM 17142223 ER PT J AU Maglott, D Ostell, J Pruitt, KD Tatusova, T AF Maglott, Donna Ostell, Jim Pruitt, Kim D. Tatusova, Tatiana TI Entrez Gene: gene-centered information at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Maglott, D (reprint author), 45 Ctr Dr,MSC 6510,Bldg 45,Rm5AS13B, Bethesda, MD 20892 USA. EM maglott@ncbi.nlm.nih.gov NR 4 TC 303 Z9 311 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D26 EP D31 DI 10.1093/nar/gkl993 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600007 PM 17148475 ER PT J AU Marchler-Bauer, A Anderson, JB Derbyshire, MK DeWeese-Scott, C Gonzales, NR Gwadz, M Hao, LN He, SQ Hurwitz, DI Jackson, JD Ke, ZX Krylov, D Lanczycki, CJ Liebert, CA Liu, CL Lu, F Lu, SN Marchler, GH Mullokandov, M Song, JS Thanki, N Yamashita, RA Yin, JJ Zhang, DC Bryant, SH AF Marchler-Bauer, Aron Anderson, John B. Derbyshire, Myra K. DeWeese-Scott, Carol Gonzales, Noreen R. Gwadz, Marc Hao, Luning He, Siqian Hurwitz, David I. Jackson, John D. Ke, Zhaoxi Krylov, Dmitri Lanczycki, Christopher J. Liebert, Cynthia A. Liu, Chunlei Lu, Fu Lu, Shennan Marchler, Gabriele H. Mullokandov, Mikhail Song, James S. Thanki, Narmada Yamashita, Roxanne A. Yin, Jodie J. Zhang, Dachuan Bryant, Stephen H. TI CDD: a conserved domain database for interactive domain family analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The conserved domain database (CDD) is part of NCBI's Entrez database system and serves as a primary resource for the annotation of conserved domain footprints on protein sequences in Entrez. Entrez's global query interface can be accessed at http://www.ncbi.nlm.nih.gov/Entrez and will search CDD and many other databases. Domain annotation for proteins in Entrez has been pre-computed and is readily available in the form of 'Conserved Domain' links. Novel protein sequences can be scanned against CDD using the CD-Search service; this service searches databases of CDD-derived profile models with protein sequence queries using BLAST heuristics, at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. Protein query sequences submitted to NCBI's protein BLAST search service are scanned for conserved domain signatures by default. The CDD collection contains models imported from Pfam, SMART and COG, as well as domain models curated at NCBI. NCBI curated models are organized into hierarchies of domains related by common descent. Here we report on the status of the curation effort and present a novel helper application, CDTree, which enables users of the CDD resource to examine curated hierarchies. More importantly, CDD and CDTree used in concert, serve as a powerful tool in protein classification, as they allow users to analyze protein sequences in the context of domain family hierarchies. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38 A,Room 8N805 Rocvkville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU Intramural NIH HHS NR 10 TC 494 Z9 515 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D237 EP D240 DI 10.1093/nar/gkl951 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600049 PM 17135202 ER PT J AU Pruitt, KD Tatusova, T Maglott, DR AF Pruitt, Kim D. Tatusova, Tatiana Maglott, Donna R. TI NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENERATION; BIOLOGY; ENTREZ AB NCBI's reference sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) is a curated non-redundant collection of sequences representing genomes, transcripts and proteins. The database includes 3774 organisms spanning prokaryotes, eukaryotes and viruses, and has records for 2 879 860 proteins (RefSeq release 19). RefSeq records integrate information from multiple sources, when additional data are available from those sources and therefore represent a current description of the sequence and its features. Annotations include coding regions, conserved domains, tRNAs, sequence tagged sites (STS), variation, references, gene and protein product names, and database cross-references. Sequence is reviewed and features are added using a combined approach of collaboration and other input from the scientific community, prediction, propagation from GenBank and curation by NCBI staff. The format of all RefSeq records is validated, and an increasing number of tests are being applied to evaluate the quality of sequence and annotation, especially in the context of complete genomic sequence. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Rm 6An 12J,45 Ctr Dr, Bethesda, MD 20892 USA. EM pruitt@ncbi.nlm.nih.gov RI Sincan, Murat /A-3794-2010 FU Intramural NIH HHS NR 12 TC 1088 Z9 1117 U1 7 U2 49 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D61 EP D65 DI 10.1093/nar/gkl842 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600014 PM 17130148 ER PT J AU Wang, YL Addess, KJ Chen, J Geer, LY He, J He, SQ Lu, SN Madej, T Marchler-Bauer, A Thiessen, PA Zhang, NG Bryant, SH AF Wang, Yanli Addess, Kenneth J. Chen, Jie Geer, Lewis Y. He, Jane He, Siqian Lu, Shennan Madej, Thomas Marchler-Bauer, Aron Thiessen, Paul A. Zhang, Naigong Bryant, Stephen H. TI MMDB: annotating protein sequences with Entrez's 3D-structure database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CONVERTING-ENZYME; BLAST AB Three-dimensional (3D) structure is now known for a large fraction of all protein families. Thus, it has become rather likely that one will find a homolog with known 3D structure when searching a sequence database with an arbitrary query sequence. Depending on the extent of similarity, such neighbor relationships may allow one to infer biological function and to identify functional sites such as binding motifs or catalytic centers. Entrez's 3D-structure database, the Molecular Modeling Database (MMDB), provides easy access to the richness of 3D structure data and its large potential for functional annotation. Entrez's search engine offers several tools to assist biologist users: (i) links between databases, such as between protein sequences and structures, (ii) pre-computed sequence and structure neighbors, (iii) visualization of structure and sequence/structure alignment. Here, we describe an annotation service that combines some of these tools automatically, Entrez's 'Related Structure' links. For all proteins in Entrez, similar sequences with known 3D structure are detected by BLAST and alignments are recorded. The 'Related Structure' service summarizes this information and presents 3D views mapping sequence residues onto all 3D structures available in MMDB (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=structure). C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 13 TC 69 Z9 73 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D298 EP D300 DI 10.1093/nar/gkl952 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600061 PM 17135201 ER PT J AU Wheeler, DL Barrett, T Benson, DA Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Edgar, R Federhen, S Geer, LY Kapustin, Y Khovayko, O Landsman, D Lipman, DJ Madden, TL Maglott, DR Ostell, J Miller, V Pruitt, KD Schuler, GD Sequeira, E Sherry, ST Sirotkin, K Souvorov, A Starchenko, G Tatusov, RL Tatusova, TA Wagner, L Yaschenko, E AF Wheeler, David L. Barrett, Tanya Benson, Dennis A. Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Edgar, Ron Federhen, Scott Geer, Lewis Y. Kapustin, Yuri Khovayko, Oleg Landsman, David Lipman, David J. Madden, Thomas L. Maglott, Donna R. Ostell, James Miller, Vadim Pruitt, Kim D. Schuler, Gregory D. Sequeira, Edwin Sherry, Steven T. Sirotkin, Karl Souvorov, Alexandre Starchenko, Grigory Tatusov, Roman L. Tatusova, Tatiana A. Wagner, Lukas Yaschenko, Eugene TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN GENES; PSI-BLAST; SEQUENCE; SEARCH; PROTEIN; GENOMES; ENTREZ; KNOWLEDGEBASE; ALGORITHM; TOOL AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link(BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace and Assembly Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Viral Genotyping Tools, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus (GEO), Entrez Probe, GENSAT, Online Mendelian Inheritance in Man (OMIM), Online Mendelian Inheritance in Animals (OMIA), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), the Conserved Domain Architecture Retrieval Tool (CDART) and the PubChem suite of small molecule databases. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 NIH, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), NIH, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Geer, Lewis/H-2714-2014; OI Landsman, David/0000-0002-9819-6675 NR 36 TC 471 Z9 491 U1 0 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D5 EP D12 DI 10.1093/nar/gkl1031 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600003 PM 17170002 ER PT J AU Zhang, Y Li, JT Kong, L Gao, G Liu, QR Wei, LP AF Zhang, Yong Li, Jiongtang Kong, Lei Gao, Ge Liu, Qing-Rong Wei, Liping TI NATsDB: Natural antisense transcripts DataBase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; HUMAN GENOME; IDENTIFICATION; SENSE; CONSERVATION; ARABIDOPSIS; INFORMATION; RESOURCES AB Natural antisense transcripts (NATs) are reverse complementary at least in part to the sequences of other endogenous sense transcripts. Most NATs are transcribed from opposite strands of their sense partners. They regulate sense genes at multiple levels and are implicated in various diseases. Using an improved whole-genome computational pipeline, we identified abundant cis-encoded exon-overlapping sense-antisense (SA) gene pairs in human (7356), mouse (6806), fly (1554), and eight other eukaryotic species (total 6534). We developed NATsDB (Natural Antisense Transcripts DataBase, http://natsdb.cbi.pku.edu.cn/) to enable efficient browsing, searching and downloading of this currently most comprehensive collection of SA genes, grouped into six classes based on their overlapping patterns. NATsDB also includes non-exon-overlapping bidirectional (NOB) genes and non-bidirectional (NBD) genes. To facilitate the study of functions, regulations and possible pathological implications, NATsDB includes extensive information about gene structures, poly(A) signals and tails, phastCons conservation, homologues in other species, repeat elements, expressed sequence tag (EST) expression profiles and OMIM disease association. NATsDB supports interactive graphical display of the alignment of all supporting EST and mRNA transcripts of the SA and NOB genes to the genomic loci. It supports advanced search by species, gene name, sequence accession number, chromosome location, coding potential, OMIM association and sequence similarity. C1 Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Ctr Bioinformat, Beijing 100871, Peoples R China. NIDA, Mol Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Wei, LP (reprint author), Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Ctr Bioinformat, Beijing 100871, Peoples R China. EM weilp@mail.cbi.pku.edu.cn RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS NR 29 TC 44 Z9 46 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2007 VL 35 SI SI BP D156 EP D161 DI 10.1093/nar/gkl782 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126EI UT WOS:000243494600032 PM 17082204 ER PT J AU Marquez, VE Comin, MJ AF Marquez, Victor E. Comin, Maria J. TI Rearranging the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve binding recognition by kinases SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT Proceedings of the 17th International Roundtable of Nucleosides, Nucleotides, and Nucleic Acids CY MAR 07-SEP 07, 2006 CL Bern, SWITZERLAND DE carbocyclic nucleosides; bicyclo[3.1.0]hexane; herpes thymidine kinase ID DISCRIMINATE; SUGAR AB A novel bicyclo[3.1.0]hexane carbocyclic nucleoside (4) with a south-like conformation amenable, to interact with the herpes thymidine kinase (HSV-tk) was synthesized with an endo-hydroxyl group positioned at the tip of the bicyclo[3.1.0]hexane ring system opposite to the tip of the fused cyclopropane ring. The introduction of the hydroxymelhyl chain through a Baylis-Hillman type reaction and the regioselective opening of a cyclic sulfite intermediate to introduce the nitrogen functionality at the correct position are highlighted. C1 [Marquez, Victor E.; Comin, Maria J.] NCI, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov FU Intramural NIH HHS NR 8 TC 2 Z9 2 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2007 VL 26 IS 6-7 BP 585 EP 588 DI 10.1080/15257770701490175 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244ON UT WOS:000251875300010 PM 18066860 ER PT J AU Jeong, LS Choe, SA Kim, AY Kim, HO Gao, ZG Jacobson, KA Chun, MW Moon, HR AF Jeong, Lak Shin Choe, Seung Ah Kim, Ae Yil Kim, Hea Ok Gao, Zhan-Guo Jacobson, Kenneth A. Chun, Moon Woo Moon, Hyung Ryong TI Synthesis of N-6-substituted 3 '-ureidoadenosine derivatives as highly potent agonists at the mutant A(3) adenosine receptor SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT Proceedings of the 17th International Roundtable of Nucleosides, Nucleotides, and Nucleic Acids CY MAR 07-SEP 07, 2006 CL Bern, SWITZERLAND DE mutant A3 adenosine receptor; 3'-ureidoadenosine derivatives; agonist; electrostatic; neoligand; neoceptor AB Several N-6-substituted 3'-ureidoadenosine derivatives were efficiently synthesized starting from D-glucose for the development of H272E mutant A(3) adenosine receptor (AR) agonists. Among compounds tested, 3'-ureido-N-6-(3-iodobenzyl)adenosine (2c) exhibited the highest binding affinity (K-i = 0. 22 mu M) at the H272E mutant A(3) AR without binding to the natural A(3) AR. C1 [Jeong, Lak Shin; Choe, Seung Ah; Kim, Ae Yil; Kim, Hea Ok] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Chun, Moon Woo] Seoul Natl Univ, Coll Pharm, Seoul, South Korea. [Moon, Hyung Ryong] Pusan Natl Univ, Coll Pharm, Pusan, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 5 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2007 VL 26 IS 6-7 BP 717 EP 719 DI 10.1080/15257770701493161 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244ON UT WOS:000251875300037 PM 18066887 ER PT J AU Jeong, LS Gunaga, P Kim, HO Tosh, DK Lee, HW Choe, SA Moon, HR Gao, ZG Jacobson, KA Chun, MW AF Jeong, Lak Shin Gunaga, Prashantha Kim, Hea Ok Tosh, Dillip K. Lee, Hyuk Woo Choe, Seung Ah Moon, Hyung Ryong Gao, Zhan-Guo Jacobson, Kenneth A. Chun, Moon Woo TI Stereoselective synthesis of 1 '-functionalized-4 '-thionucleosides SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT Proceedings of the 17th International Roundtable of Nucleosides, Nucleotides, and Nucleic Acids CY MAR 07-SEP 07, 2006 CL Bern, SWITZERLAND DE 4'-thionucleosides; S(N)2 reaction; 5-membered ring coordination; A3 adenosine receptor antagonis ID MOIETY AB Stereoselective functionalization of the 1'-position of 4'-thionucleosides was achieved using a stereoselective S(N)2 reaction controlled by 5-membered ring coordination. C1 [Jeong, Lak Shin; Gunaga, Prashantha; Kim, Hea Ok; Tosh, Dillip K.; Lee, Hyuk Woo; Choe, Seung Ah] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. [Moon, Hyung Ryong] Pusan Natl Univ, Coll Pharm, Pusan, South Korea. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Chun, Moon Woo] Seoul Natl Univ, Coll Pharm, Seoul, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 5 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2007 VL 26 IS 8-9 BP 1011 EP 1014 DI 10.1080/15257770701508588 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244OO UT WOS:000251875400030 PM 18058527 ER PT J AU Ohrui, H Kohgo, S Hayakawa, H Kodama, E Matsuoka, M Nakata, T Mitsuya, H AF Ohrui, Hiroshi Kohgo, Satoru Hayakawa, Hiroyuki Kodama, Eiichi Matsuoka, Masao Nakata, Tomohiro Mitsuya, Hiroaki TI 2 '-deoxy-4 '-C-ethynyl-2-fluoroadenosine: A nucleoside reverse transcriptase inhibitor with highly potent activity against wide spectrum of hiv-1 strains, favorable toxic profiles, and stability in plasma SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT Proceedings of the 17th International Roundtable of Nucleosides, Nucleotides, and Nucleic Acids CY MAR 07-SEP 07, 2006 CL Bern, SWITZERLAND DE 2'-Deoxy-4'-C-ethynyl nucleoside; 2,'3'-dideoxynucleoside; nucleoside reverse transcriptase inhibitors; drug resistant HIV; HAART ID HEPATITIS-B; RESISTANT; VARIANTS AB Working hypotheses to solve the critical problems of the existing highly active anti-retroviral therapy were proposed. The study based on the hypotheses proved the validity of the hypotheses and resulted in the development of 2'deoxy-4'C-ethynyl-2-fluoroadenosine, a nucleoside reverse transcriptase inhibitor, with highly potent activity against all HIV-1, very favorable toxic profiles, and stability in plasma. The nucleoside will prevent or delay the emergence of drug-resistant HIV-1 variants and be an ideal therapeutic agent for both HIV-1 and HBV infections. C1 [Ohrui, Hiroshi] Yokohama Coll Pharm, Yokohama, Kanagawa 2450066, Japan. [Kohgo, Satoru; Hayakawa, Hiroyuki] Yamasa Corp, Chiba, Japan. [Kohgo, Satoru; Hayakawa, Hiroyuki] Inst Virus Res, Kyoto, Japan. [Nakata, Tomohiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Kumamoto 860, Japan. [Mitsuya, Hiroaki] NIH, NCI, Bethesda, MD USA. RP Ohrui, H (reprint author), Yokohama Coll Pharm, 601 Matano-cho, Yokohama, Kanagawa 2450066, Japan. EM h.ohrui@hamayaku.ac.jp RI Kodama, Eiichi /C-4032-2009; OI Kodama, Eiichi /0000-0002-6622-2752; Matsuoka, Masao/0000-0002-0473-754X NR 9 TC 17 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2007 VL 26 IS 10-12 BP 1543 EP 1546 DI 10.1080/15257770701545218 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244OP UT WOS:000251875500070 PM 18066823 ER PT J AU Jeong, LS Lee, HW Kim, HO Jung, JY Gunaga, P Lee, SK Lee, EJ Chun, MW Gao, ZG Jacobson, KA Moon, HR AF Jeong, Lak Shin Lee, Hyuk Woo Kim, Hea Ok Jung, Ji Young Gunaga, Prashantha Lee, Sang Kook Lee, Eun-Jin Chun, Moon Woo Gao, Zhan-Guo Jacobson, Kenneth A. Moon, Hyung Ryong TI Design, synthesis, and anti-tumor activity of 4 '-thionucleosides as potent and selective agonists at the human A(3) adenosine receptor SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT Proceedings of the 17th International Roundtable of Nucleosides, Nucleotides, and Nucleic Acids CY MAR 07-SEP 07, 2006 CL Bern, SWITZERLAND DE bioisosteric; 4'-thionucleosides; A3 adenosine receptor agonist; anti-proliferative effect AB On the basis of potent and selective binding affinity of Cl-IB-MECA to the human A(3) adenosine receptor, its I-thioadenosine derivatives were efficiently synthesized starting from D-gulonic gamma-lactone. Among compounds tested, 2-chloro-N-6-(3-iodobenzyl)- and 2-chloro-N-6-methyl-4'-thioadenosine-5'-methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K-i = 0.38 nM and 0.28 nM, respectively) at the human A(3)AR. These compounds showed anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of Wnt signaling pathway. C1 [Jeong, Lak Shin; Kim, Hea Ok; Jung, Ji Young; Gunaga, Prashantha; Lee, Sang Kook; Lee, Eun-Jin; Chun, Moon Woo] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD USA. [Lee, Hyuk Woo] Seoul Natl Univ, Coll Pharm, Seoul 120750, South Korea. [Moon, Hyung Ryong] Pusan Natl Univ, Coll Pharm, Pusan, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 7 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2007 VL 26 IS 10-12 BP 1565 EP 1568 DI 10.1080/15257770701547107 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244OP UT WOS:000251875500074 PM 18066827 ER PT J AU Grady, PA AF Grady, Patricia A. TI A blueprint for the future SO NURSING OUTLOOK LA English DT Editorial Material C1 Natl Inst Nursing Res, Bethesda, MD USA. RP Grady, PA (reprint author), Natl Inst Nursing Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2007 VL 55 IS 1 BP 55 EP 57 DI 10.1016/j.outlook.2006.11.002 PG 3 WC Nursing SC Nursing GA 139UX UT WOS:000244459200010 ER PT S AU Milner, JA AF Milner, J. A. BE Tai, ES Gillies, PJ TI Nutrition in the 'omics' era SO NUTRIGENOMICS - OPPORTUNITIES IN ASIA SE Forum of Nutrition LA English DT Article; Proceedings Paper CT International Conference of the International-Life-Science-Institute on Nutrigenomics CY DEC 07-09, 2005 CL Singapore, SINGAPORE SP Int Life Sc Inst, Commonwealth Sci & Ind Res Org, NIH, Genome Inst Singapore ID VITAMIN-D-RECEPTOR; MANGANESE SUPEROXIDE-DISMUTASE; BIOACTIVE FOOD COMPONENTS; CANCER PREVENTION; DNA METHYLATION; DIETARY MODULATION; MOLECULAR TARGETS; FUNCTIONAL FOODS; RNA INTERFERENCE; PROSTATE-CANCER AB Consumers throughout the world are increasingly questioning the quality and safety of their diets and how the foods they eat are influencing their health. Much of this interest stems from mounting evidence that bioactive food components cannot only influence one's ability to achieve one's genetic potential, but can also have a significant influence on the quality of life as measured by both physical and cognitive performance, and modify the risk and/or severity of a variety of disease conditions. During the past century, a wealth of evidence has pointed to dietary habits as a determinant of premature death, including that associated with heart disease, stroke, diabetes, liver disease, atherosclerosis and cancer, although considerable variability in response is evident. Several factors may account for these discrepancies including individual variability due to genetic and epigenetic regulation of cellular proteins and associated small-molecular-weight compounds. This interrelationship between the food components and the 'omics' (genomics, epigenomics, transcriptomics, proteomics and metabolomics) will be briefly reviewed as a factor contributing to the variability among studies. Expanded knowledge about these ornics interrelationships will not only define the molecular target for food components but will also assist in identifying those individuals who are likely to respond C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,Suite 3164, Rockville, MD 20892 USA. EM milnerj@mail.nih.gov NR 72 TC 11 Z9 13 U1 1 U2 7 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1660-0347 BN 978-3-8055-8216-2 J9 FORUM NUTR PY 2007 VL 60 BP 1 EP 24 DI 10.1159/000107062 PG 24 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BGU54 UT WOS:000250667000001 PM 17684397 ER PT J AU McCormick, DL Johnson, WD Bosland, MC Lubet, RA Steele, VE AF McCormick, David L. Johnson, William D. Bosland, Maarten C. Lubet, Ronald A. Steele, Vernon E. TI Chemoprevention of rat prostate carcinogenesis by soy isoflavones and by Bowman-Birk inhibitor SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID SPRAGUE-DAWLEY RATS; LOBUND-WISTAR RATS; PROTEASE INHIBITOR; CANCER-CELLS; IN-VITRO; ORAL CARCINOGENESIS; HEALTHY-VOLUNTEERS; EPITHELIAL-CELLS; DIETARY ADDITION; MAMMARY-TUMORS AB Epidemiology studies suggest that soy consumption confers protection against human prostate cancer. To identify the soy component(s) that may be responsible for this chemopreventive activity, studies were conducted to determine the influence of a soy isoflavone mixture (PTI G-2535; 45% genistein, 22% daidzein, 2% glycitein) and a soy-derived protease inhibitor (Bowman-Birk Inhibitor Concentrate; BBIC) on prostate carcinogenesis in rats. Prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single intravenous injection of methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In separate studies, PTI G-2535 and BBIC were administered continuously at 0 (control), 200, or 2000 mg/kg diet, beginning I wk post-MNU. PTI G-2535 and BBIC both conferred modest, but statistically significant and dose-related protection against carcinogenesis in the dorsolateral + anterior prostate. These data demonstrate that both the isoflavone and protein (protease inhibitor) components of soy can inhibit prostate carcinogenesis in the rat. However, the modest individual activities of soy isoflavones and BBIC suggest that while both components may contribute to the chemopreventive activity of soy, combination administration (or exposure to whole soy) may be more eftective in prostate cancer prevention than is administration of either component alone. C1 IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. NYU, Sch Med, Dept Urol, New York, NY 10003 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU NCI NIH HHS [N01-CN-85177] NR 73 TC 24 Z9 29 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2007 VL 57 IS 2 BP 184 EP 193 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 187QI UT WOS:000247862700009 PM 17571952 ER PT J AU McCormick, DL Johnson, WD Haryu, TM Bosland, MC Lubet, RA Steele, VE AF McCormick, David L. Johnson, William D. Haryu, Todd M. Bosland, Maarten C. Lubet, Ronald A. Steele, Vernon E. TI Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID METHYL-N-NITROSOUREA; ENERGY RESTRICTION; CALORIE RESTRICTION; MAMMARY CARCINOGENESIS; UNITED-STATES; PHYSICAL-ACTIVITY; TUMOR DEVELOPMENT; BODY-SIZE; ACI RAT; CANCER AB Chronic dietary restriction inhibits carcinogenesis in several sites in laboratory animals. To determine the effects of dietary restriction on prostate carcinogenesis, prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate (50 mg/day; 21 days); testosterone propionate (100 mg/kg/day; 3 days); N-methyl-N-nitrosourea [MNU; 30 mg/kg; single dose]; and testosterone (subcutaneous implants of 2 pellets containing 40 mg each). Dietary restriction (0% [ad libitum control], 15%, or 30%) was initiated 2 wk post-MNU, and continued until study termination at 12 nio. Dietary restriction induced a rapid suppression of body weight gain but conferred no protection against prostate carcinogenesis. 