FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Choisy, M Rohani, P AF Choisy, Marc Rohani, Pejman TI Changing spatial epidemiology of pertussis in continental USA SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE pertussis; spatial dynamics; infectious disease re-emergence ID UNITED-STATES; WAVELET ANALYSIS; TRAVELING-WAVES; INFLUENZA; DYNAMICS; SYNCHRONY; PATTERNS; TRANSMISSION; VACCINATION; HIERARCHIES AB Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading. C1 [Choisy, Marc] Ctr IRD, MIVEGEC UM1 UM2 CNRS 5290 IRD 224, F-34394 Montpellier 5, France. [Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Choisy, M (reprint author), Ctr IRD, MIVEGEC UM1 UM2 CNRS 5290 IRD 224, 911 Ave Agropolis,BP 64501, F-34394 Montpellier 5, France. EM marc.choisy@ird.fr RI Choisy, Marc/J-7131-2016 OI Choisy, Marc/0000-0002-5187-6390 FU IRD; CNRS; Vaccine Modeling Initiative of the Bill and Melinda Gates Foundation; Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; National Institutes of Health [1R01AI101155] FX We thank Aaron King and two anonymous reviewers for comments on this paper. M.C. was funded by IRD and CNRS. M.C. and P.R. were supported by the Vaccine Modeling Initiative of the Bill and Melinda Gates Foundation and the Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health, and by a grant from the National Institutes of Health 1R01AI101155. NR 42 TC 11 Z9 11 U1 0 U2 12 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 EI 1471-2954 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD NOV 22 PY 2012 VL 279 IS 1747 BP 4574 EP 4581 DI 10.1098/rspb.2012.1761 PG 8 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 025TU UT WOS:000310218400008 PM 23015623 ER PT J AU Schneider, P Bell, AS Sim, DG O'Donnell, AJ Blanford, S Paaijmans, KP Read, AF Reece, SE AF Schneider, Petra Bell, Andrew S. Sim, Derek G. O'Donnell, Aidan J. Blanford, Simon Paaijmans, Krijn P. Read, Andrew F. Reece, Sarah E. TI Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE competition; drug resistance; fitness; genetically diverse infection; transmission; virulence evolution ID REVERSE-TRANSCRIPTION PCR; PUBLIC-HEALTH IMPACT; PARASITIC NEMATODES; RESISTANCE; FALCIPARUM; ARTEMISININ; EVOLUTION; INFECTIONS; TOLERANCE; RECRUDESCENCE AB Here, we test the hypothesis that virulent malaria parasites are less susceptible to drug treatment than less virulent parasites. If true, drug treatment might promote the evolution of more virulent parasites (defined here as those doing more harm to hosts). Drug-resistance mechanisms that protect parasites through interactions with drug molecules at the sub-cellular level are well known. However, parasite phenotypes associated with virulence might also help parasites survive in the presence of drugs. For example, rapidly replicating parasites might be better able to recover in the host if drug treatment fails to eliminate parasites. We quantified the effects of drug treatment on the in-host survival and between-host transmission of rodent malaria (Plasmodium chabaudi) parasites which differed in virulence and had never been previously exposed to drugs. In all our treatment regimens and in single- and mixed-genotype infections, virulent parasites were less sensitive to pyrimethamine and artemisinin, the two antimalarial drugs we tested. Virulent parasites also achieved disproportionately greater transmission when exposed to pyrimethamine. Overall, our data suggest that drug treatment can select for more virulent parasites. Drugs targeting transmission stages (such as artemisinin) may minimize the evolutionary advantage of virulence in drug-treated infections. C1 [Schneider, Petra; Reece, Sarah E.] Univ Edinburgh, Sch Biol Sci, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland. [Schneider, Petra; O'Donnell, Aidan J.; Reece, Sarah E.] Univ Edinburgh, Sch Biol Sci, Inst Evolut, Edinburgh EH9 3JT, Midlothian, Scotland. [Schneider, Petra; O'Donnell, Aidan J.; Reece, Sarah E.] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. [Bell, Andrew S.; Sim, Derek G.; Blanford, Simon; Paaijmans, Krijn P.; Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Bell, Andrew S.; Sim, Derek G.; Blanford, Simon; Paaijmans, Krijn P.; Read, Andrew F.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Schneider, P (reprint author), Univ Edinburgh, Sch Biol Sci, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland. EM petra.schneider@ed.ac.uk RI Reece, Sarah/C-9447-2009; OI Schneider, Petra/0000-0002-2616-237X FU Wellcome Trust [WT082234MA]; Wissenschaftskolleg zu Berlin; Centre for Immunity, Infection and Evolution, Edinburgh; National Institute of General Medical Sciences [R01GM089932]; Pennsylvania Department of Health using Tobacco Settlement Funds FX We thank R. Mooney, B. Chan and D. Kroczynski for assistance during the experiments; L. Ross and J. Hadfield for statistical advice on MCMCglmm; P. Hunt for providing primers and protocols for classical resistance genotyping; and N. Mideo, L. Pollitt, A. Rowe and laboratory members, the co-evolution discussion group at Ashworth Laboratories, and members of the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health, for discussion. For funding, we thank the Wellcome Trust (WT082234MA) and Wissenschaftskolleg zu Berlin (S.E.R.), the Centre for Immunity, Infection and Evolution, Edinburgh (P.S.), the National Institute of General Medical Sciences (R01GM089932) and a grant from the Pennsylvania Department of Health using Tobacco Settlement Funds (A.F.R.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 51 TC 14 Z9 14 U1 1 U2 22 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD NOV 22 PY 2012 VL 279 IS 1747 BP 4677 EP 4685 DI 10.1098/rspb.2012.1792 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 025TU UT WOS:000310218400021 PM 23015626 ER PT J AU Kolb, P Phan, K Gao, ZG Marko, AC Sali, A Jacobson, KA AF Kolb, Peter Phan, Khai Gao, Zhan-Guo Marko, Adam C. Sali, Andrej Jacobson, Kenneth A. TI Limits of Ligand Selectivity from Docking to Models: In Silico Screening for A(1) Adenosine Receptor Antagonists SO PLOS ONE LA English DT Article ID PROTEIN-COUPLED RECEPTORS; DRUG DESIGN; MOLECULAR DOCKING; CRYSTAL-STRUCTURE; DISCOVERY; PREDICTION; IDENTIFICATION; PHARMACOLOGY; RADIOLIGAND; DERIVATIVES AB G protein-coupled receptors (GPCRs) are attractive targets for pharmaceutical research. With the recent determination of several GPCR X-ray structures, the applicability of structure-based computational methods for ligand identification, such as docking, has increased. Yet, as only about 1% of GPCRs have a known structure, receptor homology modeling remains necessary. In order to investigate the usability of homology models and the inherent selectivity of a particular model in relation to close homologs, we constructed multiple homology models for the A(1) adenosine receptor (A(1)AR) and docked similar to 2.2 M lead-like compounds. High-ranking molecules were tested on the A(1)AR as well as the close homologs A(2A)AR and A(3)AR. While the screen yielded numerous potent and novel ligands (hit rate 21% and highest affinity of 400 nM), it delivered few selective compounds. Moreover, most compounds appeared in the top ranks of only one model. These findings have implications for future screens. C1 [Kolb, Peter; Marko, Adam C.; Sali, Andrej] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA. [Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Marko, Adam C.; Sali, Andrej] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. RP Kolb, P (reprint author), Univ Marburg, Dept Pharmaceut Chem, Marburg, Germany. EM peter.kolb@uni-marburg.de; kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Kolb, Peter/A-3782-2008 OI Jacobson, Kenneth/0000-0001-8104-1493; Kolb, Peter/0000-0003-4089-614X FU DFG Emmy-Noether Fellowship [KO 4095/1-1]; National Institutes of Health/National Institute of General Medical Sciences [R01 GM083960]; National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program [1ZIADK031117-24] FX Funding came from a DFG Emmy-Noether Fellowship KO 4095/1-1 to PK (www.dfg.de), a National Institutes of Health/National Institute of General Medical Sciences R01 GM083960 grant to AS (www.nigms.nih.gov), and a National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (1ZIADK031117-24) to KAJ (http://www2.niddk.nih.gov/NIDDKLabs/NIDDKLabsAbout.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 22 Z9 22 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 21 PY 2012 VL 7 IS 11 AR e49910 DI 10.1371/journal.pone.0049910 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 047ER UT WOS:000311821000141 PM 23185482 ER PT J AU Nissim, O Melis, M Diaz, G Kleiner, DE Tice, A Fantola, G Zamboni, F Mishra, L Farci, P AF Nissim, Oriel Melis, Marta Diaz, Giacomo Kleiner, David E. Tice, Ashley Fantola, Giovanni Zamboni, Fausto Mishra, Lopa Farci, Patrizia TI Liver Regeneration Signature in Hepatitis B Virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling SO PLOS ONE LA English DT Article ID HEPATOCELLULAR-CARCINOMA; PROGENITOR CELLS; STEM-CELLS; STELLATE CELLS; GROWTH-FACTOR; ACTIVATION; FIBROSIS; SIMILARITIES; DISEASES; CANCERS AB Introduction: The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC). The dramatic clinical course of acute liver failure (ALF) has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV)-associated ALF. Methods and Findings: Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7), whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process. Conclusion: Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between liver regeneration and liver cancer. C1 [Nissim, Oriel; Melis, Marta; Tice, Ashley; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Fantola, Giovanni; Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Mishra, Lopa] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pfarci@niaid.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU NIH, National Institute of Allergy and Infectious Diseases and National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases and National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 14 Z9 14 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 21 PY 2012 VL 7 IS 11 AR e49611 DI 10.1371/journal.pone.0049611 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 047ER UT WOS:000311821000068 PM 23185381 ER PT J AU Britt, JP Benaliouad, F McDevitt, RA Stuber, GD Wise, RA Bonci, A AF Britt, Jonathan P. Benaliouad, Faiza McDevitt, Ross A. Stuber, Garret D. Wise, Roy A. Bonci, Antonello TI Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens SO NEURON LA English DT Article ID PREFRONTAL CORTICAL INPUTS; MIDBRAIN DOPAMINE NEURONS; AMPA RECEPTOR TRAFFICKING; EXCITATORY TRANSMISSION; MOLECULAR-MECHANISMS; PROLONGED WITHDRAWAL; PROJECTION NEURONS; DIRECTED BEHAVIOR; STRIATAL NEURONS; COCAINE AB Excitatory afferents to the nucleus accumbens (NAc) are thought to facilitate reward seeking by encoding reward-associated cues. Selective activation of different glutamatergic inputs to the NAc can produce divergent physiological and behavioral responses, but mechanistic explanations for these pathway-specific effects are lacking. Here, we compared the innervation patterns and synaptic properties of ventral hippocampus, basolateral amygdala, and prefrontal cortex input to the NAc. Ventral hippocampal input was found to be uniquely localized to the medial NAc shell, where it was predominant and selectively potentiated after cocaine exposure. In vivo, bidirectional optogenetic manipulations of this pathway attenuated and enhanced cocaine-induced locomotion. Challenging the idea that any of these inputs encode motivationally neutral information, activation of each discrete pathway reinforced instrumental behaviors. Finally, direct optical activation of medium spiny neurons proved to be capable of supporting self-stimulation, demonstrating that behavioral reinforcement is an explicit consequence of strong excitatory drive to the NAc. C1 [Bonci, Antonello] Johns Hopkins Univ, Solomon H Snyder Neurosci Inst, Sch Med, Baltimore, MD 21205 USA. [Britt, Jonathan P.; Benaliouad, Faiza; McDevitt, Ross A.; Wise, Roy A.; Bonci, Antonello] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Britt, Jonathan P.; Bonci, Antonello] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA. [Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Stuber, Garret D.] Univ N Carolina, Dept Psychiat, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA. [Stuber, Garret D.] Univ N Carolina, Dept Cell Biol, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA. [Stuber, Garret D.] Univ N Carolina, Dept Physiol, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA. RP Bonci, A (reprint author), Johns Hopkins Univ, Solomon H Snyder Neurosci Inst, Sch Med, Baltimore, MD 21205 USA. EM antonello.bonci@nih.gov RI Britt, Jonathan/D-8877-2011; Stuber, Garret/E-1160-2011 OI Britt, Jonathan/0000-0003-3044-9565; FU National Institute on Drug Abuse [DA029325, DA032750]; National Institutes of Health, National Institute on Drug Abuse FX We thank Janice Joo, Dhara Patel, Stephanie Chung, Saemi Cho, and Michael Chiang for technical help. This work was supported by the National Institute on Drug Abuse (DA029325 and DA032750; G.D.S.) and the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse. NR 66 TC 155 Z9 158 U1 2 U2 49 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 21 PY 2012 VL 76 IS 4 BP 790 EP 803 DI 10.1016/j.neuron.2012.09.040 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 049JD UT WOS:000311977900012 PM 23177963 ER PT J AU Tachibana, Y Hikosaka, O AF Tachibana, Yoshihisa Hikosaka, Okihide TI The Primate Ventral Pallidum Encodes Expected Reward Value and Regulates Motor Action SO NEURON LA English DT Article ID NIGRA PARS RETICULATA; SACCADIC EYE-MOVEMENTS; BASAL GANGLIA; DOPAMINE NEURONS; GLOBUS-PALLIDUS; DECISION-MAKING; LATERAL HABENULA; MODULATION; MOTIVATION; SIGNALS AB Motor actions are facilitated when expected reward value is high. It is hypothesized that there are neurons that encode expected reward values to modulate impending actions and potentially represent motivation signals. Here, we present evidence suggesting that the ventral pallidum (VP) may participate in this process. We recorded single neuronal activity in the monkey VP using a saccade task with a direction-dependent reward bias. Depending on the amount of the expected reward, VP neurons increased or decreased their activity tonically until the reward was delivered, for both ipsiversive and contraversive saccades. Changes in expected reward values were also associated with changes in saccade performance (latency and velocity). Furthermore, bilateral muscimol-induced inactivation of the VP abolished the reward-dependent changes in saccade latencies. These data suggest that the VP provides expected reward value signals that are used to facilitate or inhibit motor actions. C1 [Tachibana, Yoshihisa; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Tachibana, Yoshihisa] Grad Univ Adv Studies, Natl Inst Physiol Sci, Div Syst Neurophysiol, Okazaki, Aichi 4448585, Japan. [Tachibana, Yoshihisa] Grad Univ Adv Studies, Dept Physiol Sci, Okazaki, Aichi 4448585, Japan. RP Tachibana, Y (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM banao@nips.ac.jp; oh@lsr.nei.nih.gov FU Intramural NIH HHS [ZIA EY000415-09] NR 50 TC 33 Z9 34 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 21 PY 2012 VL 76 IS 4 BP 826 EP 837 DI 10.1016/j.neuron.2012.09.030 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 049JD UT WOS:000311977900015 PM 23177966 ER PT J AU Li, G Cohen, P Xie, HC Low, D Li, DB Rimner, A AF Li, Guang Cohen, Patrice Xie, Huchen Low, Daniel Li, Diana Rimner, Andreas TI A novel four-dimensional radiotherapy planning strategy from a tumor-tracking beam's eye view SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DEFORMABLE IMAGE REGISTRATION; TORSO VOLUME CHANGE; CELL LUNG-CANCER; RESPIRATORY MOTION; MOVING TARGETS; MONTE-CARLO; REAL-TIME; CT SCANS; SEGMENTATION; FEASIBILITY AB To investigate the feasibility of four-dimensional radiotherapy (4DRT) planning from a tumor-tracking beam's eye view (ttBEV) with reliable gross tumor volume (GTV) delineation, realistic normal tissue representation, high planning accuracy and low clinical workload, we propose and validate a novel 4D conformal planning strategy based on a synthesized 3.5D computed tomographic (3.5DCT) image with a motion-compensated tumor. To recreate patient anatomy from a ttBEV in the moving tumor coordinate system for 4DRT planning (or 4D planning), the centers of delineated GTVs in all phase CT images of 4DCT were aligned, and then the aligned CTs were averaged to produce a new 3.5DCT image. This GTV-motion-compensated CT contains a motionless target (with motion artifacts minimized) and motion-blurred normal tissues (with a realistic temporal density average). Semi-automatic threshold-based segmentation of the tumor, lung and body was applied, while manual delineation was used for other organs at risk (OARs). To validate this 3.5DCT-based 4D planning strategy, five patients with peripheral lung lesions of small size (<5 cm(3)) and large motion range (1.2-3.5 cm) were retrospectively studied for stereotactic body radiotherapy (SBRT) using 3D conformal radiotherapy planning tools. The 3.5DCT-based 4D plan (3.5DCT plan) with 9-10 conformal beams was compared with the 4DCT-based 4D plan (4DCT plan). The 4DCT plan was derived from multiple 3D plans based on all phase CT images, each of which used the same conformal beam configuration but with an isocenter shift to aim at the moving tumor and a minor beam aperture and weighting adjustment to maintain plan conformality. The dose-volume histogram (DVH) of the 4DCT plan was created with two methods: one is an integrated DVH (iDVH(4D)), which is defined as the temporal average of all 3D-phase-plan DVHs, and the other (DVH4D) is based on the dose distribution in a reference phase CT image by dose warping from all phase plans using the displacement vector field (DVF) from a free-form deformable image registration (DIR). The DVH3.5D (for the 3.5DCT plan) was compared with both iDVH(4D) and DVH4D. To quantify the DVH difference between the 3.5DCT plan and the 4DCT plan, two methods were used: relative difference (%) of the areas underneath the DVH curves and the volumes receiving more than 20% (V20) and 50% (V50) of prescribed dose of these 4D plans. The volume of the delineated GTV from different phase CTs varied dramatically from 24% to 112% among the five patients, whereas the GTV from 3.5DCT deviated from the averaged GTV in 4DCT by only -6% +/- 6%. For planning tumor volume (PTV) coverage, the difference between the DVH3.5D and iDVH(4D) was negligible (<1% area), whereas the DVH3.5D and DVH4D were quite different, due to DIR uncertainty (similar to 2 mm), which propagates to PTV dose coverage with a pronounced uncertainty for small tumors (0.3-4.0 cm(3)) in stereotactic plans with sharp dose falloff around PTV. For OARs, such as the lung, heart, cord and esophagus, the three DVH curves (DVH3.5D, DVH4D and iDVH(4D)) were found to be almost identical for the same patients, especially in high-dose regions. For the tumor-containing lung, the relative difference of the areas underneath the DVH curves was found to be small (5.3% area on average), of which 65% resulted from the low-dose region (D < 20%). The averaged V20 difference between the two 4D plans was 1. 2% +/- 0.8%. For the mean lung dose (MLD), the 3.5DCT plan differed from the 4DCT plan by -1.1% +/- 1.3%. GTV-motion-compensated CT (3.5DCT) produces an accurate and reliable GTV delineation, which is close to the mean GTV from 4DCT. The 3.5DCT plan is equivalent to the 4DCT plan with <1% dose difference to the PTV and negligible dose difference in OARs. The 3.5DCT approach simplifies 4D planning and provides accurate dose calculation without a substantial increase of clinical workload for motion-tracking delivery to treat small peripheral lung tumors with large motion. C1 [Li, Guang; Cohen, Patrice; Li, Diana] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Xie, Huchen] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Low, Daniel] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA. [Rimner, Andreas] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Li, G (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. EM lig2@mskcc.org OI Li, Guang/0000-0002-9022-2883 NR 37 TC 4 Z9 4 U1 1 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2012 VL 57 IS 22 BP 7579 EP 7598 DI 10.1088/0031-9155/57/22/75794 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 033ZA UT WOS:000310838700025 PM 23103415 ER PT J AU Stern, MD AF Stern, Michael D. TI Coagulation Makes Waves SO BIOPHYSICAL JOURNAL LA English DT News Item C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM sternm@grc.nia.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 21 PY 2012 VL 103 IS 10 BP 2049 EP 2049 DI 10.1016/j.bpj.2012.09.042 PG 1 WC Biophysics SC Biophysics GA 041RN UT WOS:000311419000003 PM 23200038 ER PT J AU Vahedi, G Takahashi, H Nakayamada, S Sun, HW Sartorelli, V Kanno, Y O'Shea, JJ AF Vahedi, Golnaz Takahashi, Hayato Nakayamada, Shingo Sun, Hong-wei Sartorelli, Vittorio Kanno, Yuka O'Shea, John J. TI STATs Shape the Active Enhancer Landscape of T Cell Populations SO CELL LA English DT Article ID CHIP-SEQ DATA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; REGULATORY ELEMENTS; LINEAGE COMMITMENT; RNA-SEQ; BET; DIFFERENTIATION; IDENTIFICATION; ACCESSIBILITY AB Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. Although enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4(+) T cells as a model of differentiation, mapping the activity of cell-type-specific enhancer elements in T helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the activation of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells. C1 [Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo; Kanno, Yuka; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Sun, Hong-wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA. [Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Kanno, Y (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM kannoy@mail.nih.gov RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU Intramural Research Programs of NIAMS FX The authors thank Drs. K. Zhao, A. Poholek, and K. Ghoreschi for critically reading this manuscript. We also thank G. Gutierrez-Cruz (Biodata Mining Core Facility, NIAMS), J. Simone, and J. Lay (Flow Cytometry Section, NIAMS) for their excellent technical support. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH. This work was supported by the Intramural Research Programs of NIAMS. NR 41 TC 141 Z9 142 U1 0 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 21 PY 2012 VL 151 IS 5 BP 981 EP 993 DI 10.1016/j.cell.2012.09.044 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041TG UT WOS:000311423500012 PM 23178119 ER PT J AU Gilliam, JC Chang, JT Sandoval, IM Zhang, YW Li, TS Pittler, SJ Chiu, W Wensel, TG AF Gilliam, Jared C. Chang, Juan T. Sandoval, Ivette M. Zhang, Youwen Li, Tiansen Pittler, Steven J. Chiu, Wah Wensel, Theodore G. TI Three-Dimensional Architecture of the Rod Sensory Cilium and Its Disruption in Retinal Neurodegeneration SO CELL LA English DT Article ID INTRAFLAGELLAR TRANSPORT PROTEIN; BARDET-BIEDL-SYNDROME; CGMP-GATED CHANNEL; ACID-RICH PROTEINS; CRYOELECTRON TOMOGRAPHY; CILIARY ROOTLET; BETA-SUBUNIT; BASAL BODY; DISK MORPHOGENESIS; OUTER SEGMENTS AB Defects in primary cilia lead to devastating disease because of their roles in sensation and developmental signaling but much is unknown about ciliary structure and mechanisms of their formation and maintenance. We used cryo-electron tomography to obtain 3D maps of the connecting cilium and adjacent cellular structures of a modified primary cilium, the rod outer segment, from wild-type and genetically defective mice. The results reveal the molecular architecture of the cilium and provide insights into protein functions. They suggest that the ciliary rootlet is involved in cellular transport and stabilizes the axoneme. A defect in the BBSome membrane coat caused defects in vesicle targeting near the base of the cilium. Loss of the proteins encoded by the Cngb1 gene disrupted links between the disk and plasma membranes. The structures of the outer segment membranes support a model for disk morphogenesis in which basal disks are enveloped by the plasma membrane. C1 [Gilliam, Jared C.; Chang, Juan T.; Sandoval, Ivette M.; Chiu, Wah; Wensel, Theodore G.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Chang, Juan T.; Chiu, Wah] Baylor Coll Med, Natl Ctr Macromol Imaging, Houston, TX 77030 USA. [Zhang, Youwen; Pittler, Steven J.] Univ Alabama Birmingham, Dept Vis Sci, Birmingham, AL 35924 USA. [Li, Tiansen] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. RP Wensel, TG (reprint author), Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. EM twensel@bcm.edu RI Pittler, Steven/J-7091-2013; OI Pittler, Steven/0000-0002-8464-9303; Wensel, Theodore/0000-0003-3518-9352 FU NIH [EY011900, EY07981, P41RR002250, EY018143, EY10309, EY10581, EY011731, T32EY007001, EY002520]; Robert Welch Foundation [Q-0035, Q1242] FX This work was supported in part by grants from the NIH (EY011900 and EY07981 to T.G.W., P41RR002250 to W. C., EY018143 to S.J.P., EY10309 and EY10581 to T.L., support for I.M.S. by EY011731, an NIH NRSA trainee appointment on grant T32EY007001 to J.C.G., and Vision Research Core Grant EY002520) and by the Robert Welch Foundation (Q-0035 to T.G.W. and Q1242 to W.C.). We thank Mr. Ralph Nichols for help with electron microscopy of fixed samples, Dr. Vera Moiseenkova-Bell for help in the early stages of the project, and Dr. Alecia Gross for helpful suggestions and pilot experiments. NR 53 TC 50 Z9 51 U1 1 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 21 PY 2012 VL 151 IS 5 BP 1029 EP 1041 DI 10.1016/j.cell.2012.10.038 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041TG UT WOS:000311423500016 PM 23178122 ER PT J AU Yasuda, M Yamamoto, S Hikosaka, O AF Yasuda, Masaharu Yamamoto, Shinya Hikosaka, Okihide TI Robust Representation of Stable Object Values in the Oculomotor Basal Ganglia SO JOURNAL OF NEUROSCIENCE LA English DT Article ID NIGRA-PARS-RETICULATA; LONG-TERM-MEMORY; SUBSTANTIA-NIGRA; NEURAL MECHANISMS; CAUDATE-NUCLEUS; HABIT FORMATION; VISUAL-STIMULI; EYE-MOVEMENTS; REWARD; STRIATUM AB Our gaze tends to be directed to objects previously associated with rewards. Such object values change flexibly or remain stable. Here we present evidence that the monkey substantia nigra pars reticulata (SNr) in the basal ganglia represents stable, rather than flexible, object values. After across-day learning of object-reward association, SNr neurons gradually showed a response bias to surprisingly many visual objects: inhibition to high-valued objects and excitation to low-valued objects. Many of these neurons were shown to project to the ipsilateral superior colliculus. This neuronal bias remained intact even after >100 d without further learning. In parallel with the neuronal bias, the monkeys tended to look at high-valued objects. The neuronal and behavioral biases were present even if no value was associated during testing. These results suggest that SNr neurons bias the gaze toward objects that were consistently associated with high values in one's history. C1 [Yasuda, Masaharu; Yamamoto, Shinya; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Yamamoto, Shinya] Natl Inst Adv Ind Sci & Technol, Syst Neurosci Grp, Human Technol Res Inst, Tsukuba, Ibaraki 3058568, Japan. RP Yasuda, M (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Bldg 49,Rm 2C28, Bethesda, MD 20892 USA. EM yasudama@mail.nih.gov RI Yamamoto, Shinya/S-3134-2016 OI Yamamoto, Shinya/0000-0002-0505-8848 FU Intramural Research Program at the National Institutes of Health, National Eye Institute FX This work was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute. We thank E. Bromberg-Martin, H. F. Kim, I. Monosov, S. Hong, and Y. Tachibana for discussions; and A. M. Nichols, A. V. Hays, B. Nagy, D. Parker, G. Tansey, J.W. McClurkin, L. P. Jensen, M. K. Smith, and T. W. Ruffner for technical assistance. NR 54 TC 28 Z9 29 U1 4 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 21 PY 2012 VL 32 IS 47 BP 16917 EP 16932 DI 10.1523/JNEUROSCI.3438-12.2012 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 041SF UT WOS:000311420800035 PM 23175843 ER PT J AU Parkash, J Cimino, I Ferraris, N Casoni, F Wray, S Cappy, H Prevot, V Giacobini, P AF Parkash, Jyoti Cimino, Irene Ferraris, Nicoletta Casoni, Filippo Wray, Susan Cappy, Helene Prevot, Vincent Giacobini, Paolo TI Suppression of beta 1-Integrin in Gonadotropin-Releasing Hormone Cells Disrupts Migration and Axonal Extension Resulting in Severe Reproductive Alterations SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; NEURONAL MIGRATION; NEURITE OUTGROWTH; MEDIAN-EMINENCE; GENE-EXPRESSION; GNRH NEURONS; RAT UTERUS; BETA-1-CLASS INTEGRINS; SENSORY NEURONS; SEMAPHORIN 3F AB Reproduction in mammals is dependent on the function of hypothalamic neurons whose axons project to the hypothalamic median eminence (ME) where they release gonadotropin-releasing hormone (GnRH) into a specialized capillary network for delivery to the anterior pituitary. These neurons originate prenatally in the nasal placode and migrate into the forebrain along the olfactory-vomeronasal nerves. The complex developmental events leading to the correct establishment of the GnRH system are tightly regulated by the specific spatiotemporal expression patterns of guidance cues and extracellular matrix molecules, the functions of which, in part, are mediated by their binding to beta 1-subunit-containing integrins. To determine the biological role of these cell-surface proteins in reproduction, Cre/LoxP technology was used to generate GnRH neuron-specific beta 1-integrin conditional KO (GnRH-Itgb1(-/-)) mice. Loss of beta 1-integrin signaling impaired migration of GnRH neurons, their axonal extension to the ME, timing of pubertal onset, and fertility in these mice. These results identify beta 1-integrin as a gene involved in normal development of the GnRH system and demonstrate a fundamental role for this protein in acquisition of normal reproductive competence in female mice. C1 [Giacobini, Paolo] INSERM, U837, Jean Pierre Aubert Res Ctr, Unit 837, F-59045 Lille, France. [Parkash, Jyoti; Cimino, Irene; Casoni, Filippo; Cappy, Helene; Prevot, Vincent; Giacobini, Paolo] Sch Med, UDSL, F-59045 Lille, France. [Ferraris, Nicoletta; Giacobini, Paolo] Univ Turin, Dept Human & Anim Biol, I-10123 Turin, Italy. [Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Giacobini, P (reprint author), INSERM, U837, Jean Pierre Aubert Res Ctr, Unit 837, Pl Verdun, F-59045 Lille, France. EM paolo.giacobini@inserm.fr RI Prevot, Vincent/E-5720-2016; Giacobini, Paolo/P-5451-2015 OI Giacobini, Paolo/0000-0002-3075-1441 FU Compagnia di San Paolo, Turin, Italy [2008.1224]; Institut National de la Sante et de la Recherche Medicale, Inserm, France [U837]; Agence Nationale de la Recherche, ANR, France [ANR-2010-JCJC-1404-01, ANR-09-BLAN-0267]; University of Lille 2, Lille, France (Appel a Projets du Conseil Scientifique de l'Universite Lille 2); Intramural Research Program of the National Institute of Neurological Disorders and Stroke-National Institutes of Health FX This work was supported by Compagnia di San Paolo, Turin, Italy (grant number 2008.1224 to P. G.); the Institut National de la Sante et de la Recherche Medicale, Inserm, France (grant number U837); Agence Nationale de la Recherche, ANR, France (grant numbers ANR-2010-JCJC-1404-01 to P. G. and ANR-09-BLAN-0267 to V. P.); the University of Lille 2, Lille, France (Appel a Projets du Conseil Scientifique de l'Universite Lille 2 to P. G.); and the Intramural Research Program of the National Institute of Neurological Disorders and Stroke-National Institutes of Health. We thank Meryem Tardivel of the Imaging Core Facility of IFR114 of the University of Lille 2 for technical assistance, Julien Devassine and Delphine Cappe (Animal facility-IFR114) for the maintenance of transgenic mouse lines, the histology facility at University of Lille 2, Andre Defossez and Claude-Alain Maurage for the histological analyses of specimens, and Nathalie Jouy from the cytometry core facilities (BioImaging Center Lille Nord de France-IFR114). NR 65 TC 13 Z9 13 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 21 PY 2012 VL 32 IS 47 BP 16992 EP 17002 DI 10.1523/JNEUROSCI.3057-12.2012 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 041SF UT WOS:000311420800042 PM 23175850 ER PT J AU Zafonte, RD Bagiella, E Ansel, BM Novack, TA Friedewald, WT Hesdorffer, DC Timmons, SD Jallo, J Eisenberg, H Hart, T Ricker, JH Diaz-Arrastia, R Merchant, RE Temkin, NR Melton, S Dikmen, SS AF Zafonte, Ross D. Bagiella, Emilia Ansel, Beth M. Novack, Thomas A. Friedewald, William T. Hesdorffer, Dale C. Timmons, Shelly D. Jallo, Jack Eisenberg, Howard Hart, Tessa Ricker, Joseph H. Diaz-Arrastia, Ramon Merchant, Randall E. Temkin, Nancy R. Melton, Sherry Dikmen, Sureyya S. TI Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic Brain Injury Citicoline Brain Injury Treatment Trial (COBRIT) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MILD HEAD-INJURY; CDP-CHOLINE; MULTIPLE OUTCOMES; CLINICAL-TRIALS; FOLLOW-UP; HIPPOCAMPAL; SYMPTOMS; RECOVERY; TBI AB Context Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury. Objective To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI. Design, Setting, and Patients The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe. Intervention Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. Main Outcome Measures Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects. Results Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]). Conclusion Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status. C1 [Zafonte, Ross D.] Harvard Univ, Spaulding Rehabil Hosp Network, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Zafonte, Ross D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bagiella, Emilia] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Ansel, Beth M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Novack, Thomas A.; Melton, Sherry] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Friedewald, William T.] Columbia Univ, Dept Biostat, New York, NY USA. [Hesdorffer, Dale C.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Timmons, Shelly D.] Geisinger Med Ctr, Dept Neurosurg, Danville, PA 17822 USA. [Jallo, Jack] Thomas Jefferson Univ, Div Neurotrauma & Crit Care, Philadelphia, PA 19107 USA. [Eisenberg, Howard] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Hart, Tessa] Moss Rehabil Res Inst, Philadelphia, PA USA. [Ricker, Joseph H.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Rockville, MD USA. [Merchant, Randall E.] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA 23284 USA. [Temkin, Nancy R.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Zafonte, RD (reprint author), Harvard Univ, Spaulding Rehabil Hosp Network, Sch Med, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM rzafonte@partners.org FU National Institute of Child Health and Human Development at Temple University [U01HD042738]; National Institute of Child Health and Human Development at University of Alabama at Birmingham [U01HD042687]; National Institute of Child Health and Human Development at University of Maryland [U01HD042736]; National Institute of Child Health and Human Development at University of Pittsburgh [U01HD042678]; National Institute of Child Health and Human Development at University of Tennessee Health Sciences Center [U01HD042686]; National Institute of Child Health and Human Development at University of Texas Southwestern [U01HD042652]; National Institute of Child Health and Human Development grants at University of Washington [U01HD042653]; National Institute of Child Health and Human Development grants at Virginia Commonwealth University [U01HD042689]; National Institute of Child Health and Human Development grants at Columbia University [Columbia University (U01HD042823] FX This study was supported by National Institute of Child Health and Human Development grants at the following institutions: Temple University (U01HD042738); University of Alabama at Birmingham (U01HD042687); University of Maryland (U01HD042736); University of Pittsburgh (U01HD042678); University of Tennessee Health Sciences Center (U01HD042686); University of Texas Southwestern (U01HD042652); University of Washington (U01HD042653); Virginia Commonwealth University (U01HD042689); and Columbia University (U01HD042823). Ferrer Grupo provided the citicoline and identical placebo used in the study. NR 40 TC 45 Z9 47 U1 4 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 21 PY 2012 VL 308 IS 19 BP 1993 EP 2000 DI 10.1001/jama.2012.13256 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 040AQ UT WOS:000311291400023 PM 23168823 ER PT J AU Franco, EL de Sanjose, S Broker, TR Stanley, MA Chevarie-Davis, M Isidean, SD Schiffman, M AF Franco, Eduardo L. de Sanjose, Silvia Broker, Thomas R. Stanley, Margaret A. Chevarie-Davis, Myriam Isidean, Sandra D. Schiffman, Mark TI Human Papillomavirus and Cancer Prevention: Gaps in Knowledge and Prospects for Research, Policy, and Advocacy SO VACCINE LA English DT Review DE HPV; cancer prevention; policy; advocacy ID CERVICAL-CANCER; METHYLATION AB The recognition that human papillomavirus (HPV) infection is the central, necessary cause of cervical cancer paved the way to new fronts of prevention via improved screening methods and HPV vaccination. Much has been learned in all fronts, from the molecular basis of our understanding of how HPV causes disease to the health economics of preventive strategies at the individual and population levels. Progress in other areas of cancer control has yet to show the same multi- and trans-disciplinary gains seen in research on HPV-associated malignancies, which is one of the unequivocal success stories in disease prevention. Yet, as an embarrassment of riches, much more research is needed to fill the gaps in knowledge that remain before we are able to reap the benefits from the knowledge translation from all fronts. Public health research on setting-specific implementation of HPV-based preventive strategies and more concerted advocacy to counter barriers facing the adoption of these strategies are likely to yield major dividends in reducing the burden of HPV-associated diseases. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Franco, Eduardo L.; Chevarie-Davis, Myriam; Isidean, Sandra D.] McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada. [de Sanjose, Silvia] Inst Catala Oncol, CERP, Unit Infect & Canc UNIC, Lhospitalet De Llobregat, Barcelona, Spain. [Broker, Thomas R.] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL USA. [Stanley, Margaret A.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Schiffman, Mark] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Franco, EL (reprint author), McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada. EM eduardo.franco@mcgill.ca RI de Sanjose Llongueras, Silvia/H-6339-2014; OI Franco, Eduardo/0000-0002-4409-8084 FU European Commission [HEALTH-F3-2010-242061, HEALTH-F2-2011-282562]; Instituto de Salud Carlos III (Spanish Government) [FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) [AGAUR 2005SGR00695, AGAUR 2009SGR126]; Merck; GlaxoSmithKline; Sanofi Pasteur MSD; Qiagen; GSK FX The work was partially supported by public grants from the European Commission (7th Framework Programme grants HEALTH-F3-2010-242061, PREHDICT and HEALTH-F2-2011-282562, HPV AHEAD), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126), who had no role in data collection, analysis or interpretation of results.; EF: Has served as occasional consultant to companies involved with HPV vaccines (Merck and GSK) and with HPV diagnostics (Roche, Gen-Probe, BD). He has received an unrestricted grant from Merck.; SdS: Institutional support: HPV vaccine trials and epidemiological studies sponsored by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to conferences/symposia/meetings are occasionally granted by either GlaxoSmithKline, Sanofi Pasteur MSD or Qiagen.; MS: Has received free CareHPV equipment and reagents for an independent analysis of low-cost HPV testing in Africa. He has also received free specimen testing from Roche for epidemiologic projects. He was the NCI co-Project Officer and co-Medical Monitor of an independent evaluation of GSK HPV vaccine, for which GSK donated vaccine and financed the regulatory components. NR 10 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2012 VL 30 SU 5 BP F175 EP F182 DI 10.1016/j.vaccine.2012.06.092 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 063CX UT WOS:000312974900019 PM 23199961 ER PT J AU Gillison, ML Alemany, L Snijders, PJF Chaturvedi, A Steinberg, BM Schwartz, S Castellsague, X AF Gillison, Maura L. Alemany, Laia Snijders, Peter J. F. Chaturvedi, Anil Steinberg, Bettie M. Schwartz, Steve Castellsague, Xavier TI Human Papillomavirus and Diseases of the Upper Airway: Head and Neck Cancer and Respiratory Papillomatosis SO VACCINE LA English DT Review DE Oropharynx; Papillomatosis; Head and neck cancer; HPV; Epidemiology; Causality ID SQUAMOUS-CELL-CARCINOMA; ACTIVE HUMAN-PAPILLOMAVIRUS; ORAL HPV INFECTION; P53 CODON-72 POLYMORPHISM; GENE-EXPRESSION PROFILES; PHASE-III TRIAL; OROPHARYNGEAL CANCER; RISK-FACTORS; JUVENILE-ONSET; TONSILLAR CARCINOMA AB Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression to be necessary for the initiation and maintenance of the malignant phenotype of these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for secondary prevention with HPV detection. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. (C) 2012 Published by Elsevier Ltd. C1 [Gillison, Maura L.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Alemany, Laia; Castellsague, Xavier] Catalan Inst Oncol ICO, CERP, Unit Infect & Canc UNIC, Lhospitalet De Llobregat, Barcelona, Spain. [Snijders, Peter J. F.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Chaturvedi, Anil] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Steinberg, Bettie M.] Feinstein Inst Med Res, Manhasset, NY USA. [Schwartz, Steve] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. RP Gillison, ML (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. EM Maura.gillison@osumc.edu RI Castellsague Pique, Xavier/N-5795-2014; Chaturvedi, Anil/J-2024-2015; Steinberg, Bettie/K-3414-2012 OI Castellsague Pique, Xavier/0000-0002-0802-3595; Chaturvedi, Anil/0000-0003-2696-8899; Steinberg, Bettie/0000-0003-2372-8099 FU European Commission [HEALTH-F3-2010-242061, HEALTH-F2-2011-282562]; Instituto de Salud Carlos III (Spanish Government) [FIS FIS PI10/02995, FIS PI08/1535, FIS PI11/02096, FIS PI11/02104, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) [AGAUR 2005SGR00695, AGAUR 2009SGR126]; Merck; GlaxoSmithKline; Sanofi Pasteur MSD; Qiagen FX The work was partially supported by public grants from the European Commission (7th Framework Programme grants HEALTH-F3-2010-242061, PREHDICT and HEALTH-F2-2011-282562, HPV AHEAD), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS FIS PI10/02995, FIS PI08/1535, FIS PI11/02096, FIS PI11/02104, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126), who had no role in data collection, analysis or interpretation of results.; MLG: Has had scientific collaborations and has received research funding from Merck. She has acted as a consultant for Merck.; XC: Institutional support: HPV vaccine trials and epidemiological studies sponsored by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to scientific meetings and honorarium for consultancy are occasionally granted by either GlaxoSmithKline, Merck, Sanofi Pasteur MSD.; LA: Institutional support: HPV vaccine trials and epidemiological studies sponsored by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to conferences occasionally granted by Merck and Sanofi Pasteur MSD. NR 161 TC 82 Z9 82 U1 1 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2012 VL 30 SU 5 BP F34 EP F54 DI 10.1016/j.vaccine.2012.05.070 PG 21 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 063CX UT WOS:000312974900006 PM 23199965 ER PT J AU Moscicki, AB Schiffman, M Burchell, A Albero, G Giuliano, AR Goodman, MT Kjaer, SK Palefsky, J AF Moscicki, Anna-Barbara Schiffman, Mark Burchell, Ann Albero, Ginesa Giuliano, Anna R. Goodman, Marc T. Kjaer, Susanne K. Palefsky, Joel TI Updating the Natural History of Human Papillomavirus and Anogenital Cancers SO VACCINE LA English DT Review DE HPV; Natural history; Transmission; Male infections; Anal disease ID CERVICAL INTRAEPITHELIAL NEOPLASIA; RISK HUMAN-PAPILLOMAVIRUS; HAWAII HPV COHORT; POPULATION-BASED COHORT; YOUNG-WOMEN; PERSISTENT INFECTIONS; HETEROSEXUAL COUPLES; UNIVERSITY-STUDENTS; SEXUAL-BEHAVIORS; GRADE 2/3 AB This chapter addresses the natural history of anogenital human papillomavirus (HPV) infection. Cervical infections are the best understood HPV infection. Cervical HPV persistence is the known necessary event for the development of cervical cancer. New infections appearing at any age are benign unless they persist. Several long-term natural history studies have now shed light on the very low risk of cervical intraepithelial neoplasia (CIN) 3+ in women past the peak of HPV acquisition (e.g., 30 or older) who are HPV-negative or clear their HPV. Although data on transmission of HPV are finally emerging, rates of transmission between heterosexual couples vary widely among studies. Factors that affect the calculations of these rates include a) intervals between testing points, b) rates of concordance or discordance at baseline, and c) difficulty in defining established infections versus contamination. Both cervix to anus and anus to cervix autoinoculation in the same woman appears to be quite common. Whether either site serves as a long-term reservoir is unknown. Studies show that anal infections in women and in men who have sex with men are quite common with cumulative rates up to 70-90%. Similarly, clearance of anal HPV is also common, with few individuals showing persistence unless they are human immunodeficiency virus (HIV)-infected. HIV strongly influences the development of anal intraepithelial neoplasia (AIN). The few studies on the natural history of AIN in HIV-infected men suggest that high-grade AIN is a precursor to invasive anal cancer. Although no natural history studies of AIN are available in women, women with other HPV-associated lesions, including CIN3+ and vulvar cancer, have higher rates of anal cancer. Data on the natural history of HPV of the male genitalia are also emerging, although penile intraepithelial neoplasia is poorly understood. Cumulative rates of HPV are extremely high in men and risks are associated with sexual behavior. Unlike women, prevalence rates are steady across all ages, suggesting that men do not develop protection against reinfection. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, Div Adolescent Med, San Francisco, CA 94143 USA. [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Burchell, Ann] Ontario HIV Treatment Network, Toronto, ON, Canada. [Burchell, Ann] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Burchell, Ann] McGill Univ, Dept Oncol, Div Canc Epidemiol, Montreal, PQ, Canada. [Albero, Ginesa] Catalan Inst Oncol ICO, CERP, Unit Infect & Canc UNIC, Barcelona, Spain. [Albero, Ginesa] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain. [Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL USA. [Goodman, Marc T.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Kjaer, Susanne K.] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Kjaer, Susanne K.] Univ Copenhagen, Rigshosp, Juliane Marie Ctr, Dept Gynecol & Obstet, DK-1168 Copenhagen, Denmark. [Palefsky, Joel] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA USA. RP Moscicki, AB (reprint author), Univ Calif San Francisco, Dept Pediat, Div Adolescent Med, San Francisco, CA 94143 USA. EM moscickia@peds.ucsf.edu RI Albero, Ginesa/G-7248-2015; OI Albero, Ginesa/0000-0002-9400-1914; Kjaer, Susanne/0000-0002-8347-1398 FU US Public Health Service (National Cancer Institute, National Institutes of Health, Department of Health and Human Services) [R37 CA51323, NIH R01 CA098803, R01 CA077318, R01 CA 88739, R01 CA54053]; Canadian Institutes of Health Research; European Commission [HEALTH-F3-2010-242061]; Instituto de Salud Carlos III [FIS PI08/1535, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio, d'Ajuts Universitaris i de Recerca [AGAUR 2005SGR00695, AGAUR 2009SGR126]; GenProbe; Bectin Dickinson; Merck Canada Ltd.; Qiagen; GlaxoSmithKline; Merck; Sanofi Pasteur MSD; Roche; GSK; Merck Co., Inc. FX Dr. Anna-Barbara Moscicki's work is supported by US Public Health Service grant R37 CA51323 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services). Dr. Ann Burchell's work is funded by a Canadian Institutes of Health Research New Investigator award. Ginesa Albero's work is partially supported by public grants from the European Commission (7th Framework Programme grant HEALTH-F3-2010-242061, PREHDICT), from the Instituto de Salud Carlos III (grants FIS PI08/1535, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP), and from the Agencia de Gestio, d'Ajuts Universitaris i de Recerca (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126). Dr. Anna Giuliano's work is supported by US Public Health Service grant NIH R01 CA098803 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services). Dr. Marc Goodman's work is supported by US Public Health Service grant R01 CA077318 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services). Dr. Joel Palefsky's work is supported by US Public Health Service grants R01 CA 88739 and R01 CA54053 (National Cancer Institute, National Institutes of Health, Department of Health and Human Services). The authors would like to thank Anthony Kung for manuscript preparation.; ABM serves as an advisory board member for Merck and receives support for sexually transmitted disease testing from GenProbe. She has also received travel funds and an honorarium for speaking at a symposium supported by Bectin Dickinson.; In the past, AB received an unrestricted research grant, speaker fees, and media consultant fees from Merck Canada Ltd., but not since 2010.; GA: Institutional support: Vaccine trials organized by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to conferences/meetings are occasionally granted by either GlaxoSmithKline, Merck, Sanofi Pasteur MSD, Roche or Qiagen.; ARG is on the Speakers Bureau of Merck & Co., Inc., an advisor to Merck & Co., Inc., and has received research grant support from both GSK and Merck & Co., Inc.; SKK received lecture fees, advisory board fees, and research grants through her institution from Merck and Sanofi Pasteur MSD. NR 86 TC 104 Z9 106 U1 3 U2 37 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2012 VL 30 SU 5 BP F24 EP F33 DI 10.1016/j.vaccine.2012.05.089 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 063CX UT WOS:000312974900005 PM 23199964 ER PT J AU Schiller, JT Castellsague, X Garland, SM AF Schiller, John T. Castellsague, Xavier Garland, Suzanne M. TI A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines SO VACCINE LA English DT Review DE HPV; Prophylactic vaccine; Virus-like particle; Gardasil (R); Cervarix (R); Clinical trials; Cervical cancer; Genital warts; CIN; VIN; VaIN ID (HPV)-16/18 AS04-ADJUVANTED VACCINE; QUADRIVALENT HPV VACCINE; CERVICAL-CANCER VACCINE; BLIND PATRICIA TRIAL; VIRUS-LIKE PARTICLES; OF-STUDY ANALYSIS; AGED 18-45 YEARS; YOUNG-WOMEN; INTRAEPITHELIAL NEOPLASIA; POOLED ANALYSIS AB End of study analyses of the phase Ill trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil (R) (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix (R) (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naive to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil (R) also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil (R) protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix (R) protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as high value public health interventions and justify their widespread implementation to prevent anogenital HPV infections and their associated neoplasia. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Published by Elsevier Ltd. C1 [Schiller, John T.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Castellsague, Xavier] Inst Catala Oncol, Unit Infect & Canc UNIC, CERP, Lhospitalet De Llobregat, Barcelona, Spain. [Garland, Suzanne M.] Royal Womens Hosp, Reg World Hlth Org Human Papillomavirus Lab, Dept Microbiol & Infect Dis, Melbourne, Vic, Australia. [Garland, Suzanne M.] Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic 3010, Australia. [Garland, Suzanne M.] Royal Childrens Hosp, Dept Microbiol, Parkville, Vic, Australia. [Garland, Suzanne M.] Murdoch Childrens Res Inst, Murdoch, WA, Australia. RP Schiller, JT (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM schillej@mail.nih.gov RI Castellsague Pique, Xavier/N-5795-2014 OI Castellsague Pique, Xavier/0000-0002-0802-3595 FU European Commission [HEALTH-F3-2010-242061]; Instituto de Salud Carlos III (Spanish Government) [FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) [AGAUR 2005SGR00695, AGAUR 2009SGR126]; GlaxoSmithKline; Merck; Sanofi Pasteur MSD; Qiagen; Commonwealth Serum Laboratories; Merck Co. FX The work was partially supported by public grants from the European Commission (7th Framework Programme grant HEALTH-F3-2010-242061, PREHDICT), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agencia de Gestio d'Ajuts Universitaris i de Recerca - Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695 and AGAUR 2009SGR126), who had no role in data collection, analysis or interpretation of results.; XC: Institutional support: HPV vaccine trials and epidemiological studies sponsored by GlaxoSmithKline, Merck and Sanofi Pasteur MSD. Screening and HPV testing trials partially supported by Qiagen. Personal support: Travel grants to scientific meetings and honorarium for consultancy are occasionally granted by either GlaxoSmithKline, Merck, Sanofi Pasteur MSD.; SMG: Has received advisory board fees and grant support from Commonwealth Serum Laboratories and GlaxoSmithKline, and lecture and consultancy fees from Merck & Co. She has received grant support through her institution from Merck & Co. and GlaxoSmithKline to do clinical trials for HPV/cervical cancer vaccines. NR 88 TC 227 Z9 235 U1 20 U2 115 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2012 VL 30 SU 5 BP F123 EP F138 DI 10.1016/j.vaccine.2012.04.108 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 063CX UT WOS:000312974900014 PM 23199956 ER PT J AU Stanley, M Pinto, LA Trimble, C AF Stanley, Margaret Pinto, Ligia A. Trimble, Connie TI Human Papillomavirus Vaccines - Immune Responses SO VACCINE LA English DT Review DE HPV; virus like particle; VLP; antibody; B cells; L1 protein; L2 protein; cell mediated immunity ID VIRUS-LIKE PARTICLES; HPV VACCINATION PROGRAM; INTRAEPITHELIAL NEOPLASIA; ANTIBODY-RESPONSES; NATURAL-HISTORY; YOUNG-WOMEN; T-CELLS; INFECTION; L1; TYPE-16 AB Prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines are highly effective. The available evidence suggests that neutralising antibody is the mechanism of protection. However, despite the robust humoral response elicited by VLP vaccines, there is no immune correlate, no minimum level of antibody, or any other immune parameter, that predicts protection against infection or disease. The durability of the antibody response and the importance of antibody isotype, affinity and avidity for vaccine effectiveness are discussed. Once infection and disease are established, then cellular immune responses are essential to kill infected cells. These are complex processes and understanding the local mucosal immune response is a prerequisite for the rational design of therapeutic HPV vaccines. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. (C) 2012 Published by Elsevier Ltd. C1 [Stanley, Margaret] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Pinto, Ligia A.] NCI Frederick, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Trimble, Connie] Johns Hopkins Univ Hosp, Dept Obstet Gynecol, Baltimore, MD 21287 USA. [Trimble, Connie] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. [Trimble, Connie] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. RP Stanley, M (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM mas1001@cam.ac.uk NR 53 TC 55 Z9 56 U1 3 U2 28 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2012 VL 30 SU 5 BP F83 EP F87 DI 10.1016/j.vaccine.2012.04.106 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 063CX UT WOS:000312974900009 PM 23199968 ER PT J AU Schotte, F Cho, HS Kaila, VRI Kamikubo, H Dashdorj, N Henry, ER Graber, TJ Henning, R Wulff, M Hummer, G Kataoka, M Anfinrud, PA AF Schotte, Friedrich Cho, Hyun Sun Kaila, Ville R. I. Kamikubo, Hironari Dashdorj, Naranbaatar Henry, Eric R. Graber, Timothy J. Henning, Robert Wulff, Michael Hummer, Gerhard Kataoka, Mikio Anfinrud, Philip A. TI Watching a signaling protein function in real time via 100-ps time-resolved Laue crystallography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE time-resolved X-ray diffraction; photoreceptor; light sensor ID PHOTOACTIVE YELLOW PROTEIN; HALOPHILIC PHOTOTROPHIC BACTERIUM; ECTOTHIORHODOSPIRA-HALOPHILA; PHOTOCYCLE INTERMEDIATE; PHOTORECEPTOR PROTEIN; PH-DEPENDENCE; QUANTUM YIELD; E46Q MUTANT; SPECTROSCOPY; KINETICS AB To understand how signaling proteins function, it is crucial to know the time-ordered sequence of events that lead to the signaling state. We recently developed on the BioCARS 14-IDB beamline at the Advanced Photon Source the infrastructure required to characterize structural changes in protein crystals with near-atomic spatial resolution and 150-ps time resolution, and have used this capability to track the reversible photocycle of photoactive yellow protein (PYP) following trans-to-cis photoisomerization of its p-coumaric acid (pCA) chromophore over 10 decades of time. The first of four major intermediates characterized in this study is highly contorted, with the pCA carbonyl rotated nearly 90 out of the plane of the phenolate. A hydrogen bond between the pCA carbonyl and the Cys69 backbone constrains the chromophore in this unusual twisted conformation. Density functional theory calculations confirm that this structure is chemically plausible and corresponds to a strained cis intermediate. This unique structure is short-lived (similar to 600 ps), has not been observed in prior cryocrystallography experiments, and is the progenitor of intermediates characterized in previous nanosecond time-resolved Laue crystallography studies. The structural transitions unveiled during the PYP photocycle include trans/cis isomerization, the breaking and making of hydrogen bonds, formation/relaxation of strain, and gated water penetration into the interior of the protein. This mechanistically detailed, near-atomic resolution description of the complete PYP photocycle provides a framework for understanding signal transduction in proteins, and for assessing and validating theoretical/computational approaches in protein biophysics. C1 [Schotte, Friedrich; Cho, Hyun Sun; Kaila, Ville R. I.; Dashdorj, Naranbaatar; Henry, Eric R.; Hummer, Gerhard; Anfinrud, Philip A.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Kamikubo, Hironari; Kataoka, Mikio] Nara Inst Sci & Technol, Grad Sch Mat Sci, Nara 6300192, Japan. [Graber, Timothy J.; Henning, Robert] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA. [Wulff, Michael] European Synchrotron Radiat Facil, Expt Div, F-38043 Grenoble, France. RP Anfinrud, PA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM anfinrud@nih.gov RI Hummer, Gerhard/A-2546-2013; Henry, Eric/J-3414-2013; Kataoka, Mikio/H-4402-2011 OI Hummer, Gerhard/0000-0001-7768-746X; Henry, Eric/0000-0002-5648-8696; FU National Center for Research Resources [5P41RR007707]; National Institute of General Medical Sciences from NIH [8P41GM103543]; US DOE [DE-AC02-06CH11357]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH; European Molecular Biology Organization FX We thank Drs. Keith Moffat, Vukica Srajer, Hyocherl Ihee, and Yang Ouk Jung for their contributions to earlier, collaborative time-resolved Laue studies of PYP; Bernard Howder, Jr., for machining many of the components required for this study; the Biowulf cluster at the National Institutes of Health (NIH) for computer time; and the Advanced Photon Source undulator group for reconfiguring and installing two short-period undulators on the 14-IDB BioCARS beamline. Use of the BioCARS Sector 14 was supported by National Center for Research Resources Grant 5P41RR007707 and National Institute of General Medical Sciences Grant 8P41GM103543 from NIH. Use of the Advanced Photon Source, an Office of Science User Facility operated for the US Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by US DOE Contract DE-AC02-06CH11357. The time-resolved setup at Sector 14 was funded in part through collaboration with P.A.A. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. V.R.I.K. is the recipient of a European Molecular Biology Organization Long-Term Fellowship. VMD was developed by the Theoretical and Computational Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. NR 36 TC 63 Z9 63 U1 2 U2 75 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2012 VL 109 IS 47 BP 19256 EP 19261 DI 10.1073/pnas.1210938109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 049PZ UT WOS:000311997200052 PM 23132943 ER PT J AU Furuta, K Ishido, S Roche, PA AF Furuta, Kazuyuki Ishido, Satoshi Roche, Paul A. TI Encounter with antigen-specific primed CD4 T cells promotes MHC class II degradation in dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-cell activation; protein aggregation ID PEPTIDE COMPLEXES; IN-VIVO; SURFACE; MOLECULES; RAFTS; INTERNALIZATION; UBIQUITINATION; GLYCOPROTEINS; COMPARTMENTS; CHOLESTEROL AB Major histocompatibility complex class II molecules (MHC-II) on antigen presenting cells (APCs) engage the TCR on antigen-specific CD4 T cells, thereby providing the specificity required for T cell priming and the induction of an effective immune response. In this study, we have asked whether antigen-loaded dendritic cells (DCs) that have been in contactwith antigen-specific CD4 T cells retain the ability to stimulate additional naive T cells. We show that encounter with antigen-specific primed CD4 T cells induces the degradation of surface MHC-II in antigen-loaded DCs and inhibits the ability of these DCs to stimulate additional naive CD4 T cells. Cross-linking with MHC-II mAb as a surrogate for T-cell engagement also inhibits APC function and induces MHC-II degradation by promoting the clustering of MHC-II present in lipid raft membrane microdomains, a process that leads to MHC-II endocytosis and degradation in lysosomes. Encounter of DCs with antigen-specific primed T cells or engagement of MHC-II with antibodies promotes the degradation of both immunologically relevant and irrelevant MHC-II molecules. These data demonstrate that engagement of MHC-II on DCs after encounter with antigen-specific primed CD4 T cells promotes the down-regulation of cell surface MHC-II in DCs, thereby attenuating additional activation of naive CD4 T cells by these APCs. C1 [Furuta, Kazuyuki; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Ishido, Satoshi] RIKEN Res Ctr Allergy & Immunol, Lab Infect Immun, Yokohama, Kanagawa 2300045, Japan. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM rochepa@mail.nih.gov FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science; National Institutes of Health FX We thank our many colleagues for the gifts of antibodies used in this study. This work was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (S. I.), the Japan Society for the Promotion of Science (S. I.), and the Intramural Research Program of the National Institutes of Health (P.A.R.). NR 33 TC 8 Z9 8 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2012 VL 109 IS 47 BP 19380 EP 19385 DI 10.1073/pnas.1213868109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 049PZ UT WOS:000311997200073 PM 23129633 ER PT J AU Baum, BJ Alevizos, I Zheng, CY Cotrim, AP Liu, SY McCullagh, L Goldsmith, CM Burbelo, PD Citrin, DE Mitchell, JB Nottingham, LK Rudy, SF Van Waes, C Whatley, MA Brahim, JS Chiorini, JA Danielides, S Turner, RJ Patronas, NJ Chen, CC Nikolov, NP Illei, GG AF Baum, Bruce J. Alevizos, Ilias Zheng, Changyu Cotrim, Ana P. Liu, Shuying McCullagh, Linda Goldsmith, Corinne M. Burbelo, Peter D. Citrin, Deborah E. Mitchell, James B. Nottingham, Liesl K. Rudy, Susan F. Van Waes, Carter Whatley, Millie A. Brahim, Jaime S. Chiorini, John A. Danielides, Stamatina Turner, R. James Patronas, Nicholas J. Chen, Clara C. Nikolov, Nikolay P. Illei, Gabor G. TI Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; radiation damage; salivary glands; dry mouth; water channel ID GENE-TRANSFER VECTORS; INCREASED FLUID SECRETION; CYSTIC-FIBROSIS PATIENTS; PIG PAROTID-GLANDS; PHASE-I; RECOMBINANT ADENOVIRUS; LOCAL-DELIVERY; INDIVIDUALS; XEROSTOMIA; MANAGEMENT AB No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 x 10(7) to 5.8 x 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 x 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects. C1 [Baum, Bruce J.; Alevizos, Ilias; Zheng, Changyu; Cotrim, Ana P.; Liu, Shuying; McCullagh, Linda; Goldsmith, Corinne M.; Chiorini, John A.; Danielides, Stamatina; Turner, R. James; Nikolov, Nikolay P.; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Bethesda, MD 20892 USA. [Citrin, Deborah E.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nottingham, Liesl K.; Rudy, Susan F.; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Whatley, Millie A.; Chen, Clara C.] NIH, Nucl Med Sect, Bethesda, MD 20892 USA. [Patronas, Nicholas J.] NIH, Sect Neuroradiol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Brahim, Jaime S.] Univ Maryland, Dept Oral Maxillofacial Surg, Baltimore, MD 21201 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM bbaum@mail.nih.gov FU The Intramural Research Program of the National Institute of Dental and Craniofacial Research FX We thank Dr. Jane Atkinson for many helpful suggestions during this study. We thank Dr. Sarfaraz Hasni for help in the medical evaluation of several subjects; Janet Rowan, RN for assistance with many subjects; multiple physicians, for referring their patients to us; and the 11 study subjects, who gave so generously of their time and themselves, enabling this trial to be conducted. The Intramural Research Program of the National Institute of Dental and Craniofacial Research supported this study. NR 27 TC 54 Z9 54 U1 1 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2012 VL 109 IS 47 BP 19403 EP 19407 DI 10.1073/pnas.1210662109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 049PZ UT WOS:000311997200077 PM 23129637 ER PT J AU Lockwood, WW Zejnullahu, K Bradner, JE Varmus, H AF Lockwood, William W. Zejnullahu, Kreshnik Bradner, James E. Varmus, Harold TI Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug development; chromatin ID BROMODOMAIN INHIBITION; C-MYC; TRANSCRIPTION; TUMORIGENESIS; CHROMATIN; LEUKEMIA; BRD4; EXPRESSION; FAMILY; AP-1 AB Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate transcription of target genes. Inhibitors targeting the activity of BET proteins have shown potent antiproliferative effects in hematological cancers through the suppression of c-MYC and downstream target genes. However, as the epigenetic landscape of a cell varies drastically depending on lineage, transcriptional coactivators such as BETs would be expected to have different targets in cancers derived from different cells of origin, and this may influence the activity and mechanism of action of BET inhibitors. To test this hypothesis, we treated a panel of lung adenocarcinoma (LAC) cell lines with the BET inhibitor JQ1 and found that a subset is acutely susceptible to BET inhibition. In contrast to blood tumors, we showthat LAC cells are inhibited by JQ1 through a mechanism independent of cMYC down-regulation. Through gene expression profiling, we discovered that the oncogenic transcription factor FOSL1 and its targets are suppressed by JQ1 in a dose-dependant manner. Knockdown of BRD4 also decreased FOSL1 levels, and inhibition of FOSL1 phenocopied the effects of JQ1 treatment, suggesting that loss of this transcription factor may be partly responsible for the cytotoxic effects of BET inhibition in LAC cells, although ectopic expression of FOSL1 alone did not rescue the phenotype. Together, these findings suggest that BET inhibitors may be useful in solid tumors and that cell-lineage-specific differences in transcriptional targets of BETs may influence the activity of inhibitors of these proteins in different cancer types. C1 [Lockwood, William W.; Zejnullahu, Kreshnik; Varmus, Harold] NHGRI, Canc Biol & Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Zejnullahu, Kreshnik] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lockwood, WW (reprint author), NHGRI, Canc Biol & Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM william.lockwood@nih.gov; harold.varmus@nih.gov FU National Institutes of Health Intramural Research Program; Canadian Institutes of Health Research Jean-Francois Saint Denis Fellowship in Cancer Research FX We thank Nancy Colburn and Matthew Young for providing the pFB-FRA1 construct. This work was funded by the National Institutes of Health Intramural Research Program. W. W. L. is supported by the Canadian Institutes of Health Research Jean-Francois Saint Denis Fellowship in Cancer Research. NR 24 TC 120 Z9 120 U1 4 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2012 VL 109 IS 47 BP 19408 EP 19413 DI 10.1073/pnas.1216363109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 049PZ UT WOS:000311997200078 PM 23129625 ER PT J AU Lussier, MP Herring, BE Nasu-Nishimura, Y Neutzner, A Karbowski, M Youle, RJ Nicoll, RA Roche, KW AF Lussier, Marc P. Herring, Bruce E. Nasu-Nishimura, Yukiko Neutzner, Albert Karbowski, Mariusz Youle, Richard J. Nicoll, Roger A. Roche, Katherine W. TI Ubiquitin ligase RNF167 regulates AMPA receptor-mediated synaptic transmission SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampus; glutamate receptor; GluA2 ID ACTIVITY-DEPENDENT UBIQUITINATION; VENTRAL NERVE CORD; GLUTAMATE RECEPTORS; PROTEASOME SYSTEM; C-ELEGANS; DEGRADATION; PROTEINS; ABUNDANCE; NEURONS AB AMPA receptors (AMPARs) mediate the majority of fast excitatory neurotransmission, and their density at postsynaptic sites determines synaptic strength. Ubiquitination is a posttranslational modification that dynamically regulates the synaptic expression of many proteins. However, very few of the ubiquitinating enzymes implicated in the process have been identified. In a screen to identify transmembrane RING domain-containing E3 ubiquitin ligases that regulate surface expression of AMPARs, we identified RNF167. Predominantly lysosomal, a subpopulation of RNF167 is located on the surface of cultured neurons. Using a RINGmutant RNF167 or a specific shRNA to eliminate endogenous RNF167, we demonstrate that AMPAR surface expression increases in hippocampal neurons with disrupted RNF167 activity and that RNF167 is involved in activity-dependent ubiquitination of AMPARs. In addition, RNF167 regulates synaptic AMPAR currents, whereas synaptic NMDAR currents are unaffected. Therefore, our study identifies RNF167 as a selective regulator of AMPAR-mediated neurotransmission and expands our understanding of how ubiquitination dynamically regulates excitatory synapses. C1 [Herring, Bruce E.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. [Herring, Bruce E.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Lussier, Marc P.; Nasu-Nishimura, Yukiko; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA. [Neutzner, Albert; Karbowski, Mariusz; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. EM nicoll@cmp.ucsf.edu; rochek@ninds.nih.gov OI Neutzner, Albert/0000-0001-9254-5558; Roche, Katherine/0000-0001-7282-6539 FU The NINDS Intramural Research Program; National Institute of Mental Health; Le Fond de la Recherche en Sante du Quebec; Brain and Behavior Research Foundation FX We thank John D. Badger II for technical assistance, Dr. Dragan Maric for advice and expertise with the FACS analysis, and the National Institute of Neurological Disorders and Stroke (NINDS) DNA sequencing facility. The NINDS Intramural Research Program (K. W. R. and R.J.Y.) and the National Institute of Mental Health (R.A.N.) supported this research. M. P. L. is the recipient of a postdoctoral fellowship from Le Fond de la Recherche en Sante du Quebec, and B. E. H. receives support from the Brain and Behavior Research Foundation. NR 33 TC 23 Z9 24 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2012 VL 109 IS 47 BP 19426 EP 19431 DI 10.1073/pnas.1217477109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 049PZ UT WOS:000311997200081 PM 23129617 ER PT J AU Robertson, CE Martin, A Baker, CI Baron-Cohen, S AF Robertson, Caroline E. Martin, Alex Baker, Chris I. Baron-Cohen, Simon TI Atypical Integration of Motion Signals in Autism Spectrum Conditions SO PLOS ONE LA English DT Article ID DORSAL VISUAL PATHWAY; BIOLOGICAL MOTION; PARIETAL CORTEX; PERCEPTUAL DECISION; DOUBLE DISSOCIATION; TRANSPARENT MOTION; ASPERGER SYNDROME; JOINT ATTENTION; REACTION-TIME; NEURAL BASIS AB Vision in Autism Spectrum Conditions (ASC) is characterized by enhanced perception of local elements, but impaired perception of global percepts. Deficits in coherent motion perception seem to support this characterization, but the roots and robustness of such deficits remain unclear. We aimed to investigate the dynamics of the perceptual decision-making network known to support coherent motion perception. In a series of forced-choice coherent motion perception tests, we parametrically varied a single stimulus dimension, viewing duration, to test whether the rate at which evidence is accumulated towards a global decision is atypical in ASC. 40 adult participants (20 ASC) performed a classic motion discrimination task, manually indicating the global direction of motion in a random-dot kinematogram across a range of coherence levels (2-75%) and stimulus-viewing durations (200-1500 ms). We report a deficit in global motion perception at short viewing durations in ASC. Critically, however, we found that increasing the amount of time over which motion signals could be integrated reduced the magnitude of the deficit, such that at the longest duration there was no difference between the ASC and control groups. Further, the deficit in motion integration at the shortest duration was significantly associated with the severity of autistic symptoms in our clinical population, and was independent from measures of intelligence. These results point to atypical integration of motion signals during the construction of a global percept in ASC. Based on the neural correlates of decision-making in global motion perception our findings suggest the global motion deficit observed in ASC could reflect a slower or more variable response from the primary motion area of the brain or longer accumulation of evidence towards a decision-bound in parietal areas. C1 [Robertson, Caroline E.; Baron-Cohen, Simon] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. [Robertson, Caroline E.; Martin, Alex; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Robertson, CE (reprint author), Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England. EM cr419@cam.ac.uk OI , Caroline/0000-0002-1858-6594; Baker, Chris/0000-0001-6861-8964 FU Intramural Research Program of the National Institute of Mental Health; Medical Research Council (UK); Gates-Cambridge Trust; NIH-Cambridge Fellowship FX This work was supported by the Intramural Research Program of the National Institute of Mental Health and the Medical Research Council (UK) (http://www.mrc.ac.uk). CER was supported by the Gates-Cambridge Trust and the NIH-Cambridge Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 16 Z9 16 U1 2 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 20 PY 2012 VL 7 IS 11 AR e48173 DI 10.1371/journal.pone.0048173 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043II UT WOS:000311535700008 PM 23185249 ER PT J AU Saito, K Matsumoto, S Yasui, H Devasahayam, N Subramanian, S Munasinghe, JP Patel, V Gutkind, JS Mitchell, JB Krishna, MC AF Saito, Keita Matsumoto, Shingo Yasui, Hironobu Devasahayam, Nallathamby Subramanian, Sankaran Munasinghe, Jeeva P. Patel, Vyomesh Gutkind, J. Silvio Mitchell, James B. Krishna, Murali C. TI Longitudinal Imaging Studies of Tumor Microenvironment in Mice Treated with the mTOR Inhibitor Rapamycin SO PLOS ONE LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; ENDOTHELIAL GROWTH-FACTOR; NECK-CANCER; MAMMALIAN TARGET; HYPERBARIC-OXYGEN; CYCLING HYPOXIA; VASCULATURE; PATHWAY; HEAD; ANGIOGENESIS AB Rapamycin is an allosteric inhibitor of mammalian target of rapamycin, and inhibits tumor growth and angiogenesis. Recent studies suggested a possibility that rapamycin renormalizes aberrant tumor vasculature and improves tumor oxygenation. The longitudinal effects of rapamycin on angiogenesis and tumor oxygenation were evaluated in murine squamous cell carcinoma (SCCVII) by electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI) to identify an optimal time after rapamycin treatment for enhanced tumor radioresponse. Rapamycin treatment was initiated on SCCVII solid tumors 8 days after implantation (500-750 mm(3)) and measurements of tumor pO(2) and blood volume were conducted from day 8 to 14 by EPRI/MRI. Microvessel density was evaluated over the same time period by immunohistochemical analysis. Tumor blood volume as measured by MRI significantly decreased 2 days after rapamycin treatment. Tumor pO(2) levels modestly but significantly increased 2 days after rapamycin treatment; whereas, it decreased in non-treated control tumors. Furthermore, the fraction of hypoxic area (pixels with pO(2)<10 mm Hg) in the tumor region decreased 2 days after rapamycin treatments. Immunohistochemical analysis of tumor microvessel density and pericyte coverage revealed that microvessel density decreased 2 days after rapamycin treatment, but pericyte coverage did not change, similar to what was seen with anti-angiogenic agents such as sunitinib which cause vascular renormalization. Collectively, EPRI/MRI co-imaging can provide non-invasive evidence of rapamycin-induced vascular renormalization and resultant transient increase in tumor oxygenation. Improved oxygenation by rapamycin treatment provides a temporal window for anti-cancer therapies to realize enhanced response to radiotherapy. C1 [Saito, Keita; Matsumoto, Shingo; Yasui, Hironobu; Devasahayam, Nallathamby; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yasui, Hironobu] Hokkaido Univ, Grad Sch Vet Med, Dept Environm Vet Sci, Radiat Biol Lab, Sapporo, Hokkaido, Japan. [Munasinghe, Jeeva P.] Natl Inst Neurol Disorder & Stroke, NIH, Bethesda, MD USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM murali@helix.nih.gov FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 14 Z9 14 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 20 PY 2012 VL 7 IS 11 AR e49456 DI 10.1371/journal.pone.0049456 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043II UT WOS:000311535700034 PM 23185335 ER PT J AU Yoneyama, K Gjesdal, O Choi, EY Wu, CO Hundley, WG Gomes, AS Liu, CY McClelland, RL Bluemke, DA Lima, JAC AF Yoneyama, Kihei Gjesdal, Ola Choi, Eui-Young Wu, Colin O. Hundley, W. Gregory Gomes, Antoinette S. Liu, Chia-Ying McClelland, Robyn L. Bluemke, David A. Lima, Joao A. C. TI Age, Sex, and Hypertension-Related Remodeling Influences Left Ventricular Torsion Assessed by Tagged Cardiac Magnetic Resonance in Asymptomatic Individuals The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Article DE aging; blood pressure; cardiac function; cardiac output; hypertrophy; magnetic resonance imaging; ventricular remodeling ID SPECKLE-TRACKING ECHOCARDIOGRAPHY; CANINE LEFT-VENTRICLE; ROTATIONAL DEFORMATION; MYOCARDIAL-INFARCTION; SYSTOLIC FUNCTION; HEART-FAILURE; APEX ROTATION; NORMAL VALUES; DOPPLER; RELAXATION AB Background-The aim of the present study was to evaluate how torsion is influenced by left ventricular (LV) remodeling associated with age, sex, and hypertension in a large community-based population. Methods and Results-Myocardial shortening and torsion were assessed by tagged cardiac magnetic resonance in 1478 participants without clinically apparent cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Torsion was defined as the difference between apical and basal rotation divided by slice distance. In multivariable linear regression models, older age was associated with lower stroke volume (-3.6 mL per decade; P<0.001) and higher LV mass-to-volume ratio (0.03 g/mL per decade; P<0.001), along with lower circumferential shortening (-0.17% per decade; P<0.05). Torsion, however, was greater at older ages (0.14 degrees per decade; P<0.001) and in women (0.37 degrees/cm versus men; P<0.001). Hypertensive participants had higher LV mass and LV mass-to-volume ratio (15.5 g and 0.07 g/mL, respectively; P<0.001 for both). Circumferential shortening was lower in hypertensive (-0.42%; P<0.01), whereas torsion was higher after adjustment for age and sex (0.17 degrees/cm; P<0.05). Conclusions-Older age is associated with lower LV volumes and greater relative wall thickness and is accompanied by lower circumferential myocardial shortening, whereas torsion is greater with older age. Hypertensive individuals have greater LV volumes and relative wall thickness and lower circumferential shortening. Torsion, however, is greater in hypertension independently of age and sex. Torsion may therefore represent a compensatory mechanism to maintain an adequate stroke volume and cardiac output in the face of the progressively reduced LV volumes and myocardial shortening associated with hypertension and aging. (Circulation. 2012; 126: 2481-2490.) C1 [Yoneyama, Kihei; Gjesdal, Ola; Choi, Eui-Young; Liu, Chia-Ying; Lima, Joao A. C.] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD 21287 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Hundley, W. Gregory] Wake Forest Univ Hlth Sci, Dept Internal Med Cardiol, Winston Salem, NC USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA. RP Lima, JAC (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Blalock 524D1,600 N Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Gjesdal, Ola/0000-0003-1913-6445; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung and Blood Institute [N01-HC-95159, N01-HC-95169]; Fulbright Foundation; Norwegian Medical Association; Norwegian Research Council FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung and Blood Institute.; Dr Gjesdal received support from the Fulbright Foundation, the Norwegian Medical Association, and the Norwegian Research Council. NR 46 TC 36 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 BP 2481 EP 2490 DI 10.1161/CIRCULATIONAHA.112.093146 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 040SF UT WOS:000311342600013 PM 23147172 ER PT J AU Thomas, CG Li, RH Smith, HE Woodruff, GC Oliver, B Haag, ES AF Thomas, Cristel G. Li, Renhua Smith, Harold E. Woodruff, Gavin C. Oliver, Brian Haag, Eric S. TI Simplification and Desexualization of Gene Expression in Self-Fertile Nematodes SO CURRENT BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; LINKED SITES; GENOME SIZE; RNA-SEQ; EVOLUTION; SELECTION; HERMAPHRODITISM; TRANSCRIPTOME; PHYLOGENY; SEQUENCES AB Evolutionary transitions between sexual modes could be potent forces in genome evolution [1, 2]. Several Caenorhabditis nematode species have evolved self-fertile hermaphrodites from the obligately outcrossing females of their ancestors [3]. We explored the relationship between sexual mode and global gene expression by comparing two selfing species, C. elegans and C. briggsae, with three phylogenetically informative outcrossing relatives, C. remanei, C. brenneri, and C. japonica. Adult transcriptome assemblies from the selfing species are consistently and strikingly smaller than those of the outcrossing species. Against this background of overall simplification, genes conserved in multiple outcrossing species with strong sex-biased expression are even more likely to be missing from the genomes of the selfing species. In addition, the sexual regulation of remaining transcripts has diverged markedly from the ancestral pattern in both selfing lineages, though in distinct ways. Thus, both the complexity and the sexual specialization of transciptomes are rapidly altered in response to the evolution of self-fertility. These changes may result from the combination of relaxed sexual selection and a recently reported genetic mechanism favoring genome shrinkage [4] in partial selfers. C1 [Thomas, Cristel G.; Woodruff, Gavin C.; Haag, Eric S.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [Thomas, Cristel G.; Haag, Eric S.] Univ Maryland, Program Mol & Cell Biol, College Pk, MD 20742 USA. [Li, Renhua; Smith, Harold E.; Oliver, Brian] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Haag, ES (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. EM ehaag@umd.edu FU National Institutes of Health (NIH); Ron Ellis for strains; Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases; NIH [5R01GM079414] FX The authors wish to thank Ian Korf and WormBase staff for bioinformatics assistance and the Institute for Bioscience and Biotechnology Research (IBBR) sequencing core for generating C. briggsae sequencing data. We thank the Caenorhabditis Genetics Center, which is supported by awards from the National Institutes of Health (NIH), and Ron Ellis for strains. This work was supported by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (to B.O. and H.E.S.), and NIH grant 5R01GM079414 (to E.S.H.). NR 32 TC 25 Z9 25 U1 3 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD NOV 20 PY 2012 VL 22 IS 22 BP 2167 EP 2172 DI 10.1016/j.cub.2012.09.038 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 043DT UT WOS:000311523800027 PM 23103191 ER PT J AU Klein, HG Natanson, C AF Klein, Harvey G. Natanson, Charles TI Red Blood Cell Transfusion SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Klein, Harvey G.; Natanson, Charles] NIH, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 20 PY 2012 VL 157 IS 10 BP 753 EP 754 DI 10.7326/0003-4819-157-10-201211200-00019 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 043VZ UT WOS:000311580000026 PM 23165669 ER PT J AU Polis, MA AF Polis, Michael A. TI Preexposure prophylaxis reduced HIV-1 spread in serodiscordant heterosexual couples SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. RP Polis, MA (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 20 PY 2012 VL 157 IS 10 AR JC5-3 DI 10.7326/0003-4819-157-10-201211200-02003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 043VZ UT WOS:000311580000002 PM 23165679 ER PT J AU Merchant, MS Geller, JI Baird, K Chou, AJ Galli, S Charles, A Amaoko, M Rhee, EH Price, A Wexler, LH Meyers, PA Widemann, BC Tsokos, M Mackall, CL AF Merchant, Melinda S. Geller, James I. Baird, Kristin Chou, Alexander J. Galli, Susana Charles, Ava Amaoko, Martha Rhee, Eunice H. Price, Anita Wexler, Leonard H. Meyers, Paul A. Widemann, Brigitte C. Tsokos, Maria Mackall, Crystal L. TI Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID APOPTOSIS-INDUCING LIGAND; TRAIL-INDUCED APOPTOSIS; EWINGS-SARCOMA FAMILY; CELLS; SENSITIVITY; RESISTANT; TOXICITY; CANCERS AB Purpose Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. Patients and Methods This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age <= 21 years with recurrent or progressive solid tumors. Results Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. Conclusion Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects. C1 [Merchant, Melinda S.; Baird, Kristin; Galli, Susana; Widemann, Brigitte C.; Tsokos, Maria; Mackall, Crystal L.] NCI, Bethesda, MD 20892 USA. [Amaoko, Martha; Rhee, Eunice H.] NIH, Bethesda, MD 20892 USA. [Chou, Alexander J.; Charles, Ava; Price, Anita; Wexler, Leonard H.; Meyers, Paul A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Geller, James I.] Cincinnati Childrens Hosp, Cincinnati, OH USA. RP Merchant, MS (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 1W-3750, Bethesda, MD 20892 USA. EM merchanm@mail.nih.gov OI Price, Anita/0000-0002-3917-6666; Meyers, Paul/0000-0001-6146-6101; Chou, Alexander/0000-0002-7926-3326 FU Intramural Research Program of the National Cancer Institute, National Institutes of Health; Clinical Research Training Program, National Institutes of Health FX Supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, and by the Clinical Research Training Program, National Institutes of Health (M. A., E.H.R.). NR 24 TC 31 Z9 33 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2012 VL 30 IS 33 BP 4141 EP 4147 DI 10.1200/JCO.2012.44.1055 PG 7 WC Oncology SC Oncology GA 040DF UT WOS:000311300000024 PM 23071222 ER PT J AU Chirinos, JA Kips, JG Jacobs, DR Brumback, L Duprez, DA Kronmal, R Bluemke, DA Townsend, RR Vermeersch, S Segers, P AF Chirinos, Julio A. Kips, Jan G. Jacobs, David R., Jr. Brumback, Lyndia Duprez, Daniel A. Kronmal, Richard Bluemke, David A. Townsend, Raymond R. Vermeersch, Sebastian Segers, Patrick TI Arterial Wave Reflections and Incident Cardiovascular Events and Heart Failure: MESA (Multiethnic Study of Atherosclerosis) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE arterial hemodynamics; cardiovascular risk; heart failure; left ventricular afterload; wave reflections ID LEFT-VENTRICULAR MASS; INPUT IMPEDANCE; ALL-CAUSE; PRESSURE; RECLASSIFICATION; PREDICTION; STIFFNESS; VELOCITY; DISEASE; FORMS AB Objectives This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample. Background Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. Methods Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] x 100), augmentation index ([Second/First systolic peak] x 100) and pulse pressure amplification ([Radial/aortic pulse pressure] x 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years. Results After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p < 0.0001), comparing favorably to other risk factors for CHF as per various measures of model performance, reclassification, and discrimination. In a fully adjusted model, compared to nonhypertensive subjects with low RM, the HRs (95% CI) for hypertensive subjects with low RM, nonhypertensive subjects with high RM, and hypertensive subjects with high RM were 1.81 (0.85 to 3.86), 2.16 (1.07 to 5.01), and 3.98 (1.96 to 8.05), respectively. Conclusions Arterial wave reflections represent a novel strong risk factor for CHF in the general population. (J Am Coll Cardiol 2012;60:2170-7) (C) 2012 by the American College of Cardiology Foundation C1 [Chirinos, Julio A.] Univ Penn, Sch Med, Dept Cardiol, Philadelphia, PA 19104 USA. [Chirinos, Julio A.; Townsend, Raymond R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kips, Jan G.; Vermeersch, Sebastian; Segers, Patrick] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Brumback, Lyndia; Kronmal, Richard] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Duprez, Daniel A.] Univ Minnesota, Sch Med, Div Cardiol, Minneapolis, MN 55455 USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Chirinos, JA (reprint author), Univ Penn, Sch Med, Dept Cardiol, Rm 8B111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; American Heart Association grants [0885031N, R01-HL-098382]; Atcor Medical; Cardiodynamics; APC cardiovascular; Novartis; Genentech; Amarin; Merck; Pfizer; Boehringer Ingelheim; [RR-024156] FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and RR-024156 as well as American Heart Association grants 0885031N and R01-HL-098382. Dr. Chirinos has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC cardiovascular. Dr. Duprez has received research grants from Novartis, Genentech, and Amarin; and speakers' fees from Merck, Pfizer, Novartis, and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 34 TC 135 Z9 135 U1 4 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 20 PY 2012 VL 60 IS 21 BP 2170 EP 2177 DI 10.1016/j.jacc.2012.07.054 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 037CC UT WOS:000311077600007 PM 23103044 ER PT J AU Danaher, MR Schisterman, EF Roy, A Albert, PS AF Danaher, M. R. Schisterman, E. F. Roy, A. Albert, P. S. TI Estimation of gene-environment interaction by pooling biospecimens SO STATISTICS IN MEDICINE LA English DT Article DE allele frequency measurements; case-control study; cost efficiency; logistic regression; power ID SNP ALLELE FREQUENCIES; POOLED DNA SAMPLES; SINGLE-NUCLEOTIDE POLYMORPHISMS; TOF MASS-SPECTROMETRY; PRIMER EXTENSION; DISEASE; DESIGN; ASSOCIATION; BIOMARKERS; DHPLC AB Case-control studies are prone to low power for testing geneenvironment interactions (GXE) given the need for a sufficient number of individuals on each strata of disease, gene, and environment. We propose a new study design to increase power by strategically pooling biospecimens. Pooling biospecimens allows us to increase the number of subjects significantly, thereby providing substantial increase in power. We focus on a special, although realistic case, where disease and environmental statuses are binary, and gene status is ordinal with each individual having 0, 1, or 2 minor alleles. Through pooling, we obtain an allele frequency for each level of disease and environmental status. Using the allele frequencies, we develop a new methodology for estimating and testing GXE that is comparable to the situation when we have complete data on gene status for each individual. We also explore the measurement process and its effect on the GXE estimator. Using an illustration, we show the effectiveness of pooling with an epidemiologic study, which tests an interaction for fiber and paraoxonase on anovulation. Through simulation, we show that taking 12 pooled measurements from 1000 individuals achieves more power than individually genotyping 500 individuals. Our findings suggest that strategic pooling should be considered when an investigator designs a pilot study to test for a GXE. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Danaher, M. R.; Schisterman, E. F.; Roy, A.; Albert, P. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Danaher, M. R.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Schisterman, EF (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Rm 7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Long-Range Research Initiative of the American Chemistry Council FX This research was supported partially by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and by the Long-Range Research Initiative of the American Chemistry Council. NR 26 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 20 PY 2012 VL 31 IS 26 BP 3241 EP 3252 DI 10.1002/sim.5357 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019NA UT WOS:000309745400012 PM 22859290 ER PT J AU Agarwal, S Nettleton, JA de Roer, I Ix, JH Siscovick, D Eng, J Bild, D Burke, GL Herrington, DM AF Agarwal, Subhashish Nettleton, Jennifer A. de Roer, Ian Ix, Joachim H. Siscovick, David Eng, John Bild, Diane Burke, Gregory L. Herrington, David M. TI The Association of Calcium Supplementation and Incident Cardiovascular Events: Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Nutrition; Cardiovascular disease prevention; Population science C1 [Agarwal, Subhashish] Oakwood Hosp, Med Cntr, Dearborn, MI USA. [Nettleton, Jennifer A.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [de Roer, Ian] Univ Washington, Dept Nephrol, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ix, Joachim H.] San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Rsch Unit, Seattle, WA 98195 USA. [Eng, John] Johns Hopkins Univ, Baltimore, MD USA. [Bild, Diane] NHLBI, Prevent & Populat Sci Program, Bethesda, MD 20892 USA. [Burke, Gregory L.] Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA. [Herrington, David M.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 9231 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000058 ER PT J AU Ahmet, I Tae, HJ Brines, M Cerami, A Lakatta, EG Talan, M AF Ahmet, Ismayil Tae, Hyun-Jin Brines, Michael Cerami, Anthony Lakatta, Edward G. Talan, Mark TI Helix B Surface Peptide, a Small Non-erythropoictic Molecule Based on the Erythropoietin Structure, Effectively Ameliorates the Progression of Chronic Heart Failure in the Rat Post Myocardial Infarction Model SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Pharmacology; Infarction C1 [Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G.; Talan, Mark] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Brines, Michael] Araim Pharmaceut, Ossining, NY USA. [Cerami, Anthony] Araim Pharmaceut Inc, Ossining, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 9927 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000258 ER PT J AU Bild, DE McClelland, R Kaufman, J Blumenthal, R Burke, G Carr, JJ Post, W Register, T Shea, S Szklo, M Szklo, M AF Bild, Diane E. McClelland, Robyn Kaufman, Joel Blumenthal, Roger Burke, Gregory Carr, J. Jeffrey Post, Wendy Register, Thomas Shea, Steven Szklo, Moyses Szklo, Moyses TI Ten-year Trends in Coronary Calcification in Individuals Without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Subclinical atherosclerosis; Risk factors C1 [Bild, Diane E.] NHLBI, NIH, Bethesda, MD 20892 USA. [McClelland, Robyn] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kaufman, Joel] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Blumenthal, Roger] Johns Hopkins Univ, Sch Med, Dept Med Cardiol, Baltimore, MD USA. [Burke, Gregory] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Carr, J. Jeffrey] Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. [Post, Wendy] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. [Register, Thomas] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. [Shea, Steven] Columbia Univ, Div Gen Internal Med, New York, NY USA. [Szklo, Moyses; Szklo, Moyses] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14442 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004214 ER PT J AU Cater, GM Yang, E Sibley, CT Nacif, MS Rosen, B Balling, KD May, HT Anderson, JL Lappe, DL Lima, JA Bluemke, DA Muhlestein, JB AF Cater, George M. Yang, Eunice Sibley, Christopher T. Nacif, Marcelo S. Rosen, Boaz Balling, Kyle D. May, Heidi T. Anderson, Jeffery L. Lappe, Donald L. Lima, Joao A. Bluemke, David A. Muhlestein, Joseph B. TI Diabetes Severity is Associated with High Risk Plaque by Coronary CT Angiography: The FACTOR-64 Trial SO CIRCULATION LA English DT Meeting Abstract DE Angiography; Computed tomography; Plaque; Type 2 Diabetes; Risk factors C1 [Cater, George M.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Yang, Eunice] Johns Hopkins Univ, Coll Med, Baltimore, MD USA. [Sibley, Christopher T.; Nacif, Marcelo S.; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Rosen, Boaz] Harbor Hosp, Baltimore, MD USA. [Balling, Kyle D.; May, Heidi T.; Anderson, Jeffery L.; Lappe, Donald L.; Muhlestein, Joseph B.] Intermt Med Cntr, Cardiovasc Dept, Murray, UT USA. [Lima, Joao A.] Johns Hopkins Univ, Inst Heart & Vasc, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13426 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003224 ER PT J AU Chahal, H Bluemke, DA McClelland, R Liu, K Balfour, PC Herrington, D Shea, SI Burke, G Post, W Shi, PB Olson, J Watson, KE Folsom, AR Lima, JA AF Chahal, Harjit Bluemke, David A. McClelland, Robyn Liu, Kiang Balfour, Pelbreton C. Herrington, David Shea, Steven I. Burke, Gregory Post, Wendy Shi, PeiBei Olson, Jean Watson, Karol E. Folsom, Aaron R. Lima, Joao A. TI Traditional and Novel Risk Factors Can Estimate Five Year Risk of Developing Heart Failure: Results From the Multi-ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Risk factors; Epidemiology; Prevention; Biomarkers C1 [Chahal, Harjit; Post, Wendy; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, David A.] NIH, Clin Cntr, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [McClelland, Robyn] Univ Washington, Collaborat Hlth Studies Coordinating Cntr, Seattle, WA 98195 USA. [Liu, Kiang] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. [Balfour, Pelbreton C.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Herrington, David] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Shea, Steven I.] Columbia Univ, New York, NY USA. [Burke, Gregory] Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA. [Shi, PeiBei] NIH, Bethesda, MD 20892 USA. [Olson, Jean] NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Watson, Karol E.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11145 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001205 ER PT J AU Chen, MY Bandettini, WP Shanbhag, S Hsu, LY Arai, AE AF Chen, Marcus Y. Bandettini, W. P. Shanbhag, Sujata Hsu, Li-Yueh Arai, Andrew E. TI Cost effectiveness of Coronary CTA or Vasodilator Stress Cardiac MRI for Determination of Invasive Angiography Following Equivocal Nuclear SPECT SO CIRCULATION LA English DT Meeting Abstract DE Cardiac CT; Cardiac MRI; Cost-effectiveness; Coronary artery disease; Cardiovascular imaging C1 [Chen, Marcus Y.; Bandettini, W. P.; Shanbhag, Sujata; Hsu, Li-Yueh; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17902 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007329 ER PT J AU Cheng, SS Gupta, DK Shah, AM Sharrett, AR Skali, H Takeuchi, M Clagett, B Ni, HY Solomon, SD AF Cheng, Susan Gupta, Deepak K. Shah, Amil M. Sharrett, A. Richey Skali, Hicham Takeuchi, Madoka Clagett, Brian Ni, Hanyi Solomon, Sott D. TI Relation of Blood Pressure Indices with Differential Risk for Cardiovascular Events: The Atherosclerosis Risk in Communities Study SO CIRCULATION LA English DT Meeting Abstract DE Blood pressure; Epidemiology C1 [Cheng, Susan; Gupta, Deepak K.; Shah, Amil M.; Skali, Hicham; Takeuchi, Madoka; Clagett, Brian; Solomon, Sott D.] Brigham & Womens Hosp, Cardiovasc Div, Cambridge, MA USA. [Sharrett, A. Richey] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Ni, Hanyi] NHLBI, Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15476 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005210 ER PT J AU Desai, CS Ning, HY Liu, K Reis, J Gidding, SS Lima, JC Lloyd-Jones, DM AF Desai, Chintan S. Ning, Hongyan Liu, Kiang Reis, Jared Gidding, Samuel S. Lima, Joao C. Lloyd-Jones, Donald M. TI Association of Cardiovascular Health in Young Adulthood with Left Ventricular Structure and Function Later in Life: The Coronary Artery Risk Development in Young Adults (Cardia) Study SO CIRCULATION LA English DT Meeting Abstract DE Echocardiography; 2020 Goals; Risk factors C1 [Desai, Chintan S.; Ning, Hongyan; Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Reis, Jared] NHLBI, Bethesda, MD 20892 USA. [Gidding, Samuel S.] Nemours Cardiac Cntr, Wilmington, DE USA. [Lima, Joao C.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16640 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006243 ER PT J AU Donekal, S Liu, YC Liu, CY Venkatesh, BA Yoneyama, K Wu, CO Nacif, M Gomes, AS Hundley, G Bluemke, DA Lima, JA AF Donekal, Sirisha Liu, Yuan Chano Liu, Chia Ying Venkatesh, Bharath Ambale Yoneyama, Kihei wu, Colin O. Nacif, Marcelo Gomes, Antoinette S. Hundley, Gregory Bluemke, David A. Lima, Joao A. TI The Relationship Between Interstitial Fibrosis by T1 Mapping and Regional Myocardial Function by Tagging: The MESA Study SO CIRCULATION LA English DT Meeting Abstract DE Fibrosis; Myocardial contraction; Myocardial torsion and recoil; Magnetic resonance imaging; Hypertrophy C1 [Donekal, Sirisha; Liu, Yuan Chano; Liu, Chia Ying; Venkatesh, Bharath Ambale; Yoneyama, Kihei; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [wu, Colin O.; Nacif, Marcelo] NHLBI, Bethesda, MD 20892 USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Bethesda, MD USA. [Hundley, Gregory] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Bluemke, David A.] NIH, Clin Cntr, Bethesda, MD USA. RI Ambale Venkatesh, Bharath/F-4941-2016 OI Ambale Venkatesh, Bharath/0000-0002-2330-2373 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11168 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001209 ER PT J AU Dracup, K Moser, D Pelter, M Nesbitt, T Southard, J Paul, SM Biddle, MJ Robinson, S Loranger, D Cooper, LS AF Dracup, Kathleen Moser, Debra Pelter, Michele Nesbitt, Thomas Southard, Jeffrey Paul, Steven M. Biddle, Martha J. Robinson, Susan Loranger, Denise Cooper, Lawton S. TI A Focused Heart Failure Self-Care Intervention Reduces Cardiac Deaths in Rural Patients SO CIRCULATION LA English DT Meeting Abstract DE Heart failure C1 [Dracup, Kathleen; Paul, Steven M.; Robinson, Susan] UCSF, San Francisco, CA USA. [Moser, Debra; Biddle, Martha J.] Univ Kentucky, Lexington, KY USA. [Pelter, Michele] Univ Nevada, Reno, NV 89557 USA. [Nesbitt, Thomas] Univ Calif Davis, Sacramento, CA USA. [Southard, Jeffrey] Univ Calif Davis, San Francisco, CA USA. [Loranger, Denise] UCSF, Reno, NV USA. [Cooper, Lawton S.] UCSF, NHLBI, Bethseda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10687 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001019 ER PT J AU Duprez, D Jacobs, DR Brumback, L Peraita, CA Steffen, LM Alonso, A Sibley, CT Heckbert, SR Kronmal, R AF Duprez, Daniel Jacobs, David R. Brumback, Lyndia Peraita, Carmen A. Steffen, Lyn M. Alonso, Alvaro Sibley, Christopher T. Heckbert, Susan R. Kronmal, Richard TI Diastolic Pulse Wave Analysis in the Prediction of Incident Atrial Fibrillation in The Multi-ethnic Study Of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Blood pressure; Cardiovascular disease prevention; Risk factors C1 [Duprez, Daniel] Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA. [Jacobs, David R.; Steffen, Lyn M.; Alonso, Alvaro] Univ Minnesota, Minneapolis, MN USA. [Brumback, Lyndia; Kronmal, Richard] Univ Washington, Seattle, WA 98195 USA. [Peraita, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA. [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Rsch Unit, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 12133 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885002140 ER PT J AU Ebong, IA Goff, DC Rodriguez, CJ Chen, HY Sibley, CT Bertoni, AG AF Ebong, Imo A. Goff, David C. Rodriguez, Carlos J. Chen, Haiyng Sibley, Christopher T. Bertoni, Alain G. TI Association of Lipids with Incident Heart Failure among Adults with and Without Diabetes: The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Lipids; Heart failure C1 [Ebong, Imo A.; Rodriguez, Carlos J.; Chen, Haiyng; Bertoni, Alain G.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Goff, David C.] Colorado Sch Publ Hlth, Aurora, CO USA. [Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11065 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001173 ER PT J AU Gencer, B Butler, J Bauer, DC Auer, R Kalogeropoulos, A Maroues-Vidal, P Applegate, WB Satterfield, S Vittinghoff, E Harris, T Newman, A Rodondi, N AF Gencer, Baris Butler, Javed Bauer, Douglas C. Auer, Reto Kalogeropoulos, Andreas Maroues-Vidal, Pedro Applegate, William B. Satterfield, Suzanne Vittinghoff, Eric Harris, Tamara Newman, Anne Rodondi, Nicolas TI Association of ECG Abnormalities and Incident Heart Failure Events SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Electrocardiography; Epidemiologic methods C1 [Gencer, Baris] Univ Hosp Geneva, Geneva, Switzerland. [Butler, Javed; Kalogeropoulos, Andreas] Emory Clin, Cardiovas Rsch Inst, Div Cardiol, Atlanta, GA 30322 USA. [Bauer, Douglas C.] Dept Med, San Francisco, CA USA. [Auer, Reto; Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Maroues-Vidal, Pedro] Clin Rsch Cntr, Inst Social & Prevent Med, Lausanne, Switzerland. [Applegate, William B.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Harris, Tamara] NIH, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. [Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Rodondi, Nicolas] Univ Hosp Bern, Dept Gen Internal Med, CH-3010 Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14987 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005023 ER PT J AU Gjesdal, O Mewton, N Yoneyama, K Wu, C Jacobs, D Sydney, S Lewis, CE Liu, K Bluemke, DA Lima, JA AF Gjesdal, Ola Mewton, Nathan Yoneyama, Kihei Wu, Colin Jacobs, David Sydney, Stephen Lewis, Cora E. Liu, Kiang Bluemke, David A. Lima, Joao A. TI Dose Response Effect of Cigarette Smoking on Cardiac Function and Heart Failure in the Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Cardiac MRI; Myocardial contraction; Population science; Heart failure; Smoking C1 [Gjesdal, Ola; Mewton, Nathan; Yoneyama, Kihei; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Wu, Colin] NHLBI, Bethesda, MD 20892 USA. [Jacobs, David] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Sydney, Stephen] Kaiser Permanente, Div Rsch, Oakland, CA USA. [Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Liu, Kiang] Northwestern Univ, Feinberg Cardiovasc Rsch Inst, Chicago, IL 60611 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14447 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004217 ER PT J AU Goldberg, CS Lu, MM Mahle, WT Gaynor, JW Williams, I Mussatto, KA Ohye, RG Frank, D Graham, EM Jacobs, JP Krawczeski, CD Ambert, LI Lewis, A Pemberton, VL Sananes, R Sood, E Wechsler, S Newburger, JW AF Goldberg, Caren S. Lu, Minmin Mahle, William T. Gaynor, J. W. Williams, Ismee Mussatto, Kathleen A. Ohye, Richard G. Frank, Deborah Graham, Eric M. Jacobs, Jeffrey P. Krawczeski, Catherine D. Ambert, Linda I. Lewis, Alan Pemberton, Victoria L. Sananes, Renee Sood, Erica Wechsler, Stephanie Newburger, Jane W. CA Pediat Heart Network Investigators TI Factors Associated with Impaired Neurodevelopment at 3 Years of Age in Children with Single Right Ventricle Lesions SO CIRCULATION LA English DT Meeting Abstract DE Hypoplastic left heart; Pediatric cardiology C1 [Goldberg, Caren S.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Lu, Minmin] New England Res Inst, Boston, MA USA. [Mahle, William T.] Sibley Heart Cntr, Atlanta, GA USA. [Gaynor, J. W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Williams, Ismee] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Mussatto, Kathleen A.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Ohye, Richard G.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Frank, Deborah] Primary Childrens Med Ctr, Dept Pediat, Salt Lake City, UT USA. [Graham, Eric M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Jacobs, Jeffrey P.] Cardiac Surg Associates, Congenital Heart Inst Florida, St Petersburg, FL USA. [Krawczeski, Catherine D.] Cincinnati Childrens Hosp, Div Cardiol, Cincinnati, OH USA. [Ambert, Linda I.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Lewis, Alan] Childrens Hosp Los Angeles, Div Cardiol, Los Angeles, CA 90027 USA. [Pemberton, Victoria L.] NHLBI, Bethesda, MD 20892 USA. [Sananes, Renee] Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada. [Sood, Erica] Nemours Al duPont Hosp Children, Nemours Cardiac Cntr, Wilmington, DE USA. [Wechsler, Stephanie] Duke Univ, Med Ctr, Dept Pediat, Durham, NC USA. [Newburger, Jane W.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13230 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003144 ER PT J AU Guenther, F Kaufmann, BA Klibanov, AL Heidt, T Kramer, M Khanicheh, E Ferrante, EA Neudorfer, I Yasuhiro, K Peter, K Bode, C von zur Muhlent, C AF Guenther, Felix Kaufmann, Beat A. Klibanov, Alexander L. Heidt, Timo Kramer, Mara Khanicheh, Elham Ferrante, Elisa A. Neudorfer, Irene Yasuhiro, Katagiri Peter, Karlheinz Bode, Christoph von zur Muhlent, Constantin TI Dual Microbubble Targeting Improves in vitro Capture Efficiency of Ultrasound Micro-Bubbles Targeted to Selectins and Activated Platelets Although not Providing Additional Signal Effect for in vivo Imaging of Arterial Thrombosis SO CIRCULATION LA English DT Meeting Abstract DE Ultrasound; Molecular; Imaging agents; Cardiovascular imaging; Arteriosclerosis C1 [Guenther, Felix; Heidt, Timo; Kramer, Mara; Neudorfer, Irene; Bode, Christoph; von zur Muhlent, Constantin] Univ Heart Cntr, Freiburg, Germany. [Kaufmann, Beat A.; Khanicheh, Elham] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Klibanov, Alexander L.] Univ Virginia, Div Cardiovasc Med, Charlottesville, VA USA. [Ferrante, Elisa A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. [Yasuhiro, Katagiri] NIH, Dev Neurobiol Sect, Bethesda, MD 20892 USA. [Peter, Karlheinz] Baker IDI, Heart & Diabet Inst, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13226 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003142 ER PT J AU Gulati, A Krishnathasan, K Hsu, LY Ali, A Ismail, T Ferreira, P Ismail, N Goncalves, C Davendralingam, N Wage, R Roughton, M Gatehouse, P Jabbour, A Pennell, DJ Arai, AE Prasad, S AF Gulati, Ankur Krishnathasan, Kaushiga Hsu, Li-Yueh Ali, Aamir Ismail, Tevfik Ferreira, Pedro Ismail, Nizar Goncalves, Carla Davendralingam, Natasha Wage, Rick Roughton, Michael Gatehouse, Peter Jabbour, Andrew Pennell, Dudley J. Arai, Andrew E. Prasad, Sanjay TI Absolute Hyperemic Myocardial Blood Flow is Impaired in Non-Ischemic Dilated Cardiomyopathy and is Related to the Severity of Left Ventricular Systolic Dysfunction SO CIRCULATION LA English DT Meeting Abstract DE Cardiomyopathy; Cardiac MRI; Perfusion imaging; Blood flow; Ventricular function C1 [Gulati, Ankur] Royal Brompton Hosp, London SW3 6LY, England. [Krishnathasan, Kaushiga; Ali, Aamir; Ismail, Tevfik; Ferreira, Pedro; Ismail, Nizar; Goncalves, Carla; Davendralingam, Natasha; Wage, Rick; Roughton, Michael; Gatehouse, Peter; Jabbour, Andrew; Pennell, Dudley J.; Prasad, Sanjay] Royal Brompton Hosp, CMR Dept, London SW3 6LY, England. [Hsu, Li-Yueh; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10654 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001006 ER PT J AU Guvton, JR Slee, AE Anderson, T Fleg, JL Goldberg, RB Kashyap, ML Marcovina, SM Nash, SD O'Brien, KD Weintraub, W Xu, P Zhao, XQ Boden, WE AF Guvton, John R. Slee, April E. Anderson, Todd Fleg, Jerome L. Goldberg, Ronald B. Kashyap, Moti L. Marcovina, Santica M. Nash, Stephen D. O'Brien, Kevin D. Weintraub, William Xu, Ping Zhao, Xue-Qiao Boden, William E. TI Relation of Lipoprotein Levels to Cardiovascular Events in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) Trial SO CIRCULATION LA English DT Meeting Abstract DE Coronary heart disease; Lipoproteins; Cholesterol-lowering drugs; Clinical trials C1 [Guvton, John R.] Duke Univ, Med Cntr, Durham, NC USA. [Slee, April E.; Xu, Ping] Axio Rsch, Biostat, Seattle, WA USA. [Anderson, Todd] Univ Calgary, Calgary, AB, Canada. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA. [Goldberg, Ronald B.] Univ Miami, Miller Sch Med, Hollywood, FL USA. [Kashyap, Moti L.] Univ Calif Irvine, Irvine, CA USA. [Marcovina, Santica M.] Univ Washington, Seattle, WA 98195 USA. [Nash, Stephen D.] SUNY Hlth Sci Cntr Syracuse, Syracuse, NY USA. [O'Brien, Kevin D.] Univ Washington, Med Div Cardiol, Seattle, WA 98195 USA. [Weintraub, William] Cntr Heart & Vasc Hlth, Newark, DE USA. [Zhao, Xue-Qiao] Univ Washington, Sch Med, Seattle, WA USA. [Boden, William E.] Samuel S Stratton VA Med Cntr, Albany, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14501 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004238 ER PT J AU Habibi, M Chahal, H Opdahl, A Helle-Valle, TM Gjesdal, O Heckbert, SR McClelland, R Wu, CO Shea, S Hundley, WG Bluemke, DA Lima, JA AF Habibi, Mohammadali Chahal, Harjit Opdahl, Anders Helle-Valle, Thomas M. Gjesdal, Ola Heckbert, Susan R. McClelland, Robyn Wu, Colin O. Shea, Steven Hundley, W. Gregory Bluemke, David A. Lima, Joao A. TI Left Atrial Function and Incident Heart Failure: Results front The Multi-Ethnic Study of Atherosclerosis(MESA) SO CIRCULATION LA English DT Meeting Abstract DE Atrial function; Heart failure Magnetic resonance imaging; Risk factors C1 [Habibi, Mohammadali; Chahal, Harjit; Opdahl, Anders; Helle-Valle, Thomas M.; Gjesdal, Ola; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Heckbert, Susan R.; McClelland, Robyn] Univ Washington, Seattle, WA 98195 USA. [Wu, Colin O.] NHLBI, Off Biostat Rsch, Bethesda, MD 20892 USA. [Shea, Steven] Columbia Univ, New York, NY USA. [Hundley, W. Gregory] Wake Forest Univ, Winston Salem, NC 27109 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13569 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003294 ER PT J AU Hamad, YA Armstrong, AC Kishi, S Gidding, SS Jacobs, DR Sidney, S Lewis, CE Cook, NL Liu, KJ Lima, J AF Hamad, Yasir A. Armstrong, Anderson C. Kishi, Satoru Gidding, Samuel S. Jacobs, David R. Sidney, Stephen Lewis, Cora E. Cook, Nakela L. Liu, Kiang J. Lima, Joao TI Smoking at Age 18 to 30 is Associated with Diastolic Function Over a 25-Year Follow-Up Period: The CARDIA Study SO CIRCULATION LA English DT Meeting Abstract DE Smoking; Epidemiology C1 [Hamad, Yasir A.; Armstrong, Anderson C.; Kishi, Satoru; Lima, Joao] Johns Hopkins, Cardiol, Baltimore, MD USA. [Gidding, Samuel S.] Nemours Cardiac Cntr, Div Pediat Cardiol, Wilmington, DE USA. [Jacobs, David R.] Univ Minnesota, Minneapolis, MN USA. [Sidney, Stephen] Kaiser Permanente, Phys Act, Obes, Illicit Drugs, Oakland, CA USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Cook, Nakela L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Liu, Kiang J.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16927 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006331 ER PT J AU He, J Yang, W Anderson, A Dries, D Feldman, H Kallem, R Kanthety, R Kusek, J Mazurick, C Ojo, A Raj, D Rahman, M Ricardo, A Shlipak, M Soliman, E Wolf, M Hamm, L AF He, Jiang Yang, Wei Anderson, Amanda Dries, Daniel Feldman, Harold Kallem, RadhaKrishna Kanthety, Radhika Kusek, John Mazurick, Carissa Ojo, Akinlolu Raj, Dominic Rahman, Mahboob Ricardo, Ana Shlipak, Michael Soliman, Elsayed Wolf, Myles Hamm, Lee TI Risk Factors for Congestive Heart Failure in Patients with Chronic Kidney Disease: the CRIC Study SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Kidney; Risk factors C1 [He, Jiang] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Yang, Wei; Anderson, Amanda; Feldman, Harold; Mazurick, Carissa] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Dries, Daniel; Kallem, RadhaKrishna] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Kanthety, Radhika; Rahman, Mahboob] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Kusek, John] NIDDK, NIH, Bethesda, MD 20892 USA. [Ojo, Akinlolu] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Raj, Dominic] George Washington Univ, Dept Med, Washington, DC USA. [Ricardo, Ana] Univ Illinois, Dept Med, Chicago, IL USA. [Shlipak, Michael] UCSF, Dept Med, San Francisco, CA USA. [Soliman, Elsayed] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Wolf, Myles] Univ Miami, Dept Med, Miami, LA USA. [Hamm, Lee] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11651 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001379 ER PT J AU Huan, TX Zhang, B Wang, Z Joehanes, R Zhu, J Johnson, AD Ying, SX Munson, PJ Raghavachari, N Wang, R Liu, PC Courchesne, P Assimes, TL McPherson, R Samani, N Schunkert, H O'Donnell, CJ Derry, J Yang, X Levy, D AF Huan, Tianxiao Zhang, Bin Wang, Zhi Joehanes, Roby Zhu, Jun Johnson, Andrew D. Ying, Saixia Munson, Peter J. Raghavachari, Nalini Wang, Richard Liu, Poching Courchesne, Paul Assimes, Themistocles L. McPherson, Ruth Samani, Nilesh Schunkert, Heribert O'Donnell, Christopher J. Derry, Jonathan Yang, Xia Levy, Daniel CA Coronary ARteryDIs Genome Wide TI Identification of Disrupted Network Modules and Key Regulators of Coronary Artery Disease via Integration of Blood Gene Expression Profiling and Network Analysis SO CIRCULATION LA English DT Meeting Abstract DE Coronary artery disease; Biomarkers; Gene expression; Systems biology; Genome-wide association studies (GWAS) C1 [Huan, Tianxiao; Joehanes, Roby; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Zhang, Bin; Zhu, Jun] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY USA. [Wang, Zhi; Derry, Jonathan] Sage Bionetworks, Seattle, WA USA. [Ying, Saixia; Munson, Peter J.] NIH, CIT, Bethesda, MA USA. [Raghavachari, Nalini; Wang, Richard; Liu, Poching] NHLBI, Genom Core Facil, Genet & Dev Biol Cntr, Bethesda, MD 20892 USA. [Assimes, Themistocles L.] Stanford Univ, Framingham Heart Study, Stanford, CA 94305 USA. [McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON, Canada. [Samani, Nilesh] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Schunkert, Heribert] Med Univ Lubeck, Med Klin B, D-23538 Lubeck, Germany. [Yang, Xia] Univ Calif Los Angeles, Framingham Heart Study, Los Angeles, CA USA. RI Johnson, Andrew/G-6520-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16106 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006014 ER PT J AU Idris, AH Guffey, D Pepe, PE Brown, SP Aufderheide, TP Brooks, SC Callaway, CW Christenson, J Davis, DP Daya, MR Gray, R Kudenchuk, PJ Larsen, J Lin, S Menegazzi, JJ Sheehan, K Sopko, G Stiell, IG Nichol, G AF Idris, Ahamed H. Guffey, Danielle Pepe, Paul E. Brown, Siobhan P. Aufderheide, Tom P. Brooks, Steven C. Callaway, Clifton W. Christenson, Jim Davis, Daniel P. Daya, Mohamud R. Gray, Randal Kudenchuk, Peter J. Larsen, Jonathan Lin, Steven Menegazzi, James J. Sheehan, Kellie Sopko, George Stiell, Ian G. Nichol, Graham CA ROC Investigators TI Chest Compression Rates Between 100 and 120 per Minute are Independently Associated with Increased Adult Survival Following Out-of-Hospital Cardiac Arrest SO CIRCULATION LA English DT Meeting Abstract DE Cardiopulmonary resuscitation; Cardiac arrest; Emergency care; Guidelines; Health services research C1 [Idris, Ahamed H.; Pepe, Paul E.] UT Southwestern Med Cntr, Dallas, TX USA. [Guffey, Danielle; Brown, Siobhan P.; Sheehan, Kellie; Nichol, Graham] Univ Washington, Clin Trials Cntr, Seattle, WA 98195 USA. [Aufderheide, Tom P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Brooks, Steven C.] Queens Univ, Toronto, ON, Canada. [Callaway, Clifton W.; Menegazzi, James J.] Univ Pittsburgh, Pittsburgh, PA USA. [Christenson, Jim] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Davis, Daniel P.] UCSD Med Cntr, San Diego, CA USA. [Daya, Mohamud R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gray, Randal] Univ Alabama Birmingham, Birmingham, AL USA. [Kudenchuk, Peter J.] Univ Washington, Seattle, WA 98195 USA. [Larsen, Jonathan] Seattle Fire Dept, Seattle Fire Dept Training Div, Seattle, WA USA. [Lin, Steven] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Sopko, George] NIH, Heart Failure & Arrhythmia Branch, Bethesda, MD 20892 USA. [Stiell, Ian G.] Univ Ottawa, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16132 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006027 ER PT J AU Ismail, TF Hsu, LY Greve, A Goncalves, C Hewins, B Ferrera, P Jabbour, A Gulati, A Wage, R Gatehouse, P Firmin, D Pennell, D Arai, A Prasad, S AF Ismail, Tevfik F. Hsu, Li-Yueh Greve, Anders Goncalves, Carla Hewins, Benjamin Ferrera, Pedro Jabbour, Andrew Gulati, Ankur Wage, Ricardo Gatehouse, Peter Firmin, David Pennell, Dudley Arai, Andrew Prasad, Sanjay TI Novel Evidence of the Coronary Microvascular Steal Phenomenon in Hypertrophic Cardiomyopathy - A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study SO CIRCULATION LA English DT Meeting Abstract DE Perfusion imaging; Magnetic resonance imaging; Hypertrophic cardiomyopathy; Cardiac hypertrophy; Cardiac MRI C1 [Ismail, Tevfik F.; Goncalves, Carla; Hewins, Benjamin; Ferrera, Pedro; Jabbour, Andrew; Gulati, Ankur; Wage, Ricardo; Gatehouse, Peter; Firmin, David; Pennell, Dudley; Prasad, Sanjay] Royal Brompton Hosp, CMR Unit, London SW3 6LY, England. [Hsu, Li-Yueh; Greve, Anders; Arai, Andrew] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17333 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007067 ER PT J AU Kalogeropoulos, A Georgiopoulou, V Murphv, R Newman, AB Bauer, DC Harris, T Applegate, WB Kritchevsky, SB Butler, J AF Kalogeropoulos, Andreas Georgiopoulou, Vasiliki Murphv, Rachel Newman, Anne B. Bauer, Douglas C. Harris, Tamara Applegate, William B. Kritchevsky, Stephen B. Butler, Javed TI Dietary Sodium Intake and 10-Year Mortality in Older Adults: The Health, Aging, and Body Composition (Health ABC) Study SO CIRCULATION LA English DT Meeting Abstract DE Sodium; Elderly; Prognosis C1 [Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Murphv, Rachel; Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Applegate, William B.; Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17602 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007192 ER PT J AU Kalyani, RR Lazo, M Turkbey, E Chevalier, K Brancati, F Ouyang, P Becker, D Vaidya, D AF Kalyani, Rita R. Lazo, Mariana Turkbey, Evrim Chevalier, Karinne Brancati, Frederick Ouyang, Pamela Becker, Diane Vaidya, Dhananjay TI Gender Differences in the Association of Diabetes with Incident Coronary Heart Disease in Two Populations SO CIRCULATION LA English DT Meeting Abstract DE Coronary heart disease; Epidemiology; Disparities; Insulin resistance C1 [Kalyani, Rita R.] Johns Hopkins Univ Hosp, Div Endocrinol, Baltimore, MD 21287 USA. [Lazo, Mariana; Chevalier, Karinne; Brancati, Frederick; Becker, Diane; Vaidya, Dhananjay] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Turkbey, Evrim] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Ouyang, Pamela] Johns Hopkins Bayview, Internal Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14149 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004085 ER PT J AU Khan, H Kalogeropoulos, A Georgiopoulou, V Newman, AB Shlipak, M Garcia, M Harris, TB Kritchevsky, S Butler, J AF Khan, Hassan Kalogeropoulos, Andreas Georgiopoulou, Vasiliki Newman, Anne B. Shlipak, Michael Garcia, Melissa Harris, Tamara B. Kritchevsky, Stephen Butler, Javed TI Cellular Aging as Reflected by Leukocyte Telomere Length and Incident Heart Failure Risk in Older Adults SO CIRCULATION LA English DT Meeting Abstract DE Elderly; Heart failure; Gene expression; Risk factors C1 [Khan, Hassan; Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Shlipak, Michael] Univ Calif San Francisco, San Francisco, GA USA. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Kritchevsky, Stephen] Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17709 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007242 ER PT J AU Kizer, JR Benkeser, D Arnold, AM Ix, JH Mukamal, KJ Djousse, L Tracy, RP Siscovick, DS Zieman, SJ AF Kizer, Jorge R. Benkeser, David Arnold, Alice M. Ix, Joachim H. Mukamal, Kenneth J. Djousse, Luc Tracy, Russell P. Siscovick, David S. Zieman, Susan J. TI Advanced Glycation Endproduct Carboxymethyl-Lysine and Risk of Cardiovascular Disease in Older Adults SO CIRCULATION LA English DT Meeting Abstract DE Biomarkers; Aging; Cardiovascular disease C1 [Kizer, Jorge R.] Weill Cornell Med Coll, New York, NY USA. [Benkeser, David; Arnold, Alice M.] Univ Washington, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Djousse, Luc] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tracy, Russell P.] Univ Vermont, Colchester, VT USA. [Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11110 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001190 ER PT J AU Koh, K Quon, M Han, S AF Koh, Kwang Quon, Michael Han, Seung TI Pravastatin Combined with Valsartan Shows Additive Beneficial Vascular Effects in Patients with Hypercholesterolemia SO CIRCULATION LA English DT Meeting Abstract DE Arteriosclerosis; Endothelial function C1 [Koh, Kwang; Han, Seung] Gachon Univ, Inchon, South Korea. [Quon, Michael] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14163 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004094 ER PT J AU Liu, CY Liu, YC Wu, CL Armstrong, A Volpe, GJ van der Geest, RI Liu, M Hundley, WG Gomes, A Liu, ST Nacif, M Bluemke, DA Lima, JAC AF Liu, Chia-Ying Liu, Yuan Chang Wu, Colin Armstrong, Anderson Volpe, Gustavo J. van der Geest, Rob I. Liu, Mei Hundley, William G. Gomes, Antoinette Liu, Songtao Nacif, Marcelo Bluemke, David A. Lima, Joao A. C. TI Age is Related to Interstitial Myocardial Fibrosis in Asymptomatic Adults: Magnetic Resonance T-1 Mapping in the Multi-ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Cardiac MRI; Fibrosis; Biomarkers C1 [Liu, Chia-Ying; Liu, Yuan Chang] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Wu, Colin] NHLBI, Off Biostat, Bethesda, MD 20892 USA. [Armstrong, Anderson; Volpe, Gustavo J.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. [van der Geest, Rob I.] Leiden Univ, Med Cntr, Dept Radiol, Leiden, Netherlands. [Liu, Mei] Wake Forest Univ Hlth Sci, Dept Epidemiology& Prevent, Winston Salem, NC USA. [Hundley, William G.] Wake Forest Univ, Sch Med, Baltimore, NC USA. [Gomes, Antoinette] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. [Liu, Songtao; Nacif, Marcelo; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RI Armstrong, Anderson/G-8407-2012 OI Armstrong, Anderson/0000-0003-3161-8922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10747 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001043 ER PT J AU Liu, JK Hickson, DA Hairston, KG Taylor, HA Fox, CS AF Liu, Jiankang Hickson, DeMarc A. Hairston, Kristen G. Taylor, Herman A. Fox, Caroline S. TI Abdominal Visceral Adiposity, Fatty Liver and Renin-Angiotensin-Aldosterone System: The Jackson Heart Study SO CIRCULATION LA English DT Meeting Abstract DE Obesity; Adipose; Aldosterone C1 [Liu, Jiankang; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Hickson, DeMarc A.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Hairston, Kristen G.] Wake Forest Baptist Hlth, Internal Med, Winston Salem, NC USA. [Fox, Caroline S.] NHLBI, Cntr Populat Studies, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15531 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005227 ER PT J AU Maatz, H Monti, J Goesele, C Breiderhoff, T Pravenec, M Willnow, T Sack, M Hubner, N AF Maatz, Henrike Monti, Jan Goesele, Claudia Breiderhoff, Tilmann Pravenec, Michal Willnow, Thomas Sack, Michael Hubner, Norbert TI MrpL48 is Associated with Impaired Mitochondrial Function and Blood Pressure Regulation in Genetic Hypertension SO CIRCULATION LA English DT Meeting Abstract DE Hypertension; Mitochondria; Gene expression; Molecular biology C1 [Maatz, Henrike; Monti, Jan; Goesele, Claudia; Breiderhoff, Tilmann; Willnow, Thomas; Hubner, Norbert] Max Delbruck Cntr Berlin, Berlin, Germany. [Pravenec, Michal] Inst Physiol ASCR, Inst Physiol, Prague, Czech Republic. [Sack, Michael] NHLBI, Div Intramural Rsch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 18962 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885008322 ER PT J AU Manavski, Y Manavski, Y Bennewitz, K Tang, ZS Zhang, F Sakurai, A Gutkind, SJ Li, XR Kroll, J Dimmeler, S Chavakis, E AF Manavski, Yosif Carmona, Guillaume Bennewitz, Katrin Tang, Zhongshu Zhang, Fan Sakurai, Atsuko Gutkind, Silvio J. Li, Xuri Kroll, Jens Dimmeler, Stefanie Chavakis, Emmanouil TI Brag2, An Arf6 Gef, Regulates Integrin-dependent Adhesion in Endothelial Cells and is Involved in Angiogenesis SO CIRCULATION LA English DT Meeting Abstract DE Angiogenesis; Extracellular matrix; Signal transduction C1 [Manavski, Yosif] Goethe Univ Frankfurt, Inst Cardiovasc Regenerat, D-60054 Frankfurt, Germany. [Carmona, Guillaume] MIT, David H Koch Inst Integrat Canc Rsch, Cambridge, MA 02139 USA. [Bennewitz, Katrin; Kroll, Jens] Heidelberg Univ, Fac Med, Cntr Biomed & Med Technol Mannheim CBTM, Mannheim, Germany. [Tang, Zhongshu; Zhang, Fan; Li, Xuri] NEI, NIH, Rockville, MD USA. [Sakurai, Atsuko; Gutkind, Silvio J.] Natl Inst Dent & Craniofacial Rsch, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Dimmeler, Stefanie] Goethe Univ Frankfurt, Inst Cardiovasc Regenerat, D-60054 Frankfurt, Germany. [Chavakis, Emmanouil] Goethe Univ Frankfurt, Dept Internal Med 3, D-60054 Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 19123 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885008380 ER PT J AU Marti, CN Khan, H Kalogeropoulos, AP Georgiopoulou, VV Mann, DL Bibbins-Domingo, K Koster, A Newman, AB Harris, T Kritchevsky, SB Butler, J AF Marti, Catherine N. Khan, Hassan Kalogeropoulos, Andreas P. Georgiopoulou, Vasiliki V. Mann, Douglas L. Bibbins-Domingo, Kristen Koster, Annemarie Newman, Anne B. Harris, Tamara Kritchevsky, Stephen B. Butler, Javed TI Soluble Tumor Necrosis Factor Receptors and Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Biomarkers; Elderly C1 [Marti, Catherine N.; Khan, Hassan; Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Butler, Javed] Emory Univ, Sch Med, Atlanta, GA USA. [Mann, Douglas L.] Washington Univ, St Louis, MO USA. [Bibbins-Domingo, Kristen] UCSF, San Francisco, CA USA. [Koster, Annemarie] NIH, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest, Cardiol, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11673 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001385 ER PT J AU McCulloch, MA Gidding, S Canas, JA Ross, J Hossain, J Caulfield, M Sikes, K Sibley, C De Cesare, A Mauras, N AF McCulloch, Michael A. Gidding, Samuel Canas, J. Atilio Ross, Judith Hossain, Jobayer Caulfield, Michael Sikes, Kaitlin Sibley, Christopher De Cesare, Alain Mauras, Nelly TI Aortic Distensibility, Assessed by MRI, is Decreased in Adolescents with Type Diabetes Mellitus and Elevated LDL-C SO CIRCULATION LA English DT Meeting Abstract DE Arteriosclerosis; Type 1 Diabetes; Magnetic resonance imaging; Children C1 [McCulloch, Michael A.; Gidding, Samuel] Alfred I duPont Hosp Children, Nemours Cardiac Cntr, Wilmington, DE USA. [Canas, J. Atilio; Sikes, Kaitlin; Mauras, Nelly] Nemours Childrens Clin, Jacksonville, FL USA. [Ross, Judith] Thomas Jefferson Univ, Jefferson Med Coll, Endocrinol TJU, Philadelphia, PA 19107 USA. [Hossain, Jobayer] Alfred I duPont Hosp Children, Biostat Dept, Wilmington, DE USA. [Caulfield, Michael] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Sibley, Christopher] NIH, Clin Cntr, Bethesda, MD 20892 USA. [De Cesare, Alain] UMR S 678 UPMC Inserm, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13620 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003316 ER PT J AU Mehta, NN Matthews, G Krishnamoorthy, P Budoff, M Chen, J Glenn, M Go, A He, J Kanetsky, PA Master, S Rader, DJ Raj, D Shah, R Schreiber, M Fischer, MI Townsend, R Kusek, J Feldman, H Foulkes, A Reilly, MP AF Mehta, Nehal N. Matthews, Gregory Krishnamoorthy, Parasuram Budoff, Matthew Chen, Jing Glenn, Melanie Go, Alan He, Jiang Kanetsky, Peter A. Master, Stephen Rader, Daniel J. Raj, Dominic Shah, Rachana Schreiber, Martv Fischer, Michael I. Townsend, Ray Kusek, John Feldman, Harvey Foulkes, Andrea Reilly, Muredach P. TI Higher Plasma CXCL12 Levels Predict Incident Cardiovascular Disease Events: Findings from the Chronic Renal Insufficiency Cohort Study SO CIRCULATION LA English DT Meeting Abstract DE Genomics; Chemokines; Myocardial infarction; Outcomes C1 [Mehta, Nehal N.; Krishnamoorthy, Parasuram; Glenn, Melanie; Kanetsky, Peter A.; Master, Stephen; Rader, Daniel J.; Shah, Rachana; Townsend, Ray; Feldman, Harvey; Reilly, Muredach P.] Univ Penn, Philadelphia, PA 19104 USA. [Matthews, Gregory; Foulkes, Andrea] Univ Massachusetts, Amherst, MA 01003 USA. [Budoff, Matthew] Los Angeles Bio Med Rsch Inst, Torrance, CA USA. [Chen, Jing; He, Jiang] Tulane Med Cntr, New Orleans, LA USA. [Go, Alan] Kaiser, Cardiovasc Med, Oakland, CA USA. [Raj, Dominic] George Washington Univ, Washington, DC USA. [Schreiber, Martv] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Fischer, Michael I.] Univ Penn, Chicago, IL USA. [Kusek, John] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13352 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003199 ER PT J AU Mentz, RJ Bittner, V Starr, AZ Fleg, JL Moe, G Swank, AM Fitz-Gerald, M Nigam, A Kao, A Onwuanyi, A Kraus, WE Whellan, DJ Ellis, SJ O'Connor, CM AF Mentz, Robert J. Bittner, Vera Starr, Aijing Z. Fleg, Jerome L. Moe, Gordon Swank, Ann M. Fitz-Gerald, Meredith Nigam, Anil Kao, Andrew Onwuanyi, Anekwe Kraus, William E. Whellan, David J. Ellis, Stephen J. O'Connor, Christopher M. TI Race, Exercise Training and Outcomes in Chronic Heart Failure SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Exercise tests; Outcomes; Health and fitness C1 [Mentz, Robert J.; Kraus, William E.; O'Connor, Christopher M.] Duke Univ Med Cntr, Durham, NC USA. [Bittner, Vera; Fitz-Gerald, Meredith] Univ Alabama Birmingham, Birmingham, AL USA. [Starr, Aijing Z.; Ellis, Stephen J.] Duke Clin Rsch Inst, Durham, NC USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA. [Moe, Gordon] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Swank, Ann M.] Univ Louisville, Louisville, KY 40292 USA. [Nigam, Anil] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Nigam, Anil] Univ Montreal, Montreal, PQ, Canada. [Kao, Andrew] St Lukes Hosp, Kansas City, MO USA. [Onwuanyi, Anekwe] Morehouse Sch Med, Atlanta, GA 30310 USA. [Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13253 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003155 ER PT J AU Meyer, ML Love, SA Sorlie, PD Rosamond, WD Antini, C Metcalf, PA Simmons, S Suchindran, CM Heiss, G AF Meyer, Michelle L. Love, Shelly-Ann Sorlie, Paul D. Rosamond, Wayne D. Antini, Carmen Metcalf, Patricia A. Simmons, Shakia Suchindran, Chirayath M. Heiss, Gerardo TI Calibration of Heart Failure as the Cause of Death: The ARIC Study SO CIRCULATION LA English DT Meeting Abstract DE Heart failure; Epidemiologic methods; Cardiovascular disease; Epidemiology C1 [Meyer, Michelle L.; Love, Shelly-Ann; Rosamond, Wayne D.; Simmons, Shakia; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Sorlie, Paul D.] NHLBI, NIH, Bethesda, MD 20892 USA. [Antini, Carmen] Univ Chile, Dept Epidemiol, Sch Publ Hlth, Santiago, Chile. [Metcalf, Patricia A.] Univ Auckland, Dept Stat, Auckland 1142, New Zealand. [Suchindran, Chirayath M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17464 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007123 ER PT J AU Nacif, M Turkbey, E Rizzi, P McClelland, R Bild, D Liu, CY Barr, RG Shea, S Burke, G Budoff, M Folsom, AR Post, WS Eng, J Lima, JA Bluemke, DA AF Nacif, Marcelo Turkbey, Evrim Rizzi, Patricia McClelland, Robyn Bild, Diane Liu, Chia-Ying Barr, R. Graham Shea, Steven Burke, Gregory Budoff, Matthew Folsom, Aaron R. Post, Wendy S. Eng, John Lima, Joao A. Bluemke, David A. TI Prevalence and Determinants of Myocardial Scar by Late Gadolinium Enhancement CMR: The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Cardiac MRI; Heart failure; Longitudinal studies; Risk factors C1 [Nacif, Marcelo; Turkbey, Evrim; Bluemke, David A.] NIH, Clin Cntr, Bethesda, MD 20892 USA. [Rizzi, Patricia; Post, Wendy S.; Lima, Joao A.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. [McClelland, Robyn] Univ Washington, Collaborat Hlth Studies Coordinating Cntr, Seattle, WA 98195 USA. [Bild, Diane] NHLBI, Prevent & Populat Sci Program, Bethesda, MD 20892 USA. [Liu, Chia-Ying; Eng, John] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Barr, R. Graham; Shea, Steven] Columbia Univ, New York, NY USA. [Burke, Gregory] Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA. [Budoff, Matthew] Harbor UCLA Med Cntr, Los Angeles Biomed Rsch Inst, Div Cardiol, Torrance, CA USA. [Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11292 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001258 ER PT J AU Nambi, V Liu, XX Chambless, L De Lemos, JA Agarwal, S Virani, SS Aguilar, D Srinivas, P Deswal, A Mosley, T Boerwinkle, E Hoogeveen, RC Coresh, J Folsom, AR Heiss, G Ballantyne, CM AF Nambi, Vijay Liu, Xiaoxi Chambless, Lloyd De Lemos, James A. Agarwal, Sunil Virani, Salim S. Aguilar, David Srinivas, Pothur Deswal, Anita Mosley, Thomas Boerwinkle, Eric Hoogeveen, Ron C. Coresh, Joe Folsom, Aaron R. Heiss, Gerardo Ballantyne, Christie M. TI High Sensitivity Troponin T and NT-proBNP in Heart Failure Risk Prediction: an Analysis from the Atherosclerosis Risk in Communities (ARIC) Sudy SO CIRCULATION LA English DT Meeting Abstract DE Biomarkers; Heart failure; Troponin; Risk factors C1 [Nambi, Vijay] Baylor Coll Med, Pearland, TX USA. [Liu, Xiaoxi; Chambless, Lloyd; Agarwal, Sunil; Heiss, Gerardo] Univ N Carolina, Chapel Hill, NC USA. [De Lemos, James A.] Univ Texas Southwestern Med Cntr, Dallas, TX USA. [Virani, Salim S.; Deswal, Anita] Michael E Debakey Vet Affairs Hosp, Baylor Coll Med, Houston, TX USA. [Aguilar, David; Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Srinivas, Pothur] NIH, Prote Ctr, Bethesda, MD 20892 USA. [Mosley, Thomas] Univ Mississippi, Med Cntr, Jackson, MS 39216 USA. [Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Coresh, Joe] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Folsom, Aaron R.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14209 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004106 ER PT J AU Nasir, K Blaha, MJ Budoff, MJ Blankstien, R Agatston, AS Sibley, CT Shaw, LJ Blumenthal, RS Krumholz, H AF Nasir, Khurram Blaha, Michael J. Budoff, Matthew J. Blankstien, Ron Agatston, Arthur S. Sibley, Christopher T. Shaw, Leslee J. Blumenthal, Roger S. Krumholz, Harlan TI Eligibility for Lipid Lowering Therapy, Coronary Artery Calcification, and CHD Events - National Implications for the Appropriate Use of Preventive Pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Outcomes; Statins; Health services research; Calcification; Guidelines C1 [Nasir, Khurram; Agatston, Arthur S.] Baptist Hlth South Florida, Prevent & Wellness, Coral Gables, FL USA. [Blaha, Michael J.; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Cntr, Baltimore, MD USA. [Budoff, Matthew J.] Los Angeles Biomed Rsch Inst, Torrance, CA USA. [Blankstien, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Sibley, Christopher T.] NIH, Clin Res Unit, Bethesda, MD 20892 USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Emory Clin Cardiovasc Rsch Inst, Atlanta, GA USA. [Krumholz, Harlan] Yale Univ, Yale New Haven Hosp Cntr Outcomes Rsch & Evaluat, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16758 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006271 ER PT J AU Newburger, JW Sleeper, LA Pearson, GD Mahle, WT Dunbar-Masterson, C Mital, S Williams, I Atz, AM Ghanavem, N Goldberg, C Jacobs, J Krawczeski, CD Lewis, A Pasquali, S Pizarro, C Gruber, PJ Khaikin, S Gaynor, JW Ohye, R AF Newburger, Jane W. Sleeper, Lynn A. Pearson, Gail D. Mahle, William T. Dunbar-Masterson, Carolyn Mital, Seema Williams, Ismee Atz, Andrew M. Ghanavem, Nancy Goldberg, Caren Jacobs, Jeff Krawczeski, Catherine D. Lewis, Alan Pasquali, Sara Pizarro, Christian Gruber, Peter J. Khaikin, Svetlana Gaynor, J. W. Ohye, Richard CA Pediat Heart Network Investigators TI Transplant-Free Survival, Catheter Interventions, and Events at 3 Years in the Single Ventricle Reconstruction Trial SO CIRCULATION LA English DT Meeting Abstract DE Congenital heart disease; Children; Congenital heart surgery; Pediatric cardiology C1 [Newburger, Jane W.; Dunbar-Masterson, Carolyn] Boston Childrens Hosp, Boston, MA USA. [Sleeper, Lynn A.] New England Rsch Inst, Watertown, MA USA. [Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA. [Mahle, William T.] Emory Univ, Sch Med, Sibley Heart Cntr, Atlanta, GA USA. [Mital, Seema] Hosp Sick Children, Div Pediat Cardiol, Toronto, ON M5G 1X8, Canada. [Williams, Ismee] Columbia Univ, Med Cntr, New York, NY USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ghanavem, Nancy] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Goldberg, Caren; Ohye, Richard] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Jacobs, Jeff] Congenital Heart Inst Florida, Cardiac Surg Associates, St Petersburg, FL USA. [Krawczeski, Catherine D.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Lewis, Alan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pasquali, Sara] Duke Clin Rsch Inst, Durham, NC USA. [Pizarro, Christian] Alfred I duPont Hosp Children, Nemours Cardiac Cntr, Wilmington, DE USA. [Gruber, Peter J.] Primary Childrens Med Cntr, Salt Lake City, UT USA. [Khaikin, Svetlana] Hosp Sick Children, Cardiovasc Clin Rsch Unit, Toronto, ON M5G 1X8, Canada. [Gaynor, J. W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11328 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001264 ER PT J AU Nguyen, KL Bandettini, WP Shanbhag, S Leung, SW Wilson, JR Arai, AE AF Nguyen, Kim-L Bandettini, W. P. Shanbhag, Sujata Leung, Steve W. Wilson, Joel R. Arai, Andrew E. TI Safety and Tolerability of Regadenoson Stress CMR SO CIRCULATION LA English DT Meeting Abstract DE Cardiac MRI; Perfusion imaging; Coronary artery disease; Myocardial perfusion; Vasodilator agents C1 [Nguyen, Kim-L; Bandettini, W. P.; Shanbhag, Sujata; Leung, Steve W.; Wilson, Joel R.; Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RI Leung, Steve/E-5624-2011 OI Leung, Steve/0000-0003-2832-2258 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17636 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007212 ER PT J AU Olivier, L Baba, R Bandettini, WP Bakalov, V Sachdev, V Rosing, D Bondy, C Arai, A AF Olivier, Laura Baba, Ridhwan Bandettini, W. P. Bakalov, Vladimir Sachdev, Vandana Rosing, Douglas Bondy, Carolyn Arai, Andrew TI Bicuspid and 'Partially Fused' Aortic Valves are Common and Associated with Aortic Dilation Across Age Groups in Turner Syndrome SO CIRCULATION LA English DT Meeting Abstract DE Aortic valve; Aorta; Cardiac MRI; Congenital heart disease; Aortic diseases C1 [Olivier, Laura; Bandettini, W. P.; Sachdev, Vandana; Rosing, Douglas; Arai, Andrew] NHLBI, NIH, Bethesda, MD 20892 USA. [Baba, Ridhwan; Bakalov, Vladimir; Bondy, Carolyn] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10685 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001018 ER PT J AU Povsic, TJ Rao, SV Najjar, SS Melton, LG Prather, K Zhou, JY Adams, SD Zavodni, KL Kelly, F Hasselblad, V Heitner, JF Raman, SV Barsness, GW Patel, MR Kim, RJ Lakatta, EG Harrington, RA AF Povsic, Thomas J. Rao, Sunil V. Najjar, Samer S. Melton, Laura G. Prather, Kristi Zhou, Jiying Adams, Stacie D. Zavodni, Katherine L. Kelly, Francine Hasselblad, Vic Heitner, John F. Raman, Subha V. Barsness, Gregory W. Patel, Manesh R. Kim, Raymond J. Lakatta, Edward G. Harrington, Robert A. TI EPC Mobilization After Erythropoietin Treatment in Acute St-elevation Myocardial Infarction: The Reveal EPC Substudy SO CIRCULATION LA English DT Meeting Abstract DE Endothelial progenitor cell; Reperfusion injury; Myocardial infarction, STEMI; Infarct size; Regenerative medicine stem cells C1 [Povsic, Thomas J.; Rao, Sunil V.; Melton, Laura G.; Prather, Kristi; Zhou, Jiying; Hasselblad, Vic; Patel, Manesh R.] Duke Clin Rsch Inst, Durham, NC USA. [Najjar, Samer S.] MedStar Hlth Rsch Inst, Hyattsville, MD USA. [Adams, Stacie D.; Zavodni, Katherine L.; Kelly, Francine; Kim, Raymond J.] Duke Univ, Med Ctr, Durham, NC USA. [Heitner, John F.] New York Methoodist Hosp, Brooklyn, NY USA. [Raman, Subha V.] Ohio State Univ, Columbus, OH 43210 USA. [Barsness, Gregory W.] Mayo Clin, Rochester, MN USA. [Lakatta, Edward G.] NIA, Intramural Program, Baltimore, MD 21224 USA. [Harrington, Robert A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 11778 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885002002 ER PT J AU Rastegar, N Burt, JR Coronal-Villalobos, CP Te Riele, AS James, C Murray, B Calkins, H Tandri, H Bhonsale, A Bluemke, D Zimmerman, SL Kamel, IR AF Rastegar, Neda Burt, Jeremy R. Coronal-Villalobos, Celia P. Te Riele, Anneline S. James, Cynthia Murray, Brittney Calkins, Hugh Tandri, Harikrishna Bhonsale, Aditya Bluemke, David Zimmerman, Stefan L. Kamel, Ihab R. TI Spectrum of Imaging Findings on Cardiac MR in Subjects with an Arrythmogenic Right Ventricular Cardiomyopathy-Associated Gene Mutation SO CIRCULATION LA English DT Meeting Abstract DE Cardiomyopathy; Cardiac MRI; Epidemiology; Magnetic resonance imaging C1 [Rastegar, Neda; Burt, Jeremy R.; Coronal-Villalobos, Celia P.] Johns Hopkins Sch Med, Radiol Cardiac MRI Div, Baltimore, MD USA. [Te Riele, Anneline S.; Bhonsale, Aditya] Johns Hopkins Sch Med, Baltimore, MD USA. [James, Cynthia; Murray, Brittney; Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Sch Med, SOM DOM Cardiol, Baltimore, MD USA. [Bluemke, David] NIH, Radiol Cardiac MRI Div, Baltimore, MD USA. [Zimmerman, Stefan L.; Kamel, Ihab R.] Johns Hopkins Sch Med, SOM Rad Diagnost Imaging, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16086 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006005 ER PT J AU Rizzi, PB Nacif, MS Ricketts, EP Liu, CY Gomes, AS Hundley, G Prince, MR Carr, J McClelland, R Liu, K Eng, J Johnson, C Winslow, RL Bluemke, DA Lima, JA AF Rizzi, Patricia B. Nacif, Marcelo S. Ricketts, Erin P. Liu, Chia-Ying Gomes, Antoinette S. Hundley, Gregory Prince, Martin R. Carr, James McClelland, Robyn Liu, Kiang Eng, John Johnson, Craig Winslow, Raimond L. Bluemke, David A. Lima, Joao A. TI Variations in T1 Mapping and LV Functional Parameters in a Multi-Center Study: The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Magnetic resonance imaging; Quality assessment; Fibrosis; Ejection fraction C1 [Rizzi, Patricia B.; Ricketts, Erin P.; Eng, John; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Nacif, Marcelo S.] NIH, Bethesda, MD 20892 USA. [Liu, Chia-Ying] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Hundley, Gregory] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Prince, Martin R.] Cornell Univ, Cornell MRI, New York, NY 10021 USA. [Prince, Martin R.] Columbia Univ, New York, NY USA. [Carr, James; Liu, Kiang] Northwestern Univ, Sch Med, Chicago, IL USA. [McClelland, Robyn; Johnson, Craig] Univ Washington, Collaborat Hlth Studies Coordinating Cntr, Seattle, WA 98195 USA. [Winslow, Raimond L.] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA. [Bluemke, David A.] NIH, Clin Cntr, Bethesda, MD 20892 USA. RI Prince, Martin/S-6850-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15467 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005205 ER PT J AU Robinson, S Pelter, MM Nesbitt, T Moser, D Paul, SM Cooper, LS Dracup, K AF Robinson, Susan Pelter, Michele M. Nesbitt, Thomas Moser, Debra Paul, Steve M. Cooper, Lawton S. Dracup, Kathleen TI Relationship Between Poor Health Literacy and Heart Failure Readmissions SO CIRCULATION LA English DT Meeting Abstract DE Heart failure C1 [Robinson, Susan; Paul, Steve M.; Dracup, Kathleen] UCSF, San Francisco, CA USA. [Pelter, Michele M.] Univ Nevada, Reno, NV 89557 USA. [Nesbitt, Thomas] Univ Calif Davis, Sacramento, CA USA. [Moser, Debra] Univ Kentucky, Lexington, KY USA. [Cooper, Lawton S.] NHLBI, Clin Applicat & Prevent Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885001008 ER PT J AU Sasaki, T Sasaki, T Miller, CF Hansford, R Zviman, MM Marine, JE Spragg, D Cheng, A Tandri, H Sinha, S Kolandaivelu, A Zimmerman, SL Bluemke, DA Tomaselli, GF Berger, RD Halperin, HR Calkins, H Nazarian, S AF Sasaki, Takeshi Sasaki, Takeshi Miller, Christopher F. Hansford, Rozann Zviman, Menekhem M. Marine, Joseph E. Spragg, David Cheng, Alan Tandri, Harikrishna Sinha, Sunil Kolandaivelu, Aravindan Zimmerman, Stefan L. Bluemke, David A. Tomaselli, Gordon F. Berger, Ronald D. Halperin, Henry R. Calkins, Hugh Nazarian, Saman TI Association of Electrogram Features and Critical Reentrant Ventricular Tachycardia Sites with Nonischemic Scar on Late Gadolinium Enhanced Cardiac Magnetic Resonance SO CIRCULATION LA English DT Meeting Abstract DE Ventricular arrhythmia; Cardiac MRI; Cardiomyopathy; Electrophysiology C1 [Sasaki, Takeshi; Sasaki, Takeshi; Miller, Christopher F.; Hansford, Rozann; Zviman, Menekhem M.; Marine, Joseph E.; Spragg, David; Cheng, Alan; Tandri, Harikrishna; Sinha, Sunil; Kolandaivelu, Aravindan; Zimmerman, Stefan L.; Tomaselli, Gordon F.; Berger, Ronald D.; Halperin, Henry R.; Calkins, Hugh; Nazarian, Saman] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 9628 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000172 ER PT J AU Schwartz, SM Lu, MM Ohye, RG Hill, KD Atz, AM Naim, M Williams, I Goldberg, C Lewis, A Pigula, F Manning, P Pizarro, C Chai, P Burch, P Dunbar-Masterson, C Kaltman, J Kanter, K Sleeper, LA Schonbeck, J Ghanayem, N AF Schwartz, Steven M. Lu, Minmin Ohye, Richard G. Hill, Kevin D. Atz, Andrew M. Naim, Maryam Williams, Ismee Goldberg, Caren Lewis, Alan Pigula, Frank Manning, Peter Pizarro, Christian Chai, Paul Burch, Phillin Dunbar-Masterson, Carolyn Kaltman, Jonathan Kanter, Kirk Sleeper, Lynn A. Schonbeck, Julie Ghanayem, Nancy CA Pediat Heart Network Investigators TI Risk Factors for Prolonged Length of Stay Following Stage II procedure in the Single Ventricle Reconstruction Trial SO CIRCULATION LA English DT Meeting Abstract DE Congenital heart surgery; Single ventricle; Hypoplastic left heart; NHLBI; Pediatric cardiology C1 [Schwartz, Steven M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Lu, Minmin; Sleeper, Lynn A.; Schonbeck, Julie] New England Res Inst, Cntr Stat Anal & Rsch, Watertown, MA 02172 USA. [Ohye, Richard G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hill, Kevin D.] Duke Univ, Fayetteville, NC USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Naim, Maryam] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Williams, Ismee] Columbia Univ, New York, NY USA. [Goldberg, Caren] Univ Michigan, Ann Arbor, MI 48109 USA. [Lewis, Alan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pigula, Frank; Dunbar-Masterson, Carolyn] Childrens Hosp, Boston, MA 02115 USA. [Manning, Peter] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Pizarro, Christian] Alfred I duPont Hosp Children, Wilmington, DE USA. [Chai, Paul] All Childrens Hosp, Tampa, FL USA. [Burch, Phillin] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Kaltman, Jonathan] NHLBI, NIH, Bethesda, MD 20892 USA. [Kanter, Kirk] Emory Univ, Atlanta, GA 30322 USA. [Ghanayem, Nancy] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16568 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006213 ER PT J AU Sinner, MF Krijthe, B Aspelund, T Stepas, K Pencina, M Moser, C Sootodehnia, N Fontes, J Janssens, C Kronmal, R Magnani, J Witteman, J Chamberlain, A Lubitz, S Schnabel, R Vasan, R Wang, T Agarwal, S McManus, D Ellinor, P Larson, M Burke, G Launer, L Hofman, A Levy, D Gottdiener, J Kaab, S Couper, D Harris, T Soliman, E Stricker, B Gudnason, V Heckbert, S Benjamin, E Alonso, A AF Sinner, Moritz F. Krijthe, Bouwe Aspelund, Thor Stepas, Katherine Pencina, Michael Moser, Carlee Sootodehnia, Nona Fontes, Joao Janssens, Cecile Kronmal, Richard Magnani, Jared Witteman, Jacqueline Chamberlain, Alanna Lubitz, Steven Schnabel, Renate Vasan, Ramachandran Wang, Thomas Agarwal, Sunil McManus, David Ellinor, Patrick Larson, Martin Burke, Gregory Launer, Leonore Hofman, Albert Levy, Daniel Gottdiener, John Kaeaeb, Stefan Couper, David Harris, Tamara Soliman, Elsayed Stricker, Bruno Gudnason, Vilmundur Heckbert, Susan Benjamin, Emelia Alonso, Alvaro TI B-Type-Natriuretic Peptide and C-Reactive Protein in the Prediction of Atrial Fibrillation Risk: The CHARGE-AF Consortium SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Risk factors; Biomarkers; Natriuretic peptide; Epidemiology C1 [Sinner, Moritz F.; Lubitz, Steven; Ellinor, Patrick] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Charlestown, MA USA. [Krijthe, Bouwe; Janssens, Cecile; Witteman, Jacqueline; Hofman, Albert; Stricker, Bruno] Erasmus Med Cntr, Dept Epidemiolgy, Rotterdam, Netherlands. [Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Rsch Inst, Kopavogur, Iceland. [Stepas, Katherine; Pencina, Michael; Moser, Carlee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Sootodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Fontes, Joao; Magnani, Jared; Vasan, Ramachandran; Larson, Martin; Levy, Daniel; Benjamin, Emelia] Boston Univ, Framingham Heart study, Framingham, MA USA. [Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chamberlain, Alanna] Mayo Clini, Dept Hlth Sci Rsch, Rochester, MN USA. [Schnabel, Renate] Univ Heart Cntr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Wang, Thomas] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Agarwal, Sunil] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [McManus, David] Univ Massachusetts, Dept Med, Worcester, MA 01605 USA. [Burke, Gregory] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Launer, Leonore; Harris, Tamara] NIA, Lab Epidemiol, Bethesda, MD 20892 USA. [Gottdiener, John] Univ Maryland, Med Ctr, Div Cardiol, Baltimore, MD 21201 USA. [Kaeaeb, Stefan] Univ Hosp Munich, Dept Med 1, Munich, Germany. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Soliman, Elsayed] Wake Forest Sch Med, Dept Epidemiol, Winston Salem, NC USA. [Heckbert, Susan] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Alonso, Alvaro] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008 OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund, Thor/0000-0002-7998-5433 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 12621 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885002323 ER PT J AU Sundaresan, NR Vasudevan, P Lei, Z Kim, G Sadhana, S Ravindra, PV Pillai, V Jeevananadam, V Gupta, M Mostoslavsky, R Gupta, MP AF Sundaresan, Nagalingam Ravi Vasudevan, Prabhakaran Lei, Zhong Kim, Gene Sadhana, Samant Ravindra, P. V. Pillai, Vinodkumar Jeevananadam, Valluvan Gupta, Madhu Mostoslavsky, Raul Gupta, Mahesh P. TI Novel players in Hypertrophy SO CIRCULATION LA English DT Meeting Abstract DE Cardiac hypertrophy C1 [Sundaresan, Nagalingam Ravi; Vasudevan, Prabhakaran; Sadhana, Samant; Pillai, Vinodkumar; Jeevananadam, Valluvan; Gupta, Mahesh P.] Univ Chicago, Chicago, IL 60637 USA. [Lei, Zhong; Mostoslavsky, Raul] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Gene] Univ Chicago, Dept Med 4, Chicago, IL 60637 USA. [Ravindra, P. V.] NCI, Ctr Canc, Chicago, IL USA. [Gupta, Madhu] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005325 ER PT J AU Taylor, DA Perin, EC Willerson, JT Pepine, CJ Henry, TD Ellis, SG Zhao, DX Bolli, R Byrne, BJ Traverse, JH Penn, MS Hatzopoulos, AK Carlson, MA Wise, E Lai, DJ Baraniuk, S Cabreira-Hansen, MG Smith, D Moye, LA Skarlatos, SI Simari, RD Cogle, CR AF Taylor, Doris A. Perin, Emerson C. Willerson, James T. Pepine, Carl J. Henry, Timothy D. Ellis, Stephen G. Zhao, David X. Bolli, Roberto Byrne, Barry J. Traverse, Jay H. Penn, Marc S. Hatzopoulos, Antonis K. Carlson, Marjorie A. Wise, Elizabeth Lai, Dejian Baraniuk, Sarah Cabreira-Hansen, Maria G. Smith, Deirdre Moye, Lemuel A. Skarlatos, Sonia I. Simari, Robert D. Cogle, Christopher R. TI Improved Myocardial Function in Patients with Chronic Ischemic Heart Disease Treated with Transendocardial Delivery of Bone Marrow Mononuclear Cells Depends Upon Input Cell Phenotype and Function SO CIRCULATION LA English DT Meeting Abstract DE Cardiac injection; Cells; Heart failure; Clinical trials; Ejection fraction C1 [Taylor, Doris A.; Perin, Emerson C.; Willerson, James T.; Cabreira-Hansen, Maria G.; Smith, Deirdre] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. [Pepine, Carl J.] Univ Florida, Coll Med, Houston, TX USA. [Henry, Timothy D.] Univ Minnesota, Sch Med, Minneapolis Heart Inst Fdn, Minneapolis, MN 55455 USA. [Ellis, Stephen G.] Cleveland Clin, Cleveland, OH 44106 USA. [Zhao, David X.; Hatzopoulos, Antonis K.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Bolli, Roberto] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40292 USA. [Byrne, Barry J.; Wise, Elizabeth; Cogle, Christopher R.] Univ Florida, Coll Med, Gainesville, FL USA. [Traverse, Jay H.] Univ Minnesota, Sch Med, Minneapolis Heart Inst Fdn Abbott, Minneapolis, MN 55455 USA. [Penn, Marc S.] Summa Cardiovasc Inst, Rootstown, OH USA. [Carlson, Marjorie A.] Univ Minnesota, Sch Med, Cntr Cardiovasc Repair, Minneapolis, MN 55455 USA. [Lai, Dejian; Baraniuk, Sarah; Moye, Lemuel A.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Skarlatos, Sonia I.] NHLBI, Bethesda, MD 20892 USA. [Simari, Robert D.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16354 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006119 ER PT J AU Trivedi, D Loftin, C Langenbach, R AF Trivedi, Darshini Loftin, Charles Langenbach, Robert TI The Deficiency of beta-Arrestin 2 Attenuates Abdominal Aortic Aneurysm Formation in Mice SO CIRCULATION LA English DT Meeting Abstract DE Abdominal aortic aneurysm C1 [Trivedi, Darshini; Langenbach, Robert] NIEHS, Lab Toxicol & Pharmacol, Durham, NC USA. [Loftin, Charles] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 19684 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885009168 ER PT J AU Truong, QA Hayden, D Woodard, PK Kirby, R Chou, ET Wiviott, SD Fleg, JL Schoenfeld, DA Udelson, JE Hoffmann, U AF Truong, Quynh A. Hayden, Douglas Woodard, Pamela K. Kirby, Ruth Chou, Eric T. Wiviott, Stephen D. Fleg, Jerome L. Schoenfeld, David A. Udelson, James E. Hoffmann, Udo TI Women Benefit Most from Early CCTA Compared to Standard ED Evaluation for Acute Chest Pain: The ROMICAT II Trial SO CIRCULATION LA English DT Meeting Abstract DE Cardiac CT; Emergency care; Comparative effectiveness; Clinical trials; Cardiovascular imaging C1 [Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, Boston, MA 02114 USA. [Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hayden, Douglas; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Woodard, Pamela K.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Kirby, Ruth; Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Chou, Eric T.] Kaiser Permanente Fontana Med Cntr, Fontana, CA USA. [Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Udelson, James E.] Tufts Med Cntr, Cardiol & CardioVasc Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 12596 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885002314 ER PT J AU Turkbey, EB Backlund, JYC Cleary, PA Nacif, MS Gai, N van der Geest, RJ Armstrong, A Volpe, GJ Nazarian, S Lachin, JM Lima, JA Bluemke, DA AF Turkbey, Evrim B. Backlund, Jye-Yu C. Cleary, Patricia A. Nacif, Marcelo S. Gai, Neville van der Geest, Rob J. Armstrong, Anderson Volpe, Gustavo J. Nazarian, Saman Lachin, John M. Lima, Joao A. Bluemke, David A. CA DCCT EDIC Rsch Grp TI Myocardial Structural Remodeling and Tissue Composition by Cardiac Magnetic Resonance (CMR) in Relation to Metabolic Syndrome in Type 1 Diabetes: The DCCT/EDIC Study SO CIRCULATION LA English DT Meeting Abstract DE Type 1 Diabetes; Magnetic resonance Imaging; Metabolic syndromie; Ventricular remodeling C1 [Turkbey, Evrim B.] NIH, North Bethesda, MD USA. [Backlund, Jye-Yu C.; Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Nacif, Marcelo S.; Gai, Neville; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [van der Geest, Rob J.] Leiden Univ, Div Image Proc, Leiden, Netherlands. [Armstrong, Anderson; Volpe, Gustavo J.; Nazarian, Saman; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. RI Armstrong, Anderson/G-8407-2012; van der Geest, Rob/J-8193-2015 OI Armstrong, Anderson/0000-0003-3161-8922; van der Geest, Rob/0000-0002-9084-5597 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16435 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006149 ER PT J AU Vaidya, D Bennett, WL Sibley, CT Polak, JF Herrington, DM Ouyang, P AF Vaidya, Dhananjay Bennett, Wendy L. Sibley, Christopher T. Polak, Joseph F. Herrington, David M. Ouyang, Pamela TI Ever-pregnant Women Have Less Distensible Carotid Arteries Than Never-pregnant Women: Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Arteries; Ultrasound; Pregnancy C1 [Vaidya, Dhananjay; Bennett, Wendy L.; Ouyang, Pamela] Johns Hopkins Univ, Baltimore, MD USA. [Sibley, Christopher T.] NIH, Clin Cntr, Bethesda, MD 20892 USA. [Polak, Joseph F.] Tufts Univ Sch Med, Boston, MA USA. [Herrington, David M.] Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 10126 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000312 ER PT J AU Van Hee, VC Chan, SH Szpiro, AA Oron, AP DeRoo, LA London, SJ Kaufman, JD Sandler, DP AF Van Hee, Victor C. Chan, Stephanie H. Szpiro, Adam A. Oron, Assaf P. DeRoo, Lisa A. London, Stephanie J. Kaufman, Joel D. Sandler, Dale P. TI Long Term Air Pollution Exposure and Blood Pressure in the Sister Study SO CIRCULATION LA English DT Meeting Abstract DE Air pollution; Blood pressure; Epidemiology; Risk factors; Prevention C1 [Van Hee, Victor C.; Chan, Stephanie H.; Szpiro, Adam A.; Oron, Assaf P.; Kaufman, Joel D.] Univ Washington, Seattle, WA 98195 USA. [DeRoo, Lisa A.; Sandler, Dale P.] NIEHS, Chron Dis Epidemiol Grp, Rsch Triangle Pk, NC USA. [London, Stephanie J.] NIEHS, Genet Environm & Resp Dis Grp, Rsch Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 15418 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885005193 ER PT J AU Venkatesan, B Valente, AJ Siebenlist, U Chandrasekar, B AF Venkatesan, Balachandar Valente, Anthony J. Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS (Act1 Or TRAF3IP2) is Critical in High Glucose-induced Endothelial Dysfunction SO CIRCULATION LA English DT Meeting Abstract DE Endothelin; Inflammation; Adherence; Oxidative stress; Arteriosclerosis C1 [Venkatesan, Balachandar] Madras Diabet Rsch Fdn, Siruseri, India. [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 9690 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000189 ER PT J AU Venkatesh, BA Armstrong, A Liu, CY Donekal, S Yoneyama, K Wu, C Gomes, AS Hundley, GW Bluemke, DA Lima, JA AF Venkatesh, Bharath Ambale Armstrong, Anderson Liu, Chia-Ying Donekal, Sirisha Yoneyama, Kihei Wu, Colin Gomes, Antoinette S. Hundley, Gregory W. Bluemke, David A. Lima, Joao A. TI Strain Relaxation Index Predicts Heart Failure and Atrial Fibrillation Over a 10 Year Follow-Up Period: The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Diastolic function; Magnetic resonance imaging; Cardiac imaging; Heart failure; Ventricular function C1 [Venkatesh, Bharath Ambale; Liu, Chia-Ying; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Armstrong, Anderson; Donekal, Sirisha; Yoneyama, Kihei] Johns Hopkins Univ, Div Cardiovasc Imaging, Baltimore, MD USA. [Wu, Colin] NHLBI, Rockledge Cntr 2, OD, NIH, Bethesda, MD 20892 USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Hundley, Gregory W.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RI Armstrong, Anderson/G-8407-2012; Ambale Venkatesh, Bharath/F-4941-2016 OI Armstrong, Anderson/0000-0003-3161-8922; Ambale Venkatesh, Bharath/0000-0002-2330-2373 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14547 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004260 ER PT J AU Vinogradova, TM Lyashkov, AE Li, Y Lukyanenko, Y Lakatta, EG AF Vinogradova, Tatiana M. Lyashkov, Alexey E. Li, Yue Lukyanenko, Yevgeniya Lakatta, Edward G. TI Synergism of PDE3 and PDE4 Activity Regulates cAMP-Mediated PKA-Dependent Local Ca2+ Releases to Modulate Basal Spontaneous Firing of Cardiac Pacemaker Cells SO CIRCULATION LA English DT Meeting Abstract DE Sinoatrial node; Calcium; Phospholamban; Electrophysiology; Pacemakers C1 [Vinogradova, Tatiana M.; Lyashkov, Alexey E.; Li, Yue; Lukyanenko, Yevgeniya; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 13555 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885003286 ER PT J AU Volpe, GJ Nacif, MS Liu, YC Turkbey, EB Rizzi, PB Lederer, DJ Barr, RG Polak, JF Wu, C Liu, CY Bluemke, DA Lima, JA AF Volpe, Gustavo J. Nacif, Marcelo S. Liu, Yuan Chang Turkbey, Evrim B. Rizzi, Patricia B. Lederer, David J. Barr, R. Graham Polak, Joseph F. Wu, Colin Liu, Chia-Ying Bluemke, David A. Lima, Joao A. TI Factors Associated with Interstitial Fibrosis by CMR T1 Mapping After 10 Years: The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Fibrosis; Magnetic resonance imaging; Risk factors; Smoking C1 [Volpe, Gustavo J.; Liu, Yuan Chang; Liu, Chia-Ying; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Nacif, Marcelo S.] NIH, Bethesda, MD 20892 USA. [Turkbey, Evrim B.] NIH, Radiol & Imaging Sci RAD & IS, Bethesda, MD 20892 USA. [Rizzi, Patricia B.] Johns Hopkins Univ Hosp, Dvis Cardiol, Baltimore, MD 21287 USA. [Lederer, David J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Barr, R. Graham] Columbia Univ, New York, NY USA. [Polak, Joseph F.] Tufts Med Cntr, Ultrasound Reading Cntr, Boston, MA USA. [Wu, Colin] NHLBI, Rockledge Cntr 2, NIH, OD, Bethesda, MD 20892 USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 17372 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885007090 ER PT J AU Wong, TC Piehler, K Klock, AM Kang, IA Kadakkal, A Kellman, P Schwartzman, DS Mulukutla, SR Simon, MA Schelbert, EB AF Wong, Timothy C. Piehler, Kayla Klock, Amanda M. Kang, Ian A. Kadakkal, Ajay Kellman, Peter Schwartzman, David S. Mulukutla, Suresh R. Simon, Marc A. Schelbert, Erik B. TI Myocardial Fibrosis Quantified by Cardiovascular Magnetic Resonance is Associated with Diabetes and Predicts Mortality SO CIRCULATION LA English DT Meeting Abstract DE Cardiac MRI; Fibrosis; Outcomes; Diastole C1 [Wong, Timothy C.; Piehler, Kayla; Klock, Amanda M.; Kang, Ian A.; Kadakkal, Ajay; Schwartzman, David S.; Mulukutla, Suresh R.; Simon, Marc A.; Schelbert, Erik B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Kellman, Peter] NHLBI, Med Imaging Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 16452 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885006158 ER PT J AU Xie, A Kapoor, N Liu, H Bare, D Gu, LZ Boheler, KR Banach, K Dudley, SC AF Xie, An Kapoor, Nidhi Liu, Hong Bare, Dan Gu, Lianzhi Boheler, Kenneth R. Banach, Kathrin Dudley, Samuel C. TI A Role for Mitochondria in Triggered Activity from Cardiomyocytes with Reduced Sarcoplasmic Reticulum Calcium Release SO CIRCULATION LA English DT Meeting Abstract DE Arrhythmias treatment of; Mitochondria; Calcium C1 [Xie, An; Liu, Hong; Bare, Dan; Gu, Lianzhi; Banach, Kathrin; Dudley, Samuel C.] Univ Illinois, Chicago, IL USA. [Kapoor, Nidhi] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 19255 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885009001 ER PT J AU Yang, E Nacif, MS Liu, CY Donekal, S Venkatesh, BA Prince, MR Lima, JA Bluemke, DA AF Yang, Eunice Nacif, Marcelo S. Liu, Chia-Ying Donekal, Sirisha Venkatesh, Bharath A. Prince, Martin R. Lima, Joao A. Bluemke, David A. TI Assessment of Myocardial Wall Thickness and T1 Mapping is Highly Reproducible in Multi-Center Trials: The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract DE Muscle, cardiac - see Myocardium; Strain rate; Magnetic resonance imaging C1 [Yang, Eunice; Nacif, Marcelo S.; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Liu, Chia-Ying; Donekal, Sirisha; Venkatesh, Bharath A.; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Prince, Martin R.] Weill Cornell Med Coll, New York, NY USA. RI Ambale Venkatesh, Bharath/F-4941-2016; Prince, Martin/S-6850-2016 OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 14728 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885004337 ER PT J AU Yeboah, J Carr, JJ Terry, JG Ding, JZ Zeb, I Liu, ST Nasir, K Post, W Blumenthal, RS Budoff, M AF Yeboah, Joseph Carr, Jeffery J. Terry, James G. Ding, Jingzhong Zeb, Irfan Liu, Songtao Nasir, Khurram Post, Wendy Blumenthal, Roger S. Budoff, Mathew TI Computed Tomography Derived Cardiovascular Risk Markers, Incident Cardiovascular Events and All- Cause Mortality In Adults Free of Clinical Cardiovascular Disease. The Multi Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract DE Cardiac CT; Risk factors; Cardiovascular disease; Calcification; Valvular heart disease C1 [Yeboah, Joseph; Carr, Jeffery J.; Terry, James G.; Ding, Jingzhong] Wake Forest Univ, Winston Salem, NC 27109 USA. [Zeb, Irfan] Los Angeles Biomed Rsch Inst, Torrance, CA USA. [Liu, Songtao] NIH, Bethesda, MD 20892 USA. [Nasir, Khurram; Post, Wendy; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA. [Budoff, Mathew] Los Angeles Biomed Rsch Inst, Torrance, CA USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 20 PY 2012 VL 126 IS 21 SU S MA 9536 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V31LL UT WOS:000208885000148 ER PT J AU Scheidweiler, KB Desrosiers, NA Huestis, MA AF Scheidweiler, Karl B. Desrosiers, Nathalie A. Huestis, Marilyn A. TI Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry SO CLINICA CHIMICA ACTA LA English DT Article DE Cannabinoids; Cannabinoid glucuronides; Urine; Metabolites; Analytical method; LCMSMS ID SOLID-PHASE EXTRACTION; GAS-CHROMATOGRAPHY; GC-MS; 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; WHOLE-BLOOD; TETRAHYDROCANNABINOL GLUCURONIDE; AUTOMATED EXTRACTION; PLASMA; METABOLITES; STABILITY AB Background: cannabis is the most commonly abused drug of abuse and is commonly quantified during urine drug testing. We are conducting a controlled drug administration study investigating efficacy of urinary cannabinoid glucuronide metabolites for documenting recency of cannabis intake and for determining stability of urinary cannabinoids. Methods: A liquid chromatography tandem mass spectrometry method was developed and validated quantifying Delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide and THCCOOH-glucuronide in 0.5 ml human urine via supported-liquid extraction. Chromatography was performed on an Ultra Biphenyl column with a gradient of 10 mmol/l ammonium acetate, pH 6.15 and 15% methanol in acetonitrile at 0.4 ml/min. Analytes were monitored by positive and negative mode electrospray ionization and multiple reaction monitoring mass spectrometry. Results: Linear ranges were 0.5-50 ng/ml for THC-glucuronide, 1-100 ng/ml for THCCOOH, 11-OH-THC and cannabidiol, 2-100 ng/ml for THC and cannabinol, and 5-500 ng/ml for THCCOOH-glucuronide (R-2 > 0.99). Mean extraction efficiencies were 34-73% with analytical recovery (bias) 80.5-118.0% and total imprecision 3.0-10.2% coefficient of variation. Conclusion: This method simultaneously quantifies urinary cannabinoids and phase II glucuronide metabolites, and enables evaluation of urinary cannabinoid glucuronides for documenting recency of cannabis intake and cannabinoid stability. The assay is applicable for routine urine cannabinoid testing. Published by Elsevier B.V. C1 [Huestis, Marilyn A.] NIDA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX The authors recognize David M. Schwope's technical advice during method development. This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 40 TC 29 Z9 29 U1 7 U2 38 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD NOV 20 PY 2012 VL 413 IS 23-24 BP 1839 EP 1847 DI 10.1016/j.cca.2012.06.034 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 006UN UT WOS:000308844700007 PM 22771478 ER PT J AU Zheng, X Vittar, NBR Gai, XH Fernandez-Barrena, MG Moser, CD Hu, CL Almada, LL McCleary-Wheeler, AL Elsawa, SF Vrabel, AM Shire, AM Comba, A Thorgeirsson, SS Kim, Y Liu, QG Fernandez-Zapico, ME Roberts, LR AF Zheng, Xin Vittar, Natalia B. Rumie Gai, Xiaohong Fernandez-Barrena, Maite G. Moser, Catherine D. Hu, Chunling Almada, Luciana L. McCleary-Wheeler, Angela L. Elsawa, Sherine F. Vrabel, Anne M. Shire, Abdirashid M. Comba, Andrea Thorgeirsson, Snorri S. Kim, Youngsoo Liu, Qingguang Fernandez-Zapico, Martin E. Roberts, Lewis R. TI The Transcription Factor GLI1 Mediates TGF beta 1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism SO PLOS ONE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN; SONIC HEDGEHOG; RISK-FACTORS; CELLS; BETA; METASTASIS; RECURRENCE; CANCER; SNAIL AB The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-beta 1 (TGF beta 1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGF beta 1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC. C1 [Zheng, Xin; Vittar, Natalia B. Rumie; Gai, Xiaohong; Fernandez-Barrena, Maite G.; Moser, Catherine D.; Hu, Chunling; Almada, Luciana L.; McCleary-Wheeler, Angela L.; Vrabel, Anne M.; Shire, Abdirashid M.; Comba, Andrea; Fernandez-Zapico, Martin E.; Roberts, Lewis R.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Zheng, Xin; Gai, Xiaohong; Liu, Qingguang] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Xian 710049, Shaanxi, Peoples R China. [Zheng, Xin; Vittar, Natalia B. Rumie; Gai, Xiaohong; Fernandez-Barrena, Maite G.; Moser, Catherine D.; Hu, Chunling; Almada, Luciana L.; McCleary-Wheeler, Angela L.; Elsawa, Sherine F.; Vrabel, Anne M.; Shire, Abdirashid M.; Comba, Andrea; Fernandez-Zapico, Martin E.; Roberts, Lewis R.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Vittar, Natalia B. Rumie; Fernandez-Barrena, Maite G.; Almada, Luciana L.; McCleary-Wheeler, Angela L.; Elsawa, Sherine F.; Vrabel, Anne M.; Comba, Andrea; Fernandez-Zapico, Martin E.] Mayo Clin, Schulze Ctr Novel Therapeut, Rochester, MN USA. [Elsawa, Sherine F.] No Illinois Univ, Dept Biol Sci, De Kalb, IL USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Youngsoo] Isis Pharmaceut Inc, Carlsbad, CA USA. RP Roberts, LR (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. EM roberts.lewis@mayo.edu RI GARCIA FERNANDEZ DE BARRENA, MAITE/J-8040-2014 OI GARCIA FERNANDEZ DE BARRENA, MAITE/0000-0003-0375-6236 FU National Institutes of Health [CA100882, CA128633, CA165076]; Mayo Clinic Center for Cell Signaling in Gastroenterology [NIDDK P30DK084567]; Mayo Clinic Cancer Center [CA15083]; Mayo Clinic Center for Translational Science Activities (NIH/NCRR CTSA) [KL2 RR024151]; American Gastroenterological Association Foundation for Digestive Health and Nutrition Bridgin Grant FX This work was supported by National Institutes of Health Grants CA100882 and CA128633 (to LRR) and CA165076 (to LRR and MEFZ); the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567) (to MEFZ); the Mayo Clinic Cancer Center (CA15083), the Mayo Clinic Center for Translational Science Activities (NIH/NCRR CTSA Grant Number KL2 RR024151), and an American Gastroenterological Association Foundation for Digestive Health and Nutrition Bridging Grant (to LRR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 35 Z9 39 U1 0 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 19 PY 2012 VL 7 IS 11 AR e49581 DI 10.1371/journal.pone.0049581 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040PB UT WOS:000311333800040 PM 23185371 ER PT J AU Zhang, L Orban, M Lorenz, M Barocke, V Braun, D Urtz, N Schulz, C von Bruhl, ML Tirniceriu, A Gaertner, F Proia, RL Graf, T Bolz, SS Montanez, E Prinz, M Muller, A von Baumgarten, L Billich, A Sixt, M Fassler, R von Andrian, UH Junt, T Massberg, S AF Zhang, Lin Orban, Martin Lorenz, Michael Barocke, Verena Braun, Daniel Urtz, Nicole Schulz, Christian von Bruehl, Marie-Luise Tirniceriu, Anca Gaertner, Florian Proia, Richard L. Graf, Thomas Bolz, Steffen-Sebastian Montanez, Eloi Prinz, Marco Mueller, Alexandra von Baumgarten, Louisa Billich, Andreas Sixt, Michael Faessler, Reinhard von Andrian, Ulrich H. Junt, Tobias Massberg, Steffen TI A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEMARCATION MEMBRANE SYSTEM; PROTEIN-COUPLED RECEPTOR; HEMATOPOIETIC STEM-CELL; IN-VIVO; PLATELET PRODUCTION; LYMPHOCYTE EGRESS; BLOOD-PLATELETS; RETICULATED PLATELETS; HUMAN MEGAKARYOCYTES; VASCULAR MATURATION AB Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. C1 [Zhang, Lin; Orban, Martin; Lorenz, Michael; Barocke, Verena; Braun, Daniel; Urtz, Nicole; Schulz, Christian; von Bruehl, Marie-Luise; Tirniceriu, Anca; Gaertner, Florian; Massberg, Steffen] Univ Munich, Klinikum Univ, Med Klin & Poliklin 1, D-81337 Munich, Germany. [von Baumgarten, Louisa] Univ Munich, Klinikum Univ, Neurol Klin, D-81337 Munich, Germany. [Zhang, Lin; Orban, Martin; Lorenz, Michael; Barocke, Verena; Braun, Daniel; Urtz, Nicole; Schulz, Christian; von Bruehl, Marie-Luise; Tirniceriu, Anca; Gaertner, Florian; Massberg, Steffen] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany. [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Graf, Thomas] Ctr Genom Regulat, Barcelona 08003, Spain. [Graf, Thomas] Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain. [Bolz, Steffen-Sebastian] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. [Montanez, Eloi; Sixt, Michael; Faessler, Reinhard] Max Planck Inst Biochem, D-82152 Martinsried, Germany. [Prinz, Marco; Mueller, Alexandra] Univ Freiburg Klinikum, Inst Pathol, Abt Neuropathol, D-79106 Freiburg, Germany. [Prinz, Marco] Univ Freiburg, BIOSS Ctr Biol Signalling, D-79108 Freiburg, Germany. [Billich, Andreas; Junt, Tobias] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Massberg, Steffen] German Cardiovasc Res Ctr, Munich Heart Alliance, D-80802 Munich, Germany. RP Massberg, S (reprint author), Univ Munich, Klinikum Univ, Med Klin & Poliklin 1, D-81337 Munich, Germany. EM steffen.massberg@med.uni-muenchen.de RI Schulz, Christian/J-8545-2012; von Andrian, Ulrich/A-5775-2008; Graf, Thomas/B-4252-2015 OI Schulz, Christian/0000-0003-3878-7833; Sixt, Michael/0000-0002-6620-9179; Graf, Thomas/0000-0003-2774-4117 FU Deutsche Forschungsgemeinschaft; Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This study was supported by the Deutsche Forschungsgemeinschaft and by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 52 TC 46 Z9 47 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 19 PY 2012 VL 209 IS 12 BP 2165 EP 2181 DI 10.1084/jem.20121090 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 040BY UT WOS:000311295600005 PM 23148237 ER PT J AU Snow, AL Xiao, WM Stinson, JR Lu, W Chaigne-Delalande, B Zheng, LX Pittaluga, S Matthews, HF Schmitz, R Jhavar, S Kuchen, S Kardava, L Wang, W Lamborn, IT Jing, HE Raffeld, M Moir, S Fleisher, TA Staudt, LM Su, HC Lenardo, MJ AF Snow, Andrew L. Xiao, Wenming Stinson, Jeffrey R. Lu, Wei Chaigne-Delalande, Benjamin Zheng, Lixin Pittaluga, Stefania Matthews, Helen F. Schmitz, Roland Jhavar, Sameer Kuchen, Stefan Kardava, Lela Wang, Wei Lamborn, Ian T. Jing, Huie Raffeld, Mark Moir, Susan Fleisher, Thomas A. Staudt, Louis M. Su, Helen C. Lenardo, Michael J. TI Congenital B cell lymphocytosis explained by novel germline CARD11 mutations SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTORS; HEALTHY-CHILDREN; LYMPHOMA; ACTIVATION; RECEPTOR; CARMA1; PROLIFERATION; PATHOGENESIS; COMPARTMENT AB Nuclear factor-kappa B (NF-kappa B) controls genes involved in normal lymphocyte functions, but constitutive NF-kappa B activation is often associated with B cell malignancy. Using high-throughput whole transcriptome sequencing, we investigated a unique family with hereditary polyclonal B cell lymphocytosis. We found a novel germline heterozygous missense mutation (E127G) in affected patients in the gene encoding CARD11, a scaffolding protein required for antigen receptor (AgR)-induced NF-kappa B activation in both B and T lymphocytes. We subsequently identified a second germline mutation (G116S) in an unrelated, phenotypically similar patient, confirming mutations in CARD11 drive disease. Like somatic, gain-of-function CARD11 mutations described in B cell lymphoma, these germline CARD11 mutants spontaneously aggregate and drive constitutive NF-kappa B activation. However, these CARD11 mutants rendered patient T cells less responsive to AgR-induced activation. By reexamining this rare genetic disorder first reported four decades ago, our findings provide new insight into why activating CARD11 mutations may induce B cell expansion and preferentially predispose to B cell malignancy without dramatically perturbing T cell homeostasis. C1 [Snow, Andrew L.; Lu, Wei; Chaigne-Delalande, Benjamin; Zheng, Lixin; Matthews, Helen F.; Lenardo, Michael J.] NIAID, Lymphocyte Mol Genet Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Kardava, Lela; Wang, Wei; Moir, Susan] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Lamborn, Ian T.; Jing, Huie; Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Snow, Andrew L.; Stinson, Jeffrey R.