74% of carcinogen-treated ad libitum controls developed accessory sex gland cancers, versus cancer incidences of 64% and 72% in groups restricted by 15% and 30%, respectively. Similarly, 44% of dietary controls developed cancers limited to the dorsolateral/prostate, versus incidences of 45% and 53% in groups restricted by 15% and 30%. The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake. Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the Wistar-Unilever rat model. C1 IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. NYU, Sch Med, Dept Urol, New York, NY 10003 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU NCI NIH HHS [CA016087, N01-CN-25017]; NIEHS NIH HHS [ES000260] NR 45 TC 9 Z9 9 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2007 VL 57 IS 2 BP 194 EP 200 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 187QI UT WOS:000247862700010 PM 17571953 ER PT J AU Mahabir, S Baer, D Johnson, LL Roth, M Campbell, W Clevidence, B Taylor, PR AF Mahabir, Somdat Baer, David Johnson, Laura L. Roth, Mark Campbell, William Clevidence, Beverly Taylor, Philip R. TI Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study SO NUTRITION JOURNAL LA English DT Article ID BREAST-CANCER CELLS; HORMONE REPLACEMENT THERAPY; PLASMA LEPTIN; ALCOHOL-CONSUMPTION; NORMAL-WEIGHT; GROWTH-FACTOR; ADIPOSITY; INSULIN; OVERWEIGHT; EXERCISE AB Background: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. Methods: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. Results and discussion: In multivariate analysis, women who were overweight (BMI > 25 to <= 30 kg/m(2)) had a 2-fold increase, and obese women (BMI > 30 kg/m(2)) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI <= 25 kg/m(2)) women. When the models for the different measures of adiposity were assessed by multiple R-2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. Conclusion: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin. C1 [Mahabir, Somdat] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. [Baer, David; Campbell, William; Clevidence, Beverly] ARS, USDA, Beltsville, MD USA. [Johnson, Laura L.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Roth, Mark] NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Taylor, Philip R.] NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mahabir, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA. EM smahabir@mdanderson.org; baer@bhnrc.arsusda.gov; johnslau@mail.nih.gov; mroth@mail.nih.gov; campbell@bhnrc.usda.gov; clevideb@ba.ars.usda.gov; ptaylor@mail.nih.gov FU [Y1-SC-8012] FX The present work was funded in part by the interagency agreement Y1-SC-8012. SM and LLJ were involved with data analysis, interpretation and writing of the manuscript. DB, WC, and BC were involved with the design and execution of the study, and the interpretation of the results. MR was involved with the laboratory analyses. PRT was the principal investigator, oversaw all aspects of the project, and was involved with data interpretation, and manuscript preparation. NR 41 TC 17 Z9 20 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2891 J9 NUTR J JI Nutr. J. PY 2007 VL 6 AR 3 DI 10.1186/1475-2891-6-3 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V21OG UT WOS:000208216300003 PM 17229323 ER PT J AU Walling, BE Munasinghe, J Berrigan, D Bailey, MQ Simpson, RM AF Walling, Brent E. Munasinghe, Jeeva Berrigan, David Bailey, Michael Q. Simpson, R. Mark TI Intra-abdommal fat burden discriminated in vivo using proton magnetic resonance spectroscopy SO OBESITY LA English DT Article DE leptin; computer-assisted image analysis; cross-sectional anatomy; animal models; investigative techniques ID ADIPOSE-TISSUE; BODY-COMPOSITION; COMPUTED-TOMOGRAPHY; OBESE; RATS; VALIDATION; MUSCLE; MICE; TRIGLYCERIDE; RISK AB Objective: To assess proton magnetic resonance spectroscopy (H-1-MRS) as a means to distinguish among mice with disparate intra-abdominal body fat compositions, and to measure changes in intra-abdominal fat burden during weight loss and regain. Research Methods and Procedures: Intra-abdominal fat burden was analyzed as a ratio of integrated areas under the curves of fat to water H-1-MRS signals collected from a region of interest standardized across B6.V-Lep(ob) C57BL/6, and A-ZIP/F mice that exhibited various genotypically related body fat compositions, ranging from obese (B6.V-Lep(ob) ) to minimal body fat (A-ZIP/F). H-1-MRS analysis of fat burden was compared with intra-abdominal fat volume and with a single cross-sectional intra-abdominal fat area calculated from segmented magnetic resonance images. Similar measurements were made from obese B6.VLep(ob) mice before, during, and after they were induced to lose weight by leptin administration. Results: Relative amounts of intra-abdominal fat analyzed by H-1-MRS differed significantly according to body composition and genotype of the three strains of mice (p < 0.05). Intra-abdominal fat assessed by H-1-MRS correlated with both intra-abdominal fat volume (r = 0.88, p < 0.001) and body weight (r = 0.82, p < 0.001) among, but not within, all three genotypes. During weight loss and regain, there was a significant overall pattern of changes in intraabdominal fat quantity that occurred, which was reflected by H-1-MRS (p = 0.006). Discussion: Results support the use of localized H-1-MRS for assessing differences in intra-abdominal fat. Refinements in H-1-MRS voxel region of interest size and location as well as instrument precision may result in improved correlations within certain body compositions. C1 NCI, Canc Res Ctr, Mol Pathol Unit, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Magnet Resonance Imaging Res Facil, Bethesda, MD 20892 USA. RP Simpson, RM (reprint author), NCI, Canc Res Ctr, Mol Pathol Unit, 37 Convent Dr,Bldg 37,Room 2000, Bethesda, MD 20892 USA. EM ms43b@nih.gov FU Intramural NIH HHS NR 25 TC 8 Z9 8 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2007 VL 15 IS 1 BP 69 EP 77 DI 10.1038/oby.2007.523 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OA UT WOS:000249605500010 PM 17228033 ER PT J AU FitzGerald, MP Weber, AM Howden, N Cundiff, GW Brown, MB AF FitzGerald, Mary P. Weber, Anne M. Howden, Nancy Cundiff, Geoffrey W. Brown, Mort B. CA Pelvic Floor Disorders Network TI Risk factors for anal sphincter tear during vaginal delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INCONTINENCE; FORCEPS; RUPTURE; WOMEN; LACERATIONS; 3RD-DEGREE; DISRUPTION; EPISIOTOMY; VACUUM; INJURY AB OBJECTIVE: To identify risk factors associated with anal sphincter tear during vaginal delivery and to identify opportunities for preventing this cause of fecal incontinence in young women. METHODS: We used baseline data from two groups of women who participated in the Childbirth and Pelvic Symptoms (CAPS) study: those women who delivered vaginally, either those with or those without a recognized anal sphincter tear. Univariable analyses of demographic and obstetric information identified factors associated with anal sphincter tear. We calculated odds ratios (ORs) for these factors alone and in combination, adjusted for maternal age, race, and gestational age. RESULTS: We included data from 797 primaparous women: 407 with a recognized anal sphincter tear and 390 without. Based on univariable analysis, a woman with a sphincter tear was more likely to be older, to be white, to have longer gestation or prolonged second stage of labor, to have a larger infant (birth weight/head circumference), or an infant who was in occiput posterior position, or to have an episiotomy or operative delivery. Logistic regression found forceps delivery (OR 13.6, 95% confidence interval [CI] 7.9-23.2) and episiotomy (OR 5.3, 95% CI 3.8-7.6) were strongly associated with a sphincter tear. The combination of forceps and episiotomy was markedly associated with sphincter tear (OR 25.3, 95% CI 10.2-62.6). The addition of epidural anesthesia to forceps and episiotomy increased the OR to 41.0 (95% CI 13.5-124.4). CONCLUSION: Our results highlight the existence of modifiable obstetric interventions that increase the risk of anal sphincter tear during vaginal delivery. Our results may be used by clinicians and women to help inform their decisions regarding obstetric interventions. C1 Loyola Univ, Med Ctr, Div Female Pelv Med & Reconstruct Surg, Maywood, IL 60153 USA. NICHHD, Bethesda, MD USA. Western Carolina Specialty Ctr, Asheville, NC USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP FitzGerald, MP (reprint author), Loyola Univ, Med Ctr, Div Female Pelv Med & Reconstruct Surg, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA. EM Mfitzg8@lumc.edu FU NICHD NIH HHS [U10 HD41261, U01 HD41249, U10 HD41248, U10 HD41250, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269]; NIDDK NIH HHS [K24 DK068389] NR 25 TC 51 Z9 52 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2007 VL 109 IS 1 BP 29 EP 34 DI 10.1097/01.AOG.0000242616.56617.ff PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171YO UT WOS:000246771500005 PM 17197584 ER PT J AU Bettes, BA Coleman, VH Zinberg, S Spong, CY Portnoy, B DeVoto, E Schulkin, J AF Bettes, Barbara A. Coleman, Victoria H. Zinberg, Stanley Spong, Catherine Y. Portnoy, Barry DeVoto, Emily Schulkin, Jay TI Cesarean delivery on maternal request - Obstetrician-gynecologists' knowledge, perception, and practice patterns SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SECTION; HEALTH; STATE AB OBJECTIVE: To examine obstetrician-gynecologists' knowledge, opinions, and practice patterns related to cesarean delivery on maternal request. METHODS: Questionnaires were mailed to 1,031 American College of Obstetricians and Gynecologists Fellows in February 2006, with a response rate of 68%. The questionnaire queried respondents' demographic characteristics, practices and attitudes surrounding vaginal and cesarean deliveries, knowledge and beliefs regarding the risks and benefits of elective and nonelective cesarean delivery, and counseling practices and department policies for cesarean delivery on maternal request. RESULTS: About half of respondents believe women have the right to cesarean delivery on maternal request, and a similar percentage acknowledge having performed at least one cesarean delivery on maternal request. Fifty-eight percent of respondents note an increase in patient inquiries regarding cesarean delivery over the past year, yet most of their practices do not have a policy regarding this procedure. Respondents attribute the increase in inquiries to the increase of information from the media and to convenience. Respondents cited more risks than benefits of cesarean delivery on maternal request, and nearly all discuss these risks with patients who are considering one. Females were more negative toward cesarean delivery on maternal request than males and endorsed more risks and fewer benefits. There were no relationships between assessment of risks and benefits or practice with clinician age or patient characteristics. CONCLUSION: Most obstetrician-gynecologists in this study recognized an increased demand for cesarean delivery on maternal request within their practices, while believing that the risks of this procedure outweigh the benefits. Clinicians would benefit from strong evidence regarding risks and benefits, evidence that is crucial to guiding policy making with regard to cesarean delivery on maternal request. C1 Amer Coll Obstetricians & Gynecologists, Dept Res, Washington, DC 20024 USA. American Univ, Dept Res, Coll Obstet & Gynecol, Washington, DC 20016 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. Amer Coll Obstetricians & Gynecologists, Div Practice Activities, Washington, DC 20024 USA. NIH, Pregnancy & Perinatol Branch, Bethesda, MD USA. NIH, Off Dis Prevent, Bethesda, MD USA. RP Coleman, VH (reprint author), Amer Coll Obstetricians & Gynecologists, Dept Res, 409 12th St SW, Washington, DC 20024 USA. EM vcoleman@acog.org OI Coleman-Cowger, Victoria/0000-0002-7745-7223 FU PHS HHS [R60 MC 05674] NR 15 TC 63 Z9 63 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2007 VL 109 IS 1 BP 57 EP 66 DI 10.1097/01.AOG.0000249608.11864.b6 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171YO UT WOS:000246771500009 PM 17197588 ER PT J AU Lee, HJ Yun, CH Lim, SH Kim, BC Baik, KG Kim, JM Kim, WH Kim, SJ AF Lee, H-J Yun, C-H Lim, S. H. Kim, B-C Baik, K. G. Kim, J-M Kim, W-H Kim, S-J TI SRF is a nuclear repressor of Smad3-mediated TGF-beta signaling SO ONCOGENE LA English DT Article DE SRF; TGF-beta; Smad; signaling; transcription; suppression ID SERUM RESPONSE FACTOR; GROWTH-FACTOR-BETA; CELL-CYCLE ARREST; DNA-BINDING ACTIVITY; PHOSPHORYLATION SITES; CDK INHIBITOR; C-MYC; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTIONAL ACTIVATORS; RECEPTOR COMPLEX AB Serum response factor (SRF) is a widely expressed transcription factor involved in immediate-early and tissue-specific gene expression, cell proliferation and differentiation. We defined a new role of SRF as a nuclear repressor of the tumor growth factor beta 1 (TGF-beta 1) growth-inhibitory signal during cell proliferation. We show that SRF significantly inhibits the TGF-beta 1/Smad-dependent transcription by associating with Smad3. SRF causes resistance to the TGF-beta 1 cytostatic response by directly repressing the Smad transcriptional activity and Smad binding to DNA. Furthermore, we demonstrated that overexpression of SRF markedly decreases the level of Smad3 complex binding to the promoters of Smad3 target genes, p15(INK4b) and p21(Cip1). This leads to the inhibition of expression of TGF-beta 1-responsive genes. SRF therefore acts as a nuclear repressor of Smad3-mediated TGF-beta 1 signaling. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. KRIBB, Div Mol Therapeut, Taejon, South Korea. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. Kangweon Natl Univ, Div Life Sci, Chunchon, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM kims@mail.nih.gov RI Kim, Wooho/G-3703-2011 FU Intramural NIH HHS NR 51 TC 23 Z9 24 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2007 VL 26 IS 2 BP 173 EP 185 DI 10.1038/sj.onc.1209774 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124VM UT WOS:000243398300002 PM 16819512 ER PT J AU Hayat, MJ Howlader, N Reichman, ME Edwards, BK AF Hayat, Matthew J. Howlader, Nadia Reichman, Marsha E. Edwards, Brenda K. TI Cancer statistics, trends, and multiple primary cancer analyses from the surveillance, epidemiology, and end results (SEER) program SO ONCOLOGIST LA English DT Article DE cancer statistics; incidence; lifetime risk; multiple primaries; survival; SEER ID THYROID-CANCER; BREAST-CANCER; LUNG-CANCER; RATES; WOMEN; NATION; RISK AB An overview of cancer statistics and trends for selected cancers and all sites combined are given based on data from the Surveillance, Epidemiology, and End Results Program. Median age at diagnosis for all sites combined shows a 2-year increase from 1974 through 1978 to 1999 through 2003. Changes in cancer incidence rates from 1975 through 2003 are summarized by annual percent change for time periods determined by joinpoint regression analysis. After initial stability (1975-1979), incidence rates in women for all cancer sites combined increased from 1979 through 2003, although the rate of increase has recently slowed. For men, initial increases in all cancer sites combined (1975-1992) are followed by decreasing incidence rates (1992-1995) and stable trends from 1995 through 2003. Female thyroid cancer shows continued increasing incidence rates from 1981 through 2003. Blacks have the highest incidence and mortality rates for men and women for all cancer sites combined. Based on 2001 through 2003 data, the likelihood of developing cancer during one's lifetime is approximately one in two for men and one in three for women. Five-year relative survival for all stages combined (1996-2002) ranges from 16% for lung to 100% for prostate cancer patients. Cancer survival varies by stage of disease and race, with lower survival in blacks compared with whites. The risk of developing subsequent multiple primary cancers varies from 1% for an initial liver primary diagnosis to 16% for initial bladder cancer primaries. The impact on the future U. S. cancer burden is estimated based on the growing and aging U. S. population. The number of new cancer patients is expected to more than double from 1.36 million in 2000 to almost 3.0 million in 2050. C1 NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Edwards, BK (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. EM edwardsb@mail.nih.gov NR 36 TC 431 Z9 464 U1 8 U2 36 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 1 BP 20 EP 37 DI 10.1634/theoncologist.12-1-20 PG 18 WC Oncology SC Oncology GA 127NY UT WOS:000243594600003 PM 17227898 ER PT J AU Zerhouni, EA Sharp, PA Leavitt, M Niederhuber, JE AF Zerhouni, Elias A. Sharp, Phillip A. Leavitt, Michael Niederhuber, John E. TI Investiture of John E. Niederhuber, MD, Director of National Cancer Institute SO ONCOLOGIST LA English DT Editorial Material C1 NIH, Off Director, Bethesda, MD 20892 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. US Dept HHS, Off Secretary, Washington, DC 20201 USA. NCI, Off Director, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 2 BP 136 EP 141 DI 10.1634/theoncologist.12-2-136 PG 6 WC Oncology SC Oncology GA 139BO UT WOS:000244407200001 PM 17296807 ER PT J AU Zerhouni, EA Sanders, CA von Eschenbach, AC AF Zerhouni, Elias A. Sanders, Charles A. von Eschenbach, Andrew C. TI The biomarkers consortium: Public and private sectors working in partnership to improve the public health SO ONCOLOGIST LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 1,Room 126,1 Ctr Dr,MSC 0148, Bethesda, MD 20892 USA. EM ZerhounE@od.nih.gov NR 0 TC 15 Z9 15 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 3 BP 250 EP 252 DI 10.1634/theoncologist.12-3-250 PG 3 WC Oncology SC Oncology GA 154YE UT WOS:000245543600003 PM 17405889 ER PT J AU Paik, S AF Paik, Soonmyung TI Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen SO ONCOLOGIST LA English DT Article ID PARAFFIN-EMBEDDED TISSUES; TUMOR GENE-EXPRESSION; CHEMOTHERAPY; THERAPY; SUBTYPES; WOMEN AB Although patients diagnosed with axillary node-negative estrogen receptor-positive breast cancer have an excellent prognosis, about 15% of them fail after 5 years of tamoxifen treatment. Clinical trials have provided evidence that there is a significant benefit from chemotherapy for these patients, but it would be significant overtreatment if all of them were treated with chemotherapy. Therefore, context-specific prognostic assays that can identify those who need chemotherapy in addition to tamoxifen, or those who are essentially cured by tamoxifen alone, and can be performed using routinely processed tumor biopsy tissue would be clinically useful. Using a stepwise approach of going through independent model-building and validation sets, a 21-gene recurrence score (RS), based on monitoring of mRNA expression levels of 16 cancer-related genes in relation to five reference genes, has been developed. The RS identified approximately 50% of the patients who had excellent prognosis after tamoxifen alone. Subsequent study suggested that high-risk patients identified with the RS preferentially benefit from chemotherapy. Ideally the RS should be used as a continuous variable. A prospective study - the Trial Assigning Individualized Options for Treatment (Rx) (TAILORx) - to examine whether chemotherapy is required for the intermediate-risk group defined by the RS is accruing in North America. C1 Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA 15206 USA. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, 4 Allegheny Ctr 5th Floor, Pittsburgh, PA 15206 USA. EM soon.paik@nsabp.org NR 17 TC 105 Z9 111 U1 1 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 6 BP 631 EP 635 DI 10.1634/theoncologist.12-6-631 PG 5 WC Oncology SC Oncology GA 186UI UT WOS:000247803400002 PM 17602054 ER PT J AU Wan, XL Helman, LJ AF Wan, Xiaolin Helman, Lee J. TI The biology behind mTOR inhibition in sarcoma SO ONCOLOGIST LA English DT Article DE mTOR; rapamycin; sarcoma; clinical trial ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-I RECEPTOR; PROTEIN-KINASE B; PHASE-II; TEMSIROLIMUS CCI-779; MAMMALIAN TARGET; CANCER-THERAPY; CELL-GROWTH; PHOSPHOINOSITIDE 3-KINASE; EWINGS-SARCOMA AB Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been found in many human tumors and implicated in the promotion of cancer cell growth and survival. Hence, the mTOR pathway is considered an important target for anticancer drug development. Currently, the mTOR inhibitor rapamycin and its derivatives CCI-779, RAD001, and AP23573 are being evaluated in cancer clinical trials. To date, clinical results have shown good tolerability of treatment with mTOR inhibitors in most reports and varying effectiveness of mTOR inhibitors in a variety of tumors in a subset of patients. For the targeted treatment of sarcomas, AP23573 has shown promising clinical efficacy and low toxicity profiles in patients. Further studies should define the optimal dose/schedule, patient selection, and combination strategies with other biological agents, especially those targeting signaling pathways crucial for cell survival. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH,Ctr Canc Res, Bldg 10,Room CRC-1W-3816, Bethesda, MD 20892 USA. EM helmanl@nih.gov NR 89 TC 112 Z9 123 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 8 BP 1007 EP 1018 DI 10.1634/theoncologist.12-8-1007 PG 12 WC Oncology SC Oncology GA 206QB UT WOS:000249196900014 PM 17766661 ER PT J AU Balducci, L Al-Halawani, H Charu, V Tam, J Shahin, S Dreiling, L Ershler, EB AF Balducci, Lodovico Al-Halawani, Hafez Charu, Veena Tam, Jennifer Shahin, Seta Dreiling, Lyndah Ershler, William B. TI Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim SO ONCOLOGIST LA English DT Article DE elderly; neutropenia; chemotherapy; cancer ID NON-HODGKINS-LYMPHOMA; COLONY-STIMULATING FACTORS; POSITIVE BREAST-CANCER; DOSE-INTENSITY; PROGNOSTIC-SIGNIFICANCE; CHOP CHEMOTHERAPY; CLINICAL-TRIALS; CELL LYMPHOMA; LUNG-CANCER; OLDER AB Background. There is a misconception that elderly cancer patients cannot tolerate standard doses of chemotherapy because of the frequency and severity of myelosuppressive complications. The reactive use of colony-stimulating factors (i.e., in response to severe neutropenia) commonly observed in this setting contributes to the frequency and severity of these complications. This study evaluated the incidence of febrile neutropenia and related events in elderly cancer patients receiving pegfilgrastim beginning with cycle 1 (proactive) in comparison with pegfilgrastim initiated after cycle 1 at the physician's discretion (reactive). Methods. Patients (>= 65 years of age) with either solid tumors or non-Hodgkin's lymphoma (NHL) were randomly assigned to receive pegfilgrastim either proactively or reactively. The primary endpoint was the proportion of patients experiencing febrile neutropenia. Results. There were 852 patients enrolled (median age, 72 years). Proactive pegfilgrastim use resulted in a significantly lower incidence of febrile neutropenia for both solid tumor and NHL patients compared with reactive use. Proactive pegfilgrastim use also led to fewer hospitalizations resulting from neutropenia and febrile neutropenia by approximately 50%. Antibiotic use was lower for solid tumor patients receiving proactive pegfilgrastim and equivalent in the two NHL groups. Conclusions. This is the largest, randomized, prospective trial evaluating growth factor support in typical elderly cancer patients. Proactive pegfilgrastim use effectively produced a lower incidence of febrile neutropenia and related events in elderly patients with either solid tumors or NHL receiving an array of mild to moderately neutropenic chemotherapy regimens. Pegfilgrastim should be used proactively in elderly cancer patients to support the optimal delivery of standard chemotherapy. C1 [Balducci, Lodovico] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Al-Halawani, Hafez] Christus St Frances Cabrini Hosp, Cabrini Ctr Canc Care, Alexandria, LA USA. [Charu, Veena; Shahin, Seta] Pacific Canc Med Ctr, Anaheim, CA USA. [Tam, Jennifer; Ershler, William B.] GOC, Baltimore, MD USA. [Dreiling, Lyndah] Amgen Inc, Thousand Oaks, CA 91320 USA. [Ershler, William B.] NIA, Clin Res Brnach, Washington, DC USA. [Ershler, William B.] Inst Adv Studies Aging, Washington, DC USA. RP Balducci, L (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Balducci@moffitt.usf.edu NR 29 TC 71 Z9 72 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2007 VL 12 IS 12 BP 1416 EP 1424 DI 10.1634/theoncologist.12-12-1416 PG 9 WC Oncology SC Oncology GA 247NX UT WOS:000252087700005 PM 18165618 ER PT J AU Mitchell, S Beck, SL Erickson, JM AF Mitchell, Sandra Beck, Susan L. Erickson, Jeanne M. TI Fatigue during and following cancer and its treatment: A qualitative metasynthesis. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. Univ Virginia, Sch Nursing, Charlottesville, VA 22903 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 75 BP 197 EP 197 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000105 ER PT J AU Mellon, S Janisse, J Gold, R Cichon, M Tainsky, M Simon, M Korczak, J AF Mellon, Suzanne Janisse, James Gold, Robin Cichon, Michelle Tainsky, Michael Simon, Michael Korczak, Jeannette TI Predictors of decision making for cancer risk information in survivors and female relatives at risk for inherited breast/ovarian cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Detroit Mercy, Detroit, MI 48221 USA. Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 93 BP 204 EP 204 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000123 ER PT J AU Hutson, S Bakos, AB Loud, J AF Hutson, Sadie Bakos, Alexis B. Loud, Jennifer TI Experience of risk among BRCA mutation-negative women from hereditary breast/ovarian cancer (HBOC) families. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 E Tennessee State Univ, Johnson City, TN 37614 USA. NINR, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 155 BP 227 EP 227 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000185 ER PT J AU Voss, J AF Voss, Joachim TI New frontiers of objective and subjective HIV and cancer-related fatigue measures. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2007 VL 34 IS 1 MA 198 BP 243 EP 243 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 125KO UT WOS:000243441000228 ER PT J AU Sonke, GS Chang, S Strom, SS Sweeney, AM Annegers, JF Sigurdson, AJ AF Sonke, Gabe S. Chang, Shine Strom, Sara S. Sweeney, Anne M. Annegers, J. Fred Sigurdson, Alice J. TI Prenatal and perinatal risk factors and testicular cancer: A hospital-based case-control study SO ONCOLOGY RESEARCH LA English DT Article DE testicular neoplasms; estrogens; risk factors; maternal exposure; case-control studies ID GERM-CELL CANCER; ESTRADIOL LEVELS; SEX-HORMONES; MALES BORN; PREGNANCY; DIETHYLSTILBESTROL; EXPOSURE; ESTROGEN; BIRTH; AGE AB Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% Cl = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% Cl = 0.4-12.9), birth weight < 3000 g (OR = 2.4; 95% CI = 0.7-8.1), and birth weight > 4000 g (OR = 1.7; 95% Cl = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis. C1 NCI, DHHS, Div Canc Epidemiol & Genet & Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA. RP Sonke, GS (reprint author), Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Med Oncol, Plesmanlaan 21, NL-1066 CX Amsterdam, Netherlands. EM g.sonke@nki.nl FU NCI NIH HHS [R25-CA 57730] NR 33 TC 22 Z9 22 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 2007 VL 16 IS 8 BP 383 EP 387 PG 5 WC Oncology SC Oncology GA 205KW UT WOS:000249113400004 PM 17913046 ER PT J AU Mielke, S Potthoff, K Feuerhake, F Bley, TA Windfuhr, M Bertz, H Finke, J AF Mielke, Stephan Potthoff, Karin Feuerhake, Friedrich Bley, Thorsten A. Windfuhr, Marisa Bertz, Hartmut Finke, Juergen TI Fatal leukoencephalopathy after reduced-intensity allogeneic stem cell transplantation SO ONKOLOGIE LA English DT Article DE leukoencephalopathy; fludarabine; cyclosporine ID CYCLOSPORINE NEUROTOXICITY AB Background: Toxicity associated with immunosuppression and conditioning regimens represents a common cause of neurological complications after allogeneic stem cell transplantation. Case Report: We present a 56-year-old female patient with refractory acute lymphoblastic leukemia undergoing reduced-intensity conditioning with fludarabine, BCNU and melphalan followed by matched-sibling allogeneic stem cell transplantation. Under immunosuppressive treatment with cyclosporine A (CSA) the patient developed early-onset (day +33) and ultimately fatal leukoencephalopathy. Discussion: As fludarabine and CSA represent two key substances of today's reduced-intensity conditioning regimens we raise the question of whether CSA, fludarabine or a combination of both led to this outcome and discuss differential diagnoses. C1 Univ Freiburg, Ctr Med, Dept Hematol & Oncol, Freiburg, Germany. Univ Freiburg, Ctr Med, Dept Neuropathol, Freiburg, Germany. Univ Freiburg, Ctr Med, Dept Diagnost Radiol, Freiburg, Germany. RP Mielke, S (reprint author), NHLBI, Stem Cell Allogene Transplant Sect HB, NIH, Bldg 10,CRC Room 3-5288,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2007 VL 30 IS 1-2 BP 49 EP 52 DI 10.1159/000098229 PG 4 GA 130IR UT WOS:000243793800008 PM 17264526 ER PT S AU Theodore, WH Fisher, R AF Theodore, W. H. Fisher, R. BE Sakas, DE Simpson, BA TI Brain stimulation for epilepsy SO OPERATIVE NEUROMODULATION: VOL 2: NEURAL NETWORKS SURGERY SE Acta Neurochirurgica Supplementum LA English DT Article; Book Chapter DE Neuromodulation; epilepsy; seizures; brain stimulation; implanted device; treatment; review ID VAGUS-NERVE-STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; CENTROMEDIAN THALAMIC NUCLEUS; HIGH-FREQUENCY STIMULATION; QUALITY-OF-LIFE; MEDICALLY INTRACTABLE SEIZURES; CHRONIC ELECTRICAL-STIMULATION; MOTOR CORTEX EXCITABILITY; DRUG-RESISTANT EPILEPSY; LONG-TERM AB Brain stimulation has been receiving increasing attention as an alternative therapy for epilepsy that cannot be treated by either antiepileptic medication or surgical resection of the epileptogenic focus. The stimulation methods include transcranial magnetic stimulation (TMS) or electrical stimulation by implanted devices of the vagus nerve (VNS), deep brain structures (DBS) (thalamic or hippocampal), cerebellar or cortical areas. TMS is the simplest and least invasive approach. However, the most common epileptogenic areas (mesial temporal structures) probably lie too deep beneath the surface of the skull for effective TMS. The efficacy of VNS in reducing the frequency or severity of seizures is quite variable and depends on many factors which are currently investigated. VNS is well-tolerated and approved in many countries. DBS is much more invasive than either TMS or VNS. Currently, a number of targets for DBS are investigated including caudate, centromedian or anterior thalamic nuclei, and subthalamic nucleus. Direct stimulation of the epileptic cortical focus is another approach to the neuromodulation in epilepsy. Finally, another line of research investigates the usefulness of implantable seizure detection devices. The current chapter presents the most important evidence on the above methods. Furthermore, other important issues are reviewed such as the selection criteria of patients for brain stimulation and the potential role of brain stimulation in the treatment of depression in epileptic patients. C1 [Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD USA. [Fisher, R.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Theodore, WH (reprint author), NIH Bldg 10 Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 148 TC 37 Z9 38 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-1419 BN 978-3-211-33081-4 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2007 VL 97 BP 261 EP 272 D2 10.1007/978-3-211-33081-4 PN 2 PG 12 WC Clinical Neurology; Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA BNJ30 UT WOS:000274732500029 PM 17691312 ER PT J AU Miskala, PH Jefferys, JL Mangione, CM Bass, EB Bressler, NM Gilson, MM Mann, AL Toth, CA Hawkins, BS AF Miskala, Paivi H. Jefferys, Joan L. Mangione, Carol M. Bass, Eric B. Bressler, Neil M. Gilson, Marta M. Mann, Ashley L. Toth, Cynthia A. Hawkins, Barbara S. CA Submacular Surgery Res Grp TI Evaluation of minimum clinically meaningful changes in scores on the national eye institute visual function questionnaire (NEI-VFQ) SST report number 19 SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 4th United States Symposium on Ocular Epidemiology CY JAN 29-31, 2007 CL Sarasota, FL DE responsiveness; anchor-based; distribution-based ID QUALITY-OF-LIFE; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; OCULAR HISTOPLASMOSIS SYNDROME; GROUP-H TRIAL; REPORT NO. 14; MACULAR DEGENERATION; OPHTHALMIC FINDINGS; SUBMACULAR SURGERY; RANDOMIZED-TRIALS; SURGICAL REMOVAL AB Purpose: To evaluate responsiveness of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to changes in visual acuity and to provide estimates of minimum clinically meaningful changes in NEI-VFQ scores. Methods: Data were combined from three clinical trials of submacular surgery for subfoveal choroidal neovascularization. Patients who completed NEI-VFQ interviews and visual acuity measurements at baseline and 2 years later contributed data for analysis. Data were analyzed using anchor-based ( relating 2-year change in NEI-VFQ to 2-year change in visual acuity using correlation and linear regression) and distribution-based ( standardized response mean) methods. Results: Of 1,015 patients enrolled, 828 patients completed NEI-VFQ interviews and had visual acuity measurements at baseline and 2 years later. Median age of patients was 75 years ( range 18 to 94); all patients had subfoveal choroidal neovascularization in at least one eye. Median overall NEI-VFQ score at baseline was 69.9 ( mean, 66.5). Based on anchor-based methods, a 2-line change in visual acuity of the better-seeing eye translated to a 3.4-point change in the overall NEI-VFQ score and from 2.4-point to 7.0-point changes in most subscale scores. The NEI-VFQ was sensitive to both gains and losses in visual acuity; the standardized response mean for the overall NEI-VFQ score in patients with a 2-line gain was 0.6 and for patients with 2-line loss was -0.3. In the subgroup of patients with a 2-line loss of visual acuity in the better-seeing eye, patients who had overall NEI-VFQ scores at baseline greater than the median (59.8) had an standardized response mean of -0.9 for the overall NEI-VFQ score and patients who had overall NEI-VFQ scores at baseline at or below the median had a standardized response mean of 0.2 for the overall NEI-VFQ score. A 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores corresponded to a small clinically meaningful change. Conclusions: The NEI-VFQ was responsive to 2-year changes in visual acuity but was less responsive to changes among patients with poorer NEI-VFQ scores at baseline. Based on this analysis, a 4-point change in the overall NEI-VFQ and a 5-point change in individual subscale scores may be considered minimum clinically meaningful within-person changes in NEI-VFQ scores. C1 NEI, Div Extramural Res, Bethesda, MD 20892 USA. RP Miskala, PH (reprint author), NEI, Div Extramural Res, 5635 Fishers Lane,Suite 1300,MSC 9300, Bethesda, MD 20892 USA. EM miskalap@mail.nih.gov RI toth, cynthia/F-5614-2011 NR 24 TC 33 Z9 33 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PY 2007 VL 14 IS 4 BP 205 EP 215 DI 10.1080/09286580701502970 PG 11 WC Ophthalmology SC Ophthalmology GA 214GP UT WOS:000249724700011 ER PT J AU Gwiazda, J Hyman, L Dong, LM Everett, D Norton, T Kurtz, D Manny, R Marsh-Tootle, W Scheiman, M AF Gwiazda, Jane Hyman, Leslie Dong, Li Ming Everett, Don Norton, Tom Kurtz, Dan Manny, Ruth Marsh-Tootle, Wendy Scheiman, Mitch CA COMET Grp TI Factors associated with high myopia after 7 years of follow-up in the correction of myopia evaluation trial (COMET) cohort SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 4th United States Symposium on Ocular Epidemiology CY JAN 29-31, 2007 CL Sarasota, FL DE children; myopia; refraction; risk factors ID UNITED-STATES; PROGRESSION; CHILDREN; AGE AB Purpose: To evaluate factors associated with the development of high myopia ( worse than -6.00 D) over 7 years of follow-up in theCOMETcohort. Methods: COMET enrolled 469 ethnically diverse children (6-11 years) with myopia between-1.25 and -4.50 D. They were randomized to either progressive addition lenses ( PALs) or single vision lenses (SVLs), and followed for 5 years in their original lens assignment and 2 additional years wearing either spectacles ( PALs or SVLs) or contact lenses. Refractive error was measured annually by cycloplegic autorefraction and axial length by A-Scan ultrasonography. Myopia for each child was defined as the mean spherical equivalent refractive error (SER) of the 2 eyes. Analyses were based on 7 years of follow-up. Time to high myopia was analyzed by Cox proportional hazard models and linear regression. Parental refraction data were available from 240 COMET subjects. Results: Younger (6-7 years) versus older ( 11 years) age at baseline was a significant risk factor ( adjusted hazard ratio (HR) = 6.6, 95% CI = 3.4, 12.7) for having high myopia within 7 years. More ( SER from-2.26 to -4.50 D) vs. less ( SER from -1.25 to -2.25 D) baseline myopia was also a significant risk factor for high myopia at 7 years ( adjusted HR = 7.4, 95% CI = 4.4, 12.4). Gender, ethnicity, and treatment assignment were not associated with the risk of high myopia within 7 years. Increased number of myopic parents was associated with a significant risk of high myopia in the children ( p = 0.008). Conclusions: Children who developed high myopia during 7 years of follow-up were younger and had more myopia at baseline. They also were more likely to have two myopic parents. These children may be at greater risk for sight-threatening conditions later in life. C1 New England Coll Optometry, Boston, MA 02115 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Sch Optometry, Birmingham, AL 35294 USA. Univ Houston, Coll Optometry, Houston, TX USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. Comet Grp, Boston, MA USA. Comet Grp, Stony Brook, NY USA. Comet Grp, Birmingham, AL USA. Comet Grp, Houston, TX USA. Comet Grp, Philadelphia, PA USA. RP Gwiazda, J (reprint author), New England Coll Optometry, 424 Beacon St, Boston, MA 02115 USA. EM gwiazdaj@neco.edu FU NEI NIH HHS [EY11752, EY11754, EY11756, EY11740, EY11755, EY11805] NR 16 TC 18 Z9 18 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PY 2007 VL 14 IS 4 BP 230 EP 237 DI 10.1080/01658100701486459 PG 8 WC Ophthalmology SC Ophthalmology GA 214GP UT WOS:000249724700014 PM 17896302 ER PT J AU Kim, SH Lutz, RJ Wang, NS Robinson, MR AF Kim, Stephanie H. Lutz, Robert J. Wang, Nam Sun Robinson, Michael R. TI Transport barriers in transscleral drug delivery for retinal diseases SO OPHTHALMIC RESEARCH LA English DT Review DE drug delivery; pharmacokinetics; retina; transscleral; drug transport; metabolism; clearance ID RETROBULBAR TRIAMCINOLONE INFUSION; DIABETIC MACULAR EDEMA; UVEOSCLERAL DRAINAGE ROUTES; MOLECULAR-WEIGHT COMPOUNDS; HUMAN SCLERAL PERMEABILITY; PIGMENT EPITHELIAL-CELLS; AQUEOUS-HUMOR DYNAMICS; INTRAVITREAL INJECTION; SUPRACHOROIDAL SPACE; BRUCHS MEMBRANE AB Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue ( sclera, Bruch's membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Kim, SH (reprint author), NEI, NIH, 9000 Rockville Pike,Bldg 13-3N07, Bethesda, MD 20892 USA. EM kimstep@mail.nih.gov RI Wang, Nam Sun/E-4253-2016 NR 125 TC 58 Z9 60 U1 6 U2 17 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2007 VL 39 IS 5 BP 244 EP 254 DI 10.1159/000108117 PG 11 WC Ophthalmology SC Ophthalmology GA 211PY UT WOS:000249537000001 PM 17851264 ER PT J AU Liang, XL Shen, DF Huang, YS Yin, CY Bojanowski, CM Zhuang, ZP Chan, CC AF Liang, Xiaoling Shen, Defen Huang, Yongsheng Yin, Chunyue Bojanowski, Christine M. Zhuang, Zhengping Chan, Chi-Chao TI Molecular pathology and CXCR4 expression in surgically excised retinal hemangioblastomas associated with von Hippel-Lindau disease SO OPHTHALMOLOGY LA English DT Article ID RENAL-CELL-CARCINOMA; HEREDITARY CANCER SYNDROME; RECEPTOR INHIBITOR SU5416; CAPILLARY HEMANGIOMA; STEM-CELLS; VASOPROLIFERATIVE TUMORS; CHEMOKINE RECEPTORS; MACULAR DETACHMENT; VHL GENE; ANGIOMA AB Purpose: The surgical excision of retinal vascular lesions including hemangioblastomas is rarely practiced. This study investigates the pathological characteristics of 4 patients (3 with von Hippel-Lindau [VHL] disease and 1 with a vasoproliferative retinal tumor) who underwent ocular tumor resection. von Hippel-Lindau is an autosomal dominant disease caused by a defect of the VHL tumor suppressor gene. The VHL protein is required for oxygen-dependent degradation of hypoxia-inclucible factor 1 alpha. This factor regulates vascular endothelial growth factor (VEGF) and the chemokine receptor CXCR4. Retinal hemangioblastoma is the most common tumor observed in VHL disease. We investigated the expression of CXCR4; its ligand, CXCL12/SDF-1 alpha; VEGF; and the VHL gene in VHL disease-associated retinal hemangioblastomas. Design: Interventional case series with immunohistological and molecular pathological analyses. Participants: Immunohistochemistry and molecular pathology of the surgically excised retinal lesions were performed. Intervention: Large retinal hemangioblastomas (1-3 disc diameters) and vasoproliferative tumors were resected surgically after laser photocoagulation in 4 patients. The excised tissues were snap frozen and evaluated by histology. Molecular pathology was performed for the VHL gene, and immunohistochemistry and molecular detection (reverse transcription polymerase chain reaction) were carried out for VEGF, CXCR4, and CXCL12. Main Outcome Measures: Evaluation of clinical presentations and molecular pathology of the excised retinal lesions. Results: Large retinal hemangioblastomas were resected successfully from the 3 VHL cases. Postoperatively, all patients were stable. Molecular analyses disclosed the loss of heterozygosity at the VHL allele locus in the VHL retinal hemangioblastomas but not in the vasoproliferative tumor. High levels of transcript and protein were found for VEGF and CXCR4, whereas low levels of CXCL12 mRNA were expressed in the retinal hemangioblastomas associated with VHL disease. In contrast, very low levels of VEGF and CXCR4 mRNA were detected in the vasoproliferative tumor. Furthermore, increased expression of VEGF and CXCR4 was detected in more active hemangioblastomas. Conclusions: Surgical resection of large retinal hemangioblastomas may be useful for therapy in selected VHL patients. Activated VHL lesions produce more VEGF. This is the first demonstration of CXCR4 expression in VHL disease-associated retinal hemangioblastomas. We suggest targeting CXCR4 as an additional therapeutic strategy for VHL disease-associated retinal hemangioblastomas. C1 NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Sun Yat Sen Univ, Key Lab Ophthalmol, Minist Educ, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Chan, CC (reprint author), NEI, NIH, Immunol Lab, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 53 TC 14 Z9 16 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2007 VL 114 IS 1 BP 147 EP 156 DI 10.1016/j.ophtha.2006.05.068 PG 10 WC Ophthalmology SC Ophthalmology GA 123DA UT WOS:000243275300024 PM 17070589 ER PT S AU Tabak, LA AF Tabak, Lawrence A. BE Malamud, D Niedbala, RS TI Point-of-care diagnostics enter the mouth SO ORAL-BASED DIAGNOSTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral-Based Diagnostics CY OCT 10-13, 2006 CL Lake Lanier Isl, GA SP Drager Safety, Drager USA, Int Diagnost Syst Corp, K Street Associates LLC, Lehigh Univ, NIDCR, NY Univ Coll Dent, OraSure Technologies Inc, Salimetrics LLC, StatSure Diagnost Syst DE diagnostic; saliva; point-of-care ID PUBLIC-HEALTH; NECK-CANCER; SALIVA; POPULATION; INTERNET; BURDEN; VIRUS; HEAD; DNA AB In this succinct review, I delineate a case supporting point-of-care (POC) diagnostics to provide a brief outline of why oral fluid/salivabased POC offer several advantages over more traditional blood-based tests and conclude with a focused overview of the ethical, legal, and social implications of more widespread access to oral fluid/saliva-based POC diagnostics. C1 Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, 31 Ctr Dr,Rm 2C39,MSC 2290, Bethesda, MD 20892 USA. EM tabakl@mail.nih.gov NR 42 TC 25 Z9 26 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-661-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1098 BP 7 EP 14 DI 10.1196/annals.1384.043 PG 8 WC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Science & Technology - Other Topics GA BGC93 UT WOS:000246091500002 PM 17303835 ER PT S AU Cone, EJ Huestis, MA AF Cone, Edward J. Huestis, Marilyn A. BE Malamud, D Niedbala, RS TI Interpretation of oral fluid tests for drugs of abuse SO ORAL-BASED DIAGNOSTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral-Based Diagnostics CY OCT 10-13, 2006 CL Lake Lanier Isl, GA SP Drager Safety, Drager USA, Int Diagnost Syst Corp, K Street Associates LLC, Lehigh Univ, NIDCR, NY Univ Coll Dent, OraSure Technologies Inc, Salimetrics LLC, StatSure Diagnost Syst DE oral fluid; saliva; interpretation; testing; advantages; limitations ID CHROMATOGRAPHY-MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; TOBACCO-SMOKE EXPOSURE; COMMERCIAL OPIATE IMMUNOASSAYS; CAPILLARY GAS-CHROMATOGRAPHY; PLASMA-PROTEIN BINDING; HUMAN-SERUM PROTEINS; URINARY-EXCRETION; DETECTION TIMES; SALIVA COTININE AB Oral fluid testing for drugs of abuse offers significant advantages over urine as a test matrix. Collection can be performed under direct observation with reduced risk of adulteration and substitution. Drugs generally appear in oral fluid by passive diffusion from blood, but also may be deposited in the oral cavity during oral, smoked, and intranasal administration. Drug metabolites also can be detected in oral fluid. Unlike urine testing, there may be a close correspondence between drug and metabolite concentrations in oral fluid and in blood. Interpretation of oral fluid results for drugs of abuse should be an iterative process whereby one considers the test results in the context of program requirements and a broad scientific knowledge of the many factors involved in determining test outcome. This review delineates many of the chemical and metabolic processes involved in the disposition of drugs and metabolites in