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Xiao, Wenming] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Schmitz, Roland; Jhavar, Sameer; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kuchen, Stefan] NIAMSD, Genom & Immun Sect, NIH, Bethesda, MD 20892 USA. [Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Snow, AL (reprint author), NIAID, Lymphocyte Mol Genet Unit, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andrew.snow@usuhs.edu; lenardo@nih.gov RI Su, Helen/H-9541-2015; OI Su, Helen/0000-0002-5582-9110; Kuchen, Stefan/0000-0003-4899-8132; Snow, Andrew/0000-0002-8728-6691 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Cancer Institute; Uniformed Services University of Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute and an intramural grant from Uniformed Services University of the Health Sciences (to A.L. Snow and J.R. Stinson). NR 38 TC 41 Z9 44 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 19 PY 2012 VL 209 IS 12 BP 2247 EP 2261 DI 10.1084/jem.20120831 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 040BY UT WOS:000311295600010 PM 23129749 ER PT J AU McCaughtry, TM Etzensperger, R Alag, A Tai, XG Kurtulus, S Park, JH Grinberg, A Love, P Feigenbaum, L Erman, B Singer, A AF McCaughtry, Tom M. Etzensperger, Ruth Alag, Amala Tai, Xuguang Kurtulus, Sema Park, Jung-Hyun Grinberg, Alex Love, Paul Feigenbaum, Lionel Erman, Batu Singer, Alfred TI Conditional deletion of cytokine receptor chains reveals that IL-7 and IL-15 specify CD8 cytotoxic lineage fate in the thymus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; DOUBLE-POSITIVE THYMOCYTES; INTERLEUKIN-7 RECEPTOR; STROMAL LYMPHOPOIETIN; TRANSCRIPTION FACTOR; DEFICIENT MICE; GAMMA CHAIN; LYMPHOID DEVELOPMENT; NEGATIVE SELECTION; RUNX PROTEINS AB The thymus generates T cells with diverse specificities and functions. To assess the contribution of cytokine receptors to the differentiation of T cell subsets in the thymus, we constructed conditional knockout mice in which IL-7R alpha or common cytokine receptor gamma chain (gamma(c)) genes were deleted in thymocytes just before positive selection. We found that gamma(c) expression was required to signal the differentiation of MHC class I (MHC-I)-specific thymocytes into CD8(+) cytotoxic lineage T cells and into invariant natural killer T cells but did not signal the differentiation of MHC class II (MHC-II)-specific thymocytes into CD4(+) T cells, even into regulatory Foxp3(+)CD4(+) T cells which require gamma(c) signals for survival. Importantly, IL-7 and IL-15 were identified as the cytokines responsible for CD8(+) cytotoxic T cell lineage specification in vivo. Additionally, we found that small numbers of aberrant CD8(+) T cells expressing Runx3d could arise without gamma(c) signaling, but these cells were developmentally arrested before expressing cytotoxic lineage genes. Thus, gamma(c)-transduced cytokine signals are required for cytotoxic lineage specification in the thymus and for inducing the differentiation of MHC-I-selected thymocytes into functionally mature T cells. C1 [McCaughtry, Tom M.; Etzensperger, Ruth; Alag, Amala; Tai, Xuguang; Park, Jung-Hyun; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kurtulus, Sema; Erman, Batu] Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. [Grinberg, Alex; Love, Paul] NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, SAIC Frederick, Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM singera@nih.gov RI Park, Jung Hyun /B-5712-2015 OI Park, Jung Hyun /0000-0002-9547-9055 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 49 TC 29 Z9 29 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 19 PY 2012 VL 209 IS 12 BP 2263 EP 2276 DI 10.1084/jem.20121505 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 040BY UT WOS:000311295600011 PM 23109710 ER PT J AU Siao, CJ Lorentz, CU Kermani, P Marinic, T Carter, J McGrath, K Padow, VA Mark, W Falcone, DJ Cohen-Gould, L Parrish, DC Habecker, BA Nykjaer, A Ellenson, LH Tessarollo, L Hempstead, BL AF Siao, Chia-Jen Lorentz, Christina U. Kermani, Pouneh Marinic, Tina Carter, John McGrath, Kelly Padow, Victoria A. Mark, Willie Falcone, Domenick J. Cohen-Gould, Leona Parrish, Diana C. Habecker, Beth A. Nykjaer, Anders Ellenson, Lora H. Tessarollo, Lino Hempstead, Barbara L. TI ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NERVE GROWTH-FACTOR; P75 NEUROTROPHIN RECEPTOR; SMOOTH-MUSCLE-CELLS; BLOOD-VESSEL FORMATION; THERAPEUTIC INTERVENTION; SYMPATHETIC NEURONS; DEFICIENT MICE; TGF-BETA; PDGF-B; SURVIVAL AB Treatment of acute cardiac ischemia focuses on reestablishment of blood flow in coronary arteries. However, impaired microvascular perfusion damages peri-infarct tissue, despite arterial patency. Identification of cytokines that induce microvascular dysfunction would provide new targets to limit microvascular damage. Pro-nerve growth factor (NGF), the precursor of NGF, is a well characterized cytokine in the brain induced by injury. ProNGF activates p75 neurotrophin receptor (p75(NTR)) and sortilin receptors to mediate proapoptotic responses. We describe induction of proNGF by cardiomyocytes, and p75(NTR) in human arterioles after fatal myocardial infarction, but not with unrelated pathologies. After mouse cardiac ischemia-reperfusion (I-R) injury, rapid up-regulation of proNGF by cardiomyocytes and p75(NTR) by microvascular pericytes is observed. To identify proNGF actions, we generated a mouse expressing a mutant Ngf allele with impaired processing of proNGF to mature NGF. The proNGF-expressing mouse exhibits cardiac microvascular endothelial activation, a decrease in pericyte process length, and increased vascular permeability, leading to lethal cardiomyopathy in adulthood. Deletion of p75(NTR) in proNGF-expressing mice rescues the phenotype, confirming the importance of p75(NTR)-expressing pericytes in the development of microvascular injury. Furthermore, deficiency in p75(NTR) limits infarct size after I-R. These studies identify novel, nonneuronal actions for proNGF and suggest that proNGF represents a new target to limit microvascular dysfunction. C1 [Siao, Chia-Jen; Lorentz, Christina U.; Kermani, Pouneh; Marinic, Tina; McGrath, Kelly; Padow, Victoria A.; Hempstead, Barbara L.] Weill Cornell Med Coll, Div Hematol Med Oncol, New York, NY 10065 USA. [Carter, John] Weill Cornell Med Coll, Div Cardiovasc Pathophysiol, Dept Med, New York, NY 10065 USA. [Cohen-Gould, Leona] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA. [Cohen-Gould, Leona] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA. [Falcone, Domenick J.; Ellenson, Lora H.] Weill Cornell Med Coll, Dept Pathol, New York, NY 10065 USA. [Parrish, Diana C.; Habecker, Beth A.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Mark, Willie] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA. [Nykjaer, Anders] Univ Aarhus, Dept Med Biochem, DK-8000 Aarhus, Denmark. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Bethesda, MD 21702 USA. RP Hempstead, BL (reprint author), Weill Cornell Med Coll, Div Hematol Med Oncol, New York, NY 10065 USA. EM blhempst@med.cornell.edu OI Nykjaer, Anders/0000-0001-6422-6736; Habecker, Beth/0000-0002-4658-8730 FU National Institutes of Health [HL046403, NS030687]; NIH [HL093056] FX This work was supported by National Institutes of Health (HL046403 and NS030687) to B. L. Hempstead and by NIH HL093056 to B.A. Habecker. NR 60 TC 18 Z9 18 U1 1 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 19 PY 2012 VL 209 IS 12 BP 2291 EP 2305 DI 10.1084/jem.20111749 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 040BY UT WOS:000311295600013 PM 23091165 ER PT J AU Kim, S Kim, W Wei, CH Lu, ZY Wilbur, WJ AF Kim, Sun Kim, Won Wei, Chih-Hsuan Lu, Zhiyong Wilbur, W. John TI Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing semantic information SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID NAMED ENTITY RECOGNITION; BIOMEDICAL LITERATURE; FEATURES AB The Comparative Toxicogenomics Database (CTD) contains manually curated literature that describes chemical-gene interactions, chemical-disease relationships and gene-disease relationships. Finding articles containing this information is the first and an important step to assist manual curation efficiency. However, the complex nature of named entities and their relationships make it challenging to choose relevant articles. In this article, we introduce a machine learning framework for prioritizing CTD-relevant articles based on our prior system for the protein-protein interaction article classification task in BioCreative III. To address new challenges in the CTD task, we explore a new entity identification method for genes, chemicals and diseases. In addition, latent topics are analyzed and used as a feature type to overcome the small size of the training set. Applied to the BioCreative 2012 Triage dataset, our method achieved 0.8030 mean average precision (MAP) in the official runs, resulting in the top MAP system among participants. Integrated with PubTator, a Web interface for annotating biomedical literature, the proposed system also received a positive review from the CTD curation C1 [Kim, Sun; Kim, Won; Wei, Chih-Hsuan; Lu, Zhiyong; Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM wilbur@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 32 TC 4 Z9 4 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD NOV 17 PY 2012 AR bas042 DI 10.1093/database/bas042 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 106AF UT WOS:000316113100004 ER PT J AU Lu, ZY Hirschman, L AF Lu, Zhiyong Hirschman, Lynette TI Biocuration workflows and text mining: overview of the BioCreative 2012 Workshop Track II SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID GENE NORMALIZATION; TASK; ANNOTATION; ONTOLOGY; BIOLOGY; EXTRACTION; CURATION; DATABASE AB Manual curation of data from the biomedical literature is a rate- limiting factor for many expert curated databases. Despite the continuing advances in biomedical text mining and the pressing needs of biocurators for better tools, few existing text- mining tools have been successfully integrated into production literature curation systems such as those used by the expert curated databases. To close this gap and better understand all aspects of literature curation, we invited submissions of written descriptions of curation workflows from expert curated databases for the BioCreative 2012 Workshop Track II. We received seven qualified contributions, primarily from model organism databases. Based on these descriptions, we identified commonalities and differences across the workflows, the common ontologies and controlled vocabularies used and the current and desired uses of text mining for biocuration. Compared to a survey done in 2009, our 2012 results show that many more databases are now using text mining in parts of their curation workflows. In addition, the workshop participants identified text- mining aids for finding gene names and symbols (gene indexing), prioritization of documents for curation (document triage) and ontology concept assignment as those most desired by the biocurators. Database URL: http://www. biocreative. org/tasks/bc- workshop- 2012/workflow/ C1 [Lu, Zhiyong] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Hirschman, Lynette] Mitre Corp, Bedford, MA 01730 USA. RP Hirschman, L (reprint author), Mitre Corp, 202 Burlington Rd, Bedford, MA 01730 USA. EM lynette@mitre.org FU US National Science Foundation [DBI-0850319]; NIH Intramural Research Program, National Library of Medicine, National Institutes of Health; MITRE Corporation FX The US National Science Foundation Grant [DBI-0850319 (to L.H.)]; the NIH Intramural Research Program, National Library of Medicine, National Institutes of Health (to Z.L.). Funding for open access charge: The MITRE Corporation. NR 30 TC 18 Z9 18 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD NOV 17 PY 2012 AR bas043 DI 10.1093/database/bas043 PG 6 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 106AF UT WOS:000316113100005 ER PT J AU Wei, CH Harris, BR Li, DH Berardini, TZ Huala, E Kao, HY Lu, ZY AF Wei, Chih-Hsuan Harris, Bethany R. Li, Donghui Berardini, Tanya Z. Huala, Eva Kao, Hung-Yu Lu, Zhiyong TI Accelerating literature curation with text-mining tools: a case study of using PubTator to curate genes in PubMed abstracts SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID ANNOTATION AB Today's biomedical research has become heavily dependent on access to the biological knowledge encoded in expert curated biological databases. As the volume of biological literature grows rapidly, it becomes increasingly difficult for biocurators to keep up with the literature because manual curation is an expensive and time-consuming endeavour. Past research has suggested that computer-assisted curation can improve efficiency, but few text-mining systems have been formally evaluated in this regard. Through participation in the interactive text-mining track of the BioCreative 2012 workshop, we developed PubTator, a PubMed-like system that assists with two specific human curation tasks: document triage and bioconcept annotation. On the basis of evaluation results from two external user groups, we find that the accuracy of PubTator-assisted curation is comparable with that of manual curation and that PubTator can significantly increase human curatorial speed. These encouraging findings warrant further investigation with a larger number of publications to be annotated. Database URL: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/PubTator/ C1 [Wei, Chih-Hsuan; Harris, Bethany R.; Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Wei, Chih-Hsuan; Kao, Hung-Yu] Natl Cheng Kung Univ, Dept Comp Sci & Informat Engn, Tainan 70101, Taiwan. [Berardini, Tanya Z.; Huala, Eva] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA. RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM zhiyong.lu@nih.gov OI Huala, Eva/0000-0003-4631-7241 FU NIH, National Library of Medicine; National Science Foundation [DBI-0850219]; TAIR sponsors FX Intramural Research Program of the NIH, National Library of Medicine (to C.W. and Z.L.); National Library of Medicine and administered by the Oak Ridge Institute for Science and Education (to B.H.); National Science Foundation (DBI-0850219 to TAIR); TAIR sponsors (http://www. arabi dopsis. org/doc/about/tair_ sponsors/413). Funding for open access charge: National Institutes of Health, National Library of Medicine. NR 24 TC 25 Z9 25 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD NOV 17 PY 2012 AR bas041 DI 10.1093/database/bas041 PG 6 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 106AF UT WOS:000316113100003 ER PT J AU Pearce, MS Salotti, JA Little, MP McHugh, K Lee, C Kim, KP Howe, NL Ronckers, CM Rajaraman, P Craft, AW Parker, L de Gonzalez, AB AF Pearce, Mark S. Salotti, Jane A. Little, Mark P. McHugh, Kieran Lee, Choonsik Kim, Kwang Pyo Howe, Nicola L. Ronckers, Cecile M. Rajaraman, Preetha Craft, Alan W. Parker, Louise de Gonzalez, Amy Berrington TI CT scans in childhood and risk of leukaemia and brain tumours reply SO LANCET LA English DT Letter ID CHILDREN C1 [Pearce, Mark S.; Salotti, Jane A.; Howe, Nicola L.] Newcastle Univ, Royal Victoria Infirm, Inst Hlth & Soc, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Little, Mark P.; Lee, Choonsik; Ronckers, Cecile M.; Rajaraman, Preetha; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [McHugh, Kieran] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeongi Do, South Korea. [Ronckers, Cecile M.] Dutch Childhood Oncol Grp Longterm Effects Childh, The Hague, Netherlands. [Craft, Alan W.] Newcastle Univ, Royal Victoria Infirm, No Inst Canc Res, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Parker, Louise] Dalhousie Univ, Dept Med, Halifax, NS, Canada. [Parker, Louise] Dalhousie Univ, Dept Paediat, Populat Canc Res Program, Halifax, NS, Canada. RP Pearce, MS (reprint author), Newcastle Univ, Royal Victoria Infirm, Inst Hlth & Soc, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. EM mark.pearce@ncl.ac.uk NR 5 TC 3 Z9 3 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 17 PY 2012 VL 380 IS 9855 BP 1736 EP 1737 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 038CV UT WOS:000311153700022 ER PT J AU Aalbers, AM Calado, RT Young, NS Zwaan, CM Wu, CO Kajigaya, S Coenen, EA Baruchel, A Geleijns, K de Haas, V Kaspers, GJL Kuijpers, TW Reinhardt, D Trka, J Zimmermann, M Pieters, R van der Velden, VHJ Eibrink, MMV AF Aalbers, Anna M. Calado, Rodrigo T. Young, Neal S. Zwaan, Christian M. Wu, Colin O. Kajigaya, Sachiko Coenen, Eva A. Baruchel, Andre Geleijns, Karin de Haas, Valerie Kaspers, Gertjan J. L. Kuijpers, Taco W. Reinhardt, Dirk Trka, Jan Zimmermann, Martin Pieters, Rob van der Velden, Vincent H. J. Eibrink, Marry M. van den Heuvel TI Telomere Length and Telomerase Complex Mutations in Pediatric Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Aalbers, Anna M.; Young, Neal S.; Wu, Colin O.; Kajigaya, Sachiko] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.] Univ Sao Paulo, Dept Internal Med, BR-14049 Ribeirao Preto, Brazil. [Zwaan, Christian M.; Coenen, Eva A.; Pieters, Rob; Eibrink, Marry M. van den Heuvel] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Baruchel, Andre] Hop Robert Debre, Dept Pediat Hematol, F-75019 Paris, France. [Geleijns, Karin; van der Velden, Vincent H. J.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [de Haas, Valerie] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Kaspers, Gertjan J. L.] Vrije Univ Amsterdam, Dept Pediat Oncol Hematol, Med Ctr, Amsterdam, Netherlands. [Kuijpers, Taco W.] Emma Childrens Hosp, Dept Pediat Hematol Immunol & Infect Dis, Acad Med Ctr, Amsterdam, Netherlands. [Reinhardt, Dirk; Zimmermann, Martin] Hannover Med Sch, AML BFM Study Grp, Hannover, Germany. [Trka, Jan] Charles Univ Prague, Dept Pediat Hematol & Oncol, Prague, Czech Republic. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1482 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905151 ER PT J AU Aka, P Vila, M Jariwala, A Nkrumah, F Emmanuel, B Yagi, M Palacpac, N Periago, M Neequaye, J Kiruthu, C Tougan, T Levine, P Biggar, R Pfeiffer, RM Horii, T Bhatia, K Bethony, J Mbulaiteye, S AF Aka, Peter Vila, Maria Jariwala, Amar Nkrumah, Francis Emmanuel, Benjamin Yagi, Masanory Palacpac, Nirianne Periago, Maria Neequaye, Janet Kiruthu, Christine Tougan, Takahiro Levine, Paul Biggar, Robert Pfeiffer, Ruth M. Horii, Toshihiro Bhatia, Kishor Bethony, Jeffrey Mbulaiteye, Sam TI Risk of Burkitt Lymphoma Correlates with Breadth and Strength of Antibody Response to Plasmodium Falciparum Malaria Stage-Specific Antigens SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Aka, Peter; Emmanuel, Benjamin; Bhatia, Kishor; Mbulaiteye, Sam] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Vila, Maria; Jariwala, Amar; Periago, Maria; Kiruthu, Christine; Levine, Paul; Bethony, Jeffrey] George Washington Univ, Washington, DC USA. [Nkrumah, Francis] Noguchi Mem Inst, Accra, Ghana. [Yagi, Masanory; Palacpac, Nirianne; Tougan, Takahiro; Horii, Toshihiro] Osaka Univ, Suita, Osaka 565, Japan. [Neequaye, Janet] Korle Bu Univ, Korle, Ghana. [Biggar, Robert] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RI Periago, Maria/H-1054-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900050 ER PT J AU Akrawinthawong, K Piknova, B Sibmooh, N Fucharoen, S Schechter, AN AF Akrawinthawong, Krittapoom Piknova, Barbora Sibmooh, Nathawut Fucharoen, Suthat Schechter, Alan N. TI Nitrite Inhibits Platelet Reactivity in Presence of Deoxygenated Red Blood Cells As Measured by Flow Cytometry SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Akrawinthawong, Krittapoom; Piknova, Barbora; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Sibmooh, Nathawut] Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok 10400, Thailand. [Fucharoen, Suthat] Mahidol Univ, Thalassemia Res Ctr, Inst Sci & Technol Res & Dev, Nakhon Pathom, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 5146 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605442 ER PT J AU Alter, BP Giri, N Pan, YJ Quint, W de Koning, M Schiffman, M Pinto, L AF Alter, Blanche P. Giri, Neelam Pan, Yuanji Quint, Wim de Koning, Maurits Schiffman, Mark Pinto, Ligia TI The HPV Status of Patients with Fanconi Anemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Alter, Blanche P.; Giri, Neelam; Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Quint, Wim; de Koning, Maurits] DDL Diagnost Lab, Rijswijk, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2362 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601099 ER PT J AU Alter, BP Giri, N Calvo, KR Maric, I Arthur, DC Hickstein, DD Hastings, CA Lee, MA Hsu, A Holland, SM AF Alter, Blanche P. Giri, Neelam Calvo, Katherine R. Maric, Irina Arthur, Diane C. Hickstein, Dennis D. Hastings, Caroline A. Lee, Michelle A. Hsu, Amy Holland, Steven M. TI Clinically Silent Carriers in Families with Myelodysplastic Syndrome Due to GATA2 Mutations SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Alter, Blanche P.; Giri, Neelam] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Hematol Sect, Dept Lab, CCR, Bethesda, MD 20892 USA. [Arthur, Diane C.] NCI, Pathol Lab, NIH, CCR, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Hastings, Caroline A.] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Lee, Michelle A.] Dana Farber Canc Inst, Brookline, MA USA. [Hsu, Amy] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1264 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902302 ER PT J AU Arons, E Roth, L Adams, S Sapolsky, J Pastan, I Kreitman, RJ AF Arons, Evgeny Roth, Laura Adams, Sharon Sapolsky, Jeffery Pastan, Ira Kreitman, Robert J. TI The HLA-DRB1*11 Antigen Is Preferentially Expressed in Hairy Cell Leukemia, Particularly in Patients Who Had Hemolytic Uremic Syndrome with Recombinant Immunotoxin BL22 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Arons, Evgeny; Roth, Laura; Sapolsky, Jeffery; Pastan, Ira; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Adams, Sharon] NIH, Dept Transfus Med, HLA Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2488 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602193 ER PT J AU Ayyappan, S Drawz, P Nouraie, M Hildesheim, ME Zhang, YZ Gordeuk, VR Hostetter, TH Gladwin, MT Little, JA AF Ayyappan, Sabarish Drawz, Paul Nouraie, Mehdi Hildesheim, Mariana E. Zhang, Yingze Gordeuk, Victor R. Hostetter, Thomas H. Gladwin, Mark T. Little, Jane A. TI Renal Disease in Sickle Cell: Clinically Varied and Associated with Increased Mortality SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ayyappan, Sabarish; Little, Jane A.] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Cleveland, OH 44106 USA. [Drawz, Paul] Univ Minnesota, Div Renal Dis & Hypertens, Minneapolis, MN USA. [Nouraie, Mehdi] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Hildesheim, Mariana E.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Gordeuk, Victor R.] Univ Illinois, Dept Med, Sect Hematol Oncol, Ctr Comprehens Sickle Cell, Chicago, IL USA. [Hostetter, Thomas H.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 90 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900075 ER PT J AU Baird, K Fry, TJ Merchant, M Richards, K Delbrook, C Wayne, AS Mackall, CL AF Baird, Kristin Fry, Terry J. Merchant, Melinda Richards, Kelly Delbrook, Cynthia Wayne, Alan S. Mackall, Crystal L. TI Early Clinical Experience of aAPC Activated NK-DLI Following Allogeneic PBSCT in Pediatric Solid Tumor Patients. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Baird, Kristin; Fry, Terry J.; Merchant, Melinda; Richards, Kelly; Delbrook, Cynthia; Wayne, Alan S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3013 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601250 ER PT J AU Barta, SK Xue, XN Wang, D Tamari, R Lee, JY Mounier, N Kaplan, LD Ribera, JM Spina, M Tirelli, U Weiss, R Galicier, L Boue, F Wilson, WH Wyen, C Oriol, A Navarro, JT Dunleavy, K Little, RF Ratner, L Garcia, O Morgades, M Oksenhendler, E Remick, S Sparano, JA AF Barta, Stefan K. Xue, Xiaonan Wang, Dan Tamari, Roni Lee, Jeannette Y. Mounier, Nicolas Kaplan, Lawrence D. Ribera, Josep-Maria Spina, Michele Tirelli, Umberto Weiss, Rudolf Galicier, Lionel Boue, Francois Wilson, Wyndham H. Wyen, Christoph Oriol, Albert Navarro, Jose-Tomas Dunleavy, Kieron Little, Richard F. Ratner, Lee Garcia, Olga Morgades, Mireia Oksenhendler, Eric Remick, Scot Sparano, Joseph A. TI A Pooled Analysis of 1,546 Patients with HIV-Associated Lymphoma: Assessment of Lymphoma-, HIV-, and Treatment-Specific Factors On Clinical Outcomes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Barta, Stefan K.] Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. [Xue, Xiaonan] Albert Einstein Coll Med, Div Biostat, Bronx, NY 10467 USA. [Wang, Dan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Tamari, Roni] Dept Med, New York, NY USA. [Lee, Jeannette Y.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Mounier, Nicolas] Hop Archet, Serv Hematol, Nice, France. [Kaplan, Lawrence D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ribera, Josep-Maria] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IJC ICO Badalona, Badalona, Spain. [Spina, Michele] Natl Canc Inst, Div Med Oncol A, Aviano, Italy. [Tirelli, Umberto] Ctr Riferimento Oncol, Div Med Oncol A, I-33081 Aviano, Italy. [Weiss, Rudolf] Gemeinschaftspraxis Haematol & Onkol, Bremen, Germany. [Galicier, Lionel] Hop St Louis, AP HP, Paris, France. [Galicier, Lionel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Boue, Francois] Hop Antoine Beclere, Clamart, France. [Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Wyen, Christoph] Univ Cologne, D-50931 Cologne, Germany. [Oriol, Albert] Spanish Soc Hematol, PETHEMA Grp, Badalona, Spain. [Dunleavy, Kieron] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Little, Richard F.] NCI, HIV AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ratner, Lee] Washington Univ, St Louis, MO USA. [Garcia, Olga] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IJC, Badalona, Spain. [Morgades, Mireia] Hosp Badalona Germans Trias & Pujol, Josep Carreras Leukemia Res Inst, Dept Clin Hematol, ICO, Paris, France. [Oksenhendler, Eric] CHU St Louis, Paris, France. [Remick, Scot] W Virginia Univ, Dept Med, Hematol Oncol Sect, Morgantown, WV 26506 USA. RI Barta, Stefan/D-9554-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3682 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600236 ER PT J AU Barta, SK Xue, XN Wang, D Lee, JY Kaplan, LD Ribera, JM Oriol, A Garcia, O Morgades, M Spina, M Tirelli, U Boue, F Wilson, WH Wyen, C Dunleavy, K Sparano, JA AF Barta, Stefan K. Xue, Xiaonan Wang, Dan Lee, Jeannette Y. Kaplan, Lawrence D. Ribera, Josep-Maria Oriol, Albert Garcia, Olga Morgades, Mireia Spina, Michele Tirelli, Umberto Boue, Francois Wilson, Wyndham H. Wyen, Christoph Dunleavy, Kieron Sparano, Joseph A. TI ARL-IPI - A New Prognostic Score for AIDS-Related Lymphomas in the Rituximab Era SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Barta, Stefan K.] Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. [Xue, Xiaonan] Albert Einstein Coll Med, Div Biostat, Bronx, NY 10467 USA. [Wang, Dan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Lee, Jeannette Y.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Kaplan, Lawrence D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ribera, Josep-Maria] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IJC ICO Badalona, Badalona, Spain. [Oriol, Albert] Spanish Soc Hematol, PETHEMA Grp, Badalona, Spain. [Garcia, Olga] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IJC, Badalona, Spain. [Morgades, Mireia] Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Aviano, Italy. [Spina, Michele] Natl Canc Inst, Div Med Oncol A, Aviano, Italy. [Tirelli, Umberto] Ctr Riferimento Oncol, Div Med Oncol A, I-33081 Aviano, Italy. [Boue, Francois] Hop Antoine Beclere, Clamart, France. [Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Wyen, Christoph] Univ Cologne, D-50931 Cologne, Germany. [Dunleavy, Kieron] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Barta, Stefan/D-9554-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1564 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906274 ER PT J AU Bat, T Leitman, SF Calvo, KR Chauvet, D Dunbar, CE AF Bat, Taha Leitman, Susan F. Calvo, Katherine R. Chauvet, Donna Dunbar, Cynthia E. TI Measurement of the Absolute Immature Platelet Number Reflects Marrow Production and Is Not Impacted by Platelet Transfusion SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bat, Taha; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Leitman, Susan F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3425 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604102 ER PT J AU Bennardo, S Iacovelli, S Gobessi, S Suljagic, M Bilbao, D Eckl-Dorna, J Wang, HS Cornall, RJ Clarke, SH Croce, CM Efremov, DG AF Bennardo, Sara Iacovelli, Stefano Gobessi, Stefania Suljagic, Mirza Bilbao, Daniel Eckl-Dorna, Julia Wang, Hongsheng Cornall, Richard J. Clarke, Stephen H. Croce, Carlo M. Efremov, Dimitar G. TI The Nature of the Antigen Determines Leukemia Development and Behavior in the E mu-TCL1 Transgenic Mouse Model of CLL SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bennardo, Sara; Iacovelli, Stefano; Gobessi, Stefania; Suljagic, Mirza; Efremov, Dimitar G.] Int Ctr Genet Engn & Biotechnol, Rome, Italy. [Bilbao, Daniel] European Mol Biol Lab, Rome, Italy. [Eckl-Dorna, Julia] Med Univ Vienna, Dept Otorlinolaryngol, Vienna, Austria. [Wang, Hongsheng] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. [Cornall, Richard J.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Clarke, Stephen H.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 181 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900276 ER PT J AU Bergsagel, PL Affer, M Glebov, OK Chen, WDD Keats, JJ Brents, LA Chesi, M Van Wier, S Badar, SK Fonseca, R Kuehl, WM AF Bergsagel, P. Leif Affer, Maurizio Glebov, Oleg K. Chen, Wei-Dong D. Keats, Jonathan J. Brents, Leslie A. Chesi, Marta Van Wier, Scott Badar, Sandra K. Fonseca, Rafael Kuehl, W. Michael TI Promiscuous Cryptic Rearrangements of the MYC Locus Cis-Dysregulate MYC Expression and Are Present in the Majority of Patients with Hyperdiploid Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bergsagel, P. Leif; Affer, Maurizio; Chesi, Marta; Van Wier, Scott; Badar, Sandra K.; Fonseca, Rafael] Mayo Clin Arizona, Div Hematol Oncol, Scottsdale, AZ USA. [Glebov, Oleg K.; Chen, Wei-Dong D.; Brents, Leslie A.; Kuehl, W. Michael] NCI, Canc Genet Branch, Bethesda, MD 20892 USA. [Keats, Jonathan J.] Translat Genom Res Inst, Phoenix, AZ USA. RI CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 724 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900235 ER PT J AU Blimark, C Mellqvist, UH Landgren, O Bjorkholm, M Hultcrantz, ML Kjellander, C Turesson, I Holmberg, E Kristinsson, SY AF Blimark, Cecilie Mellqvist, Ulf-Henrik Landgren, Ola Bjorkholm, Magnus Hultcrantz, Malin L. Kjellander, Christian Turesson, Ingemar Holmberg, Erik Kristinsson, Sigurdur Y. TI Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Blimark, Cecilie] Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bjorkholm, Magnus; Hultcrantz, Malin L.; Kjellander, Christian; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden. [Bjorkholm, Magnus; Hultcrantz, Malin L.; Kjellander, Christian; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Skane Univ Hosp Malmo, Malmo, Sweden. [Holmberg, Erik] Univ Gothenburg, Sahlgrenska Acad, Dept Oncol, Inst Clin Sci, Gothenburg, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 945 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902016 ER PT J AU Blimark, C Mellqvist, UH Landgren, O Bjorkholm, M Hultcrantz, ML Kjellander, C Turesson, I Holmberg, E Kristinsson, SY AF Blimark, Cecilie Mellqvist, Ulf-Henrik Landgren, Ola Bjorkholm, Magnus Hultcrantz, Malin L. Kjellander, Christian Turesson, Ingemar Holmberg, Erik Kristinsson, Sigurdur Y. TI Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Blimark, Cecilie] Sahlgrens Univ Hosp, Dept Hematol, Gothenburg, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bjorkholm, Magnus; Hultcrantz, Malin L.; Kjellander, Christian; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden. [Bjorkholm, Magnus; Hultcrantz, Malin L.; Kjellander, Christian; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Skane Univ Hosp Malmo, Malmo, Sweden. [Holmberg, Erik] Univ Gothenburg, Dept Oncol, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 945 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901192 ER PT J AU Bolouri, H Ries, RE Ramamurthy, R Alonzo, TA Auvil, JMG Davidsen, TM Gesuwan, P Gamis, AS Smith, MA Gerhard, DS Arceci, RJ Meshinchi, S AF Bolouri, Hamid Ries, Rhonda E. Ramamurthy, Ranjani Alonzo, Todd A. Auvil, Jaime M. Guidry Davidsen, Tanja M. Gesuwan, Patee Gamis, Alan S. Smith, Malcolm A. Gerhard, Daniela S. Arceci, Robert J. Meshinchi, Soheil TI Integrative Network Analysis of Pediatric AML Whole Genomes, cDNA Expression and Clinical Data Elements Reveals Shared As Well As t(8;21), Inv16 and MLL Specific Pathways; A Report From COG/NCI Target AML Initiative SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bolouri, Hamid] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98104 USA. [Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Ramamurthy, Ranjani] Univ Washington, Sch Med, Seattle, WA USA. [Alonzo, Todd A.] Univ So Calif, Los Angeles, CA USA. [Auvil, Jaime M. Guidry; Davidsen, Tanja M.; Gesuwan, Patee; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Arceci, Robert J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3519 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906138 ER PT J AU Bouska, A McKeithan, T Deffenbacher, KE Lachel, C Wright, GW Iqbal, J Smith, LM Liu, ZF Kucuk, C Bertoni, F Rinaldi, A Fitzgibbon, J Fu, K Weisenburger, DD Greiner, TC Gascoyne, RD Rosenwald, A Campo, E Rimsza, LM Delabie, J Jaffe, ES Staudt, LM Chan, WC AF Bouska, Alyssa McKeithan, Timothy Deffenbacher, Karen E. Lachel, Cynthia Wright, George W. Iqbal, Javeed Smith, Lynette M. Liu, Zhongfeng Kucuk, Can Bertoni, Francesco Rinaldi, Andrea Fitzgibbon, Jude Fu, Kai Weisenburger, Dennis D. Greiner, Timothy C. Gascoyne, Randy D. Rosenwald, Andreas Campo, Elias Rimsza, Lisa M. Delabie, Jan Jaffe, Elaine S. Staudt, Louis M. Chan, Wing-Chung TI Genetic Abnormalities in Follicular Lymphoma and Transformed Follicular Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wright, George W.] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Smith, Lynette M.] Univ Nebraska Med Ctr, COPH Biostat, Omaha, NE USA. [Bertoni, Francesco; Rinaldi, Andrea] Oncol Inst So Switzerland IOSI, Lymphoma Unit, Bellinzona, Switzerland. [Rinaldi, Andrea] Oncol Inst So Switzerland IOSI, Expt Oncol Lab, Bellinzona, Switzerland. [Fitzgibbon, Jude] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London, England. [Gascoyne, Randy D.] BC Canc Agcy, Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC, Canada. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Campo, Elias] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Delabie, Jan] Univ Oslo, Dept Pathol, Norwegian Radium Hosp, Oslo, Norway. [Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2648 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602234 ER PT J AU Bouska, A McKeithan, T Deffenbacher, KE Lachel, C Wright, GW Iqbal, J Smith, LM Liu, ZF Kucuk, C Bertoni, F Rinaldi, A Fitzgibbon, J Fu, K Weisenburger, DD Greiner, TC Gascoyne, RD Rosenwald, A Campo, E Rimsza, LM Delabie, J Jaffe, ES Staudt, LM Chan, WC AF Bouska, Alyssa McKeithan, Timothy Deffenbacher, Karen E. Lachel, Cynthia Wright, George W. Iqbal, Javeed Smith, Lynette M. Liu, Zhongfeng Kucuk, Can Bertoni, Francesco Rinaldi, Andrea Fitzgibbon, Jude Fu, Kai Weisenburger, Dennis D. Greiner, Timothy C. Gascoyne, Randy D. Rosenwald, Andreas Campo, Elias Rimsza, Lisa M. Delabie, Jan Jaffe, Elaine S. Staudt, Louis M. Chan, Wing-Chung TI Genetic Abnormalities in Follicular Lymphoma and Transformed Follicular Lymphoma. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wright, George W.] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Smith, Lynette M.] Univ Nebraska Med Ctr, COPH Biostat, Omaha, NE USA. [Bertoni, Francesco; Rinaldi, Andrea] Oncol Inst So Switzerland IOSI, Lymphoma Unit, Bellinzona, Switzerland. [Rinaldi, Andrea] Oncol Inst So Switzerland IOSI, Expt Oncol Lab, Bellinzona, Switzerland. [Fitzgibbon, Jude] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London, England. [Gascoyne, Randy D.] BC Canc Agcy Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC, Canada. [Rosenwald, Andreas] Univ Wurzburg, D-97070 Wurzburg, Germany. [Campo, Elias] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Delabie, Jan] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. [Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2648 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903145 ER PT J AU Bryant, BJ Yau, YY Arceo, SM Hopkins, JA Leitman, SF AF Bryant, Barbara J. Yau, Yu Ying Arceo, Sarah M. Hopkins, Julie A. Leitman, Susan F. TI Ascertainment of Iron Depletion and Deficiency in Blood Donors Through Screening Questions for Pica and Restless Legs Syndrome SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Bryant, Barbara J.] Univ Texas Med Branch, Galveston, TX USA. [Yau, Yu Ying; Arceo, Sarah M.; Hopkins, Julie A.; Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2283 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600077 ER PT J AU Carpenter, RO Evbuomwan, MO Pittaluga, S Rose, JJ Raffeld, M Yang, SC Gress, RE Hakim, FT Kochenderfer, JN AF Carpenter, Robert O. Evbuomwan, Moses O. Pittaluga, Stefania Rose, Jeremy J. Raffeld, Mark Yang, Shicheng Gress, Ronald E. Hakim, Frances T. Kochenderfer, James N. TI B-Cell Maturation Antigen Is a Promising Target for Genetically-Modified T-Cell Therapy of Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Carpenter, Robert O.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Yang, Shicheng] Duke Univ, Dept Surg, Div Neurosurg, Durham, NC USA. [Hakim, Frances T.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 937 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902024 ER PT J AU Carpenter, RO Evbuomwan, MO Pittaluga, S Rose, JJ Raffeld, M Yang, SC Gress, RE Hakim, FT Kochenderfer, JN AF Carpenter, Robert O. Evbuomwan, Moses O. Pittaluga, Stefania Rose, Jeremy J. Raffeld, Mark Yang, Shicheng Gress, Ronald E. Hakim, Frances T. Kochenderfer, James N. TI B-Cell Maturation Antigen Is a Promising Target for Genetically-Modified T-Cell Therapy of Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Rose, Jeremy J.; Gress, Ronald E.; Kochenderfer, James N.] NCI, ETIB, Bethesda, MD 20892 USA. [Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Yang, Shicheng] Duke Univ, Div Neurosurg, Dept Surg, Durham, NC USA. [Hakim, Frances T.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 937 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901200 ER PT J AU Chen, JC Dent, JJ Desierto, MJ Bryant, MA Sheppard, N Feng, XM Young, NS AF Chen, Jichun Dent, James J. Desierto, Marie J. Bryant, Mark A. Sheppard, Nolan Feng, Xingmin Young, Neal S. TI Hematological Abnormalities in Aged Telomerase RNA Component Deficient Mice Are Associated with Intestinal Epithelial Degeneration and Bone Marrow Stromal Dysfunction SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Chen, Jichun; Dent, James J.; Desierto, Marie J.; Sheppard, Nolan; Feng, Xingmin; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bryant, Mark A.] NIH, Off Res Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1244 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902322 ER PT J AU Chen, ZS Geng, HM Buchner, M Klemm, L Hemati, K Shojaee, S Tak, MW Coligan, JE Carroll, WL Willman, CL Muschen, M AF Chen, Zhengshan Geng, Huimin Buchner, Maike Klemm, Lars Hemati, Kaveh Shojaee, Seyedmehdi Tak, Mak W. Coligan, John E. Carroll, William L. Willman, Cheryl L. Muschen, Markus TI ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Chen, Zhengshan; Geng, Huimin; Buchner, Maike; Klemm, Lars; Hemati, Kaveh; Shojaee, Seyedmehdi; Muschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Tak, Mak W.] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada. [Coligan, John E.] NIH, Receptor Cell Biol Sect, Rockville, MD USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. RI Chen, Zhengshan/J-7499-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 291 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901155 ER PT J AU Cherkasova, E Weisman, Q Kajigaya, S Takahashi, Y Reger, RN Harashima, N AF Cherkasova, Elena Weisman, Quinn Kajigaya, Sachiko Takahashi, Yoshiyuki Reger, Robert N. Harashima, Nanae TI Identification of a Human Endogenous Retrovirus Type-E (HERV-E) Envelope with Selective Expression in Clear Cell Kidney Cancer That Is Immunogenic in Vitro. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Cherkasova, Elena; Kajigaya, Sachiko; Reger, Robert N.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Takahashi, Yoshiyuki] Nagoya Univ, Dept Pediat, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Harashima, Nanae] Shimane Univ, Fac Med, Matsue, Shimane, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3015 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601248 ER PT J AU Chien, CD Hicks, ED Su, PP Qin, HY Fry, TJ AF Chien, Christopher D. Hicks, Elizabeth D. Su, Paul P. Qin, Haiying Fry, Terry J. TI Precursor B Cell Acute Lymphoblastic Leukemia Induces Pro-Leukemic Changes in the Bone Marrow Microenvironment That Contribute to Therapeutic Resistance SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Chien, Christopher D.; Qin, Haiying; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1466 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905167 ER PT J AU Connelly, JP Horwitz, MS Liu, PP AF Connelly, Jon P. Horwitz, Marshall S. Liu, Pu Paul TI Towards Cell Therapy for FPD/AML with Patient-Specific IPS Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Connelly, Jon P.; Liu, Pu Paul] NHGRI, GMBB, ODS, NIH, Bethesda, MD 20892 USA. [Horwitz, Marshall S.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4677 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049606108 ER PT J AU Cooley, S Verneris, MR Curtsinger, J McKenna, D Weisdorf, DJ Blazar, BR Waldmann, TA Miller, JS AF Cooley, Sarah Verneris, Michael R. Curtsinger, Julie McKenna, David Weisdorf, Daniel J. Blazar, Bruce R. Waldmann, Thomas A. Miller, Jeffrey S. TI Recombinant Human IL-15 Promotes in Vivo Expansion of Adoptively Transferred NK Cells in a First-in-Human Phase I Dose Escalation Study in Patients with AML SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Verneris, Michael R.; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Curtsinger, Julie] Univ Minnesota, Masonic Canc Res Ctr, Minneapolis, MN USA. [McKenna, David] Univ Minnesota, St Paul, MN 55108 USA. [Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Miller, Jeffrey S.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. NR 0 TC 3 Z9 3 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 894 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900365 ER PT J AU Cozen, W Yu, GQ Gail, M Nathwani, BN Hwang, AE Hamilton, AS Mack, TM Goedert, JJ AF Cozen, Wendy Yu, Guoqin Gail, Mitchell Nathwani, Bharat N. Hwang, Amie E. Hamilton, Ann S. Mack, Thomas M. Goedert, James J. TI Fecal Microbiota Diversity in Survivors of Adolescent/Young Adult Hodgkin Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yu, Guoqin] NCI, Div Canc Epidemiol & Genet, Infect & Immunol Branch, NIH, Rockville, MD USA. [Nathwani, Bharat N.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. [Hwang, Amie E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hamilton, Ann S.; Mack, Thomas M.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1533 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906243 ER PT J AU Cuellar-Rodriguez, J Gea-Banacloche, J Hsu, AP Zerbe, C Freeman, A Olivier, KN Calvo, KR Fry, TJ Holland, SM Hickstein, DD AF Cuellar-Rodriguez, Jennifer Gea-Banacloche, Juan Hsu, Amy P. Zerbe, Christa Freeman, Alexandra Olivier, Kenneth N. Calvo, Katherine R. Fry, Terry J. Holland, Steven M. Hickstein, Dennis D. TI Allogeneic Hematopoietic Stem Cell Transplant Reverses the Phenotype of GATA2 Deficiency. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Cuellar-Rodriguez, Jennifer; Hsu, Amy P.; Zerbe, Christa; Freeman, Alexandra; Olivier, Kenneth N.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3091 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601172 ER PT J AU de Vasconcellos, JF Lee, YT Yuan, J Byrnes, C Noh, SJ Meier, ER Kim, KS Rabel, A Muljo, SA Miller, JL AF de Vasconcellos, Jaira F. Lee, Y. Terry Yuan, Joan Byrnes, Colleen Noh, Seung-Jae Meier, Emily R. Kim, Ki Soon Rabel, Antoinette Muljo, Stefan A. Miller, Jeffery L. TI Lin28B Increases Fetal Hemoglobin and Regulates BCL11A Expression in Human Erythroid Tissues SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [de Vasconcellos, Jaira F.; Lee, Y. Terry; Byrnes, Colleen; Noh, Seung-Jae; Meier, Emily R.; Kim, Ki Soon; Rabel, Antoinette; Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD USA. [Yuan, Joan; Muljo, Stefan A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI yuan, joan/A-8185-2013; Muljo, Stefan/F-5671-2015 OI yuan, joan/0000-0001-9129-8356; Muljo, Stefan/0000-0003-1013-446X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 827 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901037 ER PT J AU Delaney, KM Gorbach, A Malik, N Maivelett, J Hon, YY Xu, DH Novelli, EM Lanzkron, S Taylor, JG Kato, GJ Minniti, CP AF Delaney, Kara M. Gorbach, Alexander Malik, Nitin Maivelett, Jordan Hon, Yuen Yi Xu, Dihua Novelli, Enrico M. Lanzkron, Sophia Taylor, James G. Kato, Gregory J. Minniti, Caterina P. TI Blood Flow Is Increased in Wounds and Peri-Wound Area by Laser Speckle Contrast Imaging and Infrared Thermography in Adults with Sickle Cell Leg Ulcers SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Delaney, Kara M.; Taylor, James G.; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Gorbach, Alexander; Malik, Nitin; Maivelett, Jordan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Hon, Yuen Yi] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Novelli, Enrico M.] Univ Pittsburgh, Dept Med, Div Hem Onc, Pittsburgh, PA USA. [Lanzkron, Sophia] Johns Hopkins Sch Med, Baltimore, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1009 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602062 ER PT J AU Desmond, RG Bat, T Kamenyeva, O Mizukawa, B Mulloy, JC Larochelle, A Dunbar, CE AF Desmond, Ronan G. Bat, Taha Kamenyeva, Olena Mizukawa, Benjamin Mulloy, James C. Larochelle, Andre Dunbar, Cynthia E. TI Leukemic and Hematopoietic Stem Cells Compete for the Same Functional Marrow Niche in a MLL-AF9 Murine Leukemia Model SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Desmond, Ronan G.; Bat, Taha; Larochelle, Andre; Dunbar, Cynthia E.] NHLBI, Bethesda, MD 20892 USA. [Mizukawa, Benjamin] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Canc & Blood Dis Inst, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4897 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604345 ER PT J AU Dumitriu, B Ueda, Y Kajigaya, S Townsley, DM Young, NS AF Dumitriu, Bogdan Ueda, Yasutaka Kajigaya, Sachiko Townsley, Danielle M. Young, Neal S. TI Very Short Telomeres of Peripheral Blood Leukocytes Precede Clinical Progression to Myelodysplasia with Monosomy 7 in Aplastic Anemia Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1265 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902301 ER PT J AU Dunleavy, K Grant, C Hessler, J Miller, BW Steinberg, SM Pittaluga, S Roschewski, M Jaffe, ES Wiestner, A Wilson, WH AF Dunleavy, Kieron Grant, Cliona Hessler, Julieanne Miller, Barry W. Steinberg, Seth M. Pittaluga, Stefania Roschewski, Mark Jaffe, Elaine S. Wiestner, Adrian Wilson, Wyndham H. TI Bortezomib plus DA-EPOCH-R Induction Therapy Followed by Maintenance Bortezomib Versus Observation in Newly Diagnosed Mantle Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Dunleavy, Kieron; Grant, Cliona; Hessler, Julieanne; Miller, Barry W.; Roschewski, Mark] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3672 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600246 ER PT J AU Duvic, M Pinter-Brown, L Foss, F Sokol, L Jorgensen, J Ni, X Challagundla, P Goswami, M Dwyer, K Mohamed, N Kim, YH AF Duvic, Madeleine Pinter-Brown, Lauren Foss, Francine Sokol, Lubomir Jorgensen, Jeffrey Ni, Xiao Challagundla, Pramoda Goswami, Meghali Dwyer, Karen Mohamed, Nehal Kim, Youn H. TI Correlation of Target Molecule Expression and Overall Response in Refractory Cutaneous T-Cell Lymphoma Patients Dosed with Mogamulizumab (KW-0761), a Monoclonal Antibody Directed Against CC Chemokine Receptor Type 4 (CCR4) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pinter-Brown, Lauren] Univ Calif Los Angeles, Los Angeles, CA USA. [Foss, Francine] Yale Canc Ctr, New Haven, CT USA. [Sokol, Lubomir] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Jorgensen, Jeffrey] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Ni, Xiao] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA. [Goswami, Meghali] NHLBI, NIH, Bethesda, MD 20892 USA. [Dwyer, Karen; Mohamed, Nehal] Kyowa Hakko Kirin Pharma Inc, Kyowa, NJ USA. [Kim, Youn H.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3697 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600221 ER PT J AU Evans, ME Tisdale, JF Uchida, N AF Evans, Molly E. Tisdale, John F. Uchida, Naoya TI Lentiviral Transduction Efficiency for Human CD34+Cells Is Affected by TRIM5 alpha Expression and Cell Proliferation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Evans, Molly E.; Tisdale, John F.; Uchida, Naoya] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4220 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906213 ER PT J AU Farooqui, M Lozier, JN Valdez, J Saba, N Wells, A Soto, S Liu, DL Aue, G Wiestner, A AF Farooqui, Mohammed Lozier, Jay Nelson Valdez, Janet Saba, Nakhle Wells, Ajunae Soto, Susan Liu, Delong Aue, Georg Wiestner, Adrian TI Ibrutinib (PCI 32765) Rapidly Improves Platelet Counts in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients and Has Minimal Effects On Platelet Aggregation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Farooqui, Mohammed; Valdez, Janet; Saba, Nakhle; Wells, Ajunae; Soto, Susan; Liu, Delong; Aue, Georg; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Lozier, Jay Nelson] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1789 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602088 ER PT J AU Farooqui, M Aue, G Valdez, J Saba, N Herman, SEM Lipsky, A Bojanowski, L Wells, A Soto, S Liu, DL Wiestner, A AF Farooqui, Mohammed Aue, Georg Valdez, Janet Saba, Nakhle Herman, Sarah E. M. Lipsky, Andrew Bojanowski, Leodayan Wells, Ajunae Soto, Susan Liu, Delong Wiestner, Adrian TI Rapid Decrease in Overall Tumor Burden On Ibrutinib (PCI-32765) in CLL Despite Transient Increase in ALC Indicates a Significant Degree of Treatment Induced Cell Death SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Farooqui, Mohammed; Aue, Georg; Valdez, Janet; Saba, Nakhle; Herman, Sarah E. M.; Lipsky, Andrew; Bojanowski, Leodayan; Wells, Ajunae; Soto, Susan; Liu, Delong; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2899 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905340 ER PT J AU Felices, M Lenvik, T Ankarlo, D Curtsinger, J Tolar, J Blazar, BR Anderson, S Miller, JS AF Felices, Martin Lenvik, Todd Ankarlo, Dave Curtsinger, Julie Tolar, Jakub Blazar, Bruce R. Anderson, Stephen Miller, Jeffrey S. TI Education and Cytokine Receptor Balance Play a Critical Role in Long Term Survival of the Most Differentiated Natural Killer (NK) Cells. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Curtsinger, Julie] Univ Minnesota, Masonic Canc Res Ctr, Minneapolis, MN USA. [Tolar, Jakub] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Anderson, Stephen] NCI, Frederick, MD 21701 USA. [Miller, Jeffrey S.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2148 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905288 ER PT J AU Fisher, R Henson, A Quarello, P Aspesi, A Farrar, JE Arceci, RJ Bodine, DM Dianzani, I Lipton, JM Ramenghi, U Vlachos, A Ellis, SR AF Fisher, Ross Henson, Adrianna Quarello, Paola Aspesi, Anna Farrar, Jason E. Arceci, Robert J. Bodine, David M. Dianzani, Irma Lipton, Jeffrey M. Ramenghi, Ugo Vlachos, Adrianna Ellis, Steven R. TI Insights Into Diagnosis and Etiology of Diamond Blackfan Anemia by Analysis of Pre-rRNA Processing SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Fisher, Ross] Loma Linda Univ, San Bernardino, CA USA. [Henson, Adrianna; Ellis, Steven R.] Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. [Quarello, Paola] Regina Margherita Childrens Hosp, Turin, Italy. [Aspesi, Anna] Univ Piemonte Orientale, Novara, Italy. [Farrar, Jason E.] Johns Hopkins Univ, Dept Oncol, Div Pediat Oncol, Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Arceci, Robert J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Dianzani, Irma] Univ Piemonte Orientale, Dept Med Sci, Novara, Italy. [Lipton, Jeffrey M.] Hofstra Univ, Steven & Alexandra Cohen Childrens Med Ctr, Div Hematol Oncol & Stem Cell Transplantat, Feinstein Inst Med Res,Sch Med, New Hyde Pk, NY USA. [Ramenghi, Ugo] Univ Turin, Dept Pediat, I-10124 Turin, Italy. [Vlachos, Adrianna] Hofstra N Shore LIJ Sch Med, Feinstein Inst Med Res, Steven & Alexandra Cohen Childrens Med Ctr, New Hyde Pk, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3476 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604051 ER PT J AU Fitzhugh, C Allen, D Coles, W Seamon, C Zhao, XC Darbari, D Wilson, J Quinn, M Hsieh, M Kato, GJ Taylor, JG AF Fitzhugh, Courtney Allen, Darlene Coles, Wynona Seamon, Cassie Zhao, Xiongce Darbari, Deepika Wilson, Jonathan Quinn, Meghan Hsieh, Matthew Kato, Gregory J. Taylor, James G. TI Etiology of and Associations with Early Death in Adult Patients with Sickle Cell Disease At a Single Referral Institution SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Fitzhugh, Courtney; Coles, Wynona; Hsieh, Matthew] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Allen, Darlene; Seamon, Cassie; Darbari, Deepika; Wilson, Jonathan; Quinn, Meghan; Kato, Gregory J.; Taylor, James G.] NHLBI, HB, NIH, Bethesda, MD 20892 USA. [Zhao, Xiongce] NIDDK, NIH, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2117 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905319 ER PT J AU Gerrie, AS White, S Harvey, KL Gill, R Toze, CL AF Gerrie, Alina S. White, Siobhan Harvey, Katherine L. Gill, Ritu Toze, Cynthia L. TI Effect of Physical Activity (PA) Interventions On Health-Related Quality of Life (HRQoL) Post Hematopoietic Stem Cell Transplantation (HSCT): A Systematic Review and Meta-Analysis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Gerrie, Alina S.; Toze, Cynthia L.] Univ British Columbia, British Columbia Canc Agcy, Leukemia & Bone Marrow Transplantat Program BC, Vancouver, BC V5Z 1M9, Canada. [White, Siobhan] NCI, Washington, DC USA. [Harvey, Katherine L.] Yale Univ, Sch Med, New Haven, CT USA. [Harvey, Katherine L.] Yale Canc Ctr, New Haven, CT USA. [Gill, Ritu] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1968 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903023 ER PT J AU Giri, N Matsui, K Alter, BP Savage, SA Pan, YJ Pinto, L AF Giri, Neelam Matsui, Ken Alter, Blanche P. Savage, Sharon A. Pan, Yuanji Pinto, Ligia TI Bone Marrow Cellular Composition and Inflammatory Cytokine Expression in Patients with Inherited Bone Marrow Failure Syndromes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Matsui, Ken; Pan, Yuanji; Pinto, Ligia] NCI, Human Papilloma Virus Immunol Lab, Frederick, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4401 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605123 ER PT J AU Grant, C Dunleavy, K Hessler, J Steinberg, SM Pittaluga, S Jaffe, ES Wilson, WH AF Grant, Cliona Dunleavy, Kieron Hessler, Julieanne Steinberg, Seth M. Pittaluga, Stefania Jaffe, Elaine S. Wilson, Wyndham H. TI A Phase II Trial of Alemtuzumab (Campath) with DA-EPOCH-R in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Grant, Cliona; Dunleavy, Kieron; Hessler, Julieanne] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3709 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600209 ER PT J AU Grkovic, L Pulanic, D Steinberg, SM Williams, KM Baird, K Mitchell, SA Cowen, EW Datiles, MB Bassim, CW Galen, J Comis, L Avila, DN Taylor, TN Zhang, D Cole, K Fowler, DH Hakim, FT Gress, RE Pavletic, SZ AF Grkovic, Lana Pulanic, Drazen Steinberg, Seth M. Williams, Kirsten M. Baird, Kristin Mitchell, Sandra A. Cowen, Edward W. Datiles, Manuel B., III Bassim, Carol W. Galen, Joe Comis, Leora Avila, Daniele N. Taylor, Tiffani N. Zhang, Dan Cole, Kristen Fowler, Dan H. Hakim, Frances T. Gress, Ronald E. Pavletic, Steven Z. TI Chronic Graft-Versus-Host Disease (cGVHD) Patients with Bronchiolitis Obliterans Syndrome (BOS) Have Worse Clinical Manifestations and Severity of cGVHD with More Impairment in Self-Assessed Physical and Mental Health than cGVHD Patients without BOS SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Grkovic, Lana; Pulanic, Drazen] Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb, Croatia. [Williams, Kirsten M.; Avila, Daniele N.; Taylor, Tiffani N.; Cole, Kristen; Fowler, Dan H.; Hakim, Frances T.; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Baird, Kristin] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Datiles, Manuel B., III] NEI, NIH, Bethesda, MD 20892 USA. [Bassim, Carol W.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Galen, Joe; Comis, Leora] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Zhang, Dan] NCI, Biostat & Data Management Sect, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1939 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903052 ER PT J AU Halverson, D Mossoba, ME Steinberg, SM Blacklock-Schuver, B Hakim, FT Kurlander, R Gea-Banacloche, J Sportes, C Hardy, NM Hickstein, DD Pavletic, SZ Khuu, H Sabatino, M Stroncek, D Leitman, SF Rowley, SD Donato, ML Goy, A Korngold, R Pecora, AL Levine, BL June, CH Bishop, MR Carini, C Feldman, T Mato, AR Gress, RE Fowler, DH AF Halverson, David Mossoba, Miriam E. Steinberg, Seth M. Blacklock-Schuver, Bazetta Hakim, Frances T. Kurlander, Roger Gea-Banacloche, Juan Sportes, Claude Hardy, Nancy M. Hickstein, Dennis D. Pavletic, Steven Z. Khuu, Hanh Sabatino, Marianna Stroncek, David Leitman, Susan F. Rowley, Scott D. Donato, Michele L. Goy, Andre Korngold, Robert Pecora, Andrew L. Levine, Bruce L. June, Carl H. Bishop, Michael R. Carini, Carol Feldman, Tatyana Mato, Anthony R. Gress, Ronald E. Fowler, Daniel H. TI Pre-Emptive T-Rapa Cell DLI for Therapy of High-Risk Lymphoma After Low-Intensity Allogeneic HCT SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mossoba, Miriam E.] NCI, Expt Transplantat & Immunol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Kurlander, Roger] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Khuu, Hanh; Sabatino, Marianna; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Rowley, Scott D.; Donato, Michele L.; Goy, Andre; Pecora, Andrew L.; Feldman, Tatyana; Mato, Anthony R.] Hackensack Univ Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Korngold, Robert] Hackensack Univ Med Ctr, Ctr Canc, Hackensack, NJ USA. [Levine, Bruce L.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [June, Carl H.] Univ Penn, Perelman Sch Med, Philadelphia, PA USA. [Bishop, Michael R.] Med Coll Wisocnson, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 471 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838902189 ER PT J AU Halverson, D Mossoba, ME Steinberg, SM Blacklock-Schuver, B Hakim, FT Kurlander, R Gea-Banacloche, J Sportes, C Hardy, NM Hickstein, DD Pavletic, SZ Khuu, H Sabatino, M Stroncek, D Leitman, SF Rowley, SD Donato, ML Goy, A Korngold, R Pecora, AL Levine, BL June, CH Bishop, MR Carini, C Feldman, T Mato, AR Gress, RE Fowler, DH AF Halverson, David Mossoba, Miriam E. Steinberg, Seth M. Blacklock-Schuver, Bazetta Hakim, Frances T. Kurlander, Roger Gea-Banacloche, Juan Sportes, Claude Hardy, Nancy M. Hickstein, Dennis D. Pavletic, Steven Z. Khuu, Hanh Sabatino, Marianna Stroncek, David Leitman, Susan F. Rowley, Scott D. Donato, Michele L. Goy, Andre Korngold, Robert Pecora, Andrew L. Levine, Bruce L. June, Carl H. Bishop, Michael R. Carini, Carol Feldman, Tatyana Mato, Anthony R. Gress, Ronald E. Fowler, Daniel H. TI Pre-Emptive T-Rapa Cell DLI for Therapy of High-Risk Lymphoma After Low-Intensity Allogeneic HCT SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mossoba, Miriam E.] NCI, Expt Transplantat & Immunol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Kurlander, Roger] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Khuu, Hanh; Sabatino, Marianna; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Rowley, Scott D.; Donato, Michele L.; Goy, Andre; Pecora, Andrew L.; Feldman, Tatyana; Mato, Anthony R.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Levine, Bruce L.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [June, Carl H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bishop, Michael R.] Med Coll Wisconsin, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 471 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838901365 ER PT J AU He, S Xie, F Tong, Q Mochizuki, K Liu, YN Lapinski, PE Mineishi, S Mani, RS Marquez, VE Chinnaiyan, AM King, PD Zhang, Y AF He, Shan Xie, Fang Tong, Qing Mochizuki, Kazuhiro Liu, Yongnian Lapinski, Philip E. Mineishi, Shin Mani, Ram Shankar Marquez, Victor E. Chinnaiyan, Arul M. King, Philip D. Zhang, Yi TI Histone Methyltransferase Ezh2 Controls T-Cell Immunity by Regulating Bioenergetic Metabolism SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [He, Shan; Xie, Fang; Tong, Qing; Mochizuki, Kazuhiro; Liu, Yongnian; Mineishi, Shin; Zhang, Yi] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Lapinski, Philip E.; King, Philip D.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Mani, Ram Shankar; Chinnaiyan, Arul M.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RI He, Shan/C-4989-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 953 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901184 ER PT J AU Helton, HL Ries, RE Alonzo, TA Gerbing, RB Trevino, LR Farrar, J Auvil, JMG Davidsen, TM Gesuwan, P Muzny, DM Gamis, AS Franklin, J Wheeler, DA Smith, MA Gerhard, DS Arceci, RJ Meshinchi, S AF Helton, Heather L. Ries, Rhonda E. Alonzo, Todd A. Gerbing, Robert B. Trevino, Lisa R. Farrar, Jason Auvil, Jaime M. Guidry Davidsen, Tanja M. Gesuwan, Patee Muzny, Donna M. Gamis, Alan S. Franklin, Janet Wheeler, David A. Smith, Malcolm A. Gerhard, Daniela S. Arceci, Robert J. Meshinchi, Soheil TI Clinically Significant Mutations, Deletions and Translocations Involving ETV6 Identified by Whole Genome and Whole Exome Sequencing; Report From NCI/COG Target AML Initiative SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Helton, Heather L.; Ries, Rhonda E.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Alonzo, Todd A.] Univ So Calif, Los Angeles, CA USA. [Gerbing, Robert B.] Childrens Oncol Grp, Arcadia, CA USA. [Trevino, Lisa R.; Muzny, Donna M.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Farrar, Jason] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Auvil, Jaime M. Guidry; Davidsen, Tanja M.; Gesuwan, Patee; Smith, Malcolm A.; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Franklin, Janet] Amgen Inc, Thousand Oaks, CA 91320 USA. [Arceci, Robert J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 125 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900334 ER PT J AU Herman, SEM Barr, PM McAuley, EM Liu, DL Friedberg, JW Wiestner, A AF Herman, Sarah E. M. Barr, Paul M. McAuley, Erin M. Liu, Delong Friedberg, Jonathan W. Wiestner, Adrian TI Fostamatinib Inhibits BCR Signaling, and Reduces Tumor Cell Activation and Proliferation in Patients with Relapsed Refractory Chronic Lymphocytic Leukemia. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Herman, Sarah E. M.; McAuley, Erin M.; Liu, Delong; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Barr, Paul M.; Friedberg, Jonathan W.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2882 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905357 ER PT J AU Herman, SEM Farooqui, M Bezabhie, R Aue, G Wiestner, A AF Herman, Sarah E. M. Farooqui, Mohammed Bezabhie, Rahel Aue, Georg Wiestner, Adrian TI In Vivo Effects of Ibrutinib On BCR Signaling, Tumor Cell Activation and Proliferation in Blood and Tissue-Resident Cells of Chronic Lymphocytic Leukemia Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Herman, Sarah E. M.; Farooqui, Mohammed; Bezabhie, Rahel; Aue, Georg; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 185 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900272 ER PT J AU HerndonMd, TM Chen, SS Gatmaitan, M Emson, C Valdez, J Saba, N Chiorazzi, N Wiestner, A AF HerndonMd, Thomas M. Chen, Shih-Shih Gatmaitan, Michelle Emson, Claire Valdez, Janet Saba, Nakhle Chiorazzi, Nicholas Wiestner, Adrian TI Direct in Vivo Evidence of Increased Chronic Lymphocytic Leukemia Cell Proliferation in Lymph Nodes Compared to Bone Marrow and Peripheral Blood SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [HerndonMd, Thomas M.; Valdez, Janet; Saba, Nakhle; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Shih-Shih; Chiorazzi, Nicholas] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Gatmaitan, Michelle; Emson, Claire] KineMed Inc, Emeryville, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 184 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900273 ER PT J AU Hillengass, J Kilk, K Listl, K Hielscher, T Neben, K Hose, D Ho, AD Weber, MA Landgren, O Goldschmidt, H AF Hillengass, Jens Kilk, Kerstin Listl, Karin Hielscher, Thomas Neben, Kai Hose, Dirk Ho, Anthony D. Weber, Marc-Andre Landgren, Ola Goldschmidt, Hartmut TI Appearance of Monoclonal Plasma Cell Diseases in Whole Body MRI in 544 Patients and Correlation with Parameters of Disease Activity SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hielscher, Thomas] DKFZ, Heidelberg, Germany. [Hose, Dirk; Ho, Anthony D.] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany. [Hose, Dirk] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Weber, Marc-Andre/C-4452-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4966 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605102 ER PT J AU Hillengass, J Kilk, K Listl, K Hielscher, T Neben, K Hose, D Weber, MA Ho, AD Goldschmidt, H Landgren, O AF Hillengass, Jens Kilk, Kerstin Listl, Karin Hielscher, Thomas Neben, Kai Hose, Dirk Weber, Marc-Andre Ho, Anthony D. Goldschmidt, Hartmut Landgren, Ola TI Over 30% of Smoldering Myeloma Patients Have Tumor Cell Bone Marrow Infiltration Patterns Similar to Multiple Myeloma: A Large (n=544) Clinical Study Using Whole-Body MRI SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hielscher, Thomas] German Canc Res Ctr, Dept Biostat, Heidelberg, Germany. [Hose, Dirk; Ho, Anthony D.] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany. [Hose, Dirk] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Weber, Marc-Andre/C-4452-2016 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2911 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905328 ER PT J AU Hultcrantz, ML Pfeiffer, RM Bjorkholm, M Goldin, L Turesson, I Schulman, S Landgren, O Kristinsson, SY AF Hultcrantz, Malin L. Pfeiffer, Ruth M. Bjorkholm, Magnus Goldin, Lynn Turesson, Ingemar Schulman, Sam Landgren, Ola Kristinsson, Sigurdur Y. TI Elevated Risk of Venous but Not Arterial Thrombosis in Waldenstrm's Macroglobulinemia and Lymphoplasmacytic Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hultcrantz, Malin L.; Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden. [Hultcrantz, Malin L.; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Pfeiffer, Ruth M.; Goldin, Lynn] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Malmo, Sweden. [Schulman, Sam] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 2 Z9 2 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1603 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906313 ER PT J AU Ikawa, Y Uchiyama, T Jagadeesh, GJ Candotti, F AF Ikawa, Yasuhiro Uchiyama, Toru Jagadeesh, Guridevi Jayashree Candotti, Fabio TI Analysis of Risk and Mechanism of Insertional Oncogenesis After Gene Transfer Into Hematopoietic Progenitors with Integrating Viral Vectors SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ikawa, Yasuhiro; Uchiyama, Toru; Jagadeesh, Guridevi Jayashree; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2049 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603246 ER PT J AU Ikeda, AK Anaebere, TC Malik, N Antalek, MD Seidel, ML Seamon, C Gorbach, A Kato, GJ Ackerman, HC AF Ikeda, Allison K. Anaebere, Tiffany C. Malik, Nitin Antalek, Matthew D. Seidel, Miles L. Seamon, Catherine Gorbach, Alexander Kato, Gregory J. Ackerman, Hans C. TI Laser Speckle Contrast Imaging Characterizes Delayed Reperfusion After Transient Brachial Artery Occlusion in Patients with Sickle Cell Diseas SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ikeda, Allison K.; Anaebere, Tiffany C.; Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [Malik, Nitin; Antalek, Matthew D.; Seidel, Miles L.; Gorbach, Alexander] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Seamon, Catherine; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1080 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601376 ER PT J AU Inamoto, Y Chai, XY Kurland, B Weisdorf, DJ Martin, PJ Jacobsohn, D Pidala, J Palmer, J Arai, S Cutler, C Jagasia, M Flowers, MED Arora, M Pavletic, SZ Vogelsang, GB Lee, SJ Carpenter, PA AF Inamoto, Yoshihiro Chai, Xiaoyu Kurland, Brenda Weisdorf, Daniel J. Martin, Paul J. Jacobsohn, David Pidala, Joseph Palmer, Jeanne Arai, Sally Cutler, Corey Jagasia, Madan Flowers, Mary E. D. Arora, Mukta Pavletic, Steven Z. Vogelsang, Georgia B. Lee, Stephanie J. Carpenter, Paul A. TI Recommended Tools for Joint Chronic Graft-Versus-Host Disease: Results From the Chronic Gvhd Consortium SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Weisdorf, Daniel J.; Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Arai, Sally] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. [Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 464 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901372 ER PT J AU Ito, S Barrett, AJ Larochelle, A Hensel, NF Keyvanfar, K Melenhorst, JJ AF Ito, Sawa Barrett, A. John Larochelle, Andre Hensel, Nancy F. Keyvanfar, Keyvan Melenhorst, J. Joseph TI Long Term Maintenance of Myeloid Leukemia Stem Cell-Like Populations Cultured with Mesenchymal Stromal Cells (MSC) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ito, Sawa; Barrett, A. John; Larochelle, Andre; Hensel, Nancy F.; Keyvanfar, Keyvan; Melenhorst, J. Joseph] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3546 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906111 ER PT J AU Jain, NA Koklanaris, EK Chawla, K Pophali, PA Klotz, JK Hourigan, CS Savani, BN Ito, S Barrett, AJ Battiwalla, M AF Jain, Natasha A. Koklanaris, Eleftheria K. Chawla, Kamna Pophali, Priyanka A. Klotz, Jeffrey K. Hourigan, Christopher S. Savani, Bipin N. Ito, Sawa Barrett, A. John Battiwalla, Minoo TI Post-Transplant Pulmonary Function Abnormalities Normalize in Survivors by the Second Decade After Allogeneic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Jain, Natasha A.; Koklanaris, Eleftheria K.; Chawla, Kamna; Pophali, Priyanka A.; Klotz, Jeffrey K.; Hourigan, Christopher S.; Savani, Bipin N.; Ito, Sawa; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Pophali, Priyanka/P-8646-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1967 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903024 ER PT J AU Jiang, X Huang, H Li, ZJ Li, YY Wang, X Gurbuxani, S Chen, P He, CJ You, DW Zhang, SD Wang, JH Arnovitz, S Elkahloun, A Price, C Hong, GM Ren, HM Kunjamma, RB Neilly, MB Larson, RA Le Beau, MM Slany, RK Liu, PP Lu, J Zhang, JW He, C Rowley, JD Chen, JJ AF Jiang, Xi Huang, Hao Li, Zejuan Li, Yuanyuan Wang, Xiao Gurbuxani, Sandeep Chen, Ping He, Chunjiang You, Dewen Zhang, Shuodan Wang, Jinhua Arnovitz, Stephen Elkahloun, Abdel Price, Colles Hong, Gia-Ming Ren, Haomin Kunjamma, Rejani B. Neilly, Mary Beth Larson, Richard A. Le Beau, Michelle M. Slany, Robert K. Liu, Paul P. Lu, Jun Zhang, Jiwang He, Chuan Rowley, Janet D. Chen, Jianjun TI Blockade of Mir-150 Maturation by MLL-Fusion/MYC/Lin-28 Is Required for MLL-Associated Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Jiang, Xi; Huang, Hao; Li, Zejuan; Li, Yuanyuan; Chen, Ping; He, Chunjiang; Zhang, Shuodan; Wang, Jinhua; Arnovitz, Stephen; Price, Colles; Hong, Gia-Ming; Ren, Haomin; Kunjamma, Rejani B.; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Wang, Xiao; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Wang, Xiao; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [You, Dewen; Zhang, Jiwang] Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Inst Oncol, Maywood, IL 60153 USA. [Elkahloun, Abdel; Liu, Paul P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Slany, Robert K.] Univ Erlangen Nurnberg, Dept Genet, D-91054 Erlangen, Germany. [Lu, Jun] Yale Univ, Dept Genet, Yale Stem Cell Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3499 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604028 ER PT J AU Johnson, KD Gao, X Sanalkumar, R Hsu, AP Ryu, MJ Wang, JY Boyer, ME Liu, YG Calvo, KR Keles, S Zhang, J Holland, SM Bresnick, EH AF Johnson, Kirby D. Gao, Xin Sanalkumar, Rajendran Hsu, Amy P. Ryu, Myung-Jeom Wang, Jinyong Boyer, Meghan E. Liu, Yangang Calvo, Katherine R. Keles, Sunduz Zhang, Jing Holland, Steven M. Bresnick, Emery H. TI Genetic Determinants of the Definitive Hematopoietic Stem/Progenitor Cell Compartment SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Johnson, Kirby D.; Gao, Xin; Sanalkumar, Rajendran; Boyer, Meghan E.; Bresnick, Emery H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, UW Carbone Canc Ctr, Madison, WI USA. [Hsu, Amy P.; Holland, Steven M.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Ryu, Myung-Jeom; Wang, Jinyong; Zhang, Jing] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. [Keles, Sunduz] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat, Madison, WI USA. [Keles, Sunduz] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Informat & Stat, Madison, WI USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1226 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902340 ER PT J AU Kang, YY Patel, B Cui, KR Zhao, KJ Qiu, Y Huang, SM AF Kang, Yuanyuan Patel, Bhavita Cui, Kairong Zhao, Keji Qiu, Yi Huang, Suming TI A T-Cell Specific Element Activates the TAL1 Oncogene Via an Interchromosomal Interaction During Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Zhao, Keji] NHLBI, NIH, Bethesda, MD 20892 USA. [Huang, Suming] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3507 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604020 ER PT J AU Khincha, P Wentzensen, I Giri, N Alter, BP Savage, SA AF Khincha, Payal Wentzensen, Ingrid Giri, Neelam Alter, Blanche P. Savage, Sharon A. TI Response to Androgen Therapy and Side Effects in Patients with Dyskeratosis Congenita SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Khincha, Payal; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Wentzensen, Ingrid] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 1 Z9 1 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2361 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601100 ER PT J AU Kim, KS Byrnes, C Lee, YT de Vasconcellos, JF Noh, SJ Miller, JL AF Kim, Ki Soon Byrnes, Colleen Lee, Y. Terry de Vasconcellos, Jaira F. Noh, Seung-Jae Miller, Jeffery L. TI Mitochondria Superoxide Is an Early Trigger of Apoptosis in an Ex Vivo Model of Human Beta Thalassemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kim, Ki Soon; Byrnes, Colleen; Lee, Y. Terry; de Vasconcellos, Jaira F.; Noh, Seung-Jae; Miller, Jeffery L.] NIDDKD, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2131 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905305 ER PT J AU Nguyen, KL Alam, S Tian, X Leung, SW Seamon, C Minniti, C Taylor, JG Sachdev, V Arai, AE Kato, GJ AF Kim-Lien Nguyen Alam, Shoaib Tian, Xian Leung, Steve W. Seamon, Catherine Minniti, Caterina Taylor, James G. Sachdev, Vandana Arai, Andrew E. Kato, Gregory J. TI Increased Transpulmonary Gradient Predicts Functional Class, Mortality, and RV Dysfunction by MRI in Patients with Sickle Cell Associated Pulmonary Hypertension SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kim-Lien Nguyen; Alam, Shoaib; Leung, Steve W.; Sachdev, Vandana; Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Tian, Xian] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Seamon, Catherine; Minniti, Caterina; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA. [Taylor, James G.] NHLBI, Genom Med Sect, Hematol Branch, Bethesda, MD 20892 USA. RI Leung, Steve/E-5624-2011; Kato, Gregory/I-7615-2014 OI Leung, Steve/0000-0003-2832-2258; Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 89 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900076 ER PT J AU Korde, N Liu, QY Kwok, M Manasanch, EE Simakova, O Mailankody, S Roschewski, M Zingone, A Costello, R Zuchlinski, D Mulquin, M Calvo, KR Braylan, RC Maric, I Landgren, O AF Korde, Neha Liu, Qing Yan Kwok, Mary Manasanch, Elisabet E. Simakova, Olga Mailankody, Sham Roschewski, Mark Zingone, Adriana Costello, Rene Zuchlinski, Diamond Mulquin, Marcia Calvo, Katherine R. Braylan, Raul C. Maric, Irina Landgren, Ola TI Early Myelodysplastic Changes Present in Substantial Proportion of Monoclonal Gammopathy of Unknown Significance (MGUS) and Smoldering Multiple Myeloma (SMM) Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Liu, Qing Yan] NIH, Hematol Sect, DLM, CC, Bethesda, MD 20892 USA. [Manasanch, Elisabet E.; Zingone, Adriana; Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Roschewski, Mark] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. [Braylan, Raul C.; Maric, Irina] NIH, Hematol Sect, Dept Lab Med, CCR, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1805 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602072 ER PT J AU Korde, N Zingone, A Kwok, M Manasanch, EE Costello, R Zuchlinski, D Mulquin, M Maric, I Calvo, KR Braylan, RC Yuan, C Tembhare, PR Stetler-Stevenson, M Arthur, DC Raffeld, M Xi, LQ Choyke, P Kurdziel, K Lindenberg, L Steinberg, SM Roschewski, M Landgren, O AF Korde, Neha Zingone, Adriana Kwok, Mary Manasanch, Elisabet E. Costello, Rene Zuchlinski, Diamond Mulquin, Marcia Maric, Irina Calvo, Katherine R. Braylan, Raul C. Yuan, Constance Tembhare, Prashant Ramesh Stetler-Stevenson, Maryalice Arthur, Diane C. Raffeld, Mark Xi, Liqiang Choyke, Peter Kurdziel, Karen Lindenberg, Liza Steinberg, Seth M. Roschewski, Mark Landgren, Ola TI Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Manasanch, Elisabet E.; Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Maric, Irina; Braylan, Raul C.] NIH, Hematol Sect, Dept Lab Med, CCR, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Yuan, Constance; Tembhare, Prashant Ramesh; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Arthur, Diane C.] NCI, Pathol Lab, NIH, CCR, Bethesda, MD 20892 USA. [Raffeld, Mark; Xi, Liqiang] NCI, Mol Diagnost Core Lab, NIH, CCR, Bethesda, MD 20892 USA. [Choyke, Peter; Kurdziel, Karen; Lindenberg, Liza] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Roschewski, Mark] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 732 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900227 ER PT J AU Kreitman, RJ Arons, E Jeffrey, S Roth, L Zhou, H Stetler-Stevenson, M Wilson, WH Raffeld, M FitzGerald, DJP Fei, J Ibrahim, R Pastan, I AF Kreitman, Robert J. Arons, Evgeny Jeffrey, Sapolsky Roth, Laura Zhou, Hong Stetler-Stevenson, Maryalice Wilson, Wyndham H. Raffeld, Mark FitzGerald, David J. P. Fei, Ji Ibrahim, Ramy Pastan, Ira TI Resolution of Hairy Cell Leukemia Minimal Residual Disease by Both BRAF and Clone-Specific Real-Time Quantitative PCR (RQ-PCR) After Treatment with Moxetumomab Pasudotox SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kreitman, Robert J.; Arons, Evgeny; Jeffrey, Sapolsky; Roth, Laura; Zhou, Hong; FitzGerald, David J. P.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Fei, Ji; Ibrahim, Ramy] MedImmune LLC, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2896 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905343 ER PT J AU Lanasa, MC Allgood, SD Goldin, LR Brander, DM McMaster, ML AF Lanasa, Mark C. Allgood, Sallie D. Goldin, Lynn R. Brander, Danielle M. McMaster, Mary L. TI Circulating B Cell Clones in Familial Waldenstrom Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lanasa, Mark C.; Allgood, Sallie D.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Goldin, Lynn R.; McMaster, Mary L.] NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2703 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903090 ER PT J AU Lancet, JE Feldman, E Foster, MC Gojo, I Odenike, O Komrokji, RS Strair, R Kaufmann, SH Knoblauch, R Karkera, JD Wright, JJ Karp, JE AF Lancet, Jeffrey E. Feldman, Eric Foster, Matthew C. Gojo, Ivana Odenike, Olatoyosi Komrokji, Rami S. Strair, Roger Kaufmann, Scott H. Knoblauch, Roland Karkera, J. D. Wright, John J. Karp, Judith E. TI Phase 2 Trial of the Farnesyltransferase Inhibitor Tipifarnib in Previously Untreated Older Adults with AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lancet, Jeffrey E.; Komrokji, Rami S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Feldman, Eric] Weill Cornell Med Coll, New York, NY USA. [Foster, Matthew C.] Lineberger Canc Ctr, Chapel Hill, NC USA. [Gojo, Ivana] Johns Hopkins Univ, Kimmel Canc Ctr, Baltimore, MD 21218 USA. [Odenike, Olatoyosi] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Strair, Roger] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Div Hematol, New Brunswick, NJ USA. [Kaufmann, Scott H.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Knoblauch, Roland; Karkera, J. D.] Janssen, Res & Dev, Raritan, NJ USA. [Wright, John J.] NCI, Bethesda, MD 20892 USA. [Karp, Judith E.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Div Hematol Malignancies, Dept Oncol, Baltimore, MD USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1508 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906218 ER PT J AU Lederman, HM Connolly, MA Kalpatthi, R Ware, RE Wang, WC Luchtman-Jones, L Waclawiw, M Goldsmith, JC Casella, JF AF Lederman, Howard M. Connolly, Margaret A. Kalpatthi, Ram Ware, Russell E. Wang, Winfred C. Luchtman-Jones, Lori Waclawiw, Myron Goldsmith, Jonathan C. Casella, James F. TI Effects of Hydroxyurea (HU) On Lymphocyte Subsets and the Immune Response to Pneumococcal, Measles, Mumps and Rubella Vaccination in the Pediatric Hydroxyurea Phase III Clinical Trial - BABY HUG - (ClinicalTrials.gov Identifier: NCT00006400) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lederman, Howard M.; Casella, James F.] Johns Hopkins Univ, Sch Med, Div Immunol, Baltimore, MD USA. [Connolly, Margaret A.] C TASC, Owings Mills, MD USA. [Kalpatthi, Ram] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Ware, Russell E.] Baylor Coll Med, Houston, TX 77030 USA. [Wang, Winfred C.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. [Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC USA. [Goldsmith, Jonathan C.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 243 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901107 ER PT J AU Li, ZJ Zhang, ZY Li, YY Arnovitz, S Chen, P Huang, H Jiang, X Hong, GM He, CJ Wang, CZ Elkahloun, A Valk, PJM Dohner, K Neilly, MB Bullinger, L Delwel, R Lowenberg, B Liu, PP Morgan, R Rowley, JD Yuan, CS Chen, JJ AF Li, Zejuan Zhang, Zhiyu Li, Yuanyuan Arnovitz, Stephen Chen, Ping Huang, Hao Jiang, Xi Hong, Gia-Ming He, Chunjiang Wang, Chong-Zhi Elkahloun, Abdel Valk, Peter J. M. Dohner, Konstanze Neilly, Mary Beth Bullinger, Lars Delwel, Ruud Lowenberg, Bob Liu, Pu Paul Morgan, Richard Rowley, Janet D. Yuan, Chun-Su Chen, Jianjun TI The HOXA/PBX3 Pathway Is an Attractive Therapeutic Target in MLL-Rearranged Acute Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Li, Zejuan; Li, Yuanyuan; Arnovitz, Stephen; Chen, Ping; Huang, Hao; Jiang, Xi; Hong, Gia-Ming; He, Chunjiang; Neilly, Mary Beth; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Zhang, Zhiyu] Univ Chicago, Dept Anesthesia & Crit Care, Chicgao, IL USA. [Wang, Chong-Zhi; Yuan, Chun-Su] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. [Valk, Peter J. M.; Lowenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Dohner, Konstanze] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. [Bullinger, Lars] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany. [Delwel, Ruud] Univ Med Ctr Rotterdam, Erasmus MC, Dept Hem, Rotterdam, Netherlands. [Liu, Pu Paul] NHGRI, GMBB, ODS, NIH, Bethesda, MD 20892 USA. [Morgan, Richard] Univ Surrey, Guildford GU2 5XH, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3522 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906135 ER PT J AU Lim, KH Romero, DL Chaudhary, D Robinson, SD Staudt, LM AF Lim, Kian-Huat Romero, Donna L. Chaudhary, Divya Robinson, Shaughnessy D. Staudt, Louis M. TI IRAK4 Kinase As A Novel Therapeutic Target in the ABC Subtype of Diffuse Large B Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lim, Kian-Huat] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Romero, Donna L.; Chaudhary, Divya] Nimbus Discovery Inc, Cambridge, MA USA. [Robinson, Shaughnessy D.] Schrodinger Inc, New York, NY USA. [Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 62 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900102 ER PT J AU Loaiza-Bonilla, A Artz, A Salerno, F Leng, SX Yeh, SS Biedenbender, R Gravenstein, S Loera, J Geloo, ZS Ershler, WB AF Loaiza-Bonilla, Arturo Artz, Andrew Salerno, Francis Leng, Sean X. Yeh, Shing-Shing Biedenbender, Rex Gravenstein, Stefan Loera, Jose Geloo, Zeba Shaheen Ershler, William B. TI Correction of Anemia in the Frail Elderly (CAFE): Results of a Randomized, Double-Blind, Placebo-Controlled Study with Darbepoetin Alfa in Elderly Patients with Chronic Unexplained Anemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Loaiza-Bonilla, Arturo] Univ Miami, Miller Sch Med, Div Hematol & Oncol, Dept Med, Miami, FL 33136 USA. [Artz, Andrew] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Salerno, Francis] Lehigh Valley Hosp, Div Geriatr, Dept Med, Allentown, PA USA. [Leng, Sean X.] Johns Hopkins Univ, Dept Med, Div Geriatr, Baltimore, MD USA. [Yeh, Shing-Shing] Vet Affairs Med Ctr, Div Geriatr, Dept Med, Northport, NY USA. [Biedenbender, Rex; Gravenstein, Stefan] Eastern Virginia Med Sch, Glennan Ctr Geriatr & Gerontol, Norfolk, VA 23501 USA. [Loera, Jose] Vet Affairs & Scott & White, Div Geriatr, Temple, TX USA. [Geloo, Zeba Shaheen] Inst Adv Studies Aging & Geriatr Med IASIA, Gaithersburg, MD USA. [Ershler, William B.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 5153 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605435 ER PT J AU Lorenzo, FR Zhuang, ZP Yang, CZ Fui, MNT Vankayalapati, H Pacak, K Prchal, JT AF Lorenzo, Felipe R. Zhuang, Zhengping Yang, Chunzhang Fui, Mark Ng Tang Vankayalapati, Hariprasad Pacak, Karel Prchal, Josef T. TI Three Novel EPAS1/HIF2A Somatic and Germline mutations Associated with Polycythemia and Pheochromocytoma/Paraganglioma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lorenzo, Felipe R.; Prchal, Josef T.] Univ Utah, Div Hematol, Salt Lake City, UT USA. [Yang, Chunzhang; Fui, Mark Ng Tang; Pacak, Karel] NIH, Bethesda, MD 20892 USA. [Fui, Mark Ng Tang] Univ Melbourne, Dept Endocrinol, Heidelberg, Vic, Australia. [Vankayalapati, Hariprasad] Univ Utah, Ctr Invest Therapeut, Salt Lake City, UT USA. [Vankayalapati, Hariprasad] Huntsman Canc Inst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2080 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603215 ER PT J AU Lozier, JN Nghiem, K Lee, M Hodsdon, B Joe, G Weitzel, RP Tisdale, JF Hsieh, M AF Lozier, Jay N. Nghiem, Khanh Lee, Martin Hodsdon, Bonnie Joe, Galen Weitzel, R. Patrick Tisdale, John F. Hsieh, Matthew TI Acquired Hemophilia A in an African-American Male After Stem Cell Transplant for Sickle Cell Disease: Successful Treatment with Recombinant Porcine Factor VIII (OBI-1) and Tolerance Induction with Rituximab and Prednisone SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Lozier, Jay N.; Nghiem, Khanh] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Lee, Martin] Inspirat Biopharmaceut Inc, E Cambridge, MA USA. [Hodsdon, Bonnie; Joe, Galen] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Weitzel, R. Patrick] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Tisdale, John F.; Hsieh, Matthew] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4631 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049606087 ER PT J AU Mamcarz, EK Berg, M Peled, T Frei, GM Reger, R Tian, X Childs, R AF Mamcarz, Ewelina K. Berg, Maria Peled, Tony Frei, Gabi M. Reger, Robert Tian, Xin Childs, Richard TI Nicotinamide (NAM) Increases Surface Expression of CD62L On in Vitro Expanded NK Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mamcarz, Ewelina K.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Berg, Maria; Reger, Robert; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Peled, Tony; Frei, Gabi M.] Gamida Cell, Jerusalem, Israel. [Tian, Xin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4355 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605167 ER PT J AU Masters, SL Gerlic, M Metcalf, D Preston, SP Pellegrini, M O'Donnell, JA McArthur, K Baldwin, TM Chevrier, S Nowell, CJ Cengia, LH Henley, KJ Collinge, JE Kastner, DL Feigenbaum, L Hilton, DJ Alexander, WS Croker, BA Kile, BT AF Masters, Seth L. Gerlic, Mordechay Metcalf, Donald Preston, Simon P. Pellegrini, Marc O'Donnell, Joanne A. McArthur, Kate Baldwin, Tracey M. Chevrier, Stephane Nowell, Cameron J. Cengia, Louise H. Henley, Katya J. Collinge, Janelle E. Kastner, Daniel L. Feigenbaum, Lionel Hilton, Douglas J. Alexander, Warren S. Croker, Ben A. Kile, Benjamin T. TI Activation of the NLRP1 Inflammasome Induces the Pyroptotic Death of Hematopoietic Progenitor Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Masters, Seth L.; Gerlic, Mordechay; Metcalf, Donald; Preston, Simon P.; Pellegrini, Marc; O'Donnell, Joanne A.; McArthur, Kate; Baldwin, Tracey M.; Chevrier, Stephane; Cengia, Louise H.; Henley, Katya J.; Collinge, Janelle E.; Hilton, Douglas J.; Alexander, Warren S.; Croker, Ben A.; Kile, Benjamin T.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Nowell, Cameron J.] Ludwig Inst Canc Res, Ctr Adv Microscopy, Parkville, Vic, Australia. [Kastner, Daniel L.] NIAMSD, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, Frederick, MD 21701 USA. RI Hilton, Douglas/C-7250-2013; Pellegrini, Marc/F-7670-2014 OI Hilton, Douglas/0000-0002-7698-2392; NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1213 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902353 ER PT J AU McDonnell, SRP Hwang, SR Basrur, V Conlon, K Fermin, D Murga-Zamalloa, C Rolland, DCM Thomas, CJ Elenitoba-Johnson, KSJ Lim, MS AF McDonnell, Scott R. P. Hwang, Steven R. Basrur, Venkatesha Conlon, Kevin Fermin, Damian Murga-Zamalloa, Carlos Rolland, Delphine C. M. Thomas, Craig J. Elenitoba-Johnson, Kojo S. J. Lim, Megan S. TI Phosphorylation of PKM2 by NPM-ALK Regulates a Metabolic Shift and Increased Oncogenic Potential SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Thomas, Craig J.] NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Lim, Megan S.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 896 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900363 ER PT J AU Meier, ER Wright, EC Luban, NLC Miller, JL AF Meier, Emily Riehm Wright, Elizabeth C. Luban, Naomi L. C. Miller, Jeffery L. TI Risk Stratification in Pediatric Sickle Cell Disease Using Absolute Reticulocyte Counts SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Meier, Emily Riehm; Miller, Jeffery L.] NIDDKD, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Bethesda, MD 20892 USA. [Luban, Naomi L. C.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1014 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602057 ER PT J AU Mendelsohn, LG Pedoeim, L van Beers, EJ Saiyed, R Nichols, JS Wang, XD Kato, GJ AF Mendelsohn, Laurel G. Pedoeim, Leah van Beers, Eduard J. Saiyed, Rehan Nichols, James S. Wang, Xunde Kato, Gregory J. TI Effect of Aes-103 Anti-Sickling Agent On Oxygen Affinity and Stability of Red Blood Cells From Patients with Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mendelsohn, Laurel G.; Pedoeim, Leah; van Beers, Eduard J.; Saiyed, Rehan; Nichols, James S.; Wang, Xunde; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 85 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900080 ER PT J AU Meshinchi, S Ries, RE Trevino, LR Hampton, OA Alonzo, T Farrar, JE Auvil, JMG Davidsen, TM Gesuwan, P Muzny, DM Gamis, AS Helton, HL Wheeler, DA Smith, MA Gerhard, DS Arceci, RJ AF Meshinchi, Soheil Ries, Rhonda E. Trevino, Lisa R. Hampton, Oliver A. Alonzo, Todd Farrar, Jason E. Auvil, Jaime M. Guidry Davidsen, Tanja M. Gesuwan, Patee Muzny, Donna M. Gamis, Alan S. Helton, Heather L. Wheeler, David A. Smith, Malcolm A. Gerhard, Daniela S. Arceci, Robert J. TI Identification of Novel Somatic Mutations, Regions of Recurrent Loss of Heterozygosity (LOH) and Significant Clonal Evolution From Diagnosis to Relapse in Childhood AML Determined by Exome Capture Sequencing - an NCI/COG Target AML Study SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Meshinchi, Soheil; Ries, Rhonda E.; Helton, Heather L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Trevino, Lisa R.; Hampton, Oliver A.; Muzny, Donna M.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Alonzo, Todd] Childrens Oncol Grp, Arcadia, CA USA. [Farrar, Jason E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Auvil, Jaime M. Guidry; Davidsen, Tanja M.; Gesuwan, Patee; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Arceci, Robert J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 123 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900335 ER PT J AU Milton, JN Rooks, H Drasar, E McCabe, EL Baldwin, CT Melista, E Gordeuk, VR Nouraie, M Kato, GJ Minniti, C Taylor, JG Campbell, A Luchtman-Jones, L Rana, SR Castro, OL Zhang, YZ Thein, SL Gladwin, MT Sebastiani, P Steinberg, MH AF Milton, Jacqueline N. Rooks, Helen Drasar, Emma McCabe, Elizabeth L. Baldwin, Clinton T. Melista, Efthymia Gordeuk, Victor R. Nouraie, Mehdi Kato, Gregory J. Minniti, Caterina Taylor, James G. Campbell, Andrew Luchtman-Jones, Lori Rana, Sohail R. Castro, Oswaldo L. Zhang, Yingze Thein, Swee Lay Gladwin, Mark T. Sebastiani, Paola Steinberg, Martin H. TI Genetic Determinants of Hemolysis in Sickle Cell Anemia. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Drasar, Emma] Kings Coll London, Sch Med, London SE5 9NU, England. [Baldwin, Clinton T.; Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gordeuk, Victor R.; Castro, Oswaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Minniti, Caterina] NHLBI, Sickle Cell Vasc Dis Sect, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Taylor, James G.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Campbell, Andrew] Univ Michigan, Ann Arbor, MI 48109 USA. [Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Zhang, Yingze; Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Thein, Swee Lay] Kings Coll London, Sch Med, Kings Coll Hosp Haematol Med, London SE5 9NU, England. [Sebastiani, Paola] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2104 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603191 ER PT J AU Minniti, CP Hon, YY Gorbach, A Delaney, KM Xu, DH Malik, N Maivelett, J Novelli, EM Lanzkron, S Kato, GJ AF Minniti, Caterina P. Hon, Yuen Yi Gorbach, Alexander Delaney, Kara M. Xu, Dihua Malik, Nitin Maivelett, Jordan Novelli, Enrico M. Lanzkron, Sophia Kato, Gregory J. TI A Phase 1, Dose-Escalation Study of Topical Sodium Nitrite in Patients with Sickle Cell Anemia and Leg Ulcers SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Delaney, Kara M.; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hon, Yuen Yi] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Gorbach, Alexander; Malik, Nitin; Maivelett, Jordan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Novelli, Enrico M.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Lanzkron, Sophia] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 86 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900079 ER PT J AU Miyazaki, T Kim, YS Yoon, JH Wang, HS Morse, HC AF Miyazaki, Takuya Kim, Yong-Soo Yoon, Jeong-Heon Wang, Hongsheng Morse, Herbert C., III TI The 3 '-5 ' Exonuclease, TREX1, Interacts with Poly(ADP-ribose) Polymerase-1 (PARP1) in Response to DNA Damage SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Miyazaki, Takuya; Kim, Yong-Soo; Yoon, Jeong-Heon; Wang, Hongsheng; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1046 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602027 ER PT J AU Morris, CR Kim, HY Wood, JC Trachtenberg, F Klings, ES Porter, JB Sweeters, N Olivieri, NF Kwiatkowski, JL Singer, ST Taher, AT Neufeld, EJ Thompson, AA Sachdev, V Larkin, SK Suh, JH Kuypers, FA Vichinsky, E AF Morris, Claudia R. Kim, Hae-Young Wood, John C. Trachtenberg, Felicia Klings, Elizabeth S. Porter, John B. Sweeters, Nancy Olivieri, Nancy F. Kwiatkowski, Janet L. Singer, Sylvia Titi Taher, Ali T. Neufeld, Ellis J. Thompson, Alexis A. Sachdev, Vandana Larkin, Sandra K. Suh, Jung H. Kuypers, Frans A. Vichinsky, Elliott TI Sildenafil Therapy in Patients with Thalassemia and an Elevated Tricuspid Regurgitant Jet Velocity (TRV) On Doppler Echocardiography At Risk for Pulmonary Hypertension: Report From the Thalassemia Clinical Research Network SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Morris, Claudia R.] Emory Univ, Sch Med, Atlanta, GA USA. [Kim, Hae-Young; Trachtenberg, Felicia] New England Res Inst, Watertown, MA 02172 USA. [Wood, John C.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Porter, John B.] UCL, London, England. [Sweeters, Nancy; Singer, Sylvia Titi; Vichinsky, Elliott] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Olivieri, Nancy F.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Kwiatkowski, Janet L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Taher, Ali T.] Amer Univ Beirut, Beirut, Lebanon. [Neufeld, Ellis J.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Thompson, Alexis A.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Sachdev, Vandana] NHLBI, Cardiovasc & Pulm Med Branch, NIH, Bethesda, MD 20892 USA. [Suh, Jung H.] Childrens Hosp Oakland, Res Inst, Nutr & Metab Ctr, Oakland, CA 94609 USA. NR 0 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1023 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602048 ER PT J AU Muller, TA Dechow, R Istyanffy, R Hennighausen, L Peschel, C Duyster, J AF Mueller, Tony Andreas Dechow, Rebekka Istyanffy, Rouzanna Hennighausen, Lothar Peschel, Christian Duyster, Justus TI The Role of STAT5 in FLT3-Mediated Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Mueller, Tony Andreas; Dechow, Rebekka; Istyanffy, Rouzanna; Peschel, Christian; Duyster, Justus] Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-80290 Munich, Germany. [Hennighausen, Lothar] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 771 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900188 ER PT J AU Nash, RA Hutton, GJ Racke, MK Popat, UR Devine, SM Georges, GE Griffith, LM Muraro, PA Openshaw, H Sayre, PH Stuve, O Arnold, DL Spychala, M Lim, N Malhotra, S Phippard, D Wundes, A Kraft, GH Bowen, JD AF Nash, Richard A. Hutton, George J. Racke, Michael K. Popat, Uday R. Devine, Steven M. Georges, George E. Griffith, Linda M. Muraro, Paolo A. Openshaw, Harry Sayre, Peter H. Stuve, Olaf Arnold, Douglas L. Spychala, Meagan Lim, Noha Malhotra, Sachin Phippard, Deborah Wundes, Annette Kraft, George H. Bowen, James D. TI Treatment of Severe Relapsing-Remitting Multiple Sclerosis with High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation: 2-Year Follow-up Results of the HALT MS Clinical Trial (Immune Tolerance Network: ITN033AI) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Nash, Richard A.] Colorado Blood Canc Inst, Denver, CO USA. [Hutton, George J.] Baylor Coll Med, Houston, TX 77030 USA. [Racke, Michael K.; Devine, Steven M.] Ohio State Univ, Columbus, OH 43210 USA. [Popat, Uday R.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Georges, George E.] Fred Hutchinson Canc Res Ctr, Transplantat Biol Program, Seattle, WA 98104 USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Div Neurosci & Mental Hlth, London SW7 2AZ, England. [Stuve, Olaf] Univ Texas SW, Sch Med, Dallas, TX USA. [Arnold, Douglas L.] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Malhotra, Sachin] Harvard Univ, Cambridge, MA 02138 USA. [Wundes, Annette; Kraft, George H.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 962 PG 3 WC Hematology SC Hematology GA 074UG UT WOS:000313838901175 ER PT J AU Natarajan, K Bhullar, J Shukla, S Burcu, M Ambudkar, SV Baer, MR AF Natarajan, Karthika Bhullar, Jasjeet Shukla, Suneet Burcu, Mehmet Ambudkar, Suresh V. Baer, Maria R. TI The Pim Kinase Inhibitor SGI-1776 Chemosensitizes Multidrug Resistant Cells by Both Inhibiting Drug Transport by ABCB1 and ABCG2 and Decreasing ABCB1 and ABCG2 Surface Expression On Cells That Overexpress Pim-1 SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Natarajan, Karthika; Bhullar, Jasjeet; Burcu, Mehmet; Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2462 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602219 ER PT J AU Nayar, U Akar, G Shoemaker, RH Sei, S Cesarman, E AF Nayar, Utthara Akar, Gunkut Shoemaker, Robert H. Sei, Shizuko Cesarman, Ethel TI Identification of a Novel Inhibitor That Selectively Targets NF-kappa B Activity in KSHV-Infected Lymphoma Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Nayar, Utthara; Akar, Gunkut] Weill Cornell Med Coll, New York, NY USA. [Shoemaker, Robert H.] NCI, Div Canc Treatment & Diag, Frederick, MD 21701 USA. [Sei, Shizuko] NCI Frederick, Frederick, MD USA. [Cesarman, Ethel] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 160 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900297 ER PT J AU Ochs, M Farrar, J Considine, M Ries, RE Trevino, LR Alonzo, TA Guidry-Auvil, J Davidsen, TM Gesuwan, P Muzny, DM Gamis, AS Wheeler, DA Helton, HL Smith, MA Gerhard, DS Meshinchi, S Arceci, RJ AF Ochs, Michael Farrar, Jason Considine, Michael Ries, Rhonda E. Trevino, Lisa R. Alonzo, Todd A. Guidry-Auvil, Jaime Davidsen, Tanja M. Gesuwan, Patee Muzny, Donna M. Gamis, Alan S. Wheeler, David A. Helton, Heather L. Smith, Malcolm A. Gerhard, Daniela S. Meshinchi, Soheil Arceci, Robert J. TI Genome Wide Promoter Methylation Patterns Predict AML Subtype Outcomes and Identify Novel Pathways Characterizing Diagnostic and Relapsed Disease in Children SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ochs, Michael; Considine, Michael] Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Farrar, Jason] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Ries, Rhonda E.; Helton, Heather L.; Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Trevino, Lisa R.; Muzny, Donna M.; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Alonzo, Todd A.] Childrens Oncol Grp, Arcadia, CA USA. [Guidry-Auvil, Jaime] NIH, Off Canc Genom, Bethesda, MD 20892 USA. [Davidsen, Tanja M.; Gesuwan, Patee; Smith, Malcolm A.; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Arceci, Robert J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1287 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902279 ER PT J AU Onozawa, M Kim, H Gough, SM Lin, YW Cui, YZ Beachy, SH Mackall, CL Aplan, P AF Onozawa, Masahiro Kim, Hyunkyung Gough, Sheryl M. Lin, Yingwei Cui, Yongzhi Beachy, Sarah H. Mackall, Crystal L. Aplan, Peter TI Illegitimate V(D)J Recombination Involving Notch1 and Bcl11b in Precursor T-Cell Lymphoblastic Leukemia/Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Onozawa, Masahiro; Kim, Hyunkyung; Gough, Sheryl M.; Beachy, Sarah H.; Aplan, Peter] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Lin, Yingwei] Date Red Cross Hosp, Date, Japan. [Cui, Yongzhi; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1323 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603168 ER PT J AU Onozawa, M Varga, T Kim, YJ Zhang, ZH Aplan, P AF Onozawa, Masahiro Varga, Tamas Kim, Yoo Jung Zhang, Zhenhua Aplan, Peter TI Repair of DNA Double Strand Breaks by RNA/DNA Patches in U937 Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Onozawa, Masahiro; Varga, Tamas; Kim, Yoo Jung; Zhang, Zhenhua; Aplan, Peter] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2375 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601086 ER PT J AU Pantin, JM Hoyt, RF Aras, O Chen, MY Sato, N Choyke, P Childs, R AF Pantin, Jeremy M. Hoyt, Robert F., Jr. Aras, Omer Chen, Marcus Y. Sato, Noriko Choyke, Peter Childs, Richard TI Optimization of an Intra-Bone Hematopoietic Stem Cell Delivery Technique in a Swine Model SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pantin, Jeremy M.] Georgia Hlth Sci Univ, Dept Med Hematol & Oncol, Augusta, GA USA. [Hoyt, Robert F., Jr.] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA. [Aras, Omer; Sato, Noriko; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Chen, Marcus Y.] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2990 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600182 ER PT J AU Paralkar, VR Mishra, T Luan, J Yao, Y Konuthula, N Bodine, DM Hardison, RC Weiss, MJ AF Paralkar, Vikram R. Mishra, Tejaswini Luan, Jing Yao, Yu Konuthula, Neeraja Bodine, David M. Hardison, Ross C. Weiss, Mitchell J. TI Long Noncoding RNAs in Erythropoiesis and Megakaryopoiesis. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Paralkar, Vikram R.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Mishra, Tejaswini; Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Luan, Jing; Yao, Yu; Konuthula, Neeraja; Weiss, Mitchell J.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2331 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601129 ER PT J AU Park, JW Piknova, B Nghiem, K Lozier, JN Schechter, AN AF Park, Ji-Won Piknova, Barbora Nghiem, Khanh Lozier, Jay N. Schechter, Alan N. TI Thrombelastographic Demonstration of Nitrite Inhibition of Platelet Function SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Park, Ji-Won; Piknova, Barbora; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Nghiem, Khanh; Lozier, Jay N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 5148 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605440 ER PT J AU Patel, B Deng, CW Litt, M Riberio, MS Cui, KR Kang, YY Qiu, Y Zhao, KJ Huang, SM AF Patel, Bhavita Deng, Changwang Litt, Michael Riberio, Mariana St Just Cui, Kairong Kang, Yuanyuan Qiu, Yi Zhao, Keji Huang, Suming TI CTCF Mediated Enhancer and Promoter Interaction Regulates Differential Expression of TAL1 Oncogene in Normal and Malignant Hematopoiesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Litt, Michael] Ball State Univ, Muncie, IN 47306 USA. [Zhao, Keji] NHLBI, NIH, Bethesda, MD 20892 USA. [Huang, Suming] Univ Florida, Coll Med, Shands Canc Ctr Biochem & Mol Biol, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 281 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901145 ER PT J AU Pawelczyk, E Degheidy, HA Branchaw, AL Holmbeck, K Bauer, SR AF Pawelczyk, Edyta Degheidy, Heba A. Branchaw, Allison L. Holmbeck, Kenn Bauer, Steven R. TI Dlk-1 Regulates B Cell Development Through Altered Bone Marrow Stromal Microenvironment, Not by Affecting Hematopoitic Stem/Progenitor Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pawelczyk, Edyta; Branchaw, Allison L.; Bauer, Steven R.] US FDA, CBER, Bethesda, MD 20014 USA. [Degheidy, Heba A.] US FDA, CDRH, OSEL, DB, Silver Spring, MD USA. [Holmbeck, Kenn] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3465 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604062 ER PT J AU Perkins, K Davis, J Price, S Niemela, J Huber, AR Wall, DA Pittaluga, S Fleisher, TA Rao, VK AF Perkins, Katie Davis, Joie Price, Susan Niemela, Julie Huber, Andreas R. Wall, Donna A. Pittaluga, Stefania Fleisher, Thomas A. Rao, V. Koneti TI Expanding Spectrum of Malignancies in ALPS: A Cancer Predisposing Syndrome?. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Perkins, Katie; Davis, Joie; Price, Susan; Rao, V. Koneti] NIAID, ALPS Unit, LCID, NIH, Bethesda, MD 20892 USA. [Niemela, Julie; Fleisher, Thomas A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Wall, Donna A.] Univ Manitoba, Winnipeg, MB, Canada. [Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2149 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905287 ER PT J AU Pidala, J Wang, T Haagenson, MD Spellman, S Askar, M Battiwalla, M Baxter-Lowe, LA Bitan, M Fernandez-Vina, M Gandhi, M Jakubowski, AA Maiers, M Marino, SR Marsh, SGE Oudshoorn, M Palmer, J Prasad, VK Reddy, V Ringden, O Saber, W Santarone, S Schultz, KR Setterholm, M Trachtenberg, E Turner, V Woolfrey, A Lee, SJ Anasetti, C AF Pidala, Joseph Wang, Tao Haagenson, Michael D. Spellman, Stephen Askar, Medhat Battiwalla, Minoo Baxter-Lowe, Lee Ann Bitan, Menachem Fernandez-Vina, Marcelo Gandhi, Manish Jakubowski, Ann A. Maiers, Martin Marino, Susana R. Marsh, Steven G. E. Oudshoorn, Machteld Palmer, Jeanne Prasad, Vinod K. Reddy, Vijay Ringden, Olle Saber, Wael Santarone, Stella Schultz, Kirk R. Setterholm, Michelle Trachtenberg, Elizabeth Turner, Vicky Woolfrey, Ann Lee, Stephanie J. Anasetti, Claudio TI Amino Acid Substitution At Peptide-Binding Pockets of HLA Class I Molecules Adversely Impacts Hematopoietic Cell Transplantation Outcomes SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Wang, Tao] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Haagenson, Michael D.] CIBMTR Minneapolis, Minneapolis, MN USA. [Spellman, Stephen] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Askar, Medhat] Cleveland Clin, Allogen Labs, Cleveland, OH 44106 USA. [Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Baxter-Lowe, Lee Ann] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bitan, Menachem] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Fernandez-Vina, Marcelo] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Gandhi, Manish] Mayo Clin, Rochester, MN USA. [Jakubowski, Ann A.] Mem Sloan Kettering Canc Ctr, Dept Med Adult Allogene Bone Marrow Transplantat, New York, NY 10021 USA. [Maiers, Martin; Setterholm, Michelle] Natl Marrow Donor Program, Minneapolis, MN USA. [Marino, Susana R.] Univ Chicago, Chicago, IL 60637 USA. [Marsh, Steven G. E.] Anthony Nolan Res Inst, HLA Informat Grp, London, England. [Oudshoorn, Machteld] Europdonor Fdn, Leiden, Netherlands. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Prasad, Vinod K.] Duke Univ, Med Ctr, Durham, NC USA. [Reddy, Vijay] Florida Ctr Cellular Therapy, Orlando, FL USA. [Ringden, Olle] Karolinska Univ, Huddinge Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Saber, Wael] Med Coll Wisconsin CIBMTR, Milwaukee, WI USA. [Santarone, Stella] Spirito Santo Hosp, Hematol Bone Marrow Transplant Ctr, Pescara, Italy. [Schultz, Kirk R.] British Columbia Childrens Hosp, Div Pediat Hem Onc BMT, Vancouver, BC V6H 3V4, Canada. [Trachtenberg, Elizabeth] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Turner, Vicky] St Jude Childrens Res Hosp, HLA Lab, Memphis, TN 38105 USA. [Woolfrey, Ann] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 467 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901369 ER PT J AU Porter, JB Walter, PB Neumayr, LD Evans, P Weyhmiller, MG Harmatz, P Wood, JC Miller, JL Weiss, G Yuan, Q Wang, ZYJ Grosse, R Schoennagel, BP Meerpohl, J Fischer, R Vichinsky, E AF Porter, John B. Walter, Patrick B. Neumayr, Lynne D. Evans, Patricia Weyhmiller, Marcela G. Harmatz, Paul Wood, John C. Miller, Jeffery L. Weiss, Guenter Yuan, Qing Wang, Zhiyue J. Grosse, Regine Schoennagel, Bjoern P. Meerpohl, Joerg Fischer, Roland Vichinsky, Elliott TI Iron Trafficking and Distribution in Transfusional Overload: Insights From Comparing Diamond Blackfan Anemia with Sickle Cell Disease and Thalassemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Porter, John B.; Evans, Patricia] UCL, London, England. [Walter, Patrick B.; Neumayr, Lynne D.; Weyhmiller, Marcela G.; Harmatz, Paul; Vichinsky, Elliott] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Wood, John C.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Miller, Jeffery L.] NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD USA. [Weiss, Guenter] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Yuan, Qing; Wang, Zhiyue J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Grosse, Regine; Schoennagel, Bjoern P.; Fischer, Roland] Univ Hosp Hamburg Eppendorf, Hamburg, Germany. [Meerpohl, Joerg] Univ Med Ctr Freiburg, German Cochrane Ctr, Freiburg, Germany. RI Meerpohl, Joerg/J-4224-2013; Wang, Zhiyue/L-3851-2014 OI Meerpohl, Joerg/0000-0002-1333-5403; Wang, Zhiyue/0000-0002-5649-2900 NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 995 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600310 ER PT J AU Rao, VK Oliveira, JB Niemela, J Davis, J Price, S Kuehn, H Calvo, KR Pittaluga, S Werner, EJ Lee, J Barbour, M Natter, M Loh, ML Fleisher, TA AF Rao, V. Koneti Oliveira, Joao Bosco Niemela, Julie Davis, Joie Price, Susan Kuehn, Hyesun Calvo, Katherine R. Pittaluga, Stefania Werner, Eric J. Lee, Joohee Barbour, Mustafa Natter, Marc Loh, Mignon L. Fleisher, Thomas A. TI Clinical Spectrum of RAS-Associated Autoimmune Leukoproliferative Disorder (RALD): A Distinct Clinical Entity Mimicking Juvenile Myelomonocytioc Leukemia (JMML) or Chronic Myelomonocytic Leukemia (CMML) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Rao, V. Koneti; Davis, Joie; Price, Susan; Lee, Joohee] NIAID, ALPS Unit, LCID, NIH, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Werner, Eric J.] Childrens Hosp, Kings Daughters, Norfolk, VA USA. [Barbour, Mustafa] Sanford Childrens Hosp, Sioux Falls, SD USA. [Natter, Marc] Tufts Med Ctr, Floating Hosp Children, Boston, MA USA. [Loh, Mignon L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1033 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602038 ER PT J AU Rissone, A Jagadeesh, J Karen, S Bishop, K Blake, T Sood, RB Candotti, F AF Rissone, Alberto Jagadeesh, Jaya Karen, Simon Bishop, Kevin Blake, Trevor Sood, Raman B. Candotti, Fabio TI Adenylate Kinase 2 Regulates Zebrafish Primitive and Definitive Hematopoiesis SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Rissone, Alberto; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Bishop, Kevin; Blake, Trevor; Sood, Raman B.] NHGRI, Oncogenesis & Dev Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1208 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902358 ER PT J AU Roschewski, M Farooqui, M Aue, G Mo, CC Valdez, J Soto, S Perez-Galan, P Wilhelm, F Wiestner, A AF Roschewski, Mark Farooqui, Mohammed Aue, Georg Mo, Clifton C. Valdez, Janet Soto, Susan Perez-Galan, Patricia Wilhelm, Francois Wiestner, Adrian TI Phase I Study of On 01910.Na (rigosertib), a Multikinase PI3K Inhibitor in Relapsed/Refractory B-Cell Malignancies SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Roschewski, Mark] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Farooqui, Mohammed; Aue, Georg; Mo, Clifton C.; Valdez, Janet; Soto, Susan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Perez-Galan, Patricia] IDIAPS, Barcelona, Spain. [Wilhelm, Francois] Onconova Therapeut Inc, Newtown, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1803 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602074 ER PT J AU Roulland, S Sungalee, JS Morgado, E Mamessier, E Gregoire, E Monvoisin, C Menard, C Navarro, JM Eberle, FC Ruminy, P Jaffe, ES Schiff, C Hardwigsen, J Tarte, K Nadel, B AF Roulland, Sandrine Sungalee, Jocelyne Stephanie Morgado, Ester Mamessier, Emilie Gregoire, Emilie Monvoisin, Celine Menard, Cedric Navarro, Jean-Marc Eberle, Franziska C. Ruminy, Philippe Jaffe, Elaine S. Schiff, Claudine Hardwigsen, Jean Tarte, Karin Nadel, Bertrand TI Iterative Germinal Center Re-Entries of Memory B-Cells with t(14;18) Translocation and Early Steps of Follicular Lymphoma Progression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Roulland, Sandrine; Sungalee, Jocelyne Stephanie; Morgado, Ester; Mamessier, Emilie; Navarro, Jean-Marc; Schiff, Claudine; Nadel, Bertrand] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, INSERM, U1104, Marseille, France. [Gregoire, Emilie; Hardwigsen, Jean] Hop Conception, AP HM, Serv Chirurg Digest & Transplantat Hepat, Marseille, France. [Eberle, Franziska C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Jaffe, Elaine S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Tarte, Karin] Fac Med, INSERM, U917, Rennes, France. RI Nadel, Bertrand/J-2197-2014; Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 150 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900309 ER PT J AU Saba, N Shen, M Gias, M Farooqui, M Austin, C Farooqui, M Austin, C Schorno, K Weir, S Bhalla, K Wiestner, A AF Saba, Nakhle Shen, Min Gias, Mondana Farooqui, Mohammed Austin, Christopher Farooqui, Mohammed Austin, Christopher Schorno, Kevin Weir, Scott Bhalla, Kapil Wiestner, Adrian TI The Gold Compound Auranofin Induces Oxidative Stress and Apoptosis in Primary CLL Cells Independent of Classic Prognostic Markers and the Protective Effect of the Tissue Microenvironment SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Saba, Nakhle] Tulane Univ, Dept Hematol & Med Oncol, New Orleans, LA 70118 USA. [Shen, Min; Austin, Christopher] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Gias, Mondana; Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Schorno, Kevin; Weir, Scott; Bhalla, Kapil] Univ Kansas, Inst Adv Med Innovat, Kansas City, KS USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 865 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900393 ER PT J AU Salit, RB Hakim, FT Bishop, MR Friedman, TM Korngold, R Goldgirsh, K Memon, S Steinberg, SM Liewehr, D Peaceman, D Wilder, J Bryant, K Fowler, DH Gea-Banacloche, J Gress, RE Pavletic, SZ AF Salit, Rachel B. Hakim, Frances T. Bishop, Michael R. Friedman, Thea M. Korngold, Robert Goldgirsh, Kira Memon, Sarfraz Steinberg, Seth M. Liewehr, David Peaceman, Daniel Wilder, Jennifer Bryant, Kelly Fowler, Daniel H. Gea-Banacloche, Juan Gress, Ronald E. Pavletic, Steven Z. TI Influence of Graft Versus-Host Disease Prophylaxis Regimen On T-Cell Repertoire Diversity Following Reduced-Intensity HLA-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Salit, Rachel B.; Hakim, Frances T.; Memon, Sarfraz; Peaceman, Daniel; Bryant, Kelly; Fowler, Daniel H.; Gea-Banacloche, Juan; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Bishop, Michael R.] Med Coll Wisconsin, Ctr Clin Canc, Milwaukee, WI 53226 USA. [Friedman, Thea M.; Korngold, Robert; Goldgirsh, Kira] Hackensack Univ, Ctr Canc, Med Ctr, Hackensack, NJ USA. [Steinberg, Seth M.; Liewehr, David] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Wilder, Jennifer] SAIC, Clin Res Directorate, CMRP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3054 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601209 ER PT J AU Sanda, T Tyner, JW Gutierrez, A Ngo, VN Glover, JM Chang, BH Yost, AJ Weng, AP Ma, WX Tatarek, J Fleischman, AG Ahn, Y Yang, YD Zhou, WJ Neuberg, DS Moriggl, R Muller, M Kelliher, M Jamieson, C Gray, NS Staudt, LM Druker, BJ Look, T AF Sanda, Takaomi Tyner, Jeffrey W. Gutierrez, Alejandro Ngo, Vu N. Glover, Jason M. Chang, Bill H. Yost, Arla J. Weng, Andrew P. Ma, Wenxue Tatarek, Jessica Fleischman, Angela G. Ahn, Yebin Yang, Yandan Zhou, Wenjun Neuberg, Donna S. Moriggl, Richard Mueller, Mathias Kelliher, Michelle Jamieson, Catriona Gray, Nathanael S. Staudt, Louis M. Druker, Brian J. Look, Thomas TI TYK2-STAT1 Pathway Positively Regulates BCL2 Gene Expression in T-Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tyner, Jeffrey W.; Glover, Jason M.; Chang, Bill H.; Fleischman, Angela G.; Druker, Brian J.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Ngo, Vu N.] City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA USA. [Yost, Arla J.] BC Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. [Weng, Andrew P.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Ma, Wenxue] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Tatarek, Jessica] UMass Med Sch, Worcester, MA USA. [Zhou, Wenjun] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Moriggl, Richard] Ludwig Boltzmann Inst Canc Res, Vienna, Austria. [Mueller, Mathias] Univ Vet Med Vienna, Dept Biomed Sci, Vienna, Austria. [Kelliher, Michelle] Univ Massachusetts, Sch Med, Worcester, MA USA. [Staudt, Louis M.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RI Weng, Andrew/I-5015-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1470 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905163 ER PT J AU Sato, K Feng, XM Chen, JC Desierto, MJ Keyvanfar, K Malide, D Kajigaya, S Young, NS AF Sato, Kazuya Feng, Xingmin Chen, Jichun Desierto, Marie J. Keyvanfar, Keyvan Malide, Daniela Kajigaya, Sachiko Young, Neal S. TI Adipocytes and Aplastic Anemia: Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Antagonists Attenuate Bone Marrow Failure in an Aplastic Anemia Mouse Model but Not in Radiation Marrow Destruction SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Desierto, Marie J.; Keyvanfar, Keyvan; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Malide, Daniela] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3483 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604044 ER PT J AU Scheinberg, P Townsley, DM Dumitriu, B Rios, O Weinstein, B Battiwalla, M Childs, R Dunbar, CE Barrett, AJ Wu, CO Young, NS AF Scheinberg, Phillip Townsley, Danielle M. Dumitriu, Bogdan Rios, Olga Weinstein, Barbara Battiwalla, Minoo Childs, Richard Dunbar, Cynthia E. Barrett, A. John Wu, Colin O. Young, Neal S. TI Even "Moderate" Dose Cyclophosphamide for Severe Aplastic Anemia Is Associated with Significant Toxicities and Does Not Prevent Relapse and Clonal Evolution SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Scheinberg, Phillip; Townsley, Danielle M.; Dumitriu, Bogdan; Rios, Olga; Weinstein, Barbara; Battiwalla, Minoo; Childs, Richard; Dunbar, Cynthia E.; Barrett, A. John; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Reserach, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1259 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902307 ER PT J AU Shaffer, BC Tremblay, C Peaceman, D Hsu, J Steinberg, SM Uribe, M Adams, S Flegel, WA Pavletic, SZ AF Shaffer, Brian C. Tremblay, Christine Peaceman, Daniel Hsu, Jennifer Steinberg, Seth M. Uribe, Marcela Adams, Sharon Flegel, Willy A. Pavletic, Steven Z. TI Minor Histocompatibility Antigen Mismatch and Incidence of Graft Versus Host Disease, Event-Free, and Overall Survival in Patients Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shaffer, Brian C.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Tremblay, Christine; Uribe, Marcela; Adams, Sharon; Flegel, Willy A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4201 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604129 ER PT J AU Shaffer, BC Leitner, J Wiestner, A Bishop, MR Pavletic, SZ Gress, RE Steinberger, P Baskar, S Rader, C AF Shaffer, Brian C. Leitner, Judith Wiestner, Adrian Bishop, Michael R. Pavletic, Steven Z. Gress, Ronald E. Steinberger, Peter Baskar, Sivasubramanian Rader, Christoph TI Generation of a Platform for Identification of CLL Specific Cell Surface Proteins Targeted by Anti-Tumor Antibodies in Patient Sera After Allogeneic Hematopoietic Cell Transplantion SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shaffer, Brian C.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Leitner, Judith; Steinberger, Peter] Med Univ Vienna, Inst Immunol, Vienna, Austria. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bishop, Michael R.] Med Coll Wisconsin, Ctr Clin Canc, Milwaukee, WI 53226 USA. [Pavletic, Steven Z.; Gress, Ronald E.; Baskar, Sivasubramanian] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA. [Rader, Christoph] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1349 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603142 ER PT J AU Shah, NN Borowitz, MJ Robey, N Gamper, C Symons, HJ Loeb, D Wayne, AS Chen, AR AF Shah, Nirali N. Borowitz, Michael J. Robey, Nancy Gamper, Christopher Symons, Heather J. Loeb, David Wayne, Alan S. Chen, Allen R. TI Outcomes of Children with Hematologic Malignancies Who Relapse After Allogeneic Hematopoietic Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shah, Nirali N.; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Borowitz, Michael J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4205 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604125 ER PT J AU Shah, NN Borowitz, MJ Steinberg, SM Lefell, M Robey, N Gamper, C Symons, HJ Loeb, D Wayne, AS Chen, AR AF Shah, Nirali N. Borowitz, Michael J. Steinberg, Seth M. Lefell, Mary Robey, Nancy Gamper, Christopher Symons, Heather J. Loeb, David Wayne, Alan S. Chen, Allen R. TI Factors Predictive of Relapse of Hematologic Malignancies in Pediatric Patients Post Allogeneic Hematopoietic Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shah, Nirali N.; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Borowitz, Michael J.; Robey, Nancy; Gamper, Christopher; Symons, Heather J.; Loeb, David; Chen, Allen R.] Johns Hopkins Univ, Baltimore, MD USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Lefell, Mary] Johns Hopkins Univ Hosp, DOM Immunogenet, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4206 PG 3 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604124 ER PT J AU Shah, NN Merchant, M Cole, D Richards, K Delbrook, C Widemann, BC Wayne, AS AF Shah, Nirali N. Merchant, Melinda Cole, Diane Richards, Kelly Delbrook, Cindy Widemann, Brigitte C. Wayne, Alan S. TI Vincristine Sulfate Liposomes Injection (VSLI, Marqibo): Interim Results From a Phase I Study in Children and Adolescents with Refractory Cancer SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Shah, Nirali N.; Merchant, Melinda; Cole, Diane; Richards, Kelly; Delbrook, Cindy; Widemann, Brigitte C.; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1497 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838905136 ER PT J AU Shand, JC Kanu, A Fry, TJ AF Shand, Jessica C. Kanu, Alieu Fry, Terry J. TI CD8 Suppressor Cells Can Be Induced by Pre-B Acute Lymphoblastic Leukemia As a Potential Mechanism of Immune Escape SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kanu, Alieu] George Washington Univ, Sch Publ Hlth, Washington, DC USA. [Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4797 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604291 ER PT J AU Shand, JC Capitini, CM Qin, HY Nasholm, N Fry, TJ AF Shand, Jessica C. Capitini, Christian M. Qin, Haiying Nasholm, Nicole Fry, Terry J. TI Tissue Distribution of a Minor Antigen, but Not PD-1 Expression, Predicts the Antileukemia Efficacy of Adoptively Transferred, Antigen-Specific T-Cells in a Preclinical Model of Allogeneic Transplant SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Capitini, Christian M.; Qin, Haiying; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 456 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902204 ER PT J AU Shand, JC Capitini, CM Qin, HY Nasholm, N Fry, TJ AF Shand, Jessica C. Capitini, Christian M. Qin, Haiying Nasholm, Nicole Fry, Terry J. TI Tissue Distribution of a Minor Antigen, but Not PD-1 Expression, Predicts the Antileukemia Efficacy of Adoptively Transferred, Antigen-Specific T-Cells in a Preclinical Model of Allogeneic Transplant SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Capitini, Christian M.; Qin, Haiying; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 456 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902004 ER PT J AU Sivina, M Kreitman, RJ Arons, E Buggy, JJ Ravandi, F Burger, JA AF Sivina, Mariela Kreitman, Robert J. Arons, Evgeny Buggy, Joseph J. Ravandi, Farhad Burger, Jan A. TI Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Blocks Hairy Cell Leukemia (HCL) Survival, Proliferation, and BCR Signaling: A New Therapeutic Approach for HCL SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Sivina, Mariela; Ravandi, Farhad; Burger, Jan A.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kreitman, Robert J.; Arons, Evgeny] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Buggy, Joseph J.] Pharmacyclics Inc, Sunnyvale, CA USA. RI Jones, Jeffrey/E-9827-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 1802 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049602075 ER PT J AU Smith, MA Carol, H Evans, K Richmond, J Kang, M Reynolds, CP Chunduru, S Graham, MA Geier, B Kurmasheva, R Houghton, PJ Lock, RB AF Smith, Malcolm A. Carol, Hernan Evans, Kathryn Richmond, Jennifer Kang, Min Reynolds, C. Patrick Chunduru, Srinivas Graham, Martin A. Geier, Brian Kurmasheva, Raushan Houghton, Peter J. Lock, Richard B. TI Birinapant (TL32711), a Small Molecule Smac Mimetic, Induces Regressions in Childhood Acute Lymphoblastic Leukemia (ALL) Xenografts That Express TNF alpha and Synergizes with TNF alpha in Vitro - A Report From the Pediatric Preclinical Testing Program (PPTP) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Smith, Malcolm A.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Carol, Hernan; Evans, Kathryn; Richmond, Jennifer; Lock, Richard B.] Univ New S Wales, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia. [Kang, Min; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79409 USA. [Chunduru, Srinivas; Graham, Martin A.] TetraLogic Pharmaceut, Malvern, PA USA. [Geier, Brian; Kurmasheva, Raushan; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. RI Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013 OI Carol, Hernan/0000-0002-9443-8032; NR 0 TC 0 Z9 0 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3565 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906092 ER PT J AU Spyridonidis, A Muranski, P Kerkar, S Tanimoto, K Hensel, NF Melenhorst, JJ Barrett, AJ AF Spyridonidis, Alexandros Muranski, Pawel Kerkar, Sid Tanimoto, Kazushi Hensel, Nancy F. Melenhorst, J. Joseph Barrett, A. John TI Improved Strategy for Rapid Generation of Quadrivirus-Specific CD8+and CD4+Cytotoxic T Lymphocytes (CTLs) for Adoptive Transfer After Stem Cell Transplantation (SCT) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Kerkar, Sid; Tanimoto, Kazushi; Hensel, Nancy F.; Melenhorst, J. Joseph; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4121 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604207 ER PT J AU St Louis, J Kruse-Jarres, R Greist, A Shapiro, AD Smith, H Drebes, AB Lozier, JN Gomperts, ED AF St Louis, Jean Kruse-Jarres, Rebecca Greist, Anne Shapiro, Amy D. Smith, Hedy Drebes, Anja B. Lozier, Jay N. Gomperts, Edward D. TI Recombinant B-Domain Deleted Porcine Factor VIII (OBI-1) Safety and Efficacy in the Treatment of Acquired Hemophilia A: Interim Results SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [St Louis, Jean] Hop Maison Neuve Rosemont, Dept Hematol, Montreal, PQ H1T 2M4, Canada. [Kruse-Jarres, Rebecca] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Greist, Anne; Shapiro, Amy D.] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA. [Smith, Hedy] Tufts Med Ctr, Dept Hematol Oncol, Boston, MA USA. [Drebes, Anja B.] Royal Free NHS Trust, Thrombosis Unit, London, England. [Drebes, Anja B.] Royal Free NHS Trust, Katharine Dormandy Haemophilia Ctr, London, England. [Lozier, Jay N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2224 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600018 ER PT J AU Staudt, LM AF Staudt, Louis M. TI Chronic Active B-Cell Receptor Signaling in Lymphoma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 26 PG 1 WC Hematology SC Hematology GA 074UG UT WOS:000313838900002 ER PT J AU Suryani, S Sia, KCS Bracken, L Carol, H Evans, K Kurmasheva, R Houghton, PJ Smith, MA Lock, RB AF Suryani, Santi Sia, Keith C. S. Bracken, Lauryn Carol, Hernan Evans, Kathryn Kurmasheva, Raushan Houghton, Peter J. Smith, Malcolm A. Lock, Richard B. TI Dual Inhibition of JAK/STAT and MAPK Pathways Results in Synergistic Cell Killing of JAK-Mutated Pediatric Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Suryani, Santi; Sia, Keith C. S.; Bracken, Lauryn; Carol, Hernan; Evans, Kathryn; Lock, Richard B.] Univ New S Wales, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia. [Kurmasheva, Raushan; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. [Smith, Malcolm A.] NCI, Ctep, Cib, NIH, Bethesda, MD 20892 USA. RI Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013 OI Carol, Hernan/0000-0002-9443-8032; NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3562 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838906095 ER PT J AU Tanimoto, K Muranski, P Hensel, NF Keyvanfar, K Fujiwara, H Barrett, AJ Melenhorst, JJ AF Tanimoto, Kazushi Muranski, Pawel Hensel, Nancy F. Keyvanfar, Keyvan Fujiwara, Hiroshi Barrett, A. John Melenhorst, J. Joseph TI Abrogation of Myeloid Derived Suppressor Cell-Like Inhibitory Activity of K562 Restores Antigen Presenting Cell Functions SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tanimoto, Kazushi; Muranski, Pawel; Hensel, Nancy F.; Keyvanfar, Keyvan; Barrett, A. John; Melenhorst, J. Joseph] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Fujiwara, Hiroshi] Ehime Univ, Grad Sch Med, Toon, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4118 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604210 ER PT J AU Tembhare, PR Yuan, C Korde, N Manasanch, EE Kwok, M Roschewski, M Maric, I Calvo, KR Mulquin, M Zuchlinski, D Landgren, O Stetler-Stevenson, M AF Tembhare, Prashant Ramesh Yuan, Constance Korde, Neha Manasanch, Elisabet E. Kwok, Mary Roschewski, Mark Maric, Irina Calvo, Katherine R. Mulquin, Marcia Zuchlinski, Diamond Landgren, Ola Stetler-Stevenson, Maryalice TI Peripheral Blood Involvement with Minimal Disease Is Common in Multiple Myeloma but Not in Smoldering Myeloma SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Tembhare, Prashant Ramesh; Yuan, Constance; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Korde, Neha; Kwok, Mary; Mulquin, Marcia; Zuchlinski, Diamond] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Manasanch, Elisabet E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Roschewski, Mark; Landgren, Ola] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Maric, Irina; Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4994 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049605042 ER PT J AU Townsley, DM Hsu, A Dumitriu, B Holland, SM Young, NS AF Townsley, Danielle M. Hsu, Amy Dumitriu, Bogdan Holland, Steven M. Young, Neal S. TI Regulatory Mutations in GATA2 Associated with Aplastic Anemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Townsley, Danielle M.; Dumitriu, Bogdan; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hsu, Amy] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3488 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604039 ER PT J AU Townsley, DM Dumitriu, B Kajigaya, S Calado, RT Scheinberg, P Young, NS AF Townsley, Danielle M. Dumitriu, Bogdan Kajigaya, Sachiko Calado, Rodrigo T. Scheinberg, Phillip Young, Neal S. TI Clinical and Genetic Heterogeneity of Telomere Diseases SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Townsley, Danielle M.; Dumitriu, Bogdan; Kajigaya, Sachiko; Scheinberg, Phillip; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.] Univ Sao Paulo, Dept Internal Med, BR-14049 Ribeirao Preto, Brazil. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2373 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601088 ER PT J AU Ueda, K Yoshimi, A Nakagawa, M Nishikawa, S Marquez, VE Kumano, K Kurokawa, M AF Ueda, Koki Yoshimi, Akihide Nakagawa, Masahiro Nishikawa, Satoshi Marquez, Victor E. Kumano, Keiki Kurokawa, Mineo TI Inhibition of EZH2 Depletes MLL Fusion Leukemia Stem Cells Through Restoration of p16 Expression SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Ueda, Koki; Nakagawa, Masahiro; Nishikawa, Satoshi; Kumano, Keiki] Univ Tokyo, Tokyo, Japan. [Yoshimi, Akihide; Kurokawa, Mineo] Tokyo Univ Hosp, Dept Cell Therapy & Transplantat, Tokyo 113, Japan. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3510 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604017 ER PT J AU Uldrick, TS Polizzotto, MN Filie, A Aleman, K Wyvill, KM Little, RF Steinberg, SM Jaffe, ES Whitby, D Pittaluga, S Yarchoan, R AF Uldrick, Thomas S. Polizzotto, Mark N. Filie, Armando Aleman, Karen Wyvill, Kathleen M. Little, Richard F. Steinberg, Seth M. Jaffe, Elaine S. Whitby, Denise Pittaluga, Stefania Yarchoan, Robert TI Clinical, Immunologic, and Virologic Findings in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Lymphomas Suggest KSHV-Associated Inflammatory Syndromes Contribute to Symptoms and Disease Pathogenesis. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Uldrick, Thomas S.; Polizzotto, Mark N.; Aleman, Karen; Wyvill, Kathleen M.; Little, Richard F.; Yarchoan, Robert] NCI, HIV AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Filie, Armando; Jaffe, Elaine S.; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2708 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838903085 ER PT J AU van Beers, EJ Samsel, L Mendelsohn, LG Saiyed, R Nichols, JS McCoy, JP Kato, GJ AF van Beers, Eduard J. Samsel, Leigh Mendelsohn, Laurel G. Saiyed, Rehan Nichols, James S. McCoy, J. Philip, Jr. Kato, Gregory J. TI Imaging Flow Cytometry for Fully Automated Quantification of Percentage of Sickled Cells in Sickle Cell Anemia. SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [van Beers, Eduard J.; Mendelsohn, Laurel G.; Saiyed, Rehan; Nichols, James S.; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA. [Samsel, Leigh] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip, Jr.] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014; van Beers, Eduard/I-3561-2012 OI Kato, Gregory/0000-0003-4465-3217; van Beers, Eduard/0000-0002-3934-7189 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2105 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603190 ER PT J AU van Beers, EJ Yang, YQ Yuditskaya, S Raghavachari, N Kato, GJ AF van Beers, Eduard J. Yang, Yanqin Yuditskaya, Susan Raghavachari, Nalini Kato, Gregory J. TI Turnover of Heme-Bound Iron Is Associated with Activation of TLR4 and Chemokine Receptor Pathways in the Peripheral Blood Mononuclear Cell Transcriptome in Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [van Beers, Eduard J.] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands. [Yang, Yanqin] NHLBI, Genom Core Facil, Bethesda, MD 20892 USA. [Yuditskaya, Susan; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 819 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901045 ER PT J AU Wang, DP Yu, Y Semple, KM Haarberg, KMK Fu, JN Kaosaard, K Anasetti, C Srinivas, N Gabrilovich, D Yu, XZ AF Wang, Dapeng Yu, Yu Semple, Kenrick M. Haarberg, Kelley M. K. Fu, Jianing Kaosaard, Kane Anasetti, Claudio Srinivas, Nagaraj Gabrilovich, Dmitry Yu, Xue-Zhong TI Dynamic Changes and Impact of Myeloid Derived Suppressor Cells in Allogeneic Bone Marrow Transplantation in Mice SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Semple, Kenrick M.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Haarberg, Kelley M. K.; Anasetti, Claudio; Yu, Xue-Zhong] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA. [Haarberg, Kelley M. K.; Anasetti, Claudio; Yu, Xue-Zhong] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Fu, Jianing] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RI Fu, Jianing/F-4031-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2999 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049600190 ER PT J AU Wang, WX Corrigan-Cummins, M Vinh, DC Hsu, AP Hickstein, DD Holland, SM Calvo, KR AF Wang, Weixin Corrigan-Cummins, Meghan Vinh, Donald C. Hsu, Amy P. Hickstein, Dennis D. Holland, Steven M. Calvo, Katherine R. TI MCL-1 and Mir-181c in GATA2 Mutation Associated Monomac and Familial Myelodysplastic Syndrome SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wang, Weixin; Corrigan-Cummins, Meghan; Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Vinh, Donald C.] McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ, Canada. [Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 3807 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049601258 ER PT J AU Weed, J Keyvanfar, K Swamy, P Kajigaya, S Calado, RT Young, NS AF Weed, Jason Keyvanfar, Keyvan Swamy, Prashanth Kajigaya, Sachiko Calado, Rodrigo T. Young, Neal S. TI Interphase Chromosome Flow-FISH SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Keyvanfar, Keyvan; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Calado, Rodrigo T.] Univ Sao Paulo, Dept Internal Med, BR-14049 Ribeirao Preto, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4925 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604319 ER PT J AU Weitzel, RP Biancotto, A Fitzhugh, CD McCoy, JP Hsieh, M Tisdale, JF AF Weitzel, R. Patrick Biancotto, Angelique Fitzhugh, Courtney D. McCoy, J. Philip Hsieh, Matthew Tisdale, John F. TI Characterization of Early Lymphocytes Emerging After Nonmyeloablative Conditioning and Hematopoietic Stem Cell Transplant Supported with Sirolimus SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Weitzel, R. Patrick; Fitzhugh, Courtney D.; Hsieh, Matthew; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Biancotto, Angelique; McCoy, J. Philip] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4150 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049604178 ER PT J AU West, RR Hsu, A Calvo, KR Cuellar-Rodriguez, J Holland, SM Hickstein, DD AF West, Robert R. Hsu, Amy Calvo, Katherine R. Cuellar-Rodriguez, Jennifer Holland, Steven M. Hickstein, Dennis D. TI ASXL1 mutations in GATA2-Deficiency Correlate with Leukemic Transformation SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [West, Robert R.] NIH, ETIB, Bethesda, MD 20892 USA. [Hsu, Amy] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Calvo, Katherine R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Cuellar-Rodriguez, Jennifer; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 405 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838902255 ER PT J AU Wu, CF Hong, SG Jares, A Guo, V Winkler, T Dunbar, CE AF Wu, Chuanfeng Hong, So Gun Jares, Alexander Guo, Vicky Winkler, Thomas Dunbar, Cynthia E. TI Development of an Inducible Caspase-9 Safety Switch for Pluripotent Stem Cell Based Therapies SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Wu, Chuanfeng; Hong, So Gun; Jares, Alexander; Guo, Vicky; Winkler, Thomas; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 2047 PG 2 WC Hematology SC Hematology GA 077SZ UT WOS:000314049603248 ER PT J AU Xu, BY Zhi, N Hu, GQ Wan, ZH Kajigaya, S Zhao, KJ Mao, Q Young, NS AF Xu, Baoyan Zhi, Ning Hu, Gangqing Wan, Zhihong Kajigaya, Sachiko Zhao, Keji Mao, Qing Young, Neal S. TI Identification and Characterization of a Novel Parvovirus-Like Virus in Seronegative Hepatitis Patients by Next Generation Sequencing SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Hu, Gangqing] NIH, Syst Biol Ctr, Bethesda, MD 20892 USA. [Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Mao, Qing] Third Mil Med Univ, Inst Infect Dis, Chongqing, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 273 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901137 ER PT J AU Yang, JJ Xu, H Yang, WJ Perez-Andreu, V Dmidas, M Fan, YP Cheng, C Pei, DQ Scheet, P Burchard, EG Eng, C Huntsman, S Torgerson, DG Dean, M Winick, N Martin, PL Camitta, B Bowman, WP Willman, CL Carroll, WL Mullighan, CG Bhojwani, D Hunger, SP Pui, CH Evans, WE Belling, MV Loh, ML AF Yang, Jun J. Xu, Heng Yang, Wenjian Perez-Andreu, Virginia Dmidas, Meenakshi Fan, Yiping Cheng, Cheng Pei, Deqing Scheet, Paul Burchard, Esteban Gonzalez Eng, Celeste Huntsman, Scott Torgerson, Dara G. Dean, Michael Winick, Naomi Martin, Paul L. Camitta, Bruce Bowman, W. Paul Willman, Cheryl L. Carroll, William L. Mullighan, Charles G. Bhojwani, Deepa Hunger, Stephen P. Pui, Ching-Hon Evans, William E. Belling, Mary V. Loh, Mignon L. TI Genome-Wide Association Study Identifies a Novel Susceptibility Locus At 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethinically Diverse Populations SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yang, Jun J.; Xu, Heng; Yang, Wenjian; Perez-Andreu, Virginia; Evans, William E.; Belling, Mary V.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Dmidas, Meenakshi] Univ Florida, Dept Epidemiol & Hlth Policy Res Med, Gainesville, FL USA. [Fan, Yiping] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Cheng, Cheng; Pei, Deqing] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Burchard, Esteban Gonzalez; Eng, Celeste; Huntsman, Scott; Torgerson, Dara G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci & Med, San Francisco, CA 94143 USA. [Dean, Michael] NCI, Expt Immunol Lab, Bethesda, MD 20892 USA. [Winick, Naomi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Martin, Paul L.] Duke Univ, Durham, NC USA. [Camitta, Bruce] Med Coll Wisconsin, Wauwatosa, WI USA. [Bowman, W. Paul] Cook Childrens Med Ctr, Ft Worth, TX USA. [Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. [Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. [Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 877 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900381 ER PT J AU Yu, WM Liu, X Shen, JH Jovanovic, O Pohl, EE Gerson, SL Finkel, T Broxmeyer, HE Qu, CK AF Yu, Wen-Mei Liu, Xia Shen, Jinhua Jovanovic, Olga Pohl, Elena E. Gerson, Stanton L. Finkel, Toren Broxmeyer, Hal E. Qu, Cheng-Kui TI Disruption of Mitochondrial Phosphatase Ptpmt1 Induces Bioenergetic Stress and Differentiation Block in Hematopoietic Stem Cells SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Yu, Wen-Mei; Liu, Xia; Shen, Jinhua; Gerson, Stanton L.; Qu, Cheng-Kui] Case Western Reserve Univ, Dept Med, Ctr Stem Cell & Regenerat Med, Div Hematol & Oncol,Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Jovanovic, Olga; Pohl, Elena E.] Univ Vet Med, Dept Mol Physiol & Biophys, Vienna, Austria. [Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Broxmeyer, Hal E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 857 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838901007 ER PT J AU Zeidner, JF Gerber, JM Blackford, A Litzow, M Foster, MC Morris, LE Gojo, I Lancet, JE Bose, P Tibes, R Strickland, SA Greer, JM Drye, M Meads, K Doyle, A Little, RF Wright, JJ Karp, JE AF Zeidner, Joshua F. Gerber, Jonathan M. Blackford, Amanda Litzow, Mark Foster, Matthew C. Morris, Lawrence E., Jr. Gojo, Ivana Lancet, Jeffrey E. Bose, Prithviraj Tibes, Raoul Strickland, Stephen A. Greer, Jacqueline M. Drye, Michelle Meads, Kevin Doyle, Austin Little, Richard F. Wright, John J. Karp, Judith E. TI Randomized Phase II Trial of Timed-Sequential Therapy (TST) with Flavopiridol (Alvocidib), Ara-C and Mitoxantrone (FLAM) Versus "7+3" for Adults Ages 70 Years and Under with Newly Diagnosed Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Zeidner, Joshua F.; Greer, Jacqueline M.; Drye, Michelle; Meads, Kevin; Karp, Judith E.] Johns Hopkins Univ Hosp, Sidney Kimnrl Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Gerber, Jonathan M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA. [Blackford, Amanda] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Div Biostat, Dept Oncol, Baltimore, MD USA. [Litzow, Mark] Mayo Clin, Rochester, MN USA. [Foster, Matthew C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Morris, Lawrence E., Jr.] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Gojo, Ivana] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Lancet, Jeffrey E.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Bose, Prithviraj] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Tibes, Raoul] Mayo Clin Arizona, Scottsdale, AZ USA. [Strickland, Stephen A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Doyle, Austin; Little, Richard F.; Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 47 PG 2 WC Hematology SC Hematology GA 074UG UT WOS:000313838900117 ER PT J AU Zhao, XH Lwin, T Zhang, XW Huang, A Wang, J Marquez, VE Chen-Kiang, S Bradner, JE Dalton, WS Sotomayor, EM Tao, JG AF Zhao, Xiaohong Lwin, Tint Zhang, Xinwei Huang, Andy Wang, Jian Marquez, Victor E. Chen-Kiang, Selina Bradner, James E. Dalton, William S. Sotomayor, Eduardo M. Tao, Jianguo TI Silencing c-Myc Using Myc Inhibitor JQ1 and EZH2 Inhibitor DZNep Blocks Converging Survival Signals in Aggressive B-Cell Lymphomas SO BLOOD LA English DT Meeting Abstract CT 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) CY DEC 08-11, 2012 CL Atlanta, GA SP Amer Soc Hematol (ASH) C1 [Zhao, Xiaohong] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Tao, Jianguo] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA. [Zhang, Xinwei] Tianjin Med Univ, Canc Inst & Hosp, Dept Biotherapy, Tianjin, Peoples R China. [Huang, Andy; Wang, Jian] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Marquez, Victor E.] NCI, Frederick, MD 21701 USA. [Chen-Kiang, Selina] Weill Cornell Med Coll, New York, NY USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dalton, William S.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL USA. [Dalton, William S.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Expt Therapeut Program, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2012 VL 120 IS 21 MA 4618 PG 1 WC Hematology SC Hematology GA 077SZ UT WOS:000314049606049 ER PT J AU Raran-Kurussi, S Waugh, DS AF Raran-Kurussi, Sreejith Waugh, David S. TI The Ability to Enhance the Solubility of Its Fusion Partners Is an Intrinsic Property of Maltose-Binding Protein but Their Folding Is Either Spontaneous or Chaperone-Mediated SO PLOS ONE LA English DT Article ID ESCHERICHIA-COLI STRAIN; ETCH VIRUS PROTEASE; HPV E6 ONCOPROTEIN; IN-VIVO; DIHYDROFOLATE-REDUCTASE; RECOMBINANT PROTEINS; MOLECULAR CHAPERONE; DISULFIDE BONDS; HIGH-AFFINITY; PURIFICATION AB Escherichia coli maltose binding protein (MBP) is commonly used to promote the solubility of its fusion partners. To investigate the mechanism of solubility enhancement by MBP, we compared the properties of MBP fusion proteins refolded in vitro with those of the corresponding fusion proteins purified under native conditions. We fused five aggregation-prone passenger proteins to 3 different N-terminal tags: His(6)-MBP, His(6)-GST and His(6). After purifying the 15 fusion proteins under denaturing conditions and refolding them by rapid dilution, we recovered far more of the soluble MBP fusion proteins than their GST- or His-tagged counterparts. Hence, we can reproduce the solubilizing activity of MBP in a simple in vitro system, indicating that no additional factors are required to mediate this effect. We assayed both the soluble fusion proteins and their TEV protease digestion products (i.e., with the N-terminal tag removed) for biological activity. Little or no activity was detected for some fusion proteins whereas others were quite active. When the MBP fusions proteins were purified from E. coli under native conditions they were all substantially active. These results indicate that the ability of MBP to promote the solubility of its fusion partners in vitro sometimes, but not always, results in their proper folding. We show that the folding of some passenger proteins is mediated by endogenous chaperones in vivo. Hence, MBP serves as a passive participant in the folding process; passenger proteins either fold spontaneously or with the assistance of chaperones. C1 [Raran-Kurussi, Sreejith; Waugh, David S.] Frederick Natl Lab Canc Res, Ctr Canc Res, Prot Engn Sect, Macromol Crystallog Lab, Frederick, MD USA. RP Waugh, DS (reprint author), Frederick Natl Lab Canc Res, Ctr Canc Res, Prot Engn Sect, Macromol Crystallog Lab, Frederick, MD USA. EM waughd@mail.nih.gov FU Center for Cancer Research, National Cancer Institute; Frederick National Laboratory for Cancer Research; National Institutes of Health FX This work was funded by the intramural research program of the Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 27 Z9 28 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 16 PY 2012 VL 7 IS 11 AR e49589 DI 10.1371/journal.pone.0049589 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048BN UT WOS:000311885300055 PM 23166722 ER PT J AU Yu, SY Zhou, XY Steinke, FC Liu, CY Chen, SC Zagorodna, O Jing, XF Yokota, Y Meyerholz, DK Mullighan, CG Knudson, CM Zhao, DM Xue, HH AF Yu, Shuyang Zhou, Xinyuan Steinke, Farrah C. Liu, Chengyu Chen, Shann-Ching Zagorodna, Oksana Jing, Xuefang Yokota, Yoshifumi Meyerholz, David K. Mullighan, Charles G. Knudson, C. Michael Zhao, Dong-Mei Xue, Hai-Hui TI The TCF-1 and LEF-1 Transcription Factors Have Cooperative and Opposing Roles in T Cell Development and Malignancy SO IMMUNITY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; WNT SIGNALING PATHWAY; MOLECULAR PATHOGENESIS; NOTCH1 MUTATIONS; CANCER; DIFFERENTIATION; TRANSFORMATION; EXPRESSION; SURVIVAL; SPECIFICATION AB The TCF-1 and LEF-1 transcription factors are known to play critical roles in normal thymocyte development. Unexpectedly, we found that TCF-1-deficient (Tcf7(-/-)) mice developed aggressive T cell malignancy, resembling human T cell acute lymphoblastic leukemia (T-ALL). LEF-1 was aberrantly up-regulated in premalignant Tcf7(-/-) early thymocytes and lymphoma cells. We further demonstrated that TCF-1 directly repressed LEF-1 expression in early thymocytes and that conditional inactivation of Lef1 greatly delayed or prevented T cell malignancy in Tcf7(-/-) mice. In human T-ALLs, an early thymic progenitor (ETP) subtype was associated with diminished TCF7 expression, and two of the ETP-ALL cases harbored TCF7 gene deletions. We also showed that TCF-1 and LEF-1 were dispensable for T cell lineage commitment but instead were required for early thymocytes to mature beyond the CD4(-)CD8(-) stage. TCF-1 thus has dual roles, i.e., acting cooperatively with LEF-1 to promote thymocyte maturation while restraining LEF-1 expression to prevent malignant transformation of developing thymocytes. C1 [Yu, Shuyang; Zhou, Xinyuan; Steinke, Farrah C.; Jing, Xuefang; Zhao, Dong-Mei; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA. [Zagorodna, Oksana; Meyerholz, David K.; Knudson, C. Michael] Univ Iowa, Dept Pathol, Carver Coll Med, Iowa City, IA 52242 USA. [Zhao, Dong-Mei] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Xue, Hai-Hui] Univ Iowa, Interdisciplinary Immunol Grad Program, Carver Coll Med, Iowa City, IA 52242 USA. [Liu, Chengyu] NHLBI, Transgen Core Facil, NIH, Bethesda, MD 20892 USA. [Chen, Shann-Ching; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Yokota, Yoshifumi] Univ Fukui, Sch Med, Dept Biochem & Bioinformat Sci, Div Mol Genet, Fukui 9101193, Japan. RP Zhao, DM (reprint author), Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA. EM dong-mei-zhao@uiowa.edu; hai-hui-xue@uiowa.edu OI Mullighan, Charles/0000-0002-1871-1850 FU American Cancer Society [RSG-11-161-01-MPC]; NIH [HL095540, AI080966] FX We thank H. Clevers for permission to use the Tcf7-/- mice, D.L. Court and N.G. Copland (NCI) for providing all the recombineering reagents, F. McCormick (UCSF) for WT and mutant beta-catenin constructs, W.S. Pear (UPenn) for the ICN and DN-MAML constructs, D.G. Tenen (Harvard) for the self-inactivating retroviral reporter construct, and J.C. Zuniga-Pflucker (Sunnybrook Research Institute, Canada) for the OP9-DL1 cells. We thank J. Harty and A. Dupuy for critical reading of the manuscript, G. Hauser and T. Bair (DNA Facility) for performing microarray analysis and assistance with the data analysis, H. Vignes and G. Rasmussen (Flow Cytometry Facility) for cell sorting, and S. Martin for cell cycle analysis. This study is supported by grants from the American Cancer Society (RSG-11-161-01-MPC to H.-H.X.) and the NIH (HL095540 and AI080966 to H.-H.X.). NR 44 TC 54 Z9 55 U1 3 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 16 PY 2012 VL 37 IS 5 BP 813 EP 826 DI 10.1016/j.immuni.2012.08.009 PG 14 WC Immunology SC Immunology GA 042GP UT WOS:000311460000009 PM 23103132 ER PT J AU Jones, JL Esber, GR McDannald, MA Gruber, AJ Hernandez, A Mirenzi, A Schoenbaum, G AF Jones, Joshua L. Esber, Guillem R. McDannald, Michael A. Gruber, Aaron J. Hernandez, Alex Mirenzi, Aaron Schoenbaum, Geoffrey TI Orbitofrontal Cortex Supports Behavior and Learning Using Inferred But Not Cached Values SO SCIENCE LA English DT Article ID VENTROMEDIAL PREFRONTAL CORTEX; VENTRAL STRIATUM; REWARD VALUE; LESIONS; AMYGDALA; NEURONS; HUMANS; INACTIVATION; ASSOCIATIONS; DEVALUATION AB Computational and learning theory models propose that behavioral control reflects value that is both cached (computed and stored during previous experience) and inferred (estimated on the fly on the basis of knowledge of the causal structure of the environment). The latter is thought to depend on the orbitofrontal cortex. Yet some accounts propose that the orbitofrontal cortex contributes to behavior by signaling "economic" value, regardless of the associative basis of the information. We found that the orbitofrontal cortex is critical for both value-based behavior and learning when value must be inferred but not when a cached value is sufficient. The orbitofrontal cortex is thus fundamental for accessing model-based representations of the environment to compute value rather than for signaling value per se. C1 [Jones, Joshua L.; Hernandez, Alex; Schoenbaum, Geoffrey] Univ Maryland, Dept Anat & Neurobiol, Sch Med, Baltimore, MD 21201 USA. [Esber, Guillem R.; McDannald, Michael A.; Mirenzi, Aaron; Schoenbaum, Geoffrey] NIDA, Behav Neurophysiol Res Sect, Cellular Neurobiol Res Branch, Intramural Res Program, Baltimore, MD 21201 USA. [Gruber, Aaron J.] Univ Lethbridge, Dept Neurosci, Lethbridge, AB T1K 3M4, Canada. RP Jones, JL (reprint author), Univ Maryland, Dept Anat & Neurobiol, Sch Med, 20 Penn St, Baltimore, MD 21201 USA. EM josh.jones@nih.gov; geoffrey.schoenbaum@nih.gov OI Hernandez, Alex/0000-0002-2267-4781 FU National Institute on Drug Abuse (NIDA), NIH [F32-031517]; NIDA [R01-DA015718]; Natural Sciences and Engineering Research Council of Canada; Intramural Research Program at NIDA FX This work was supported by National Institute on Drug Abuse (NIDA), NIH, F32-031517 to J.L.J., NIDA R01-DA015718 to G. S., funding from Natural Sciences and Engineering Research Council of Canada to A.J.G., and by the Intramural Research Program at NIDA. The opinions expressed in this article are the authors' own and do not reflect the view of the NIH or U.S. Department of Health and Human Services. The authors declare that they have no conflicts of interest related to the data presented in this manuscript. NR 30 TC 60 Z9 61 U1 1 U2 25 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 16 PY 2012 VL 338 IS 6109 BP 953 EP 956 DI 10.1126/science.1227489 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037DY UT WOS:000311083600045 PM 23162000 ER PT J AU Lopez, CM Pelkey, KA Chittajallu, R Nakashiba, T Toth, K Tonegawa, S McBain, CJ AF Lopez, Carla M. Pelkey, Kenneth A. Chittajallu, Ramesh Nakashiba, Toshiaki Toth, Katalin Tonegawa, Susumu McBain, Chris J. TI Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus SO FRONTIERS IN NEURAL CIRCUITS LA English DT Article DE neurogenesis; mossy fibers; hippocampal; activity-dependent circuit refinement; tetanus toxin; Moloney virus ID SPATIAL-PATTERN SEPARATION; MOSSY FIBER SYNAPSES; IN-VIVO; SYNAPTIC PLASTICITY; NEURAL ACTIVITY; DENTATE GYRUS; NEURONS BORN; NEUROGENESIS; ZINC; LOCALIZATION AB In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition-based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus (DG) subfield exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs) and immature recently born GCs that are generated throughout adult life (young GCs), providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX) to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3-6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the adult brain. C1 [Lopez, Carla M.; Pelkey, Kenneth A.; Chittajallu, Ramesh; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA. [Nakashiba, Toshiaki; Tonegawa, Susumu] MIT, RIKEN MIT Ctr Neural Circuit Genet, Cambridge, MA 02139 USA. [Nakashiba, Toshiaki; Tonegawa, Susumu] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Toth, Katalin] Univ Laval, Quebec Mental Hlth Inst, Dept Psychiat & Neurosci, Quebec City, PQ, Canada. RP Pelkey, KA (reprint author), Porter Neurosci Res Ctr, 35 Lincoln Dr,MSC 3715, Bethesda, MD 20892 USA. EM pelkeyk2@mail.nih.gov FU Howard Hughes Medical Institute; Otsuka Maryland Research Institute; Picower Foundation; NIH [R01-MH078821, P50-MH58880]; NICHD; CIHR grant [MOP 81142] FX We thank Daniel Abebe, Xiaoqing Yuan, Modesto R. Peralta III, and Philippe Lemieux for providing expert technical assistance as well as Jennie Z. Young for critical reading. RGS14 anti-body was generously provided by Dr. John Helper. This work was supported by the Howard Hughes Medical Institute, Otsuka Maryland Research Institute, the Picower Foundation, and NIH grants R01-MH078821 and P50-MH58880 to Susumu Tonegawa; NICHD intramural funding to Chris J. McBain; and CIHR grant MOP 81142 to Katalin Toth. NR 40 TC 4 Z9 4 U1 0 U2 12 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5110 J9 FRONT NEURAL CIRCUIT JI Front. Neural Circuits PD NOV 16 PY 2012 VL 6 AR 85 DI 10.3389/fncir.2012.00085 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 037SU UT WOS:000311127600003 PM 23162435 ER PT J AU Okano, J Levy, C Lichti, U Sun, HW Yuspa, SH Sakai, Y Morasso, MI AF Okano, Junko Levy, Clara Lichti, Ulrike Sun, Hong-Wei Yuspa, Stuart H. Sakai, Yasuo Morasso, Maria I. TI Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN ACTIVITY; DERMAL PAPILLA CELLS; GENE-EXPRESSION; SEBACEOUS GLAND; THYROID-HORMONE; SONIC HEDGEHOG; KERATIN GENE; RNA-SEQ; DIFFERENTIATION; GROWTH AB Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss. In the present study, we demonstrate that specific levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1 (Cyp26b1(-/-)) have excessive endogenous RA, resulting in arrest of hf growth at the hair germ stage. The altered hf development is rescued by grafting the mutant skin on immunodeficient mice. Our results show that normalization of RA levels is associated with reinitiation of hf development. Conditional deficiency of Cyp26b1 in the dermis (En1Cre; Cyp26b1f/-) results in decreased hair follicle density and specific effect on hair type, indicating that RA levels also influence regulators of hair bending. Our results support the model of RA-dependent dermal signals regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we performed microarray and RNA-Seq profiling of genes differentially expressed in Cyp26b1(-/-) skin and En1Cre; Cyp26b1f/- tissues. We show specific effects on the Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, indicating that RA modulates pathways and factors implicated in hf downgrowth and bending. Our results establish that proper RA distribution is essential for morphogenesis, development, and differentiation of hfs. C1 [Okano, Junko; Levy, Clara; Morasso, Maria I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA. [Lichti, Ulrike; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Sun, Hong-Wei] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA. [Sakai, Yasuo] Osaka Univ, Dept Plast Surg, Sch Med, Suita, Osaka 5650871, Japan. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Sect, NIH, 50 South Dr,Rm 1523, Bethesda, MD 20892 USA. EM morassom@mail.nih.gov FU National Institutes of Health grant from the Intramural Research Program of the NIAMS FX This work was supported by a National Institutes of Health grant from the Intramural Research Program of the NIAMS. NR 54 TC 5 Z9 5 U1 2 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2012 VL 287 IS 47 DI 10.1074/jbc.M112.397273 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039GY UT WOS:000311233800003 PM 23007396 ER PT J AU Plenge, P Shi, L Beuming, T Te, J Newman, AH Weinstein, H Gether, U Loland, CJ AF Plenge, Per Shi, Lei Beuming, Thijs Te, Jerez Newman, Amy Hauck Weinstein, Harel Gether, Ulrik Loland, Claus J. TI Steric Hindrance Mutagenesis in the Conserved Extracellular Vestibule Impedes Allosteric Binding of Antidepressants to the Serotonin Transporter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROTRANSMITTER-SODIUM SYMPORTER; R-CITALOPRAM; DOPAMINE TRANSPORTER; H-3 IMIPRAMINE; BACTERIAL HOMOLOG; 5-HT TRANSPORTER; S-CITALOPRAM; OPEN STATES; IN-VITRO; SITE AB The serotonin transporter (SERT) controls synaptic serotonin levels and is the primary target for antidepressants, including selective serotonin reuptake inhibitors (e.g. (S)-citalopram) and tricyclic antidepressants (e.g. clomipramine). In addition to a high affinity binding site, SERT possesses a low affinity allosteric site for antidepressants. Binding to the allosteric site impedes dissociation of antidepressants from the high affinity site, which may enhance antidepressant efficacy. Here we employ an induced fit docking/molecular dynamics protocol to identify the residues that may be involved in the allosteric binding in the extracellular vestibule located above the central substrate binding (S1) site. Indeed, mutagenesis of selected residues in the vestibule reduces the allosteric potency of (S)-citalopram and clomipramine. The identified site is further supported by the inhibitory effects of Zn2+ binding in an engineered site and the covalent attachment of benzocaine-methanethiosulfonate to a cysteine introduced in the extracellular vestibule. The data provide a mechanistic explanation for the allosteric action of antidepressants at SERT and suggest that the role of the vestibule is evolutionarily conserved among neurotransmitter: sodium symporter proteins as a binding pocket for small molecule ligands. C1 [Shi, Lei; Te, Jerez; Weinstein, Harel] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Shi, Lei; Weinstein, Harel] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Plenge, Per; Gether, Ulrik; Loland, Claus J.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Mol Neuropharmacol Lab, DK-2200 Copenhagen, Denmark. [Beuming, Thijs] Schrodinger Inc, New York, NY 10036 USA. [Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Shi, L (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. EM les2007@med.cornell.edu; cllo@sund.ku.dk RI Loland, Claus/E-5975-2014; OI Loland, Claus/0000-0002-1773-1446; Gether, Ulrik/0000-0002-0020-3807 FU National Institutes of Health [DA12408, DA023694]; National Institutes of Health, NIDA, Intramural Research Program; Danish Independent Research Council-Sapere Aude; Danish Health Science Research Council; Lundbeck Foundation; Novo Nordic Foundation; Maersk Foundation; BioSCART center of excellence program; Lundbeck A/S FX This work was supported, in whole or in part, by National Institutes of Health Grants DA12408 (to U. G. and H. W.) and DA023694 (to L. S.) and the National Institutes of Health, NIDA, Intramural Research Program (to A. H. N.). This work was also supported in part by the Danish Independent Research Council-Sapere Aude (to C. J. L.), the Danish Health Science Research Council (to C. J. L. and U. G.), the Lundbeck Foundation (to C. J. L. and U. G.), the Novo Nordic Foundation (to C. J. L. and U. G.), the Maersk Foundation (to C. J. L.), the BioSCART center of excellence program (to C. J. L. and U. G.), and Lundbeck A/S (to P. P.). NR 53 TC 35 Z9 36 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2012 VL 287 IS 47 DI 10.1074/jbc.M112.371765 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039GY UT WOS:000311233800004 PM 23007398 ER PT J AU Xu, M Liu, K Swaroop, M Porter, FD Sidhu, R Finkes, S Ory, DS Marugan, JJ Xiao, JB Southall, N Pavan, WJ Davidson, C Walkley, SU Remaley, AT Baxa, U Sun, W McKew, JC Austin, CP Zheng, W AF Xu, Miao Liu, Ke Swaroop, Manju Porter, Forbes D. Sidhu, Rohini Finkes, Sally Ory, Daniel S. Marugan, Juan J. Xiao, Jingbo Southall, Noel Pavan, William J. Davidson, Cristin Walkley, Steven U. Remaley, Alan T. Baxa, Ulrich Sun, Wei McKew, John C. Austin, Christopher P. Zheng, Wei TI delta-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYSOSOMAL ACID LIPASE; ALPHA-TOCOPHEROL; VITAMIN-E; OMEGA-HYDROXYLASE; DISEASE; EXOCYTOSIS; FIBROBLASTS; PLASMA; SUPPLEMENTATION; TOCOTRIENOLS AB Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that delta-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a delta-tocopherol-induced intracellular Ca2+ response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that delta-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. C1 [Xu, Miao; Liu, Ke; Swaroop, Manju; Marugan, Juan J.; Xiao, Jingbo; Southall, Noel; Sun, Wei; McKew, John C.; Austin, Christopher P.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Porter, Forbes D.] Eunice Kennedy Shriver NICHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Sidhu, Rohini; Finkes, Sally; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA. [Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Davidson, Cristin; Walkley, Steven U.] Albert Einstein Coll Med, Rose F Kennedy Ctr, Sidney Weisner Lab Genet Neurol Dis, Bronx, NY 10461 USA. [Remaley, Alan T.] NHLBI, Lab Lipoprot Metab, NIH, Bethesda, MD 20892 USA. [Xu, Miao] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou 310016, Zhejiang, Peoples R China. [Baxa, Ulrich] NCI, Electron Microscopy Lab, NIH, Bethesda, MD 20892 USA. RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov RI Southall, Noel/H-8991-2012; Sidhu, Rohini/G-3547-2012; Zheng, Wei/J-8889-2014; Davidson, Cristin/F-4889-2017 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757; Davidson, Cristin/0000-0002-5508-8113 FU National Institutes of Health Intramural Research Program of the National Center for Advancing Translational Sciences; Intramural Research Program of the National Human Genome Research Institute; Intramural Research Program of the Eunice Kennedy Shriver NICHD; NCI, National Institutes of Health [HHSN26120080001E]; Ara Parseghian Medical Research Foundation; National Institutes of Health [P60 DK020579] FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the National Center for Advancing Translational Sciences, by the Intramural Research Program of the National Human Genome Research Institute, by the Intramural Research Program of the Eunice Kennedy Shriver NICHD, and by NCI, National Institutes of Health, Contract HHSN26120080001E. This work was also supported by a grant from the Ara Parseghian Medical Research Foundation.; We thank Support of Accelerated Research for Niemann-Pick Disease Type C (SOAR-NPC) for fostering a collaborative research environment and stimulating discussion. Mass spectrometry analysis was performed in the Washington University Metabolomics Facility, supported by National Institutes of Health Grant P60 DK020579. We thank Dr. Yiannis A. Ioannou (Mount Sinai School of Medicine) for technical assistance with the exocytosis assays and Ferri Soheilian and Christina Burks for assistance with electron microscopy. NR 49 TC 39 Z9 40 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2012 VL 287 IS 47 DI 10.1074/jbc.M112.357707 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039GY UT WOS:000311233800007 PM 23035117 ER PT J AU Lee, S Chang, J Renvoise, B Tipirneni, A Yang, S Blackstone, C AF Lee, Seongju Chang, Jaerak Renvoise, Benoit Tipirneni, Anita Yang, Sarah Blackstone, Craig TI MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; AAA ATPASE VPS4; STRUCTURAL BASIS; MEMBRANE DEFORMATION; PROTEIN IST1; MACHINERY; AUTOINHIBITION; LOCALIZATION; RECOGNITION; ATLASTIN AB Diverse cellular processes, including multivesicular body formation, cytokinesis, and viral budding, require the sequential functions of endosomal sorting complexes required for transport (ESCRTs) 0 to III. Of these multiprotein complexes, ESCRT-III in particular plays a key role in mediating membrane fission events by forming large, ring-like helical arrays. A number of proteins playing key effector roles, most notably the ATPase associated with diverse cellular activities protein VPS4, harbor present in microtubule-interacting and trafficking molecules (MIT) domains comprising asymmetric three-helical bundles, which interact with helical MIT-interacting motifs in ESCRT-III subunits. Here we assess comprehensively the ESCRT-III interactions of the MIT-domain family member MITD1 and identify strong interactions with charged multivesicular body protein 1B (CHMP1B), CHMP2A, and increased sodium tolerance-1 (IST1). We show that these ESCRT-III subunits are important for the recruitment of MITD1 to the midbody and that MITD1 participates in the abscission phase of cytokinesis. MITD1 also dimerizes through its C-terminal domain. Both types of interactions appear important for the role of MITD1 in negatively regulating the interaction of IST1 with VPS4. Because IST1 binding in turn regulates VPS4, MITD1 may function through downstream effects on the activity of VPS4, which plays a critical role in the processing and remodeling of ESCRT filaments in abscission. C1 [Lee, Seongju; Chang, Jaerak; Renvoise, Benoit; Tipirneni, Anita; Yang, Sarah; Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Cell Biol Sect, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health; National Institutes of Health Clinical Research Training Program FX We thank J. Nagle and D. Kauffman (National Institute of Neurological Disorders and Stroke DNA Sequencing Facility) for DNA sequencing. This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and the National Institutes of Health Clinical Research Training Program (to A.T.). NR 33 TC 14 Z9 16 U1 0 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV 15 PY 2012 VL 23 IS 22 BP 4347 EP 4361 DI 10.1091/mbc.E12-04-0292 PG 15 WC Cell Biology SC Cell Biology GA 082PP UT WOS:000314404700002 PM 23015756 ER PT J AU Go, JT Belisle, SE Tchitchek, N Tumpey, TM Ma, WJ Richt, JA Safronetz, D Feldmann, H Katze, MG AF Go, Jennifer T. Belisle, Sarah E. Tchitchek, Nicolas Tumpey, Terrence M. Ma, Wenjun Richt, Juergen A. Safronetz, David Feldmann, Heinz Katze, Michael G. TI 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models SO BMC GENOMICS LA English DT Article DE Pandemic; Influenza virus; Genomics; Inflammation; Lipid metabolism; Glucocorticoid receptor; LXR/RXR ID INNATE IMMUNE-RESPONSE; GENE-EXPRESSION; VITAMIN-D; A H1N1; IN-VITRO; RECEPTOR; PIGS; MACROPHAGES; CIRCULATION; METABOLISM AB Background: The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this we have performed a comparative transcriptomic analysis of acute phase responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine. Results: Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. We found genes associated with the retinoid X receptor (RXR) signaling pathway known to control pro-inflammatory and metabolic processes that were differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns varied among the three species. Conclusions: By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another. C1 [Go, Jennifer T.; Belisle, Sarah E.; Tchitchek, Nicolas; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Katze, Michael G.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Ma, Wenjun; Richt, Juergen A.] Kansas State Univ, Dept Diagnost Med Pathobiol, Coll Vet Med, Manhattan, KS 66506 USA. [Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA. [Safronetz, David; Feldmann, Heinz] NIAID, Lab Virol, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Go, JT (reprint author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. EM tisoncik@u.washington.edu OI Tchitchek, Nicolas/0000-0003-3307-0446 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800060C, HHSN266200700005C]; Intramural research Program of the NIAID, NIH FX We thank Elizabeth Rosenzweig, Sara Kelly, and Jean Chang for microarray technical support. We are grateful to Marcus Korth, Lynn Law, and Janine Bryan for their critical review of the manuscript. This work was supported by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200800060C (M. G. K.) and contract HHSN266200700005C (J.A.R.). We thank the staff of the Rocky Mountain Veterinary Branch (Division of Intramural Research (DIR), NIAID, NIH) for their assistance with the nonhuman primate work. In addition, we thank Friederike Feldmann (DIR, NIAID, NIH) for technical assistance in biocontainment. The study was partially funded by the Intramural research Program of the NIAID, NIH. We thank Deborah Clouser, Darlene Sheffer, Xi Li, Qinfang Liu, and Chuanling Qiao of Kansas State University for their assistance with the pig work. NR 50 TC 20 Z9 21 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 15 PY 2012 VL 13 AR 627 DI 10.1186/1471-2164-13-627 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 061UJ UT WOS:000312873600001 PM 23153050 ER PT J AU Alonso, WJ McCormick, BJJ AF Alonso, Wladimir J. McCormick, Benjamin J. J. TI EPIPOI: A user-friendly analytical tool for the extraction and visualization of temporal parameters from epidemiological time series SO BMC PUBLIC HEALTH LA English DT Article DE Epidemiology; Time series; Trends; Seasonality; Anomalies; Data visualization ID SPATIAL HIERARCHIES; INFLUENZA EPIDEMICS; TRAVELING-WAVES; MORTALITY; THAILAND; PATTERNS; VECTORS; IMAGERY; MODELS; IMPACT AB Background: There is an increasing need for processing and understanding relevant information generated by the systematic collection of public health data over time. However, the analysis of those time series usually requires advanced modeling techniques, which are not necessarily mastered by staff, technicians and researchers working on public health and epidemiology. Here a user-friendly tool, EPIPOI, is presented that facilitates the exploration and extraction of parameters describing trends, seasonality and anomalies that characterize epidemiological processes. It also enables the inspection of those parameters across geographic regions. Although the visual exploration and extraction of relevant parameters from time series data is crucial in epidemiological research, until now it had been largely restricted to specialists. Methods: EPIPOI is freely available software developed in Matlab (The Mathworks Inc) that runs both on PC and Mac computers. Its friendly interface guides users intuitively through useful comparative analyses including the comparison of spatial patterns in temporal parameters. Results: EPIPOI is able to handle complex analyses in an accessible way. A prototype has already been used to assist researchers in a variety of contexts from didactic use in public health workshops to the main analytical tool in published research. Conclusions: EPIPOI can assist public health officials and students to explore time series data using a broad range of sophisticated analytical and visualization tools. It also provides an analytical environment where even advanced users can benefit by enabling a higher degree of control over model assumptions, such as those associated with detecting disease outbreaks and pandemics. C1 [Alonso, Wladimir J.; McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM alonsow@mail.nih.gov FU MISMS project, MAL-ED; Bill and Melinda Gates Foundation; Premio Santander Universidades FX EPIPOI is available at http://www.epipoi.info. The authors are grateful to the Department of Vital Statistics from the Brazilian Ministry of Health for providing the mortality data used as an example dataset. We thank Cynthia Schuck-Paim, Jennifer Weisent and Camille Pelat for their valuable comments on manuscript. The development of this tool has been possible using the support of MISMS project, MAL-ED funded by the Bill and Melinda Gates Foundation, and the Premio Santander Universidades. Torrence and Compo (Torrence and Compo 1998) graciously made codes which have been integrated in EPIPOI to perform wavelet analyses freely available. This tool has certainly benefited from comments from users. We are grateful for this and hope to keep receiving such feedback in the future (for this, please go to www.epipoi.info). NR 29 TC 9 Z9 9 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD NOV 15 PY 2012 VL 12 AR 982 DI 10.1186/1471-2458-12-982 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 060QU UT WOS:000312793900001 PM 23153033 ER PT J AU Gozzelino, R Andrade, BB Larsen, R Luz, NF Vanoaica, L Seixas, E Coutinho, A Cardoso, S Rebelo, S Poli, M Barral-Netto, M Darshan, D Kuhn, LC Soares, MP AF Gozzelino, Raffaella Andrade, Bruno Bezerril Larsen, Rasmus Luz, Nivea F. Vanoaica, Liviu Seixas, Elsa Coutinho, Antonio Cardoso, Silvia Rebelo, Sofia Poli, Maura Barral-Netto, Manoel Darshan, Deepak Kuehn, Lukas C. Soares, Miguel P. TI Metabolic Adaptation to Tissue Iron Overload Confers Tolerance to Malaria SO CELL HOST & MICROBE LA English DT Article ID NF-KAPPA-B; ALPHA-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; FERRITIN HEAVY-CHAIN; INDUCED CELL-DEATH; HEME OXYGENASE-1; IN-VITRO; INFECTIOUS-DISEASES; BRAZILIAN AMAZON; OXIDATIVE STRESS AB Disease tolerance is a defense strategy that limits the fitness costs of infection irrespectively of pathogen burden. While restricting iron (Fe) availability to pathogens is perceived as a host defense strategy, the resulting tissue Fe overload can be cytotoxic and promote tissue damage to exacerbate disease severity. Examining this interplay during malaria, the disease caused by Plasmodium infection, we find that expression of the Fe sequestering protein ferritin H chain (FtH) in mice, and ferritin in humans, is associated with reduced tissue damage irrespectively of pathogen burden. FtH protection relies on its ferroxidase activity, which prevents labile Fe from sustaining proapoptotic c-Jun N-terminal kinase (JNK) activation. FtH expression is inhibited by JNK activation, promoting tissue Fe overload, tissue damage, and malaria severity. Mimicking FtH's antioxidant effect or inhibiting JNK activation pharmacologically confers therapeutic tolerance to malaria in mice. Thus, FtH provides metabolic adaptation to tissue Fe overload, conferring tolerance to malaria. C1 [Gozzelino, Raffaella; Larsen, Rasmus; Seixas, Elsa; Coutinho, Antonio; Cardoso, Silvia; Rebelo, Sofia; Soares, Miguel P.