oral fluid that are important to the appropriate interpretation of oral fluid tests. Chemical, metabolic, kinetic, and analytic parameters are summarized for selected drugs of abuse, and general guidelines are offered for understanding the significance of oral fluid tests. C1 Johns Hopkins Sch Med, Baltimore, MD USA. NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD USA. RP Cone, EJ (reprint author), ConeChem Res LLC, 441 Fairtree Dr, Severna Park, MD 21146 USA. EM edward.cone@comcast.net FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000413-10, Z01 DA000414-10] NR 193 TC 68 Z9 70 U1 2 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-661-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1098 BP 51 EP 103 DI 10.1196/annals.1384.037 PG 53 WC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Science & Technology - Other Topics GA BGC93 UT WOS:000246091500005 PM 17332074 ER PT S AU Huestis, MA Cone, EJ AF Huestis, Marilyn A. Cone, Edward J. BE Malamud, D Niedbala, RS TI Methamphetamine disposition in oral fluid, plasma, and urine SO ORAL-BASED DIAGNOSTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral-Based Diagnostics CY OCT 10-13, 2006 CL Lake Lanier Isl, GA SP Drager Safety, Drager USA, Int Diagnost Syst Corp, K Street Associates LLC, Lehigh Univ, NIDCR, NY Univ Coll Dent, OraSure Technologies Inc, Salimetrics LLC, StatSure Diagnost Syst DE methamphetamine; collection; oral fluid; saliva; urine; plasma ID AMPHETAMINE; PHARMACOKINETICS; EXCRETION; HUMANS AB This review of the disposition of methamphetamine in oral fluid, plasma, and urine is based on a comprehensive controlled dosing study involving five healthy, drug-free research volunteers who resided on a closed clinical ward for 12 weeks. Subjects were administered four low (10 mg) and high (20 mg) daily oral doses of methamphetamine in two separate sessions. Near-simultaneous collections of oral fluid and plasma were performed on the first day of each low- and high-dose session. Thereafter, oral fluid was provided on each day of dosing by different oral fluid collection methods. All urine specimens were collected on an ad libitum basis throughout the study. Specimens were analyzed by gas-chromatography mass spectrometry for methamphetamine and the metabolite, amphetamine, with a limit of quantification of 2.5 ng/mL for each analyte. Methamphetamine and metabolite concentrations in oral fluid appeared to follow a similar time course in oral fluid as in plasma and were dose-proportional, but oral fluid concentrations exceeded plasma concentrations. Urine drug concentrations were substantially higher than those in oral fluid. Some drug accumulation was noted with daily dosing, but generally did not markedly influence detection times or detection rates of oral fluid tests. Detection times and detection rates for oral fluid and urine were determined at cessation of 4 days of dosing. Generally, detection times and rates for urine were longer than those observed for oral fluid at conventional cutoff concentrations. When contemplating selection of oral fluid as a test matrix, the advantages of oral fluid collection should be weighed against its shorter time of detection compared to that of urine. C1 NIDA, Chem & Drug Metab Sect, IRP, NIH, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD USA. EM MHUESTIS@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000413-10, Z01 DA000412-10] NR 8 TC 38 Z9 40 U1 1 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-661-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1098 BP 104 EP 121 DI 10.1196/annals.1384.038 PG 18 WC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Science & Technology - Other Topics GA BGC93 UT WOS:000246091500006 PM 17332086 ER PT S AU Gannot, G Tangrea, MA Chuaqui, RF Gillespie, JW Emmert-Buck, MR AF Gannot, Gallya Tangrea, Michael A. Chuaqui, Rodrigo F. Gillespie, John W. Emmert-Buck, Michael R. BE Malamud, D Niedbala, RS TI Layered peptide arrays - A diverse technique for antibody screening of clinical samples SO ORAL-BASED DIAGNOSTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oral-Based Diagnostics CY OCT 10-13, 2006 CL Lake Lanier Isl, GA SP Drager Safety, Drager USA, Int Diagnost Syst Corp, K Street Associates LLC, Lehigh Univ, NIDCR, NY Univ Coll Dent, OraSure Technologies Inc, Salimetrics LLC, StatSure Diagnost Syst DE layered peptide array; multiplex; high-throughput; ELISA; immunohistochemistry ID PROTEIN MICROARRAYS; ANTIGENS AB The layered peptide array (LPA) is a recently developed technique designed to measure antibody levels in a multiplex, highthroughput manner. LPAs can assess antibody presence either in fluid samples or from tissues while maintaining the two-dimensional orientation of the life science platform. In this manuscript, we evaluated and assessed the performance of the LPA platform, focusing on throughput capability, sensitivity, and specificity of the assay in several different systems. C1 NCI, Ctr Canc Res, Ctr Adv Technol, Pathogenet Unit,Lab Pathol,NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Urol Oncol Branch, Surg Branch,NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Tumor Angiogenesis Sect, Surg Branch,NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Ctr Canc Res, Ctr Adv Technol, Pathogenet Unit,Lab Pathol,NIH, 8717 Grovement Circle, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov FU Intramural NIH HHS NR 15 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-661-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1098 BP 451 EP 453 DI 10.1196/annals.1384.041 PG 3 WC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Multidisciplinary Sciences SC Dentistry, Oral Surgery & Medicine; Medical Laboratory Technology; Science & Technology - Other Topics GA BGC93 UT WOS:000246091500033 PM 17435150 ER PT J AU Maria, OM Khosravi, R Mezey, E Tran, SD AF Maria, O. M. Khosravi, R. Mezey, E. Tran, S. D. TI Cells from bone marrow that evolve into oral tissues and their clinical applications SO ORAL DISEASES LA English DT Review DE bone marrow; cell plasticity; cell-based therapies; oral tissues; stem cells; tissue engineering ID MESENCHYMAL STEM-CELLS; IN-VIVO; HEMATOPOIETIC-CELLS; EPITHELIAL-CELLS; PROGENITOR CELLS; ENGINEERED BONE; REGENERATION; TRANSPLANTATION; PLASTICITY; PLURIPOTENCY AB There are two major well-characterized populations of post-natal (adult) stem cells in bone marrow: hematopoietic stem cells which give rise to blood cells of all lineages, and mesenchymal stem cells which give rise to osteoblasts, adipocytes, and fibroblasts. For the past 50 years, strict rules were taught governing developmental biology. However, recently, numerous studies have emerged from researchers in different fields suggesting the unthinkable - that stem cells isolated from a variety of organs are capable of ignoring their cell lineage boundaries and exhibiting more plasticity in their fates. Plasticity is defined as the ability of post-natal (tissue-specific adult) stem cells to differentiate into mature and functional cells of the same or of a different germ layer of origin. There are reports that bone marrow stem cells can evolve into cells of all dermal lineages, such as hepatocytes, skeletal myocytes, cardiomyocytes, neural, endothelial, epithelial, and even endocrine cells. These findings promise significant therapeutic implications for regenerative medicine. This article will review recent reports of bone marrow cells that have the ability to evolve or differentiate into oral and craniofacial tissues, such as the periodontal ligament, alveolar bone, condyle, tooth, bone around dental and facial implants, and oral mucosa. C1 McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Tran, SD (reprint author), McGill Univ, Fac Dent, 3640 Univ St,Room M-43, Montreal, PQ H3A 2B2, Canada. EM simon.tran@mcgill.ca OI Khosravi, Roozbeh/0000-0002-9070-0339 NR 64 TC 24 Z9 31 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2007 VL 13 IS 1 BP 11 EP 16 DI 10.1111/j.1601-0825.2006.01324.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 123PH UT WOS:000243307300002 PM 17241424 ER PT J AU Liu, F Worthy, KM Bindu, L Giubellino, A Bottaro, DP Fisher, RJ Burke, TR AF Liu, Fa Worthy, Karen M. Bindu, Lakshman Giubellino, Alessio Bottaro, Donald P. Fisher, Robert J. Burke, Terrence R., Jr. TI Utilization of achiral alkenyl amines for the preparation of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing metathesis SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID PEPTIDE INHIBITORS; OLEFIN METATHESIS; KINASE INHIBITORS; LIGANDS; DESIGN; MIMETICS; AGENTS AB A family of previously reported ring-closing metathesis (RCM)-derived macrocycles that exhibit potent Grb2 SH2 domain-binding affinity is characterized by stereoselectively-introduced upper ring junctions that bear bicyclic aryl substituents. However, the synthetic complexity of these macrocycles presents a potential limit to their therapeutic application. Therefore, the current study was undertaken to simplify these macrocycles through the use of achiral 4-pentenylamides as ring-forming components. A series of macrocycles (5a - f) was prepared bearing both open and cyclic constructs at the upper ring junction. The Grb2 SH2 domain-binding affinities of these macrocycles varied, with higher affinities being obtained with cyclo-substituents. The most potent analogue (5d) contained a cyclohexyl group and exhibited Grb2 SH2 domain-binding affinity (K-D = 1.3 nM) that was nearly equal to the parent macrocycle ( 2), which bore a stereoselectively-introduced naphthylmethyl substituent at the upper ring junction (K-D = 0.9 nM). The results of this study advance design considerations that should facilitate the development of Grb2 SH2 domain-binding antagonists. C1 NCI Frederick, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20989 USA. RP Burke, TR (reprint author), NCI Frederick, Ctr Canc Res, Med Chem Lab, Bldg 376 Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014; OI Bottaro, Donald/0000-0002-5057-5334; Giubellino, Alessio/0000-0002-5352-0662 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 32 TC 5 Z9 5 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2007 VL 5 IS 2 BP 367 EP 372 DI 10.1039/b611887a PG 6 WC Chemistry, Organic SC Chemistry GA 123AS UT WOS:000243269300024 PM 17205182 ER PT J AU Cheng, K Kim, IJ Lee, MJ Adah, SA Raymond, TJ Bilsky, EJ Aceto, MD May, EL Harris, LS Coop, A Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Cheng, Kejun Kim, In Jong Lee, Mei-Jing Adah, Steven A. Raymond, Tyler J. Bilsky, Edward J. Aceto, Mario D. May, Everette L. Harris, Louis S. Coop, Andrew Dersch, Christina M. Rothman, Richard B. Jacobson, Arthur E. Rice, Kenner C. TI Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-phenylmorphans. Synthesis of a mu-agonist delta-antagonist and delta-inverse agonists SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID RECEPTOR-MEDIATED PHENOMENA; (+)-4-<(ALPHA-R)-ALPHA-((2S,5R)-4-ALLYL-2,5-DIMETHYL-1-PIPERAZINYL)-3-ME THOXYBE SNC-80; PEPTIDE RECEPTOR; MORPHINE; BINDING; PROBES; STEREOCHEMISTRY; IDENTIFICATION; DERIVATIVES; MODULATION AB Enantiomeric N-phenethyl-m-hydroxyphenylmorphans with various substituents in the ortho, meta or para positions of the aromatic ring in the phenethylamine side-chain (chloro, hydroxy, methoxy, nitro, methyl), as well as a pyridylethyl and a indolylethyl moiety on the nitrogen atom, were synthesized and their binding affinity to the mu-, delta-, and kappa- opioid receptors was examined. The higher affinity ligands were further examined in the [S-35] GTP gamma S assay to study their function and efficacy. 3-((1R,5S)-(-)- 2-(4-Nitrophenethyl)-2-aza-bicyclo[3.3.1] nonan-5-yl) phenol ((-)-10m) was found to be a mu-agonist and d- antagonist in that functional assay and was about 50 fold more potent than morphine in vivo. 3-((1R,5S)-(-)-2-(4-Chlorophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-10i) and several other ligands displayed inverse agonist activity at the d- opioid receptor. The absolute configuration of all of the reported compounds was established by chemical conversion of (-)- 6 to 1R,5S-(-)- 8b center dot HBr. C1 NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ New England, Coll Osteopath Med, Biddeford, ME 04005 USA. Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kr21f@nih.gov FU Intramural NIH HHS; NIDA NIH HHS [DA K02-19634, K02 DA019634, K02 DA019634-01] NR 33 TC 15 Z9 16 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2007 VL 5 IS 8 BP 1177 EP 1190 DI 10.1039/b618875c PG 14 WC Chemistry, Organic SC Chemistry GA 153MO UT WOS:000245439800009 PM 17406716 ER PT S AU Bortner, CD Sifre, MI Cidlowski, JA AF Bortner, Carl D. Sifre, Maria I. Cidlowski, John A. BE Haussinger, D Sies, H TI New approaches for determining apoptotic volume decrease in cells SO OSMOSENSING AND OSMOSIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID THYMOCYTE APOPTOSIS; FLOW-CYTOMETRY; RAT THYMOCYTES; SHRINKAGE; K+; ACTIVATION; DEATH; PHOSPHATIDYLSERINE; PHAGOCYTOSIS AB The loss of cell volume or cell shrinkage, termed apoptotic volume decrease (AVD), is a classical characteristic of apoptosis. Microscopy, Coulter electronic sizing, and/or flow cytometry has traditionally been the means to measure this characteristic of apoptosis. Although electronic cell sizing allows for precise determination of changes in cell size, these measurements provide data on the entire population of apoptotic cells. In contrast, flow cytometry examines and separates unique populations of apoptotic cells based on the light-scattering properties of the cells to determine alterations in cellular dimensions. However, this technique does not provide exact measurements of cell size and volume. The Cell Lab Quanta SC flow cytometer combines the power of electronic sizing with the ability to isolate and examine unique populations of apoptotic cells to determine exact changes in cell size as they undergo cell death. This chapter describes several methods for using the Cell Lab Quanta SC to study AVD during apoptosis. C1 NIH, NIEHS, Dept Hlth & Human Serv, Lab Signal Tranduct, Res Triangle Pk, NC USA. RP Bortner, CD (reprint author), NIH, NIEHS, Dept Hlth & Human Serv, Lab Signal Tranduct, Res Triangle Pk, NC USA. FU Intramural NIH HHS NR 22 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373921-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 428 BP 161 EP + DI 10.1016/S0076-6879(07)28009-7 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGR95 UT WOS:000250200300009 PM 17875417 ER PT S AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. BE Haussinger, D Sies, H TI Osmotic stress and DNA damage SO OSMOSENSING AND OSMOSIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID MURINE KIDNEY-CELLS; IN-SITU; STRAND BREAKS; COMET ASSAY; NICK TRANSLATION; DEOXYRIBONUCLEIC ACID; GEL-ELECTROPHORESIS; HYPERTONIC STRESS; INDIVIDUAL CELLS; MAMMALIAN-CELLS AB Mammalian renal inner medullary cells are normally exposed to extremely high NaCl concentrations. The interstitial NaCl concentration in parts of a normal renal medulla can be 500 mM or more, depending on the species. Remarkably, under these normal conditions, the high NaCl causes DNA damage, yet the cells survive and function both in cell culture and in vivo. Both in cell culture and in vivo the breaks are repaired rapidly if the NaCl concentration is lowered. This chapter describes two methods used to detect and study the DNA damage induced by osmotic stress: comet assay or single cell electrophoresis and TUNEL assay or in situ labeling of 3'-OH ends of DNA strands. This chapter also discusses how specifics of the protocols influence the conclusions about types of DNA damage and what the limitations of these methods are for detecting different types of DNA damage. C1 NIH, NHLBI, Lab Kidney & Electrolyte Metab, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NIH, NHLBI, Lab Kidney & Electrolyte Metab, Bldg 10, Bethesda, MD 20892 USA. RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 42 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373921-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 428 BP 241 EP 252 DI 10.1016/S0076-6879(07)28013-9 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGR95 UT WOS:000250200300013 PM 17875421 ER PT S AU Ferraris, JD Burg, MB AF Ferraris, Joan D. Burg, Maurice B. BE Haussinger, D Sies, H TI Tonicity-regulated gene expression SO OSMOSENSING AND OSMOSIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID ENHANCER-BINDING PROTEIN; ALDOSE REDUCTASE GENE; TRANSCRIPTION FACTOR TONEBP/OREBP; MEDULLARY EPITHELIAL-CELLS; DAMAGE-INDUCIBLE KINASE; OSMOTIC RESPONSE; HIGH NACL; NUCLEAR-LOCALIZATION; MAMMALIAN-CELLS; DNA-BINDING AB Hypertonicity activates several different transcription factors, including TonEBP/OREBP, that in turn increase transcription of numerous genes. Hypertonicity elevates TonEBP/OREBP transcriptional activity by moving it into the nucleus, where it binds to its cognate DNA element (ORE), and by increasing its transactivational activity. This chapter presents protocols for measuring the transcriptional activity of TonEBP/OREBP and determining its subcellular localization, its binding to ORES, and activity of its transactivation domain. C1 NIH, NHLBI, US Dept HHS, Kidney & Electrolyte Metab Lab, Bethesda, MD USA. RP Ferraris, JD (reprint author), NIH, NHLBI, US Dept HHS, Kidney & Electrolyte Metab Lab, Bethesda, MD USA. FU Intramural NIH HHS NR 63 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373921-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 428 BP 279 EP 296 DI 10.1016/S0076-6879(07)28016-4 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGR95 UT WOS:000250200300016 PM 17875424 ER PT J AU Sharrock, WJ AF Sharrock, William J. TI Interactions of the immune and skeletal systems - Preface SO OSTEOIMMUNOLOGY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Editorial Material ID OSTEOCLAST DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; T-CELLS; ACTIVATION; CYTOKINE; BONE C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Sharrock, WJ (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM sharrocw@ep.niams.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 602 BP V EP VII PG 3 WC Immunology; Medicine, Research & Experimental; Orthopedics SC Immunology; Research & Experimental Medicine; Orthopedics GA BGR94 UT WOS:000250200200001 ER PT S AU Melillo, G AF Melillo, Giovanni BE Sies, H Brune, B TI Hypoxia-inducible factor 1 inhibitors SO OXYGEN BIOLOGY AND HYPOXIA SE Methods in Enzymology LA English DT Review; Book Chapter ID SMALL-MOLECULE INHIBITORS; ENDOTHELIAL GROWTH-FACTOR; DNA-BINDING ACTIVITY; FACTOR-I; CANCER-THERAPY; TRANSCRIPTIONAL ACTIVITY; STRUCTURAL BASIS; TUMOR-GROWTH; HIF-1; PATHWAY AB The tremendous progress in our understanding of the molecular mechanisms underlying the presence and consequences of hypoxia in human cancers has been accompanied by renewed enthusiasm for the development of therapeutic strategies targeting hypoxic cells signaling pathways. Hypoxia-inducible factor 1 (HIF-1), a key transcriptional activator that mediates hypoxic responses, has been the focus of intense investigation and efforts to identify small molecule inhibitors or novel strategies for HIF-1 inhibition have multiplied over the last few years. Despite challenges associated with targeting transcription factors, which hamper these efforts, several strategies have been pursued. In this chapter, protocols related to screening assays, both cell-based and cell-free, are described and discussed in the context of their application for the identification of HIF-1 inhibitors. While cell-based assays offer the opportunity to reveal unidentified components of the hypoxic cell signaling pathway, cell-free targeted approaches may lead to the identification of more selective HIF-1 inhibitors. Validation of "hits" and characterization of their mechanism of action are essential for a rational development of putative HIF-1 inhibitors in preclinical models and early clinical trials. C1 SAIC Frederick Inc, Natl Canc Inst, Dev Therapeut Program, Frederick, MD USA. RP Melillo, G (reprint author), SAIC Frederick Inc, Natl Canc Inst, Dev Therapeut Program, Frederick, MD USA. FU NCI NIH HHS [N01-CO-12400] NR 34 TC 25 Z9 29 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373970-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 435 BP 385 EP 402 DI 10.1016/S0076-6879(07)35020-9 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGX74 UT WOS:000251162300020 PM 17998065 ER PT B AU Kann, M Ofran, Y Punta, M Radivojac, P AF Kann, Maricel Ofran, Yanay Punta, Marco Radivojac, Predrag BE Altman, RB Dunker, AK Hunter, L Murray, T Klein, TE TI Protein interactions and disease SO Pacific Symposium on Biocomputing 2007 LA English DT Proceedings Paper CT 13th Pacific Symposium on Biocomputing (PSB) CY JAN 03-07, 2007 CL Maui, HI C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Kann, M (reprint author), Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-270-417-5 PY 2007 BP 1 EP 3 PG 3 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Biochemistry & Molecular Biology; Computer Science; Engineering GA BFX58 UT WOS:000245296300001 ER PT B AU Ahlers, CB Fiszman, M Demner-Fushman, D Lang, FM Rindflesch, TC AF Ahlers, Caroline B. Fiszman, Marcelo Demner-Fushman, Dina Lang, Francois-Michel Rindflesch, Thomas C. BE Altman, RB Dunker, AK Hunter, L Murray, T Klein, TE TI Extracting semantic predications from MEDLINE citations for pharmacogenomics SO Pacific Symposium on Biocomputing 2007 LA English DT Proceedings Paper CT 13th Pacific Symposium on Biocomputing (PSB) CY JAN 03-07, 2007 CL Maui, HI ID BIOMEDICAL TEXT; GENE; KNOWLEDGE; DISEASE AB We describe a natural language processing system (Enhanced SemRep) to identify core assertions on pharmacogenomics in Medline citations. Extracted information is represented as semantic predications covering a range of relations relevant to this domain. The specific relations addressed by the system provide greater precision than that achievable with methods that rely on entity co-occurrence. The development of Enhanced SemRep is based on the adaptation of an existing system and crucially depends on domain knowledge in the Unified Medical Language System. We provide a preliminary evaluation (55% recall and 73% precision) and discuss the potential of this system in assisting both clinical practice and scientific investigation. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Ahlers, CB (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. FU Intramural NIH HHS NR 30 TC 26 Z9 26 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-270-417-5 PY 2007 BP 209 EP 220 PG 12 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Biochemistry & Molecular Biology; Computer Science; Engineering GA BFX58 UT WOS:000245296300021 PM 17990493 ER PT B AU Neveol, A Shooshan, SE Humphrey, SM Rindflesh, TC Aronson, AR AF Neveol, Aurelie Shooshan, Sonya E. Humphrey, Susanne M. Rindflesh, Thomas C. Aronson, Alan R. BE Altman, RB Dunker, AK Hunter, L Murray, T Klein, TE TI Multiple approaches to fine-grained indexing of the biomedical literature SO Pacific Symposium on Biocomputing 2007 LA English DT Proceedings Paper CT 13th Pacific Symposium on Biocomputing (PSB) CY JAN 03-07, 2007 CL Maui, HI ID DOCUMENTS; KNOWLEDGE; TEXT AB The number of articles in the MEDLINE database is expected to increase tremendously in the coming years. To ensure that all these documents are indexed with continuing high quality, it is necessary to develop tools and methods that help the indexers in their daily task. We present three methods addressing a novel aspect of automatic indexing of the biomedical literature, namely producing MeSH main heading/subheading pair recommendations. The methods, (dictionary-based, post-processing rules and Natural Language Processing rules) are described and evaluated on a genetics-related corpus. The best overall performance is obtained for the subheading genetics (70% precision and 17% recall with post-processing rules, 48% precision and 37% recall with the dictionary-based method). Future work will address extending this work to all MeSH subheadings and a more thorough study of method combination. C1 Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Neveol, A (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA. FU Intramural NIH HHS NR 14 TC 9 Z9 9 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-270-417-5 PY 2007 BP 292 EP 303 PG 12 WC Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Biochemistry & Molecular Biology; Computer Science; Engineering GA BFX58 UT WOS:000245296300028 PM 17990500 ER PT S AU Kellman, P AF Kellman, Peter BE Schoenberg, SO Dietrich, O Reiser, MF TI The Development of TSENSE SO PARALLEL IMAGING IN CLINICAL MR APPLICATIONS SE Medical Radiology Diagnostic Imaging LA English DT Article; Book Chapter ID SENSE; MRI; UNFOLD C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, NIH Bldg 10-B1D-416,10 Ctr Dr,Msc-1061, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-540-68879-2 J9 MED RADIOL DIAGN IMA PY 2007 BP 141 EP 152 DI 10.1007/978-3-540-68879-2_12 D2 10.1007/978-3-540-68879-2 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BNP81 UT WOS:000275189700012 ER PT J AU Chlocco, MJ Harvey, BK Wang, Y Hoffer, BJ AF Chlocco, Matthew J. Harvey, Brandon K. Wang, Yun Hoffer, Barry J. TI Neurotrophic factors for the treatment of Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article; Proceedings Paper CT 17th World Congress on Parkinsons Disease and Related Disorders CY DEC 09-13, 2007 CL Amsterdam, NETHERLANDS SP World Federat Neurol DE glial cell line-derived neurotrophic factor; GENF; neurturin; NTN; brain-derived neurotrophic factor; BDNF; bone morphogenetic protein 7; BMP7; Parkinson's disease; neurotrophic factor; neurodegenerative disease ID NIGROSTRIATAL DOPAMINERGIC SYSTEM; BONE MORPHOGENETIC PROTEINS; NEURAL STEM-CELLS; GDNF-PRODUCING CELLS; NEURONS IN-VIVO; RAT MODEL; SUBSTANTIA-NIGRA; GENE-TRANSFER; LESION MODEL; SYMPATHETIC NEURONS AB Parkinson's disease (PD) is a slowly progressive disorder with no known etiology. Pathologically, there is a loss of the dopaminergic neurons in the substantia nigra that project to the striatum. Current available therapies for PD are targeted to the restoration of striatal dopamine. These approaches may alleviate symptoms transiently, but fail to slow the progression of disease. One emergent therapeutic approach is the use of neurotrophic factors to halt or reverse the loss of dopaminergic neurons. There have been intensive research efforts both preclinically and clinically testing the efficacy and safety of neurotrophic factors for the treatment of PD. In this review, we discuss the neuroprotective and neuroregenerative properties of various trophic factors, both old and recent, and then, status as therapeutic molecules for PD. (C) 2007 Elsevier B.V. All rights reserved. C1 [Chlocco, Matthew J.; Harvey, Brandon K.; Wang, Yun; Hoffer, Barry J.] NIDA, IRP, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Hoffer, BJ (reprint author), NIDA, IRP, Natl Inst Hlth, 5500 Nathan Shock Dr,Suite 270, Baltimore, MD 21224 USA. EM bhoffer@intra.nida.nih.gov RI Harvey, Brandon/A-5559-2010 NR 108 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2007 VL 13 SU 3 BP S321 EP S328 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 333ER UT WOS:000258136100024 ER PT J AU Qian, L Gao, X Pei, Z Wu, XF Block, M Wilson, B Hong, JS Flood, PM AF Qian, Li Gao, Xi Pei, Zhong Wu, Xuefei Block, Michelle Wilson, Belinda Hong, Jau-Shyong Flood, Patrick M. TI NADPH oxidase inhibitor DPI is neuroprotective at femtomolar concentrations through inhibition of microglia over-activation SO PARKINSONISM & RELATED DISORDERS LA English DT Article; Proceedings Paper CT 17th World Congress on Parkinsons Disease and Related Disorders CY DEC 09-13, 2007 CL Amsterdam, NETHERLANDS SP World Federat Neurol DE femtomolar DPI; LPS; inflammation; microglia; ROS ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; TETRAZOLIUM SALT; RAT; NEUTROPHILS; EXPRESSION; NEURONS; WST-1; ASSAY AB In this paper we report that diphenyliodonium (DPI), a NADPH oxidase inhibitor, shows potent anti-inflammatory and neuroprotective effects at femtomolar concentrations (10(-13) to 10(-14) M) in primary midbrain cultures. Mechanistic studies revealed that DPI-elicited effects were mediated by the inhibition of LPS-induced microglial ROS production and the subsequent release of pro-inflammatory cytokine TNF alpha, and the production of nitric oxide. Further studies showed that 10(-14) M DPI significantly reduced LPS-induced ERK phosphorylation. Taken together, our results demonstrate that femtomolar concentrations of DPI exert potent anti-inflammatory and neuroprotective effects by inhibiting microglial activation through the inhibition of ERK-regulated PHOX activity. (C) 2007 Elsevier B.V. All rights reserved. C1 [Qian, Li; Flood, Patrick M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. [Qian, Li; Gao, Xi; Wu, Xuefei; Block, Michelle; Wilson, Belinda; Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Flood, PM (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU Intramural NIH HHS; NIDCR NIH HHS [DE-13079] NR 19 TC 30 Z9 31 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2007 VL 13 SU 3 BP S316 EP S320 DI 10.1016/S1353-8020(08)70023-3 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 333ER UT WOS:000258136100023 PM 18267257 ER PT J AU Skinner, CS Kobrin, SC Monahan, PO Daggy, J Menon, U Todora, HS Champion, VL AF Skinner, Celette Sugg Kobrin, Sarah C. Monahan, Patrick O. Daggy, Joanne Menon, Usha Todora, Helen Smith Champion, Victoria L. TI Tailored interventions for screening mammography among a sample of initially non-adherent women: When is a booster dose important? SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE mammography; tailored interventions ID AFRICAN-AMERICAN WOMEN; HEALTH INTERVIEW SURVEY; LOW-INCOME; REPEAT MAMMOGRAPHY; STEPPED-CARE; HMO WOMEN; CANCER; MESSAGES; IMPACT; BREAST AB Objective: To assess added value of a booster dose of a tailored mammography intervention. Methods: Participants, non-adherent at baseline, were randomly assigned to usual care or one of three tailored interventions. Intervention group members (it = 657) were further randomly assigned to receive/not receive a booster intervention dose. Electronic record mammography data were collected following initial intervention and at 6 and 15 months post-booster. Results: Booster had no effect among women not screened after first intervention dose (n = 337). Among women screened after initial dose (n = 320), booster predicted re-screening at 6 but not 15 months. A booster x race interaction showed a booster effect at 6 months for African Americans (OR = 4.66, p = .0005) but not Caucasians (OR = 0.74, p = .44). Conclusions: Findings suggest if a first-dose intervention does not facilitate screening, neither will a booster dose. However, among women for whom a first dose is effective, boosters can facilitate timely repeat adherence, especially among African Americans. At 6 months booster recipients were less likely to be off-schedule but, by 15 months, the groups were similar. Practice implications: Boosters may effect when, but not whether, women continue screening. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27705 USA. Duke Univ, Program Prevent Detect & Control Res, Comprehens Canc, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Univ Illinois, Coll Nursing, Chicago, IL 60680 USA. RP Skinner, CS (reprint author), Duke Univ, Med Ctr, Dept Surg, 2424 Erwin Rd,Ste 602,DUMC 2715, Durham, NC 27705 USA. EM skinn008@mc.duke.edu RI Menon, Usha/G-3531-2012; OI Daggy, Joanne/0000-0003-0815-1746 NR 29 TC 9 Z9 9 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2007 VL 65 IS 1 BP 87 EP 94 DI 10.1016/j.pec.2006.06.013 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 123GU UT WOS:000243285200011 PM 16872787 ER PT J AU Hutson, SP Alter, BP AF Hutson, Sadie P. Alter, Blanche P. TI Experiences of siblings of patients with Fanconi anemia SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cancer; chronic disease; Fanconi anemia; genetics; psychosocial aspects; siblings ID CHILDHOOD-CANCER SURVIVORS; QUALITY-OF-LIFE; PEDIATRIC CANCER; CHILDREN; ADJUSTMENT; ADAPTATION; STRESS; FAMILY; DIAGNOSIS AB Background. Clinical management of families with autosomal recessive genetic disorders focuses almost exclusively on the affected family members. However, clinically unaffected members of such families may also be severely troubled by the serious illness in a family member. The purpose of this study was to explore the experiences of healthy siblings of patients with a chronic genetic disease, Fanconi Anemia (FA). Procedure. We used a qualitative, descriptive design, which consisted of in-depth, semi-structured interviews. A convenience sample of nine silblings of patients with FA was recruited from a National Cancer Institute clinical research protocol, which targets families with inherited bone marrow failure syndromes. NVivo 2.0 software facilitated qualitative content analysis of the data. Results. Siblings' rich descriptions provided novel insights into the intricate hardships of living within a family in which a rare, life-threatening, chronic genetic illness in one member is the focus of daily life. Four major themes of the sibling experience emerged from the interview data: (1) containment, (2) invisibility, (3) worry, and (4) despair. Conclusions. Our data Suggest that unrecognized psychosocial issues exist for the apparently healthy siblings of patients with FA. This study explores the psychosocial consequences of living in a family with FA and one of only a few studies to explore the sibling experience of chronic illness using a contemporaneous approach. These findings support the need for an increased awareness among health care providers; future hypothesis driven investigation, and improved assessment of problems with potential psychological morbidity. C1 E Tennessee State Univ, Coll Nursing, Dept Family Community Nursing, Johnson City, TN 37614 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. RP Hutson, SP (reprint author), E Tennessee State Univ, Coll Nursing, Dept Family Community Nursing, Room 254,POB 70676, Johnson City, TN 37614 USA. EM hutsons@mail.etsu.edu FU PHS HHS [T32] NR 40 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2007 VL 48 IS 1 BP 72 EP 79 DI 10.1002/pbc.20913 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 111BF UT WOS:000242425000014 PM 16779804 ER PT J AU Tamary, H Alter, BP AF Tamary, Hannah Alter, Blanche P. TI Current diagnosis of inherited bone marrow failure syndromes SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE inherited bone marrow failure syndrome; Fanconi anemia; dyskeratosis congenital; Shwachman-Diamond syndrome; Diamond Black fan anemia; severe congenital neutropenia; congenital amegakaryocytic thrombocytopenia ID SHWACHMAN-DIAMOND-SYNDROME; SEVERE CONGENITAL NEUTROPENIA; TELOMERASE REVERSE-TRANSCRIPTASE; DOMINANT DYSKERATOSIS-CONGENITA; FANCONI-ANEMIA; BLACKFAN-ANEMIA; AMEGAKARYOCYTIC THROMBOCYTOPENIA; APLASTIC-ANEMIA; SOMATIC MOSAICISM; GENETIC-BASIS AB Prompt and accurate diagnosis is required for optimal treatment and genetic counseling of patients with inherited bone marrow failure syndromes (IBMFS). However, the diverse clinical picture of these syndromes and their rareness is often associated with diagnostic difficulties. Recently, an improved diagnostic approach is possible by the cloning of many of the causative genes. Fanconi anemia ( FA) patients belong to at least 12 complementation groups, of which 11 genes have been cloned. An approach combining an induced chromosomal breakage test, detection of FANCD2-L by Western blot analysis, complementation group analysis, and detailed mutation analysis enables unraveling the causative mutation in the majority of patients. With the use of such strategies, genotype/phenotype correlations in FA are evolving. In dyskeratosis congenita mutations in DCK1, TERC, and TERT genes have been identified, but mutations have been found in less than half of these patients. In patients with Shwachman-Diamond syndrome, mutations in the SBDS gene were found in approximately 90% of patients. In Diamond-Blackfan anemia the RSP19 gene is mutated in 20-25% of patients. Heterozygote ELA2 mutations are found in 60-80% of severe congenital neutropenia patients. All patients with congenital amegakaryocytic thrombocytopenia have mutations in the thrombopoietin receptor gene c-Mpl. C1 Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA. RP Tamary, H (reprint author), Schneider Childrens Med Ctr, Dept Pediat Hematol Oncol, IL-49202 Petah Tiqwa, Israel. EM htamary@post.tau.ac.il NR 68 TC 19 Z9 19 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PY 2007 VL 24 IS 2 BP 87 EP 99 DI 10.1080/08880010601123240 PG 13 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 187UZ UT WOS:000247875700001 PM 17454774 ER PT J AU Kato, GJ Onyekwere, OC Gladwin, MT AF Kato, Gregory J. Onyekwere, Onyinye C. Gladwin, Mark T. TI Pulmonary hypertension in sickle cell disease: Relevance to children SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Editorial Material DE sickle cell; thalassemia; pulmonary hypertension; nitric oxide; arginase ID BETA-THALASSEMIA MAJOR; NITRIC-OXIDE BIOAVAILABILITY; REGURGITANT JET VELOCITY; PLASMA HEMOGLOBIN; CARDIAC DYSFUNCTION; FENTON REAGENT; COR-PULMONALE; PAIN CRISIS; RISK-FACTOR; HEMOLYSIS AB Pulmonary arterial hypertension (PAH), once considered a rare complication of sickle cell disease (SCD) and thalassemia, appears to be more common in adults with hemoglobinopathy than previously appreciated. On prospective screening of adults with SCD, approximately one-third of adults are found on echocardiography to have a tricuspid regurgitant jet velocity (TRV) of 2.5 m/s or higher, many of whom are asymptomatic. Dyspnea on exertion is the most common presenting symptom. This TRV abnormality is a marker for approximately 40% 3-year mortality in adults, and it is associated with laboratory values suggestive of more severe intravascular hemolysis. Release of hemoglobin and arginase from lysed red cells causes scavenging of nitric oxide (NO) and catabolism of L-arginine, the obligate substrate for NO synthase. The resulting impairment in NO bioavailability is associated with pulmonary vasoconstriction, endothelial dysfunction, thrombosis, and eventual development of plexogenic arterial lesions, the histological hallmark of all forms of PAH. Undoubtedly, additional pathophysiological mechanisms will also play a role in its multifactorial pathogenesis. Early data from children with SCD indicate a similar prevalence of elevated TRV, but the prognostic implications of this remain to be established. Individual patient diagnosis of PAH requires confirmation by right heart catheterization studies and individualized management. Hemolysis-associated PAH with impairments in NO bioavailability is being identified in thalassemia and other hemolytic disorders, and may be a general consequence of long-standing, severe intravascular hemolytic anemia. C1 NIH, NHLBI, Dept Crit Care Med, Vascular Med Branch Clin Ctr, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA. RP Kato, GJ (reprint author), NIH, NHLBI, Dept Crit Care Med, Vascular Med Branch Clin Ctr, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z01 CL008070-04, Z99 HL999999, ZIA HL006014-02] NR 59 TC 56 Z9 58 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PY 2007 VL 24 IS 3 BP 159 EP 170 DI 10.1080/08880010601185892 PG 12 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 187VC UT WOS:000247876000001 PM 17454785 ER PT J AU Chantry, CJ Frederick, MM Meyer, WA Handelsman, E Rich, K Paul, ME Diaz, C Cooper, ER Foca, M Adeniyi-Jones, SK Moye, J AF Chantry, Caroline J. Frederick, Marga'ret M. Meyer, William A., III Handelsman, Edward Rich, Kenneth Paul, Mary E. Diaz, Clemente Cooper, Ellen R. Foca, Marc Adeniyi-Jones, Samuel K. Moye, Jack TI Endocrine abnormalities and impaired growth in human immunodeficiency virus-infected children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE growth; body composition; HIV; children; thyroid; growth hormone; insulin-like growth factor binding protein-3; DHEA; cortisol ID ANTIRETROVIRAL THERAPY; 1-INFECTED CHILDREN; HORMONE-SECRETION; BINDING PROTEIN-3; SOMATIC GROWTH; DYSFUNCTION; DEFICIENCY; WOMEN; BORN; ADOLESCENTS AB Objectives: Identify endocrine differences between human immunodeficiency virus- (HIV) infected versus uninfected children and evaluate associations of growth and body composition with endocrine measures. Study Design: Nested case-control study in 21 HIV-infected and 46 age- and sex-matched uninfected children in the Women and Infant Transmission Study. Plasma specimens from children between 2.5 to 7.0 years of age, taken during 3-4 visits, were tested for insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, dehydroepiandrosterone (DHEA), growth hormone and thyroid studies. Longitudinal mixed and generalized estimating equation models compared group means and examined effects of endocrine measures on growth and body composition, respectively. Results: HlV-infected children had lower IGFBP-3 than uninfected children (1.96 +/- 0.09 mg/L versus 2.34 +/- 0.06 mg/L, P < 0.001). In infected but not in uninfected children, IGFBP-3 values and DHEA:cortisol ratios were associated with weight- and body mass index-for-age z scores ([WAZ] P = 0.019, <.001 respectively, and [BMZ] P = 0.029, 0.038). DHEA concentration was associated with height-for-age z score (P = 0.049). Conclusions: In these HIV-infected children compared with their uninfected counterparts, IGFBP-3 concentration was different between groups. Infected children had multiple endocrine associations with growth and body composition not found in their uninfected peers. We hypothesize that in HIV-infected children, growth hormone resistance and shunting of precursors from adrenal androgen to cortisol production contributes to altered body composition and stunting. C1 Univ Calif Davis, Med Ctr, Dept Pediat, Sacramento, CA 95817 USA. Clin Trials & Survey Corp, Baltimore, MD USA. Quest Incorp, Baltimore, MD USA. SUNY, Brooklyn, NY USA. Univ Illinois, Sch Med, Chicago, IL 60680 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Boston Med Ctr, Boston, MA USA. Columbia Presbyterian Med Ctr, New York, NY USA. NIAID, NIH, DHHS, Bethesda, MD USA. NICHD, NIH, DHHS, Bethesda, MD USA. RP Chantry, CJ (reprint author), Univ Calif Davis, Med Ctr, Dept Pediat, 2516 Stockton Blvd, Sacramento, CA 95817 USA. EM caroline.chantry@ucdme.ucdavis.edu OI moye, john/0000-0001-9976-8586 FU NCRR NIH HHS [RR00645, RR00188]; NIAID NIH HHS [N01-AI-85339, U01-AI-34841, U01-AI-34858, 1-U01-AI-50274-01]; NICHD NIH HHS [U01 HD 36117, U01-HD- 41983]; NIDA NIH HHS [U01-DA-15053, 9U01-DA-15054] NR 34 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2007 VL 26 IS 1 BP 53 EP 60 DI 10.1097/01.inf.0000247131.76584.af PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 122PD UT WOS:000243238000011 PM 17195707 ER PT J AU Martin, S Elliott-DeSorbo, DK Wolters, PL Toledo-Tamula, MA Roby, G Zeichner, S Wood, LV AF Martin, Staci Elliott-DeSorbo, Deborah K. Wolters, Pamela L. Toledo-Tamula, Mary Anne Roby, Gregg Zeichner, Steve Wood, Lauren V. TI Patient, Caregiver and regimen characteristics associated with adherence to highly active antiretroviral therapy among HIV-infected children and adolescents SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pediatric HIV disease; medication adherence; HAART; disease knowledge; regimen complexity; treatment responsibility ID SELF-REPORTED ADHERENCE; MEDICATION ADHERENCE; DRUG-RESISTANCE; DISEASE; PREDICTORS; COMPLEXITY; EFFICACY; COHORT AB Background: This study assesses the relationship between child and caregiver perceptions of medication responsibility, disease knowledge, regimen complexity and adherence to highly active antiretroviral therapy among HIV-positive children. We also examine the association of adherence to child and caregiver demographic characteristics and surrogate markers of HIV disease. Methods: For this 6-month longitudinal study, 24 HIV-positive children (mean age = 14.0 years) being treated with highly active antiretroviral therapy and their caregivers completed measures of medication responsibility and disease knowledge. Medication Event Monitoring System caps calculated adherence across months I through 3 (time 1) and 4 through 6 (time 2). Results: Medication Event Monitoring System data revealed adherence rates of 81% at time 1 and 79% at time 2. Only 8% (n = 2) of child-caregiver pairs reported complete agreement regarding who held responsibility for medication-related tasks. Patients' responsibility for medication was correlated with age based on child (r = .51) and caregiver (r = .57; Ps < 0.05) perceptions, although their regimen knowledge was not. Greater regimen knowledge among caregivers and fewer child-caregiver discrepancies about medication responsibility predicted better adherence (adjusted R-2 = .45). Finally, adherence was correlated with CD4 percentages at time 1 (r = .50) and viral load at time 1 (r = -.56) and time 2 (r = -.68; Ps < 0.05). Conclusions: Medication adherence among HIV-infected children is lower than required for optimal viral suppression. Adherence is related to surrogate markers of HIV disease but not to child or caregiver demographic variables. Responsibilities for medication-related tasks should be clarified among family members, regimen knowledge should be emphasized and caregivers should avoid assigning treatment responsibility to a child prematurely. C1 Natl Canc Inst, Canc Res Ctr, HIV & AIDS Malignancy Branch, Bethesda, MD USA. NIH, Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD USA. Med Illness Counseling Ctr, Chevy Chase, MD USA. RP Martin, S (reprint author), 9030 Old Georgetown, Bethesda, MD 20892 USA. EM martins@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-SC-07006] NR 27 TC 53 Z9 58 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2007 VL 26 IS 1 BP 61 EP 67 DI 10.1097/01.inf.0000250625.80340.48 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 122PD UT WOS:000243238000012 PM 17195708 ER PT J AU Gipson, DS Gibson, K Gipson, PE Watkins, S Moxey-Mims, M AF Gipson, Debbie S. Gibson, Keisha Gipson, Patrick E. Watkins, Sandra Moxey-Mims, Marva TI Therapeutic approach to FSGS in children SO PEDIATRIC NEPHROLOGY LA English DT Article DE ESRD; proteinuria; children; FSGS ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RESISTANT NEPHROTIC SYNDROME; CONVERTING-ENZYME-INHIBITOR; PUROMYCIN AMINONUCLEOSIDE NEPHROSIS; ACTIVATED RECEPTOR-GAMMA; CHRONIC RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; FAMILIAL HYPERCHOLESTEROLEMIA; MYCOPHENOLATE-MOFETIL AB Therapy of primary focal segmental glomerulosclerosis (FSGS) in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function. In long-term cohort studies in adults and children with primary FSGS, renal survival has been directly associated with degree of proteinuria control. This educational article reviews the current therapeutic approach toward children with primary FSGS. C1 Univ N Carolina, Sch Med, Kidney Ctr, Chapel Hill, NC 27599 USA. Childrens Hosp, Seattle, WA USA. Reg Med Ctr, Seattle, WA USA. NIDDK, NIH, Bethesda, MD USA. RP Gipson, DS (reprint author), Univ N Carolina, Sch Med, Kidney Ctr, 7012 Burnett Womack Hall,CB 7155, Chapel Hill, NC 27599 USA. EM Debbie_Gipson@med.unc.edu FU NCRR NIH HHS [M01 RR000046-451353, M01 RR000046] NR 88 TC 12 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JAN PY 2007 VL 22 IS 1 BP 28 EP 36 DI 10.1007/s00467-006-0310-4 PG 9 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 112GG UT WOS:000242513200007 PM 17109140 ER PT J AU Raghuram, V Beck, EJ Zhaou, S Sefton, L Yang, Y AF Raghuram, V. Beck, E. J. Zhaou, S. Sefton, L. Yang, Y. TI Conformational changes in the extracellular loops control CFTR gating SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Raghuram, V.; Beck, E. J.; Zhaou, S.; Sefton, L.; Yang, Y.] NHLBI, NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 13 BP 205 EP 206 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000091 ER PT J AU Raghuram, V Yang, Y Yaemsiri, S AF Raghuram, V. Yang, Y. Yaemsiri, S. TI Physiological role of NHERF1 in the regulation of CFTR SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Raghuram, V.; Yang, Y.; Yaemsiri, S.] NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 MA 14 BP 206 EP 206 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000092 ER PT J AU Birkenkamp, K Holland, SM Knowles, MR Olivier, KN AF Birkenkamp, K. Holland, S. M. Knowles, M. R. Olivier, K. N. TI Airway surface defense abnormalities in the pathogenesis of nontuberculous mycobacterial pulmonary disease SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Birkenkamp, K.; Holland, S. M.; Olivier, K. N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Knowles, M. R.] Univ N Carolina, CF Pulm Res & Treatment Ctr, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2007 SU 30 BP 330 EP 330 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 219SM UT WOS:000250105000441 ER PT J AU Giedd, JN Clasen, LS Wallace, GL Lenroot, RK Lerch, JP Wells, EM Blumenthal, JD Nelson, JE Tossell, JW Stayer, C Evans, AC Samango-Sprouse, CA AF Giedd, Jay N. Clasen, Liv S. Wallace, Gregory L. Lenroot, Rhoshel K. Lerch, Jason P. Molloy Wells, Elizabeth Blumenthal, Jonathan D. Nelson, Jean E. Tossell, Julia W. Stayer, Catherine Evans, Alan C. Samango-Sprouse, Carole A. TI XXY (Klinefelter syndrome): A pediatric quantitative brain magnetic resonance imaging case-control study SO PEDIATRICS LA English DT Article DE sex chromosome aneuploidy; Klinefelter syndrome; magnetic resonance imaging; children; adolescents; brain; XXY ID SEX-CHROMOSOME ABNORMALITIES; EXTRA X-CHROMOSOME; MRI DATA; LANGUAGE; 47,XXY; BOYS; CHILDREN; MALES; ADOLESCENTS; DISORDER AB OBJECTIVE. An extra X chromosome in males (XXY), known as Klinefelter syndrome, is associated with characteristic physical, cognitive, and behavioral features of variable severity. The objective of this study was to examine possible neuroana-tomical substrates of these cognitive and behavioral features during childhood and adolescence. METHODS. MRI brain scans were acquired for 42 XXY and 87 healthy XY age-matched control males. We compared these 2 groups on regional brain volumes and cortical thickness. RESULTS. Total cerebral volume and all lobar volumes except parietal white matter were significantly smaller in the XXY group, whereas lateral-ventricle volume was larger. Consistent with the cognitive profile, the cortex was significantly thinner in the XXY group in left inferior frontal, temporal, and superior motor regions. CONCLUSION. The brain-imaging findings of preferentially affected frontal, temporal, and motor regions and relative sparing of parietal regions are consistent with observed cognitive and behavioral strengths and weaknesses in XXY subjects. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD USA. McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. George Washington Univ, Dept Pediat, Washington, DC USA. Neurodev Diagnost Ctr Young Children, Davidson, MD USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Wallace, Gregory/A-4789-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054 FU Intramural NIH HHS NR 48 TC 71 Z9 72 U1 0 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2007 VL 119 IS 1 BP E232 EP E240 DI 10.1542/peds.2005-2969 PG 9 WC Pediatrics SC Pediatrics GA 121YB UT WOS:000243191800033 PM 17200249 ER PT J AU Dilks, DD Baker, C Liu, Y Kanwisher, N AF Dilks, D. D. Baker, C. Liu, Y. Kanwisher, N. TI Rapid reorganization in the adult human visual system SO PERCEPTION LA English DT Meeting Abstract C1 [Dilks, D. D.; Liu, Y.; Kanwisher, N.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Baker, C.] NIH, Bethesda, MD 20892 USA. EM dilks@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2007 VL 36 SU S BP 10 EP 10 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 226NA UT WOS:000250594600033 ER PT J AU Martin, A AF Martin, A. TI How is ventral temporal cortex organized? Clues from the study of 'tools' SO PERCEPTION LA English DT Meeting Abstract C1 [Martin, A.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM alexmartin@mail.nih.gov RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2007 VL 36 SU S BP 12 EP 13 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 226NA UT WOS:000250594600043 ER PT J AU Haushofer, J Baker, CI Kanwisher, N AF Haushofer, J. Baker, C. I. Kanwisher, N. TI Frequency-based categorization of complex visual objects SO PERCEPTION LA English DT Meeting Abstract C1 [Haushofer, J.] Harvard Univ, Dept Neurobiol, Cambridge, MA 02138 USA. [Baker, C. I.] NIH, NIMH, Bethesda, MD 20892 USA. [Kanwisher, N.] MIT, McGroven Inst Brain Res, Cambridge, MA 02139 USA. EM haushof@fas.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2007 VL 36 SU S BP 100 EP 100 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 226NA UT WOS:000250594600359 ER PT J AU Williams, MA Baker, CI Op de Beeck, HP Dang, S Triantafyllou, C Kanwisher, NG AF Williams, M. A. Baker, C. I. Op de Beeck, H. P. Dang, S. Triantafyllou, C. Kanwisher, N. G. TI Are spatial patterns in the lateral occipital complex position-invariant? SO PERCEPTION LA English DT Meeting Abstract C1 [Williams, M. A.] Macquarie Univ, MIT, Macquarie Ctr Cognit Sci, Somerville, NJ USA. [Baker, C. I.] NIMH, Bethesda, MD 20892 USA. [Op de Beeck, H. P.] Univ Leuven, Louvain, Belgium. [Dang, S.; Triantafyllou, C.; Kanwisher, N. G.] MIT, McGrovern Inst Mental Hlth, Cambridge, MA 02139 USA. EM mwilliam@maccs.mq.edu.au RI Triantafyllou, Christina/E-7724-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2007 VL 36 SU S BP 111 EP 111 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 226NA UT WOS:000250594600397 ER PT J AU Berman, RA Wurtz, R AF Berman, R. A. Wurtz, R. TI Pulvinar pathway for modulation of cortical visual processing SO PERCEPTION LA English DT Meeting Abstract C1 [Berman, R. A.; Wurtz, R.] NIH, NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. EM bermanr@nei.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2007 VL 36 SU S BP 117 EP 118 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 226NA UT WOS:000250594600419 ER PT J AU Moore, DF Ries, M Forget, EL Schiffmann, R AF Moore, David F. Ries, Markus Forget, Evelyn L. Schiffmann, Raphael TI Enzyme replacement therapy in orphan and ultra-orphan diseases - The limitations of standard economic metrics as exemplified by Fabry-Anderson disease SO PHARMACOECONOMICS LA English DT Article ID EFFECTIVENESS ACCEPTABILITY CURVES; COST-EFFECTIVENESS; AGALSIDASE-ALPHA; HEALTH-CARE; TRIAL; VALUATIONS; DISORDERS; SAFETY; DRUGS; LIFE AB Background: Fabry-Anderson disease is an x-linked deficiency of lysosomal (alpha-galactosidase A (GALA), resulting in chronic renal failure, cardiac arrhythmia, hypertrophy, valvular disease, pain (acro-paraesthesiae) and stroke, together with premature mortality. The disease has a significant impact on quality of life (QOL), as illustrated by studies using the EQ-5D. A specific treatment is available for Fabry-Anderson disease consisting of intravenous enzyme replacement therapy (ERT) of the deficient enzyme. The variable clinical efficacy and cost of ERT has resulted in reluctance by some health providers to approve it. Methods: We use the limited QOL data available in the Fabry-Anderson disease literature on ERT to derive standard economic metrics. These were derived by bootstrap estimates of the incremental net benefit (INB) statistics together with a cost-effectiveness acceptability curve relating the willingness to pay to the probability that the INB was >0. The estimates were further developed by adoption of a supplementary Bayesian approach utilising a sceptical and enthusiastic prior of the INB of ERT in Fabry-Anderson disease. Results: ERT for Fabry-Anderson disease is not economically viable by standard health programme evaluation metrics. Based on current ERT costs (year 2005 values), derivation of the INB distribution, and a Bayesian analysis using an enthusiastic and sceptical prior of the INB, an upper ($US350 000 over 1 year) and lower ($US 175 000 over 1 year) economic cost, respectively, of ERT was derived. Conclusion: The cost of ERT will always result in a net deficit to society under current costing and ERT efficacy as determined by the QALY metric. The rules of fair cooperation should govern decision making both for ERT in Fabry-Anderson disease and for funding therapeutic advances in other rare diseases belonging to the orphan and ultra-orphan categories. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Neurol Sect, Winnipeg, MB, Canada. Univ Manitoba, Sect Prote & Syst Biol, Winnipeg, MB, Canada. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Room 3D03,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM rs4e@nih.gov NR 30 TC 10 Z9 10 U1 1 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2007 VL 25 IS 3 BP 201 EP 208 DI 10.2165/00019053-200725030-00003 PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 153PP UT WOS:000245447700003 PM 17335306 ER PT J AU Kimchi-Sarfaty, C Marple, AH Shinar, S Kimchi, AM Scavol, D Roma, MI Kim, IW Jones, A Arora, M Gribar, J Gurwitz, D Gottesman, MM AF Kimchi-Sarfaty, Chava Marple, Andrew H. Shinar, Shiri Kimchi, Avraham M. Scavol, David Roma, M. Isabella Kim, In-Wha Jones, Adam Arora, Mili Gribar, John Gurwitz, David Gottesman, Michael M. TI Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene SO PHARMACOGENOMICS LA English DT Article DE ABCB1; ethnicity; haplotypes; P-glycoprotein; SNPs ID ASHKENAZI-JEWISH POPULATION; MDR1 MULTIDRUG TRANSPORTER; P-GLYCOPROTEIN EXPRESSION; C3435T POLYMORPHISM; DRUG-TRANSPORTER; PARKINSONS-DISEASE; CYSTIC-FIBROSIS; CROHN-DISEASE; RESISTANCE; CANCER AB Introduction: The human multidrug resistance gene ATP-binding cassette B1 (ABCB1) codes for P-glycoprotein (P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have an effect on P-gp expression levels and function. Haplotype as well as genotype analysis of SNPs is becoming increasingly important in identifying genetic variants underlying susceptibility to human disease. Three SNPs, 1236C -> T, 2677G -> T and 3435C -> T, have been repeatedly shown to predict changes in the function of P-gp. The frequencies with which these polymorphisms exist in a population have also been shown to be ethnically related. Methods: In this study, 95 individuals representative of the entire ethnic make-up of the USA were compared with 101 individuals from an Ashkenazi-Jewish population. These individuals were analyzed by genomic sequencing and polymerase chain reaction, using restriction fragment length polymorphisms, to calculate their genotype frequencies. Results: A total of 25 SNPs were located in the exons of the ABCB1 gene. All of the polymorphisms identified were in parts of the ABCB1 gene product predicted to be intracellular, and 16 appear to be novel as compared with those listed by the National Center for Biotechnological Information. Frequencies of the 1236C -> T and 2677G -> T/A/C SNPs were similar for the US and Ashkenazi populations (64.2 and 60.4%, respectively for 1236C -> T [chi(2): 0.30; p <= 1]; 55.8 and 64.4%, respectively for 2677G -> T/A/C [chi(2): 1.49; p <= 1]), but were different for 3435C -> T (24.2% for the US population and 69.3% for the Ashkenazi population [chi 2: 39.927; p <= 0.001]). The 1236T/ 2677T/3435T haplotype occurred in 23.6% (standard error: 0.013) of the Ashkenazi population. Conclusion: The SNP at location 3435C -> T plays a significant role in the ABCB1 gene. The haplotype and genotype analysis from these data may be used as a basis for studies on the relationship between ABCB1 genotypes and drug efficacy, drug toxicity, disease susceptibility or other phenotypes. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NIH, Natl Ctr Bioinformat, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, Natl Lab Genet Israeli Populat, IL-69978 Tel Aviv, Israel. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Gurwitz, David/E-7642-2013 OI Gurwitz, David/0000-0002-9363-1869 FU Intramural NIH HHS [Z01 BC005598-16] NR 56 TC 55 Z9 58 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2007 VL 8 IS 1 BP 29 EP 39 DI 10.2217/14622416.8.1.29 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129YJ UT WOS:000243765700011 PM 17187507 ER PT J AU Goldsmith, P Golder, Z Hunt, J Berghmans, S Jones, D Stables, JP Murphree, L Howden, D Newton, PE Richards, FM AF Goldsmith, Paul Golder, Zoe Hunt, Julia Berghmans, Stephane Jones, Derek Stables, James P. Murphree, Lauren Howden, Diane Newton, Paul E. Richards, Frances M. TI GBR12909 possesses anticonvulsant activity in zebrafish and rodent models of generalized epilepsy but cardiac ion channel effects limit its clinical utility SO PHARMACOLOGY LA English DT Article DE anticonvulsant; arrhythmia; dopamine reuptake inhibitor; GBR12909; therapeutic window; zebrafish ID DOPAMINE UPTAKE; GBR-12909; SEIZURES; MECHANISM; DRUGS; MICE AB Background/Aims: GBR12909 has been reported to possess anticonvulsant activity with focal brain perfusion to the hippocampus of pilocarpine, although an earlier publication suggested any anticonvulsant effects were only mild. Here we further explored the anticonvulsant potential of GBR12909 with a suite of anticonvulsant assays in both zebrafish and mammals and then explored whether it possessed any QT effects which might limit clinical utility. Methods: We assessed the anticonvulsant effects of GBR12909 in zebrafish pentylenetetrazole ( PTZ), mammalian maximal electroshock and PTZ models of generalized epilepsy and a rodent hippocampal kindling model. Cardiac effects were assessed in zebrafish and man. Results: GBR12909 possesses anticonvulsant activity in zebrafish and rodent models of generalized epilepsy. However, phase 1 human data indicated potential QT effects. Subsequent testing in a zebrafish QT assay confirmed marked arrhythmogenic potential. Conclusion: Further clinical development of GBR12909 in epilepsy was considered inappropriate because of insufficient window between the therapeutic effects and the cardiac arrhythmia problems identified in zebrafish assays. Any further development based on this mechanism of action should avoid the GBR12909 chemical scaffold, or involve structure-activity dissociation of its neurological and cardiac effects. Copyright (c) 2007 S. Karger AG, Basel. C1 DanioLabs Ltd, Cambridge CB5 9TN, England. Addenbrookes Hosp, Dept Neurol, Cambridge CB2 2QB, England. Natl Inst Neurol Disorders & Stroke, NIH, Rockville, MD USA. SRA Int, Fairfax, VA USA. MPI Res Inc, Mattawan, MI USA. RP Goldsmith, P (reprint author), DanioLabs Ltd, 7330 Cambridge Res Pk, Cambridge CB5 9TN, England. EM paul.goldsmith@daniolabs.com OI Berghmans, Stephane/0000-0001-5414-8674 NR 23 TC 7 Z9 8 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PY 2007 VL 79 IS 4 BP 250 EP 258 DI 10.1159/000102061 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 175QR UT WOS:000247028600008 PM 17476122 ER PT J AU Schloesser, RJ Chen, G Manji, HK AF Schloesser, Robert J. Chen, Guang Manji, Husseini K. TI Neurogenesis and neuroenhancement in the pathophysiology and treatment of bipolar disorder SO PHARMACOLOGY OF NEUROGENESIS AND NEUROENHANCEMENT SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID RAT DENTATE GYRUS; MAGNETIC-RESONANCE SPECTROSCOPY; INCREASES CELL-PROLIFERATION; SUBGENUAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; NEURAL PROGENITOR CELLS; LONG-TERM POTENTIATION; STRESSFUL LIFE EVENTS; CORTICOTROPIN-RELEASING HORMONE; ADULT HIPPOCAMPAL NEUROGENESIS C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP Schloesser, RJ (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 248 TC 10 Z9 11 U1 4 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2007 VL 77 BP 143 EP 178 DI 10.1016/S0074-7742(06)77005-2 PG 36 WC Neurosciences SC Neurosciences & Neurology GA BFP47 UT WOS:000243623500005 PM 17178474 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Pheochromocytoma Diagnosis, Localization, and Treatment Introduction SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Editorial Material; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 1 EP + D2 10.1002/9780470692196 PG 48 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200001 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Historical comments SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Editorial Material; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 3 EP 3 D2 10.1002/9780470692196 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200002 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Pathology SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 4 EP 7 D2 10.1002/9780470692196 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200003 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Clinical presentation of pheochromocytoma SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 8 EP 29 D2 10.1002/9780470692196 PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200004 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Current trends in genetics of pheochromocytoma SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 30 EP 40 D2 10.1002/9780470692196 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200005 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Catecholamines and adrenergic receptors SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 41 EP 71 D2 10.1002/9780470692196 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200006 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Current trends in biochemical diagnosis of pheochromocytoma SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 72 EP 92 D2 10.1002/9780470692196 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200007 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Current trends in localization of pheochromocytoma SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 93 EP 108 D2 10.1002/9780470692196 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200008 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Treatment of pheochromocytoma SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 109 EP 113 D2 10.1002/9780470692196 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200009 ER PT B AU Pacak, K Lenders, JWM Eisenhofer, G AF Pacak, Karel Lenders, Jacques W. M. Eisenhofer, Graeme BA Pacak, K Lenders, JWM Eisenhofer, G BF Pacak, K Lenders, JWM Eisenhofer, G TI Future trends and perspectives SO PHEOCHROMOCYTOMA: DIAGNOSIS, LOCALIZATION, AND TREATMENT LA English DT Article; Book Chapter C1 [Pacak, Karel] NICHHD, NIH, Bethesda, MD 20892 USA. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69219-6; 978-1-4051-4950-1 PY 2007 BP 114 EP 119 D2 10.1002/9780470692196 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA BCJ36 UT WOS:000310281200010 ER PT J AU Tannenbaum, J AF Tannenbaum, Julie TI Emotional expressions of moral value SO PHILOSOPHICAL STUDIES LA English DT Article DE agent-regret; guilt; moral value; moral obligation; moral luck; Kant; Aristotle; Bernard Williams AB In "Moral Luck" Bernard Williams describes a lorry driver who, through no fault of his own, runs over a child, and feels "agent-regret." I believe that the driver's feeling is moral since the thought associated with this feeling is a negative moral evaluation of his action. I demonstrate that his action is not morally inadequate with respect his moral obligations. However, I show that his negative evaluation is nevertheless justified since he acted in way that does not live up to his moral values. I then use this distinctive negative moral evaluation to distinguish agent-regret from guilt and mere regret. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Tannenbaum, J (reprint author), NIH, Dept Clin Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM tannenbaumj@cc.nih.gov NR 17 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0031-8116 J9 PHILOS STUD JI Philos. Stud. PD JAN PY 2007 VL 132 IS 1 BP 43 EP 57 DI 10.1007/s11098-006-9056-x PG 15 WC Philosophy SC Philosophy GA 139WN UT WOS:000244463400004 ER PT J AU Bourgeois, D Schotte, F Brunori, M Vallone, B AF Bourgeois, Dominique Schotte, Friedrich Brunori, Maurizio Vallone, Beatrice TI Time-resolved methods in biophysics. 6. Time-resolved Laue crystallography as a tool to investigate photo-activated protein dynamics SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID X-RAY CRYSTALLOGRAPHY; SINGULAR-VALUE DECOMPOSITION; PHOTOACTIVE YELLOW PROTEIN; STRUCTURAL DYNAMICS; DIFFRACTION PATTERNS; LIGAND MIGRATION; REAL-TIME; MYOGLOBIN; NANOSECOND; CRYSTALS AB When polychromatic X-rays are shined onto crystalline material, they generate a Laue diffraction pattern. At third generation synchrotron radiation sources, a single X-ray pulse of similar to 100 ps duration is enough to produce interpretable Laue data from biomolecular crystals. Thus, by initiating biological turnover in a crystalline protein, structural changes along the reaction pathway may be filmed by ultra-fast Laue diffraction. Using laser-light as a trigger, transient species in photosensitive macromolecules can be captured at near atomic resolution with sub-nanosecond time-resolution. Such pump-probe Laue experiments have now reached an outstanding level of sophistication and have found a domain of excellence in the investigation of light-sensitive proteins undergoing cyclic photo-reactions and producing stiff crystals. The main theoretical concepts of Laue diffraction and the challenges associated with time-resolved experiments on biological crystals are recalled. The recent advances in the design of experiments are presented in terms of instrumental choices, data collection strategy and data processing, and some of the inherent difficulties of the method are highlighted. The discussion is based on the example of myoglobin, a protein that has traversed the whole history of pump-probe Laue diffraction, and for which a massive amount of data have provided considerable insight into the understanding of protein dynamics. C1 Univ Grenoble 1, IBS, CEA, F-38027 Grenoble, France. European Synchrotron Radiat Facil, F-38043 Grenoble, France. NIDDK, NIH, Phys Chem Lab, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dipartimento Sci Biochim, I-00185 Rome, Italy. Univ Roma La Sapienza, Inst Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy. RP Bourgeois, D (reprint author), Univ Grenoble 1, IBS, CEA, 41 Rue Jules Horowitz, F-38027 Grenoble, France. EM dominique.bourgeois@ibs.fr RI Vallone, Beatrice/F-4174-2012; OI Brunori, Maurizio/0000-0002-7795-1635 NR 43 TC 17 Z9 17 U1 3 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2007 VL 6 IS 10 BP 1047 EP 1056 DI 10.1039/b704249c PG 10 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 217CJ UT WOS:000249925700009 PM 17914477 ER PT J AU Akimov, SA Kuzmin, PI Zimmerberg, J Cohen, FS AF Akimov, Sergey A. Kuzmin, Peter I. Zimmerberg, Joshua Cohen, Fredric S. TI Lateral tension increases the line tension between two domains in a lipid bilayer membrane SO PHYSICAL REVIEW E LA English DT Article ID T-CELL-RECEPTOR; TYROSINE PHOSPHORYLATION; BENDING ELASTICITY; FLUID MEMBRANES; PLASMA-MEMBRANE; RAFTS; CHOLESTEROL; ACTIVATION; ENERGY; MODEL AB The effect of an external applied lateral tension on the line tension between two domains of different thickness in a lipid bilayer membrane is calculated. The thick domain is treated as a liquid-ordered phase in order to model a raft in a biological membrane; the thin domain is considered a liquid-disordered phase to model the surrounding region. In our model, the monolayers elastically distort at the boundary to create a smooth rather than steplike boundary to avoid exposure of the hydrophobic interior of the thick raft to water. The energy of this distortion is described by the fundamental deformations of splay and tilt. This energy per unit length of boundary yields the line tension of the raft. Applying lateral tension alters the fundamental deformations such that line tension increases. This increase in line tension is larger when the spontaneous curvature of a raft is greater than that of the surround; if the spontaneous curvature of the raft is less than that of the surround, the increase of the line tension due to application of the lateral tension is more modest. C1 Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Lab Bioelectrochem, Moscow 119991, Russia. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RP Akimov, SA (reprint author), Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Lab Bioelectrochem, Moscow 119991, Russia. RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 40 TC 39 Z9 39 U1 2 U2 18 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD JAN PY 2007 VL 75 IS 1 AR 011919 DI 10.1103/PhysRevE.75.011919 PN 1 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 131TR UT WOS:000243893400095 PM 17358196 ER PT J AU Small, A Pine, D AF Small, Alex Pine, David TI Delocalization of classical waves in highly anisotropic random media SO PHYSICAL REVIEW E LA English DT Article ID RESONANT TRANSMISSION; LOCALIZATION; LIGHT AB We discuss localization phenomena in multilayer films doped with scattering particles. If the films exhibit a particular type of transmission resonance then above a critical frequency waves in the sample can decay as a power law rather than exponentially. This phenomenon is independent of the scattering strength of the particles, in stark contrast to previous work. We find that this phenomenon has many similarities to a second order phase transition. This work points to interesting avenues in the study of waves in anisotropic disordered media. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NYU, Dept Phys, New York, NY 10003 USA. RP Small, A (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM smallalex@mail.nih.gov NR 19 TC 1 Z9 1 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD JAN PY 2007 VL 75 IS 1 AR 016617 DI 10.1103/PhysRevE.75.016617 PN 2 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 131TU UT WOS:000243893700075 PM 17358285 ER PT J AU Pacher, P Beckman, JS Liaudet, L AF Pacher, Pal Beckman, Joseph S. Liaudet, Lucas TI Nitric oxide and peroxynitrite in health and disease SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ISCHEMIA-REPERFUSION INJURY; AMYOTROPHIC-LATERAL-SCLEROSIS; FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; PROTEIN-KINASE-C; POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; LOW-DENSITY-LIPOPROTEIN; TRAUMATIC BRAIN-INJURY; MANGANESE-SUPEROXIDE-DISMUTASE; SOLUBLE GUANYLATE-CYCLASE AB The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review. C1 NIAAA, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, NIH, Lab Physiol Studies, 5625 Fishers Lane MSC 9413,Room 2N-17, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02]; NCCIH NIH HHS [AT-02034, P01 AT002034]; NIEHS NIH HHS [ES-00040, ES-00240, P01 ES000040, P01 ES000040-390003, P01 ES000040-436360] NR 1476 TC 2264 Z9 2376 U1 32 U2 331 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JAN PY 2007 VL 87 IS 1 BP 315 EP 424 DI 10.1152/physrev.00029.2006 PG 110 WC Physiology SC Physiology GA 127NX UT WOS:000243594500008 PM 17237348 ER PT J AU Kumar, S Arya, S Nussinov, R AF Kumar, Sandeep Arya, Sunil Nussinov, Ruth BE Gerday, C Glansdorff, N TI Temperature-Dependent Molecular Adaptation Features in Proteins SO PHYSIOLOGY AND BIOCHEMISTRY OF EXTREMOPHILES LA English DT Article; Book Chapter ID COLD SHOCK PROTEIN; INTRINSICALLY UNSTRUCTURED PROTEINS; OPTIMIZED ELECTROSTATIC SURFACES; REVERSIBLE 2-STATE PROTEINS; ADAPTED ALPHA-AMYLASE; REDUCED HEAT-CAPACITY; SALT BRIDGES; THERMOPHILIC PROTEINS; THERMAL-STABILITY; THERMOTOGA-MARITIMA C1 [Kumar, Sandeep] Johns Hopkins Univ, Zanvyl Krieger Sch Arts & Sci, Dept Biol, Baltimore, MD 21218 USA. [Arya, Sunil] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India. [Nussinov, Ruth] NCI, SAIC Intramural Res Program, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. RP Kumar, S (reprint author), Johns Hopkins Univ, Zanvyl Krieger Sch Arts & Sci, Dept Biol, Baltimore, MD 21218 USA. OI Kumar, Sandeep/0000-0003-2840-6398 NR 99 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-581-3 PY 2007 BP 75 EP 85 PG 11 WC Microbiology SC Microbiology GA BPD98 UT WOS:000278640400008 ER PT J AU Klausmeyer, P McCloud, TG Melillo, G Scudiero, DA Cardellina, JH Shoemaker, RH AF Klausmeyer, Paul McCloud, Thomas G. Melillo, Giovanni Scudiero, Dominic A. Cardellina, John H., II Shoemaker, Robert H. TI Identification of a new natural camptothecin analogue in targeted screening for HIF-1 alpha inhibitors SO PLANTA MEDICA LA English DT Article DE HIF-1 alpha; camptothecin; Ophiorrhiza trichocarpon; Rubiaceae; dereplication ID HYPOXIA-INDUCIBLE FACTOR-1; SMALL-MOLECULE INHIBITOR; NOTHAPODYTES-FOETIDA; ANTITUMOR AGENTS; CANCER-THERAPY; FACTOR-I; HIF-1; 9-METHOXYCAMPTOTHECIN; ALKALOIDS; PATHWAY AB Screening to detect compounds that inhibit the HIF-1 a transcriptional activation pathway identified an extract of Ophiorrhiza trichocarpon for investigation. A high throughput dereplication strategy was employed, involving chromatography with spectral data acquisition supported by bioactivity testing and literature referencing, which led to rapid identification of camptothecin (1) and three analogues (2-4) as the active compounds. 9,10-Methylenedioxy-(20S)-camptothecin (4) was found for the first time from a plant. C1 NCI, SAIC Frederick, Nat Prod Support Grp, Frederick, MD 21702 USA. NCI, SAIC Frederick, DTP Tumor Hypoxia Lab, Frederick, MD 21702 USA. NCI, SAIC Frederick, In Vitro Cell Line Screening Program, Frederick, MD 21702 USA. NCI, Screnning Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,FCRDC, Frederick, MD 21701 USA. RP McCloud, TG (reprint author), NCI, SAIC Frederick, Nat Prod Support Grp, Frederick, MD 21702 USA. EM mccloud@dtpax2.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 29 TC 19 Z9 19 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JAN PY 2007 VL 73 IS 1 BP 49 EP 52 DI 10.1055/s-2006-951767 PG 4 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 134MD UT WOS:000244086400008 PM 17315309 ER PT J AU Akel, S Bertolette, D Petrow-Sadowski, C Ruscetti, FW AF Akel, Salem Bertolette, Daniel Petrow-Sadowski, Cari Ruscetti, Francis W. TI Levels of Smad7 regulate Smad and mitogen activated kinases (MAPKs) signaling and controls erythroid and megakaryocytic differentiation of erythroleukemia cells SO PLATELETS LA English DT Article DE Smad7; TGF-alpha; activin; erythropoiesis; megakaryopoiesis; K562 ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; CANCER CELLS; K562 CELLS; ACTIVIN-A; PATHWAY; P38; INHIBITION; HEMATOPOIESIS; LEUKEMIA AB Smad and MAPK signaling cascades are involved in erythroid and megakaryocytic differentiation. The inhibitory Smad for TGF-beta/activin signaling, Smad7, may directly or indirectly affect these signaling pathways. By modulating Smad7 expression, we attempted to delineate the relevance of Smad7 during erythro-megakaryocytic (E/M) differentiation of human erythroleukemia cells. Smad7 transcripts were detected at low levels in different erythroleukemia cell lines (TF-1, HEL and K562). Reduction of expression of endogenous Smad7 by RNA interference enhanced erythroid differentiation of K562 cells in response to physiological doses of activin-A/TGF-beta 1. Stable over-expression of Smad7 in K562 cells (K562/7) prevented activation of Smad2/3 and MAPK (ERK1/2, p38 and JNK1/2) proteins by activin-A/TGF-beta 1 and subsequent induction of erythroid differentiation. High levels of Smad7 also interfered with hydroxyurea-and butyrate-, but not hemin-induced erythroid differentiation. Interestingly, K562/7 cells were found to harbor a significant proportion (about 35%) of large ploy nucleated cells compared to fewer than 12% in control cells. K562/7 cells treated with phorbol 12-myristate 13-acetate (PMA), showed a great shift in ploidy towards high ploidy classes (>= 8N) accompanied with an increase in the expression of the maturation marker CD42b. We showed here that: (a) low levels of endogenous Smad7 in erythroleukemia cells are physiologically relevant, and (b) high levels of Smad7 interferes with TGF-beta/activin-induced Smad/MAPK signaling and erythro-differentiation and promotes megakaryocytic differentiation, possibly by blocking autocrine TGF-beta. C1 Hashemite Univ, Dept Med Lab Sci, Zarka, Jordan. NCI, Ctr Canc Res, Expt Immunol Lab, Leukocyte Biol Sect, Frederick, MD USA. Sci Applicat Int Corp, Frederick Inc, Basic Res Program, Frederick, MD USA. RP Akel, S (reprint author), Hashemite Univ, Fac Allied Hlth Sci, Dept Med Lab Sci, Zarqa 13115, Jordan. EM sakel@hu.edu.jo FU NCI NIH HHS [N01-CO-56000] NR 39 TC 7 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2007 VL 18 IS 8 BP 566 EP 578 DI 10.1080/09537100701549546 PG 13 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 235NA UT WOS:000251239800002 PM 18041647 ER PT J AU Xu, XM Carlson, BA Mix, H Zhang, Y Saira, K Glass, RS Berry, MJ Gladyshev, VN Hatfield, DL AF Xu, Xue-Ming Carlson, Bradley A. Mix, Heiko Zhang, Yan Saira, Kazima Glass, Richard S. Berry, Marla J. Gladyshev, Vadim N. Hatfield, Dolph L. TI Biosynthesis of selenocysteine on its tRNA in eukaryotes SO PLOS BIOLOGY LA English DT Article ID SYNTHETASE 2 SPS2; SELENOPHOSPHATE SYNTHETASE; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; SELENIUM DONOR; SYNTHASE; IDENTIFICATION; PURIFICATION; PROTEIN; MACHINERY AB Selenocysteine (Sec) is cotranslationally inserted into protein in response to UGA codons and is the 21st amino acid in the genetic code. However, the means by which Sec is synthesized in eukaryotes is not known. Herein, comparative genomics and experimental analyses revealed that the mammalian Sec synthase (SecS) is the previously identified pyridoxal phosphate-containing protein known as the soluble liver antigen. SecS required selenophosphate and O-phosphoseryl-tRNA([Ser]Sec) as substrates to generate selenocysteyl-tRNA([Ser]Sec). Moreover, it was found that Sec was synthesized on the tRNA scaffold from selenide, ATP, and serine using tRNA([Ser]Sec), seryl-tRNA synthetase, O-phosphoseryl-tRNA([Ser]Sec) kinase, selenophosphate synthetase, and SecS. By identifying the pathway of Sec biosynthesis in mammals, this study not only functionally characterized SecS but also assigned the function of the O-phosphoseryl-tRNA([Ser]Sec) kinase. In addition, we found that selenophosphate synthetase 2 could synthesize monoselenophosphate in vitro but selenophosphate synthetase 1 could not. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that synthesize selenoproteins. C1 NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Univ Hawaii Manoa, Dept Cell & Mol Biol, Honolulu, HI 96822 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA-41108, CA080946, P01 CA041108, R01 CA080946]; NIDDK NIH HHS [R01 DK047320, DK47320, DK52963, R01 DK052963, R56 DK047320]; NIGMS NIH HHS [GM061603, GM065204, R01 GM061603, R01 GM065204, R37 GM065204] NR 31 TC 138 Z9 140 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2007 VL 5 IS 1 BP 96 EP 105 AR e4 DI 10.1371/journal.pbio.005004 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 150TS UT WOS:000245243100010 PM 17194211 ER PT J AU Efroni, S Harel, D Cohen, IR AF Efroni, Sol Harel, David Cohen, Irun R. TI Emergent dynamics of thymocyte development and lineage determination SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID T-CELL DEVELOPMENT; REACTIVE ANIMATION; IMMUNE-SYSTEM; ANTIGEN; THYMUS; GLUCOCORTICOIDS; COMPLEXITY; MIGRATION; SELECTION; CCR9 AB Experiments have generated a plethora of data about the genes, molecules, and cells involved in thymocyte development. Here, we use a computer-driven simulation that uses data about thymocyte development to generate an integrated dynamic representation-a novel technology we have termed reactive animation ( RA). RA reveals emergent properties in complex dynamic biological systems. We apply RA to thymocyte development by reproducing and extending the effects of known gene knockouts: CXCR4 and CCR9. RA simulation revealed a previously unidentified role of thymocyte competition for major histocompatability complex presentation. We now report that such competition is required for normal anatomical compartmentalization, can influence the rate of thymocyte velocities within chemokine gradients, and can account for the disproportion between single-positive CD4 and CD8 lineages developing from double-positive precursors. C1 NCI, Ctr Bioinformat, NIH, Rockville, MD USA. Weizmann Inst Sci, Dept Comp Sci, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Efroni, S (reprint author), NCI, Ctr Bioinformat, NIH, Rockville, MD USA. EM sefroni@mail.nih.gov RI Cohen, Irun/B-3542-2009; Efroni, Sol/I-6752-2012 OI Efroni, Sol/0000-0001-7927-6349 NR 31 TC 47 Z9 48 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2007 VL 3 IS 1 BP 127 EP 136 AR e13 DI 10.1371/journal.pcbi.0030013 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 130ZY UT WOS:000243838700013 PM 17257050 ER PT J AU An, P Duggal, P Wang, LH O'Brien, SJ Donfield, S Goedert, JJ Phair, J Buchbinder, S Kirk, GD Winkler, CA AF An, Ping Duggal, Priya Wang, Li Hua O'Brien, Stephen J. Donfield, Sharyne Goedert, James J. Phair, John Buchbinder, Susan Kirk, Gregory D. Winkler, Cheryl A. TI Polymorphisms of CUL5 are associated with CD4(+) T cell loss in HIV-1 infected individuals SO PLOS GENETICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; E3 UBIQUITIN LIGASE; HIV-1 INFECTION; VIF PROTEIN; ANTIVIRAL ACTIVITY; ENZYME APOBEC3G; AIDS; PROGRESSION; DEGRADATION; GENE AB Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms ( SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters of evolutionarily related haplotypes. Cox survival analysis and mixed effects models were used to assess time to AIDS outcomes and CD4(+)T cell trajectories, respectively. Relative to cluster I haplotypes, the collective cluster II haplotypes were associated with more rapid CD4(+)T cell loss ( relative hazards [ RH] 1.47 and p = 0.009), in a dose-dependent fashion. This effect was mainly attributable to a single cluster II haplotype (Hap10) (RH = 2.49 and p = 0.00001), possibly due to differential nuclear protein-binding efficiencies of a Hap10-specifying SNP as indicated by a gel shift assay. Consistent effects were observed for CD4(+)T cell counts and HIV-1 viral load trajectories over time. The findings of both functional and genetic epidemiologic consequences of CUL5 polymorphism on CD4(+)T cell and HIV-1 levels point to a role for Cullin 5 in HIV-1 pathogenesis and suggest interference with the Vif-Cullin 5 pathway as a possible anti-HIV-1 therapeutic strategy. C1 SAIC Frederick Inc, Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. SAIC Frederick, Basic Res Program, Natl Canc Inst, Frederick, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Rho Inc, Chapel Hill, NC USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Winkler, CA (reprint author), SAIC Frederick Inc, Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. EM winkler@mail.ncifcrf.gov RI Kirk, Gregory/A-8484-2009 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIDA NIH HHS [DA-04334, R01 DA004334, R37 DA004334, R56 DA004334] NR 47 TC 39 Z9 40 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2007 VL 3 IS 1 AR e19 DI 10.1371/journal.pgen.0030019 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 130ZX UT WOS:000243838600014 PM 17257057 ER PT J AU Nikolaev, S Montoya-Burgos, JI Margulies, EH Rougemont, J Nyffeler, B Antonarakis, SE AF Nikolaev, Sergey Montoya-Burgos, Juan I. Margulies, Elliott H. Rougemont, Jacques Nyffeler, Bruno Antonarakis, Stylianos E. CA NISC Comparative Sequencing Progra TI Early history of mammals is elucidated with the ENCODE multiple species sequencing data SO PLOS GENETICS LA English DT Article ID NON-GENIC SEQUENCES; MAXIMUM-LIKELIHOOD; PLACENTAL MAMMALS; EVOLUTIONARY TREES; PROTEIN SEQUENCES; PHYLOGENIES; DNA; MITOCHONDRIAL; SUBSTITUTION; XENARTHRANS AB Understanding the early evolution of placental mammals is one of the most challenging issues in mammalian phylogeny. Here, we addressed this question by using the sequence data of the ENCODE consortium, which include 1% of mammalian genomes in 18 species belonging to all main mammalian lineages. Phylogenetic reconstructions based on an unprecedented amount of coding sequences taken from 218 genes resulted in a highly supported tree placing the root of Placentalia between Afrotheria and Exafroplacentalia ( Afrotheria hypothesis). This topology was validated by the phylogenetic analysis of a new class of genomic phylogenetic markers, the conserved noncoding sequences. Applying the tests of alternative topologies on the coding sequence dataset resulted in the rejection of the Atlantogenata hypothesis ( Xenarthra grouping with Afrotheria), while this test rejected the second alternative scenario, the Epitheria hypothesis ( Xenarthra at the base), when using the noncoding sequence dataset. Thus, the two datasets support the Afrotheria hypothesis; however, none can reject both of the remaining topological alternatives. C1 Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. Univ Geneva, Dept Zool & Anim Biol, CH-1211 Geneva, Switzerland. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. Swiss Inst Bioinformat, Lausanne, Switzerland. RP Nikolaev, S (reprint author), Univ Geneva, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. EM Sergey.Nikolaev@medecine.unige.ch; Stylianos.Antonarakis@medecine.unige.ch RI Nikolaev, Sergey/F-3148-2012; Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU Intramural NIH HHS NR 40 TC 59 Z9 62 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2007 VL 3 IS 1 AR e2 DI 10.1371/journal.pgen.0030002 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 130ZX UT WOS:000243838600002 PM 17206863 ER PT J AU Williamson, P Halleck, MS Malowitz, J Ng, S Fan, XX Krahling, S Remaley, AT Schlegel, RA AF Williamson, Patrick Halleck, Margaret S. Malowitz, Jonathan Ng, Susan Fan, Xiaoxuan Krahling, Stephen Remaley, Alan T. Schlegel, Robert A. TI Transbilayer Phospholipid Movements in ABCA1-Deficient Cells SO PLOS ONE LA English DT Article AB Tangier disease is an inherited disorder that results in a deficiency in circulating levels of HDL. Although the disease is known to be caused by mutations in the ABCA1 gene, the mechanism by which lesions in the ABCA1 ATPase effect this outcome is not known. The inability of ABCA1 knockout mice (ABCA1(-/-)) to load cholesterol and phospholipids onto apoA1 led to a proposal that ABCA1 mediates the transbilayer externalization of phospholipids, an activity integral not only to the formation of HDL particles but also to another, distinct process: the recognition and clearance of apoptotic cells by macrophages. Expression of phosphatidylserine (PS) on the surface of both macrophages and their apoptotic targets is required for efficient engulfment of the apoptotic cells, and it has been proposed that ABCA1 is required for transbilayer externalization of PS to the surface of both cell types. To determine whether ABCA1 is responsible for any of the catalytic activities known to control transbilayer phospholipid movements, these activities were measured in cells from ABCA1(-/-) mice and from Tangier individuals as well as ABCA1-expressing HeLa cells. Phospholipid movements in either normal or apoptotic lymphocytes or in macrophages were not inhibited when cells from knockout and wildtype mice or immortalized cells from Tangier individuals vs normal individuals were compared. Exposure of PS on the surface of normal thymocytes, apoptotic thymocytes and elicited peritoneal macrophages from wildtype and knockout mice or B lymphocytes from normal and Tangier individuals, as measured by annexin V binding, was also unchanged. No evidence was found of ABCA1-stimulated active PS export, and spontaneous PS movement to the outer leaflet in the presence or absence of apoA1 was unaffected by the presence or absence of ABCA1. Normal or Tangier B lymphocytes and macrophages were also identical in their ability to serve as targets or phagocytes, respectively, in apoptotic cell clearance assays. No evidence was found to support the suggestion that ABCA1 is involved in transport to the macrophage cell surface of annexins I and II, known to enhance phagocytosis of apoptotic cells. These results show that mutations in ABCA1 do not measurably reduce the rate of transbilayer movements of phospholipids in either the engulfing macrophage or the apoptotic target, thus discounting catalysis of transbilayer movements of phospholipids as the mechanism by which ABCA1 facilitates loading of phospholipids and cholesterol onto apoA1. C1 [Williamson, Patrick; Malowitz, Jonathan; Ng, Susan] Amherst Coll, Dept Biol, Amherst, MA 01002 USA. [Halleck, Margaret S.; Fan, Xiaoxuan; Krahling, Stephen; Schlegel, Robert A.