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Andrade, Bruno Bezerril] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Luz, Nivea F.; Barral-Netto, Manoel] Fdn Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, BR-40296710 Salvador, BA, Brazil. [Luz, Nivea F.; Barral-Netto, Manoel] Univ Fed Bahia, Fac Med, BR-40110100 Salvador, BA, Brazil. [Vanoaica, Liviu; Darshan, Deepak; Kuehn, Lukas C.] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland. [Poli, Maura] Univ Brescia, Dipartimento Materno Infantile & Tecnol Biomed, I-25123 Brescia, Italy. RP Soares, MP (reprint author), Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. EM mpsoares@igc.gulbenkian.pt RI Darshan, Deepak/B-8259-2013; Barral Netto, Manoel/B-3904-2009; Imunologia, Inct/I-2124-2013; Gozzelino, Raffaella/J-4524-2013; Andrade, Bruno/J-9111-2012; Gozzelino, Raffaella/E-8147-2017 OI Coutinho, Antonio/0000-0002-0857-9227; Darshan, Deepak/0000-0001-9719-5980; Barral Netto, Manoel/0000-0002-5823-7903; Gozzelino, Raffaella/0000-0002-1195-8527; Farias Luz, Nivea/0000-0003-1958-7043; Soares, Miguel/0000-0002-9314-4833; Andrade, Bruno/0000-0001-6833-3811; Gozzelino, Raffaella/0000-0002-1195-8527 FU Fundacao pars a Ciencia e Tecnologia (Portugal) [PTDC/BIA-BCM/101311/2008, PTDC/SAU-FCF/100762/2008, PTDC/SAU-TOX/116627/2010]; European Community [LSH-2005-1.2.5-1, ERC-2011-AdG. 294709]; Financiadora de Estudos e Projetos/Fundo Nacional de Desenvolvimento Cientifico e Tecnologico Amazonia, Brazil [010409605]; Conselho Nacional de Pesquisa e Tecnologia (Brazil); intramural research program of the National Institute of Allergy and Infectious Diseases, NIH FX We thank John Eaton (University of Louisville) and Luis Teixeira and Thiago Carvalho (Instituto Gulbenkian de Ciencia) for critical review of the manuscript; Viktoria Jeney (University of Debrecen, Hungary) for help in heme measurement; Emanuela Tolosano and Francesca Vinchi (University of Turin) for help in Fe measurements; and Aldina Barral, Antonio Reis-Filho, Sebastiao Souza-Neto, Jorge Tolentino, and Elze Leite (Centro de Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz, Brazil) and Marcelo Camargo (Faculdades Sao Lucas and University of Sao Paulo, Brazil) for critical help in logistics of the clinical study. Funding was provided by Fundacao pars a Ciencia e Tecnologia (Portugal) grants to R.G., R.L., E.S., and M.P.S. (PTDC/BIA-BCM/101311/2008, PTDC/SAU-FCF/100762/2008, and PTDC/SAU-TOX/116627/2010) and European Community 6th Framework Grant LSH-2005-1.2.5-1 and 7th Framework Grant ERC-2011-AdG. 294709 DAMAGECONTROL to M.P.S. The clinical study was funded by Financiadora de Estudos e Projetos (Grant 010409605)/Fundo Nacional de Desenvolvimento Cientifico e Tecnologico Amazonia, Brazil. N.F.L. receives a fellowship from Conselho Nacional de Pesquisa e Tecnologia (Brazil). M.B.-N. is a senior investigator from the Conselho Nacional de Ciencia e Tecnologia (CNPq), Brazil. B.B.A. is supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, NIH. R.G. performed all the experimental work, with help from R.L., E.S., and S.C., and contributed to the study design. L.V., D.D., and L.C.K. generated Fthlox/lox mice. M.P. generated reagents/protocols. S.R. and S.C. established Fthlox/lox and FthDelta/Delta mouse colony. B.B.A. and M.B.-N. designed and implemented the clinical protocol. B.B.A. coordinated the clinical evaluation of the patients and the experiments to estimate hepatic damage. N.F.L. analyzed ferritin and free heme plasma concentrations with the help of R.G. M.P.S. formulated the hypothesis that FtH confers tolerance to Plasmodium infection, supervised the study design and execution, and wrote the manuscript with R.G. All authors read and approved the manuscript. NR 52 TC 32 Z9 33 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD NOV 15 PY 2012 VL 12 IS 5 BP 693 EP 704 DI 10.1016/j.chom.2012.10.011 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 046KY UT WOS:000311765100011 PM 23159058 ER PT J AU Fiskus, W Rao, R Balusu, R Ganguly, S Tao, JG Sotomayor, E Mudunuru, U Smith, JE Hembruff, SL Atadja, P Marquez, VE Bhalla, K AF Fiskus, Warren Rao, Rekha Balusu, Ramesh Ganguly, Siddhartha Tao, Jianguo Sotomayor, Eduardo Mudunuru, Uma Smith, Jacqueline E. Hembruff, Stacey L. Atadja, Peter Marquez, Victor E. Bhalla, Kapil TI Superior Efficacy of a Combined Epigenetic Therapy against Human Mantle Cell Lymphoma Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID GROUP PROTEIN EZH2; HISTONE DEACETYLASE INHIBITORS; POLYCOMB-GROUP PROTEINS; ACUTE-LEUKEMIA CELLS; DNA METHYLATION; HEMATOLOGICAL MALIGNANCIES; METHYLTRANSFERASE EZH2; GENE-EXPRESSION; CANCER; OVEREXPRESSION AB Purpose: A deregulated epigenome contributes to the transformed phenotype of mantle cell lymphoma (MCL). This involves activity of the polycomb repressive complex (PRC) 2, containing three core proteins, EZH2, SUZ12, and EED, in which the SET domain of EZH2 mediates the histone methyltransferase activity. We determined the effects of 3-deazaneplanocin A (DZNep), an S-adenosylhomocysteine hydrolase inhibitor, and/or pan-histone deacetylase inhibitor panobinostat (PS) on cultured and primary MCL cells. Experimental Design: Following treatment with DZNep and/or PS, apoptosis and the levels and activity of EZH2 and PRC2 proteins in cultured and primary MCL cells were determined. Results: Treatment with DZNep depleted EZH2, SUZ12, and 3MeK27H3 in the cultured human MCL cells. DZNep also increased expression of p21, p27, and FBXO32, whereas it depleted Cyclin D1 and Cyclin E1 levels in MCL cells. In addition, DZNep treatment induced cell-cycle arrest and apoptosis in cultured and primary MCL cells. Furthermore, as compared with treatment with each agent alone, cotreatment with DZNep and PS caused greater depletion of EZH2, SUZ12, 3MeK27H3, and Cyclin D1 levels, whereas it induced greater expression of FBXO32, p16, p21, and p27. Combined treatment with DZNep and PS synergistically induced apoptosis of cultured and primary MCL cells while relatively sparing normal CD34 + cells. Cotreatment with DZNep and PS also caused significantly greater inhibition of tumor growth of JeKo-1 xenografts in NOD/SCID mice. Conclusions: These preclinical in vitro and in vivo findings show that cotreatment with DZNep and PS is an active combined epigenetic therapy worthy of further in vivo testing against MCL. Clin Cancer Res; 18(22); 6227-38. (C)2012 AACR. C1 [Fiskus, Warren; Rao, Rekha; Balusu, Ramesh; Ganguly, Siddhartha; Mudunuru, Uma; Smith, Jacqueline E.; Hembruff, Stacey L.; Bhalla, Kapil] Univ Kansas, Ctr Canc, Kansas City, KS 66160 USA. [Tao, Jianguo; Sotomayor, Eduardo] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Atadja, Peter] Novartis Inst Biomed Res Inc, Cambridge, MA USA. [Marquez, Victor E.] NIH, Bethesda, MD 20892 USA. RP Bhalla, K (reprint author), Univ Kansas, Ctr Canc, 3901 Rainbow Blvd,4030 Robinson,MS 1027, Kansas City, KS 66160 USA. EM kbhalla@kumc.edu FU Novartis Pharmaceuticals FX K.N. Bhalla: commercial research grant and honoraria of speakers' bureau from Novartis Pharmaceuticals. No potential conflicts of interest were disclosed by the other authors. NR 50 TC 28 Z9 29 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2012 VL 18 IS 22 BP 6227 EP 6238 DI 10.1158/1078-0432.CCR-12-0873 PG 12 WC Oncology SC Oncology GA 050AC UT WOS:000312023800017 PM 22932665 ER PT J AU Chahal, H Backlund, JYC Cleary, PA Lachin, JM Polak, JF Lima, JAC Bluemke, DA AF Chahal, Harjit Backlund, Jye-Yu C. Cleary, Patricia A. Lachin, John M. Polak, Joseph F. Lima, Joao A. C. Bluemke, David A. CA DCCT EDIC Res Grp TI Relation Between Carotid Intima-Media Thickness and Left Ventricular Mass in Type 1 Diabetes Mellitus (from the Epidemiology of Diabetes Interventions and Complications [EDIC] Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SECONDARY HYPERTENSION; ARTERY; GEOMETRY; TRIAL AB Type 1 diabetes mellitus (DM) is associated with early atherosclerosis and increased cardiovascular mortality. The relation between carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, and left ventricular (LV) mass, an independent predictor of cardiovascular morbidity, has not been previously studied in type 1 DM. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter observational study designed to follow up the Diabetes Control and Complications Trial (DCCT) cohort. LV mass was measured with cardiac magnetic resonance imaging at EDIC year 15 and common cIMT was assessed using B-mode ultrasound at EDIC year 12. Multivariable linear regression models were used to assess the relation between cIMT at year 12 and LV mass at year 15. In total 889 participants had cardiac magnetic resonance imaging and cIMT measurements available for these analyses. At EDIC year 15, mean age of the participants was 49 +/- 7 years, mean DM duration was 28 +/- 5 years, and 52% were men. Spearman correlation coefficient (r) between LV mass and cIMT was 0.33 (p <0.0001). After adjusting for basic covariates (machine, reader, age, and gender), a significant association between LV mass and cIMT (estimate 2.0 g/m(2) per 0.1-mm cIMT increment, p <0.0001) was observed. This association was decreased by the addition of systolic blood pressure, in particular 1.15 g/m(2) per 0.1-mm cIMT increment (p <0.0001), and to a lesser extent other cardiovascular disease risk factors. Furthermore, the relation observed between LV mass and cIMT was stronger in patients with shorter duration. of DM. In conclusion, cIMT was an independent predictor of larger LV mass in a well-characterized population with type 1 DM. (C) 2012 Published by Elsevier Inc. (Am J Cardiol 2012;110: 1534-1540) C1 [Chahal, Harjit; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Chahal, Harjit; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Sch Med, Dept Cardiol, Baltimore, MD USA. [Backlund, Jye-Yu C.; Cleary, Patricia A.; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Polak, Joseph F.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21205 USA. EM bluemked@nih.gov OI Lachin, John/0000-0001-9838-2841; Bluemke, David/0000-0002-8323-8086 FU Division of Diabetes Endocrinology and Metabolic Diseases of National Institute of Diabetes and Digestive and Kidney Disease; National Eye Institute; National Institute of Neurologic Disorders and Stroke; Genetic Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, Maryland FX Acknowledgement for The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1983-93) and contracts (1994-present) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease, and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the Genetic Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland. NR 17 TC 3 Z9 3 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2012 VL 110 IS 10 BP 1534 EP 1540 DI 10.1016/j.amjcard.2012.07.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 043DU UT WOS:000311523900024 PM 22884107 ER PT J AU Mahavadi, P Guenther, A Gochuico, BR AF Mahavadi, Poornima Guenther, Andreas Gochuico, Bernadette R. TI Hermansky-Pudlak Syndrome Interstitial Pneumonia It's the Epithelium, Stupid! SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID IDIOPATHIC PULMONARY-FIBROSIS; ENDOPLASMIC-RETICULUM STRESS; MOUSE MODEL; APOPTOSIS; TYPE-2 C1 [Mahavadi, Poornima; Guenther, Andreas] Univ Giessen, Marburg Lung Ctr, Giessen, Germany. [Guenther, Andreas] Agaples Lung Clin Waldhof Elgershausen, Greifenstein, Germany. [Guenther, Andreas] German Ctr Lung Res, Giessen, Germany. [Gochuico, Bernadette R.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Mahavadi, P (reprint author), Univ Giessen, Marburg Lung Ctr, Giessen, Germany. NR 18 TC 2 Z9 2 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2012 VL 186 IS 10 BP 939 EP 940 DI 10.1164/rccm.201210-1771ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 046LI UT WOS:000311766100004 PM 23155210 ER PT J AU Vanden Berghe, W Sabbe, L Kaileh, M Haegeman, G Heyninck, K AF Vanden Berghe, Wim Sabbe, Linde Kaileh, Mary Haegeman, Guy Heyninck, Karen TI Molecular insight in the multifunctional activities of Withaferin A SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Withaferin A; Carcinogenesis; Inflammation; Angiogenesis; Therapy ID NF-KAPPA-B; BREAST-CANCER CELLS; FIBRILLARY ACIDIC PROTEIN; EHRLICH ASCITES-CARCINOMA; ESTROGEN-RECEPTOR-ALPHA; HERBAL DRUG WITHAFERIN; LIVER-X-RECEPTORS; WITHANIA-SOMNIFERA; IN-VIVO; DOWN-REGULATION AB Herbal medicine which involves the use of plants for their medicinal value, dates as far back as the origin of mankind and demonstrates an array of applications including cardiovascular protection and anticancer activities, via antioxidant, anti-inflammatory and metabolic activities. Even today the popularity of medicinal herbs is still growing like in traditional medicines such as the Indian medicine, Ayurveda. One of the Ayurvedic medicinal plants is Withania somnifera Dunal, of which the important constituents are the withanolides. Among them, Withaferin A is one of the most bioactive compounds, exerting anti-inflammatory, pro-apoptotic but also anti-invasive and anti-angiogenic effects. In the context of modern pharmacology, a better insight in the underlying mechanism of the broad range of bioactivities exerted by Withaferin A is compulsory. Therefore, a lot of effort was made to explore the intracellular effects of Withaferin A and to characterize its target proteins. This review provides a decisive insight on the molecular basis of the health-promoting potential of Withaferin A. (C) 2012 Elsevier Inc. All rights reserved. C1 [Vanden Berghe, Wim; Sabbe, Linde; Haegeman, Guy; Heyninck, Karen] Univ Ghent, Dept Physiol, Lab Eukaryot Gene Express & Signal Transduct, B-9000 Ghent, Belgium. [Vanden Berghe, Wim] Univ Antwerp, Dept Biomed Sci, Lab Prot Sci Prote & Epigenet Signalling PPES, Antwerp, Belgium. [Kaileh, Mary] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Heyninck, K (reprint author), Univ Ghent, Dept Physiol, Lab Eukaryot Gene Express & Signal Transduct, Proeftuinstr 86, B-9000 Ghent, Belgium. EM karen.heyninck@ugent.be FU FLAVIOLA [FP7-KBBE-2008-2B]; Multiple Myeloma Research Foundation (MMRF) FX This research is partially financial supported by FP7-KBBE-2008-2B grant FLAVIOLA ("Targeted delivery of dietary flavanol for optimal human cell function: Effects on cardiovascular health" (www.flaviola.org)) and the Research Grant from the Multiple Myeloma Research Foundation (MMRF). NR 116 TC 28 Z9 28 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2012 VL 84 IS 10 SI SI BP 1282 EP 1291 DI 10.1016/j.bcp.2012.08.027 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 047VV UT WOS:000311870500008 PM 22981382 ER PT J AU Brenchley, JM Vinton, C Tabb, B Hao, XP Connick, E Paiardini, M Lifson, JD Silvestri, G Estes, JD AF Brenchley, Jason M. Vinton, Carol Tabb, Brian Hao, Xing Pei Connick, Elizabeth Paiardini, Mirko Lifson, Jeffrey D. Silvestri, Guido Estes, Jacob D. TI Differential infection patterns of CD4(+) T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections SO BLOOD LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; AFRICAN-GREEN MONKEYS; NATURAL SIV HOSTS; SOOTY MANGABEYS; IN-VIVO; HIV-1 INFECTION; RHESUS MACAQUES; REPLICATION; VIREMIA; AIDS AB Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4(+) T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4(+) T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4(+) T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency. (Blood. 2012; 120(20): 4172-4181) C1 [Brenchley, Jason M.; Vinton, Carol] NIAID, Program Barrier Immun & Repair, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Tabb, Brian; Lifson, Jeffrey D.; Estes, Jacob D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Hao, Xing Pei] SAIC Frederick Inc, Pathol & Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Connick, Elizabeth] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA. [Paiardini, Mirko; Silvestri, Guido] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Brenchley, JM (reprint author), NIAID, Program Barrier Immun & Repair, Mol Microbiol Lab, NIH, 4 Ctr Dr,Rm 201,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov; estesj@mail.nih.gov FU Intramural National Institute of Allergy and Infectious Diseases, National Institutes of Health program; National Cancer Institute, National Institutes of Health [HHSN261200800001E, R01AI-084836] FX This work was supported by the Intramural National Institute of Allergy and Infectious Diseases, National Institutes of Health program, and the National Cancer Institute, National Institutes of Health (contract HHSN261200800001E and R01AI-084836, M.P.). NR 54 TC 61 Z9 61 U1 3 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2012 VL 120 IS 20 BP 4172 EP 4181 DI 10.1182/blood-2012-06-437608 PG 10 WC Hematology SC Hematology GA 044QN UT WOS:000311637400012 PM 22990012 ER PT J AU Bergman, A Ryden, A Law, RJ de Boer, J Covaci, A Alaee, M Birnbaum, L Petreas, M Rose, M Sakai, S Van den Eede, N van der Veen, I AF Bergman, Ake Ryden, Andreas Law, Robin J. de Boer, Jacob Covaci, Adrian Alaee, Mehran Birnbaum, Linda Petreas, Myrto Rose, Martin Sakai, Shinichi Van den Eede, Nele van der Veen, Ike TI A novel abbreviation standard for organobromine, organochlorine and organophosphorus flame retardants and some characteristics of the chemicals SO ENVIRONMENT INTERNATIONAL LA English DT Review DE Brominated flame retardants; Chlorinated flame retardants; Phosphorus flame retardants; Nomenclature; Abbreviations; Physico-chemical properties ID POLYCHLORINATED-BIPHENYLS; ENVIRONMENT; TRENDS; DIPHENYLETHERS; METABOLITES AB Ever since the interest in organic environmental contaminants first emerged 50 years ago, there has been a need to present discussion of such chemicals and their transformation products using simple abbreviations so as to avoid the repetitive use of long chemical names. As the number of chemicals of concern has increased, the number of abbreviations has also increased dramatically, sometimes resulting in the use of different abbreviations for the same chemical. In this article, we propose abbreviations for flame retardants (FRs) substituted with bromine or chlorine atoms or including a functional group containing phosphorus, i.e. BFRs, CFRs and PFRs, respectively. Due to the large number of halogenated and organophosphorus FRs, it has become increasingly important to develop a strategy for abbreviating the chemical names of FRs. In this paper, a two step procedure is proposed for deriving practical abbreviations (PRABs) for the chemicals discussed. In the first step, structural abbreviations (STABs) are developed using specific STAB criteria based on the FR structure. However, since several of the derived STABs are complicated and long, we propose instead the use of PRABs. These are, commonly, an extract of the most essential part of the STAB, while also considering abbreviations previously used in the literature. We indicate how these can be used to develop an abbreviation that can be generally accepted by scientists and other professionals involved in FR related work. Tables with PRABs and STABs for BFRs, CFRs and PERs are presented, including CAS (Chemical Abstract Service) numbers, notes of abbreviations that have been used previously, CA (Chemical Abstract) name, common names and trade names, as well as some fundamental physicochemical constants. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Bergman, Ake; Ryden, Andreas] Stockholm Univ, Dept Mat & Environm Chem, Environm Chem Unit, SE-10691 Stockholm, Sweden. [Law, Robin J.] Cefas Lowestoft Lab, Ctr Environm Fisheries & Aquaculture Sci, Lowestoft NR33 OHT, Suffolk, England. [de Boer, Jacob; van der Veen, Ike] Vrije Univ Amsterdam, Inst Environm Studies, NL-1081 HV Amsterdam, Netherlands. [Covaci, Adrian; Van den Eede, Nele] Univ Antwerp, Toxicol Ctr, B-2610 Antwerp, Belgium. [Alaee, Mehran] Environm Canada, Canada Ctr Inland Waters, Natl Water Res Inst, Burlington, ON L7R 4A6, Canada. [Birnbaum, Linda] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Petreas, Myrto] Calif Dept Tox Subst Control, Environm Chem Lab, Berkeley, CA 94710 USA. [Rose, Martin] Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. [Sakai, Shinichi] Kyoto Univ, Environm Preservat Res Ctr, Kyoto, Japan. RP Bergman, A (reprint author), Stockholm Univ, Dept Mat & Environm Chem, Environm Chem Unit, SE-10691 Stockholm, Sweden. EM ake.bergman@mmk.su.se RI Covaci, Adrian/A-9058-2008; van der veen, ike/B-7228-2014; de Boer, Jacob/L-5094-2013; OI Covaci, Adrian/0000-0003-0527-1136; de Boer, Jacob/0000-0001-6949-4828; van der Veen, ike/0000-0003-0237-093X; Van den Eede, Nele/0000-0002-0198-6591; Rose, Martin/0000-0001-7071-180X FU Flanders Research Foundation (FWO); Stockholm University; Stockholm University's Strategic Marine Environmental Research Funds through the Baltic Ecosystem Adaptive Management (BEAM) FX NVDE and AC acknowledge PhD and post-doctoral fellowships from the Flanders Research Foundation (FWO). AR acknowledges faculty funding from Stockholm University and Stockholm University's Strategic Marine Environmental Research Funds through the Baltic Ecosystem Adaptive Management (BEAM). The opinions expressed here are those of the authors and do not necessarily reflect the views of the California Department of Toxic Substances Control, or of NIEHS, NIH, or the U.S. Government. NR 45 TC 110 Z9 114 U1 26 U2 191 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 J9 ENVIRON INT JI Environ. Int. PD NOV 15 PY 2012 VL 49 BP 57 EP 82 DI 10.1016/j.envint.2012.08.003 PG 26 WC Environmental Sciences SC Environmental Sciences & Ecology GA 044DV UT WOS:000311600500008 PM 22982223 ER PT J AU Mason, RP Ganini, D Ranguelova, K Bonini, MG AF Mason, Ronald P. Ganini, Douglas Ranguelova, Kalina Bonini, Marcelo G. TI Two hypotheses for the oxidation of SOD1-Cu(I) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Letter ID CU,ZN-SUPEROXIDE DISMUTASE; HYDROGEN-PEROXIDE; PEROXYMONOCARBONATE; MECHANISM; KINETICS C1 [Mason, Ronald P.; Ganini, Douglas; Ranguelova, Kalina] NIEHS, Lab Pharmacol & Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Bonini, Marcelo G.] Univ Illinois, Dept Med, Cardiol Sect, Chicago, IL USA. [Bonini, Marcelo G.] Univ Illinois, Dept Pharmacol, Chicago, IL USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Toxicol, NIH, MD F0-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov NR 7 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 15 PY 2012 VL 53 IS 10 BP 1991 EP 1992 DI 10.1016/j.freeradbiomed.2012.10.524 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 040MZ UT WOS:000311328300019 PM 23137624 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI Highlights, predictions, and changes SO RETROVIROLOGY LA English DT Editorial Material ID HIV-1; RESTRICTION AB Recent literature highlights at Retrovirology are described. Predictions are made regarding "hot" retrovirology research trends for the coming year based on recent journal access statistics. Changes in Retrovirology editor and the frequency of the Retrovirology Prize are announced. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kjeang@nih.gov FU Intramural NIH HHS NR 13 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD NOV 15 PY 2012 VL 9 AR 96 DI 10.1186/1742-4690-9-96 PG 2 WC Virology SC Virology GA 046DH UT WOS:000311745200001 PM 23153244 ER PT J AU Morgan, HP Walsh, MJ Blackburn, EA Wear, MA Boxer, MB Shen, M Veith, H McNae, IW Nowicki, MW Michels, PAM Auld, DS Fothergill-Gilmore, LA Walkinshaw, MD AF Morgan, Hugh P. Walsh, Martin J. Blackburn, Elizabeth A. Wear, Martin A. Boxer, Matthew B. Shen, Min Veith, Henrike McNae, Iain W. Nowicki, Matthew W. Michels, Paul A. M. Auld, Douglas S. Fothergill-Gilmore, Linda A. Walkinshaw, Malcolm D. TI A new family of covalent inhibitors block nucleotide binding to the active site of pyruvate kinase SO BIOCHEMICAL JOURNAL LA English DT Article DE covalent inhibitor; Leishmania mexicana; lysine covalent modification; nucleotide binding; pyruvate kinase; saccharin analogue ID FORM TRYPANOSOMA-BRUCEI; GLYCOLYTIC-ENZYMES; DEFICIENCY; ADENOSINE; DESIGN; TARGET; TERMS; DRUGS AB PYK (pyruvate kinase) plays a central role in the metabolism of many organisms and cell types, but the elucidation of the details of its function in a systems biology context has been hampered by the lack of specific high-affinity small-molecule inhibitors. High-throughput screening has been used to identify a family of saccharin derivatives which inhibit LmPYK (Leishmania mexicana PYK) activity in a time- (and dose-) dependent manner, a characteristic of irreversible inhibition. The crystal structure of DBS {4-[(1,1-dioxo-1,2-benzothiazol-3-yl)sulfanyl]benzoic acid} complexed with LmPYK shows that the saccharin moiety reacts with an active-site lysine residue (Lys(335)), forming a covalent bond and sterically hindering the binding of ADP/ATP. Mutation of the lysine residue to an arginine residue eliminated the effect of the inhibitor molecule, providing confirmation of the proposed inhibitor mechanism. This lysine residue is conserved in the active sites of the four human PYK isoenzymes, which were also found to be irreversibly inhibited by DBS. X-ray structures of PYK isoforms show structural differences at the DBS-binding pocket, and this covalent inhibitor of PYK provides a chemical scaffold for the design of new families of potentially isoform-specific irreversible inhibitors. C1 [Morgan, Hugh P.; Blackburn, Elizabeth A.; Wear, Martin A.; McNae, Iain W.; Nowicki, Matthew W.; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.] Univ Edinburgh, Sch Biol Sci, Ctr Translat & Chem Biol, Edinburgh EH9 3JR, Midlothian, Scotland. [Walsh, Martin J.; Boxer, Matthew B.; Shen, Min; Veith, Henrike; Auld, Douglas S.] NHGRI, Chem Genom Ctr, Ctr Translat Therapeut, NIH, Rockville, MD 20850 USA. [Michels, Paul A. M.] Catholic Univ Louvain, Biochem Lab, B-1200 Brussels, Belgium. [Michels, Paul A. M.] Catholic Univ Louvain, Res Unit Trop Dis, de Duve Inst, B-1200 Brussels, Belgium. RP Walkinshaw, MD (reprint author), Univ Edinburgh, Sch Biol Sci, Ctr Translat & Chem Biol, Michael Swann Bldg,Kings Bldg,Mayfield Rd, Edinburgh EH9 3JR, Midlothian, Scotland. EM m.walkinshaw@ed.ac.uk RI Michels, Paul/A-5637-2009; OI walkinshaw, malcolm/0000-0001-5955-9325 FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; National Human Genome Research Institute, National Institutes of Health; Medical Research Council; European Commission through its INCO-DEV programme; Wellcome Trust; Biotechnology and Biological Sciences Research Council FX This work was supported, in part, by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Additional funding was from the Medical Research Council, and the European Commission through its INCO-DEV programme. The Centre for Translational and Chemical Biology and the Edinburgh Protein Production Facility are funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council. NR 25 TC 8 Z9 8 U1 0 U2 18 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2012 VL 448 BP 67 EP 72 DI 10.1042/BJ20121014 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042HP UT WOS:000311462600007 PM 22906073 ER PT J AU Triquigneaux, MM Ehrenshaft, M Roth, E Silman, I Ashani, Y Mason, RP Weiner, L Deterding, LJ AF Triquigneaux, Mathilde M. Ehrenshaft, Marilyn Roth, Esther Silman, Israel Ashani, Yakov Mason, Ronald P. Weiner, Lev Deterding, Leesa J. TI Targeted oxidation of Torpedo californica acetylcholinesterase by singlet oxygen: identification of N-formylkynurenine tryptophan derivatives within the active-site gorge of its complex with the photosensitizer Methylene Blue SO BIOCHEMICAL JOURNAL LA English DT Article DE acetylcholinesterase (AChE); active-site gorge; mass spectrometry; N-formylkynurenine; singlet oxygen; site-specific photo-oxidation ID TANDEM MASS-SPECTROMETRY; IMMUNOLOGICAL DETECTION; PEPTIDES; BINDING; RESIDUES; MS/MS AB The principal role of AChE (acetylcholinesterase) is termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. The active site of AChE is near the bottom of a long and narrow gorge lined with aromatic residues. It contains a CAS (catalytic 'anionic' subsite) and a second PAS (peripheral 'anionic' site), the gorge mouth, both of which bind acetylcholine via pi-cation interactions, primarily with two conserved tryptophan residues. It was shown previously that generation of O-1(2) by illumination of MB (Methylene Blue) causes irreversible inactivation of TcAChE (Torpedo californica AChE), and suggested that photo-oxidation of tryptophan residues might be responsible. In the present study, structural modification of the TcAChE tryptophan residues induced by MB-sensitized oxidation was investigated using anti-N-formylkynurenine antibodies and MS. From these analyses, we determined that N-formylkynurenine derivatives were specifically produced from Trp(84) and Trp(279), present at the CAS and PAS respectively. Peptides containing these two oxidized tryptophan residues were not detected when the competitive inhibitors, edrophonium and propidium (which should displace MB from the gorge) were present during illumination, in agreement with their efficient protection against the MB-induced photo-inactivation. Thus the bound MB elicited selective action of O-1(2), on the tryptophan residues facing on to the water-filled active-site gorge. The findings of the present study thus demonstrate the localized action and high specificity of MB-sensitized photo-oxidation of TcAChE, as well as the value of this enzyme as a model system for studying the mechanism of action and specificity of photosensitizing agents. C1 [Triquigneaux, Mathilde M.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Roth, Esther; Silman, Israel; Ashani, Yakov] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Weiner, Lev] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel. [Deterding, Leesa J.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Triquigneaux, MM (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. EM triquigneauxm@mail.nih.gov FU NIH (National Institutes of Health), National Institutes of Environmental Health Sciences [ES050139, ES050171] FX This work was supported by the Intramural Research Program of the NIH (National Institutes of Health), National Institutes of Environmental Health Sciences [projects ES050139 and ES050171]. NR 28 TC 6 Z9 6 U1 5 U2 24 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2012 VL 448 BP 83 EP 91 DI 10.1042/BJ20120992 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042HP UT WOS:000311462600009 PM 22888904 ER PT J AU Cunningham, MD Gause, M Cheng, YZ Noyes, A Dorsett, D Kennison, JA Kassis, JA AF Cunningham, Melissa D. Gause, Maria Cheng, Yuzhong Noyes, Amanda Dorsett, Dale Kennison, James A. Kassis, Judith A. TI Wapl antagonizes cohesin binding and promotes Polycomb-group silencing in Drosophila SO DEVELOPMENT LA English DT Article DE Cohesin; Polycomb; Gene expression ID TRITHORAX GROUP PROTEINS; RESPONSE ELEMENTS; ENGRAILED GENE; HOMEOTIC GENE; NIPPED-B; MELANOGASTER; CHROMOSOME; ASSOCIATION; MECHANISMS; REGULATORS AB Wapl protein regulates binding of the cohesin complex to chromosomes during interphase and helps remove cohesin from chromosomes at mitosis. We isolated a dominant mutation in wapl (wapl(AG)) in a screen for mutations that counteract silencing mediated by an engrailed Polycomb-group response element. wapl(AG) hemizygotes die as pharate adults and have an extra sex combs phenotype characteristic of males with mutations in Polycomb-group (PcG) genes. The wapl gene encodes two proteins, a long form and a short form. wapl(AG) introduces a stop codon at amino acid 271 of the long form and produces a truncated protein. The expression of a transgene encoding the truncated Wapl-AG protein causes an extra-sex-comb phenotype similar to that seen in the wapl(AG) mutant. Mutations in the cohesin-associated genes Nipped-B and pds5 suppress and enhance wapl(AG) phenotypes, respectively. A Pds5-Wapl complex (releasin) removes cohesin from DNA, while Nipped-B loads cohesin. This suggests that Wapl-AG might exert its effects through changes in cohesin binding. Consistent with this model, Wapl-AG was found to increase the stability of cohesin binding to polytene chromosomes. Our data suggest that increasing cohesin stability interferes with PcG silencing at genes that are co-regulated by cohesin and PcG proteins. C1 [Cunningham, Melissa D.; Cheng, Yuzhong; Noyes, Amanda; Kennison, James A.; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Gause, Maria; Dorsett, Dale] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM jk14p@nih.gov OI Kassis, Judith/0000-0001-9268-3213; Dorsett, Dale/0000-0002-0507-2762 FU National Institutes of Health (NIH) [R01 GM055683]; National Institute of Child Health and Human Development, NIH FX This research was supported by the National Institutes of Health (NIH) [R01 GM055683 to D. D. and M. G.] and by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH. Deposited in PMC for release after 12 months. NR 31 TC 14 Z9 14 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 15 PY 2012 VL 139 IS 22 BP 4172 EP 4179 DI 10.1242/dev.084566 PG 8 WC Developmental Biology SC Developmental Biology GA 028OZ UT WOS:000310433200010 PM 23034634 ER PT J AU Okamura, D Maeda, I Taniguchi, H Tokitake, Y Ikeda, M Ozato, K Mise, N Abe, K Noce, T Belmonte, JCI Matsui, Y AF Okamura, Daiji Maeda, Ikuma Taniguchi, Hirofumi Tokitake, Yuko Ikeda, Makiko Ozato, Keiko Mise, Nathan Abe, Kuniya Noce, Toshiaki Izpisua Belmonte, Juan Carlos Matsui, Yasuhisa TI Cell cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells SO GENES & DEVELOPMENT LA English DT Article DE primordial germ cell; CDK inhibitor; transcription; P-TEFb; 7SK snRNP; Larp7 ID BROMODOMAIN PROTEIN BRD4; P-TEFB; MOUSE EMBRYOS; ELONGATION; MICE; EXPRESSION; PROGRESSION; REGULATORS; COMPONENT; CHROMATIN AB Transcription elongation is stimulated by positive transcription elongation factor b (P-TEFb), for which activity is repressed in the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. We show here a critical role of 7SK snRNP in growth control of primordial germ cells (PGCs). The expression of p15(INK4b), a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated by P-TEFb and its recruiting molecule, Brd4, when the amount of active P-TEFb is increased due to reduction of the 7SK snRNP, and PGCs consequently undergo growth arrest. These results indicate that CDKI gene-specific control of transcription by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation. C1 [Okamura, Daiji; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Okamura, Daiji; Maeda, Ikuma; Taniguchi, Hirofumi; Tokitake, Yuko; Ikeda, Makiko; Matsui, Yasuhisa] Tohoku Univ, Cell Resource Ctr Biomed Res, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan. [Ozato, Keiko] NICHHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. [Mise, Nathan; Abe, Kuniya] RIKEN, BioResource Ctr, Tsukuba, Ibaraki 3050074, Japan. [Noce, Toshiaki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1130021, Japan. [Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain. RP Belmonte, JCI (reprint author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM belmonte@salk.edu; ymatsui@idac.tohoku.ac.jp RI noce, toshiaki/L-1739-2013 FU Ministry of Education, Culture, Sports, Science, and Technology of Japan FX We are grateful to Dr. Anup Dey for the antibody recognizing Brd4, Dr. Shin-ichiro Chuma for the antibodies recognizing Scp3 and TDRD1, Dr. Shinya Yamanaka for the antibody recognizing Dnmt3L, and Dr. Takeshi Egawa for helpful advice on the experiments. Y.M. was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 34 TC 9 Z9 9 U1 2 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2012 VL 26 IS 22 BP 2477 EP 2482 DI 10.1101/gad.202242.112 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 039VS UT WOS:000311275800005 PM 23154982 ER PT J AU Liu, SY Chow, HM Xu, YS Erkkinen, MG Swett, KE Eagle, MW Rizik-Baer, DA Braun, AR AF Liu, Siyuan Chow, Ho Ming Xu, Yisheng Erkkinen, Michael G. Swett, Katherine E. Eagle, Michael W. Rizik-Baer, Daniel A. Braun, Allen R. TI Neural Correlates of Lyrical Improvisation: An fMRI Study of Freestyle Rap SO SCIENTIFIC REPORTS LA English DT Article ID MEDIAL FRONTAL-CORTEX; PREFRONTAL CORTEX; COGNITIVE CONTROL; MACAQUE MONKEY; MOTOR AREAS; GENERATION; BRAIN; ORGANIZATION; PERFORMANCE; DECISIONS AB The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior. C1 [Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G.; Swett, Katherine E.; Braun, Allen R.] Nat Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Liu, SY (reprint author), Nat Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. EM siyuan.liu@nih.gov RI Liu, Siyuan/D-2227-2012 FU NIH intramural program FX This study was funded by NIH intramural program. The authors thank Steven Wise for critical discussions and comments on the manuscript. We also thank the rap musicians who participated in the study. NR 47 TC 38 Z9 38 U1 4 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 15 PY 2012 VL 2 AR 834 DI 10.1038/srep00834 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040RM UT WOS:000311340600001 PM 23155479 ER PT J AU Portal-Nunez, S Shankavaram, UT Rao, M Datrice, N Atay, S Aparicio, M Camphausen, KA Fernandez-Salguero, PM Chang, H Lin, PP Schrump, DS Garantziotis, S Cuttitta, F Zudaire, E AF Portal-Nunez, Sergio Shankavaram, Uma T. Rao, Mahadev Datrice, Nicole Atay, Scott Aparicio, Marta Camphausen, Kevin A. Fernandez-Salguero, Pedro M. Chang, Han Lin, Pinpin Schrump, David S. Garantziotis, Stavros Cuttitta, Frank Zudaire, Enrique TI Aryl Hydrocarbon Receptor-Induced Adrenomedullin Mediates Cigarette Smoke Carcinogenicity in Humans and Mice SO CANCER RESEARCH LA English DT Article ID POSSIBLE PROMOTION MECHANISM; LUNG-CANCER; AH-RECEPTOR; IN-VIVO; ENDOMETRIAL CANCER; TUMOR ANGIOGENESIS; DIOXIN RECEPTOR; GENE-EXPRESSION; UP-REGULATION; CELL-LINES AB Cigarette smoking (CS) is a leading cause of death worldwide. The aryl hydrocarbon receptor (AHR) is partially responsible for tobacco-induced carcinogenesis although the underlying mechanisms involving early effector genes have yet to be determined. Here, we report that adrenomedullin (ADM) significantly contributes to the carcinogenicity of tobacco-activated AHR. CS and AHR activating ligands induced ADM in vitro and in vivo but not in AHR-deficient fibroblasts and mice. Ectopic transfection of AHR rescued ADM expression in AHR(-/-) fibroblasts whereas AHR blockage with siRNA in wild type cells significantly decreased ADM expression. AHR regulates ADM expression through two intronic xenobiotic response elements located close to the start codon in the ADM gene. Using tissue microarrays we showed that ADM and AHR were coupregulated in lung tumor biopsies from smoker patients. Microarray meta-analysis of 304 independent microarray experiments showed that ADM is elevated in smokers and smokers with cancer. In addition, ADM coassociated with a subset of AHR responsive genes and efficiently differentiated patients with lung cancer from nonsmokers. In a novel preclinical model of CS-induced tumor progression, host exposure to CS extracts significantly elevated tumor ADM although systemic treatment with the ADM antagonist NSC16311 efficiently blocked tobacco-induced tumor growth. In conclusion, ADM significantly contributes the carcinogenic effect of AHR and tobacco combustion products. We suggest that therapeutics targeting the AHR/ADM axis may be of clinical relevance in the treatment of tobacco-induced pulmonary malignancies. Cancer Res; 72(22); 5790-800. (C) 2012 AACR. C1 [Zudaire, Enrique] NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. [Portal-Nunez, Sergio; Aparicio, Marta; Cuttitta, Frank; Zudaire, Enrique] NCI, Angiogenesis Core Facil, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Rao, Mahadev; Datrice, Nicole; Atay, Scott; Schrump, David S.] NCI, Sect Thorac Oncol, Surg Branch, NIH, Bethesda, MD 20892 USA. [Fernandez-Salguero, Pedro M.] Univ Extremadura, Dept Bioquim & Biol Mol, Badajoz, Spain. [Chang, Han] China Med Univ, China Med Univ Hosp, Dept Pathol, Shenyang, Peoples R China. [Chang, Han] China Med Univ, Sch Med, Shenyang, Peoples R China. [Lin, Pinpin] Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, Miaoli, Taiwan. [Garantziotis, Stavros] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Zudaire, E (reprint author), NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, POB B,Bldg 560,1050 Boyles St, Frederick, MD 21702 USA. EM zudairee@mail.nih.gov RI Lin, Pinpin/B-2668-2010; Portal-Nunez, Sergio/L-7391-2014; Cuttitta, Frank/B-4758-2016; Garantziotis, Stavros/A-6903-2009; OI Portal-Nunez, Sergio/0000-0003-0659-1545; Garantziotis, Stavros/0000-0003-4007-375X; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU Intramural NIH HHS [ZIA ES102605-02, ZIA ES102605-03, ZIA ES102605-04, Z99 CA999999, ZIA ES102605-05, ZIA ES102605-06, Z01 ES102605-01, ZIA ES102605-07] NR 51 TC 17 Z9 17 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5790 EP 5800 DI 10.1158/0008-5472.CAN-12-0818 PG 11 WC Oncology SC Oncology GA 037YB UT WOS:000311141300016 PM 22993405 ER PT J AU Wan, XL Yeung, C Kim, SY Dolan, JG Ngo, VN Burkett, S Khan, J Staudt, LM Helman, LJ AF Wan, Xiaolin Yeung, Choh Kim, Su Young Dolan, Joseph G. Ngo, Vu N. Burkett, Sandra Khan, Javed Staudt, Louis M. Helman, Lee J. TI Identification of FoxM1/Bub1b Signaling Pathway as a Required Component for Growth and Survival of Rhabdomyosarcoma SO CANCER RESEARCH LA English DT Article ID PREMATURE CHROMATID SEPARATION; ONCOGENIC TRANSCRIPTION FACTOR; MOSAIC VARIEGATED ANEUPLOIDY; MITOTIC-SPINDLE CHECKPOINT; BUBR1 INSUFFICIENCY; CANCER; CELLS; ENDOREDUPLICATION; INSTABILITY; PROTEIN AB We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen. Knockdown of Bub1b resulted in suppression of tumor growth in vivo, including the regression of established tumors. The mechanism by which this occurs is via postmitotic endoreduplication checkpoint and mitotic catastrophe. Furthermore, using a chromatin immunoprecipitation assay, we found that Bub1b is a direct transcriptional target of Forkhead Box M1 (FoxM1). Suppression of FoxM1 either by shRNA or the inhibitor siomycin A resulted in reduction of Bub1b expression and inhibition of cell growth and survival. These results show the important role of the Bub1b/FoxM1 pathway in RMS and provide potential therapeutic targets. Cancer Res; 72(22); 5889-99. (C) 2012 AACR. C1 [Wan, Xiaolin; Helman, Lee J.] NCI, Mol Oncol Sect, Pediat Oncol Branch, CCR,CRC,NIH, Bethesda, MD 20892 USA. [Burkett, Sandra] NCI, Oncogen Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ngo, Vu N.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Khan, Javed] NCI, Comparat Mol Cytogenet Core Facil, NIH, Bethesda, MD 20892 USA. RP Wan, XL (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, CCR,CRC,NIH, 1-3860,10 Ctr Dr, Bethesda, MD 20892 USA. EM xiaolinw@mail.nih.gov; helmanl@nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU Intramural NIH HHS [Z99 CA999999] NR 44 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5889 EP 5899 DI 10.1158/0008-5472.CAN-12-1991 PG 11 WC Oncology SC Oncology GA 037YB UT WOS:000311141300025 PM 23002205 ER PT J AU Qian, XL Durkin, ME Wang, DR Tripathi, BK Olson, L Yang, XY Vass, WC Popescu, NC Lowy, DR AF Qian, Xiaolan Durkin, Marian E. Wang, Dunrui Tripathi, Brajendra K. Olson, Lyra Yang, Xu-Yu Vass, William C. Popescu, Nicholas C. Lowy, Douglas R. TI Inactivation of the Dlc1 Gene Cooperates with Downregulation of p15(INK4b) and p16(Ink4a), Leading to Neoplastic Transformation and Poor Prognosis in Human Cancer SO CANCER RESEARCH LA English DT Article ID GTPASE-ACTIVATING PROTEIN; TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; EMBRYONIC-DEVELOPMENT; RAS TRANSFORMATION; CELL CARCINOMA; SH2 DOMAIN; RHO; IDENTIFICATION; METASTASIS AB The tumor suppressor gene deleted in liver cancer-1 (DLC1), which encodes a protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc42GAP activity, is inactivated in various human malignancies. Following Dlc1 inactivation, mouse embryo fibroblasts (MEF) with a conditional Dlc1 knockout allele reproducibly underwent neoplastic transformation. In addition to inactivation of Dlc1 and increased activity of Rho and Cdc42, transformation depended on the subsequent decreased expression of the Cdk4/6 inhibitors p15(Ink4b) and p16(Ink4a) together with increased expression and activation of Cdk4/6. The level of expression of these cell-cycle regulatory genes was relevant to human tumors with low DLC1 expression. Analysis of publicly available annotated datasets of lung and colon cancer with gene expression microarray profiles indicated that, in pairwise comparisons, low DLC1 expression occurred frequently together (P < 0.01) with downregulation of p15(Ink4b) or p16(Ink4a) or upregulation of CDK4 or CDK6. In addition, an unfavorable prognosis (P < 0.05) was associated with low DLC1 and low p15(Ink4b) in lung cancer and colon cancer, low DLC1 and low p16(Ink4a) in lung cancer, low DLC1 and high CDK4 in lung cancer, and low DLC1 and high CDK6 in colon cancer. Thus, several genes and biochemical activities collaborate with the inactivation of DLC1 to give rise to cell transformation in MEFs, and the identified genes are relevant to human tumors with low DLC1 expression. Cancer Res; 72(22); 5900-11. (C) 2012 AACR. C1 [Qian, Xiaolan; Tripathi, Brajendra K.; Olson, Lyra; Vass, William C.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Durkin, Marian E.; Yang, Xu-Yu; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wang, Dunrui] W2MOTIF LLC, San Diego, CA USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Room 4106, Bethesda, MD 20892 USA. EM Lowyd@mail.nih.gov FU Intramural Research Program, NIH, National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program, NIH, National Cancer Institute, and Center for Cancer Research. NR 36 TC 12 Z9 14 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5900 EP 5911 DI 10.1158/0008-5472.CAN-12-2368 PG 12 WC Oncology SC Oncology GA 037YB UT WOS:000311141300026 PM 23010077 ER PT J AU Weaver, Z Difilippantonio, S Carretero, J Martin, PL El Meskini, R Iacovelli, AJ Gumprecht, M Kulaga, A Guerin, T Schlomer, J Baran, M Kozlov, S McCann, T Mena, S Al-Shahrour, F Alexander, D Wong, KK Van Dyke, T AF Weaver, Zoe Difilippantonio, Simone Carretero, Julian Martin, Philip L. El Meskini, Rajaa Iacovelli, Anthony J. Gumprecht, Michelle Kulaga, Alan Guerin, Theresa Schlomer, Jerome Baran, Maureen Kozlov, Serguei McCann, Thomas Mena, Salvador Al-Shahrour, Fatima Alexander, Danny Wong, Kwok-Kin Van Dyke, Terry TI Temporal Molecular and Biological Assessment of an Erlotinib-Resistant Lung Adenocarcinoma Model Reveals Markers of Tumor Progression and Treatment Response SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; CELL-GROWTH; THERAPY; PERTURBATION; GLUTATHIONE; DISCOVERY; ONCOGENES; GLUTAMINE; PLASMA; MTOR AB Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared with quantitative imaging and histopathology at several time points during tumor progression and treatment. Responses to single-drug treatments were temporary, whereas combination therapy elicited a sustained response. During tumor development, metabolomic signatures indicated a shift to high anabolic activity and suppression of antitumor programs with 11 metabolites consistently present in both lung tissue and blood. Combination drug treatment reversed many of the molecular changes found in tumored lung. Data integration linking cancer signaling networks with metabolic activity identified key pathways such as glutamine and glutathione metabolism that signified response to single or dual treatments. Results from combination drug treatment suggest that metabolic transcriptional control through C-MYC and SREBP, as well as ELK1, NRF1, and NRF2, depends on both EGFR and mTORC1 signaling. Our findings establish the importance of kinetic therapeutic studies in preclinical assessment and provide in vivo evidence that TKI-mediated antiproliferative effects also manifest in specific metabolic regulation. Cancer Res; 72(22); 5921-33. (C) 2012 AACR. C1 [Van Dyke, Terry] NCI, Mouse Canc Genet Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Weaver, Zoe; Difilippantonio, Simone; Martin, Philip L.; El Meskini, Rajaa; Iacovelli, Anthony J.; Gumprecht, Michelle; Kulaga, Alan; Guerin, Theresa; Schlomer, Jerome; Baran, Maureen; Kozlov, Serguei; Van Dyke, Terry] SAIC Frederick Inc, Ctr Adv Preclin Res, Frederick Natl Lab Canc Res, NCI, Frederick, MD USA. [Carretero, Julian; Wong, Kwok-Kin] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med,Dept Med, Boston, MA 02115 USA. [Al-Shahrour, Fatima] Harvard Univ, Brigham & Womens Hosp, Div Hematol, Sch Med,Dept Med, Boston, MA 02115 USA. [Carretero, Julian; Wong, Kwok-Kin] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA USA. [Mena, Salvador] Univ Valencia, Dept Physiol, E-46100 Burjassot, Spain. [McCann, Thomas] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Al-Shahrour, Fatima] Broad Inst MIT & Harvard, Cambridge, MA USA. [Alexander, Danny] Metabolon Inc, Durham, NC USA. RP Van Dyke, T (reprint author), NCI, Mouse Canc Genet Program, Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD 21702 USA. EM vandyket@mail.nih.gov RI Mena, Salvador/L-8780-2014; Carretero, Julian/N-5214-2014; Mena, Salvador/F-6696-2016; OI Mena, Salvador/0000-0002-6423-4741; Carretero, Julian/0000-0001-7269-8506; wong, kwok kin/0000-0001-6323-235X FU National Cancer Institute, Intramural Research Program, NIH FX This research was supported with federal funds from the National Cancer Institute, Intramural Research Program, NIH. NR 35 TC 16 Z9 16 U1 1 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5921 EP 5933 DI 10.1158/0008-5472.CAN-12-0736 PG 13 WC Oncology SC Oncology GA 037YB UT WOS:000311141300028 PM 22969147 ER PT J AU Pouliot, LM Chen, YC Bai, J Guha, R Martin, SE Gottesman, MM Hall, MD AF Pouliot, Lynn M. Chen, Yu-Chi Bai, Jennifer Guha, Rajarshi Martin, Scott E. Gottesman, Michael M. Hall, Matthew D. TI Cisplatin Sensitivity Mediated by WEE1 and CHK1 Is Mediated by miR-155 and the miR-15 Family SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; RESISTANT CELL-LINES; CANCER-CELLS; MULTIDRUG-RESISTANCE; CHECKPOINT KINASE-1; REDUCED EXPRESSION; BINDING-PROTEINS; DRUG-RESISTANCE; TARGETING BCL2; OVARIAN-CANCER AB Resistance to platinum-based therapies arises by multiple mechanisms, including by alterations to cell-cycle kinases that mediate G(2)-M phase arrest. In this study, we conducted parallel high-throughput screens for microRNAs (miRNA) that could restore sensitivity to cisplatin-resistant cells, and we screened for kinases targeted by miRNAs that mediated cisplatin resistance. Overexpression of the cell-cycle kinases WEE1 and CHK1 occurred commonly in cisplatin-resistant cells. miRNAs in the miR-15/16/195/424/497 family were found to sensitize cisplatin-resistant cells to apoptosis by targeting WEE1 and CHK1. Loss-of-function and gain-of-function studies showed that miR-15 family members controlled the expression of WEE1 and CHK1. Supporting these results, we found that in the presence of cisplatin altering expression of miR-16 or related genes altered cell cycle distribution. Our findings reveal critical regulation of miRNAs and their cell-cycle-associated kinase targets in mediating resistance to cisplatin. Cancer Res; 72(22); 5945-55. (C) 2012 AACR. C1 [Pouliot, Lynn M.; Bai, Jennifer; Gottesman, Michael M.; Hall, Matthew D.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Pouliot, Lynn M.] Georgetown Univ, Dept Microbiol & Immunol, Washington, DC USA. [Chen, Yu-Chi; Guha, Rajarshi; Martin, Scott E.] NIH, RNAi Screening Facil, Natl Ctr Adv Translat Sci, Rockville, MD USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 2108, Bethesda, MD 20892 USA. EM gottesmm@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 43 TC 44 Z9 51 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5945 EP 5955 DI 10.1158/0008-5472.CAN-12-1400 PG 11 WC Oncology SC Oncology GA 037YB UT WOS:000311141300030 PM 22942255 ER PT J AU Chow, HY Jubb, AM Koch, JN Jaffer, ZM Stepanova, D Campbell, DA Duron, SG O'Farrell, M Cai, KQ Klein-Szanto, AJP Gutkind, JS Hoeflich, KP Chernoff, J AF Chow, Hoi Yee Jubb, Adrian M. Koch, Jennifer N. Jaffer, Zahara M. Stepanova, Dina Campbell, David A. Duron, Sergio G. O'Farrell, Marie Cai, Kathy Q. Klein-Szanto, Andres J. P. Gutkind, J. Silvio Hoeflich, Klaus P. Chernoff, Jonathan TI p21-Activated Kinase 1 Is Required for Efficient Tumor Formation and Progression in a Ras-Mediated Skin Cancer Model SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; MEK INHIBITOR PD0325901; PAK PROTEIN-KINASES; CONDITIONAL EXPRESSION; BREAST-CANCER; PD 0325901; IN-VITRO; K-RAS; GROWTH; MUTATIONS AB The RAS genes are the most commonly mutated oncogenes in human cancer and present a particular therapeutic dilemma, as direct targeting of Ras proteins by small molecules has proved difficult. Signaling pathways downstream of Ras, in particular Raf/Mek/Erk and PI3K/Akt/mTOR, are dominated by lipid and protein kinases that provide attractive alternate targets in Ras-driven tumors. As p21-activated kinase 1 (Pak1) has been shown to regulate both these signaling pathways and is itself upregulated in many human cancers, we assessed the role of Pak1 in Ras-driven skin cancer. In human squamous cell carcinoma (SCC), we found a strong positive correlation between advanced stage and grade and PAK1 expression. Using a mouse model of Kras-driven SCC, we showed that deletion of the mouse Pak1 gene led to markedly decreased tumorigenesis and progression, accompanied by near total loss of Erk and Akt activity. Treatment of Kras(G12D) mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity. Tumor regression was also seen in mice treated with a specific Mek inhibitor, but not with an Akt inhibitor. These findings establish Pak1 as a new target in KRAS-driven tumors and suggest a mechanism of action through the Erk, but not the Akt, signaling pathway. Cancer Res; 72(22); 5966-75. (C) 2012 AACR. C1 [Chow, Hoi Yee; Koch, Jennifer N.; Jaffer, Zahara M.; Stepanova, Dina; Cai, Kathy Q.; Klein-Szanto, Andres J. P.; Chernoff, Jonathan] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. [Jubb, Adrian M.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England. [Hoeflich, Klaus P.] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA. [Campbell, David A.; Duron, Sergio G.; O'Farrell, Marie] Afraxis, La Jolla, CA USA. [Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Chernoff, J (reprint author), Fox Chase Canc Ctr, Canc Biol Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Jonathan.Chernoff@fccc.edu RI Chernoff, Jonathan/I-7631-2014 OI Chernoff, Jonathan/0000-0002-4803-7836 FU NIH [R01 CA142928, R01 CA117884]; Fox Chase Cancer Center [P30 CA006927]; state of Pennsylvania FX This work was supported by grants from the NIH to J. Chernoff (R01 CA142928 and R01 CA117884) and to the Fox Chase Cancer Center (P30 CA006927), as well as by an appropriation from the state of Pennsylvania. NR 43 TC 52 Z9 53 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 5966 EP 5975 DI 10.1158/0008-5472.CAN-12-2246 PG 10 WC Oncology SC Oncology GA 037YB UT WOS:000311141300032 PM 22983922 ER PT J AU Kim, HS Woolard, K Lai, C Bauer, PO Maric, D Song, H Li, AG Kotliarova, S Zhang, W Fine, HA AF Kim, Hong Sug Woolard, Kevin Lai, Chen Bauer, Peter O. Maric, Dragan Song, Hua Li, Aiguo Kotliarova, Svetlana Zhang, Wei Fine, Howard A. TI Gliomagenesis Arising from Pten- and Ink4a/Arf-Deficient Neural Progenitor Cells Is Mediated by the p53-Fbxw7/Cdc4 Pathway, Which Controls c-Myc SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; CANCER STEM-CELLS; MALIGNANT ASTROCYTOMA; INITIATING CELLS; IN-VIVO; DIFFERENTIATION; GLIOBLASTOMA; GLIOMA; PROLIFERATION; PROTEIN AB Glioblastoma multiforme is the most common type of primary malignant brain tumor and may arise from a cell with neural stem-like properties. Deregulation of the retinoblastoma, phosphoinositide-3 kinase (PI3K), and p53 pathways are molecular hallmarks of this disease. Recent work has shown that p53(-/-)Pten(-/-) mice form gliomas in a c-Myc-dependent manner. To explore the role of the INK4A/ARF locus and Pten deletions in gliomagenesis, we generated Pten(-/-)Ink4a/Arf(-/-) mouse neural stem cells (mNSC) and such cells were highly proliferative, self-renewing, relatively refractory to differentiation, and induced both low-and high-grade glioma formation in vivo. In contrast to p53(-/-)Pten(-/-) mNSCs, however, Pten(-/-)Ink4a/Arf(-/-) mNSCs do not express appreciable levels of c-Myc in vitro, although glioma stem cells derived from thesecells did. Sequencing of Pten(-/-)Ink4a/Arf(-/-) mNSC-derived tumors revealed spontaneous mutations in Tp53 in vivo with subsequent downregulation of Fbxw7. Expression of p53 mutants in Pten(-/-)Ink4a/Arf(-/-) mNSC or knockdown of Fbxw7 resulted in reexpression of c-Myc with enhanced Pten(-/-)Ink4a/Arf(-/-) mNSC tumorigenecity. We propose that p53 mutations contribute to gliomagenesis by both allowing the overexpression of c-Myc through downregulation of Fbxw7 and by protecting against c-Myc-induced apoptosis. Cancer Res; 72(22); 6065-75. (C) 2012 AACR. C1 [Kim, Hong Sug; Woolard, Kevin; Lai, Chen; Bauer, Peter O.; Maric, Dragan; Song, Hua; Li, Aiguo; Kotliarova, Svetlana; Zhang, Wei; Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NCI, NIH, Bethesda, MD USA. RP Fine, HA (reprint author), NYU, Langone Med Ctr, 522 1st Ave,Smilow 1101, New York, NY 10016 USA. EM Howard.Fine@nyumc.org FU Intramural Research Program of the NIH, National Cancer Institute; Center for Cancer Research FX This research was supported by grants from the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research. NR 35 TC 13 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2012 VL 72 IS 22 BP 6065 EP 6075 DI 10.1158/0008-5472.CAN-12-2594 PG 11 WC Oncology SC Oncology GA 037YB UT WOS:000311141300040 PM 22986743 ER PT J AU Popuri, V Croteau, DL Brosh, RM Bohr, VA AF Popuri, Venkateswarlu Croteau, Deborah L. Brosh, Robert M., Jr. Bohr, Vilhelm A. TI RECQ1 is required for cellular resistance to replication stress and catalyzes strand exchange on stalled replication fork structures SO CELL CYCLE LA English DT Article DE strand exchange; RecQ helicases; DNA replication; chromosomal condensation; RECQ1; RPA phosphorylation ID INTERSTRAND CROSS-LINKS; DNA-REPLICATION; SUBSTRATE-SPECIFICITY; ANNEALING ACTIVITIES; HOLLIDAY JUNCTIONS; HELICASE ACTIVITY; ESCHERICHIA-COLI; BRANCH MIGRATION; HUMAN RECQ5-BETA; PROTEIN AB RECQ1 is the most abundant of the five human RecQ helicases, but little is known about its biological significance. Recent studies indicate that RECQ1 is associated with origins of replication, suggesting a possible role in DNA replication. However, the functional role of RECQ1 at damaged or stalled replication forks is still unknown. Here, for the first time, we show that RECQ1 promotes strand exchange on synthetic stalled replication fork-mimicking structures and comparatively analyze RECQ1 with the other human RecQ helicases. RECQ1 actively unwinds the leading strand of the fork, similar to WRN, while RECQ4 and RECQ5 beta can only unwind the lagging strand of the replication fork. Human replication protein A modulates the strand exchange activity of RECQ1 and shifts the equilibrium more to the unwinding mode, an effect also observed for WRN. Stable depletion of RECQ1 affects cell proliferation and renders human cells sensitive to various DNA damaging agents that directly or indirectly block DNA replication fork progression. Consequently, loss of RECQ1 activates DNA damage response signaling, leads to hyper-phosphorylation of RPA32 and activation of CHK1, indicating replication stress. Furthermore, depletion of RECQ1 leads to chromosomal condensation defects and accumulation of undercondensed chromosomes. Collectively, our observations provide a new insight into the role of RECQ1 in replication fork stabilization and its role in the DNA damage response to maintain genomic stability. C1 [Popuri, Venkateswarlu; Croteau, Deborah L.; Brosh, Robert M., Jr.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural Research Program of the National Institute on Aging, NIH [AG000726-20] FX We thank Drs. Chandrika Cangovi and Takashi Tadokoro for critical reading of the manuscript. We thank Dr. Mahesh Ramamoorthy for his technical expertise in the preparation of lentivirus. We thank Dr. Sommers Joshua for the expression and purification of recombinant RECQ1. This work was supported by funds from the Intramural Research Program of the National Institute on Aging, NIH, AG000726-20. NR 61 TC 18 Z9 18 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2012 VL 11 IS 22 BP 4252 EP 4265 DI 10.4161/cc.22581 PG 14 WC Cell Biology SC Cell Biology GA 038FT UT WOS:000311161300027 PM 23095637 ER PT J AU Braunschweig, D Golub, MS Koenig, CM Qi, LH Pessah, IN Van de Water, J Berman, RF AF Braunschweig, Daniel Golub, Mari S. Koenig, Claire M. Qi, Lihong Pessah, Isaac N. Van de Water, Judy Berman, Robert F. TI Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Autism; Maternal antibodies; Passive transfer; Immune; Mouse behavior ID FETAL-BRAIN; MICE; DISORDERS; CHILDREN; BEHAVIOR; MOTHERS; SYSTEM; IMPAIRMENT; TRANSPORT; LUPUS AB A murine passive transfer model system was employed to ascertain the effects of gestational exposure to a single, intravenous dose of purified, brain-reactive IgG antibodies from individual mothers of children with autism (MAU) or mothers with typically developing children (MTD). Growth and behavioral outcomes in offspring were measured from postnatal days 8 to 65 in each group. Comparisons revealed alterations in early growth trajectories, significantly impaired motor and sensory development, and increased anxiety. This report demonstrates for the first time the effects of a single, low dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development. Published by Elsevier BM. C1 [Braunschweig, Daniel; Pessah, Isaac N.; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Braunschweig, Daniel; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Braunschweig, Daniel; Koenig, Claire M.; Qi, Lihong; Pessah, Isaac N.; Van de Water, Judy; Berman, Robert F.] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA. [Qi, Lihong] Univ Calif Davis, Sch Med, Div Biostat, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Golub, Mari S.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. [Pessah, Isaac N.] Univ Calif Davis, Dept Vet Mol Biosci, Davis, CA 95616 USA. [Koenig, Claire M.; Berman, Robert F.] Univ Calif Davis, Sch Med, Dept Neurol Surg, Davis, CA 95616 USA. RP Braunschweig, D (reprint author), Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. EM dnau@ucdavis.edu FU NIEHS [1P01ES11269-0]; U.S. EPA [R829388]; Autism Speaks; JB Johnson Foundation FX This work was supported in part by NIEHS 1P01ES11269-0 and U.S. EPA Grant R829388, a Targeted Research Grant from Autism Speaks and an unrestricted research grant from the JB Johnson Foundation. NR 36 TC 23 Z9 23 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV 15 PY 2012 VL 252 IS 1-2 BP 56 EP 65 DI 10.1016/j.jneuroim.2012.08.002 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 037UR UT WOS:000311132500007 PM 22951357 ER PT J AU Kucka, M Pogrmic-Majkic, K Fa, S Stojilkovic, SS Kovacevic, R AF Kucka, Marek Pogrmic-Majkic, Kristina Fa, Svetlana Stojilkovic, Stanko S. Kovacevic, Radmila TI Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Endocrine disrupters; Atrazine; Pituitary cells; Leydig cells; cAMP-specific phosphodiesterases ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; LEYDIG-CELL STEROIDOGENESIS; PERIPUBERTAL MALE RATS; ESTROGEN-RECEPTOR; IN-VITRO; AROMATASE EXPRESSION; PROLACTIN-RELEASE; GENE-EXPRESSION; EXPOSURE; LACTOTROPHS AB Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of CAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on CAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. (C) 2012 Elsevier Inc. All rights reserved. C1 [Pogrmic-Majkic, Kristina; Fa, Svetlana; Kovacevic, Radmila] Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Lab Ecotoxicol, Novi Sad 21000, Serbia. [Kucka, Marek; Stojilkovic, Stanko S.] NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD USA. RP Kovacevic, R (reprint author), Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Lab Ecotoxicol, Dositej Obradov Sq 2, Novi Sad 21000, Serbia. EM radmila.kovacevic@dbe.uns.ac.rs FU Ministry of Science, Republic of Serbia [173037]; Eunce Kennedy Shiver National Institute of Health and Human Development Intramural Grant FX We are grateful to Dr. G. D. Niswender for the supply of testosterone antiserum. This work is supported by the Ministry of Science, Republic of Serbia (grant no. 173037), and a Eunce Kennedy Shiver National Institute of Health and Human Development Intramural Grant. NR 38 TC 26 Z9 27 U1 5 U2 39 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2012 VL 265 IS 1 BP 19 EP 26 DI 10.1016/j.taap.2012.09.019 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 037WD UT WOS:000311136300003 PM 23022511 ER PT J AU Chouker, A Ohta, A Martignoni, A Lukashev, D Zacharia, LC Jackson, EK Schnermann, J Ward, JM Kaufmann, I Klaunberg, B Sitkovsky, MV Thiel, M AF Chouker, Alexander Ohta, Akio Martignoni, Andre Lukashev, Dmitriy Zacharia, Lefteris C. Jackson, Edwin K. Schnermann, Juergen Ward, Jerrold M. Kaufmann, Ines Klaunberg, Brenda Sitkovsky, Michail V. Thiel, Manfred TI In Vivo Hypoxic Preconditioning Protects From Warm Liver Ischemia-Reperfusion Injury Through the Adenosine A2B Receptor SO TRANSPLANTATION LA English DT Article DE Hypoxia; Murine liver ischemia; Preconditioning; Hepatoprotection ID ADENYLATE ENERGY-CHARGE; ISCHEMIA/REPERFUSION INJURY; CYTOSOL 5'-NUCLEOTIDASE; A(2A) RECEPTORS; PATHWAY; A(1); TRANSPLANTATION; INFLAMMATION; ANTAGONIST; ACTIVATION AB Background. Liver ischemia-reperfusion injury (IRI) is a known risk factor for the postoperative outcome of patients undergoing liver surgery/transplantation. Attempts to protect from organ damage require multidisciplinary strategies and are of emerging interest in view of patients with higher age and American Society of Anesthesiology status. Ischemic preconditioning has been successfully applied to prevent from IRI during liver resection/transplantation. Because even short periods of ischemia during preconditioning inevitably lead to hypoxia and formation of anti-inflammatory/cytoprotective acting adenosine, we reasoned that short nonischemic hypoxia also protects against hepatic IRI. Methods. Mice underwent hypoxic preconditioning (HPC) by breathing 10% oxygen for 10 min followed by 10 min of 21% oxygen before left liver lobe ischemia (45 min) and reperfusion (4 hr). The interactions of hypoxia -> adenosine -> adenosine receptors were tested by pharmacologic antagonism at adenosine receptor (AR) sites in wild-type mice and in mice with genetic deletions at the A1, A2A, A2B, and A3 ARs. Hepatocellular damage, inflammation, and metabolic effects were quantified by enzyme activities, cytokines, liver myeloperoxidase, blood adenosine, and tissue AMP, respectively. Results. Hepatoprotection by HPC was significant in wild-type and A1, A2A, and A3 AR knockout mice as quantified by lower alanine aminotransferase serum activities, cytokine levels, histologic damage scores, tissue myeloperoxidase concentrations, and preserved AMP concentrations. Protection by HPC was blunted in mice pretreated with the A2B AR antagonist MRS1754 or in A2B AR knockout mice. Conclusions. Because liver protective effects of HPC are negated when the A2B receptor is nonfunctional, the hypoxia -> adenosine -> A2B receptor pathway plays a critical role in the prevention of warm IRI in vivo. Hypoxic activation of this pathway warrants use of selective A2B AR agonists or even intermittent hypoxia (e. g., in deceased organ donors) to protect from liver IRI. C1 [Chouker, Alexander; Martignoni, Andre; Kaufmann, Ines] Univ Munich, Dept Anesthesiol, D-81377 Munich, Germany. [Chouker, Alexander; Ohta, Akio; Lukashev, Dmitriy; Ward, Jerrold M.; Sitkovsky, Michail V.] NIAID, NIH, Bethesda, MD 20892 USA. [Ohta, Akio; Lukashev, Dmitriy; Sitkovsky, Michail V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst Conso, Boston, MA 02115 USA. [Zacharia, Lefteris C.] Ctr Res & Technol Thessaly, Dept Biomed Res & Technol, Larisa, Greece. [Jackson, Edwin K.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Schnermann, Juergen] NIDDKD, NIH, Bethesda, MD 20892 USA. [Klaunberg, Brenda] NINDS, MIF, NIH, Bethesda, MD 20892 USA. [Thiel, Manfred] Univ Heidelberg, Dept Anaesthesiol & Intens Care, Med Fac Mannheim, D-6800 Mannheim, Germany. RP Chouker, A (reprint author), Univ Munich, Dept Anesthesiol, Marchioninistr 15, D-81377 Munich, Germany. EM achouker@med.uni-muenchen.de OI Zacharia, Lefteris/0000-0002-0327-2373 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; John E. Fogarty research grant; Department of Anesthesiology of the LMU-Munich; National Institutes of Health [DK079307, HL109002, DK068575] FX This research work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, John E. Fogarty research grant (awarded to A.C.); Department of Anesthesiology of the LMU-Munich; and National Institutes of Health grants DK079307, HL109002, and DK068575 (awarded to E.K.J.). NR 46 TC 16 Z9 17 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2012 VL 94 IS 9 BP 894 EP 902 DI 10.1097/TP.0b013e31826a9a46 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 033JN UT WOS:000310791500005 PM 23073466 ER PT J AU Sam, WJ Chamberlain, CE Lee, SJ Goldstein, JA Hale, DA Mannon, RB Kirk, AD Hon, YY AF Sam, Wai-Johnn Chamberlain, Christine E. Lee, Su-Jun Goldstein, Joyce A. Hale, Douglas A. Mannon, Roslyn B. Kirk, Allan D. Hon, Yuen Yi TI Associations of ABCB1 and IL-10 Genetic Polymorphisms With Sirolimus-Induced Dyslipidemia in Renal Transplant Recipients SO TRANSPLANTATION LA English DT Article DE Sirolimus; ABCB1; Total and LDL cholesterol; Triglyceride; Pharmacogenetics ID RESISTANCE P-GLYCOPROTEINS; APOLIPOPROTEIN-E GENOTYPES; CORONARY-HEART-DISEASE; FRAMINGHAM RISK SCORE; IMMUNOSUPPRESSIVE REGIMENS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; COMMON VARIANTS; ATORVASTATIN; HYPERLIPIDEMIA AB Background. Hyperlipidemia is a common adverse effect of sirolimus (SRL). We previously showed significant associations of ABCB1 3435C>T and IL-10 -1082G>A with log-transformed SRL dose-adjusted weighted-normalized trough. We further examined to see whether these polymorphisms were also associated with SRL-induced dyslipidemia. Methods. Genotyping was performed for ABCB1 1236C>T, 2677 G>T/A, and 3435C>T; CYP3A4 -392A>G; CYP3A5 6986A>G and 14690G>A; IL-10 -1082G>A; TNF -308G>A; and ApoE epsilon 2, epsilon 3, and epsilon 4 alleles. The longitudinal changes of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels after SRL treatment before statin therapy were analyzed by a linear mixed-effects model, with adjustments for selected covariates for each lipid. Results. Under the dominant genetic model, ABCB1 3435C>T was associated with TC (P=0.0001) and LDL-C (P<0.0001) values after SRL administration. Mean TC and LDL-C levels were 26.9 and 24.9 mg/dL higher, respectively, in ABCB1 3435T carriers than 3435CC homozygotes at an average SRL trough concentration of 4 ng/mL without concomitant medication. ABCB1 1236C>T under the recessive model and IL-10 -1082G>A under the dominant model were associated with log-transformed TG values (P=0.0051 and 0.0436, respectively). Mean TG value was 25.1% higher in ABCB1 1236TT homozygotes compared with ABCB1 1236C carriers and was 12.4% higher in IL-10 -1082AA homozygotes than -1082G carriers. Conclusions. ABCB1 polymorphisms were found to be associated with lipid responses to SRL treatment, confirming the role of ABCB1 gene in SRL pharmacokinetics and pharmacodynamics. Further studies are necessary to define the role of ABCB1 and IL-10 polymorphisms on SRL-induced dyslipidemia in renal transplantation. C1 [Sam, Wai-Johnn; Chamberlain, Christine E.; Hon, Yuen Yi] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Lee, Su-Jun; Goldstein, Joyce A.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Res Triangle Pk, NC USA. [Hale, Douglas A.; Mannon, Roslyn B.; Kirk, Allan D.] NIDDKD, Transplantat Branch, Bethesda, MD 20892 USA. [Lee, Su-Jun] Inje Univ, Dept Pharmacol, Coll Med, Pusan, South Korea. [Hale, Douglas A.] Vanderbilt Univ, Div Kidney Pancreas Transplantat, Nashville, TN USA. [Mannon, Roslyn B.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Kirk, Allan D.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Kirk, Allan D.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. RP Hon, YY (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Rm 1C240,10 Ctr Dr, Bethesda, MD 20892 USA. EM chon@cc.nih.gov FU National Institutes of Health Clinical Center Pharmacy Department, National Institute of Diabetes and Digestive and Kidney Diseases Transplantation Branch; National Institute of Environmental Health Sciences [Z01ES02124] FX This work was supported by the Intramural Research Program of the National Institutes of Health Clinical Center Pharmacy Department, National Institute of Diabetes and Digestive and Kidney Diseases Transplantation Branch, and National Institute of Environmental Health Sciences (Z01ES02124). There was no commercial sponsorship. NR 48 TC 2 Z9 4 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2012 VL 94 IS 9 BP 971 EP 977 DI 10.1097/TP.0b013e31826b55e2 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 033JN UT WOS:000310791500016 PM 23073467 ER PT J AU Yang, G Shu, XO Chow, WH Zhang, XL Li, HL Ji, BT Cai, H Wu, SH Gao, YT Zheng, W AF Yang, Gong Shu, Xiao Ou Chow, Wong-Ho Zhang, Xianglan Li, Hong-Lan Ji, Bu-Tian Cai, Hui Wu, Shenghui Gao, Yu-Tang Zheng, Wei TI Soy Food Intake and Risk of Lung Cancer: Evidence From the Shanghai Womens Health Study and a Meta-Analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE cohort studies; lung neoplasms; meta-analysis; risk; soy foods; women ID ESTROGEN-RECEPTOR-BETA; BREAST-CANCER; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT; ISOFLAVONE INTAKE; NORTHEAST CHINA; IN-VITRO; CELLS; GENISTEIN; MECHANISMS AB The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Womens Health Study (Shanghai, China) in 19972000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (P-trend 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95 confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (P-interaction 0.01) and for aggressive lung cancer as defined by length of survival (12 months vs. epsilon 12 months; P-heterogeneity 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95 confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens. C1 [Yang, Gong; Shu, Xiao Ou; Zhang, Xianglan; Cai, Hui; Wu, Shenghui; Zheng, Wei] Vanderbilt Univ, Div Epidemiol, Dept Med, Sch Med, Nashville, TN 37203 USA. [Yang, Gong; Shu, Xiao Ou; Zhang, Xianglan; Cai, Hui; Wu, Shenghui; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Med Ctr, Nashville, TN 37203 USA. [Chow, Wong-Ho; Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Yang, G (reprint author), Vanderbilt Univ, Div Epidemiol, Dept Med, Sch Med, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA. EM gong.yang@vanderbilt.edu FU US National Cancer Institute, National Institutes of Health [R37CA070867, RFP N02 CP1101066] FX This work was supported by the US National Cancer Institute, National Institutes of Health (grants R37CA070867 to W. Z. and RFP N02 CP1101066 to X. O. S.). NR 54 TC 10 Z9 12 U1 0 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2012 VL 176 IS 10 BP 846 EP 855 DI 10.1093/aje/kws168 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 034SH UT WOS:000310892700002 PM 23097255 ER PT J AU Schmader, KE Oxman, MN Levin, MJ Johnson, G Zhang, JH Betts, R Morrison, VA Gelb, L Guatelli, JC Harbecke, R Pachucki, C Keay, S Menzies, B Griffin, MR Kauffman, C Marques, A Toney, J Keller, PM Li, X Chan, ISF Annunziato, P AF Schmader, K. E. Oxman, M. N. Levin, M. J. Johnson, G. Zhang, J. H. Betts, R. Morrison, V. A. Gelb, L. Guatelli, J. C. Harbecke, R. Pachucki, C. Keay, S. Menzies, B. Griffin, M. R. Kauffman, C. Marques, A. Toney, J. Keller, P. M. Li, X. Chan, I. S. F. Annunziato, P. CA Shingles Prevention Study Grp TI Persistence of the Efficacy of Zoster Vaccine in the Shingles Prevention Study and the Short-Term Persistence Substudy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HERPES-ZOSTER; POSTHERPETIC NEURALGIA; OLDER-ADULTS; TRIALS; BURDEN; PAIN AB Background. The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. Methods. The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. Results. In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. Conclusions. Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point. C1 [Schmader, K. E.] Durham Dept Vet Affairs VA Med Ctr MC, GRECC, Durham, NC USA. [Schmader, K. E.] Duke Univ, Durham, NC USA. [Oxman, M. N.; Guatelli, J. C.; Harbecke, R.] VA San Diego Healthcare Syst, San Diego, CA USA. [Oxman, M. N.; Guatelli, J. C.; Harbecke, R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Levin, M. J.] Univ Colorado Denver, Aurora, CO USA. [Levin, M. J.] Hlth Sci Ctr, Aurora, CO USA. [Johnson, G.; Zhang, J. H.] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Betts, R.] Univ Rochester, New York, NY USA. [Morrison, V. A.] VAMC, Minneapolis, MN USA. [Morrison, V. A.] Univ Minnesota, Minneapolis, MN USA. [Gelb, L.] VAMC, St Louis, MO USA. [Pachucki, C.] Hines VAMC, Chicago, IL USA. [Keay, S.] Baltimore VAMC, Baltimore, MD USA. [Keay, S.] Univ Maryland, Baltimore, MD 21201 USA. [Marques, A.] NIAID, Bethesda, MD 20892 USA. [Menzies, B.] VAMC, Seattle, WA USA. [Griffin, M. R.] Vanderbilt Univ, GRECC, Nashville, TN USA. [Griffin, M. R.] VA Tennessee Valley Hlth Care Syst, Nashville, TN USA. [Kauffman, C.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Kauffman, C.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Toney, J.] VAMC, Tampa, FL USA. [Keller, P. M.; Li, X.; Chan, I. S. F.; Annunziato, P.] Merck Sharp & Dhome Corp, Whitehouse Stn, NJ USA. RP Schmader, KE (reprint author), Durham VA Med Ctr, 182 GRECC,508 Fulton St, Durham, NC 27705 USA. EM kenneth.schmader@dm.duke.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU VA CSP [403]; Merck FX This work was supported by funding from VA CSP 403 and a grant from Merck to the VA Cooperative Studies Program and, subsequently, to the Veterans Medical Research Foundation and the VA Connecticut Research and Education Foundation. NR 13 TC 60 Z9 61 U1 0 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2012 VL 55 IS 10 BP 1320 EP 1328 DI 10.1093/cid/cis638 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 027SV UT WOS:000310374600013 PM 22828595 ER PT J AU Gamaletsou, MN Kontoyiannis, DP Sipsas, NV Moriyama, B Alexander, E Roilides, E Brause, B Walsh, TJ AF Gamaletsou, Maria N. Kontoyiannis, Dimitrios P. Sipsas, Nikolaos V. Moriyama, Brad Alexander, Elizabeth Roilides, Emmanuel Brause, Barry Walsh, Thomas J. TI Candida Osteomyelitis: Analysis of 207 Pediatric and Adult Cases (1970-2011) SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TROPICALIS VERTEBRAL OSTEOMYELITIS; TORULOPSIS-GLABRATA OSTEOMYELITIS; LIPOSOMAL AMPHOTERICIN-B; OF-THE-LITERATURE; CHRONIC-RENAL-FAILURE; ALBICANS OSTEOMYELITIS; SPINAL OSTEOMYELITIS; STERNAL OSTEOMYELITIS; DIABETIC FOOT AB Background. The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood. Methods. Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases. Results. Median age was 30 years (range, <= 1 month to 88 years) with a >2:1 male: female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had >= 2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04-.25), rib, and sternum; for pediatric patients (<= 18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4-48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response. Conclusions. Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6-12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome. C1 [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Ctr, Transplantat Oncol Infect Dis Program, Div Infect Dis, New York, NY 10065 USA. [Gamaletsou, Maria N.; Sipsas, Nikolaos V.] Univ Athens, Sch Med, Dept Pathophysiol, Athens, Greece. [Gamaletsou, Maria N.; Sipsas, Nikolaos V.; Roilides, Emmanuel; Brause, Barry; Walsh, Thomas J.] Hosp Special Surg, Ctr Osteoarticular Mycoses, New York, NY 10021 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Moriyama, Brad] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Sch Med, Hippokrat Hosp, Dept Pediat 3, GR-54006 Thessaloniki, Greece. RP Walsh, TJ (reprint author), Cornell Univ, Weill Cornell Med Ctr, Transplantat Oncol Infect Dis Program, Div Infect Dis, 1300 York Ave,Rm A-421, New York, NY 10065 USA. EM thw2003@med.cornell.edu FU Special Account for Research Funds of the National and Kapodistrian University of Athens; National Institutes of Health through an MD Anderson Cancer Center Support Grant [CA016672]; Save Our Sick Children Foundation; Weill Cornell Clinical and Translational Science Center; Postdoctoral Scientist Award [KL2RR024997] FX This work was supported by the Special Account for Research Funds (to M. N. G., N. V. S.) of the National and Kapodistrian University of Athens; National Institutes of Health through an MD Anderson Cancer Center Support Grant (CA016672); Save Our Sick Children Foundation (T. J. W.); Weill Cornell Clinical and Translational Science Center; and Postdoctoral Scientist Award (KL2RR024997 to E. A.). NR 145 TC 24 Z9 26 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2012 VL 55 IS 10 BP 1338 EP 1351 DI 10.1093/cid/cis660 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 027SV UT WOS:000310374600015 PM 22911646 ER PT J AU Shiels, MS Landgren, O Costello, R Zingone, A Goedert, JJ Engels, EA AF Shiels, Meredith S. Landgren, Ola Costello, Rene Zingone, Adriana Goedert, James J. Engels, Eric A. TI Free Light Chains and the Risk of AIDS-Defining Opportunistic Infections in HIV-Infected Individuals SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SOLUBLE CD30; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PROGRESSION; HEMOPHILIA; PREVALENCE; LYMPHOMA; DISEASE AB Background. The relevance of B-cell dysfunction for progression to AIDS among human immunodeficiency virus (HIV)-infected individuals has not been clearly defined. We evaluated the association between circulating kappa and. free light chains (FLCs), which are markers of B-cell dysfunction, and risk of developing an AIDS-defining opportunistic infection in HIV-infected men. Methods. The study included 252 case patients with clinical AIDS and 252 HIV-infected controls from the Multicenter Hemophilia Cohort Study I. Case patients were matched to controls on birth date, specimen type, blood sample collection date, and CD4 cell count. Levels of kappa and lambda FLCs were measured in serum or plasma collected 0-2.5 years before selection. Elevated FLC levels (kappa or lambda, above the upper limit of normal) were classified as polyclonal (normal kappa-lambda ratio) or monoclonal (abnormally skewed kappa-lambda ratio). We used conditional logistic regression to estimate odds ratios (ORs) for AIDS. Results. FLC levels were higher in case patients than in controls, for kappa (median, 4.03 vs 2.98 mg/dL) and lambda (3.77 vs 2.42 mg/dL) FLCs. Compared with normal levels, above-normal FLC levels were associated with AIDS (OR, 3.13 [95% confidence interval (CI), 1.78-5.49] for kappa and 3.47 [2.31-5.20] for lambda FLCs), and the association with AIDS was strengthened with increasing kappa and lambda FLC levels (P trends < .0001). Polyclonal FLC elevation was associated with a 4-fold increase in the risk of AIDS (OR, 3.85; 95% CI, 1.97-7.54), but monoclonal FLC elevation was not associated with AIDS. Conclusions. Circulating FLCs are associated with elevated risk of AIDS in HIV-infected individuals. Polyclonal B-cell dysfunction may contribute to HIV-related immune suppression and predispose to clinical AIDS events. C1 [Shiels, Meredith S.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Landgren, Ola; Costello, Rene; Zingone, Adriana] NCI, Multiple Myeloma Sect, Ctr Canc Res, Rockville, MD 20892 USA. RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA. EM shielsms@mail.nih.gov FU Intramural Research Program of the National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute. NR 21 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2012 VL 55 IS 10 BP E103 EP E108 DI 10.1093/cid/cis692 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 027SV UT WOS:000310374600006 PM 22893577 ER PT J AU Martin, LK Grecula, J Jia, G Wei, L Yang, XY Otterson, GA Wu, X Harper, E Kefauver, C Zhou, BS Yen, Y Bloomston, M Knopp, M Ivy, SP Grever, M Bekaii-Saab, T AF Martin, Ludmila Katherine Grecula, John Jia, Guang Wei, Lai Yang, Xiangyu Otterson, Gregory A. Wu, Xin Harper, Erica Kefauver, Cheryl Zhou, Bing-Sen Yen, Yun Bloomston, Mark Knopp, Michael Ivy, S. Percy Grever, Michael Bekaii-Saab, Tanios TI A Dose Escalation and Pharmacodynamic Study of Triapine and Radiation in Patients With Locally Advanced Pancreas Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; PHASE-I; SOLID TUMORS; ADENOCARCINOMA; SCHEDULE; SUBUNIT AB Purpose: Triapine, a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR), is a potent radiosensitizer. This phase 1 study, sponsored by the National Cancer Institute Cancer Therapy Evaluation Program, assessed the safety and tolerability of triapine in combination with radiation (RT) in patients with locally advanced pancreas cancer (LAPCA). Methods and Materials: We evaluated 3 dosage levels of triapine (24 mg/m(2), 48 mg/m(2), 72 mg/m(2)) administered with 50.4 Gy of RT in 28 fractions. Patients with LAPCA received triapine thrice weekly, every other week during the course of RT. Dose-limiting toxicity (DLT) was assessed during RT and for 4 weeks after its completion. Dynamic contrast-enhanced magnetic resonance imaging and serum RR levels were evaluated as potential predictors for early response. Results: Twelve patients were treated. Four patients (1 nonevaluable) were enrolled at dosage level 1 (DL1), 3 patients at DL2, and 5 patients (2 nonevaluable) at DL3. No DLTs were observed, and the maximum tolerated dose was not reached. Two patients (17%) achieved partial response, and 6 patients (50%) had stable disease. One patient underwent R0 resection after therapy. Ninety-two percent of patients (100% at DL3) experienced freedom from local tumor progression. In 75% of patients who eventually experienced progression, metastases developed without local progression. RR levels did not seem to predict outcome. In 4 patients with available data, dynamic contrast-enhanced magnetic resonance imaging may predict early response or resistance to therapy. Conclusion: The combination of triapine at 72 mg/m(2) 3 times weekly every other week and standard RT is tolerable with interesting activity in patients with LAPCA. (C) 2012 Elsevier Inc. C1 [Martin, Ludmila Katherine; Otterson, Gregory A.; Grever, Michael; Bekaii-Saab, Tanios] Ohio State Univ, Dept Internal Med, Div Surg Oncol, Columbus, OH 43210 USA. [Grecula, John] Ohio State Univ, Dept Radiat Oncol, Div Surg Oncol, Columbus, OH 43210 USA. [Jia, Guang; Yang, Xiangyu; Knopp, Michael] Ohio State Univ, Dept Radiol, Div Surg Oncol, Columbus, OH 43210 USA. [Bloomston, Mark] Ohio State Univ, Dept Surg, Div Surg Oncol, Columbus, OH 43210 USA. [Wei, Lai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Wu, Xin; Harper, Erica; Kefauver, Cheryl] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Zhou, Bing-Sen; Yen, Yun] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Ivy, S. Percy] NCI, Canc Therapeut Evaluat Program, Rockville, MD USA. RP Bekaii-Saab, T (reprint author), A454 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM Tanios.Saab@osumc.edu RI Jia, Guang/E-3312-2011; Bloomston, Mark/E-2767-2011; Bekaii-Saab, Tanios/E-2733-2011; Grecula, John/E-3149-2011; Mendez, Pedro /J-8955-2016; Yang, Xiangyu/E-4342-2011; Jia, Guang/A-1275-2016 OI Mendez, Pedro /0000-0001-6713-7907; Yang, Xiangyu/0000-0002-1541-667X; FU National Cancer Institute-Cancer Therapy Evaluation Program [U01CA 76576-03] FX Supported by the National Cancer Institute-Cancer Therapy Evaluation Program U01CA 76576-03. NR 20 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2012 VL 84 IS 4 BP E475 EP E481 DI 10.1016/j.ijrobp.2012.06.003 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030IV UT WOS:000310565300005 PM 22818416 ER PT J AU Ota, T Doyle-Cooper, C Cooper, AB Huber, M Falkowska, E Doores, KJ Hangartner, L Le, K Sok, D Jardine, J Lifson, J Wu, XL Mascola, JR Poignard, P Binley, JM Chakrabarti, BK Schief, WR Wyatt, RT Burton, DR Nemazee, D AF Ota, Takayuki Doyle-Cooper, Colleen Cooper, Anthony B. Huber, Michael Falkowska, Emilia Doores, Katherine J. Hangartner, Lars Le, Khoa Sok, Devin Jardine, Joseph Lifson, Jeffrey Wu, Xueling Mascola, John R. Poignard, Pascal Binley, James M. Chakrabarti, Bimal K. Schief, William R. Wyatt, Richard T. Burton, Dennis R. Nemazee, David TI Anti-HIV B Cell Lines as Candidate Vaccine Biosensors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; BROADLY NEUTRALIZING ANTIBODIES; PBL-SCID MICE; IN-VITRO; POTENT NEUTRALIZATION; PASSIVE-IMMUNIZATION; CRYSTAL-STRUCTURE; CD4-BINDING SITE; DOMAIN EXCHANGE AB Challenge studies following passive immunization with neutralizing Abs suggest that an HIV vaccine could be efficacious were it able to elicit broadly neutralizing Abs (bNAbs). To better understand the requirements for activation of B cells producing bNAbs, we generated cell lines expressing bNAbs or their germline-reverted versions (gl-bNAbs) as BCRs. We then tested the abilities of the bNAb-expressing cells to recognize HIV pseudovirions and vaccine candidate proteins by binding and activation assays. The results suggest that HIV envelope (Env) Ag-expressing, infection-competent virions are poorly recognized by high-affinity bNAb-expressing cells, as measured by the inability of Ags to induce rapid increases in intracellular calcium levels. Other Ag forms appear to be highly stimulatory, in particular, soluble gp140 trimers and a multimerized, scaffolded epitope protein. Virions failed to efficiently activate bNAb-expressing B cells owing to delayed or inefficient BCR recognition, most likely caused by the low density of Env spikes. Importantly, B cells carrying gl-bNAb BCRs were not stimulated by any of the tested vaccine candidates. These data provide insight into why many HIV immunogens, as well as natural HIV infections, fail to rapidly stimulate bNAb responses and suggest that bNAb-expressing cell lines might be useful tools in evaluation of vaccine Ags for infectious diseases. Because soluble Env trimers or multimerized scaffolded epitopes are best at activating B cell-expressing bNAbs, these antigenic forms should be considered as preferred vaccine components, although they should be modified to better target naive gl-bNAb B cells. The Journal of Immunology, 2012, 189: 4816-4824. C1 [Ota, Takayuki; Doyle-Cooper, Colleen; Cooper, Anthony B.; Huber, Michael; Falkowska, Emilia; Doores, Katherine J.; Hangartner, Lars; Le, Khoa; Sok, Devin; Jardine, Joseph; Poignard, Pascal; Chakrabarti, Bimal K.; Schief, William R.; Wyatt, Richard T.; Burton, Dennis R.; Nemazee, David] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Huber, Michael; Hangartner, Lars] Univ Zurich, Inst Med Virol, CH-8057 Zurich, Switzerland. [Jardine, Joseph; Poignard, Pascal; Chakrabarti, Bimal K.; Schief, William R.; Wyatt, Richard T.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Lifson, Jeffrey] Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Wu, Xueling; Mascola, John R.] NIAID, Vaccine Res Ctr, Nihon Univ, Bethesda, MD 20892 USA. [Binley, James M.] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. [Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. RP Nemazee, D (reprint author), Scripps Res Inst, 10550 N Torrey Pines Rd,Mail Drop IM29, La Jolla, CA 92130 USA. EM nemazee@scripps.edu RI poignard, pascal/N-6678-2013; Huber, Michael/B-8509-2015; Hangartner, Lars/H-3503-2011; OI Doores, Katie/0000-0002-5507-1725 FU National Institutes of Health Research [R01 AI073148, U01 AI078224, UM1 AI100663]; International AIDS Vaccine Initiative Neutralizing Antibody Center; Ragon Institute of MGH; Ragon Institute of MIT; Ragon Institute of Harvard; Creative and Novel Ideas in HIV Research award FX This work was supported by National Institutes of Health Research Grants R01 AI073148, U01 AI078224, and UM1 AI100663, as well as by the International AIDS Vaccine Initiative Neutralizing Antibody Center and the Ragon Institute of MGH, MIT and Harvard. T.O. is a recipient of a Creative and Novel Ideas in HIV Research award. NR 60 TC 27 Z9 27 U1 0 U2 12 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2012 VL 189 IS 10 BP 4816 EP 4824 DI 10.4049/jimmunol.1202165 PG 9 WC Immunology SC Immunology GA 032IU UT WOS:000310710600015 PM 23066156 ER PT J AU Peters, NC Bertholet, S Lawyer, PG Charmoy, M Romano, A Ribeiro-Gomes, FL Stamper, LW Sacks, DL AF Peters, Nathan C. Bertholet, Sylvie Lawyer, Phillip G. Charmoy, Melanie Romano, Audrey Ribeiro-Gomes, Flavia L. Stamper, Lisa W. Sacks, David L. TI Evaluation of Recombinant Leishmania Polyprotein Plus Glucopyranosyl Lipid A Stable Emulsion Vaccines against Sand Fly-Transmitted Leishmania major in C57BL/6 Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CANINE VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; LEISH-F1+MPL-SE VACCINE; MEGLUMINE ANTIMONIATE; CLINICAL-TRIAL; T-CELLS; PROTECTIVE IMMUNITY; VIRULENT CHALLENGE; SUSCEPTIBLE MICE; INFECTION AB Numerous experimental Leishmania vaccines have been developed to prevent the visceral and cutaneous forms of Leishmaniasis, which occur after exposure to the bite of an infected sand fly, yet only one is under evaluation in humans. KSAC and L110f, recombinant Leishmania polyproteins delivered in a stable emulsion (SE) with the TLR4 agonists monophosphoryl lipid A or glucopyranosyl lipid A (GLA) have shown protection in animal models. KSAC+GLA-SE protected against cutaneous disease following sand fly transmission of Leishmania major in susceptible BALB/c mice. Similar polyprotein adjuvant combinations are the vaccine candidates most likely to see clinical evaluation. We assessed immunity generated by KSAC or L110f vaccination with GLA-SE following challenge with L. major by needle or infected sand fly bite in resistant C57BL/6 mice. Polyprotein-vaccinated mice had a 60-fold increase in CD4(+)IFN-gamma T+ cell numbers versus control animals at 2 wk post-needle inoculation of L. major, and this correlated with a 100-fold reduction in parasite load. Immunity did not, however, reach levels observed in mice with a healed primary infection. Following challenge by infected sand fly bite, polyprotein-vaccinated animals had comparable parasite loads, greater numbers of neutrophils at the challenge site, and reduced CD4(+)IFN-gamma(+)/IL-17(+) ratios versus nonvaccinated controls. In contrast, healed animals had significantly reduced parasite loads and higher CD4(+) IFN-gamma(+)/IL-17(+) ratios. These observations demonstrate that vaccine-induced protection against needle challenge does not necessarily translate to protection following challenge by infected sand fly bite. The Journal of Immunology, 2012, 189: 4832-4841. C1 [Peters, Nathan C.; Lawyer, Phillip G.; Charmoy, Melanie; Romano, Audrey; Ribeiro-Gomes, Flavia L.; Stamper, Lisa W.; Sacks, David L.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Bertholet, Sylvie] Infect Dis Res Inst, Seattle, WA 98104 USA. RP Peters, NC (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. EM NPeters@niaid.nih.gov RI Ribeiro-Gomes, Flavia/F-7609-2015 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 49 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2012 VL 189 IS 10 BP 4832 EP 4841 DI 10.4049/jimmunol.1201676 PG 10 WC Immunology SC Immunology GA 032IU UT WOS:000310710600017 PM 23045616 ER PT J AU White, KL Roth, BL AF White, Kate L. Roth, Bryan L. TI Psychotomimetic Effects of Kappa Opioid Receptor Agonists SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID SALVINORIN-A; PATHWAYS; BEHAVIOR; RATS C1 [White, Kate L.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Program Neurosci, Sch Med, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Neurodev Disorders Res Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Sch Med, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA. RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01 DA017204]; NIGMS NIH HHS [T32 GM007040] NR 10 TC 3 Z9 3 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2012 VL 72 IS 10 BP 797 EP 798 DI 10.1016/j.biopsych.2012.08.014 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 027KT UT WOS:000310351800004 PM 23083945 ER PT J AU Fucito, LM Park, A Gulliver, SB Mattson, ME Gueorguieva, RV O'Malley, SS AF Fucito, Lisa M. Park, Aesoon Gulliver, Suzy Bird Mattson, Margaret E. Gueorguieva, Ralitza V. O'Malley, Stephanie S. TI Cigarette Smoking Predicts Differential Benefit from Naltrexone for Alcohol Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Acamprosate; alcohol dependence; behavioral treatment; cigarette smoking; naltrexone; pharmacotherapy ID LOW-DOSE NALTREXONE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL PREDICTORS; DRINKING RATES; HEAVY DRINKING; NICOTINE; CESSATION; SMOKERS; INTERVENTIONS; REINFORCEMENT AB Background: Identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. Cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. Nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. Methods: We examined the association between cigarette smoking and drinking outcomes in the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management, combined behavioral therapy) in 1383 alcohol-dependent individuals. Results: Smokers (i.e., more than one half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. However, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. This pattern of findings occurred independent of whether patients received combined behavioral intervention or medical management and remained after controlling for alcoholism typology and baseline demographic differences. Approximately 9% of smokers quit smoking, and an additional 10% reduced their cigarette intake during treatment. Reductions in smoking did not vary by treatment assignment. Conclusions: These results suggest that naltrexone might be particularly beneficial for improving alcohol use outcomes in alcohol-dependent smokers. C1 [Fucito, Lisa M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [O'Malley, Stephanie S.] Yale Canc Ctr, New Haven, CT USA. [Gueorguieva, Ralitza V.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Park, Aesoon] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Gulliver, Suzy Bird] VA VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [Gulliver, Suzy Bird] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Mattson, Margaret E.] Natl Inst Alcohol Abuse & Alcoholism, Div Treatment Res, Bethesda, MD USA. [Mattson, Margaret E.] Subst Abuse & Mental Hlth Serv Adm, Ctr Behav Hlth Stat & Qual, Rockville, MD USA. RP Fucito, LM (reprint author), Yale Univ, Sch Med, Dept Psychiat, 1 Long Wharf Dr,Box 18, New Haven, CT 06511 USA. EM lisa.fucito@yale.edu OI Gueorguieva, Ralitza/0000-0003-0944-5973 FU National Institute on Alcohol Abuse and Alcoholism [K05-AA014715, R01-AA016621, K23-AA02000, T32-AA015496]; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services; Eli Lilly; Janssen; Johnson Johnson; Schering Plough; Lundbeck; GlaxoSmithKline; Alkermes FX This research was supported in part by grants from the National Institute on Alcohol Abuse and Alcoholism: K05-AA014715 (SSO), R01-AA016621 (SSO, RG), K23-AA02000 (LMF), and T32-AA015496 (LMF).We acknowledge that the reported results are, in whole or in part, based on analyses of the COMBINE Data Set. These data were collected as part of a multisite clinical trial of alcoholism treatments supported by a series of grants from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services. This report has not been reviewed or endorsed by National Institute on Alcohol Abuse and Alcoholism or the COMBINE Research Group and does not necessarily represent the opinions of its members or National Institute on Alcohol Abuse and Alcoholism, who are not responsible for the contents.; Dr. Stephanie O'Malley is a member American College of Neuropsychopharmacogy workgroup, the Alcohol Clinical Trial Initiative, sponsored by Eli Lilly, Janssen, Johnson & Johnson, Schering Plough, Lundbeck, GlaxoSmithKline, and Alkermes; has served as partner with Applied Behavioral Research; has been under contract with Nabi Biopharmaceuticals; has received medication supplies from Pfizer; has served on the Advisory Board of Gilead Pharmaceuticals; has served as consultant to GlaxoSmithKline, Lundbeck, Brown University; and has served on the Scientific Panel of Advisors of Hazelden. All other authors report no biomedical financial interests or potential conflicts of interest. NR 51 TC 16 Z9 16 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2012 VL 72 IS 10 BP 832 EP 838 DI 10.1016/j.biopsych.2012.03.023 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 027KT UT WOS:000310351800011 PM 22541040 ER PT J AU Martin, DJ FitzMorris, PE Li, B Ayestas, M Sally, EJ Dersch, CM Rothman, RB Deveau, AM AF Martin, David J. FitzMorris, Paul E. Li, Bo Ayestas, Mario Sally, Ellicott J. Dersch, Christina M. Rothman, Richard B. Deveau, Amy M. TI An efficient synthesis of 3-OBn-6 beta,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Naltrexone; Naltrexol; Antagonist; Inverse Agonist; Opiate; 6 beta,14-Epoxymorphinan; Conformation; Rigid analog ID MU-OPIOID RECEPTOR; CONFORMATIONAL RESTRICTION; FUNCTIONAL SELECTIVITY; NARCOTIC DEPENDENCE; NALOXONE; 6-BETA-NALTREXOL; DERIVATIVES; ANTAGONISTS; AFFINITY; PHARMACOLOGY AB In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6 beta,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through the OBn-6 alpha-triflate intermediate 8. Key steps to the synthesis include benzylation (96% yield), reduction (90% yield, alpha:beta:3:2), followed by a one-pot triflation/displacement sequence (96% yield) to yield the desired bridged epoxy derivative 4. X-ray crystallographic analysis of intermediate 3-OBn-6 alpha-naltrexol 7a supports population of the key boat conformation required for the epoxy ring closure. We also report that the 6 beta-mesylate 10-a high affinity opioid receptor ligand, the epimeric derivative of 11, and an analog of 12-functions as an inverse agonist at the mu opioid receptor using herkinorin pre-conditioned cells and an agonist at the kappa opioid receptor when evaluated in independent in vitro [S-35]-GTP-gamma-S assays. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Martin, David J.; FitzMorris, Paul E.; Deveau, Amy M.] Univ New England, Coll Arts & Sci, Dept Chem & Phys, Biddeford, ME 04005 USA. [Martin, David J.] Univ New England, Coll Osteopath Med, Biddeford, ME 04005 USA. [Li, Bo] Boston Coll, Xray Crystallog Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. [Ayestas, Mario; Sally, Ellicott J.; Dersch, Christina M.; Rothman, Richard B.] NIDA, NIH, Addict Res Ctr, Baltimore, MD 21224 USA. RP Deveau, AM (reprint author), Univ New England, Coll Arts & Sci, Dept Chem & Phys, Biddeford, ME 04005 USA. EM adeveau@une.edu FU University of New England; Research Mini-Grants; Chemistry & Physics Department; Carman Pettapiece Student Research Fund of the College of Osteophatic Medicine (COM) at UNE; CAS; COM Dean's Offices; Provost's office; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health FX This Letter is dedicated to Professor Timothy Macdonald for his many contributions to the field of Organic and Medicinal Chemistry. The authors are indebted to Dr. Kenner C. Rice and Kejun Chung of the Drug Design and Synthesis Section, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, for providing a sample of KC-2-009 for use in functional binding assays. The authors are also grateful to Mallinckrodt, Inc. for generously donating naltrexone free base. We thank Dr. Rebecca Conry (Colby College, Waterville, ME) for valuable advice and assistance in preparing X-ray quality crystals of 7a. We gratefully acknowledge the support of the University of New England (UNE) for College of Arts & Sciences (CAS) Research Mini-Grants and the Chemistry & Physics Department for monies to support research & conference travel (awarded to A. M. D.). We thank the Carman Pettapiece Student Research Fund of the College of Osteophatic Medicine (COM) at UNE as well as the CAS and COM Dean's Offices and the Provost's office for research support (awarded to D.J.M./A.M.D.). Portions of this work were supported by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. NR 45 TC 0 Z9 0 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2012 VL 22 IS 22 BP 6801 EP 6805 DI 10.1016/j.bmcl.2012.06.056 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 027LL UT WOS:000310353700003 PM 22771010 ER PT J AU Gildersleeve, JC Wang, BM Achilefu, S Tu, Z Xu, M AF Gildersleeve, Jeffrey C. Wang, Baomei Achilefu, Samuel Tu, Zhude Xu, Mai TI Glycan array analysis of the antigen repertoire targeted by tumor-binding antibodies SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Glycan array; Antibody; Carbohydrate; Tumor antigen; Cancer vaccine ID BLOOD GROUP ANTIGENS; MONOCLONAL-ANTIBODIES; COLON-CANCER; VACCINES; IMMUNOTHERAPY; MICROARRAY; CELLS; SPECIFICITY; MELANOMA; EPITOPES AB Immunization with whole cells has been used extensively to generate monoclonal antibodies, produce protective immune responses, and discover new disease antigens. While glycans are abundant on cell surfaces, anti-glycan immune responses have not been well-characterized. We used glycan microarrays to profile 49 tumor-binding monoclonal antibodies generated by immunizing mice with whole cancer cells. A substantial proportion (41%) of the tumor binding antibodies bound carbohydrate antigens. The antibodies primarily recognize a group of 5 glycan antigens: Sialyl Lewis A (SLeA), Lewis A (LeA), Lewis X (LeX), blood group A (BG-A), and blood group H on a type 2 chain (BG-H2). The results have important implications for monoclonal antibody production and cancer vaccine development. Published by Elsevier Ltd. C1 [Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Frederick, MD 21702 USA. [Wang, Baomei] Univ Louisville, James Graham Brown Canc Ctr, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Achilefu, Samuel; Tu, Zhude; Xu, Mai] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov; xum@mir.wustl.edu RI Gildersleeve, Jeffrey/N-3392-2014; OI Achilefu, Samuel/0000-0002-3133-6717 FU Intramural Research Program of the NIH, NCI FX We thank Jack Simpson (Protein Chemistry Laboratory, SAIC/NCI-Frederick) for MALDI-MS analysis of BSA conjugates. This research was supported in part by the Intramural Research Program of the NIH, NCI. NR 45 TC 7 Z9 8 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2012 VL 22 IS 22 BP 6839 EP 6843 DI 10.1016/j.bmcl.2012.09.055 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 027LL UT WOS:000310353700011 PM 23063402 ER PT J AU Scott, JG Bauchet, L Fraum, TJ Nayak, L Cooper, AR Chao, ST Suh, JH Vogelbaum, MA Peereboom, DM Zouaoui, S Mathieu-Daude, H Fabbro-Peray, P Rigau, V Taillandier, L Abrey, LE DeAngelis, LM Shih, JH Iwamoto, FM AF Scott, Jacob G. Bauchet, Luc Fraum, Tyler J. Nayak, Lakshmi Cooper, Anna R. Chao, Samuel T. Suh, John H. Vogelbaum, Michael A. Peereboom, David M. Zouaoui, Sonia Mathieu-Daude, Helene Fabbro-Peray, Pascale Rigau, Valerie Taillandier, Luc Abrey, Lauren E. DeAngelis, Lisa M. Shih, Joanna H. Iwamoto, Fabio M. TI Recursive Partitioning Analysis of Prognostic Factors for Glioblastoma Patients Aged 70 Years or Older SO CANCER LA English DT Article DE glioblastoma; elderly; surgery; prognosis; aging ID MALIGNANT GLIOMAS; ELDERLY-PATIENTS; BRAIN-TUMORS; PATTERNS; CARE; EPIDEMIOLOGY; RADIOTHERAPY; SURVIVAL AB BACKGROUND: The most-used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients >= 70 years of age with newly diagnosed glioblastoma. METHODS: A total of 437 patients >= 70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients >= 70 years of age from a data set independently compiled by a French consortium. RESULTS: RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients <75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients >= 75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status <70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P < .0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months). CONCLUSIONS: This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers. Cancer 2012. (c) 2012 American Cancer Society. C1 [Fraum, Tyler J.; Iwamoto, Fabio M.] NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Scott, Jacob G.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Tampa, FL 33682 USA. [Bauchet, Luc; Zouaoui, Sonia] CHU Montpellier, Hop St Eloi Gui de Chauliac, Dept Neurosurg, Montpellier, France. [Bauchet, Luc; Zouaoui, Sonia] CHU Montpellier, Hop St Eloi Gui de Chauliac, INSERM, U1051, Montpellier, France. [Fraum, Tyler J.] Duke Univ, Sch Med, Durham, NC USA. [Nayak, Lakshmi; Abrey, Lauren E.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. [Nayak, Lakshmi; Abrey, Lauren E.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Cooper, Anna R.] Univ Rochester, Med Ctr, Dept Orthoped, Rochester, NY 14642 USA. [Chao, Samuel T.; Suh, John H.; Vogelbaum, Michael A.; Peereboom, David M.] Cleveland Clin, Brain Tumor Inst, Cleveland, OH 44106 USA. [Mathieu-Daude, Helene] Ctr Lutte Canc Val dAurelle, Registre Tumeurs Herault, Neurooncol Grp Languedoc Roussillon, Dept Epidemiol, Montpellier, France. [Fabbro-Peray, Pascale] Inst Univ Rech Clin, Dept Biostat, Montpellier, France. [Fabbro-Peray, Pascale] Ctr Hosp Univ, Nimes, France. [Rigau, Valerie] CHU Montpellier, Hop Gui de Chauliac, Dept Pathol, Montpellier, France. [Taillandier, Luc] Hop Neurol, Dept Neurooncol, Nancy, France. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Iwamoto, FM (reprint author), NCI, Neurooncol Branch, Ctr Canc Res, NIH, 9030 Old Georgetown Rd,Room 221, Bethesda, MD 20892 USA. EM fi2146@columbia.edu OI ZOUAOUI, Sonia/0000-0003-0467-3280 FU US National Institutes of Health (NIH) Intramural Research Program [1ZIDBC011098-02]; NIH; Pfizer Inc.; National Cancer Institute Clinical Investigator Development Program; NIH Intramural Program [1ZIABC011347-01, 1ZIABC011348-01]; French government (INCa); Association des Neuro-Oncologues d'Expression Francaise (ANOCEF); Societe Francaise de NeuroChirurgie (SFNC); Societe Francaise de Neuropathologie (SFNP) FX This study has been supported by the US National Institutes of Health (NIH) Intramural Research Program (1ZIDBC011098-02). Dr. Fraum is a Fellow in the Clinical Research Training Program, a public-private partnership supported jointly by NIH and Pfizer Inc. (via a grant to the Foundation for NIH from Pfizer Inc.). Dr. Iwamoto is supported by the National Cancer Institute Clinical Investigator Development Program and the NIH Intramural Program (1ZIABC011347-01 and 1ZIABC011348-01). Drs. Zouaoui, Mathieu-Daude, Fabbro-Peray, Rigau, Taillandier, and Bauchet acknowledge the support of the French government (INCa), Association des Neuro-Oncologues d'Expression Francaise (ANOCEF), Societe Francaise de NeuroChirurgie (SFNC), and Societe Francaise de Neuropathologie (SFNP). NR 21 TC 28 Z9 28 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5595 EP 5600 DI 10.1002/cncr.27570 PG 6 WC Oncology SC Oncology GA 029GW UT WOS:000310483800017 PM 22517216 ER PT J AU Shiels, MS Engels, EA Shi, JX Landi, MT Albanes, D Chatterjee, N Chanock, SJ Caporaso, NE Chaturvedi, AK AF Shiels, Meredith S. Engels, Eric A. Shi, Jianxin Landi, Maria Teresa Albanes, Demetrius Chatterjee, Nilanjan Chanock, Stephen J. Caporaso, Neil E. Chaturvedi, Anil K. TI Genetic Variation in Innate Immunity and Inflammation Pathways Associated With Lung Cancer Risk SO CANCER LA English DT Article DE lung cancer; genetics; inflammation; immunity; epidemiology ID SUSCEPTIBILITY LOCUS; POLYMORPHISMS; PREVENTION; LYMPHOMA; SMOKING; NFKB1 AB BACKGROUND: Pulmonary inflammation may contribute to lung cancer etiology. The authors conducted a broad evaluation of the association of single nucleotide polymorphisms (SNPs) in innate immunity and inflammation pathways with lung cancer risk and conducted comparisons with a lung cancer genome-wide association study (GWAS). METHODS: In total, 378 patients with lung cancer (cases) and a group of 450 controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were included. A proprietary oligonucleotide pool assay was used to genotype 1429 SNPs. Odds ratios and 95% confidence intervals were estimated for each SNP, and P values for trend (P-trend) were calculated. For statistically significant SNPs (P-trend < .05), the results were replicated with genotyped or imputed SNPs in the GWAS, and P values were adjusted for multiple testing. RESULTS: In the PLCO analysis, a significant association was observed between lung cancer and 81 SNPs located in 44 genes (P-trend < .05). Of these 81 SNPS, there was evidence for confirmation in the GWAS for 10 SNPs. However, after adjusting for multiple comparisons, the only SNP that retained a significant association with lung cancer in the replication phase was reference SNP rs4648127 (nuclear factor of kappa light polypeptide gene enhancer of B-cells 1 [NFKB1]) (multiple testing-adjusted P-trend = .02). The cytosine-thymine (CT)/TT genotype of NFKB1 was associated with reduced odds of lung cancer in the PLCO study (odds ratio, 0.56; 95% confidence interval, 0.37-0.86) and the in the GWAS (odds ratio, 0.79; 95% confidence interval, 0.69-0.90). CONCLUSIONS: A significant association was observed between a variant in the NFKB1 gene and the risk of lung cancer. The current findings add to evidence implicating inflammation and immunity in lung cancer etiology. Cancer 2012. Published 2012 by the American Cancer Society. C1 [Shiels, Meredith S.; Engels, Eric A.; Chaturvedi, Anil K.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Shi, Jianxin; Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Landi, Maria Teresa; Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA. EM shielsms@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU National Cancer Institute; National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics; NCI [NO1-CN-25,514, NO1-CN-25,522, NO1-CN-25,515, NO1-CN-25,512, NO1-CN-25,513, NO1-CN-25,516, NO1-CN-25,511, NO1-CN-25,524, NO1-CN-75,022, NO1-CN-25,476, NO1-CN-25,404]; US. Public Health Service from the NCI [N01-CN-45,165, N01-RC-45,035, N01-RC-37,004]; American Cancer Society FX This study was supported by the Intramural Research Program of the National Cancer Institute. The Environment and Genetics in Lung Cancer Etiology (EAGLE), Prostate, Lung, Colon, Ovary Screening Trial (PLCO), and Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) studies were supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. PLCO also was supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25,514), Georgetown University (NO1-CN-25,522), the Pacific Health Research Institute (NO1-CN-25,515), the Henry Ford Health System (NO1-CN-25,512), the University of Minnesota, (NO1-CN-25,513), Washington University (NO1-CN-25,516), the University of Pittsburgh (NO1-CN-25,511), the University of Utah (NO1-CN-25,524), the Marshfield Clinic Research Foundation (NO1-CN-25,518), the University of Alabama at Birmingham (NO1-CN-75,022), Westat, Inc. (NO1-CN-25,476), and the University of California, Los Angeles (NO1-CN-25,404). ATBC also was supported by US. Public Health Service contracts (N01-CN-45,165, N01-RC-45,035, and N01-RC-37,004) from the NCI. The Cancer Prevention Study-II (CPS-II) Nutrition Cohort was supported by the American Cancer Society. NR 26 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5630 EP 5636 DI 10.1002/cncr.27605 PG 7 WC Oncology SC Oncology GA 029GW UT WOS:000310483800022 PM 23044494 ER PT J AU Feuer, EJ Lee, M Mariotto, AB Cronin, KA Scoppa, S Penson, DF Hachey, M Cynkin, L Carter, GA Campbell, D Percy-Laurry, A Zou, ZH Schrag, D Hankey, BF AF Feuer, Eric J. Lee, Minjung Mariotto, Angela B. Cronin, Kathy A. Scoppa, Steve Penson, David F. Hachey, Mark Cynkin, Laurie Carter, Ginger A. Campbell, David Percy-Laurry, Antoinette Zou, Zhaohui Schrag, Deborah Hankey, Benjamin F. TI The Cancer Survival Query System: Making Survival Estimates From the Surveillance, Epidemiology, and End Results Program More Timely and Relevant for Recently Diagnosed Patients SO CANCER LA English DT Article DE competing risk analysis; survival analysis; proportional hazards; prostate cancer; nomograms; prognosis; shared decision-making ID BREAST AB BACKGROUND: Population-based cancer registries that include patient follow-up generally provide information regarding net survival (ie, survival associated with the risk of dying of cancer in the absence of competing risks). However, registry data also can be used to calculate survival from cancer in the presence of competing risks, which is more clinically relevant. METHODS: Statistical methods were developed to predict the risk of death from cancer and other causes, as well as natural life expectancy if the patient did not have cancer based on a profile of prognostic factors including characteristics of the cancer, demographic factors, and comorbid conditions. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to calculate the risk of dying of cancer. Because the risks of dying of cancer versus other causes are assumed to be independent conditional on the prognostic factors, a wide variety of independent data sources can be used to calculate the risk of death from other causes. Herein, the risk of death from other causes was estimated using SEER and Medicare claims data, and was matched to the closest fitting portion of the US life table to obtain a health status-adjusted age. RESULTS: A nomogram was developed for prostate cancer as part of a Web-based Cancer Survival Query System that is targeted for use by physicians and patients to obtain information on a patient's prognosis. More nomograms currently are being developed. CONCLUSIONS: Nomograms of this type can be used as one tool to assist cancer physicians and their patients to better understand their prognosis and to weigh alternative treatment and palliative strategies. Cancer 2012. (c) 2012 American Cancer Society. C1 [Hankey, Benjamin F.] CANSTAT, Plano, TX 75024 USA. [Feuer, Eric J.; Lee, Minjung; Mariotto, Angela B.; Cronin, Kathy A.; Cynkin, Laurie; Percy-Laurry, Antoinette] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Scoppa, Steve; Hachey, Mark; Carter, Ginger A.; Campbell, David; Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Ctr Surg Qual & Outcomes Res, Nashville, TN USA. [Penson, David F.] Tennessee Valley Geriatr Res Educ & Clin Ctr GREC, Vet Adm, Nashville, TN USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Hankey, BF (reprint author), CANSTAT, 6805 Colonnade Dr, Plano, TX 75024 USA. EM bhankey0411@aol.com FU National Cancer Institute FX Supported by the National Cancer Institute. NR 24 TC 11 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5652 EP 5662 DI 10.1002/cncr.27615 PG 11 WC Oncology SC Oncology GA 029GW UT WOS:000310483800025 PM 22569947 ER PT J AU Reeve, BB Stover, AM Jensen, RE Chen, RC Taylor, KL Clauser, SB Collins, SP Potosky, AL AF Reeve, Bryce B. Stover, Angela M. Jensen, Roxanne E. Chen, Ronald C. Taylor, Kathryn L. Clauser, Steven B. Collins, Sean P. Potosky, Arnold L. TI Impact of Diagnosis and Treatment of Clinically Localized Prostate Cancer on Health-Related Quality of Life for Older Americans A Population-Based Study SO CANCER LA English DT Article DE prostate cancer; health-related quality of life; population-based; prospective; older Americans ID ANDROGEN DEPRIVATION THERAPY; RANDOMIZED DOSE-ESCALATION; 5-YEAR FOLLOW-UP; PROPENSITY-SCORE; SEXUAL FUNCTION; MANAGED CARE; RADIOTHERAPY; OUTCOMES; CARCINOMA; SURVEILLANCE AB BACKGROUND: Few studies have measured longitudinal changes in health-related quality of life (HRQOL) among patients with prostate cancer starting before their cancer diagnosis or have provided simultaneous comparisons with a matched noncancer cohort. In the current study, the authors addressed these gaps by providing unique estimates of the effects of a cancer diagnosis on HRQOL accounting for the confounding effects of ageing and comorbidity. METHODS: Data from the Surveillance, Epidemiology, and End Results registry were linked with Medicare Health Outcomes Survey (MHOS) data. Eligible patients (n = 445) were Medicare beneficiaries aged >= 65 years from 1998 to 2003 whose first prostate cancer diagnosis occurred between their baseline and follow-up MHOS. By using propensity score matching, 2225 participants without cancer were identified from the MHOS data. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form-36 survey and the activities of daily living scale. RESULTS: Before diagnosis, patients with prostate cancer reported HRQOL similar to that of men without cancer. After diagnosis, men with prostate cancer experienced significant decrements in physical, mental, and social aspects of their lives relative to controls, especially within the first 6 months after diagnosis. For men who were surveyed beyond 1 year after diagnosis, HRQOL was similar to that for controls. However, an increased risk for major depressive disorder was observed among men who received either conservative management or external beam radiation. CONCLUSIONS: The current findings illustrated the time-sensitive nature of decline in HRQOL after a cancer diagnosis and enhanced understanding of the impact of prostate cancer diagnosis and treatment on physical, mental, and social well being among older men. Cancer 2012;118;5679-87. (C) 2012 American Cancer Society. C1 [Reeve, Bryce B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Stover, Angela M.] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Jensen, Roxanne E.; Taylor, Kathryn L.; Potosky, Arnold L.] Georgetown Univ, Dept Oncol, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. [Clauser, Steven B.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Collins, Sean P.] Georgetown Univ Hosp, Dept Radiat Oncol, Washington, DC 20007 USA. RP Reeve, BB (reprint author), 135 Dauer Dr,1101-D McGavran Greenberg Bldg, Chapel Hill, NC 27599 USA. EM bbreeve@email.unc.edu FU National Cancer Institute [HHSN261201000642P] FX Dr. Reeve's work was supported under a National Cancer Institute contract to the University of North Carolina at Chapel Hill (HHSN261201000642P). NR 54 TC 33 Z9 33 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5679 EP 5687 DI 10.1002/cncr.27578 PG 9 WC Oncology SC Oncology GA 029GW UT WOS:000310483800028 PM 22544633 ER PT J AU Jain, M Zhang, LS He, M Patterson, EE Nilubol, N Fojo, AT Joshi, B Puri, R Kebebew, E AF Jain, Meenu Zhang, Lisa He, Mei Patterson, Erin E. Nilubol, Naris Fojo, Antonio T. Joshi, Bharat Puri, Raj Kebebew, Electron TI Interleukin-13 Receptor Alpha2 Is a Novel Therapeutic Target for Human Adrenocortical Carcinoma SO CANCER LA English DT Article DE interleukin-13 receptor alpha2; interleuken-13-Pseudomonas exotoxin; adrenocortical carcinoma; invasion ID CHIMERIC FUSION PROTEINS; SQUAMOUS-CELL CARCINOMA; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMAS; CANCER THERAPY; EXPRESSION; CHAIN; TUMORS; HEAD AB BACKGROUND. Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome-wide expression studies have demonstrated the overexpression of interleukin-13 receptor alpha2 (IL13R alpha 2) in some human malignancies. METHODS. The authors evaluated IL13R alpha 2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 R alpha 2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI-H295R [high IL13R alpha 2 expression] and SW13 [low IL13R alpha 2 expression]) to a highly specific IL-13 conjugated with Pseudomonas exotoxin (IL-13-PE) also was evaluated in both in vitro and in vivo models. RESULTS. IL13R alpha 2 was overexpressed in malignant tumors compared with benign and normal samples (15-fold higher; P < .05). Immunohistochemistry also confirmed higher protein expression in malignant and benign tumors than in normal adrenocortical tissues (P < .05). The half-maximal inhibitory concentration for IL-13-PE was 1.3 ng/mL in the NCI-H295R cell line and 1000 ng/mL in the SW13 cell line. Mice that received intratumoral or intraperitoneal IL-13-PE injection had a significant reduction in tumor size and increased tumor necrosis compared with control groups (P < .05) and also had prolonged survival (P < .05). IL13R alpha 2 protein expression increased in cells that were treated with IL-13 ligand along with cell invasion (P < .05). Direct IL13R alpha 2 knockdown decreased cellular proliferation and invasion (P < .05). CONCLUSIONS. The current results indicated that IL13R alpha 2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13R alpha 2 is a novel therapeutic target for the treatment of human ACC. Cancer 2012;118;5698-708 (C) 2012 American Cancer Society. C1 [Kebebew, Electron] NCI, Endocrine Oncol Branch, CRC Hatfield Clin Res Ctr 10, NIH, Bethesda, MD 20892 USA. [Joshi, Bharat; Puri, Raj] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Fojo, Antonio T.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, CRC Hatfield Clin Res Ctr 10, NIH, Bethesda, MD 20892 USA. EM electron.kebebew@nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health [1ZIABC011286-01, 1ZIABC011275-01] FX This study was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (grants 1ZIABC011286-01 and 1ZIABC011275-01). NR 41 TC 8 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2012 VL 118 IS 22 BP 5698 EP 5708 DI 10.1002/cncr.27629 PG 11 WC Oncology SC Oncology GA 029GW UT WOS:000310483800030 PM 22570059 ER PT J AU Mollersen, L Rowe, AD Illuzzi, JL Hildrestrand, GA Gerhold, KJ Tveteras, L Bjolgerud, A Wilson, DM Bjoras, M Klungland, A AF Mollersen, Linda Rowe, Alexander D. Illuzzi, Jennifer L. Hildrestrand, Gunn A. Gerhold, Katharina J. Tveteras, Linda Bjolgerud, Anja Wilson, David M., III Bjoras, Magnar Klungland, Arne TI Neil1 is a genetic modifier of somatic and germline CAG trinucleotide repeat instability in R6/1 mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID OXIDATIVELY DAMAGED DNA; HUNTINGTONS-DISEASE; TRANSGENIC MICE; GLYCOSYLASES NEIL1; OXIDIZED BASES; IN-VIVO; REPAIR; EXCISION; MUTATION; EXPANSION AB Huntingtons disease (HD) is a progressive neurodegenerative disorder caused by trinucleotide repeat (TNR) expansions. We show here that somatic TNR expansions are significantly reduced in several organs of R6/1 mice lacking exon 2 of Nei-like 1 (Neil1) (R6/1/Neil1(/)), when compared with R6/1/Neil1(/) mice. Somatic TNR expansion is measured by two different methods, namely mean repeat change and instability index. Reduced somatic expansions are more pronounced in male R6/1/Neil1(/) mice, although expansions are also significantly reduced in brain regions of female R6/1/Neil1(/) mice. In addition, we show that the lack of functional Neil1 significantly reduces germline expansion in R6/1 male mice. In vitro, purified human NEIL1 protein binds and excises 5-hydroxycytosine in duplex DNA more efficiently than in hairpin substrates. NEIL1 excision of cytosine-derived oxidative lesions could therefore be involved in initiating the process of TNR expansion, although other DNA modifications might also contribute. Altogether, these results imply that Neil1 contributes to germline and somatic HD CAG repeat expansion. C1 [Mollersen, Linda; Rowe, Alexander D.; Hildrestrand, Gunn A.; Tveteras, Linda; Bjoras, Magnar; Klungland, Arne] Natl Hosp Norway, Oslo Univ Hosp, Inst Med Microbiol, NO-0027 Oslo, Norway. [Illuzzi, Jennifer L.; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, IRP,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Klungland, A (reprint author), Natl Hosp Norway, Oslo Univ Hosp, Inst Med Microbiol, Sognsvannsveien 20, NO-0027 Oslo, Norway. EM arne.klungland@rr-research.no FU Norwegian Research Council; Norwegian Cancer Society; Centre for Molecular Biology and Neuroscience; Health Region South-East of Norway; Oslo University Hospital; National Institute on Aging, NIH FX This work was supported by the Norwegian Research Council (L. M., K.J.G., A. B.), the Norwegian Cancer Society (G. A. H., L. T.), the Centre for Molecular Biology and Neuroscience (A. D. R.), the Health Region South-East of Norway (A. D. R.), Oslo University Hospital (M. B., A. K.) and the Intramural Research Program of the National Institute on Aging, NIH (J.L.I. and D. M. W.). Funding to pay the Open Access publication charges for this article was provided by the Health Region South-East of Norway. NR 39 TC 23 Z9 23 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2012 VL 21 IS 22 BP 4939 EP 4947 DI 10.1093/hmg/dds337 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 027QV UT WOS:000310369000012 PM 22914735 ER PT J AU Timofeeva, MN Hung, RJ Rafnar, T Christiani, DC Field, JK Bickeboller, H Risch, A McKay, JD Wang, YF Dai, JC Gaborieau, V McLaughlin, J Brenner, D Narod, SA Caporaso, NE Albanes, D Thun, M Eisen, T Wichmann, HE Rosenberger, A Han, YH Chen, W Zhu, DK Spitz, M Wu, XF Pande, M Zhao, Y Zaridze, D Szeszenia-Dabrowska, N Lissowska, J Rudnai, P Fabianova, E Mates, D Bencko, V Foretova, L Janout, V Krokan, HE Gabrielsen, ME Skorpen, F Vatten, L Njolstad, I Chen, C Goodman, G Lathrop, M Benhamou, S Vooder, T Valk, K Nelis, M Metspalu, A Raji, O Chen, Y Gosney, J Liloglou, T Muley, T Dienemann, H Thorleifsson, G Shen, HB Stefansson, K Brennan, P Amos, CI Houlston, R Landi, MT AF Timofeeva, Maria N. Hung, Rayjean J. Rafnar, Thorunn Christiani, David C. Field, John K. Bickeboeller, Heike Risch, Angela McKay, James D. Wang, Yufei Dai, Juncheng Gaborieau, Valerie McLaughlin, John Brenner, Darren Narod, Steven A. Caporaso, Neil E. Albanes, Demetrius Thun, Michael Eisen, Timothy Wichmann, H. -Erich Rosenberger, Albert Han, Younghun Chen, Wei Zhu, Dakai Spitz, Margaret Wu, Xifeng Pande, Mala Zhao, Yang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Mates, Dana Bencko, Vladimir Foretova, Lenka Janout, Vladimir Krokan, Hans E. Gabrielsen, Maiken Elvestad Skorpen, Frank Vatten, Lars Njolstad, Inger Chen, Chu Goodman, Gary Lathrop, Mark Benhamou, Simone Vooder, Tonu Vaelk, Kristjan Nelis, Mari Metspalu, Andres Raji, Olaide Chen, Ying Gosney, John Liloglou, Triantafillos Muley, Thomas Dienemann, Hendrik Thorleifsson, Gudmar Shen, Hongbing Stefansson, Kari Brennan, Paul Amos, Christopher I. Houlston, Richard Landi, Maria Teresa CA TRICL Res Team TI Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; DNA DOUBLE-STRAND; SUSCEPTIBILITY LOCI; LARGE-SCALE; JAPANESE POPULATION; GENOTYPE IMPUTATION; NICOTINE DEPENDENCE; IN-VIVO; VARIANTS AB Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p216p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P 7.2 10(16)), 6p21 (P 2.3 10(14)) and 15q25 (P 2.2 10(63)). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL; rs1333040, P 3.0 10(7)) which was replicated in a series of 5415 Han Chinese (P 0.03; combined analysis, P 2.3 10(8)). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer. C1 [Wu, Xifeng; Pande, Mala] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Spitz, Margaret] Baylor Coll Med, Houston, TX 77030 USA. [Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany. [Wichmann, H. -Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, D-85764 Neuherberg, Germany. [Eisen, Timothy] Cambridge Univ Hosp NHS Fdn Trust, Dept Oncol, Cambridge, England. [Thun, Michael] Amer Canc Soc Epidemiol & Surveillance Res, Atlanta, GA 30301 USA. [Narod, Steven A.] Womens Coll Res Inst, Toronto, ON, Canada. [Caporaso, Neil E.; Albanes, Demetrius; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, US Publ Hlth Serv, Bethesda, MD 20892 USA. [Dai, Juncheng; Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Wang, Yufei; Houlston, Richard] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England. [Risch, Angela] DKFZ German Canc Res Ctr, Translat Lung Res Ctr Heidelberg TLRC H, D-69120 Heidelberg, Germany. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Dept Genet Epidemiol, Univ Med Ctr, D-37073 Gottingen, Germany. [Field, John K.; Raji, Olaide; Chen, Ying; Gosney, John; Liloglou, Triantafillos] Univ Liverpool, Roy Castle Lung Canc Res Programme, Dept Mol & Clin Canc Med, Canc Res Ctr,Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Christiani, David C.; Zhao, Yang] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rafnar, Thorunn; Thorleifsson, Gudmar; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Hung, Rayjean J.; McLaughlin, John; Brenner, Darren] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Timofeeva, Maria N.; McKay, James D.; Gaborieau, Valerie; Brennan, Paul] Int Agcy Res Canc, F-69008 Lyon, France. [Zaridze, David] Russian NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia. [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, PL-91348 Lodz, Poland. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica 97556, Slovakia. [Rudnai, Peter] Natl Inst Environm Hlth, H-1097 Budapest, Hungary. [Mates, Dana] Natl Inst Publ Hlth, Bucharest 050463, Romania. [Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague 12800 2, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic. [Janout, Vladimir] Palacky Univ, Olomouc 77515, Czech Republic. [Krokan, Hans E.; Gabrielsen, Maiken Elvestad] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway. [Skorpen, Frank] Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, Fac Med, N-7489 Trondheim, Norway. [Vatten, Lars] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, N-7489 Trondheim, Norway. [Njolstad, Inger] Univ Tromso, Dept Community Med, N-9037 Tromso, Norway. [Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Lathrop, Mark] Ctr Etud Polymorphisme Humain, F-75010 Paris, France. [Benhamou, Simone] INSERM, U946, F-75010 Paris, France. [Vooder, Tonu] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia. [Vaelk, Kristjan] Competence Ctr Reprod Med & Biol, EE-50410 Tartu, Estonia. [Nelis, Mari; Metspalu, Andres] Estonian Genome Ctr, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia. [Nelis, Mari] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Muley, Thomas] Univ Klinikum Heidelberg, Translat Res Unit, Heidelberg, Germany. [Dienemann, Hendrik] Univ Klinikum Heidelberg, Dept Thorac Surg, Thoraxklin, Heidelberg, Germany. [Amos, Christopher I.] Dartmouth Coll, Dept Community & Family Med, Geisel Sch Med, Hanover, NH 03750 USA. [Han, Younghun; Chen, Wei; Zhu, Dakai; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. RP Amos, CI (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, 46 Centerra Pkwy,Suite 330, Lebanon, NH 03766 USA. EM Christopher.I.Amos@Dartmouth.edu RI Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013; Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Albanes, Demetrius/B-9749-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010; Benhamou, Simone/K-6554-2015; Risch, Angela/H-2669-2013; Chen, Ying/I-4349-2013; OI Houlston, Richard/0000-0002-5268-0242; Risch, Angela/0000-0002-8026-5505; mates, dana/0000-0002-6219-9807; Lissowska, Jolanta/0000-0003-2695-5799; Field, John/0000-0003-3951-6365 FU National Institute of Health (NIH) [U19CA148127, 5R01CA055769, 5R01CA127219, 5R01CA133996, 5R01CA121197, P50 CA70907, R01CA121197, RO1 CA127219, U19 CA148127, RO1 CA55769, HHSN268200782096C, CA074386, CA092824, CA090578]; Canadian Cancer Society Research Institute [020214]; Ontario Institute of Cancer; Cancer Care Ontario Chair Award; Cancer Research UK [C1298/A8780, C1298/A8362]; NCRN, HEAL; Sanofi-Aventis; Roy Castle Lung Cancer Foundation, UK; Deutsche Krebshilfe [70-2919]; Helmholtz-DAAD fellowship [A/07/97379]; National Institute of Health (USA) [U19CA148127]; GSF; German Federal Ministry of Education, Science, Research and Technology; State of Bavaria; National Genome Research Network (NGFN); DFG [BI 576/2-1, BI 576/2-2]; Helmholtzgemeinschaft (HGF); Federal office for Radiation Protection [BfS: STSch4454]; Institut National du Cancer, France; European Community [LSHG-CT-2005-512113]; Norwegian Cancer Association and the Functional Genomics Programme of Research Council of Norway; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; National Cancer Institute of the U.S. National Institutes of Health [R01 CA111703, UO1 CA63673]; Fred Hutchinson Cancer Research Center; US National Cancer Institute [R01 CA092039]; FP7 grant [REGPOT 245536]; Estonian Government [SF0180142s08]; EU RDF; IARC; NCI, Division of Cancer Epidemiology and Genetics; U.S. Public Health Service from the NCI [N01-CN-45165, N01-RC-45035, N01-RC-37004]; NCI [NO1-CN-25514]; Georgetown University [NO1-CN-25522]; Pacific Health Research Institute [NO1-CN-25515]; Henry Ford Health System [NO1-CN-25512]; University of Minnesota [NO1-CN-25513]; Washington University [NO1-CN-25516]; University of Pittsburgh [NO1-CN-25511]; University of Utah [NO1-CN-25524]; Marshfield Clinic Research Foundation [NO1-CN-25518]; University of Alabama at Birmingham [NO1-CN-75022]; University of Alabama at Birmingham, Westat, Inc. [NO1-CN-25476]; University of California, Los Angeles [NO1-CN-25404]; American Cancer Society; NIH Genes, Environment and Health Initiative (GEI) [HG-06-033-NCI-01, RO1HL091172-01]; CPRIT grant [RP100443]; China National High-Tech Research and Development Program Grant [2009AA022705]; National Key Basic Research Program Grant [2011CB503805]; National Natural Science Foundation of China [30730080, 30972541, 30901233, 30872178] FX This study was supported by the grant from the National Institute of Health (NIH) (U19CA148127). The SLRI study was supported by Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R. H. The ICR study was supported by Cancer Research UK (C1298/A8780 and C1298/A8362-Bobby Moore Fund for Cancer Research UK) and NCRN, HEAL and Sanofi-Aventis. Additional funding was obtained from NIH grants (5R01CA055769, 5R01CA127219, 5R01CA133996, and 5R01CA121197). The Liverpool Lung Project (LLP) was supported by The Roy Castle Lung Cancer Foundation, UK. The ICR and LLP studies made use of genotyping data from the Wellcome Trust Case Control Consortium 2 (WTCCC2); a full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Sample collection for the Heidelberg lung cancer study was in part supported by a grant (70-2919) from the Deutsche Krebshilfe. The work was additionally supported by a Helmholtz-DAAD fellowship (A/07/97379 to M.N.T.) and by the National Institute of Health (USA) (U19CA148127). The KORA Surveys were financed by the GSF, which is funded by the German Federal Ministry of Education, Science, Research and Technology and the State of Bavaria. The LUng Cancer in the Young study (LUCY) was funded in part by the National Genome Research Network (NGFN), the DFG (BI 576/2-1; BI 576/2-2), the Helmholtzgemeinschaft (HGF) and the Federal office for Radiation Protection (BfS: STSch4454). Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum Muenchen. Support for the Central Europe, HUNT2/Tromso and CARET genome-wide studies was provided by Institut National du Cancer, France. Support for the HUNT2/Tromso genome-wide study was also provided by the European Community (Integrated Project DNA repair, LSHG-CT-2005-512113), the Norwegian Cancer Association and the Functional Genomics Programme of Research Council of Norway. Support for the Central Europe study, Czech Republic, was also provided by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Support for the CARET genome-wide study was also provided by grants from the National Cancer Institute of the U.S. National Institutes of Health (R01 CA111703 and UO1 CA63673) and by funds from the Fred Hutchinson Cancer Research Center. Additional funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Cancer Institute (R01 CA092039). The lung cancer GWAS from Estonia was partly supported by a FP7 grant (REGPOT 245536), by the Estonian Government (SF0180142s08), by EU RDF in the frame of Centre of Excellence in Genomics and Estoinian Research Infrastructure's Roadmap and by University of Tartu (SP1GVARENG). The work reported in this paper was partly undertaken during the tenure of a Postdoctoral Fellowship from the IARC (for MNT). The Environment and Genetics in Lung Cancer Etiology (EAGLE), the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and the Prostate, Lung, Colon, Ovary Screening Trial (PLCO) studies and the genotyping of ATBC, the Cancer Prevention Study II Nutrition Cohort (CPS-II) and part of PLCO were supported by the Intramural Research Program of NIH, NCI, Division of Cancer Epidemiology and Genetics. ATBC was also supported by U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035 and N01-RC-37004) from the NCI.; PLCO was also supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), Pacific Health Research Institute (NO1-CN-25515), Henry Ford Health System (NO1-CN-25512), University of Minnesota (NO1-CN-25513), Washington University (NO1-CN-25516), University of Pittsburgh (NO1-CN-25511), University of Utah (NO1-CN-25524), Marshfield Clinic Research Foundation (NO1-CN-25518), University of Alabama at Birmingham (NO1-CN-75022, Westat, Inc. NO1-CN-25476), University of California, Los Angeles (NO1-CN-25404). The Cancer Prevention Study II Nutrition Cohort was supported by the American Cancer Society. The NIH Genes, Environment and Health Initiative (GEI) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438 and NIH HHSN268200782096C) and study coordination at the GENEVA Coordination Center (U01 HG004446) for EAGLE and part of PLCO studies. Funding for the MD Anderson Cancer Study was provided by NIH grants (P50 CA70907, R01CA121197, RO1 CA127219, U19 CA148127, RO1 CA55769) and CPRIT grant (RP100443). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). The Harvard Lung Cancer Study was funded by Funded by National Institutes of Health (CA074386, CA092824, CA090578). The Nanjing study and Beijing studies were funded by the China National High-Tech Research and Development Program Grant (2009AA022705), the National Key Basic Research Program Grant (2011CB503805) and the National Natural Science Foundation of China (30730080, 30972541, 30901233 and 30872178). Funding to pay the Open Access publication charges for this article was provided by the grant from the National Institute of Health (NIH) (U19CA148127). NR 92 TC 68 Z9 70 U1 0 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2012 VL 21 IS 22 BP 4980 EP 4995 DI 10.1093/hmg/dds334 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 027QV UT WOS:000310369000016 PM 22899653 ER PT J AU Keller, MF Saad, M Bras, J Bettella, F Nicolaou, N Simon-Sanchez, J Mittag, F Buchel, F Sharma, M Gibbs, JR Schulte, C Moskvina, V Durr, A Holmans, P Kilarski, LL Guerreiro, R Hernandez, DG Brice, A Ylikotila, P Stefansson, H Majamaa, K Morris, HR Williams, N Gasser, T Heutink, P Wood, NW Hardy, J Martinez, M Singleton, AB Nalls, MA AF Keller, Margaux F. Saad, Mohamad Bras, Jose Bettella, Francesco Nicolaou, Nayia Simon-Sanchez, Javier Mittag, Florian Buechel, Finja Sharma, Manu Gibbs, J. Raphael Schulte, Claudia Moskvina, Valentina Durr, Alexandra Holmans, Peter Kilarski, Laura L. Guerreiro, Rita Hernandez, Dena G. Brice, Alexis Ylikotila, Pauli Stefansson, Hreinn Majamaa, Kari Morris, Huw R. Williams, Nigel Gasser, Thomas Heutink, Peter Wood, Nicholas W. Hardy, John Martinez, Maria Singleton, Andrew B. Nalls, Michael A. CA IPDGC WTCCC2 TI Using genome-wide complex trait analysis to quantify 'missing heritability' in Parkinson's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID FAMILIAL AGGREGATION; GLUCOCEREBROSIDASE MUTATIONS; RARE VARIANTS; COMMON SNPS; EARLY-ONSET; ASSOCIATION; METAANALYSIS; GENETICS; TWINS; SUSCEPTIBILITY AB Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinsons disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27 (95 CI 1738, P 8.08E 08) phenotypic variance associated with all types of PD, 15 (95 CI 0.2 to 33, P 0.09) phenotypic variance associated with early-onset PD and 31 (95 CI 1744, P 1.34E 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered. C1 [Nalls, Michael A.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Keller, Margaux F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA. [Saad, Mohamad; Mittag, Florian; Buechel, Finja; Martinez, Maria] Ctr Physiopathol Toulouse Purpan, INSERM, UMR 1043, F-31073 Toulouse, France. [Saad, Mohamad; Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France. [Bras, Jose; Gibbs, J. Raphael; Guerreiro, Rita; Hernandez, Dena G.; Wood, Nicholas W.; Hardy, John] UCL, Dept Mol Neurosci, Inst Neurol, London, England. [Wood, Nicholas W.] UCL, UCL Genet Inst, London, England. [Bettella, Francesco; Stefansson, Hreinn; Heutink, Peter] DeCODE Genet, Sci Serv, IS-101 Reykjavik, Iceland. [Nicolaou, Nayia; Simon-Sanchez, Javier] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Gen, Amsterdam, Netherlands. [Sharma, Manu; Schulte, Claudia; Gasser, Thomas] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany. [Sharma, Manu; Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis, Tubingen, Germany. [Moskvina, Valentina; Holmans, Peter; Kilarski, Laura L.; Morris, Huw R.; Williams, Nigel] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Sch Med, Cardiff, S Glam, Wales. [Moskvina, Valentina; Holmans, Peter; Kilarski, Laura L.; Morris, Huw R.; Williams, Nigel] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales. [Durr, Alexandra; Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France. [Durr, Alexandra; Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France. [Durr, Alexandra; Brice, Alexis] INSERM, UMR S975, Paris, France. [Durr, Alexandra; Brice, Alexis] CNRS, UMR 7225, Paris, France. [Ylikotila, Pauli] Turku Univ Hosp, Dept Neurol, Turku, Finland. [Ylikotila, Pauli] Univ Turku, SF-20500 Turku, Finland. [Majamaa, Kari] Univ Oulu, Dept Clin Med, Oulu, Finland. RP Nalls, MA (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA. EM nallsm@mail.nih.gov RI Blackwell, Jenefer/H-3015-2015; Trabzuni, Daniah/C-4034-2012; Mathew, Christopher/G-3434-2015; Martinez, Maria/B-3111-2013; Guerreiro, Rita/A-1327-2011; corvol, jean-christophe/I-6387-2012; Revesz, Tamas/A-8732-2010; Deuschl, Gunther/A-7986-2010; Morris, Huw/B-8527-2008; Hardy, John/C-2451-2009; Scheffer, Hans/E-4644-2012; lambert, jean-charles/F-8787-2013; Wood, Nicholas/C-2505-2009; LICEND, CEMND/F-1296-2015; Traynor, Bryan/G-5690-2010; Bloem, Bastiaan/E-3812-2010; Bras, Jose/A-1428-2011; Charlesworth, Gavin/B-5895-2011; Singleton, Andrew/C-3010-2009; O'Sullivan, Sean/C-9333-2012; Jankowski, Janusz/H-2706-2012 OI Chen, Honglei/0000-0003-3446-7779; Pirinen, Matti/0000-0002-1664-1350; Kilarski, Laura/0000-0003-0645-3134; Gillman, Matthew/0000-0002-2340-6930; Holmans, Peter/0000-0003-0870-9412; Plomin, Robert/0000-0002-0756-3629; Stefansson, Hreinn/0000-0002-9331-6666; Escott-Price, Valentina/0000-0003-1784-5483; Rivadeneira, Fernando/0000-0001-9435-9441; Palmer, Colin/0000-0002-6415-6560; Bhatia, Kailash/0000-0001-8185-286X; Trabzuni, Daniah/0000-0003-4826-9570; Mathew, Christopher/0000-0003-4178-1838; Martinez, Maria/0000-0003-2180-4537; corvol, jean-christophe/0000-0001-7325-0199; Revesz, Tamas/0000-0003-2501-0259; Bras, Jose/0000-0001-8186-0333; Corvin, Aiden/0000-0001-6717-4089; Morris, Huw/0000-0002-5473-3774; Scheffer, Hans/0000-0002-2986-0915; Wood, Nicholas/0000-0002-9500-3348; O'Sullivan, Sean/0000-0002-0583-7956; Jankowski, Janusz/0000-0003-2130-9181 FU National Institute on Aging, National Institute of Neurological Disorders and Stroke, NIEHS; NHGRI of the National Institutes of Health, Department of Health and Human Services [Z01-AG000949-02, Z01-ES101986]; US Department of Defense [W81XWH-09-2-0128]; National Institutes of Health [NS057105, RR024992]; American Parkinson Disease Association (APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; Prinses Beatrix Fonds; section of medical genomics; Forschungszentrum fur Umwelt und Gesundheit; German Federal Ministry of Education, Science, Research, and Technology; State of Bavaria; German National Genome Network (NGFNplus) [01GS08134]; German Ministry for Education and Research; German Federal Ministry of Education and Research [NGFN 01GR0468, PopGen]; ERA-NET NEURON [01EW0908]; Helmholtz Alliance Mental Health in an Ageing Society [HA-215]; Helmholtz Association; French National Agency of Research [ANR-08-MNP-012]; Michael J. Fox Foundation; Landspitali University Hospital; Icelandic Research Council; European Community [PIAP-GA-2008-230596]; Wellcome Trust [083948/Z/07/Z]; Medical Research Council; Wellcome Trust disease centre [WT089698/Z/09/Z]; Parkinson's UK [8047, J-0804]; Medical Research Council [G0700943]; Department of Health's National Institute for Health Research Biomedical Research Centres; Wellcome Trust/Medical Research Council Joint Call in Neurodegeneration award [WT089698]; France Parkinson Association FX This work was supported by the Intramural Research Programs of the National Institute on Aging, National Institute of Neurological Disorders and Stroke, NIEHS and NHGRI of the National Institutes of Health, Department of Health and Human Services (project numbers Z01-AG000949-02 and Z01-ES101986), human subjects protocol 2003-077. This work was also supported by the US Department of Defense (award number W81XWH-09-2-0128); National Institutes of Health (grants NS057105 and RR024992); American Parkinson Disease Association (APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; and the section of medical genomics, the Prinses Beatrix Fonds. The KORA (Cooperative Research in the Region of Augsburg) research platform was started and financed by the Forschungszentrum fur Umwelt und Gesundheit, which is funded by the German Federal Ministry of Education, Science, Research, and Technology and by the State of Bavaria. This study was also funded by the German National Genome Network (NGFNplus number 01GS08134, German Ministry for Education and Research); by the German Federal Ministry of Education and Research (NGFN 01GR0468, PopGen); and 01EW0908 in the frame of ERA-NET NEURON and Helmholtz Alliance Mental Health in an Ageing Society (HA-215), which was funded by the Initiative and Networking Fund of the Helmholtz Association. The French GWAS work was supported by the French National Agency of Research (ANR-08-MNP-012). This study was also funded by the Michael J. Fox Foundation (MS), and sponsored by the Landspitali University Hospital Research Fund (grant to S.Sv.); Icelandic Research Council (grant to S.Sv.); and European Community Framework Programme 7, People Programme and IAPP on novel genetic and phenotypic markers of Parkinson's disease and Essential Tremor (MarkMD), contract number PIAP-GA-2008-230596 MarkMD (to H. P. and J.Hu.). Genotyping of UK replication cases on ImmunoChip was part of the WTCCC2 project, which was funded by the Wellcome Trust (083948/Z/07/Z). This study was supported by the Medical Research Council and Wellcome Trust disease centre (grant WT089698/Z/09/Z to N.W.W., J. Ha. and A.Sc.). This study was also supported by Parkinson's UK (grants 8047 and J-0804) and the Medical Research Council (G0700943). DNA extraction work that was done in the UK was undertaken at University College London Hospitals, University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding. This study was supported in part by the Wellcome Trust/Medical Research Council Joint Call in Neurodegeneration award (WT089698) to the Parkinson's Disease Consortium (UKPDC), whose members are from the UCL Institute of Neurology, University of Sheffield and the Medical Research Council Protein Phosphorylation Unit at the University of Dundee. Mohamad Saad was funded by the France Parkinson Association. NR 48 TC 59 Z9 61 U1 3 U2 44 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2012 VL 21 IS 22 BP 4996 EP 5009 DI 10.1093/hmg/dds335 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 027QV UT WOS:000310369000017 PM 22892372 ER PT J AU Song, YQ Yeung, E Liu, AY VanderWeele, TJ Chen, LW Lu, C Liu, CL Schisterman, EF Ning, Y Zhang, CL AF Song, Yiqing Yeung, Edwina Liu, Aiyi VanderWeele, Tyler J. Chen, Liwei Lu, Chen Liu, Chunling Schisterman, Enrique F. Ning, Yi Zhang, Cuilin TI Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CLINICAL-TRIALS; TCF7L2; GENETICS; GLUCOSE; EPIDEMIOLOGY; MECHANISMS; MELLITUS; ISLETS AB The objective of the study is to quantify the causal effect of -cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of -cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of -cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of -cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95 confidence interval (CI)] was 0.87 (0.810.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-B) (P 3.0 10(5)). In addition, for measures based on intravenous glucose tolerance test, ORs (95 CI) associated with type 2 diabetes risk were 0.24 (0.080.74) (P 0.01) and 0.14 (0.040.48) (P 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic -cell function itself in the etiology of type 2 diabetes. C1 [Yeung, Edwina; Schisterman, Enrique F.; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinfomat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Song, Yiqing] Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China. [Song, Yiqing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Liwei] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, New Orleans, LA USA. [Lu, Chen] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Liu, Chunling] Hong Kong Polytech Univ, Dept Appl Math, Hong Kong, Hong Kong, Peoples R China. [Ning, Yi] Virginia Commonwealth Univ, Sch Med, Dept Epidemiol & Community Med, Richmond, VA USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA. EM zhangcu@mail.nih.gov RI Lu, Chen/D-8514-2015; Yeung, Edwina/F-5992-2015; Liu, Chunling/A-4827-2015; OI Yeung, Edwina/0000-0002-3851-2613; Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health; National Institutes of Health [ES017876, HD060696] FX C.Z., E.Y., C. L. and E. F. S. are supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. T.J.V. is supported by grants from the National Institutes of Health (ES017876 and HD060696). NR 38 TC 8 Z9 8 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2012 VL 21 IS 22 BP 5010 EP 5018 DI 10.1093/hmg/dds339 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 027QV UT WOS:000310369000018 PM 22936689 ER PT J AU Ghedin, E Holmes, EC DePasse, JV Pinilla, LT Fitch, A Hamelin, ME Papenburg, J Boivin, G AF Ghedin, Elodie Holmes, Edward C. DePasse, Jay V. Pinilla, Lady Tatiana Fitch, Adam Hamelin, Marie-Eve Papenburg, Jesse Boivin, Guy TI Presence of Oseltamivir-Resistant Pandemic A/H1N1 Minor Variants Before Drug Therapy With Subsequent Selection and Transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NEURAMINIDASE INHIBITORS; MIXED INFECTION; HIV-1 INFECTION; INFLUENZA-VIRUS; H1N1 VIRUS; EMERGENCE; GENOME AB A small proportion (1%-1.5%) of 2009 pandemic influenza A/H1N1 virus strains (A[H1N1]pdm09) are oseltamivir resistant, almost exclusively because of a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated individuals before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we used ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from 2 individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts before the onset of therapy. We also found evidence for the transmission of this drug-resistant variant with drug-susceptible viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir treatment. C1 [Ghedin, Elodie; DePasse, Jay V.; Fitch, Adam] Univ Pittsburgh, Ctr Vaccine Res, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Pinilla, Lady Tatiana; Hamelin, Marie-Eve; Boivin, Guy] Ctr Hosp Univ Quebec, Ctr Rech, Quebec City, PQ, Canada. [Pinilla, Lady Tatiana; Hamelin, Marie-Eve; Boivin, Guy] Univ Laval, Quebec City, PQ, Canada. [Papenburg, Jesse] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. RP Ghedin, E (reprint author), Univ Pittsburgh, Ctr Vaccine Res, Sch Med, Dept Computat & Syst Biol, 3501 5th Ave,BST3 Rm 9043B, Pittsburgh, PA 15261 USA. EM elg21@pitt.edu; guy.boivin@crchul.ulaval.ca OI Holmes, Edward/0000-0001-9596-3552 FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health [U54 GM088491]; National Institute of General Medical Sciences at the National Institutes of Health [2R01 GM080533-06]; Canadian Institutes of Health Research; GlaxoSmithKline FX This work was supported in part by National Institute of Allergy and Infectious Diseases at the National Institutes of Health (U54 GM088491), National Institute of General Medical Sciences at the National Institutes of Health (2R01 GM080533-06 to E. C. H.), and the Canadian Institutes of Health Research (to G. B.).; G. B. has received a research grant from GlaxoSmithKline. All other authors: No conflicts. NR 26 TC 30 Z9 30 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2012 VL 206 IS 10 BP 1504 EP 1511 DI 10.1093/infdis/jis571 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 025UI UT WOS:000310220000006 PM 22966122 ER PT J AU Fowkes, FJI McGready, R Cross, NJ Hommel, M Simpson, JA Elliott, SR Richards, JS Lackovic, K Viladpai-Nguen, J Narum, D Tsuboi, T Anders, RF Nosten, F Beeson, JG AF Fowkes, Freya J. I. McGready, Rose Cross, Nadia J. Hommel, Mirja Simpson, Julie A. Elliott, Salenna R. Richards, Jack S. Lackovic, Kurt Viladpai-Nguen, Jacher Narum, David Tsuboi, Takafumi Anders, Robin F. Nosten, Francois Beeson, James G. TI New Insights into Acquisition, Boosting, and Longevity of Immunity to Malaria in Pregnant Women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; MEROZOITE ANTIGENS; ANTIBODY-RESPONSES; VIVAX MALARIA; CHILDREN; PARASITEMIA; PROTECTION; DURATION; VAR2CSA AB Background. How antimalarial antibodies are acquired and maintained during pregnancy and boosted after reinfection with Plasmodium falciparum and Plasmodium vivax is unknown. Methods. A nested case-control study of 467 pregnant women (136 Plasmodium-infected cases and 331 uninfected control subjects) in northwestern Thailand was conducted. Antibody levels to P. falciparum and P. vivax merozoite antigens and the pregnancy-specific PfVAR2CSA antigen were determined at enrollment (median 10 weeks gestation) and throughout pregnancy until delivery. Results. Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection. There was evidence of boosting with each successive infection for P. falciparum responses, suggesting the presence of immunological memory. However, the half-lives of Plasmodium antibody responses were relatively short, compared with measles (457 years), and much shorter for merozoite responses (0.8-7.6 years), compared with PfVAR2CSA responses (36-157 years). The longer half-life of antibodies to PfVAR2CSA suggests that antibodies acquired in one pregnancy may be maintained to protect subsequent pregnancies. Conclusions. These findings may have important practical implications for predicting the duration of vaccine-induced responses by candidate antigens and supports the development of malaria vaccines to protect pregnant women. C1 [Fowkes, Freya J. I.; Cross, Nadia J.; Hommel, Mirja; Richards, Jack S.; Beeson, James G.] Macfarlane Burnet Inst Med Res, Melbourne, Vic 3004, Australia. [Fowkes, Freya J. I.; Simpson, Julie A.] Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Richards, Jack S.] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia. [Fowkes, Freya J. I.; Cross, Nadia J.; Hommel, Mirja; Elliott, Salenna R.; Richards, Jack S.; Lackovic, Kurt; Beeson, James G.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Anders, Robin F.] La Trobe Univ, Dept Biochem, Bundoora, Vic 3086, Australia. [McGready, Rose; Viladpai-Nguen, Jacher; Nosten, Francois] Mae Sot, Shoklo Malaria Res Unit, Bangkok, Thailand. [McGready, Rose; Nosten, Francois] Mahidol Univ, Fac Trop Med, Bangkok, Thailand. [McGready, Rose; Nosten, Francois] Univ Oxford, Ctr Trop Med, Nuffield Dept Clin Med, CCVTM, Oxford OX1 2JD, England. [Narum, David] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 790, Japan. RP Fowkes, FJI (reprint author), Macfarlane Burnet Inst Med Res, 85 Commercial Rd, Melbourne, Vic 3004, Australia. EM fowkes@burnet.edu.au; beeson@burnet.edu.au OI Fowkes, Freya/0000-0001-5832-9464; Simpson, Julie/0000-0002-2660-2013; Nosten, Francois/0000-0002-7951-0745; McGready, Rose/0000-0003-1621-3257 FU National Health and Medical Research Council of Australia; Australian Research Council; Victorian State Government; Wellcome Trust of Great Britain FX This work was supported by the National Health and Medical Research Council of Australia (to J.B., F. F., and J. R.), Infrastructure for Research Institutes Support Scheme Grant, Australian Research Council (to J. B.), and Victorian State Government Operational Infrastructure Support. SMRU is part of the Mahidol Oxford University Tropical Medicine Research Unit supported by the Wellcome Trust of Great Britain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 40 Z9 40 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2012 VL 206 IS 10 BP 1612 EP 1621 DI 10.1093/infdis/jis566 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 025UI UT WOS:000310220000018 PM 22966126 ER PT J AU Huang, JH Ofek, G Laub, L Louder, MK Doria-Rose, NA Longo, NS Imamichi, H Bailer, RT Chakrabarti, B Sharma, SK Alam, SM Wang, T Yang, YP Zhang, BS Migueles, SA Wyatt, R Haynes, BF Kwong, PD Mascola, JR Connors, M AF Huang, Jinghe Ofek, Gilad Laub, Leo Louder, Mark K. Doria-Rose, Nicole A. Longo, Nancy S. Imamichi, Hiromi Bailer, Robert T. Chakrabarti, Bimal Sharma, Shailendra K. Alam, S. Munir Wang, Tao Yang, Yongping Zhang, Baoshan Migueles, Stephen A. Wyatt, Richard Haynes, Barton F. Kwong, Peter D. Mascola, John R. Connors, Mark TI Broad and potent neutralization of HIV-1 by a gp41-specific human antibody SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; MONOCLONAL-ANTIBODIES; GLYCOPROTEIN GP41; T-CELLS; EPITOPE; MEMBRANE; BINDING; 4E10; SPECIFICITIES AB Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes similar to 98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein. C1 [Huang, Jinghe; Laub, Leo; Imamichi, Hiromi; Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Ofek, Gilad; Louder, Mark K.; Doria-Rose, Nicole A.; Longo, Nancy S.; Bailer, Robert T.; Wang, Tao; Yang, Yongping; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Chakrabarti, Bimal; Sharma, Shailendra K.; Wyatt, Richard] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Alam, S. Munir; Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA. RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM mconnors@nih.gov RI Huang, Jinghe/O-1986-2015 FU NIAID; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX We thank C. W. Hallahan for statistical analyses. We thank K. Lloyd. R. Parks, J. Eudailey and J. Blinn for performing autoantibody assays. We also thank M. Zwick for providing us with the HIV-1 JR2 MPER alanine mutant pseudovirus plasmids. HIV-2/HIV-1 chimaeras were provided by G. Shaw and L. Morris. We thank J. Stuckey for assistance with figures, and members of the Structural Biology Section and Structural Bioinformatics Core, Vaccine Research Center, for discussions and comments on the manuscript. This project has been funded in part with federal funds from the Intramural Research Programs of NIAID and the National Cancer Institute, National Institutes of Health, under Contract no. HHSN261200800001E. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 56 TC 337 Z9 340 U1 6 U2 92 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 15 PY 2012 VL 491 IS 7424 BP 406 EP + DI 10.1038/nature11544 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 036MY UT WOS:000311031600038 PM 23151583 ER PT J AU Liu, ZM de Zwart, JA Yao, B van Gelderen, P Kuo, LW Duyn, JH AF Liu, Zhongming de Zwart, Jacco A. Yao, Bing van Gelderen, Peter Kuo, Li-Wei Duyn, Jeff H. TI Finding thalamic BOLD correlates to posterior alpha EEG SO NEUROIMAGE LA English DT Article DE EEG-fMRI; Alpha; Thalamus; Pulvinar; Lateral geniculate nucleus ID CHOLINERGIC RETICULAR SYSTEM; VISUOSPATIAL ATTENTION; RESPONSE FUNCTION; VISUAL-ATTENTION; HUMAN PULVINAR; METABOLIC-RATE; RHYTHM; CORTEX; FMRI; BRAIN AB Oscillatory electrical brain activity in the alpha (8-13 Hz) band is a prominent feature of human electroencephalography (EEG) during alert wakefulness, and is commonly thought to arise primarily from the occipital and parietal parts of the cortex. While the thalamus is considered to play a supportive role in the generation and modulation of cortical alpha rhythms, its precise function remains controversial and incompletely understood. To address this, we evaluated the correlation between the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals in the thalamus and the spontaneous modulation of posterior alpha rhythms based on EEG fMRI data acquired concurrently during an eyes-closed task-free condition. We observed both negative and positive correlations in the thalamus. The negative correlations were mostly seen within the visual thalamus, with a preference for the pulvinar over lateral geniculate nuclei. The positive correlations were found at the anterior and medial dorsal nuclei. Through functional connectivity analysis of the fMRI data, the pulvinar was found to be functionally associated with the same widespread cortical visual areas where the fMRI signals were negatively correlated with the posterior alpha modulation. In contrast, the dorsal nuclei were part of a distinct functional network that included brain stem, cingulate cortex and cerebellum. These observations are consistent with previous animal electrophysiology studies and the notion that the visual thalamus, and the pulvinar in particular, is intimately involved in the generation and spontaneous modulation of posterior alpha rhythms, facilitated by its reciprocal and widespread interaction with the cortical visual areas. We further postulate that the anterior and medial dorsal nuclei, being part of the ascending neuromodulatory system, may indirectly modulate cortical alpha rhythms by affecting vigilance and arousal levels. Published by Elsevier Inc. C1 [Liu, Zhongming; de Zwart, Jacco A.; Yao, Bing; van Gelderen, Peter; Kuo, Li-Wei; Duyn, Jeff H.] NINDS, Adv MRI Sect, LEMI, NIH,Lab Funct & Mol Imaging, Bethesda, MD 20982 USA. RP Liu, ZM (reprint author), NINDS, Adv MRI Sect, LEMI, NIH,Lab Funct & Mol Imaging, Bldg 10,Room B1D-723,9000 Rockville Pike,MSC 106, Bethesda, MD 20982 USA. EM liuz5@mail.nih.gov RI Kuo, Li-Wei/G-4007-2011 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 66 TC 20 Z9 20 U1 2 U2 18 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 NOV 15 PY 2012 VL 63 IS 3 BP 1060 EP 1069 DI 10.1016/j.neuroimage.2012.08.025 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100007 PM 22986355 ER PT J AU Zanotti-Fregonara, P Hines, CS Zoghbi, SS Liow, JS Zhang, Y Pike, VW Drevets, WC Mallinger, AG Zarate, CA Fujita, M Innis, RB AF Zanotti-Fregonara, Paolo Hines, Christina S. Zoghbi, Sami S. Liow, Jeih-San Zhang, Yi Pike, Victor W. Drevets, Wayne C. Mallinger, Alan G. Zarate, Carlos A., Jr. Fujita, Masahiro Innis, Robert B. TI Population-based input function and image-derived input function for [C-11](R)-rolipram PET imaging: Methodology, validation and application to the study of major depressive disorder SO NEUROIMAGE LA English DT Article DE Population-based input function; Image-derived input function; [C-11](R)-rolipram; Major depressive disorder ID BODY-SURFACE-AREA; INDEPENDENT COMPONENT ANALYSIS; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL METABOLIC-RATE; BLOOD-SAMPLING SITE; BRAIN PET; DRUG CONCENTRATION; MARKED DEPENDENCE; FDG PET; QUANTIFICATION AB Quantitative PET studies of neuroreceptor tracers typically require that arterial input function be measured. The aim of this study was to explore the use of a population-based input function (PBIF) and an image-derived input function (IDIF) for [C-11](R)-rolipram kinetic analysis, with the goal of reducing - and possibly eliminating - the number of arterial blood samples needed to measure parent radioligand concentrations. Methods: A PBIF was first generated using [C-11](R)-rolipram parent time-activity curves from 12 healthy volunteers (Group 1). Both invasive (blood samples) and non-invasive (body weight, body surface area, and lean body mass) scaling methods for PBIF were tested. The scaling method that gave the best estimate of the Logan-V-T values was then used to determine the test-retest variability of PBIF in Group 1 and then prospectively applied to another population of 25 healthy subjects (Group 2), as well as to a population of 26 patients with major depressive disorder (Group 3). Results were also compared to those obtained with an image-derived input function (IDIF) from the internal carotid artery. In some subjects, we measured arteriovenous differences in [C-11](R)-rolipram concentration to see whether venous samples could be used instead of arterial samples. Finally, we assessed the ability of IDIF and PBIF to discriminate depressed patients (MDD) and healthy subjects. Results: Arterial blood-scaled PBIF gave better results than any non-invasive scaling technique. Excellent results were obtained when the blood-scaled PBIF was prospectively applied to the subjects in Group 2 (V-T ratio 1.02 +/- 0.05; mean +/- SD) and Group 3 (V-T ratio 1.03 +/- 0.04). Equally accurate results were obtained for two subpopulations of subjects drawn from Groups 2 and 3 who had very differently shaped (i.e. "flatter" or "steeper") input functions compared to PBIF (V-T ratio 1.07 +/- 0.04 and 0.99 +/- 0.04, respectively). Results obtained via PBIF were equivalent to those obtained via IDIF (V-T ratio 0.99 +/- 0.05 and 1.00 +/- 0.04 for healthy subjects and MDD patients, respectively). Retest variability of PBIF was equivalent to that obtained with full input function and IDIF (14.5%, 15.2%, and 14.1%, respectively). Due to [C-11](R)-rolipram arteriovenous differences, venous samples could not be substituted for arterial samples. With both IDIF and PBIF, depressed patients had a 20% reduction in [C-11](R)-rolipram binding as compared to control (two-way ANOVA: p = 0.008 and 0.005, respectively). These results were almost equivalent to those obtained using 23 arterial samples. Conclusion: Although some arterial samples are still necessary, both PBIF and IDIF are accurate and precise alternatives to full arterial input function for [C-11](R)-rolipram PET studies. Both techniques give accurate results with low variability, even for clinically different groups of subjects and those with very differently shaped input functions. Published by Elsevier Inc. C1 [Zanotti-Fregonara, Paolo; Hines, Christina S.; Zoghbi, Sami S.; Liow, Jeih-San; Zhang, Yi; Pike, Victor W.; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Drevets, Wayne C.] Univ Oklahoma, Hlth Sci Ctr, Sch Community Med, Dept Psychiat, Tulsa, OK USA. [Mallinger, Alan G.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) FX Dr. Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression. Dr. Zarate has assigned his rights in the patent to the U.S. government but will share a percentage of any royalties that may be received by the government. This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). NR 54 TC 15 Z9 15 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2012 VL 63 IS 3 BP 1532 EP 1541 DI 10.1016/j.neuroimage.2012.08.007 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100054 PM 22906792 ER PT J AU Handwerker, DA Roopchansingh, V Gonzalez-Castillo, J Bandettini, PA AF Handwerker, Daniel A. Roopchansingh, Vinai Gonzalez-Castillo, Javier Bandettini, Peter A. TI Periodic changes in fMRI connectivity SO NEUROIMAGE LA English DT Article DE BOLD; fMRI; Posterior cingulate; Default mode; Spontaneous fluctuations; Resting-state ID FUNCTIONAL CONNECTIVITY; BRAIN ACTIVITY; RESTING BRAIN; FLUCTUATIONS; REGRESSION; NETWORKS; SIGNAL AB The first two decades of brain research using fMRI have been dominated by studies that measure signal changes in response to a presented task. A rapidly increasing number of studies are showing that consistent activation maps appear by assessment of signal correlations during time periods in which the subjects were not directed to perform any specific task (i.e. "resting state correlations"). Even though neural interactions can happen on much shorter time scales, most "resting state" studies assess these temporal correlations over a period of about 5 to 10 min. Here we investigate how these temporal correlations change on a shorter time scale. We examine changes in brain correlations to the posterior cingulate cortex (PCC) across a 10-minute scan. We show: (1) fMRI correlations fluctuate over time, (2) these fluctuations can be periodic, and (3) correlations between the PCC and other brain regions fluctuate at distinct frequencies. While the precise frequencies of correlation fluctuations vary across subjects and runs, it is still possible to parse brain regions and combinations of brain regions based on fluctuation frequency differences. To evaluate the potential biological significance of these empirical observations, we then use synthetic time series data with identical amplitude spectra, but randomized phase to show that similar effects can still appear even if the timing relationships between voxels are randomized. This implies that observed correlation fluctuations could occur between regions with distinct amplitude spectra, whether or not there are dynamic changes in neural connectivity between such regions. As more studies of brain connectivity dynamics appear, particularly studies using correlation as a key metric, it is vital to better distinguish true neural connectivity dynamics from connectivity fluctuations that are inherently part of this method. Our results also highlight the rich information in the power spectra of fMRI data that can be used to parse brain regions. Published by Elsevier Inc. C1 [Handwerker, Daniel A.; Gonzalez-Castillo, Javier; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Roopchansingh, Vinai; Bandettini, Peter A.] NIMH, Funct MRI Facil, Bethesda, MD 20892 USA. RP Handwerker, DA (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Rm 1D80,10 Ctr Dr,MSC 1148, Bethesda, MD 20892 USA. EM handwerkerd@mail.nih.gov OI Gonzalez-Castillo, Javier/0000-0002-6520-5125 FU NIMH Intramural Research Program at NIH FX Some of these data were collected by K. Murphy and R.M. Birn. Comments from the handling editor, Stephen Smith, and anonymous reviewers significantly altered and improved this manuscript. Catie Chang gave advice and suggested useful references. This research was supported by the NIMH Intramural Research Program at NIH. NR 25 TC 96 Z9 96 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2012 VL 63 IS 3 BP 1712 EP 1719 DI 10.1016/j.neuroimage.2012.06.078 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100069 PM 22796990 ER PT J AU Nasr, S Tootell, RBH AF Nasr, Shahin Tootell, Roger B. H. TI Role of fusiform and anterior temporal cortical areas in facial recognition SO NEUROIMAGE LA English DT Article DE fMRI; Face recognition; Face inversion; Contrast reversal; FFA; Anterior temporal face patch ID SURFACE-BASED ANALYSIS; FACE RECOGNITION; CONGENITAL PROSOPAGNOSIA; OBJECT RECOGNITION; CEREBRAL-CORTEX; OCCIPITAL FACE; NEURAL BASIS; PERCEPTION; FMRI; INVERSION AB Recent fMRI studies suggest that cortical face processing extends well beyond the fusiform face area (FFA), including unspecified portions of the anterior temporal lobe. However, the exact location of such anterior temporal region(s), and their role during active face recognition, remain unclear. Here we demonstrate that (in addition to FFA) a small bilateral site in the anterior tip of the collateral sulcus ('AT: the anterior temporal face patch) is selectively activated during recognition of faces but not houses (a non-face object). In contrast to the psychophysical prediction that inverted and contrast reversed faces are processed like other non-face objects, both FFA and AT (but not other visual areas) were also activated during recognition of inverted and contrast reversed faces. However, response accuracy was better correlated to recognition-driven activity in AT, compared to FFA. These data support a segregated, hierarchical model of face recognition processing, extending to the anterior temporal cortex. (C) 2012 Elsevier Inc. All rights reserved. C1 [Nasr, Shahin; Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Tootell, Roger B. H.] MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Nasr, S (reprint author), Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM shahin@nmr.mgh.harvard.edu FU National Institutes of Health (NIH) [R01 MH67529, R01 EY017081]; Martinos Center for Biomedical Imaging; NCRR; MIND Institute FX We thank Xiaomin Yue, Garth Coombs and Ellen Lau for help with data collection, and Jon Polimini for help with imaging protocols. We thank Daphne Holt for review and suggestions on the manuscript. This study was supported by the National Institutes of Health (NIH grants R01 MH67529 and R01 EY017081 to RBHT), the Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute. NR 64 TC 42 Z9 42 U1 1 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 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2012 VL 63 IS 3 BP 1743 EP 1753 DI 10.1016/j.neuroimage.2012.08.031 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 027UK UT WOS:000310379100072 PM 23034518 ER PT J AU Svoboda, MD Christie, JM Eroglu, Y Freeman, KA Steiner, RD AF Svoboda, Melissa D. Christie, Jill M. Eroglu, Yasemen Freeman, Kurt A. Steiner, Robert D. TI Treatment of Smith-Lemli-Opitz Syndrome and Other Sterol Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE Smith-Lemli-Opitz syndrome; sterol disorders; cholesterol supplementation; simvastatin; behavior ID ABNORMAL CHOLESTEROL-METABOLISM; MULTIPLE CONGENITAL-ANOMALIES; AUTISM SPECTRUM DISORDERS; PLASMA CHOLESTANOL LEVELS; CEREBROTENDINOUS XANTHOMATOSIS; CHENODEOXYCHOLIC ACID; 7-DEHYDROCHOLESTEROL-DERIVED OXYSTEROLS; SIMVASTATIN TREATMENT; RETINAL DEGENERATION; DIETARY-CHOLESTEROL AB Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic condition with a broad phenotype that results from deficiency of the final enzyme of the cholesterol synthesis pathway. This defect causes low or low-normal plasma cholesterol levels and increased 7- and 8-dehydrocholesterol (DHC) levels. Many therapies for SLOS and other disorders of sterol metabolism have been proposed, and a few of them have been undertaken in selected patients, but robust prospective clinical trials with validated outcome measures are lacking. We review the current literature and expert opinion on treatments for SLOS and other selected sterol disorders, including dietary cholesterol therapy, statin treatment, bile acid supplementation, medical therapies, and surgical interventions, as well as directions for future therapies and treatment research. (C) 2012 Wiley Periodicals, Inc. C1 [Steiner, Robert D.] Oregon Hlth & Sci Univ, Dept Pediat, Fac Pediat Mol & Med Genet, Portland, OR 97239 USA. [Eroglu, Yasemen] Oregon Hlth & Sci Univ, Div Pediat Gastroenterol, Portland, OR 97239 USA. [Steiner, Robert D.] Oregon Hlth & Sci Univ, Program Mol & Cellular Biosci, Portland, OR 97239 USA. [Steiner, Robert D.] NIH, Sterol & Isoprenoid Res Consortium, STAIR, Rare Dis Clin Res Consortium RDCRC, Bethesda, MD 20892 USA. RP Steiner, RD (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, Fac Pediat Mol & Med Genet, 707 SW Gaines St CDRC P, Portland, OR 97239 USA. EM steinerr@ohsu.edu OI Steiner, Robert/0000-0003-4177-4590 FU NIH Rare Diseases Clinical Research Network (RDCRN) via the Sterol and Isoprenoid Research (STAIR) consortium; HHS [U54 HD 061939, R01 HL 073980]; [HHS U54 HD061939]; [HHS R01 HL 073980] FX Grant sponsor: HHS U54 HD061939.; Grant sponsor: HHS R01 HL 073980.; The authors thank Mary Lou Oster-Granite for her review of the manuscript. R. D. S. is supported by the NIH Rare Diseases Clinical Research Network (RDCRN) via the Sterol and Isoprenoid Research (STAIR) consortium, HHS grant U54 HD 061939, and by HHS grant R01 HL 073980. The authors thank Jean-Baptiste Roullet for creation of the figure. NR 87 TC 10 Z9 10 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2012 VL 160C IS 4 SI SI BP 285 EP 294 DI 10.1002/ajmg.c.31347 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 023YB UT WOS:000310072700005 PM 23042642 ER PT J AU Wolfe, LA Morava, E He, M Vockley, J Gibson, KM AF Wolfe, Lynne A. Morava, Eva He, Miao Vockley, Jerry Gibson, K. Michael TI Heritable disorders in the metabolism of the dolichols: A bridge from sterol biosynthesis to molecular glycosylation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE ichthyosis; retinitis pigmentosa; muscular dystrophy; dolichol; glycosylation; mannosylation; isoprene; isoprenoids; cholesterol ID PHOSPHATE-MANNOSE SYNTHASE; CONGENITAL DISORDER; DPM1; DEFICIENCY; MUTATION; IE AB Dolichols, polyisoprene alcohols derived from the mevalonate pathway of cholesterol synthesis, serve as carriers of glycan precursors for the formation of oligosaccharides important in protein glycosylation. Seven autosomal-recessively inherited disorders in the metabolism (synthesis, utilization, recycling) of the dolichols have recently been described, and all are associated with decreased lipid-linked oligosaccharides leading to underglycosylated proteins or lipids which facilitate their detection in the diagnostic laboratory. Multisystem pathology encompasses developmental delays and eye, heart, skin and muscle abnormalities; outcomes range from death in infancy to mild, late-onset diseasdisease. (C) 2012 Wiley Periodicals, Inc. C1 [Wolfe, Lynne A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Morava, Eva] Tulane Univ, Hayward Genet Ctr, New Orleans, LA 70118 USA. [Morava, Eva] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Disorders Glycosylat, IGMD, Nijmegen, Netherlands. [He, Miao] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [He, Miao] Emory Univ, Emory Biochem Genet Lab, Atlanta, GA 30322 USA. [Vockley, Jerry; Gibson, K. Michael] Emory Univ, Emory Biochem Genet Lab, Atlanta, GA 30322 USA. [Vockley, Jerry] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Vockley, Jerry] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Gibson, K. Michael] Washington State Univ, Coll Pharm, Pullman, WA 99164 USA. [Gibson, K. Michael] Oregon Hlth & Sci Univ, Biochem Genet Labs, Portland, OR 97201 USA. RP Wolfe, LA (reprint author), NIH, Undiagnosed Dis Program, 10 Ctr DR,MSC 1205,RM 3-2551, Bethesda, MD 20892 USA. EM lynne.wolfe@nih.gov RI Morava, E./L-4529-2015; OI Vockley, Jerry/0000-0002-8180-6457 FU Sterol and Isoprenoid Diseases (STAIR), a component of the NIH Rare Diseases Clinical Research Network (RDCRN) [U54HD61939]; NIH Office of Rare Diseases Research (ORDR) FX The authors are indebted to Drs. F. D. Porter and W. A. Gahl for their assistance in manuscript preparation. Partial support from the Sterol and Isoprenoid Diseases (STAIR) consortium (U54HD61939), a component of the NIH Rare Diseases Clinical Research Network (RDCRN), and the NIH Office of Rare Diseases Research (ORDR) is gratefully acknowledged (MH, JV, and KMG). The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 31 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2012 VL 160C IS 4 SI SI BP 322 EP 328 DI 10.1002/ajmg.c.31345 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 023YB UT WOS:000310072700008 PM 23059969 ER PT J AU Hooth, MJ Nyska, A Fomby, LM Vasconcelos, DY Vallant, M DeVito, MJ Walker, NJ AF Hooth, Michelle J. Nyska, Abraham Fomby, Laurene M. Vasconcelos, Daphne Y. Vallant, Molly DeVito, Michael J. Walker, Nigel J. TI Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats SO TOXICOLOGY LA English DT Article DE 1,2,3,4,6,7-hexachloronaphthalene (PCN 66); 1,2,3,5,6,7-hexachloronaphthalene (PCN 67); 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); Toxic equivalency factor; Relative potency; TEF ID DIOXIN-LIKE COMPOUNDS; DIBENZO-P-DIOXINS; POLYCHLORINATED NAPHTHALENES; ORGANOCHLORINE CONTAMINANTS; AROMATIC-HYDROCARBONS; EQUIVALENCY FACTORS; ADIPOSE-TISSUE; LESIONS; BIPHENYLS; EXPOSURE AB In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50,000 and 500,000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO toxic equivalency factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity. (c) 2012 Published by Elsevier Ireland Ltd. C1 [Hooth, Michelle J.; Vallant, Molly; DeVito, Michael J.; Walker, Nigel J.