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Williamson, P (reprint author), Amherst Coll, Dept Biol, Amherst, MA 01002 USA. EM plwilliamson@amherst.edu FU American Heart Association, Pennsylvania; Faculty Research Awards Program of Amherst College; Howard Hughes Medical Institute FX Supported by the American Heart Association, Pennsylvania Affiliate (to RAS), the Faculty Research Awards Program of Amherst College (to PLW) and the Howard Hughes Medical Institute through an Undergraduate Biological Sciences Education Program award to Amherst College. Study sponsors had no role in either study design; collection, analysis, and interpretation of the data; writing of the paper; or decision to submit for publication. NR 53 TC 21 Z9 21 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PY 2007 VL 2 IS 8 AR e729 DI 10.1371/journal.pone.0000729 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HN UT WOS:000207455200006 PM 17710129 ER PT J AU Roberts, A Deming, D Paddock, CD Cheng, A Yount, B Vogel, L Herman, BD Sheahan, T Heise, M Genrich, GL Zaki, SR Baric, R Subbarao, K AF Roberts, Anjeanette Deming, Damon Paddock, Christopher D. Cheng, Aaron Yount, Boyd Vogel, Leatrice Herman, Brian D. Sheahan, Tim Heise, Mark Genrich, Gillian L. Zaki, Sherif R. Baric, Ralph Subbarao, Kanta TI A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice SO PLOS PATHOGENS LA English DT Article ID ACUTE RESPIRATORY SYNDROME; INFLUENZA-VIRUS VARIANT; AMINO-ACID CHANGE; MATRIX PROTEIN; ANIMAL-MODEL; REPLICATION; VIRULENCE; PATHOGENESIS; SEVERITY; MANIFESTATIONS AB No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals. C1 NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. Ctr Dis Control & Prevent, Infect Dis Pathol Act, Atlanta, GA USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP Subbarao, K (reprint author), NIAID, Lab Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI059443, R01 AI059136, AI059136, P01 AI059443] NR 37 TC 146 Z9 148 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2007 VL 3 IS 1 BP 23 EP 37 AR e5 DI 10.1371/journal.ppat.0030005 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196OS UT WOS:000248492500003 PM 17222058 ER PT J AU Feldmann, H Jones, SM Daddario-DiCaprio, KM Geisbert, JB Stroher, U Grolla, A Bray, M Fritz, EA Fernando, L Feldmann, F Hensley, LE Geisbert, TW AF Feldmann, Heinz Jones, Steven M. Daddario-DiCaprio, Kathleen M. Geisbert, Joan B. Stroher, Ute Grolla, Allen Bray, Mike Fritz, Elizabeth A. Fernando, Lisa Feldmann, Friederike Hensley, Lisa E. Geisbert, Thomas W. TI Effective post-exposure treatment of Ebola infection SO PLOS PATHOGENS LA English DT Article ID VESICULAR STOMATITIS VIRUSES; HUMAN-IMMUNODEFICIENCY-VIRUS; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; CYNOMOLGUS MACAQUES; RABIES VACCINATION; PROPHYLAXIS; CELLS; PROTECTION; SMALLPOX AB Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective postexposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release. C1 Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. USA, Med Res Inst Infect Dis, Frederick, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIAID, Biodef Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Feldmann, H (reprint author), Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. EM Heinz_Feldmann@phac-aspc.gc.ca; Steven_Jones@phac-aspc.gc.ca NR 44 TC 154 Z9 163 U1 2 U2 51 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2007 VL 3 IS 1 BP 54 EP 61 AR e2 DI 10.1371/journal.ppat.0030002 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196OS UT WOS:000248492500006 PM 17238284 ER PT J AU Oswald, WB Geisbert, TW Davis, KJ Geisbert, JB Sullivan, NJ Jahrling, PB Parren, PWHI Burton, DR AF Oswald, Wendelien B. Geisbert, Thomas W. Davis, Kelly J. Geisbert, Joan B. Sullivan, Nancy J. Jahrling, Peter B. Parren, Paul W. H. I. Burton, Dennis R. TI Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys SO PLOS PATHOGENS LA English DT Article ID HEMORRHAGIC-FEVER; ENDOTHELIAL-CELLS; NONHUMAN-PRIMATES; RHESUS-MONKEYS; IN-VITRO; PROPHYLAXIS; PATHOGENESIS; MACROPHAGES; RESPONSES; THERAPY AB Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Vaccine Res Ctr, NIH, Bethesda, MD USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. EM burton@scripps.edu OI Parren, Paul/0000-0002-4365-3859 FU PHS HHS [A148053] NR 29 TC 112 Z9 119 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2007 VL 3 IS 1 BP 62 EP 66 AR e9 DI 10.1371/journal.ppat.0030009 PG 5 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 196OS UT WOS:000248492500007 PM 17238286 ER PT J AU Badr, MZ Shnyra, A Zoubine, M Norkin, M Herndon, B Quinn, T Miranda, RN Cunningham, ML Molteni, A AF Badr, Mostafa Z. Shnyra, Alexander Zoubine, Mikhail Norkin, Maxim Herndon, Betty Quinn, Tim Miranda, Roberto N. Cunningham, Michael L. Molteni, Agostino TI Phthalate-Induced Liver Protection against Deleterious Effects of the Th1 Response: A Potentially Serious Health Hazard SO PPAR RESEARCH LA English DT Article AB Infection with Mycobacterium tuberculosis (TB) induces pulmonary immunopathology mediated by classical Th1 type of acquired immunity with hepatic involvement in up to 80% of disseminated cases. Since PPAR agonists cause immune responses characterized by a decrease in the secretion of Th1 cytokines, we investigated the impact of activating these receptors on hepatic pathology associated with a well-characterized model of Th1-type pulmonary response. Male Fischer 344 rats were either maintained on a drug-free diet (groups I and II), or a diet containing diethylhexylphthalate (DEHP), a compound transformed in vivo to metabolites known to activate PPARs, for 21 days (groups III and IV). Subsequently, animals were primed with Mycobacterium bovis purified protein derivative (PPD) in a Complete Freund's Adjuvant. Fifteen days later, animals in groups II and IV were challenged with Sepharose 4B beads covalently coupled with PPD, while animals in groups I and III received blank Sepharose beads. Animals with Th1 response (group II) showed a marked structural disruption in the hepatic lobule. Remarkably, these alterations were conspicuously absent in animals which received DEHP (group IV), despite noticeable accumulation of T cells in the periportal triads. Immunostaining and confocal microscopy revealed hepatic accumulation of IFN gamma(+) Th1 and IL-4(+) Th2 cells in animals from groups II and IV, respectively. Our data suggest a PPAR alpha-mediated suppression of the development of a Th1 immune response in the liver, resulting in hepatoprotective effect. However, potentially negative consequences of PPAR activation, such as decreased ability of the immune system to fight infection and interference with the efficacy of vaccines designed to evoke Th1 immune responses, remain to be investigated. Copyright (C) 2007 Mostafa Z. Badr et al. C1 [Badr, Mostafa Z.] Univ Missouri, Sch Pharm, Div Pharmacol & Toxicol, Kansas City, MO 64108 USA. [Shnyra, Alexander] Kansas City Univ Med & Biosci, Dept Pharmacol & Microbiol, Kansas City, MO 64106 USA. [Zoubine, Mikhail; Norkin, Maxim; Herndon, Betty; Quinn, Tim; Molteni, Agostino] Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. [Miranda, Roberto N.; Molteni, Agostino] Univ Missouri, Sch Med, Dept Pathol, Kansas City, MO 64108 USA. [Cunningham, Michael L.] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Badr, MZ (reprint author), Univ Missouri, Sch Pharm, Div Pharmacol & Toxicol, Kansas City, MO 64108 USA. EM badrm@umkc.edu OI Miranda, Roberto/0000-0002-8467-5464 NR 23 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2007 AR 49671 DI 10.1155/2007/49671 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13MJ UT WOS:000207670600001 ER PT J AU Gil-da-Costa, R AF Gil-da-Costa, Ricardo BE Gursky, SL Nekaris, KAI TI Howler Monkeys and Harpy Eagles: A Communication Arms Race SO PRIMATE ANTI-PREDATOR STRATEGIES SE Developments in Primatology-Progress and Prospects LA English DT Article; Book Chapter ID SEMANTIC COMMUNICATION; ANTIPREDATOR RESPONSE; ALOUATTA-PALLIATA; DIANA MONKEYS; ALARM CALLS; BEHAVIOR; PREDATOR; VOCALIZATIONS; PRIMATE; PREY C1 NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Gil-da-Costa, R (reprint author), NIH, Lab Brain & Cognit, 10 Ctr Dr MSC 1366,Bldg 10,Room 4C103, Bethesda, MD 20892 USA. NR 57 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-34810-0 J9 DEV PRIMATOL-PROG PR JI Dev Primatol PY 2007 BP 289 EP 307 DI 10.1007/978-0-387-34810-0_14 D2 10.1007/978-0-387-34810-0 PG 19 WC Zoology SC Zoology GA BMH34 UT WOS:000272341500015 ER PT J AU Gallin, JI AF Gallin, John I. BE Gallin, JI Ognibene, FP TI A Historical Perspective on Clinical Research SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 1 EP 13 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900002 ER PT J AU Gallin, JI Ognibene, FP AF Gallin, John I. Ognibene, Frederick P. BE Gallin, JI Ognibene, FP TI PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH Second Edition Preface SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [Gallin, John I.; Ognibene, Frederick P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP XI EP XI DI 10.1016/B978-012369440-9/50000-1 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900001 ER PT J AU Grady, C AF Grady, Christine BE Gallin, JI Ognibene, FP TI Ethical Principles in Clinical Research SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID RESEARCH PARTICIPANTS; DEVELOPING-COUNTRIES; INFORMED-CONSENT; TRIALS C1 NIH, Sect Human Subjects Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Sect Human Subjects Res, Dept Clin Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 39 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 15 EP 26 DI 10.1016/B978-012369440-9/50004-9 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900003 ER PT B AU Emanuel, EJ AF Emanuel, Ezekiel J. BE Gallin, JI Ognibene, FP TI Researching a Bioethical Question SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID PHYSICIAN-ASSISTED SUICIDE; COST SAVINGS; DEVELOPING-COUNTRIES; ACTIVE EUTHANASIA; CLINICAL-RESEARCH; CONTROLLED TRIAL; CANCER-PATIENTS; OF-INTEREST; HOSPICE; LIFE C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8; 978-0-12-369440-9 PY 2007 BP 27 EP 38 DI 10.1016/B978-012369440-9/50005-0 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900004 ER PT J AU Schwartz, JP AF Schwartz, Joan P. BE Gallin, JI Ognibene, FP TI Integrity in Research: Individual and Institutional Responsibility SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIH, Off Intramural Res, Off Director, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NIH, Off Intramural Res, Off Director, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 39 EP 46 DI 10.1016/B978-012369440-9/50006-2 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900005 ER PT J AU Wichman, A AF Wichman, Alison BE Gallin, JI Ognibene, FP TI Institutional Review Boards SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID CLINICAL-RESEARCH C1 NIH, Off Human Subjects Res, Intramural Res Program, Bethesda, MD 20892 USA. RP Wichman, A (reprint author), NIH, Off Human Subjects Res, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 47 EP 58 DI 10.1016/B978-012369440-9/50007-4 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900006 ER PT J AU Friedman, LM AF Friedman, Lawrence M. BE Gallin, JI Ognibene, FP TI Data and Safety Monitoring Boards SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID RANDOMIZED-TRIAL; ATRIAL-FIBRILLATION; CLINICAL-TRIALS; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; LUNG-CANCER; THERAPY; PREVENTION; ASPIRIN C1 [Friedman, Lawrence M.] NIH, Bethesda, MD 20892 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 59 EP 65 DI 10.1016/B978-012369440-9/50008-6 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900007 ER PT J AU Tompkins, A AF Tompkins, Anne BE Gallin, JI Ognibene, FP TI Data Management in Clinical Trials SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Tompkins, A (reprint author), NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 67 EP 76 DI 10.1016/B978-012369440-9/50009-8 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900008 ER PT J AU Straus, SE AF Straus, Stephen E. BE Gallin, JI Ognibene, FP TI Unanticipated Risk in Clinical Research SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID CHRONIC HEPATITIS-B; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MITOCHONDRIAL-DNA; ANTIVIRAL AGENT; ULTRASTRUCTURAL-CHANGES; FIALURIDINE FIAU; CONTROLLED-TRIAL; LACTIC-ACIDOSIS; VIRUS INFECTION; GENE-TRANSFER C1 [Straus, Stephen E.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Straus, Stephen E.] NIH, Off Director, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 77 EP 95 DI 10.1016/B978-012369440-9/50010-4 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900009 ER PT J AU Zoon, KC Yetter, RA AF Zoon, Kathryn C. Yetter, Robert A. BE Gallin, JI Ognibene, FP TI The Regulation of Drugs and Biological Products by the Food and Drug Administration SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 [Zoon, Kathryn C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Yetter, Robert A.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Zoon, KC (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 97 EP 107 DI 10.1016/B978-012369440-9/50011-6 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900010 ER PT J AU Kvochak, PA AF Kvochak, Patricia A. BE Gallin, JI Ognibene, FP TI Legal Issues SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID JOURNALS; AUTHORS C1 NIH, Legal Advisors Off, Off Gen Counsel, US Dept HHS, Bethesda, MD 20892 USA. RP Kvochak, PA (reprint author), NIH, Legal Advisors Off, Off Gen Counsel, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 109 EP 120 DI 10.1016/B978-012369440-9/50012-8 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900011 ER PT J AU Nussenblatt, RB Gottesman, MM AF Nussenblatt, Robert B. Gottesman, Michael M. BE Gallin, JI Ognibene, FP TI Rules to Prevent Conflict of Interest for Clinical Investigators Conducting Human Subjects Research SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Nussenblatt, Robert B.] NIH, Off Protocol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Gottesman, Michael M.] NIH, Off Director, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 121 EP 127 DI 10.1016/B978-012369440-9/50014-1 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900012 ER PT J AU Kelty, M Bates, A Pinn, VW AF Kelty, Miriam Bates, Angela Pinn, Vivian W. BE Gallin, JI Ognibene, FP TI National Institutes of Health Policy on the Inclusion of Women and Minorities as Subjects in Clinical Research SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID CHRONIC HEPATITIS-C; BIOMEDICAL-RESEARCH; HEART-FAILURE; THERAPY; RACE; DISEASE; INTERFERON; BLACK C1 [Kelty, Miriam] NIA, NIH, Bethesda, MD 20892 USA. [Bates, Angela; Pinn, Vivian W.] NIH, Off Res Womens Hlth, Off Director, Bethesda, MD 20892 USA. RP Kelty, M (reprint author), NIA, NIH, Bethesda, MD 20892 USA. NR 41 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 129 EP 142 DI 10.1016/B978-012369440-9/50016-5 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900013 ER PT J AU Burklow, J AF Burklow, John BE Gallin, JI Ognibene, FP TI The Clinical Researcher and the Media SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIH, Off Commun & Publ Liaison, Bethesda, MD 20892 USA. RP Burklow, J (reprint author), NIH, Off Commun & Publ Liaison, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 155 EP 164 DI 10.1016/B978-012369440-9/50018-9 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900015 ER PT J AU Johnson, LL Borkowf, CB Albert, PS AF Johnson, Laura Lee Borkowf, Craig B. Albert, Paul S. BE Gallin, JI Ognibene, FP TI An Introduction to Biostatistics: Randomization, Hypothesis Testing, and Sample Size Estimation SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID II CLINICAL-TRIALS; ACUTE MYOCARDIAL-INFARCTION; MULTIPLE-SCLEROSIS; INTRAVENOUS MAGNESIUM; NONCYTOTOXIC AGENTS; DISEASE-ACTIVITY; DESIGNS; CONFIDENCE; RISK C1 [Johnson, Laura Lee] NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Borkowf, Craig B.] NCI, Canc Prevent Studies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Johnson, LL (reprint author), NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. NR 46 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 165 EP 196 DI 10.1016/B978-012369440-9/50019-0 PG 32 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900016 ER PT J AU Guralnik, JM Manolio, TA AF Guralnik, Jack M. Manolio, Teri A. BE Gallin, JI Ognibene, FP TI Design and Conduct of Observational Studies and Clinical Trials SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID ISOLATED SYSTOLIC HYPERTENSION; PREVENTION; DISEASE; STROKE; ADULTS; RISK; ADOLESCENTS; PREVALENCE; MORTALITY C1 [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 197 EP 217 DI 10.1016/B978-012369440-9/50020-7 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900017 ER PT J AU Max, MB AF Max, Mitchell B. BE Gallin, JI Ognibene, FP TI Small Clinical Trials SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID PAINFUL DIABETIC-NEUROPATHY; PLACEBO-CONTROLLED TRIALS; POSTHERPETIC NEURALGIA; RANDOMIZED-TRIALS; HIV-INFECTION; RUN-IN; DRUGS; ANTIDEPRESSANTS; ANALGESIA; EFFICACY C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Program, NIH, Bethesda, MD USA. RP Max, MB (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Program, NIH, Bethesda, MD USA. NR 88 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 219 EP 235 DI 10.1016/B978-012369440-9/50021-9 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900018 ER PT J AU Freeman, BD Banks, S Natanson, C AF Freeman, Bradley D. Banks, Steven Natanson, Charles BE Gallin, JI Ognibene, FP TI Using Secondary Data in Statistical Analysis SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MULTICENTER CLINICAL-TRIAL; HUMAN MONOCLONAL-ANTIBODY; GRAM-NEGATIVE BACTEREMIA; ESCHERICHIA-COLI J5; SEPTIC SHOCK; DOUBLE-BLIND; FACTOR-ALPHA C1 [Freeman, Bradley D.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Banks, Steven; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Freeman, BD (reprint author), Washington Univ, Sch Med, St Louis, MO 63130 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 265 EP 271 DI 10.1016/B978-012369440-9/50023-2 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900020 ER PT J AU Johnson, LL Shih, JH AF Johnson, Laura Lee Shih, Joanna H. BE Gallin, JI Ognibene, FP TI An Introduction to Survival Analysis SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter ID HAZARDS REGRESSION-MODEL; TRIAL C1 [Johnson, Laura Lee] NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Johnson, LL (reprint author), NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 273 EP 282 DI 10.1016/B978-012369440-9/50024-4 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900021 ER PT J AU Goldstein, B AF Goldstein, Bruce BE Gallin, JI Ognibene, FP TI Overview of Technology Development SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIH, Off Technol Transfer, Rockville, MD USA. RP Goldstein, B (reprint author), NIH, Off Technol Transfer, Rockville, MD USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 291 EP 314 DI 10.1016/B978-012369440-9/50026-8 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900023 ER PT J AU Spiegel, J AF Spiegel, Jack BE Gallin, JI Ognibene, FP TI Technology Transfer SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIH, Off Technol Transfer, Off Director, Rockville, MD USA. RP Spiegel, J (reprint author), NIH, Off Technol Transfer, Off Director, Rockville, MD USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 315 EP 334 DI 10.1016/B978-012369440-9/50027-X PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900024 ER PT J AU Nussenblatt, RB AF Nussenblatt, Robert B. BE Gallin, JI Ognibene, FP TI Writing a Protocol SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Nussenblatt, Robert B.] NIH, Off Protocol Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 335 EP 339 DI 10.1016/B978-012369440-9/50028-1 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900025 ER PT J AU Matula, MA AF Matula, Margaret A. BE Gallin, JI Ognibene, FP TI Evaluating a Protocol Budget SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 NIAID, Clin Res Management Branch, NIH, Bethesda, MD 20892 USA. RP Matula, MA (reprint author), NIAID, Clin Res Management Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 341 EP 349 DI 10.1016/B978-012369440-9/50029-3 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900026 ER PT J AU Bartlett, OT Postow, E AF Bartlett, Olivia T. Postow, Elliot BE Gallin, JI Ognibene, FP TI Getting the Funding You Need to Support Your Research: Navigating the National Institutes of Health Peer Review Process SO PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2ND EDITION LA English DT Article; Book Chapter C1 [Bartlett, Olivia T.] NCI, Res Programs Review Branch, NIH, Bethesda, MD 20892 USA. [Postow, Elliot] NIH, Div Biol Basis Dis, Ctr Sci Review, Bethesda, MD 20892 USA. RP Bartlett, OT (reprint author), NCI, Res Programs Review Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-048956-8 PY 2007 BP 359 EP 390 DI 10.1016/B978-012369440-9/50031-1 PG 32 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BCS45 UT WOS:000311278900028 ER PT J AU Atkinson, AJ AF Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Introduction to Clinical Pharmacology SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Editorial Material; Book Chapter ID GLOMERULAR-FILTRATION-RATE; ADVERSE DRUG-REACTIONS; CREATININE CLEARANCE; SERUM CREATININE C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 1 EP 7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900003 ER PT J AU Atkinson, AJ AF Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Clinical Pharmacokinetics SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID SERUM DIGOXIN CONCENTRATION; HEART-FAILURE C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 11 EP 23 DI 10.1016/B978-012369417-1/50042-0 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900004 ER PT J AU Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP AF Atkinson, Arthur J., Jr. Abernethy, Darrell R. Daniels, Charles E. Dedrick, Robert L. Markey, Sanford P. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI PRINCIPLES OF CLINICAL PHARMACOLOGY Second Edition Preface to the Second Edition SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Abernethy, Darrell R.] NIA, Geriatr Res Ctr, Clin Invest Lab, Baltimore, MD 21224 USA. [Daniels, Charles E.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92093 USA. [Dedrick, Robert L.] NIH, Off Res Serv, OD, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Markey, Sanford P.] NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP XV EP XV DI 10.1016/B978-012369417-1/50039-0 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900002 ER PT B AU Atkinson, AJ AF Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Compartmental Analysis of Drug Distribution SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID GENTAMICIN; KINETICS; ACCUMULATION; INSULIN; VOLUME; MODEL; FLOW C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2; 978-0-12-369417-1 PY 2007 BP 25 EP 36 DI 10.1016/B978-012369417-1/50043-2 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900005 ER PT J AU Atkinson, AJ AF Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Drug Absorption and Bioavailability SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID STABLE-ISOTOPE METHOD; INTESTINAL-ABSORPTION; N-ACETYLPROCAINAMIDE; P-GLYCOPROTEIN; METABOLISM; PHARMACOKINETICS; DIGOXIN; GUT; DISCOVERY; CACO-2 C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 40 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 37 EP 49 DI 10.1016/B978-012369417-1/50044-4 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900006 ER PT J AU Atkinson, AJ Reidenberg, MM AF Atkinson, Arthur J., Jr. Reidenberg, Marcus M. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Effects of Renal Disease on Pharmacokinetics SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID SERUM CREATININE; PROTEIN BINDING; FAILURE; CLEARANCE; ACETYLPROCAINAMIDE; PREDICTION; CIMETIDINE; DIGOXIN; DRUGS C1 [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Reidenberg, Marcus M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 51 EP 58 DI 10.1016/B978-012369417-1/50045-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900007 ER PT J AU Atkinson, AJ Susla, GM AF Atkinson, Arthur J., Jr. Susla, Gregory M. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Pharmacokinetics in Patients Requiring Renal Replacement Therapy SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; CONTINUOUS VENOVENOUS HEMOFILTRATION; CRITICALLY-ILL PATIENTS; CONTINUOUS HEMODIALYSIS; PERITONEAL-DIALYSIS; ARTIFICIAL KIDNEY; DRUG REMOVAL; BLOOD FLOW; FAILURE; CLEARANCE C1 [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Susla, Gregory M.] VHA Consulting Serv Inc, Frederick, MD 21704 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 59 EP 72 DI 10.1016/B978-012369417-1/50046-8 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900008 ER PT J AU Susla, GM Atkinson, AJ AF Susla, Gregory M. Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Effect of Liver Disease on Pharmacokinetics SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID ACUTE VIRAL-HEPATITIS; OXIDATIVE DRUG-METABOLISM; II RECEPTOR ANTAGONIST; ENTEROHEPATIC CIRCULATION; HEPATORENAL-SYNDROME; ESOPHAGEAL-VARICES; COCKTAIL APPROACH; PROTEIN-BINDING; RENAL-FUNCTION; BLOOD-FLOW C1 [Susla, Gregory M.] VHA Consulting Serv Inc, Frederick, MD 21704 USA. [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Susla, GM (reprint author), VHA Consulting Serv Inc, Frederick, MD 21704 USA. NR 71 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 73 EP 87 DI 10.1016/B978-012369417-1/50047-X PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900009 ER PT J AU Morrison, PF AF Morrison, Paul F. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Distributed Models of Drug Kinetics SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID CONVECTION-ENHANCED DELIVERY; DIRECT INTERSTITIAL INFUSION; BINDING-SITE BARRIER; MONOCLONAL-ANTIBODY; QUINOLINIC ACID; SPINAL-CORD; RAT-BRAIN; IN-VIVO; QUANTITATIVE MICRODIALYSIS; COMPUTATIONAL MODEL C1 NIH, Off Res Serv, OD, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Morrison, PF (reprint author), NIH, Off Res Serv, OD, Div Bioengn & Phys Sci, Bldg 10, Bethesda, MD 20892 USA. NR 44 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 107 EP 128 DI 10.1016/B978-012369417-1/50049-3 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900011 ER PT J AU Markey, SP AF Markey, Sanford P. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Pathways of Drug Metabolism SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID MICROSOMAL EPOXIDE HYDROLASE; TISSUE-SPECIFIC EXPRESSION; GRAPEFRUIT JUICE; CHEMICAL METABOLISM; COVALENT BINDING; POLYMORPHISMS; SULFATION; ENZYMES; HUMANS; SULFOTRANSFERASES C1 NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. NR 54 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 143 EP 162 DI 10.1016/B978-012369417-1/50051-1 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900013 ER EF