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Nyska, Abraham] Tel Aviv Univ, Timrat, Israel. [Fomby, Laurene M.; Vasconcelos, Daphne Y.] Battelle Mem Inst, Columbus, OH 43201 USA. RP Walker, NJ (reprint author), NIEHS, Div Natl Toxicol Program, NIH, 111 Alexander Dr,POB 12233,K2-02, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov; anyska@bezeqint.net; fombyl@battelle.org; vasconcelosd@columbus.rr.com; vallant@niehs.nih.gov; devitom@niehs.nih.gov; walker3@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS; Intramural Research Program of the NIH FX This research was supported by NIEHS and by the Intramural Research Program of the NIH. This article is the work product of group which includes employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the United States government. The authors would like to thank Drs Angelique Braen, Alexander Fucarelli, Raj Chhabra, Hiroyoshi Toyoshiba and colleagues at NIEHS for their help in the conduct of this project. We would also like to thank Drs Susan Elmore and Kembra Howdeshell at NIEHS for critical review of this manuscript. NR 32 TC 7 Z9 7 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 15 PY 2012 VL 301 IS 1-3 BP 85 EP 93 DI 10.1016/j.tox.2012.07.005 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 003RN UT WOS:000308629100011 PM 22813907 ER PT J AU Balduino, A Mello-Coelho, V Wang, Z Taichman, RS Krebsbach, PH Weeraratna, AT Becker, KG de Mello, W Taub, DD Borojevic, R AF Balduino, Alex Mello-Coelho, Valeria Wang, Zhou Taichman, Russell S. Krebsbach, Paul H. Weeraratna, Ashani T. Becker, Kevin G. de Mello, Wallace Taub, Dennis D. Borojevic, Radovan TI Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Bone marrow; Trabecular bone; Microenvironment; Osteoblast; Niche ID COLONY-STIMULATING FACTOR; STEM-CELLS; PROGENITOR CELLS; SELF-RENEWAL; NICHE; OSTEOBLASTS; MOBILIZATION; MAINTENANCE; EXPANSION; SUPPORT AB In the bone marrow cavity, hematopoietic stem cells (HSC) have been shown to reside in the endosteal and subendosteal perivascular niches, which play specific roles on HSC maintenance. Although cells with long-term ability to reconstitute full hematopoietic system can be isolated from both niches, several data support a heterogenous distribution regarding the cycling behavior of HSC. Whether this distinct behavior depends upon the role played by the stromal populations which distinctly create these two niches is a question that remains open. In the present report, we used our previously described in vivo assay to demonstrate that endosteal and subendosteal stromal populations are very distinct regarding skeletal lineage differentiation potential. This was further supported by a microarray-based analysis, which also demonstrated that these two stromal populations play distinct, albeit complementary, roles in HSC niche. Both stromal populations were preferentially isolated from the trabecular region and behave distinctly in vitro, as previously reported. Even though these two niches are organized in a very close range, in vivo assays and molecular analyses allowed us to identify endosteal stroma (F-OST) cells as fully committed osteoblasts and subendosteal stroma (F-RET) cells as uncommitted mesenchymal cells mainly represented by perivascular reticular cells expressing high levels of chemokine ligand, CXCL12. Interestingly, a number of cytokines and growth factors including interleukin-6 (IL-6), IL-7, IL-15, Hepatocyte growth factor (HGF) and stem cell factor (SCF) matrix metalloproteases (MMPs) were also found to be differentially expressed by F-OST and F-RET cells. Further microarray analyses indicated important mechanisms used by the two stromal compartments in order to create and coordinate the "quiescent" and "proliferative" niches in which hematopoietic stem cells and progenitors reside. Published by Elsevier Inc. C1 [Balduino, Alex] Univ Veiga de Almeida, Ctr Pesquisa Inovacao & Tecnol, Sch Dent, BR-20271020 Rio De Janeiro, RJ, Brazil. [Mello-Coelho, Valeria; Borojevic, Radovan] Univ Fed Rio de Janeiro, Inst Biomed Sci, Rio De Janeiro, RJ, Brazil. [Mello-Coelho, Valeria; Weeraratna, Ashani T.; Becker, Kevin G.; Taub, Dennis D.] NIA, NIH, Baltimore, MD 21224 USA. [Wang, Zhou; Taichman, Russell S.; Krebsbach, Paul H.] Univ Michigan, Sch Dent, Dept Periodont Prevent & Geriatr, Ann Arbor, MI 48109 USA. [de Mello, Wallace] Inst Oswaldo Cruz, BR-20001 Rio De Janeiro, RJ, Brazil. RP Balduino, A (reprint author), Univ Veiga de Almeida, Ctr Pesquisa Inovacao & Tecnol, Sch Dent, Rua Ibituruna,108 Maracana, BR-20271020 Rio De Janeiro, RJ, Brazil. EM balduino@uva.edu.br OI Taichman, Russell S./0000-0002-7890-0020; Borojevic, Radovan/0000-0002-2393-7280; Becker, Kevin/0000-0002-6794-6656 FU CNPq; FAPERJ; National Institute on Aging, National Institutes of Health; NIH [CA-93900, DK082481]; National Counsel of Technological and Scientific Development FX This research was, in part, supported by CNPq, FAPERJ, and the Intramural Research Program of the National Institute on Aging, National Institutes of Health, and by NIH awards CA-93900 and DK082481.; National Counsel of Technological and Scientific Development and NIH awards CA-93900 and DK082481. This work has also been supported, in part, by the National Institute on Aging, NIH. NR 45 TC 13 Z9 14 U1 0 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 15 PY 2012 VL 318 IS 19 BP 2427 EP 2437 DI 10.1016/j.yexcr.2012.07.009 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 013KB UT WOS:000309303200002 PM 22841688 ER PT J AU Ambs, S AF Ambs, Stefan TI Analysis of stromal gene expression for the identification of prognostic and predictive molecular markers in cancer therapy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Editorial Material ID BREAST-CANCER; TUMOR STROMA; FIBROBLASTS; METASTASES; SIGNATURE; CD99 C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2213 EP 2214 DI 10.1002/ijc.27568 PG 2 WC Oncology SC Oncology GA 011SM UT WOS:000309185300001 PM 22528763 ER PT J AU Subbaiah, VK Narayan, N Massimi, P Banks, L AF Subbaiah, Vanitha Krishna Narayan, Nisha Massimi, Paola Banks, Lawrence TI Regulation of the DLG tumor suppressor by beta-catenin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE DLG; ss-catenin; proteasome ID PROTEASOME-MEDIATED DEGRADATION; CELL-ADHESION; HUMAN HOMOLOG; COLORECTAL-CANCER; E6 PROTEINS; WNT PATHWAY; APC GENE; NE-DLG; PDZ; EXPRESSION AB The discs-large (DLG) tumor suppressor plays essential roles in regulating cell polarity and proliferation. It localizes at sites of cellcell contact where it acts as a scaffold for multiple protein interactions, including with the adenomatous polyposis coli (APC) tumor suppressor, which in turn regulates beta-catenin. Furthermore, many tumor types including breast and colon have increased levels of beta-catenin activity with correspondingly low levels of DLG expression. Here we provide evidence of a direct functional link between these apparently separate phenomena. We show that overexpressed beta-catenin can enhance the turnover of DLG in a proteosome dependent manner. This effect is specific to DLG and is not seen with two other PDZ domain-containing targets of beta-catenin, MAGI-1 and Scribble. Furthermore, siRNA-mediated ablation of endogenous beta-catenin expression also enhances DLG stability. beta-catenin-induced degradation of DLG appears to be a consequence of a direct association between the two proteins and requires beta-catenin PDZ binding potential. In contrast, the enhanced turnover of DLG requires the unique N-terminal sequences and its PDZ domains. Finally, we also show that the capacity of DLG to inhibit transformed cell growth in an oncogene cooperation assay is inhibited by beta-catenin. Taken together these studies suggest that one mechanism by which deregulated beta-catenin can contribute to tumorigenesis is through enhancing DLG degradation. C1 [Subbaiah, Vanitha Krishna; Massimi, Paola; Banks, Lawrence] ICGEB, I-34012 Trieste, Italy. [Narayan, Nisha] NHLBI, NIH, Bethesda, MD 20892 USA. RP Banks, L (reprint author), ICGEB, Padriciano 99, I-34012 Trieste, Italy. EM banks@icgeb.org FU Associazione Italiana per la Ricerca sul Cancro; Wellcome Trust FX Grant sponsors: Associazione Italiana per la Ricerca sul Cancro, Wellcome Trust NR 49 TC 12 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2223 EP 2233 DI 10.1002/ijc.27519 PG 11 WC Oncology SC Oncology GA 011SM UT WOS:000309185300003 PM 22392736 ER PT J AU Xi, LF Schiffman, M Koutsky, LA Hulbert, A Lee, SK DeFilippis, V Shen, ZP Kiviat, NB AF Xi, Long Fu Schiffman, Mark Koutsky, Laura A. Hulbert, Ayaka Lee, Shu-Kuang DeFilippis, Victor Shen, Zhenping Kiviat, Nancy B. TI Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2-3 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; variants; cervical intraepithelial neoplasia ID NATURAL VARIANTS; CANCER; E6; HUMAN-PAPILLOMAVIRUS-16; WOMEN; POLYMORPHISM; BRAZIL; VIRUS AB Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 23 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.02.9) for infections with A variants and 2.2 (95% CI: 1.23.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.04.8) and 2.0-fold greater for those with B variants (95% CI: 0.94.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression. C1 [Xi, Long Fu] Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, Seattle, WA 98104 USA. [Xi, Long Fu; Koutsky, Laura A.; Lee, Shu-Kuang] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98104 USA. [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [DeFilippis, Victor] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. RP Xi, LF (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA. EM longfu@u.washington.edu FU Public Health Service [CA133569] FX Grant sponsor: Public Health Service; Grant number: CA133569 NR 33 TC 17 Z9 17 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2300 EP 2307 DI 10.1002/ijc.27520 PG 8 WC Oncology SC Oncology GA 011SM UT WOS:000309185300011 PM 22396129 ER PT J AU Becker, N Falster, MO Vajdic, CM de Sanjose, S Martinez-Maza, O Bracci, PM Melbye, M Smedby, KE Engels, EA Turner, J Vineis, P Costantini, AS Holly, EA Spinelli, JJ La Vecchia, C Zheng, TZ Chiu, BCH Montella, M Cocco, P Maynadie, M Foretova, L Staines, A Brennan, P Davis, S Severson, R Cerhan, JR Breen, EC Birmann, B Cozen, W Grulich, AE Newton, R AF Becker, Nikolaus Falster, Michael O. Vajdic, Claire M. de Sanjose, Silvia Martinez-Maza, Otoniel Bracci, Paige M. Melbye, Mads Smedby, Karin Ekstrom Engels, Eric A. Turner, Jennifer Vineis, Paolo Costantini, Adele Seniori Holly, Elizabeth A. Spinelli, John J. La Vecchia, Carlo Zheng, Tongzhang Chiu, Brian C. -H. Montella, Maurizio Cocco, Pierluigi Maynadie, Marc Foretova, Lenka Staines, Anthony Brennan, Paul Davis, Scott Severson, Richard Cerhan, James R. Breen, Elizabeth C. Birmann, Brenda Cozen, Wendy Grulich, Andrew E. Newton, Robert TI Self-reported history of infections and the risk of non-Hodgkin lymphoma: An InterLymph pooled analysis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Non-Hodgkin lymphoma; Infection; pooled analysis ID MEDICAL HISTORY; EPIDEMIOLOGY; IMMUNE; ATOPY AB We performed a pooled analysis of data on self-reported history of infections in relation to the risk of non-Hodgkin lymphoma (NHL) from 17 casecontrol studies that included 12,585 cases and 15,416 controls aged 1696 years at recruitment. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated in two-stage random-effect or joint fixed-effect models, adjusting for age, sex and study centre. Data from the 2 years before diagnosis (or date of interview for controls) were excluded. A self-reported history of infectious mononucleosis was associated with an excess risk of NHL (OR = 1.26, 95% CI = 1.011.57 based on data from 16 studies); study-specific results indicate significant (I2 = 51%, p = 0.01) heterogeneity. A self-reported history of measles or whooping cough was associated with an approximate 15% reduction in risk. History of other infection was not associated with NHL. We find little clear evidence of an association between NHL risk and infection although the limitations of data based on self-reported medical history (particularly of childhood illness reported by older people) are well recognized. C1 [Newton, Robert] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. [Newton, Robert] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Birmann, Brenda] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Birmann, Brenda] Harvard Univ, Sch Med, Boston, MA USA. [Breen, Elizabeth C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Severson, Richard] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Severson, Richard] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Davis, Scott] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Davis, Scott] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Maynadie, Marc] Registry Hematol Malignancies Cote dOr, Dijon, France. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. [Montella, Maurizio] Fdn G Pascale, Ist Nazl Tumori, Serv Epidemiol, Naples, Italy. [Chiu, Brian C. -H.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy. [Spinelli, John J.] BC Canc Agcy, Canc Control Res Program, Vancouver, BC, Canada. [Costantini, Adele Seniori] Inst Study & Prevent Canc, Occupat & Environm Epidemiol Unit, Florence, Italy. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Turner, Jennifer] Douglass Hanly Moir Pathol, Dept Histopathol, Sydney, NSW, Australia. [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, Rockville, MD USA. [Smedby, Karin Ekstrom] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Obstet & Gynaecol, Los Angeles, CA USA. [de Sanjose, Silvia] Inst Catala Oncol, Unit Infect & Canc, Barcelona, Spain. [Falster, Michael O.; Grulich, Andrew E.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Falster, Michael O.; Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Integrated Canc Res Grp, UNSW Canc Res Ctr, Sydney, NSW, Australia. [Becker, Nikolaus] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. RP Newton, R (reprint author), Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, Seebohm Rowntree Bldg,Area 3, York YO10 5DD, N Yorkshire, England. EM Robert.Newton@york.ac.uk RI Spinelli, John/B-6210-2013; Martinez-Maza, Otoniel/B-2667-2009; de Sanjose Llongueras, Silvia/H-6339-2014; OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357; La Vecchia, Carlo/0000-0003-1441-897X; Falster, Michael/0000-0001-6444-7272 FU Leukemia Foundation of Australia [LFA GIA 24]; Italian Association for Cancer Research; Italian League Against Cancer (Avi-N, Northern Italy); Canadian Cancer Society; Canadian Institutes for Health Research (British Columbia); National Cancer Institute, Connecticut [CA62006]; European Commission, EpiLymph [QLK4-CT-2000-00422]; Association pour la Recherche contre le Cancer [5111]; Fondation de France; EpiLymph, France [1999 008471]; Compagnia di San Paolo di Torino; Programma Oncologia 2001; EpiLymph, Italy; Health Research Board; EpiLymph, Ireland; Spanish Ministry of Health FISS [PI040091]; CIBERESP; EpiLymph, Spain [06/06/0073]; German Federal Office for Radiation Protection; EpiLymph, Germany [StSch4261, StSch4420]; National Institutes of Health [CA51086, CA69269-02]; European Community; Italian League against Cancer, Italy; National Cancer Institute, Mayo [CA92153]; National Cancer Institute (NCI-SEER) [PC65064, PC67008, PC67009, PC67010, PC71105]; American Institute for Cancer Research, Nebraska [99B083]; National Health and Medical Research Council of Australia (NSW) [990920]; Swedish Cancer Society (SCALE) [04 0458]; National Institutes of Health (UCSF) [CA45614, CA89745, CA87014, CA104682]; Leukemia Research Fund of Great Britain (UK) FX Grant sponsor: Leukemia Foundation of Australia; Grant number: LFA GIA 24; Grant sponsor: Italian Association for Cancer Research and the Italian League Against Cancer (Avi-N, Northern Italy), The Canadian Cancer Society and the Canadian Institutes for Health Research (British Columbia); Grant sponsor: National Cancer Institute, Connecticut; Grant number: CA62006; Grant sponsor: European Commission, EpiLymph; Grant number: QLK4-CT-2000-00422; Grant sponsor: Association pour la Recherche contre le Cancer; Grant number: 5111; Grant sponsor: Fondation de France, EpiLymph, France; Grant number: 1999 008471; Grant sponsors: Compagnia di San Paolo di Torino, Programma Oncologia 2001, EpiLymph, Italy, Health Research Board, EpiLymph, Ireland; Grant sponsor: Spanish Ministry of Health FISS; Grant number: PI040091; Grant sponsor: CIBERESP, EpiLymph, Spain; Grant number: 06/06/0073; Grant sponsor: German Federal Office for Radiation Protection, EpiLymph, Germany; Grant numbers: StSch4261, StSch4420; Grant sponsor: National Institutes of Health; Grant number: CA51086; Grant sponsor: European Community and the Italian League against Cancer, Italy, National Cancer Institute, Mayo; Grant number: CA92153; Grant sponsor: National Cancer Institute (NCI-SEER); Grant numbers: PC65064, PC67008, PC67009, PC67010, PC71105; Grant sponsor: American Institute for Cancer Research, Nebraska; Grant number: 99B083; Grant sponsor: National Health and Medical Research Council of Australia (NSW); Grant number: 990920; Grant sponsor: National Institutes of Health; Grant number: CA69269-02; Grant sponsor: The Swedish Cancer Society (SCALE); Grant number: 04 0458; Grant sponsor: National Institutes of Health (UCSF); Grant numbers: CA45614, CA89745, CA87014, CA104682; Grant sponsor: The Leukemia Research Fund of Great Britain (UK) NR 23 TC 10 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2342 EP 2348 DI 10.1002/ijc.27438 PG 7 WC Oncology SC Oncology GA 011SM UT WOS:000309185300015 PM 22266776 ER PT J AU Sultana, R McNeill, DR Abbotts, R Mohammed, MZ Zdzienicka, MZ Qutob, H Seedhouse, C Laughton, CA Fischer, PM Patel, PM Wilson, DM Madhusudan, S AF Sultana, Rebeka McNeill, Daniel R. Abbotts, Rachel Mohammed, Mohammed Z. Zdzienicka, Malgorzata Z. Qutob, Haitham Seedhouse, Claire Laughton, Charles A. Fischer, Peter M. Patel, Poulam M. Wilson, David M., III Madhusudan, Srinivasan TI Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE base excision repair (BER); BRCA deficiency; human apurinic; apyrimidinic endonuclease 1 (APE1); synthetic lethal targeting; DNA repair; small molecule inhibitors ID HUMAN ABASIC ENDONUCLEASE; SMALL-MOLECULE INHIBITOR; BASE EXCISION-REPAIR; PARP INHIBITORS; POLY(ADP-RIBOSE) POLYMERASE; DEOXYRIBONUCLEIC-ACID; GENE-EXPRESSION; APE1; INSTABILITY; HYPOXIA AB An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In this study, we have investigated the ability of APE1 inhibitors to induce synthetic lethality (SL) in a panel of DNA double-strand break (DSB) repair deficient and proficient cells; i) Chinese hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79) and BRCA2 revertant [V-C8(Rev1)]. ii) Human cancer cells: BRCA1 deficient (MDA-MB-436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested SL in CH ovary cells expressing a dominant-negative form of APE1 (E8 cells) using ATM inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. SL was also demonstrated in CH cells expressing a dominant-negative form of APE1 treated with ATM or DNA-PKcs inhibitors. We conclude that APE1 is a promising SL target in cancer. C1 [Madhusudan, Srinivasan] Univ Nottingham, Translat DNA Repair Grp, Univ Nottingham Hosp, Lab Mol Oncol,Acad Unit Oncol,Sch Mol Med Sci, Nottingham NG5 1PB, England. [McNeill, Daniel R.; Wilson, David M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Zdzienicka, Malgorzata Z.] Nicolaus Copernicus Univ Torun, Dept Mol Cell Genet, Coll Med Bydgoszcz, PL-85094 Bydgoszcz, Poland. [Qutob, Haitham; Seedhouse, Claire] Univ Nottingham, Dept Acad Haematol, Univ Nottingham Hosp, Sch Mol Med Sci, Nottingham NG5 1PB, England. [Laughton, Charles A.; Fischer, Peter M.] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England. [Laughton, Charles A.; Fischer, Peter M.] Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England. RP Madhusudan, S (reprint author), Univ Nottingham, Translat DNA Repair Grp, Univ Nottingham Hosp, Lab Mol Oncol,Acad Unit Oncol,Sch Mol Med Sci, Nottingham NG5 1PB, England. EM srinivasan.madhusudan@nottingham.ac.uk RI SEEDHOUSE, CLAIRE/B-3570-2009; Laughton, Charles/E-5667-2010; Fischer, Peter/E-5657-2010 OI Laughton, Charles/0000-0003-4090-3960; Madhusudan, Srinivasan/0000-0002-5354-5480; Seedhouse, Claire/0000-0003-2280-4045; Fischer, Peter/0000-0002-5866-9271 FU Breast Cancer Campaign, UK; Intramural Research Program of NIH, National Institute on Aging, USA; University of Nottingham, UK; Medical Research Council, UK FX Grant sponsors: Breast Cancer Campaign, UK, Intramural Research Program of NIH, National Institute on Aging, USA, University of Nottingham, UK (M.Z. Mohammed, R Sultana and S Madhusudan), Medical Research Council, UK (R. Abbotts) NR 44 TC 36 Z9 36 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2433 EP 2444 DI 10.1002/ijc.27512 PG 12 WC Oncology SC Oncology GA 011SM UT WOS:000309185300025 PM 22377908 ER PT J AU Pacak, K Sirova, M Giubellino, A Lencesova, L Csaderova, L Laukova, M Hudecova, S Krizanova, O AF Pacak, Karel Sirova, Marta Giubellino, Alessio Lencesova, Lubomira Csaderova, Lucia Laukova, Marcela Hudecova, Sona Krizanova, Olga TI NF-kappa B inhibition significantly upregulates the norepinephrine transporter system, causes apoptosis in pheochromocytoma cell lines and prevents metastasis in an animal model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE NF-?B inhibition; pheochromocytoma; apoptosis; norepinephrine transporter ID NECROSIS-FACTOR-ALPHA; MALIGNANT PHEOCHROMOCYTOMA; B ACTIVITY; I-131-METAIODOBENZYLGUANIDINE THERAPY; TRIPTERYGIUM-WILFORDII; EPITHELIAL-CELLS; PC12 CELLS; TRIPTOLIDE; ACTIVATION; NEUROBLASTOMA AB Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are specific types of neuroendocrine tumors that originate in the adrenal medulla or sympathetic/parasympathetic paraganglia, respectively. Although these tumors are intensively studied, a very effective treatment for metastatic PHEO or PGL has not yet been established. Preclinical evaluations of novel therapies for these tumors are very much required. Therefore, in this study we tested the effect of triptolide (TTL), a potent nuclear factor-kappaB (NF-?B) inhibitor, on the cell membrane norepinephrine transporter (NET) system, considered to be the gatekeeper for the radiotherapeutic agent 131I-metaiodobenzylguanidine (131I-MIBG). We measured changes in the mRNA and protein levels of NET and correlated them with proapoptotic factors and metastasis inhibition. The study was performed on three different stable PHEO cell lines. We found that blocking NF-?B with TTL or capsaicin increased both NET mRNA and protein levels. Involvement of NF-?B in the upregulation of NET was verified by mRNA silencing of this site and also by using NF-?B antipeptide. Moreover, in vivo treatment with TTL significantly reduced metastatic burden in an animal model of metastatic PHEO. The present study for the first time shows how NF-?B inhibitors could be successfully used in the treatment of metastatic PHEO/PGL by a significant upregulation of NET to increase the efficacy of 131I-MIBG and by the induction of apoptosis. C1 [Sirova, Marta; Lencesova, Lubomira; Laukova, Marcela; Hudecova, Sona; Krizanova, Olga] Slovak Acad Sci, Inst Mol Physiol & Genet, Ctr Excellence Studying Metab Aspects Dev Diagnos, Bratislava 83334, Slovakia. [Pacak, Karel; Giubellino, Alessio] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Csaderova, Lucia] Slovak Acad Sci, Mol Med Ctr, Bratislava 83334, Slovakia. RP Krizanova, O (reprint author), Slovak Acad Sci, Inst Mol Physiol & Genet, Ctr Excellence Studying Metab Aspects Dev Diagnos, Vlarska 5, Bratislava 83334, Slovakia. FU Intramural Research Program of the NICHD, NIH [VEGA/0049/10, APVV 51/0397] FX Grant sponsor: Intramural Research Program of the NICHD, NIH; Grant numbers: VEGA/0049/10, APVV 51/0397 NR 43 TC 16 Z9 16 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2012 VL 131 IS 10 BP 2445 EP 2455 DI 10.1002/ijc.27524 PG 11 WC Oncology SC Oncology GA 011SM UT WOS:000309185300026 PM 22407736 ER PT J AU Bussard, KM Smith, GH AF Bussard, Karen M. Smith, Gilbert H. TI Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo SO PLOS ONE LA English DT Article ID TUMOR STEM-CELLS; TERATOCARCINOMA CELLS; DIFFERENTIATION; METASTASIS; SUPPRESSOR; EXPRESSION; PROLACTIN; PREGNANCY; TISSUES; BRMS1 AB Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts) confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini) were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic) respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo. C1 [Bussard, Karen M.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Bussard, KM (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU Intramural NIH HHS NR 38 TC 11 Z9 12 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2012 VL 7 IS 11 AR e49221 DI 10.1371/journal.pone.0049221 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038CD UT WOS:000311151900103 PM 23155468 ER PT J AU Chiang, YJ Difilippantonio, MJ Tessarollo, L Morse, HC Hodes, RJ AF Chiang, Y. Jeffrey Difilippantonio, Michael J. Tessarollo, Lino Morse, Herbert C. Hodes, Richard J. TI Exon 1 Disruption Alters Tissue-Specific Expression of Mouse p53 and Results in Selective Development of B Cell Lymphomas SO PLOS ONE LA English DT Article ID P53-DEFICIENT MICE; SUPPRESSION; INSTABILITY; CROSSROADS; ACTIVATION; LEUKEMIA; SPECTRUM; DELETION; MODELS; REPAIR AB p53 is a tumor suppressor gene mutated in >50% of human cancers, while p53 deficiency in mice results in cancers and accelerated mortality. Thymic T cell lymphoma is the most common malignancy in p53-deficient mice, making it difficult to study the role of p53 in other malignancies. To overcome this limitation, we attempted to generate mice with a reversible p53 knockout (p53(rev/rev)) by inserting a floxed transcriptional stop into the first exon of p53, anticipating that this would allow tissue-specific Cre-mediated expression of p53. Contrary to expectations, functional p53 protein was expressed in the thymus and multiple other tissues of p53(rev/rev) mice in the absence of Cre, whereas B cells expressed p53 protein only in the presence of B cell-specific CD19-Cre. In the absence of Cre, 76% of p53(rev/rev) mice developed splenic marginal zone B cell lymphomas, indicating sensitivity of this B cell subset to transformation caused by p53 deficiency. 5'-RACE identified p53 mRNA transcribed from a novel start site utilized in thymocytes but not normal B cells or B cell lymphomas from p53(rev/rev) mice. The p53(rev/rev) mouse thus demonstrates an effect of p53 deficiency in development of splenic marginal zone lymphomas and provides a model for study of p53-deficient human B cell lymphomas. RP Chiang, YJ (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. EM chiangj@mail.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS [Z99 CA999999] NR 34 TC 3 Z9 3 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2012 VL 7 IS 11 AR e49305 DI 10.1371/journal.pone.0049305 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038CD UT WOS:000311151900119 PM 23166633 ER PT J AU Makarova, KS Anantharaman, V Aravind, L Koonin, EV AF Makarova, Kira S. Anantharaman, Vivek Aravind, L. Koonin, Eugene V. TI Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes SO BIOLOGY DIRECT LA English DT Article ID ADAPTIVE BACTERIAL IMMUNITY; TOXIN-ANTITOXIN SYSTEMS; CRISPR-CAS SYSTEMS; ESCHERICHIA-COLI; RESTRICTION ENDONUCLEASES; COMPARATIVE GENOMICS; PHAGE RESISTANCE; S-MODIFICATION; SEED SEQUENCE; RNA DECAY AB Background: The virus-host arms race is a major theater for evolutionary innovation. Archaea and bacteria have evolved diverse, elaborate antivirus defense systems that function on two general principles: i) immune systems that discriminate self DNA from nonself DNA and specifically destroy the foreign, in particular viral, genomes, whereas the host genome is protected, or ii) programmed cell suicide or dormancy induced by infection. Presentation of the hypothesis: Almost all genomic loci encoding immunity systems such as CRISPR-Cas, restriction-modification and DNA phosphorothioation also encompass suicide genes, in particular those encoding known and predicted toxin nucleases, which do not appear to be directly involved in immunity. In contrast, the immunity systems do not appear to encode antitoxins found in typical toxin-antitoxin systems. This raises the possibility that components of the immunity system themselves act as reversible inhibitors of the associated toxin proteins or domains as has been demonstrated for the Escherichia coli anticodon nuclease PrrC that interacts with the PrrI restriction-modification system. We hypothesize that coupling of diverse immunity and suicide/dormancy systems in prokaryotes evolved under selective pressure to provide robustness to the antivirus response. We further propose that the involvement of suicide/dormancy systems in the coupled antivirus response could take two distinct forms: 1) induction of a dormancy-like state in the infected cell to 'buy time' for activation of adaptive immunity; 2) suicide or dormancy as the final recourse to prevent viral spread triggered by the failure of immunity. Testing the hypothesis: This hypothesis entails many experimentally testable predictions. Specifically, we predict that Cas2 protein present in all cas operons is a mRNA-cleaving nuclease (interferase) that might be activated at an early stage of virus infection to enable incorporation of virus-specific spacers into the CRISPR locus or to trigger cell suicide when the immune function of CRISPR-Cas systems fails. Similarly, toxin-like activity is predicted for components of numerous other defense loci. Implications of the hypothesis: The hypothesis implies that antivirus response in prokaryotes involves key decision-making steps at which the cell chooses the path to follow by sensing the course of virus infection. Reviewers: This article was reviewed by Arcady Mushegian, Etienne Joly and Nick Grishin. For complete reviews, go to the Reviewers' reports section. C1 [Makarova, Kira S.; Anantharaman, Vivek; Aravind, L.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU US Department of Health and Human Services intramural funds FX We thank Yuri Wolf and Tatiana Senkevich for critical reading of the manuscript and useful discussions. The authors' research is supported by the US Department of Health and Human Services intramural funds (to National Library of Medicine). NR 63 TC 25 Z9 25 U1 2 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 14 PY 2012 VL 7 AR 40 DI 10.1186/1745-6150-7-40 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 042PK UT WOS:000311483100001 PM 23151069 ER PT J AU Henderson, LJ Sharma, A Monaco, MCG Major, EO Al-Harthi, L AF Henderson, Lisa J. Sharma, Amit Monaco, Maria Chiara G. Major, Eugene O. Al-Harthi, Lena TI Human Immunodeficiency Virus Type 1 (HIV-1) Transactivator of Transcription through Its Intact Core and Cysteine-Rich Domains Inhibits Wnt/beta-Catenin Signaling in Astrocytes: Relevance to HIV Neuropathogenesis SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; TAT-MEDIATED NEUROTOXICITY; LONG TERMINAL REPEAT; BETA-CATENIN; NEUROCOGNITIVE DISORDERS; ANTIRETROVIRAL THERAPY; REV FUNCTION; PROTEIN; REPLICATION; PATHWAY AB Wnt/beta-catenin is a neuroprotective pathway regulating cell fate commitment in the CNS and many vital functions of neurons and glia. Its dysregulation is linked to a number of neurodegenerative diseases. Wnt/beta-catenin is also a repressor of HIV transcription in multiple cell types, including astrocytes, which are dysregulated in HIV-associated neurocognitive disorder. Given that HIV proteins can overcome host restriction factors and that perturbations of Wnt/beta-catenin signaling can compromise astrocyte function, we evaluated the impact of HIV transactivator of transcription (Tat) on Wnt/beta-catenin signaling in astrocytes. HIV clade B Tat, in primary progenitor-derived astrocytes and U87MG cells, inhibited Wnt/beta-catenin signaling as demonstrated by its inhibition of active beta-catenin, TOPflash reporter activity, and Axin-2 (a downstream target of Wnt/beta-catenin signaling). Point mutations in either the core region (K41A) or the cysteine-rich region (C30G) of Tat abrogated its ability to inhibit beta-catenin signaling. Clade C Tat, which lacks the dicysteine motif, did not alter beta-catenin signaling, confirming that the dicysteine motif is critical for Tat inhibition of beta-catenin signaling. Tat coprecipitated with TCF-4 (a transcription factor that partners with beta-catenin), suggesting a physical interaction between these two proteins. Furthermore, knockdown of beta-catenin or TCF-4 enhanced docking of Tat at the TAR region of the HIV long terminal repeat. These findings highlight a bidirectional interference between Tat and Wnt/beta-catenin that negatively impacts their cognate target genes. The consequences of this interaction include alleviation of Wnt/beta-catenin-mediated suppression of HIV and possible astrocyte dysregulation contributing to HIV neuropathogenesis. C1 [Henderson, Lisa J.; Sharma, Amit; Al-Harthi, Lena] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. [Monaco, Maria Chiara G.; Major, Eugene O.] NINDS, NIH, Bethesda, MD 20892 USA. RP Al-Harthi, L (reprint author), Rush Univ, Med Ctr, Dept Immunol & Microbiol, 1735 W Harrison St,614 Cohn, Chicago, IL 60612 USA. EM lena_al-harthi@rush.edu FU National Institutes of Health [R01 NS060632, F31 NS071999]; Chicago Developmental Center for AIDS Research [P30 AI 082151]; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of Mental Health; National Institute on Drug Abuse; National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; National Center for Complementary and Alternative Medicine FX This work was supported by National Institutes of Health Grants R01 NS060632 (L.A.-H.) and F31 NS071999 (L.J.H.), and the Chicago Developmental Center for AIDS Research (Grant P30 AI 082151) supported by National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, and National Center for Complementary and Alternative Medicine. NR 39 TC 20 Z9 20 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 14 PY 2012 VL 32 IS 46 BP 16306 EP 16313 DI 10.1523/JNEUROSCI.3145-12.2012 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 037GU UT WOS:000311091000024 PM 23152614 ER PT J AU Ko, SJ Isozaki, K Kim, I Lee, JH Cho, HJ Sohn, SY Oh, SR Park, S Kim, DG Kim, CH Roche, KW AF Ko, Suk Jin Isozaki, Kaname Kim, Insook Lee, Jeong Ho Cho, Ho Jin Sohn, Sun Young Oh, So Ra Park, Steven Kim, Dong Goo Kim, Chul Hoon Roche, Katherine W. TI PKC Phosphorylation Regulates mGluR5 Trafficking by Enhancing Binding of Siah-1A SO JOURNAL OF NEUROSCIENCE LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; PROTEIN-KINASE-C; FRAGILE-X-SYNDROME; UBIQUITIN LIGASE; CALMODULIN; DEGRADATION; ENDOCYTOSIS; MONOUBIQUITYLATION; DISEASE; CELLS AB Glutamate is the major excitatory neurotransmitter in the mammalian CNS and acts on both ionotropic and metabotropic glutamate receptors (mGluRs). The mGluRs are widely distributed in the CNS and modulate a variety of neuronal processes, including neurotransmitter release and ion channel function. In hippocampus and cortex, mGluR5 is highly expressed and plays an important role in the regulation of synaptic plasticity. Calmodulin (CaM) binding dynamically regulates mGluR5 surface expression; however, the mechanisms linking CaM to mGluR5 trafficking are not clear. Recent studies showed that CaM binding to mGluR7 regulates its trafficking in a phosphorylation-dependent manner by disrupting the binding of protein interacting with C kinase 1. The E3 ligase seven in absentia homolog (Siah)-1A binds to mGluR5 and competes with CaM binding, making it an intriguing molecule to regulate phosphorylation-dependent trafficking of mGluR5. In the present study, we find that CaM competes with Siah-1A for mGluR5 binding in a phosphorylation-dependent manner in rat hippocampal neurons. Specifically, phosphorylation of mGluR5 S901 favors Siah-1A binding by displacing CaM. We identified critical residues regulating Siah-1A binding to mGluR5 and showed that binding is essential for the Siah-1A effects on mGluR5 trafficking. Siah-1A binding decreases mGluR5 surface expression and increases endosomal trafficking and lysosomal degradation of mGluR5. Thus CaM-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking. These findings support a conserved role for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor-binding proteins. C1 [Ko, Suk Jin; Lee, Jeong Ho; Cho, Ho Jin; Sohn, Sun Young; Oh, So Ra; Park, Steven; Kim, Dong Goo; Kim, Chul Hoon] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea. [Ko, Suk Jin; Lee, Jeong Ho; Cho, Ho Jin; Kim, Dong Goo; Kim, Chul Hoon] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea. [Isozaki, Kaname; Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA. [Kim, Insook] Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, Osong 363951, South Korea. [Kim, Chul Hoon] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea. RP Kim, CH (reprint author), 134 Shinchon Dong, Seoul 120752, South Korea. EM kimhoon@yuhs.ac RI Lee, Jeong Ho/G-7361-2012; OI Roche, Katherine/0000-0001-7282-6539 FU Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science, and Technology [2011-0003351, 2011-0001174]; Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at the National Institutes of Health; National Institute of Neurological Disorders and Stroke Intramural Research Program; National Institute of Child Health and Human Development FX This work was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (No. 2011-0003351 and 2011-0001174) (to C. H. K.), by the Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at the National Institutes of Health (to K. I.) and by the National Institute of Neurological Disorders and Stroke Intramural Research Program (to K. W. R.). We thank the Yonsei-Carl Zeiss Advanced Imaging Center at Yonsei University College of Medicine and Dr. Carolyn Smith at National Institute of Neurological Disorders and Stroke Light Imaging Facility for technical assistance. The alpha-tubulin monoclonal antibody developed by J. Frankel and E. M. Nelsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa, Department of Biology, Iowa City, Iowa. NR 32 TC 14 Z9 14 U1 0 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 14 PY 2012 VL 32 IS 46 BP 16391 EP 16401 DI 10.1523/JNEUROSCI.1964-12.2012 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 037GU UT WOS:000311091000031 PM 23152621 ER PT J AU Palm-Meinders, IH Koppen, H Terwindt, GM Launer, LJ Konishi, J Moonen, JME Bakkers, JTN Hofman, PAM van Lew, B Middelkoop, HAM van Buchem, MA Ferrari, MD Kruit, MC AF Palm-Meinders, Inge H. Koppen, Hille Terwindt, Gisela M. Launer, Lenore J. Konishi, Junya Moonen, Juliette M. E. Bakkers, Jacobus T. N. Hofman, Paul A. M. van Lew, Baldur Middelkoop, Huub A. M. van Buchem, Mark A. Ferrari, Michel D. Kruit, Mark C. TI Structural Brain Changes in Migraine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; SMALL-VESSEL DISEASE; CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; VERBAL FLUENCY; POPULATION; LESIONS; MRI; METAANALYSIS; HEADACHE AB Context A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain. Objective To determine whether women or men with migraine (with and without aura) have a higher incidence of brain lesions 9 years after initial MRI, whether migraine frequency was associated with progression of brain lesions, and whether progression of brain lesions was associated with cognitive decline. Design, Setting, and Participants In a follow-up of the 2000 Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis cohort, a prospective population-based observational study of Dutch participants with migraine and an age-and sex-matched control group, 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions. Comparisons were adjusted for age, sex, hypertension, diabetes, and educational level. The participants in the migraine group were a mean 57 years (range, 43-72 years), and 71% were women. Those in the control group were a mean 55 years (range, 44-71 years), and 69% were women. Main Outcome Measures Progression of MRI-measured cerebral deep white matter hyperintensities, infratentorial hyperintensities, and posterior circulation territory infarctlike lesions. Change in cognition was also measured. Results Of the 145 women in the migraine group, 112 (77%) vs 33 of 55 women (60%) in the control group had progression of deep white matter hyperintensities (adjusted odds ratio [OR], 2.1; 95% CI, 1.0-4.1; P = .04). There were no significant associations of migraine with progression of infratentorial hyperintensities: 21 participants (15%) in the migraine group and 1 of 57 participants (2%) in the control group showed progression (adjusted OR, 7.7; 95% CI, 1.0-59.5; P = .05) or new posterior circulation territory infarctlike lesions: 10 of 203 participants (5%) in the migraine group but none of 83 in the control group (P = .07). There was no association of number or frequency of migraine headaches with progression of lesions. There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores (-3.7 in the migraine group vs 1.4 in the control group; 95% CI, -4.4 to 0.2; adjusted P = .07). Conclusions In a community-based cohort followed up after 9 years, women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes. There was no association of migraine with progression of any MRI-measured brain lesions in men. JAMA. 2012;308(18):1889-1897 www.jama.com C1 [Palm-Meinders, Inge H.; Konishi, Junya; Moonen, Juliette M. E.; van Buchem, Mark A.; Kruit, Mark C.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [van Lew, Baldur] Leiden Univ, Med Ctr, Div Image Proc, NL-2300 RC Leiden, Netherlands. [Koppen, Hille; Terwindt, Gisela M.; Ferrari, Michel D.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Middelkoop, Huub A. M.] Leiden Univ, Med Ctr, Dept Neuropsychol, NL-2300 RC Leiden, Netherlands. [Koppen, Hille] Haga Hosp, Dept Neurol, The Hague, Netherlands. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bakkers, Jacobus T. N.] Slingeland Hosp, Dept Radiol, Doetinchem, Netherlands. [Hofman, Paul A. M.] Acad Hosp Maastricht, Dept Radiol, Maastricht, Netherlands. RP Kruit, MC (reprint author), Leiden Univ, Med Ctr, Dept Radiol, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X FU Almirall; Coherex; Colucid; Eisai; GlaxoSmithKline; Linde; MAP; Medtronic; Menarini; Merck; Minster; Pfizer; St Jude; National Institutes of Health [1R01NS061382-01]; Netherlands Heart Foundation [2007B016]; Netherlands Organisation for Scientific Research [903-52-291, VICI 918-56-602]; National Institute on Aging [907-00-217, Vidi 917-11-319] FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Ferrari reported receiving grants and consultancy or industry support from Almirall, Coherex, Colucid, Eisai, GlaxoSmithKline, Linde, MAP, Medtronic, Menarini, Merck, Minster, Pfizer, and St Jude, and independent support from the Netherlands Organisation for Scientific Research (NOW). Dr Terwindt reported receiving consultancy support from Merck, Janssen-Cilag, Almirall, and Menarini. Dr Koppen reported consultancy or industry support from Allergan, Benecke congres, Pfizer, and In circulation website. The other authors reported no financial disclosures.; This work was supported by grants 1R01NS061382-01 from the National Institutes of Health, 2007B016 from the Netherlands Heart Foundation, and 903-52-291, VICI 918-56-602, and Spinoza 2009 from the Netherlands Organisation for Scientific Research, and 907-00-217 and Vidi 917-11-319 from the Intramural Research Program at the National Institute on Aging. NR 35 TC 56 Z9 60 U1 1 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2012 VL 308 IS 18 BP 1889 EP 1897 DI 10.1001/jama.2012.14276 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 035NA UT WOS:000310952700025 PM 23150008 ER PT J AU Levin, GP Robinson-Cohen, C de Boer, IH Houston, DK Lohman, K Liu, YM Kritchevsky, SB Cauley, JA Tanaka, T Ferrucci, L Bandinelli, S Patel, KV Hagstrom, E Michaelsson, K Melhus, H Wang, T Wolf, M Psaty, BM Siscovick, D Kestenbaum, B AF Levin, Gregory P. Robinson-Cohen, Cassianne de Boer, Ian H. Houston, Denise K. Lohman, Kurt Liu, Yongmei Kritchevsky, Stephen B. Cauley, Jane A. Tanaka, Toshiko Ferrucci, Luigi Bandinelli, Stefania Patel, Kushang V. Hagstrom, Emil Michaelsson, Karl Melhus, Hakan Wang, Thomas Wolf, Myles Psaty, Bruce M. Siscovick, David Kestenbaum, Bryan TI Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID D-RECEPTOR GENE; FALSE DISCOVERY RATE; VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; OLDER-ADULTS; CANCER-RISK; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; SEASONAL-VARIATION; FRACTURE RISK AB Context Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. Objective To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes. Design, Setting, and Participants Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n=922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n=835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n=970; follow-up: 1991-1995 through 2008) cohort studies. Main Outcome Measure Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. Results Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism. Conclusion Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor. JAMA. 2012;308(18):1898-1905 www.jama.com C1 [Levin, Gregory P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Robinson-Cohen, Cassianne; de Boer, Ian H.; Psaty, Bruce M.; Siscovick, David; Kestenbaum, Bryan] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [de Boer, Ian H.; Psaty, Bruce M.; Siscovick, David; Kestenbaum, Bryan] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Patel, Kushang V.] Univ Washington, Dept Anasthesiol & Pain Med, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Patel, Kushang V.] Univ Washington, Ctr Pain Res Impact Measurement & Effectiveness, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Grp Hlth Res Inst & Cooperat, Seattle, WA 98195 USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA. [Lohman, Kurt] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Houston, Denise K.; Lohman, Kurt; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Hagstrom, Emil; Melhus, Hakan] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Michaelsson, Karl] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Wang, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Levin, GP (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM glevin11@uw.edu OI Kritchevsky, Stephen/0000-0003-3336-6781; Robinson-Cohen, Cassianne/0000-0003-4783-7046; Cauley, Jane A/0000-0003-0752-4408 FU Abbott Laboratories; National Institute on Aging, National Institutes of Health; American Society for Nutrition; Department of Veteran Affairs; Abbott Nutrition Health Institute; National Institutes of Health; Shire; Amgen; Abbott; Genzyme; Medtronic FX The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr de Boer reported receiving research grant funding from Abbott Laboratories. Dr Houston reported pending institutional grant support from the National Institute on Aging, National Institutes of Health; and receiving payment for lectures from the American Society for Nutrition, the Department of Veteran Affairs, and Abbott Nutrition Health Institute. Dr Wang reported serving as a consultant to Diasorin; receiving an investigatorinitiated grant from Diasorin; and receiving payment for lectures from Diasorin. Dr Wolf reported serving as a consultant to Abbott, Genzyme, Luitpold, Mitsubishi, Cytochroma, Astellas, and Kai; receiving institutional grants from the National Institutes of Health, Shire, and Amgen; receiving payment for lectures from Abbott, Genzyme, and Shire; and having a pending patent. Dr Psaty reported serving on a data and safety monitoring board for a clinical trial of a device funded by Zoll ZifeCor; and serving on a steering committee for the Yale Open Data Access Project funded by Medtronic. Dr Kestenbaum reported receiving institutional grant support from Amgen. No other authors reported disclosures. NR 46 TC 79 Z9 83 U1 0 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2012 VL 308 IS 18 BP 1898 EP 1905 DI 10.1001/jama.2012.17304 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 035NA UT WOS:000310952700026 PM 23150009 ER PT J AU Wang, YJ Abu-Asab, MS Li, W Aronow, ME Singh, AD Chan, CC AF Wang, Yujuan Abu-Asab, Mones S. Li, Wei Aronow, Mary E. Singh, Arun D. Chan, Chi-Chao TI Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy SO BMC OPHTHALMOLOGY LA English DT Article DE Paraneoplastic vitelliform retinopathy; Autoimmune retinopathy; Transient receptor potential channel; Bipolar cell; Melanoma-associated retinopathy; Autoantibody ID MELANOMA-ASSOCIATED RETINOPATHY; CUTANEOUS MALIGNANT-MELANOMA; GLUTAMATE-RECEPTOR; GENE-EXPRESSION; MESSENGER-RNA; TRPM1; PATIENT; LOCALIZATION; MACULOPATHY; CARCINOMA AB Background: Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation: We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive) with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive) in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively degenerated and replaced with empty vacuoles and disintegrated organelles. Conclusion: This case provides a convincing histological evidence of melanoma-associated autoantibodies directly against transient receptor potential M1 channels that target the ON bipolar cell structures in the inner nuclear and outer plexiform layers in paraneoplastic vitelliform retinopathy. C1 [Wang, Yujuan; Abu-Asab, Mones S.; Chan, Chi-Chao] NEI, Sect Immunopathol, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA. [Aronow, Mary E.; Singh, Arun D.] Cleveland Clin, Dept Ophthalm Oncol, Cole Eye Inst, Cleveland, OH 44106 USA. RP Chan, CC (reprint author), NEI, Sect Immunopathol, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016; OI Abu-Asab, Mones/0000-0002-4047-1232 FU National Eye Institute Intramural Research Program FX The National Eye Institute Intramural Research Program supported the study. NR 39 TC 7 Z9 7 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD NOV 13 PY 2012 VL 12 AR 56 DI 10.1186/1471-2415-12-56 PG 6 WC Ophthalmology SC Ophthalmology GA 048CG UT WOS:000311887200001 PM 23148706 ER PT J AU Chowell, G Towers, S Viboud, C Fuentes, R Sotomayor, V Simonsen, L Miller, MA Lima, M Villarroel, C Chiu, M Villarroel, JE Olea, A AF Chowell, Gerardo Towers, Sherry Viboud, Cecile Fuentes, Rodrigo Sotomayor, Viviana Simonsen, Lone Miller, Mark A. Lima, Mauricio Villarroel, Claudia Chiu, Monica Villarroel, Jose E. Olea, Andrea TI The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile SO BMC INFECTIOUS DISEASES LA English DT Article DE A/H1N1 influenza pandemic; Acute respiratory infection; Influenza-like-illness; Reproduction number; Spatial heterogeneity; School cycles; Climatological variables; Specific humidity; Temperature; Chile ID A H1N1 VIRUS; REPRODUCTION NUMBER; UNITED-STATES; ABSOLUTE-HUMIDITY; EPIDEMIC; SEASONALITY; INFECTION; IMPACT; SCHOOL; WINTER AB Background: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17 S to 56 S. Methods: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. Results: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. Conclusions: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes. C1 [Chowell, Gerardo; Towers, Sherry] Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85069 USA. [Chowell, Gerardo; Viboud, Cecile; Simonsen, Lone; Miller, Mark A.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Towers, Sherry] Purdue Univ, Dept Math, W Lafayette, IN 47907 USA. [Fuentes, Rodrigo; Sotomayor, Viviana; Chiu, Monica; Villarroel, Jose E.; Olea, Andrea] Minist Salud, Dept Epidemiol, Santiago, Chile. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. [Lima, Mauricio] Pontificia Univ Catolica Chile, Ctr Adv Studies Ecol & Biodivers, Santiago, Chile. [Villarroel, Jose E.] Direcc Meteorol Chile, Santiago, Chile. RP Chowell, G (reprint author), Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85069 USA. EM gchowell@asu.edu RI Lima, Mauricio/F-2722-2013; Chowell, Gerardo/F-5038-2012; OI Lima, Mauricio/0000-0002-3700-2945; Chowell, Gerardo/0000-0003-2194-2251; Simonsen, Lone/0000-0003-1535-8526 FU International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services; RAPIDD (Research and Policy for Infectious Disease Dynamics) program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center; NSF grant [DMS-1022758] FX This research was conducted in the context of the MISMS (Multinational Influenza Seasonal Mortality Study), an ongoing international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health (http://www.origem.info/misms/index.php). The MISMS study is funded by the International Influenza Unit, Office of Global Health Affairs, Department of Health and Human Services. LS acknowledges support from the RAPIDD (Research and Policy for Infectious Disease Dynamics) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center. ST acknowledges support of NSF grant DMS-1022758. NR 68 TC 17 Z9 17 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD NOV 13 PY 2012 VL 12 AR 298 DI 10.1186/1471-2334-12-298 PG 12 WC Infectious Diseases SC Infectious Diseases GA 054WH UT WOS:000312375400001 PM 23148597 ER PT J AU Vogel, SS Nguyen, TA van der Meer, BW Blank, PS AF Vogel, Steven S. Nguyen, Tuan A. van der Meer, B. Wieb Blank, Paul S. TI The Impact of Heterogeneity and Dark Acceptor States on FRET: Implications for Using Fluorescent Protein Donors and Acceptors SO PLOS ONE LA English DT Article ID RESONANCE ENERGY-TRANSFER; LIVING CELLS; MOLECULAR-SPECTROSCOPY; ORIENTATION FACTOR; HOMO-FRET; MICROSCOPY; DYNAMICS; GFP; STOICHIOMETRY; ACTIVATION AB Forster resonance energy transfer (FRET) microscopy is widely used to study protein interactions in living cells. Typically, spectral variants of the Green Fluorescent Protein (FPs) are incorporated into proteins expressed in cells, and FRET between donor and acceptor FPs is assayed. As appreciable FRET occurs only when donors and acceptors are within 10 nm of each other, the presence of FRET can be indicative of aggregation that may denote association of interacting species. By monitoring the excited-state (fluorescence) decay of the donor in the presence and absence of acceptors, dual-component decay analysis has been used to reveal the fraction of donors that are FRET positive (i.e., in aggregates). However, control experiments using constructs containing both a donor and an acceptor FP on the same protein repeatedly indicate that a large fraction of these donors are FRET negative, thus rendering the interpretation of dual-component analysis for aggregates between separately donor-containing and acceptor-containing proteins problematic. Using Monte-Carlo simulations and analytical expressions, two possible sources for such anomalous behavior are explored: 1) conformational heterogeneity of the proteins, such that variations in the distance separating donor and acceptor FPs and/or their relative orientations persist on time-scales long in comparison with the excited-state lifetime, and 2) FP dark states. C1 [Vogel, Steven S.; Nguyen, Tuan A.] NIAAA, Lab Mol Physiol, NIH, Bethesda, MD USA. [van der Meer, B. Wieb] Western Kentucky Univ, Dept Phys & Astron, Bowling Green, KY 42101 USA. [Blank, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Vogel, SS (reprint author), NIAAA, Lab Mol Physiol, NIH, Bethesda, MD USA. EM stevevog@mail.nih.gov OI Vogel, Steven/0000-0002-3005-2667 FU National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda [MD 20892] FX This work was supported by the intramural programs of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 15 Z9 15 U1 0 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 13 PY 2012 VL 7 IS 11 AR e49593 DI 10.1371/journal.pone.0049593 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039HF UT WOS:000311234600048 PM 23152925 ER PT J AU Ketkar, A Zafar, MK Banerjee, S Marquez, VE Egli, M Eoff, RL AF Ketkar, Amit Zafar, Maroof K. Banerjee, Surajit Marquez, Victor E. Egli, Martin Eoff, Robert L. TI Differential Furanose Selection in the Active Sites of Archaeal DNA Polymerases Probed by Fixed-Conformation Nucleotide Analogues SO BIOCHEMISTRY LA English DT Article ID NUCLEIC-ACID STRUCTURES; SULFOLOBUS-SOLFATARICUS; NUCLEOSIDE ANALOGS; SUGAR PUCKER; Y-FAMILY; FIDELITY; DPO4; RIBONUCLEOTIDES; VISUALIZATION; SUBSTITUTION AB DNA polymerases select for the incorporation of deoxyribonucleotide triphosphates (dNTPs) using amino acid side chains that act as a "steric-gate" to bar improper incorporation of rNTPs. An additional factor in the selection of nucleotide substrates resides in the preferred geometry for the furanose moiety of the incoming nucleotide triphosphate. We have probed the role of sugar geometry during nucleotide selection by model DNA polymerases from Sulfolobus solfataricus using fixed conformation nucleotide analogues. North-methanocarba-dATP (N-MC-dATP) locks the central ring into a RNA type (C2'-exo, North) conformation near a C3'-endo Pucker, and South-methariocarba-dATP (S-MC-dATP) locks the central ring system into a (C3'-exo, South) conformation near a C2'-endo pucker. Dpo4 Preferentially inserts N-MC-dATP and in the crystal structure of Dpo4 in complex with N-MC-dAMP the nucleotide analogue superimposes almost perfectly with Dpo4 bound to unmodified dATP. Biochemical assays indicate that the S. solfataricus B-family DNA polymerase Dpo1 can insert and extend from both N-MC-dATP and S-MC-dATP. In this respect, Dpo1 is unexpectedly more tolerant of substrate conformation than Dpo4. The crystal structure of Dpo4 bound to S-MC-dADP shows that poor incorporation of the Southern pucker by the Y-family polymerase results from a hydrogen bond between the 3'-OH group of the nucleotide analogue and the OH group of the steric gate residue, Tyr12, shifting the S-MC-dADP molecule away from the dNTP binding pocket and distorting the base pair at the primer-template junction. These results provide insights into substrate specificity of DNA polymerases, as well as molecular mechanisms that act as a barrier against insertion of rNTPs. C1 [Ketkar, Amit; Zafar, Maroof K.; Eoff, Robert L.] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Banerjee, Surajit] Cornell Univ, NE Collaborat Access Team, Argonne, IL 60439 USA. [Banerjee, Surajit] Cornell Univ, Dept Chem & Chem Biol, Argonne, IL 60439 USA. [Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Egli, Martin] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. RP Eoff, RL (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. EM rleoff@uams.edu OI Banerjee, Surajit/0000-0002-9414-7163 FU U.S.P.H. Service Grants [R00 GM084460, R01 GM055237]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Center for Research Resources [5P41RR015301-10]; National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103403-10]; U.S. DOE [DE-AC02-06CH11357] FX This work was supported in part by U.S.P.H. Service Grants R00 GM084460 (R.L.E.) and R01 GM055237 (M.E.). Supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This work is based upon research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8 P41 GM103403-10) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. NR 38 TC 1 Z9 1 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 13 PY 2012 VL 51 IS 45 BP 9234 EP 9244 DI 10.1021/bi301043k PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038QT UT WOS:000311189900021 PM 23050956 ER PT J AU Gurnev, PA Bezrukov, SM AF Gurnev, Philip A. Bezrukov, Sergey M. TI Inversion of Membrane Surface Charge by Trivalent Cations Probed with a Cation-Selective Channel SO LANGMUIR LA English DT Article ID LIPID BILAYER MEMBRANES; GRAMICIDIN-A CHANNELS; ION-CHANNEL; NANOFLUIDIC DIODE; MULTIVALENT IONS; CONDUCTANCE; ADSORPTION; PHOSPHOLIPIDS; RECTIFICATION; CONDENSATION AB We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying. the Multivalent ion accumulation at the surfaces. of charged lipid membranes and the ''charge inversion phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the Channel exhibits.. current rectification, which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly "asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed SO mV. Analysis of the changes in the voltage dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations, which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine. C1 [Gurnev, Philip A.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Gurnev, PA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM gurnevp@mail.nih.gov FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 66 TC 14 Z9 14 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV 13 PY 2012 VL 28 IS 45 BP 15824 EP 15830 DI 10.1021/la302676t PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 038RH UT WOS:000311191300010 PM 23088396 ER PT J AU Wentzensen, N Follansbee, S Borgonovo, S Tokugawa, D Schwartz, L Lorey, TS Sahasrabuddhe, VV Lamere, B Gage, JC Fetterman, B Darragh, TM Castle, PE AF Wentzensen, Nicolas Follansbee, Stephen Borgonovo, Sylvia Tokugawa, Diane Schwartz, Lauren Lorey, Thomas S. Sahasrabuddhe, Vikrant V. Lamere, Brandon Gage, Julia C. Fetterman, Barbara Darragh, Teresa M. Castle, Philip E. TI Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM SO AIDS LA English DT Article DE anal cancer screening; HIV; human papillomavirus; human papillomavirus mRNA; MSM; p16 ID HIGH-RESOLUTION ANOSCOPY; CERVICAL-CANCER; INTRAEPITHELIAL NEOPLASIA; METAANALYSIS; PERFORMANCE; PREVENTION; RISK; MEN; SEX AB Objective: Anal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM. Methods: A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs). Results: For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P < 0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3. Conclusion: Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Wentzensen, Nicolas; Schwartz, Lauren; Sahasrabuddhe, Vikrant V.; Gage, Julia C.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Follansbee, Stephen; Borgonovo, Sylvia] Kaiser Permanente Med Ctr, San Francisco, CA USA. [Tokugawa, Diane; Lorey, Thomas S.; Fetterman, Barbara] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA USA. [Lamere, Brandon] Kaiser Permanente, Div Res, Womens Hlth Res Inst, Oakland, CA USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA. EM wentzenn@mail.nih.gov FU NIH/National Cancer Institute FX The study was supported by the Intramural Research Program of NIH/National Cancer Institute. Roche and NorChip provided free testing for HPV DNA, p16, and HPV mRNA for this study. NR 22 TC 21 Z9 22 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 13 PY 2012 VL 26 IS 17 BP 2185 EP 2192 DI 10.1097/QAD.0b013e328359f255 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 032WQ UT WOS:000310750800007 PM 23018436 ER PT J AU Iyer, LM Aravind, L AF Iyer, Lakshminarayan M. Aravind, L. TI ALOG domains: provenance of plant homeotic and developmental regulators from the DNA-binding domain of a novel class of DIRS1-type retroposons SO BIOLOGY DIRECT LA English DT Article DE DIRS1; Tyrosine recombinase; Plant development; DNA-binding; Retroposon; Transcription factor; Chromatin protein; Plant defense ID TRANSCRIPTION FACTORS; STRUCTURE PREDICTION; STRUCTURAL BASIS; NATURAL-HISTORY; GENE FAMILY; PROTEIN; RETROTRANSPOSONS; RECOMBINATION; TRANSPOSONS; ALIGNMENT AB Members of the Arabidopsis LSH1 and Oryza G1 (ALOG) family of proteins have been shown to function as key developmental regulators in land plants. However, their precise mode of action remains unclear. Using sensitive sequence and structure analysis, we show that the ALOG domains are a distinct version of the N-terminal DNA-binding domain shared by the XerC/D-like, protelomerase, topoisomerase-IA, and Flp tyrosine recombinases. ALOG domains are distinguished by the insertion of an additional zinc ribbon into this DNA-binding domain. In particular, we show that the ALOG domain is derived from the XerC/D-like recombinases of a novel class of DIRS-1-like retroposons. Copies of this element, which have been recently inactivated, are present in several marine metazoan lineages, whereas the stramenopile Ectocarpus, retains an active copy of the same. Thus, we predict that ALOG domains help establish organ identity and differentiation by binding specific DNA sequences and acting as transcription factors or recruiters of repressive chromatin. They are also found in certain plant defense proteins, where they are predicted to function as DNA sensors. The evolutionary history of the ALOG domain represents a unique instance of a domain, otherwise exclusively found in retroelements, being recruited as a specific transcription factor in the streptophyte lineage of plants. Hence, they add to the growing evidence for derivation of DNA-binding domains of eukaryotic specific TFs from mobile and selfish elements. C1 [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU US Department of Health and Human Services (National Library of Medicine, NIH) FX The authors' research is supported by the intramural funds of the US Department of Health and Human Services (National Library of Medicine, NIH). We thank Dr. R. F. de Souza for writing a script that was useful for this analysis. This article was reviewed by Valerian Dolja and Gaspar Jekely. Additional file 1 can also be accessed from ftp://ftp.ncbi.nih.gov/pub/aravind/ALOG/ALOG.html NR 39 TC 7 Z9 26 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 12 PY 2012 VL 7 AR 39 DI 10.1186/1745-6150-7-39 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 100TO UT WOS:000315726700001 PM 23146749 ER PT J AU Kuhn, A Kumar, A Beilina, A Dillman, A Cookson, MR Singleton, AB AF Kuhn, Alexandre Kumar, Azad Beilina, Alexandra Dillman, Allissa Cookson, Mark R. Singleton, Andrew B. TI Cell population-specific expression analysis of human cerebellum SO BMC GENOMICS LA English DT Article DE Genomics; Computational biology; Cerebellum; Gene expression; Aging; Astrocyte ID GENE-EXPRESSION; MICROARRAY DATA; ALZHEIMERS-DISEASE; COMPLEX TISSUES; RAT CEREBELLUM; GLIAL-CELLS; BRAIN; PROTEIN; CANCER; DECONVOLUTION AB Background: Interpreting gene expression profiles obtained from heterogeneous samples can be difficult because bulk gene expression measures are not resolved to individual cell populations. We have recently devised Population-Specific Expression Analysis (PSEA), a statistical method that identifies individual cell types expressing genes of interest and achieves quantitative estimates of cell type-specific expression levels. This procedure makes use of marker gene expression and circumvents the need for additional experimental information like tissue composition. Results: To systematically assess the performance of statistical deconvolution, we applied PSEA to gene expression profiles from cerebellum tissue samples and compared with parallel, experimental separation methods. Owing to the particular histological organization of the cerebellum, we could obtain cellular expression data from in situ hybridization and laser-capture microdissection experiments and successfully validated computational predictions made with PSEA. Upon statistical deconvolution of whole tissue samples, we identified a set of transcripts showing age-related expression changes in the astrocyte population. Conclusions: PSEA can predict cell-type specific expression levels from tissues homogenates on a genome-wide scale. It thus represents a computational alternative to experimental separation methods and allowed us to identify age-related expression changes in the astrocytes of the cerebellum. These molecular changes might underlie important physiological modifications previously observed in the aging brain. C1 [Kuhn, Alexandre; Kumar, Azad; Beilina, Alexandra; Dillman, Allissa; Cookson, Mark R.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Kuhn, A (reprint author), ASTAR, Inst Mat Res & Engn, 3 Res Link, Singapore 117602, Singapore. EM alexandre.m.kuhn@gmail.com FU Swiss National Science Foundation; Intramural Research Program of the National Institutes of Health (NIH); National Institute on Aging FX This work was supported by the Swiss National Science Foundation and in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging. We are grateful to Jean-Marc Taymans for helpful discussions and Xavier Le Guezennec for comments on the manuscript. We would like to thank the LCM Core Facility at the National Cancer Institute for help with microdissection and the Helix Systems group (NIH) for providing high-performance computing infrastructure. NR 55 TC 7 Z9 7 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 12 PY 2012 VL 13 AR 610 DI 10.1186/1471-2164-13-610 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 085XN UT WOS:000314647700001 PM 23145530 ER PT J AU Tobias, DK Hu, FB Chavarro, J Rosner, B Mozaffarian, D Zhang, CL AF Tobias, Deirdre K. Hu, Frank B. Chavarro, Jorge Rosner, Bernard Mozaffarian, Dariush Zhang, Cuilin TI Healthful Dietary Patterns and Type 2 Diabetes Mellitus Risk Among Women With a History of Gestational Diabetes Mellitus SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; HISPANIC WOMEN; PREVENTION; QUALITY; METAANALYSIS; VALIDATION AB Background: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions. Women with gestational diabetes mellitus (GDM) are at high risk for T2DM after pregnancy. Adherence to healthful dietary patterns has been inversely associated with T2DM in the general population; however, whether these dietary patterns are associated with progression to T2DM among a susceptible population is unknown. Methods: Four thousand four hundred thirteen participants from the Nurses' Health Study II cohort with prior GDM were followed up from 1991 to 2005. We derived the alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and alternate Healthy Eating Index (aHEI) dietary pattern adherence scores from a post-GDM validated food-frequency questionnaire, with cumulative average updating every 4 years. Multivariable Cox proportional hazards models estimated the relative risk (hazard ratios) and 95% confidence intervals. Results: We observed 491 cases of incident T2DM during 52 743 person-years. All 3 patterns were inversely associated with T2DM risk with adjustment for age, total calorie intake, age at first birth, parity, ethnicity, parental diabetes, oral contraceptive use, menopause, and smoking. When we compared participants with the highest adherence (quartile 4) vs lowest (quartile 1), the aMED pattern was associated with 40% lower risk of T2DM (hazard ratio, 0.60 [95% CI, 0.44-0.82; P = .002]); the DASH pattern, with 46% lower risk (0.54 [0.39-0.73; P < .001]); and the aHEI pattern, with 57% lower risk (0.43 [0.31-0.59; P < .001]). Adjustment for body mass index moderately attenuated these findings. Conclusions: Adherence to healthful dietary patterns is associated with lower T2DM risk among women with a history of GDM. The inverse associations are partly mediated by body mass index. C1 [Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hu, Frank B.; Chavarro, Jorge; Rosner, Bernard; Mozaffarian, Dariush] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hu, Frank B.; Chavarro, Jorge; Rosner, Bernard; Mozaffarian, Dariush] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Tobias, DK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM dbanel@hsph.harvard.edu; zhangcu@mail.nih.gov FU GlaxoSmithKline; Sigma Tau; Pronova; National Institutes of Health; Foodminds; McKinsey Health Systems Institute; National Institute of Diabetes and Digestive and Kidney Diseases [DK58845, P30 DK46200-18]; National Cancer Institute [CA50385]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Dr Mozaffarian has received research grants from GlaxoSmithKline, Sigma Tau, Pronova, and the National Institutes of Health for an investigator-initiated, not-for-profit clinical trial of fish oil supplements and postsurgical complications; ad hoc travel reimbursement and/or honoraria for research presentations on diet and cardiometabolic diseases from the International Life Sciences Institute, Aramark, Unilever, Bunge, SPRIM, and Nutrition Impact; ad hoc consulting fees from Foodminds and McKinsey Health Systems Institute; and royalties from UpToDate for an online chapter on fish oil. In addition, Harvard University has filed a provisional patent application that has been assigned to Harvard University, listing Dr Mozaffarian as a coinventor, to the US Patent and Trademark Office for use of trans-palmitoleic acid to prevent and treat insulin resistance, T2DM, and related conditions.; This study was supported by grants DK58845 and P30 DK46200-18 from the National Institute of Diabetes and Digestive and Kidney Diseases; by grant CA50385 from the National Cancer Institute; and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Dr Zhang). NR 36 TC 53 Z9 54 U1 0 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 12 PY 2012 VL 172 IS 20 BP 1566 EP 1572 DI 10.1001/archinternmed.2012.3747 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 035XR UT WOS:000310987300007 PM 22987062 ER PT J AU Hellmich, KA Levinsohn, JL Fattah, R Newman, ZL Maier, N Sastalla, I Liu, SH Leppla, SH Moayeri, M AF Hellmich, Kristina A. Levinsohn, Jonathan L. Fattah, Rasem Newman, Zachary L. Maier, Nolan Sastalla, Inka Liu, Shihui Leppla, Stephen H. Moayeri, Mahtab TI Anthrax Lethal Factor Cleaves Mouse Nlrp1b in Both Toxin-Sensitive and Toxin-Resistant Macrophages SO PLOS ONE LA English DT Article ID SUSCEPTIBILITY; PROTEOLYSIS; KINASE AB Anthrax lethal factor (LF) is the protease component of anthrax lethal toxin (LT). LT induces pyroptosis in macrophages of certain inbred mouse and rat strains, while macrophages from other inbred strains are resistant to the toxin. In rats, the sensitivity of macrophages to toxin-induced cell death is determined by the presence of an LF cleavage sequence in the inflammasome sensor Nlrp1. LF cleaves rat Nlrp1 of toxin-sensitive macrophages, activating caspase-1 and inducing cell death. Toxin-resistant macrophages, however, express Nlrp1 proteins which do not harbor the LF cleavage site. We report here that mouse Nlrp1b proteins are also cleaved by LF. In contrast to the situation in rats, sensitivity and resistance of Balb/cJ and NOD/LtJ macrophages does not correlate to the susceptibility of their Nlrp1b proteins to cleavage by LF, as both proteins are cleaved. Two LF cleavage sites, at residues 38 and 44, were identified in mouse Nlrp1b. Our results suggest that the resistance of NOD/LtJ macrophages to LT, and the inability of the Nlrp1b protein expressed in these cells to be activated by the toxin are likely due to polymorphisms other than those at the LF cleavage sites. C1 [Hellmich, Kristina A.; Levinsohn, Jonathan L.; Fattah, Rasem; Newman, Zachary L.; Maier, Nolan; Sastalla, Inka; Liu, Shihui; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moayeri, M (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov OI , /0000-0001-6103-6726 FU Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 13 TC 37 Z9 37 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 12 PY 2012 VL 7 IS 11 AR e49741 DI 10.1371/journal.pone.0049741 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039HA UT WOS:000311234000075 PM 23152930 ER PT J AU Bleyer, A Siegel, SE Coccia, PF Stock, W Seibel, NL AF Bleyer, Archie Siegel, Stuart E. Coccia, Peter F. Stock, Wendy Seibel, Nita L. TI Children, Adolescents, and Young Adults With Leukemia: The Empty Half of the Glass Is Growing SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ONCOLOGY GROUP; SURVIVAL C1 [Bleyer, Archie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bleyer, Archie] St Charles Hlth Care Syst, Portland, OR USA. [Siegel, Stuart E.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Siegel, Stuart E.] Univ So Calif, Los Angeles, CA USA. [Coccia, Peter F.] Univ Nebraska Med Ctr, Omaha, NE USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Bleyer, A (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 11 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2012 VL 30 IS 32 BP 4037 EP 4038 DI 10.1200/JCO.2012.44.7466 PG 2 WC Oncology SC Oncology GA 035AU UT WOS:000310914800031 PM 23032621 ER PT J AU Fox, CS Matsushita, K Woodward, M Bilo, HJG Chalmers, J Lambers Heerspink, HJ Lee, BJ Perkins, RM Rossing, P Sairenchi, T Tonelli, M Vassalotti, JA Yamagishi, K Coresh, J de Jong, PE Wen, CP Nelson, RG AF Fox, Caroline S. Matsushita, Kunihiro Woodward, Mark Bilo, Henk J. G. Chalmers, John Lambers Heerspink, Hiddo J. Lee, Brian J. Perkins, Robert M. Rossing, Peter Sairenchi, Toshimi Tonelli, Marcello Vassalotti, Joseph A. Yamagishi, Kazumasa Coresh, Josef de Jong, Paul E. Wen, Chi-Pang Nelson, Robert G. CA Chronic Kidney Dis Prognosis Conso TI Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis SO LANCET LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RISK POPULATION COHORTS; COLLABORATIVE METAANALYSIS; HIGHER ALBUMINURIA; ALL-CAUSE; UNITED-STATES; ESTIMATED GFR; PREVALENCE; OUTCOMES; PROTEINURIA AB Background Chronic kidney disease is characterised by low estimated glomerular fi ltration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modifi ed by diabetes is unknown. Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. Findings We analysed data for 1 024 977 participants (128 505 with diabetes) from 30 general population and highrisk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and highrisk cohorts with data for all-cause mortality, 75 306 deaths occurred during a mean follow-up of 8.5 years (SD 5.0). In the 23 studies with data for cardiovascular mortality, 21 237 deaths occurred from cardiovascular disease during a mean follow-up of 9.2 years (SD 4.9). In the general and high-risk cohorts, mortality risks were 1.2-1.9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-tocreatinine ratio (ACR). With fi xed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1.73 m y [vs 95 mL/min per 1.73 m y], HR 1.35; 95% CI 1.18-1.55; vs 1.33; 1.19-1.48 and at ACR 30 mg/g [vs 5 mg/g], 1.50; 1.35-1.65 vs 1.52; 1.38-1.67). The overall interactions were not signifi cant. We identifi ed much the same fi ndings for ESRD in the chronic kidney disease cohorts. Interpretation Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. C1 [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Matsushita, Kunihiro; Woodward, Mark; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Woodward, Mark; Chalmers, John] Univ Sydney, George Inst Glocal Hlth, Sydney, NSW 2006, Australia. [Bilo, Henk J. G.] Isala Clin, Dept Internal Med, Zwolle, Netherlands. [Lambers Heerspink, Hiddo J.] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharmacol, Groningen, Netherlands. [de Jong, Paul E.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [Lee, Brian J.] Moanalua Med Ctr, Honolulu, HI USA. [Perkins, Robert M.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. [Rossing, Peter] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Rossing, Peter] Univ Aarhus, HEALTH, Aarhus, Denmark. [Sairenchi, Toshimi] Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Mibu, Tochigi, Japan. [Sairenchi, Toshimi; Yamagishi, Kazumasa] Ibaraki Hlth Serv Assoc, Mito, Ibaraki, Japan. [Tonelli, Marcello] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Vassalotti, Joseph A.] Natl Kidney Fdn, New York, NY USA. [Yamagishi, Kazumasa] Univ Tsukuba, Fac Med, Dept Publ Hlth Med, Tsukuba, Ibaraki, Japan. [Yamagishi, Kazumasa] Osaka Med Ctr Hlth Sci & Promot, Osaka, Japan. [Wen, Chi-Pang] China Med Univ Hosp, Taichung, Taiwan. [Wen, Chi-Pang] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan. [Nelson, Robert G.] NIDDKD, NIH, Phoenix, AZ USA. RP Coresh, J (reprint author), Chron Kidney Dis Prognosis Consortium Data Coordi, Baltimore, MD 21205 USA. EM ckdpc@jhmi.edu RI Schottker, Ben/F-8183-2014; Lambers Heerspink, Hiddo/K-3358-2014; Wetzels, Jack/A-1720-2014; Tonelli, Marcello/B-3028-2009; Stengel, Benedicte/G-5730-2015; Brenner, Hermann/B-4627-2017; Kronenberg, Florian/B-1736-2008; Woodward, Mark/D-8492-2015; de Zeeuw, Dick/E-9080-2014; Bakker, Stephan/J-4023-2015; OI Schottker, Ben/0000-0002-1217-4521; Lambers Heerspink, Hiddo/0000-0002-3126-3730; Brenner, Hermann/0000-0002-6129-1572; Townend, Jonathan/0000-0002-5881-5806; Kronenberg, Florian/0000-0003-2229-1120; de Zeeuw, Dick/0000-0003-3434-7777; Bakker, Stephan/0000-0003-3356-6791; rossing, peter/0000-0002-1531-4294; yamagishi, kazumasa/0000-0003-3301-5519 FU US National Kidney Foundation; Amgen; US National Institutes of Health; Servier; Roche; Sanofi; Abbott; Kidney Disease; AstraZeneca; Bristol-Myers Squibb; Boehringer Ingelheim; Lilly; Novo Nordisk; Novartis; Pfizer; CTI Clinical Trial Services; Litholink Chronic Kidney Disease Advisory Board; US National Institutes of Health, and Amgen; Merck; Dutch Kidney Foundation FX KM's institution has received grants from the US National Kidney Foundation, Amgen, and US National Institutes of Health. MW's institution has received a grant from Servier; he has received consultancy fees from Roche and speaker's fees from Sanofi and Servier. JCh's institution has received grants from Servier; and he has received speaker's fees from them. HJLH has served as a consultant for Abbott, Reata, Johnson & Johnson, and Vitae; and he has received speaker's fees from Abbott. BJL has received travel expenses from Kidney Disease: Improving Global Outcomes. RMP has received grants from the US National Kidney Foundation. PR's institution has received consultancy fees from Abbott, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, and Novo Nordisk, and has received grants from Abbott, Novartis, Pfizer, and speaker's fees from Abbott, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, and Novo Nordisk; he holds stock in Novo Nordisk. JAV has received consultancy fees from CTI Clinical Trial Services and Litholink Chronic Kidney Disease Advisory Board; his institution has received grants from the US National Institutes of Health; and he has received speaker's fees from Gore Creative Technologies and Elsevier. JCo's institution has received grants from the US National Kidney Foundation, US National Institutes of Health, and Amgen, and has received consultancy fees from Amgen and Merck. PEdJ's institution has received a grant from the Dutch Kidney Foundation. CSF, HJGB, TS, MT, KY, C-PW and RGN declare that they have no conflicts of interest. NR 34 TC 244 Z9 248 U1 3 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 10 PY 2012 VL 380 IS 9854 BP 1662 EP 1673 DI 10.1016/S0140-6736(12)61350-6 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 035MN UT WOS:000310951400028 PM 23013602 ER PT J AU Waclawiw, MA Wu, CO Yang, S AF Waclawiw, Myron A. Wu, Colin O. Yang, Song TI Special Issue: Papers from the 2010 National Heart, Lung and Blood Institute Clinical Trial Workshop Preface SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 [Waclawiw, Myron A.; Wu, Colin O.; Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Waclawiw, MA (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,Room 9216, Bethesda, MD 20892 USA. EM Myron.Waclawiw@nih.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 2937 EP 2937 DI 10.1002/sim.5407 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200001 PM 23055179 ER PT J AU Zheng, G Wu, CO Yang, S Waclawiw, MA DeMets, DL Geller, NL AF Zheng, Gang Wu, Colin O. Yang, Song Waclawiw, Myron A. DeMets, David L. Geller, Nancy L. TI NHLBI clinical trials workshop: an executive summary SO STATISTICS IN MEDICINE LA English DT Article DE Adaptive design; Bayesian clinical trials; comparative effectiveness research; genomic trials; missing data; personalized medicine; reporting clinical trials; surrogate endpoints ID ADAPTIVE SIGNATURE DESIGN; CHOLESTEROL AB On September 1314, 2010, the National Heart, Lung and Blood Institute (NHLBI) organized a workshop: Clinical Trials: Past, Present and Future. The workshop covered many areas in clinical trials, including the history of clinical trials at NHLBI, Bayesian clinical trials, surrogate endpoints, reporting clinical trials, handling missing data, flexible designs and adaptive trials, personalized medicine and genomic clinical trials, and comparative effectiveness research. In this report, we summarize the main discussions and conclusions based on the presentations of the invited speakers at the workshop. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Zheng, Gang; Wu, Colin O.; Yang, Song; Waclawiw, Myron A.; Geller, Nancy L.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [DeMets, David L.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Sci, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 17 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 2938 EP 2943 DI 10.1002/sim.5406 PG 6 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200002 PM 22733431 ER PT J AU Fleming, TR Powers, JH AF Fleming, Thomas R. Powers, John H. TI Biomarkers and surrogate endpoints in clinical trials SO STATISTICS IN MEDICINE LA English DT Article DE validation; accelerated approval; correlate; indirect measure; clinically meaningful endpoint; replacement endpoint; clinical efficacy measure; effect modifiers ID CHRONIC KIDNEY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; VENOUS THROMBOEMBOLISM; PREVENTION; XIMELAGATRAN; ALTEPLASE; RETEPLASE; WARFARIN; EPOETIN; EVENTS AB One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function, and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures, and radiological tests, often are considered as replacement endpoints or surrogates for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Fleming, Thomas R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Powers, John H.] Sci Applicat Int Corp, Frederick, MD USA. [Powers, John H.] NIH, Bethesda, MD 20892 USA. [Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM tfleming@u.washington.edu FU NIH/NIAID [R37 AI 29168]; National Cancer Institute, National Institutes of Health [N01-CO-12400]; National Institute of Allergy and Infectious Disease FX For T. Fleming, the source of financial support for research described in this article is an NIH/NIAID grant entitled 'Statistical Issues in AIDS Research' (R37 AI 29168). For JH Powers, this project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported in part by the National Institute of Allergy and Infectious Disease. Collaborative Clinical Research Branch, John H Powers, MD, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702. NR 30 TC 93 Z9 93 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 2973 EP 2984 DI 10.1002/sim.5403 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200005 PM 22711298 ER PT J AU Proschan, MA Lan, KKG AF Proschan, Michael A. Lan, K. K. Gordon TI Spending functions and continuous-monitoring boundaries SO STATISTICS IN MEDICINE LA English DT Article DE boundaries; Brownian motion; B-value; group-sequential monitoring; information fraction; interim analyses; power; spending functions ID CLINICAL-TRIALS; BROWNIAN-MOTION AB Clinical trials are monitored periodically for safety, efficacy, and futility. The spending function is a popular tool for efficacy monitoring because it does not require pre-specification of the number or timing of interim analyses. But there are infinitely many spending functions, so some guidance on how to choose one is helpful. We consider spending functions that are generated from different continuous-monitoring boundaries for Brownian motion. We use properties of the continuous-monitoring boundaries to derive properties of the associated spending function. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Proschan, Michael A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Lan, K. K. Gordon] Johnson & Johnson, Raritan, NJ USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM proscham@niaid.nih.gov NR 14 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3024 EP 3030 DI 10.1002/sim.5481 PG 7 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200009 PM 22807204 ER PT J AU Simon, R AF Simon, Richard TI Clinical trials for predictive medicine SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; predictive medicine; predictive biomarkers; re-sampling methods ID REQUIRING PROLONGED OBSERVATION; ADAPTIVE SIGNATURE DESIGN; SUBSET; EFFICIENCY; PATIENT; CANCER AB Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials. In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction-based approach to the analysis of randomized clinical trials that both preserves the Type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 19 TC 22 Z9 22 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3031 EP 3040 DI 10.1002/sim.5401 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200010 PM 22714719 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Commentary: How the debate about comparative effectiveness research should impact the future of clinical trials SO STATISTICS IN MEDICINE LA English DT Article DE comparative effectiveness; randomized trials; observational studies ID POLICY; GISSI; STORY AB Comparative effectiveness research represents the kind of research that arguably more directly affects clinical practice and policy. It includes observational studies, clinical trials, and systematic syntheses of existing literature. In this commentary, I argue for the ongoing and critical role of randomization in comparative effectiveness, noting the key differences between practical and explanatory trials. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 15 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3051 EP 3053 DI 10.1002/sim.5400 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200012 PM 23055180 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Responses to commentaries SO STATISTICS IN MEDICINE LA English DT Article C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3066 EP 3067 DI 10.1002/sim.5396 PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200017 ER PT J AU D'Agostino, R DeMets, D Friedewald, W Goodman, S Witte, J Geller, NL AF D'Agostino, Ralph, Sr. DeMets, David Friedewald, William Goodman, Steven Witte, John Geller, Nancy L. TI The future of clinical trials: A panel discussion SO STATISTICS IN MEDICINE LA English DT Article C1 [D'Agostino, Ralph, Sr.; DeMets, David; Friedewald, William; Goodman, Steven; Witte, John; Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Geller, NL (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. EM ng@helix.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2012 VL 31 IS 25 SI SI BP 3068 EP 3072 DI 10.1002/sim.5484 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 019MY UT WOS:000309745200018 PM 22806631 ER PT J AU Ferrarone, J Knoper, RC Li, R Kozak, CA AF Ferrarone, John Knoper, Ryan C. Li, Randolph Kozak, Christine A. TI Second site mutation in the virus envelope expands the host range of a cytopathic variant of Moloney murine leukemia virus SO VIROLOGY LA English DT Article DE Mouse ecotropic gammaretrovirus; Retrovirus host range; Cat-1 retrovirus receptor; Retrovirus entry; Virus-induced syncytia; Receptor binding domain ID ENDOTHELIAL-CELL TROPISM; SYNCYTIUM FORMATION; RECEPTOR-BINDING; PROTEIN; ENTRY; IDENTIFICATION; GLYCOSYLATION; RETROVIRUSES; PVC-211; LINES AB Spl574 MLV (murine leukemia virus) is a variant of Moloney ecotropic MLV (MoMLV) that is cytopathic in Mus dunni cells and restricted by other mouse cells. Its host range and cytopathicity are due to a mutation, S82F, at a site critical for binding to the CAT-1 receptor. To identify residues that affect affinity for receptor variants, virus with S82F was passed in restrictive cells. The env genes of the adapted viruses contained 18 novel mutations, including one, E114G, present in 6 of 30 sequenced envs. MoMLV-E114G efficiently infected all mouse cells as well as ecotropic MLV resistant Chinese hamster cells. Virus with E114G and S82F induced large multinucleated syncytia in NIH 3T3 and SC-1 cells as well as M. dunni cells. Inoculation of Mo-S82F,E114G into mice produced lymphomas typical of MoMLV. Residues at env position 114 are thus important determinants of host range, and E114G suppresses host range restriction due to S82F, but does not affect S82F-governed cytopathicity. Published by Elsevier Inc. C1 [Kozak, Christine A.] NIAID, NIH, LMM, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, NIH, LMM, Bldg 4,Room 329,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM john.ferrarone@gmail.com; knoperr@gmail.com; bludragen88@gmail.com; ckozak@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. We thank Esther Shaffer and Qingping Liu for expert technical assistance, Alicia Buckler-White and Ronald Plishka for sequencing, Michael A. Dolan of the Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID for assistance with figure preparation, and the following members of the Division of Veterinary Resources, Office of Research Services, NIH, for pathological evaluation: Lauren Brinster, Mark Bryant, Michael Eckhaus, Randy Elkins, Victoria Hoffmann, and Matthew Starost. NR 31 TC 3 Z9 3 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2012 VL 433 IS 1 BP 7 EP 11 DI 10.1016/j.virol.2012.06.031 PG 5 WC Virology SC Virology GA 020GS UT WOS:000309797600002 PM 22835818 ER PT J AU Escalera-Zamudio, M Cobian-Guemes, G Soto-del Rio, MD Isa, P Sanchez-Betancourt, I Parissi-Crivelli, A Martinez-Cazares, MT Romero, P Velazquez-Salinas, L Huerta-Lozano, B Nelson, M Montero, H Vinuesa, P Lopez, S Arias, CF AF Escalera-Zamudio, Marina Cobian-Gueemes, Georgina de los Dolores Soto-del Rio, Maria Isa, Pavel Sanchez-Betancourt, Ivan Parissi-Crivelli, Aurora Teresa Martinez-Cazares, Maria Romero, Pedro Velazquez-Salinas, Lauro Huerta-Lozano, Belem Nelson, Martha Montero, Hilda Vinuesa, Pablo Lopez, Susana Arias, Carlos F. TI Characterization of an influenza A virus in Mexican swine that is related to the A/H1N1/2009 pandemic clade SO VIROLOGY LA English DT Article DE Influenza; Pandemics; Swine; Genetic diversity; Evolution; La Gloria; Mexico ID RECEPTOR-BINDING PROPERTIES; H1N1 VIRUS; ALIGNMENT; INFECTION; EMERGENCE AB In the spring of 2009, swine-origin influenza H1N1pdm09 viruses caused the first influenza pandemic of this century. We characterized the influenza viruses that circulated early during the outbreak in Mexico, including one newly sequenced swine H1N1pdm09 virus and three newly sequenced human H1N1pdm09 viruses that circulated in the outbreak of respiratory disease in La Gloria, Veracruz. Phylogenetic analysis revealed that the swine isolate (A/swine/Mexico/4/2009) collected in April 2009 is positioned in a branch that is basal to the rest of the H1N1pdm09 clade in two (NP and PA) of the eight single-gene trees. In addition, the concatenated HA-NA and the complete whole-genome trees also showed a basal position for A/swine/Mexico/4/2009. Furthermore, this swine virus was found to share molecular traits with non-HIN1pdm09 H1N1 viral lineages. These results suggest that this isolate could potentially be the first one detected from a sister lineage closely related to the H1N1pdm09 viruses. (C) 2012 Elsevier Inc. All rights reserved. C1 [Escalera-Zamudio, Marina; Cobian-Gueemes, Georgina; de los Dolores Soto-del Rio, Maria; Isa, Pavel; Romero, Pedro; Lopez, Susana; Arias, Carlos F.] Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62210, Morelos, Mexico. [Sanchez-Betancourt, Ivan] Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, Cuernavaca 62210, Morelos, Mexico. [Parissi-Crivelli, Aurora; Teresa Martinez-Cazares, Maria] Serv Salud Veracruz, Lab Estatal Salud Publ, Orizaba, Veracruz, Mexico. [Velazquez-Salinas, Lauro; Huerta-Lozano, Belem] Comis Mexico Estados Unidos Prevenc Fiebre Aftosa, Mexico City, DF, Mexico. [Nelson, Martha] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Montero, Hilda] Univ Veracruzana, Inst Salud Publ, Xalapa 91000, Veracruz, Mexico. [Vinuesa, Pablo] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca 62210, Morelos, Mexico. RP Arias, CF (reprint author), Univ Nacl Autonoma Mexico, Inst Biotecnol, Av Univ 2001, Cuernavaca 62210, Morelos, Mexico. EM arias@ibt.unam.mx FU National Council for Science and Technology (Conacyt)-Mexico [5549, 10110/184/09]; Instituto de Ciencia y Tecnologia del Distrito Federal, Mexico [PICOSI09-209]; CONACYT-Mexico FX We thank Ricardo Grande and Veronica Jimenez, of the next-generation sequencing core facility of the National University of Mexico for their technical support. We are grateful to all personnel from the molecular biology and virus isolation units of CPA for their work in the diagnosis of the Queretaro swine pandemic influenza virus. This work was supported by Grants 5549 and 10110/184/09 from the National Council for Science and Technology (Conacyt)-Mexico, and Grant PICOSI09-209 from the Instituto de Ciencia y Tecnologia del Distrito Federal, Mexico. Marina Escalera-Zamudio, Maria de los Dolores Soto del Rio y Georgina Cobian-Guemes were supported by a scholarship from CONACYT-Mexico. NR 26 TC 6 Z9 6 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2012 VL 433 IS 1 BP 176 EP 182 DI 10.1016/j.virol.2012.08.003 PG 7 WC Virology SC Virology GA 020GS UT WOS:000309797600020 PM 22921315 ER PT J AU Hanyu, O Nakae, H Miida, T Higashi, Y Fuda, H Endo, M Kohjitani, A Sone, H Strott, CA AF Hanyu, Osamu Nakae, Hanako Miida, Takashi Higashi, Yuko Fuda, Hirotoshi Endo, Motohiro Kohjitani, Atsushi Sone, Hirohito Strott, Charles A. TI Cholesterol sulfate induces expression of the skin barrier protein filaggrin in normal human epidermal keratinocytes through induction of ROR alpha SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Cholesterol sulfate; ROR alpha; Filaggrin; SULT2B1b; NHEKs ID ORPHAN RECEPTOR-ALPHA; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; RETINOIC ACID; DIFFERENTIATION; PROMOTER; ENVELOPE; ANGSTROM; LIGAND; AP-1 AB Cholesterol sulfate is abundant in the human epidermis and is a putative natural ligand for retinoic acid receptor-related orphan receptor alpha (ROR alpha). Although direct binding of cholesterol sulfate is expected to activate ROR alpha, cholesterol sulfate can also induce ROR alpha expression and increase ROR alpha target gene expression. The purpose of this study was to determine whether cholesterol sulfate induces profilaggrin expression, a precursor of the barrier protein filaggrin in the epidermis, through activation of ROR alpha by directly binding to ROR alpha, or through increased ROR alpha expression. Immunohistochemical and polymerase chain reaction (PCR) analyses showed that ROR alpha was expressed in normal human epidermal keratinocytes (NHEKs) and that its expression increased during keratinocyte differentiation in parallel with that of profilaggrin and cholesterol sulfotransferase, which catalyzes the synthesis of cholesterol sulfate. Exogenous cholesterol sulfate significantly increased both ROR alpha and profilaggrin expression in NHEKs, whereas no effect on profilaggrin expression was observed in cells in which ROR alpha was knocked down with small interfering RNA (siRNA). Additionally, a luciferase reporter gene assay revealed that exogenous ROR alpha dose-dependently increased the activity of the profilaggrin gene promoter even in the absence of cholesterol sulfate, and that this response involves activator protein-1. In conclusion, the results of this study indicate that cholesterol sulfate induces filaggrin expression through increased ROR alpha expression. Further studies are required to fully elucidate the mechanisms involved. (C) 2012 Elsevier Inc. All rights reserved. C1 [Hanyu, Osamu; Sone, Hirohito] Niigata Univ, Grad Sch Med & Dent Sci, Div Endocrinol & Metab, Chuo Ku, Niigata 9518510, Japan. [Hanyu, Osamu; Nakae, Hanako; Higashi, Yuko; Fuda, Hirotoshi; Endo, Motohiro; Kohjitani, Atsushi; Strott, Charles A.] NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. [Miida, Takashi] Juntendo Univ, Sch Med, Dept Clin Lab Med, Bunkyo Ku, Tokyo 1138421, Japan. RP Hanyu, O (reprint author), Niigata Univ, Grad Sch Med & Dent Sci, Div Endocrinol & Metab, Chuo Ku, 1-757 Asahimachi, Niigata 9518510, Japan. EM hanyuo@med.niigata-u.ac.jp; tmiida@juntendo.ac.jp RI Miida, Takashi/A-5589-2012 OI Miida, Takashi/0000-0002-4294-8030 NR 24 TC 10 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 2012 VL 428 IS 1 BP 99 EP 104 DI 10.1016/j.bbrc.2012.10.013 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 043DN UT WOS:000311523200017 PM 23063684 ER PT J AU Bond, LM Arden, SD Kendrick-Jones, J Buss, F Sellers, JR AF Bond, Lisa M. Arden, Susan D. Kendrick-Jones, John Buss, Folma Sellers, James R. TI Dynamic Exchange of Myosin VI on Endocytic Structures SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; SNELLS-WALTZER MICE; LARGE STEP-SIZE; CELLULAR FUNCTIONS; ACTIN-FILAMENTS; MOTOR; DEAFNESS; BINDING; DOMAIN; MYO6 AB The actin-based molecular motor myosin VI functions in the endocytic uptake pathway, both during the early stages of clathrin-mediated uptake and in later transport to/from early endosomes. This study uses fluorescence recovery after photobleaching (FRAP) to examine the turnover rate of myosin VI during endocytosis. The results demonstrate that myosin VI turns over dynamically on endocytic structures with a characteristic half-life common to both the large insert isoform of myosin VI on clathrin-coated structures and the no-insert isoform on early endosomes. This half-life is shared by the myosin VI-binding partner Dab2 and is identical for full-length myosin VI and the cargo-binding tail region. The 4-fold slower half-life of an artificially dimerized construct of myosin VI on clathrin-coated structures suggests that wild type myosin VI does not function as a stable dimer, but either as a monomer or in a monomer/dimer equilibrium. Taken together, these FRAP results offer insight into both the basic turnover dynamics and the monomer/dimer nature of myosin VI. C1 [Bond, Lisa M.; Arden, Susan D.; Buss, Folma] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Bond, Lisa M.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Kendrick-Jones, John] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Buss, F (reprint author), Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust Med Res Council Bldg,Hills Rd, Cambridge CB2 0XY, England. EM fb1@mole.bio.cam.ac.uk; sellersj@nhlbi.nih.gov FU NHLBI, National Institutes of Health, Intramural Program; Wellcome Trust; Winston Churchill Foundation of the United States; National Institutes of Health-Oxford-Cambridge Ph.D. studentship; Medical Research Council FX This work was supported, in whole or in part, by the NHLBI, National Institutes of Health, Intramural Program (to J. R. S.). This work was also supported by the Wellcome Trust (to F. B.), a scholarship from the Winston Churchill Foundation of the United States (to L. M. B.), a National Institutes of Health-Oxford-Cambridge Ph.D. studentship (to L. M. B.), and the Medical Research Council (to J. K-J.). The Cambridge Institute for Medical Research received a strategic award from the Wellcome Trust. NR 48 TC 5 Z9 6 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2012 VL 287 IS 46 BP 38637 EP 38646 DI 10.1074/jbc.M112.373969 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035WJ UT WOS:000310982800023 PM 22992744 ER PT J AU Devaiah, BN Singer, DS AF Devaiah, Ballachanda N. Singer, Dinah S. TI Cross-talk Among RNA Polymerase II Kinases Modulates C-terminal Domain Phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BROMODOMAIN PROTEIN BRD4; ELONGATION-FACTOR-B; P-TEFB; TRANSCRIPTION ELONGATION; ACTIVATING KINASE; CTD KINASE; CHROMATIN; TFIIH; TAF7; REGULATOR AB The RNA polymerase II (Pol II) C-terminal domain (CTD) serves as a docking site for numerous proteins, bridging various nuclear processes to transcription. The recruitment of these proteins is mediated by CTD phospho-epitopes generated during transcription. The mechanisms regulating the kinases that establish these phosphorylation patterns on the CTD are not known. We report that three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their subsequent CTD phosphorylation. BRD4 phosphorylates PTEFb/CDK9 at either Thr-29 or Thr-186, depending on its relative abundance, which represses or activates CDK9 CTD kinase activity, respectively. Conversely, CDK9 phosphorylates BRD4 enhancing its CTD kinase activity. The CTD Ser-5 kinase CDK7 also interacts with and phosphorylates BRD4, potently inhibiting BRD4 kinase activity. Additionally, the three kinases regulate each other indirectly through the general transcription factor TAF7. An inhibitor of CDK9 and CDK7 CTD kinase activities, TAF7 also binds to BRD4 and inhibits its kinase activity. Each of these kinases phosphorylates TAF7, affecting its subsequent ability to inhibit the other two. Thus, a complex regulatory network governs Pol II CTD kinases. C1 [Devaiah, Ballachanda N.; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov FU NCI, Center for Cancer Research, National Institutes of Health FX This work was supported, by the Intramural Research Program of the NCI, Center for Cancer Research, National Institutes of Health. NR 27 TC 18 Z9 18 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2012 VL 287 IS 46 BP 38755 EP 38766 DI 10.1074/jbc.M112.412015 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035WJ UT WOS:000310982800033 PM 23027873 ER PT J AU Ghosh, A Corbett, GT Gonzalez, FJ Pahan, K AF Ghosh, Arunava Corbett, Grant T. Gonzalez, Frank J. Pahan, Kalipada TI Gemfibrozil and Fenofibrate, Food and Drug Administration-approved Lipid-lowering Drugs, Up-regulate Tripeptidyl-peptidase 1 in Brain Cells via Peroxisome Proliferator-activated Receptor alpha IMPLICATIONS FOR LATE INFANTILE BATTEN DISEASE THERAPY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; RETINOID-X-RECEPTOR; DENSITY-LIPOPROTEIN-CHOLESTEROL; LYSOSOMAL STORAGE DISORDERS; KAPPA-B; MOUSE MODEL; ADOPTIVE TRANSFER; HUMAN ASTROCYTES; GENE-EXPRESSION; MESSENGER-RNAS AB The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene is Cln2, encoding tripeptidyl-peptidase I (TPP1). At the molecular level, LINCL is caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there is no established treatment for this fatal disease. This study reveals a novel use of gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, in up-regulating TPP1 in brain cells. Both gemfibrozil and fenofibrate up-regulated mRNA, protein, and enzymatic activity of TPP1 in primary mouse neurons and astrocytes as well as human astrocytes and neuronal cells. Because gemfibrozil and fenofibrate are known to activate peroxisome proliferator-activated receptor-alpha (PPAR alpha), the role of PPAR alpha in gemfibrozil-and fenofibrate-mediated up-regulation of TPP1 was investigated revealing that both drugs up-regulated TPP1 mRNA, protein, and enzymatic activity both in vitro and in vivo in wild type (WT) and PPAR alpha(-/-), but not PPAR alpha(-/-), mice. In an attempt to delineate the mechanism of TPP1 up-regulation, it was found that the effects of the fibrate drugs were abrogated in the absence of retinoid X receptor-alpha (RXR alpha), a molecule known to form a heterodimer with PPAR alpha. Accordingly, all-trans-retinoic acid, alone or together with gemfibrozil, up-regulated TPP1. Co-immuno-precipitation and ChIP studies revealed the formation of a PPAR alpha/RXR alpha heterodimer and binding of the heterodimer to an RXR-binding site on the Cln2 promoter. Together, this study demonstrates a unique mechanism for the up-regulation of TPP1 by fibrate drugs via PPAR alpha /RXR alpha pathway. C1 [Ghosh, Arunava; Corbett, Grant T.; Pahan, Kalipada] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pahan, K (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1735 W Harrison St,Ste Cohn 320, Chicago, IL 60612 USA. EM Kalipada_Pahan@rush.edu FU National Institutes of Health [AT6681, NS64564, NS71479]; Noah's Hope Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants AT6681, NS64564, and NS71479. This work was also supported by a generous donation from Noah's Hope Foundation. NR 48 TC 15 Z9 15 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2012 VL 287 IS 46 BP 38922 EP 38935 DI 10.1074/jbc.M112.365148 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035WJ UT WOS:000310982800048 PM 22989886 ER PT J AU Della-Maria, J Hegde, ML McNeill, DR Matsumoto, Y Tsai, MS Ellenberger, T Wilson, DM Mitra, S Tomkinson, AE AF Della-Maria, Julie Hegde, Muralidhar L. McNeill, Daniel R. Matsumoto, Yoshihiro Tsai, Miaw-Sheue Ellenberger, Tom Wilson, David M., III Mitra, Sankar Tomkinson, Alan E. TI The Interaction between Polynucleotide Kinase Phosphatase and the DNA Repair Protein XRCC1 Is Critical for Repair of DNA Alkylation Damage and Stable Association at DNA Damage Sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE EXCISION-REPAIR; STRAND BREAK REPAIR; N-TERMINAL DOMAIN; LIGASE III-ALPHA; POLYMERASE-BETA; AP ENDONUCLEASE; HUMAN-CELLS; POLY(ADP-RIBOSE) POLYMERASE; BRCT DOMAIN; IN-VITRO AB XRCC1 plays a key role in the repair of DNA base damage and single-strand breaks. Although it has no known enzymatic activity, XRCC1 interacts with multiple DNA repair proteins and is a subunit of distinct DNA repair protein complexes. Here we used the yeast two-hybrid genetic assay to identify mutant versions of XRCC1 that are selectively defective in interacting with a single protein partner. One XRCC1 mutant, A482T, that was defective in binding to polynucleotide kinase phosphatase (PNKP) not only retained the ability to interact with partner proteins that bind to different regions of XRCC1 but also with aprataxin and aprataxin-like factor whose binding sites overlap with that of PNKP. Disruption of the interaction between PNKP and XRCC1 did not impact their initial recruitment to localized DNA damage sites but dramatically reduced their retention there. Furthermore, the interaction between PNKP and the DNA ligase III alpha-XRCC1 complex significantly increased the efficiency of reconstituted repair reactions and was required for complementation of the DNA damage sensitivity to DNA alkylation agents of xrcc1 mutant cells. Together our results reveal novel roles for the interaction between PNKP and XRCC1 in the retention of XRCC1 at DNA damage sites and in DNA alkylation damage repair. C1 [Della-Maria, Julie] Univ Maryland, Sch Med, Radiat Oncol Res Lab, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Della-Maria, Julie] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Hegde, Muralidhar L.; Mitra, Sankar] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. [McNeill, Daniel R.; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Matsumoto, Yoshihiro; Tomkinson, Alan E.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Matsumoto, Yoshihiro; Tomkinson, Alan E.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Tsai, Miaw-Sheue] Univ Calif Berkeley, Ernest Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Ellenberger, Tom] Washington Univ, Sch Med, Div Oncol, Dept Med, St Louis, MO 63110 USA. RP Tomkinson, AE (reprint author), 1 Univ New Mexico, Canc Res Facil, 915 Camino Salud, Albuquerque, NM 87131 USA. EM atomkinson@salud.unm.edu OI Hegde, Muralidhar/0000-0001-7333-8123 FU National Institutes of Health [R01 ES 012512, R01 CA81063, R01 GM052504, P01 CA 92584]; Intramural Research Program of the NIA, National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 ES 012512 (to A. E. T.), R01 CA81063 (to S. M.), R01 GM052504 (to T. E.), and P01 CA 92584 (to A. E. T., S. M., and T. E.) and by the Intramural Research Program of the NIA, National Institutes of Health. NR 49 TC 9 Z9 9 U1 2 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2012 VL 287 IS 46 BP 39233 EP 39244 DI 10.1074/jbc.M112.369975 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035WJ UT WOS:000310982800078 PM 22992732 ER PT J AU Bintu, L Ishibashi, T Dangkulwanich, M Wu, YY Lubkowska, L Kashlev, M Bustamante, C AF Bintu, Lacramioara Ishibashi, Toyotaka Dangkulwanich, Manchuta Wu, Yueh-Yi Lubkowska, Lucyna Kashlev, Mikhail Bustamante, Carlos TI Nucleosomal Elements that Control the Topography of the Barrier to Transcription SO CELL LA English DT Article ID RNA-POLYMERASE-II; HISTONE TAIL DOMAINS; DNA TRANSLOCATION; KINETIC-MODEL; ELONGATION; CHROMATIN; ACETYLATION; STABILITY; DYNAMICS; ARREST AB The nucleosome represents a mechanical barrier to transcription that operates as a general regulator of gene expression. We investigate how each nucleosomal component-the histone tails, the specific histone-DNA contacts, and the DNA sequence-contributes to the strength of the barrier. Removal of the tails favors progression of RNA polymerase II into the entry region of the nucleosome by locally increasing the wrapping-unwrapping rates of the DNA around histones. In contrast, point mutations that affect histone-DNA contacts at the dyad abolish the barrier to transcription in the central region by decreasing the local wrapping rate. Moreover, we show that the nucleosome amplifies sequence-dependent transcriptional pausing, an effect mediated through the structure of the nascent RNA. Each of these nucleosomal elements controls transcription elongation by affecting distinctly the density and duration of polymerase pauses, thus providing multiple and alternative mechanisms for control of gene expression by chromatin remodeling and transcription factors. C1 [Bintu, Lacramioara; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA. [Bintu, Lacramioara; Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. [Ishibashi, Toyotaka; Bustamante, Carlos] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94720 USA. [Dangkulwanich, Manchuta; Bustamante, Carlos] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Wu, Yueh-Yi; Bustamante, Carlos] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Lubkowska, Lucyna; Kashlev, Mikhail] NCI Ctr Canc Res, Frederick, MD 21702 USA. RP Bustamante, C (reprint author), Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA. EM carlos@alice.berkeley.edu OI Ishibashi, Toyotaka/0000-0001-8015-2319 FU NIH [R01-GM032543-31]; U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [DE-AC02-05CH11231]; JSPS FX We thank C. Hodges, S. Kassube, S. Sternberg, B. Zamft, and members of the Bustamante laboratory for assistance and discussions. T. I. is supported by a fellowship from JSPS. This work was supported by NIH grant R01-GM032543-31 (C. B.) and by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Contract No. DE-AC02-05CH11231 (C.B.). NR 41 TC 59 Z9 62 U1 1 U2 60 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 9 PY 2012 VL 151 IS 4 BP 738 EP 749 DI 10.1016/j.cell.2012.10.009 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 035CV UT WOS:000310921200007 PM 23141536 ER PT J AU Zhu, XW Westcott, MM Bi, X Liu, MX Gowdy, KM Seo, J Cao, Q Gebre, AK Fessler, MB Hitbold, EM Parks, JS AF Zhu, Xuewei Westcott, Marlena M. Bi, Xin Liu, Mingxia Gowdy, Kymberly M. Seo, Jeongmin Cao, Qiang Gebre, Abraham K. Fessler, Michael B. Hitbold, Elizabeth M. Parks, John S. TI Myeloid Cell-Specific ABCA1 Deletion Protects Mice From Bacterial Infection SO CIRCULATION RESEARCH LA English DT Article DE ATP-binding cassette transporter A1; bacterial killing; chemotaxis; macrophage ID CASSETTE TRANSPORTER 1; LISTERIA-MONOCYTOGENES; TANGIER-DISEASE; CHEMOKINE RECEPTOR; FREE-CHOLESTEROL; GENE-EXPRESSION; BONE-MARROW; APOA-I; MACROPHAGES; ATHEROSCLEROSIS AB Rationale: ATP-binding cassette transporter A1 (ABCA1) plays a critical role in eliminating excess free cholesterol from tissues by effluxing cellular free cholesterol and phospholipids to lipid-poor apolipoprotein AI. Macrophage ABCA1 also dampens proinflammatory myeloid differentiation primary-response protein 88-dependent toll-like receptor signaling by reducing cellular membrane free cholesterol and lipid raft content, indicating a role of ABCA1 in innate immunity. However, whether ABCA1 expression has a role in regulating macrophage function in vivo is unknown. Objective: We investigated whether macrophage ABCA1 expression impacts host defense function, including microbial killing and chemotaxis. Methods and Results: Myeloid cell-specific ABCA1 knockout (MSKO) vs wild-type mice were infected with Listeria monocytogenes (Lm) for 36 hours or 72 hours before euthanasia. Lm-induced monocytosis was similar for wild-type and MSKO mice; however, MSKO mice were more resistant to Lm infection, with significantly less body weight loss, less Lm burden in liver and spleen, and less hepatic damage 3 days postinfection. In addition, Lminfected MSKO mouse livers had: (1) greater monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 expression; (2) more monocyte/macrophage infiltration; (3) less neutral lipid accumulation; and (4) diminished expression of lipogenic genes. MSKO macrophages showed enhanced chemotaxis toward chemokines in vitro and increased migration from peritoneum in response to lipopolysaccharide in vivo. Lm infection of wildtype macrophages markedly reduced expression of ABCA1 protein, as well as other cholesterol export proteins (such as ATP-binding cassette transporter G1 and apolipoprotein E). Conclusions: Myeloid-specific ABCA1 deletion favors host response to and clearance of Lm. Macrophage Lm infection reduces expression of cholesterol export proteins, suggesting that diminished cholesterol efflux enhances innate immune function of macrophages. (Circ Res. 2012;111:1398-1409.) C1 [Zhu, Xuewei; Bi, Xin; Liu, Mingxia; Seo, Jeongmin; Gebre, Abraham K.; Parks, John S.] Wake Forest Sch Med, Dept Pathol Lipid Sci, Winston Salem, NC 27157 USA. [Gowdy, Kymberly M.; Fessler, Michael B.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Parks, JS (reprint author), Wake Forest Sch Med, Dept Pathol, Sect Lipid Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jparks@wakehealth.edu FU Mass Spectroscopy Facility of the Comprehensive Cancer Center [5P30CA12197]; North Carolina Biotechnology Center of Wake Forest School of Medicine [2007-IDG-1021]; National Institutes of Health [HL49373, HL94525]; American Heart Association fellowship [09POST2250225] FX The authors gratefully acknowledge Karen Klein (Research Support Core, Wake Forest School of Medicine) for editing the manuscript, and Dr Michael J. Thomas (Department of Biochemistry, Wake Forest School of Medicine) and the Mass Spectroscopy Facility of the Comprehensive Cancer Center (5P30CA12197 and North Carolina Biotechnology Center 2007-IDG-1021) of Wake Forest School of Medicine for the macrophage oxysterol measurements.; This study was supported by National Institutes of Health Grants HL49373, HL94525 (J.S. Parks) and by American Heart Association fellowship 09POST2250225 (X. Zhu). NR 35 TC 15 Z9 17 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 9 PY 2012 VL 111 IS 11 BP 1398 EP U108 DI 10.1161/CIRCRESAHA.112.269043 PG 22 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 035AM UT WOS:000310914000006 PM 22955730 ER PT J AU Xu, ZX Felsenfeld, G AF Xu, Zhixiong Felsenfeld, Gary TI Order from Chaos in the Nucleus SO MOLECULAR CELL LA English DT Editorial Material ID CHROMOSOME CONFORMATION; GENOME; ORGANIZATION; PRINCIPLES C1 [Xu, Zhixiong; Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov FU Intramural NIH HHS [ZIA DK036148-06] NR 10 TC 1 Z9 1 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 9 PY 2012 VL 48 IS 3 BP 327 EP 328 DI 10.1016/j.molcel.2012.10.021 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 039QF UT WOS:000311260900002 PM 23141201 ER PT J AU Jo, HJ Saad, ZS Gotts, SJ Martin, A Cox, RW AF Jo, Hang Joon Saad, Ziad S. Gotts, Stephen J. Martin, Alex Cox, Robert W. TI Quantifying Agreement between Anatomical and Functional Interhemispheric Correspondences in the Resting Brain SO PLOS ONE LA English DT Article ID HUMAN CEREBRAL-CORTEX; SPONTANEOUS FLUCTUATIONS; VISUAL-CORTEX; STATE FMRI; CALLOSAL PROJECTIONS; CORTICAL NETWORK; CORPUS-CALLOSUM; MACAQUE MONKEY; NEURAL BASIS; CONNECTIVITY AB The human brain is composed of two broadly symmetric cerebral hemispheres, with an abundance of reciprocal anatomical connections between homotopic locations. However, to date, studies of hemispheric symmetries have not identified correspondency precisely due to variable cortical folding patterns. Here we present a method to establish accurate correspondency using position on the unfolded cortical surface relative to gyral and sulcal landmarks. The landmark method is shown to outperform the method of reversing standard volume coordinates, and it is used to quantify the functional symmetry in resting fMRI data throughout the cortex. Resting brain activity was found to be maximally correlated with locations less than 1 cm away on the cortical surface from the corresponding anatomical location in nearly half of the cortex. While select locations exhibited asymmetric patterns, precise symmetric relationships were found to be the norm, with fine-grained symmetric functional maps demonstrated in motor, occipital, and inferior frontal cortex. Citation: Jo HJ, Saad ZS, Gotts SJ, Martin A, Cox RW (2012) Quantifying Agreement between Anatomical and Functional Interhemispheric Correspondences in the Resting Brain. PLoS ONE 7(11): e48847. doi: 10.1371/journal.pone.0048847 C1 [Jo, Hang Joon; Saad, Ziad S.; Cox, Robert W.] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. [Gotts, Stephen J.; Martin, Alex] NIMH, Cognit Neuropsychol Sect, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Jo, HJ (reprint author), NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. EM hangjoon.jo@nih.gov RI JO, HANG JOON/D-1775-2011; Gotts, Stephen/J-4842-2012 OI JO, HANG JOON/0000-0002-9180-3831; FU Intramural NIH HHS NR 69 TC 11 Z9 11 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 8 PY 2012 VL 7 IS 11 AR e48847 DI 10.1371/journal.pone.0048847 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053KE UT WOS:000312269500038 PM 23144995 ER PT J AU Roeseler, DA Sachdev, S Buckley, DM Joshi, T Wu, DK Xu, D Hannink, M Waters, ST AF Roeseler, David A. Sachdev, Shrikesh Buckley, Desire M. Joshi, Trupti Wu, Doris K. Xu, Dong Hannink, Mark Waters, Samuel T. TI Elongation Factor 1 alpha1 and Genes Associated with Usher Syndromes Are Downstream Targets of GBX2 SO PLOS ONE LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; IN-VITRO TRANSCRIPTION; CREST CELL-MIGRATION; INNER-EAR; HOMEOBOX GENE; ISTHMIC ORGANIZER; TATA BOX; MID/HINDBRAIN ORGANIZER; INTRON ENHANCER; ZEBRAFISH GBX1 AB Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during embryogenesis. Gain-and loss-of-function studies in several vertebrate species have demonstrated a requirement for Gbx2 in development of the anterior hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the target genes through which GBX2 exerts its effects remain obscure. Using chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq) analysis in a human prostate cancer cell line, we identified cis-regulatory elements bound by GBX2 to provide insight into its direct downstream targets. The analysis revealed more than 286 highly significant candidate target genes, falling into various functional groups, of which 51% are expressed in the nervous system. Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1, and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and USH2A, and are plausible candidates contributing to the developmental defects in Gbx2(-/-) mice. We show through gel shift analyses that sequences within the promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/-) embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates transcriptional activity through the promoter of EEF1A1, suggesting that GBX2 could also regulate gene expression indirectly via EEF1A. Taken together, our studies show that GBX2 plays a dynamic role in development and diseases. Citation: Roeseler DA, Sachdev S, Buckley DM, Joshi T, Wu DK, et al. (2012) Elongation Factor 1 alpha1 and Genes Associated with Usher Syndromes Are Downstream Targets of GBX2. PLoS ONE 7(11): e47366. doi:10.1371/journal.pone.0047366 C1 [Roeseler, David A.; Buckley, Desire M.; Waters, Samuel T.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Roeseler, David A.; Sachdev, Shrikesh; Buckley, Desire M.; Joshi, Trupti; Xu, Dong; Hannink, Mark; Waters, Samuel T.] Univ Missouri, Christopher S Bond Life Sci Ctr, Columbia, MO 65211 USA. [Sachdev, Shrikesh; Hannink, Mark] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. [Joshi, Trupti; Xu, Dong] Univ Missouri, Dept Comp Sci, Columbia, MO 65211 USA. [Wu, Doris K.] NIDCD, Mol Biol Lab, NIH, Bethesda, MD USA. [Joshi, Trupti; Xu, Dong] Univ Missouri, Inst Informat, Columbia, MO 65211 USA. RP Waters, ST (reprint author), Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. EM waterssa@missouri.edu FU National Science Foundation [NSF 1021288] FX This work has been funded by the National Science Foundation, NSF 1021288. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 5 Z9 7 U1 3 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 8 PY 2012 VL 7 IS 11 AR e47366 DI 10.1371/journal.pone.0047366 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053KE UT WOS:000312269500008 PM 23144817 ER PT J AU Micci, L Cervasi, B Ende, ZS Iriele, RI Reyes-Aviles, E Vinton, C Else, J Silvestri, G Ansari, AA Villinger, F Pahwa, S Estes, JD Brenchley, JM Paiardini, M AF Micci, Luca Cervasi, Barbara Ende, Zachary S. Iriele, Robin I. Reyes-Aviles, Elane Vinton, Carol Else, James Silvestri, Guido Ansari, Aftab A. Villinger, Francois Pahwa, Savita Estes, Jacob D. Brenchley, Jason M. Paiardini, Mirko TI Paucity of IL-21-producing CD4(+) T cells is associated with Th17 cell depletion in SIV infection of rhesus macaques SO BLOOD LA English DT Article ID CHRONIC VIRAL-INFECTION; PROGRESSIVE HIV-INFECTION; IMMUNE ACTIVATION; SOOTY MANGABEYS; T(H)17 CELLS; IL-21; VIRUS; AIDS; DIFFERENTIATION; INTERLEUKIN-21 AB IL-21 regulates Th17 cell homeostasis, enhances the differentiation of memory B cells and antibody-secreting plasma cells, and promotes the maintenance of CD8(+) T-cell responses. In this study, we investigated the phenotype, function, and frequency of blood and intestinal IL-21-producing cells in nonhuman primates that are hosts of progressive (rhesus macaques [RMs]) and nonprogressive (sooty mangabeys [SMs]) SIV infection. We found that, in both species, memory CD4(+)CD95(+)CCR6(-) T cells are the main IL-21 producers, and that only a small fraction of CD4(+)IL-21(+) T cells produce IL-17. During chronic SIV infection of RMs, CD4(+)IL-21(+) T cells were significantly depleted in both blood and rectal mucosa, with the extent of this depletion correlating with the loss of Th17 cells. Furthermore, treatment with IL-21 increased the in vivo levels of Th17 cells in SIV-infected RMs. In contrast, normal levels of CD4(+)IL-21(+) T cells were found in SIV-infected SMs. Collectively, these data indicate that depletion of IL-21-producing CD4(+) T cells distinguishes progressive from nonprogressive SIV infection of RMs and SMs, and suggest that depletion of CD4(+)IL-21(+) T cells is involved in the preferential loss of Th17 cells that is associated with SIV disease progression. Further preclinical studies of IL-21 as a potential immunotherapeutic agent for HIV infection may be warranted. (Blood. 2012;120(19):3925-3935) C1 [Paiardini, Mirko] Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30329 USA. [Reyes-Aviles, Elane] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Vinton, Carol; Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Vinton, Carol; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Else, James; Silvestri, Guido; Ansari, Aftab A.; Villinger, Francois; Paiardini, Mirko] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA. [Villinger, Francois] Emory Univ, Div Pathol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Pahwa, Savita] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Estes, Jacob D.] NCI Frederick, AIDS Canc Virus Program, Frederick, MD USA. RP Paiardini, M (reprint author), Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM mirko.paiardini@emory.edu FU National Institutes of Health (NIH) [R01-AI084836, R56-AI087186, R37-AI66998, P01-AI 76174]; National Cancer Institute, NIH [HHSN261200800001E]; National Center for Research Resources [P51RR165]; Office of Research Infrastructure Programs/OD [P51OD11132] FX This work was supported by the National Institutes of Health (NIH; grants R01-AI084836 and R56-AI087186, M. P.; grants R37-AI66998 and P01-AI 76174, G. S.), and in part by the National Cancer Institute, NIH (contract HHSN261200800001E), and the National Center for Research Resources P51RR165 (currently supported by the Office of Research Infrastructure Programs/OD P51OD11132). NR 52 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 8 PY 2012 VL 120 IS 19 BP 3925 EP 3935 DI 10.1182/blood-2012-04-420240 PG 11 WC Hematology SC Hematology GA 044OL UT WOS:000311629600014 PM 22990011 ER PT J AU Segarra, M Ohnuki, H Maric, D Salvucci, O Hou, X Kumar, A Li, XR Tosato, G AF Segarra, Marta Ohnuki, Hidetaka Maric, Dragan Salvucci, Ombretta Hou, Xu Kumar, Anil Li, Xuri Tosato, Giovanna TI Semaphorin 6A regulates angiogenesis by modulating VEGF signaling SO BLOOD LA English DT Article ID LAMINA-RESTRICTED PROJECTION; HIPPOCAMPAL MOSSY FIBERS; VASCULAR-PERMEABILITY; NEUROPILIN-1 INTERNALIZATION; RETINAL VASCULATURE; TUMOR ANGIOGENESIS; CELLS; MICE; PLEXIN-A4; GROWTH AB Formation of new vessels during development and in the mature mammal generally proceeds through angiogenesis. Although a variety of molecules and signaling pathways are known to underlie endothelial cell sprouting and remodeling during angiogenesis, many aspects of this complex process remain unexplained. Here we show that the transmembrane semaphorin6A (Sema6A) is expressed in endothelial cells, and regulates endothelial cell survival and growth by modulating the expression and signaling of VEGFR2, which is known to maintain endothelial cell viability by autocrine VEGFR signaling. The silencing of Sema6A in primary endothelial cells promotes cell death that is not rescued by exogenous VEGF-A or FGF2, attributable to the loss of prosurvival signaling from endogenous VEGF. Analyses of mouse tissues demonstrate that Sema6A is expressed in angiogenic and remodeling vessels. Mice with null mutations of Sema6A exhibit significant defects in hyaloid vessels complexity associated with increased endothelial cell death, and in retinal vessels development that is abnormally reduced. Adult Sema6A-null mice exhibit reduced tumor, matrigel, and choroidal angiogenesis compared with controls. Sema6A plays important roles in development of the nervous system. Here we show that it also regulates vascular development and adult angiogenesis. (Blood. 2012; 120(19): 4104-4115) C1 [Segarra, Marta; Ohnuki, Hidetaka; Salvucci, Ombretta; Tosato, Giovanna] NCI, Cellular Oncol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Maric, Dragan] NINDS, Lab Neurophysiol, NIH, Bethesda, MD 20892 USA. [Hou, Xu; Kumar, Anil; Li, Xuri] NEI, NIH, Rockville, MD USA. RP Ohnuki, H (reprint author), NCI, Cellular Oncol Lab, CCR, NIH, Bldg 37,Rm 4124, Bethesda, MD 20892 USA. EM ohnukih@mail.nih.gov RI Kumar, Anil/K-8504-2012 FU Intramural Research Program at NIH; CCR; NCI; Fulbright/Ministerio Educacion y Ciencia postdoctoral grant; Strategic Young Researcher Overseas Visiting Program for accelerating Brain Research Circulation; JSPS (Japan Society for the Promotion of Science); [S2207] FX This research was supported by the Intramural Research Program at NIH, CCR, NCI. M.S. was supported in part by a Fulbright/Ministerio Educacion y Ciencia postdoctoral grant; and H.O. was supported in part by Grant-in-Aid for Scientific Research (S2207 S. Higashiyama); and Strategic Young Researcher Overseas Visiting Program for accelerating Brain Research Circulation, JSPS (Japan Society for the Promotion of Science). NR 50 TC 26 Z9 28 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 8 PY 2012 VL 120 IS 19 BP 4104 EP 4115 DI 10.1182/blood-2012-02-410076 PG 12 WC Hematology SC Hematology GA 044OL UT WOS:000311629600033 PM 23007403 ER PT J AU Ndebele, PM Wassenaar, D Munalula, E Masiye, F AF Ndebele, Paul M. Wassenaar, Douglas Munalula, Esther Masiye, Francis TI Improving understanding of clinical trial procedures among low literacy populations: an intervention within a microbicide trial in Malawi SO BMC MEDICAL ETHICS LA English DT Article DE Assessment; Comprehension; Double-blinding; Informed consent; Intervention; Randomisation; Placebo; Malawi; Understanding ID INFORMED-CONSENT PROCESS; PSYCHOTIC DISORDERS; PARTICIPATION; PREVENTION; CANCER AB Background: The intervention reported in this paper was a follow up to an empirical study conducted in Malawi with the aim of assessing trial participants' understanding of randomisation, double-blinding and placebo use. In the empirical study, the majority of respondents (61.1%; n=124) obtained low scores (lower than 75%) on understanding of all three concepts under study. Based on these findings, an intervention based on a narrative which included all three concepts and their personal implications was designed. The narrative used daily examples from the field of Agriculture because Malawi has an agro-based economy. Methods: The intervention was tested using a sample of 36 women who had been identified as low scorers during the empirical study. The 36 low scorers were randomly assigned to control (n=18) and intervention arms (n=18). The control arm went through a session in which they were provided with standard informed consent information for the microbicide trial. The intervention arm went through a session in which they were provided with a narrative in ChiChewa, the local language, with the assistance of a power point presentation which included pictures as well as discussions on justification and personal implications of the concepts under study. Results: The findings on the efficacy of the intervention suggest that the 3 scientific concepts and their personal implications can be understood by low literacy populations using simple language and everyday local examples. The findings also suggest that the intervention positively impacted on understanding of trial procedures under study, as 13 of the 18 women in the intervention arm, obtained high scores (above 75%) during the post intervention assessment and none of the 18 in the control arm obtained a high score. Using Fischer's exact test, it was confirmed that the effect of the intervention on understanding of the three procedures was statistically significant (p=0.0001). Conclusions: Potential trial participants can be assisted to understand key clinical trial procedures, their justification and personal implications by using innovative tailored local narratives. C1 [Ndebele, Paul M.] NIAID, HJF DAIDS, NIH, Bethesda, MD 20817 USA. [Wassenaar, Douglas] Univ KwaZulu Natal, Pietermaritzburg, South Africa. [Munalula, Esther] Univ Zambia, Lusaka, Zambia. [Masiye, Francis] Univ Malawi, Coll Med, Blantyre, Malawi. RP Ndebele, PM (reprint author), NIAID, HJF DAIDS, NIH, 6700A Rockledge Dr,Room 42A193,2nd Floor, Bethesda, MD 20817 USA. EM pndexas@yahoo.com RI Wassenaar, Douglas/N-5301-2013 OI Wassenaar, Douglas/0000-0003-0839-9231 FU South African Research Ethics Training Initiative (SARETI) (National Institutes of Health Fogarty International Center [5 R25 TW001599-09]; Scholars Rescue Fund (SRF) FX The authors are very grateful to all the microbicide trial participants who volunteered to participate in this study, and to the Principal Investigators and study staff at the two sites. The work was partly supported by the South African Research Ethics Training Initiative (SARETI) (National Institutes of Health Fogarty International Center grant number 5 R25 TW001599-09 and Scholars Rescue Fund (SRF). The authors are also grateful to all colleagues that participated in the various components of the project including design of tools, statistical support and data collection. NR 42 TC 4 Z9 4 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD NOV 8 PY 2012 VL 13 AR 29 DI 10.1186/1472-6939-13-29 PG 14 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA 044HY UT WOS:000311611400001 PM 23136958 ER PT J AU Bandettini, PA AF Bandettini, Peter A. TI The BOLD Plot Thickens: Sign- and Layer-Dependent Hemodynamic Changes with Activation SO NEURON LA English DT Editorial Material ID HUMAN BRAIN AB In this issue of Neuron, Goense et al. (2012) report on high-resolution, layer-specific measurements of BOLD, cerebral blood volume, and cerebral blood flow in regions of positive and negative BOLD associated with a simple visual stimulus. The findings strongly suggest that the hemodynamic mechanisms behind negative signal changes are quite different from those behind positive signal changes. C1 NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Bandettini, PA (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM bandettp@mail.nih.gov NR 10 TC 3 Z9 3 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 8 PY 2012 VL 76 IS 3 BP 468 EP 469 DI 10.1016/j.neuron.2012.10.026 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 036WT UT WOS:000311063700003 PM 23141059 ER PT J AU Veran, J Kumar, J Pinheiro, PS Athane, A Mayer, ML Perrais, D Mulle, C AF Veran, Julien Kumar, Janesh Pinheiro, Paulo S. Athane, Axel Mayer, Mark L. Perrais, David Mulle, Christophe TI Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface SO NEURON LA English DT Article ID MOSSY-FIBER SYNAPSES; GLUK3-CONTAINING KAINATE RECEPTORS; NMDA RECEPTOR; CRYSTAL-STRUCTURE; SUBUNIT; DESENSITIZATION; INHIBITION; MODULATION; MECHANISM; GLUR7 AB Kainate receptors (KARs) play a key role in the regulation of synaptic networks. Here, we show that zinc, a cation released at a subset of glutamatergic synapses, potentiates glutamate currents mediated by homomeric and heteromeric KARs containing GluK3 at 10-100 mu M concentrations, whereas it inhibits other KAR subtypes. Potentiation of GluK3 currents is mainly due to reduced desensitization, as shown by kinetic analysis and desensitization mutants. Crystallographic and mutation analyses revealed that a specific zinc binding site is formed at the base of the ligand binding domain (LBD) dimer interface by a GluK3-specific aspartate (Asp759), together with two conserved residues, His762 and Asp730, the latter located on the partner subunit. In addition, we propose that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer interface, slows desensitization, and potentiates currents, providing a mechanism for KAR potentiation at glutamatergic synapses. C1 [Veran, Julien; Pinheiro, Paulo S.; Athane, Axel; Perrais, David; Mulle, Christophe] Univ Bordeaux, F-33000 Bordeaux, France. [Veran, Julien; Pinheiro, Paulo S.; Athane, Axel; Perrais, David; Mulle, Christophe] CNRS, Interdisciplinary Inst Neurosci, UMR 5297, F-33000 Bordeaux, France. [Kumar, Janesh; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mulle, C (reprint author), Univ Bordeaux, F-33000 Bordeaux, France. EM mulle@u-bordeaux2.fr RI Mayer, Mark/H-5500-2013; OI Perrais, David/0000-0002-5878-5408; Pinheiro, Paulo/0000-0002-9024-1021; Mulle, Christophe/0000-0003-2709-6615 FU Centre National de la Recherche Scientifique; Fondation pour la Recherche Medicale; Conseil Regional d'Aquitaine; Agence Nationale de la Recherche (contract SynapticZinc); NICHD, NIH; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357] FX This work was supported by the Centre National de la Recherche Scientifique, the Fondation pour la Recherche Medicale, the Conseil Regional d'Aquitaine, the Agence Nationale de la Recherche (contract SynapticZinc), and the intramural research program of NICHD, NIH. Synchrotron diffraction data were collected at SER-CAT beamline 22 ID. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. We thank Remi Sterling for cell culture maintenance, and Francoise Coussen, Severine Desforges, and Carla Glasser for help with molecular biology. Pierre Paoletti provided insightful suggestions along the course of this study. We are also grateful for members of the C.M. laboratory for helpful discussions. NR 55 TC 21 Z9 21 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD NOV 8 PY 2012 VL 76 IS 3 BP 565 EP 578 DI 10.1016/j.neuron.2012.08.027 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 036WT UT WOS:000311063700012 PM 23141068 ER PT J AU Goense, J Merkle, H Logothetis, NK AF Goense, Jozien Merkle, Hellmut Logothetis, Nikos K. TI High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses SO NEURON LA English DT Article ID CEREBRAL-BLOOD-FLOW; CLASSICAL RECEPTIVE-FIELD; PRIMARY SOMATOSENSORY CORTEX; VASCULAR SPACE OCCUPANCY; MACAQUE STRIATE CORTEX; PRIMARY VISUAL-CORTEX; NEURONAL-ACTIVITY; FUNCTIONAL MRI; HUMAN-BRAIN; HEMODYNAMIC-RESPONSE AB The six cortical layers have distinct anatomical and physiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, as well as laminar differences in neurovascular coupling. C1 [Goense, Jozien; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. [Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20814 USA. [Logothetis, Nikos K.] Univ Manchester, Div Imaging Sci & Biomed Engn, Manchester M13 9PT, Lancs, England. RP Goense, J (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. EM jozien.goense@tuebingen.mpg.de FU Max-Planck Society; National Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA FX We are grateful to Dr. Daniel Gembris and Dr. Franek Hennel from Bruker BioSpin GmbH for the sequence to simultaneously measure the BOLD, CBF, and VASO signals and Dr. Mark Augath for technical support. Dr. Kevin Whittingstall provided comments on earlier versions of the manuscript. We also thank the reviewers for their suggestions. The research was supported by the Max-Planck Society and in part by the Intramural Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA (to H.M.). NR 81 TC 83 Z9 83 U1 2 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD NOV 8 PY 2012 VL 76 IS 3 BP 629 EP 639 DI 10.1016/j.neuron.2012.09.019 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 036WT UT WOS:000311063700017 PM 23141073 ER PT J AU Visco, AG Brubaker, L Richter, HE Nygaard, I Paraiso, MFR Menefee, SA Schaffer, J Lowder, J Khandwala, S Sirls, L Spino, C Nolen, TL Wallace, D Meikle, SF AF Visco, Anthony G. Brubaker, Linda Richter, Holly E. Nygaard, Ingrid Paraiso, Marie Fidela R. Menefee, Shawn A. Schaffer, Joseph Lowder, Jerry Khandwala, Salil Sirls, Larry Spino, Cathie Nolen, Tracy L. Wallace, Dennis Meikle, Susan F. CA Pelvic Floor Disorders Network TI Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OVERACTIVE BLADDER QUESTIONNAIRE; TOXIN TYPE-A; DETRUSOR OVERACTIVITY; OAB-Q; PERSISTENCE; TRIAL; WOMEN; EFFICACY AB Background Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. Methods We performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events. Results Of 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P = 0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P = 0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P = 0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P = 0.01) and urinary tract infections (13% vs. 33%, P<0.001). Conclusions Oral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.) C1 [Visco, Anthony G.] Duke Univ, Dept Obstet & Gynecol, Med Ctr, Durham, NC 27707 USA. [Nolen, Tracy L.; Wallace, Dennis] RTI Int, Res Triangle Pk, NC USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Urol, Chicago, IL 60611 USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA. [Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Paraiso, Marie Fidela R.] Cleveland Clin, Dept Obstet & Gynecol, Cleveland, OH USA. [Menefee, Shawn A.] Kaiser Permanente San Diego, Dept Obstet & Gynecol, San Diego, CA USA. [Schaffer, Joseph] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Lowder, Jerry] Univ Pittsburgh, Pittsburgh, PA USA. [Khandwala, Salil] Oakwood Hosp & Med Ctr, Dearborn, MI USA. [Sirls, Larry] Oakland Univ, William Beaumont Sch Med, Dept Urol, Beaumont Hlth Syst, Royal Oak, MI USA. [Spino, Cathie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Rockville, MD USA. RP Visco, AG (reprint author), Duke Univ, Dept Obstet & Gynecol, Med Ctr, 5324 McFarland Dr,Suite 310, Durham, NC 27707 USA. EM anthony.visco@duke.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Office of Research on Women's Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development [2-U10-HD04267-12, U10-HD054136, 2-U10-HD041261-11, U10-HD041250, 2-U10-HD054215-06, 2-U10-HD054214-06, 1-U10-HD069006-01, 2-U10-HD054241-06, U01-HD41249, 1-U01-HD069010-01]; Astellas Pharma; GlaxoSmithKline; Uromedica; IDEO; Pfizer; Xanodyne Pharmaceuticals; Pelvalon; Warner Chilcott; Ethicon; Ferring Pharmaceuticals; Cadence FX Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.; Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (2-U10-HD04267-12, to Duke University Medical Center; U10-HD054136, to Loyola University; 2-U10-HD041261-11, to the University of Alabama at Birmingham; U10-HD041250, to the University of Utah; 2-U10-HD054215-06, to the Cleveland Clinic; 2-U10-HD054214-06, to the University of California, San Diego; 1-U10-HD069006-01, to the University of Pittsburgh; 2-U10-HD054241-06, to the University of Texas Southwestern Medical Center; U01-HD41249, to the University of Michigan; and 1-U01-HD069010-01, to RTI International) and the National Institutes of Health Office of Research on Women's Health.; Dr. Richter reports receiving consulting fees from Astellas Pharma, GlaxoSmithKline, Uromedica, IDEO, Pfizer, and Xanodyne Pharmaceuticals and grant support on behalf of her institution from Pelvalon, Astellas Pharma, Warner Chilcott, and Pfizer; Dr. Paraiso, receiving consulting fees from Ethicon; and Dr. Shaffer, receiving consulting fees from Astellas Pharma, Ferring Pharmaceuticals, and Cadence, lecture fees from Astellas Pharma and Cadence, and royalties from McGraw-Hill Companies. No other potential conflict of interest relevant to this article was reported. NR 22 TC 57 Z9 57 U1 1 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 8 PY 2012 VL 367 IS 19 BP 1803 EP 1813 DI 10.1056/NEJMoa1208872 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 033DG UT WOS:000310773200007 PM 23036134 ER PT J AU Teicher, BA Doroshow, JH AF Teicher, Beverly A. Doroshow, James H. TI The Promise of Antibody-Drug Conjugates SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; CANCER C1 [Teicher, Beverly A.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Teicher, BA (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 7 TC 27 Z9 27 U1 0 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 8 PY 2012 VL 367 IS 19 BP 1847 EP 1848 DI 10.1056/NEJMe1211736 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 033DG UT WOS:000310773200015 PM 23134386 ER PT J AU Caporaso, NE AF Caporaso, Neil E. TI Statins and Cancer-Related Mortality - Let's Work Together SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID THERAPY; RISK C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Caporaso, NE (reprint author), NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NR 7 TC 8 Z9 8 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 8 PY 2012 VL 367 IS 19 BP 1848 EP 1850 DI 10.1056/NEJMe1210002 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 033DG UT WOS:000310773200016 PM 23134387 ER PT J AU Liu, MY Chen, KQ Yoshimura, T Liu, Y Gong, WH Wang, AM Gao, JL Murphy, PM Wang, JM AF Liu, Mingyong Chen, Keqiang Yoshimura, Teizo Liu, Ying Gong, Wanghua Wang, Aimin Gao, Ji-Liang Murphy, Philip M. Wang, Ji Ming TI Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes SO SCIENTIFIC REPORTS LA English DT Article ID FORMYL-PEPTIDE RECEPTORS; IMMUNE-RESPONSES; MICE LACKING; INFECTION; EPIDEMIOLOGY; INFLAMMATION; MACROPHAGE; INTERNALIN; MIGRATION; CXCR1/2 AB Listeria monocytogenes ( Listeria) causes opportunistic infection in immunocompromised hosts with high mortality. Resistance to Listeria depends on immune responses and recruitment of neutrophils of the immune system into infected sites is an early and critical step. Mouse neutrophils express two G protein-coupled formylpeptide receptor subtypes Fpr1 and Fpr2 that recognize bacterial and host-derived chemotactic molecules including Listeria peptides for cell migration and activation. Here we report deficiency in Fprs exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide. Thus, Fprs are essential sentinels to guide the first wave of neutrophil infiltration in the liver of Listeria-infected mice for effective elimination of the invading pathogen. C1 [Liu, Mingyong] Third Mil Med Univ, Daping Hosp, Dept Spine Surg, Chongqing 400042, Peoples R China. [Liu, Mingyong; Chen, Keqiang; Yoshimura, Teizo; Liu, Ying; Wang, Ji Ming] Frederick Natl Lab Canc Res, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Gong, Wanghua] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. [Wang, Aimin] Third Mil Med Univ, Daping Hosp, Ctr Orthoped, Chongqing 400042, Peoples R China. [Gao, Ji-Liang; Murphy, Philip M.] NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Liu, MY (reprint author), Third Mil Med Univ, Daping Hosp, Dept Spine Surg, Chongqing 400042, Peoples R China. EM liu_mingyong@yahoo.com.cn; wangji@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank Drs. J.J. Oppenheim and G. Trinchieri for critically reviewing the manuscript; C. Lamb for secretarial assistance. This project was funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and was supported in part by the Intramural Research Program of the NCI, NIH. NR 37 TC 27 Z9 31 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 8 PY 2012 VL 2 AR 786 DI 10.1038/srep00786 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034MM UT WOS:000310877600002 PM 23139859 ER PT J AU Grivennikov, SI Wang, KP Mucida, D Stewart, CA Schnabl, B Jauch, D Taniguchi, K Yu, GY Osterreicher, CH Hung, KE Datz, C Feng, Y Fearon, ER Oukka, M Tessarollo, L Coppola, V Yarovinsky, F Cheroutre, H Eckmann, L Trinchieri, G Karin, M AF Grivennikov, Sergei I. Wang, Kepeng Mucida, Daniel Stewart, C. Andrew Schnabl, Bernd Jauch, Dominik Taniguchi, Koji Yu, Guann-Yi Oesterreicher, Christoph H. Hung, Kenneth E. Datz, Christian Feng, Ying Fearon, Eric R. Oukka, Mohamed Tessarollo, Lino Coppola, Vincenzo Yarovinsky, Felix Cheroutre, Hilde Eckmann, Lars Trinchieri, Giorgio Karin, Michael TI Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth SO NATURE LA English DT Article ID PROMOTES COLON TUMORIGENESIS; COLORECTAL-CANCER; APC(MIN/+) MICE; CUTTING EDGE; HELPER-CELLS; MOUSE MODEL; INFLAMMATION; RECEPTOR; COLITIS; DIFFERENTIATION AB Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and activation of beta-catenin are followed by mutations in K-Ras, PIK3CA and TP53, as the tumour emerges and progresses(1,2). Curiously, however, 'inflammatory signature' genes characteristic of colitis-associated cancer are also upregulated in colorectal cancer(3,4). Further, like most solid tumours, colorectal cancer exhibits immune/inflammatory infiltrates(5), referred to as 'tumour-elicited inflammation'(6). Although infiltrating CD4(+) T(H)1 cells and CD8(+) cytotoxic T cells constitute a positive prognostic sign in colorectal cancer(7,8), myeloid cells and T-helper interleukin (IL)-17-producing (T(H)17) cells promote tumorigenesis(5,6), and a 'T(H)17 expression signature' in stage I/II colorectal cancer is associated with a drastic decrease in disease-free survival(9). Despite its pathogenic importance, the mechanisms responsible for the appearance of tumour-elicited inflammation are poorly understood. Many epithelial cancers develop proximally to microbial communities, which are physically separated from immune cells by an epithelial barrier(10). We investigated mechanisms responsible for tumour-elicited inflammation in a mouse model of colorectal tumorigenesis, which, like human colorectal cancer, exhibits upregulation of IL-23 and IL-17. Here we show that IL-23 signalling promotes tumour growth and progression, and development of a tumoural IL-17 response. IL-23 is mainly produced by tumour-associated myeloid cells that are likely to be activated by microbial products, which penetrate the tumours but not adjacent tissue. Both early and late colorectal neoplasms exhibit defective expression of several barrier proteins. We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth. C1 [Grivennikov, Sergei I.; Wang, Kepeng; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Karin, Michael] Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA. [Grivennikov, Sergei I.; Wang, Kepeng; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Karin, Michael] Univ Calif San Diego, Dept Pathol, Sch Med, La Jolla, CA 92093 USA. [Wang, Kepeng] Shenzhen PKU HKUST Med Ctr, Biomed Res Inst, Shenzhen, Guangdong, Peoples R China. [Mucida, Daniel; Cheroutre, Hilde] La Jolla Inst Allergy & Immunol, La Jolla, CA 92093 USA. [Mucida, Daniel] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10065 USA. [Stewart, C. Andrew; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Schnabl, Bernd; Oesterreicher, Christoph H.; Eckmann, Lars] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. [Taniguchi, Koji] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan. [Oesterreicher, Christoph H.] Med Univ Vienna, Ctr Physiol & Pharmacol, Inst Pharmacol, Vienna, Austria. [Hung, Kenneth E.] Tufts Med Ctr, Dept Med, Boston, MA 02111 USA. [Datz, Christian] Paracelsus Med Univ, Oberndorf Hosp, Dept Internal Med, Salzburg, Austria. [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Oukka, Mohamed] Seattle Childrens Res Inst, Seattle, WA 98105 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. [Coppola, Vincenzo] Ohio State Univ, Ctr Comprehens Canc, Wexner Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. RP Karin, M (reprint author), Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM karinoffice@ucsd.edu RI Coppola, Vincenzo/E-2917-2011; Stewart, Charles/G-2470-2012; Wang, Kepeng/F-8363-2014; OI Coppola, Vincenzo/0000-0001-6163-1779; Wang, Kepeng/0000-0001-6428-4709; Mucida, Daniel/0000-0002-0000-0452 FU Crohn's and Colitis Foundation of America [2693]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [K99-DK088589]; University of California, San Diego, Digestive Disease Research Development Center Pilot Grant [DK080506]; Croucher Foundation; China Postdoctoral Science Foundation [20110490919]; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; SPAR Austria; NIH [R01CA082223, AI043477, DK035108]; American Association for Cancer Research [07-60-21-KARI] FX We thank eBioscience, GeneTex, Santa Cruz, BioLegend and Cell Signaling for antibodies; Genentech and Amgen for Il23-/- and Il17ra-/- mice, respectively, and S. Reid and E. Southon for the help in generating Il23rF/F mice. This work was supported by Crohn's and Colitis Foundation of America (Career Development Award number 2693), NIH/National Institute of Diabetes and Digestive and Kidney Diseases (K99-DK088589) and a University of California, San Diego, Digestive Disease Research Development Center Pilot Grant (DK080506) to S. I. G.; Croucher Foundation and China Postdoctoral Science Foundation (20110490919) to K. W.; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation to K. T.; SPAR Austria to C. D.; NIH (R01CA082223) to E. R. F.; and NIH (AI043477; DK035108) and American Association for Cancer Research (07-60-21-KARI) grants to M. K., who is an American Cancer Society Research Professor. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 44 TC 317 Z9 333 U1 6 U2 94 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2012 VL 491 IS 7423 BP 254 EP + DI 10.1038/nature11465 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 033DP UT WOS:000310774300044 PM 23034650 ER PT J AU Yoshizaki, A Miyagaki, T DiLillo, DJ Matsushita, T Horikawa, M Kountikov, EI Spolski, R Poe, JC Leonard, WJ Tedder, TF AF Yoshizaki, Ayumi Miyagaki, Tomomitsu DiLillo, David J. Matsushita, Takashi Horikawa, Mayuka Kountikov, Evgueni I. Spolski, Rosanne Poe, Jonathan C. Leonard, Warren J. Tedder, Thomas F. TI Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions SO NATURE LA English DT Article ID B10 CELLS; TRANSGENIC MICE; LYMPHOCYTE DEVELOPMENT; CUTTING EDGE; PLASMA-CELLS; HUMAN CD19; MEMORY B; IN-VIVO; IL-21; IL-10 AB B cells regulate immune responses by producing antigen-specific antibodies(1). However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells(2-4). Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified(2-5). Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice(5-7). How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies. C1 [Yoshizaki, Ayumi; Miyagaki, Tomomitsu; DiLillo, David J.; Matsushita, Takashi; Horikawa, Mayuka; Kountikov, Evgueni I.; Poe, Jonathan C.; Tedder, Thomas F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Tedder, TF (reprint author), Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. EM thomas.tedder@duke.edu RI Matsushita, Takashi /C-4750-2015 OI Matsushita, Takashi /0000-0002-1617-086X FU National Institutes of Health (NIH) [AI56363, AI057157]; Lymphoma Research Foundation; Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH FX We thank D. Maseda, E. Weimer, J. Bryant, K. Candando and G. Venturi for help and comments. These studies were supported by grants from the National Institutes of Health (NIH; AI56363 and AI057157), the Lymphoma Research Foundation, and the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. NR 37 TC 227 Z9 238 U1 5 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2012 VL 491 IS 7423 BP 264 EP + DI 10.1038/nature11501 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 033DP UT WOS:000310774300046 PM 23064231 ER PT J AU Kim, S Bolton, EE Bryant, SH AF Kim, Sunghwan Bolton, Evan E. Bryant, Stephen H. TI Effects of multiple conformers per compound upon 3-D similarity search and bioassay data analysis SO JOURNAL OF CHEMINFORMATICS LA English DT Article ID DATA FUSION; BIOLOGICAL-ACTIVITIES; MOLECULAR SHAPE; PUBCHEM3D; CONFORMATIONS; COEFFICIENTS; PERFORMANCE; DESIGN; VALIDATION; CATALYST AB Background: To improve the utility of PubChem, a public repository containing biological activities of small molecules, the PubChem3D project adds computationally-derived three-dimensional (3-D) descriptions to the small-molecule records contained in the PubChem Compound database and provides various search and analysis tools that exploit 3-D molecular similarity. Therefore, the efficient use of PubChem3D resources requires an understanding of the statistical and biological meaning of computed 3-D molecular similarity scores between molecules. Results: The present study investigated effects of employing multiple conformers per compound upon the 3-D similarity scores between ten thousand randomly selected biologically-tested compounds (10-K set) and between non-inactive compounds in a given biological assay (156-K set). When the "best-conformer-pair" approach, in which a 3-D similarity score between two compounds is represented by the greatest similarity score among all possible conformer pairs arising from a compound pair, was employed with ten diverse conformers per compound, the average 3-D similarity scores for the 10-K set increased by 0.11, 0.09, 0.15, 0.16, 0.07, and 0.18 for STST-opt, CTST-opt, ComboT(ST-opt), STCT-opt, CTCT-opt, and ComboT(CT-opt), respectively, relative to the corresponding averages computed using a single conformer per compound. Interestingly, the best-conformer-pair approach also increased the average 3-D similarity scores for the non-inactive-non-inactive (NN) pairs for a given assay, by comparable amounts to those for the random compound pairs, although some assays showed a pronounced increase in the per-assay NN-pair 3-D similarity scores, compared to the average increase for the random compound pairs. Conclusion: These results suggest that the use of ten diverse conformers per compound in PubChem bioassay data analysis using 3-D molecular similarity is not expected to increase the separation of non-inactive from random and inactive spaces "on average", although some assays show a noticeable separation between the non-inactive and random spaces when multiple conformers are used for each compound. The present study is a critical next step to understand effects of conformational diversity of the molecules upon the 3-D molecular similarity and its application to biological activity data analysis in PubChem. The results of this study may be helpful to build search and analysis tools that exploit 3-D molecular similarity between compounds archived in PubChem and other molecular libraries in a more efficient way. C1 [Kim, Sunghwan; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA. RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM bolton@ncbi.nlm.nih.gov RI Kim, Sunghwan/A-6738-2008 OI Kim, Sunghwan/0000-0001-9828-2074 FU Intramural Research Program of the National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services FX We are grateful to the NCBI Systems staff, especially Ron Patterson, Charlie Cook, and Don Preuss, whose efforts helped to make the PubChem3D project possible. We are also thankful to the reviewers for their insightful suggestions and comments. SK thanks to Volker Hahnke for fruitful discussion on this study. This research was supported in part by the Intramural Research Program of the National Library of Medicine, National Institutes of Health, U.S. Department of Health and Human Services. NR 54 TC 9 Z9 10 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PD NOV 7 PY 2012 VL 4 AR 28 DI 10.1186/1758-2946-4-28 PG 30 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 067ED UT WOS:000313275800001 PM 23134593 ER PT J AU Gassman, NR Stefanick, DF Kedar, PS Horton, JK Wilson, SH AF Gassman, Natalie R. Stefanick, Donna F. Kedar, Padmini S. Horton, Julie K. Wilson, Samuel H. TI Hyperactivation of PARP Triggers Nonhomologous End-Joining in Repair-Deficient Mouse Fibroblasts SO PLOS ONE LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-POLYMERASE-BETA; DEPENDENT PROTEIN-KINASE; CELL-DEATH PARTHANATOS; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; DAMAGE; KU; IDENTIFICATION; PATHWAY AB Regulation of poly(ADP-ribose) (PAR) synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose) polymerase-1 (PARP-1) occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase beta (pol beta). The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS), or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol beta null cells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol b null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ) protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised. C1 [Gassman, Natalie R.; Stefanick, Donna F.; Kedar, Padmini S.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov OI Gassman, Natalie/0000-0002-8488-2332 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES050158, Z01-ES050159] FX This research was supported by Research Project Numbers Z01-ES050158 and Z01-ES050159 in the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 10 Z9 10 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e49301 DI 10.1371/journal.pone.0049301 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800242 PM 23145148 ER PT J AU Golkar, A Lonsdorf, TB Olsson, A Lindstrom, KM Berrebi, J Fransson, P Schalling, M Ingvar, M Ohman, A AF Golkar, Armita Lonsdorf, Tina B. Olsson, Andreas Lindstrom, Kara M. Berrebi, Jonathan Fransson, Peter Schalling, Martin Ingvar, Martin Ohman, Arne TI Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation SO PLOS ONE LA English DT Article ID THREAT-RELATED STIMULI; COGNITIVE CONTROL; NEGATIVE EMOTION; VOLUNTARY SUPPRESSION; WORKING-MEMORY; AMYGDALA; FMRI; RESPONSES; ANXIETY; NEUROSCIENCE AB The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task. C1 [Golkar, Armita; Lonsdorf, Tina B.; Olsson, Andreas; Lindstrom, Kara M.; Berrebi, Jonathan; Fransson, Peter; Ingvar, Martin; Ohman, Arne] Karolinska Inst, Stockholm Brain Inst, Dept Clin Neurosci, Solna, Sweden. [Golkar, Armita; Lonsdorf, Tina B.; Olsson, Andreas; Ingvar, Martin; Ohman, Arne] Nord Ctr Excellence Cognit Control, Stockholm, Sweden. [Lonsdorf, Tina B.] Univ Hosp Hamburg Eppendorf, Inst Syst Neurosci, Hamburg, Germany. [Lindstrom, Kara M.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. [Schalling, Martin] Karolinska Inst, Ctr Mol Med & Surg, Solna, Sweden. [Ingvar, Martin] Osher Ctr Integrat Med, Stockholm, Sweden. [Ohman, Arne] NIH, Ctr Study Emot & Attent, Gainesville, FL USA. RP Golkar, A (reprint author), Karolinska Inst, Stockholm Brain Inst, Dept Clin Neurosci, Solna, Sweden. EM armita.golkar@ki.se RI Fransson, Peter/M-5679-2014; OI Fransson, Peter/0000-0002-1305-9875; Ingvar, Martin/0000-0002-9041-5714; Golkar, Armita/0000-0003-3077-0391 FU Swedish Research Council; Nordic Research Council for the Humanities and Social Sciences (NOS-HS); National Institute of Mental Health, Center for the Study of Emotion and Attention; Barbro and Bernard Osher Foundation; Swedish Governmental Agency for Innovation Systems (VINNOVA); Swedish Foundation for Strategic Research FX This work was supported by grants from the Swedish Research Council (to A.O., M.S., M.I.), the Nordic Research Council for the Humanities and Social Sciences (NOS-HS, to A.O.), the National Institute of Mental Health, Center for the Study of Emotion and Attention (to A.O.), the Barbro and Bernard Osher Foundation (M.I.), The Swedish Governmental Agency for Innovation Systems (VINNOVA) and The Swedish Foundation for Strategic Research (A.O., M.I.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 36 Z9 36 U1 5 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e48107 DI 10.1371/journal.pone.0048107 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800035 PM 23144849 ER PT J AU Hajnal, A Zharikov, A Polston, JE Fields, MR Tomasko, J Rogers, AM Volkow, ND Thanos, PK AF Hajnal, Andras Zharikov, Alevtina Polston, James E. Fields, Maxine R. Tomasko, Jonathan Rogers, Ann M. Volkow, Nora D. Thanos, Panayotis K. TI Alcohol Reward Is Increased after Roux-en-Y Gastric Bypass in Dietary Obese Rats with Differential Effects following Ghrelin Antagonism SO PLOS ONE LA English DT Article ID STIMULATES LOCOMOTOR-ACTIVITY; BARIATRIC SURGERY; NUCLEUS-ACCUMBENS; GUT HORMONE; GASTROINTESTINAL HORMONES; INSULIN SENSITIVITY; RECEPTOR ANTAGONISM; DEFICIENT MICE; FOOD REWARD; SWEET TASTE AB Roux-en-Y gastric bypass (RYGB) is one of the most successful treatments for severe obesity and associated comorbidities. One potential adverse outcome, however, is increased risk for alcohol use. As such, we tested whether RYGB alters motivation to self-administer alcohol in outbred dietary obese rats, and investigated the involvement of the ghrelin system as a potential underlying mechanism. High fat (60% kcal from fat) diet-induced obese, non-diabetic male Sprague Dawley rats underwent RYGB (n = 9) or sham operation (Sham, n = 9) and were tested 4 months after surgery on a progressive ratio-10 (PR10) schedule of reinforcement operant task for 2, 4, and 8% ethanol. In addition, the effects of the ghrelin-1a-receptor antagonist D-[Lys3]-GHRP-6 (50, 100 nmol/kg, IP) were tested on PR10 responding for 4% ethanol. Compared to Sham, RYGB rats made significantly more active spout responses to earn reward, more consummatory licks on the ethanol spout, and achieved higher breakpoints. Pretreatment with a single peripheral injection of D-[Lys3]-GHRP-6 at either dose was ineffective in altering appetitive or consummatory responses to 4% ethanol in the Sham group. In contrast, RYGB rats demonstrated reduced operant performance to earn alcohol reward on the test day and reduced consummatory responses for two subsequent days following the drug. Sensitivity to threshold doses of D-[LYS3]-GHRP-6 suggests that an augmented ghrelin system may contribute to increased alcohol reward in RYGB. Further research is warranted to confirm applicability of these findings to humans and to explore ghrelin-receptor targets for treatment of alcohol-related disorders in RYGB patients. C1 [Hajnal, Andras; Zharikov, Alevtina; Polston, James E.; Fields, Maxine R.] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. [Hajnal, Andras; Tomasko, Jonathan; Rogers, Ann M.] Penn State Univ, Coll Med, Dept Surg, Hershey, PA USA. [Volkow, Nora D.; Thanos, Panayotis K.] NIAAA, Lab Neuroimaging, Intramural Program, NIH, Bethesda, MD 90034 USA. [Thanos, Panayotis K.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. RP Hajnal, A (reprint author), Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. EM ahajnal@psu.edu OI Hajnal, Andras/0000-0001-7297-7134 FU National Institute of Diabetes and Digestive and Kidney Diseases Grant [DK080899] FX This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK080899 (to AH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 18 Z9 18 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e49121 DI 10.1371/journal.pone.0049121 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800211 PM 23145091 ER PT J AU Huang, SH Wu, CH Chang, YC Kwon-Chung, KJ Brown, RJ Jong, A AF Huang, Sheng-He Wu, Chun-Hua Chang, Yun C. Kwon-Chung, Kyung J. Brown, Robert J. Jong, Ambrose TI Cryptococcus neoformans-Derived Microvesicles Enhance the Pathogenesis of Fungal Brain Infection SO PLOS ONE LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; CAPSULE-ASSOCIATED GENE; EXTRACELLULAR VESICLES; MEMBRANE-VESICLES; EXOSOMES; VIRULENCE; INVASION; POLYSACCHARIDE; MACROPHAGES; LEISHMANIA AB Cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance the traversal of the blood-brain barrier (BBB) by C. neoformans in vitro. The immunofluorescence imaging demonstrates that CnMVs can fuse with human brain microvascular endothelial cells (HBMECs), the constituents of the BBB. This activity is presumably due to the ability of the CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs also enhanced C. neoformans infection of the brain, found in both infected brains and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic protein)-positive astrocytes were found surrounding the cystic lesions, overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion) signals. Substantial changes could be observed in areas that have a high density of CnMV staining. This is the first demonstration that C. neoformans-derived microvesicles can facilitate cryptococcal traversal across the BBB and accumulate at lesion sites of C. neoformans-infected brains. Results of this study suggested that CnMVs play an important role in the pathogenesis of cryptococcal meningoencephalitis. C1 [Wu, Chun-Hua; Brown, Robert J.; Jong, Ambrose] Univ So Calif, Keck Sch Med, Div Hematol Oncol, Saban Res Inst,Childrens Hosp Los Angeles,Dept Pe, Los Angeles, CA 90033 USA. [Huang, Sheng-He] Univ So Calif, Keck Sch Med, Div Infect Dis, Saban Res Inst,Childrens Hosp Los Angeles,Dept Pe, Los Angeles, CA 90033 USA. [Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Jong, A (reprint author), Univ So Calif, Keck Sch Med, Div Hematol Oncol, Saban Res Inst,Childrens Hosp Los Angeles,Dept Pe, Los Angeles, CA 90033 USA. EM ajong@chla.usc.edu FU Public Health Service grants from National Institutes of Health [R01-NS047599, R01-AI40635]; intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This project was financially supported by Public Health Service grants R01-NS047599 (A.J.) and R01-AI40635 (S. H. H.) from the National Institutes of Health. The work of Kyung J. Kwon-Chung and Yun C. Chang was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 23 Z9 25 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e48570 DI 10.1371/journal.pone.0048570 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800077 PM 23144903 ER PT J AU Martin-Manso, G Navarathna, DHMLP Galli, S Soto-Pantoja, DR Kuznetsova, SA Tsokos, M Roberts, DD AF Martin-Manso, Gema Navarathna, Dhammika H. M. L. P. Galli, Susana Soto-Pantoja, David R. Kuznetsova, Svetlana A. Tsokos, Maria Roberts, David D. TI Endogenous Thrombospondin-1 Regulates Leukocyte Recruitment and Activation and Accelerates Death from Systemic Candidiasis SO PLOS ONE LA English DT Article ID HUMAN-NEUTROPHILS; MACROPHAGE ACTIVATION; EXTRACELLULAR-MATRIX; IMMUNE-RESPONSE; IN-VIVO; EXPRESSION; CELL; CHEMOKINE; ALBICANS; PROMOTES AB Disseminated Candida albicans infection results in high morbidity and mortality despite treatment with existing antifungal drugs. Recent studies suggest that modulating the host immune response can improve survival, but specific host targets for accomplishing this goal remain to be identified. The extracellular matrix protein thrombospondin-1 is released at sites of tissue injury and modulates several immune functions, but its role in C. albicans pathogenesis has not been investigated. Here, we show that mice lacking thrombospondin-1 have an advantage in surviving disseminated candidiasis and more efficiently clear the initial colonization from kidneys despite exhibiting fewer infiltrating leukocytes. By examining local and systemic cytokine responses to C. albicans and other standard inflammatory stimuli, we identify a crucial function of phagocytes in this enhanced resistance. Subcutaneous air pouch and systemic candidiasis models demonstrated that endogenous thrombospondin-1 enhances the early innate immune response against C. albicans and promotes activation of inflammatory macrophages (inducible nitric oxide synthase(+), IL-6(high), TNF-alpha(high), IL-10(low)), release of the chemokines MIP-2, JE, MIP-1 alpha, and RANTES, and CXCR2-driven polymorphonuclear leukocytes recruitment. However, thrombospondin-1 inhibited the phagocytic capacity of inflammatory leukocytes in vivo and in vitro, resulting in increased fungal burden in the kidney and increased mortality in wild type mice. Thus, thrombospondin-1 enhances the pathogenesis of disseminated candidiasis by creating an imbalance in the host immune response that ultimately leads to reduced phagocytic function, impaired fungal clearance, and increased mortality. Conversely, inhibitors of thrombospondin-1 may be useful drugs to improve patient recovery from disseminated candidiasis. C1 [Martin-Manso, Gema; Navarathna, Dhammika H. M. L. P.; Galli, Susana; Soto-Pantoja, David R.; Kuznetsova, Svetlana A.; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Martin Manso, Maria Gema/D-4612-2013 OI Roberts, David/0000-0002-2481-2981; FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; grant BEFI from Instituto de Salud Carlos III FX Grant support: This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (DDR, MT). GMM was recipient of a grant BEFI from Instituto de Salud Carlos III (www.isciii.es). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 10 Z9 10 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e48775 DI 10.1371/journal.pone.0048775 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800128 PM 23144964 ER PT J AU Minamimoto, T Hori, Y Richmond, BJ AF Minamimoto, Takafumi Hori, Yukiko Richmond, Barry J. TI Is Working More Costly than Waiting in Monkeys? SO PLOS ONE LA English DT Article ID PREFRONTAL CORTEX; DECISION-MAKING; REWARD; DELAY; MOTIVATION; PIGEONS; HUMANS AB We studied how value for instrumental action is discounted by predicted effort and delay. The monkeys were trained to perform instrumental trials that required a bar release when a visual target changed from red-to-green. There were two trial conditions. In delay trials, after the monkeys performed one instrumental trial correctly a reward was delivered 0-7 seconds later. In work trials, the monkeys had to perform 0, 1, or 2 additional instrumental trials to obtain a reward. The lengths of trials in delay matched the time it took to complete work trials. The length of delay or number of trials was indicated by a visual cue presented throughout the trial. Our hypothesis was that the monkeys would all show temporal discounting of reward in the delay trials, and that in the work trials the monkeys' performance might reflect an additional cost due to working. The error rate increased linearly as remaining cost increased for all 8 monkeys. For 4 monkeys the error rate was significantly larger in work trials than in delay trials (effort sensitive monkeys). For the other 4 monkeys there was no significant difference in error rate (effort insensitive monkeys). Since the error rate has an inverse relation with value for action, these results suggest that value is discounted hyperbolically by effort as well as by delay. Error rates generally increased as the testing sessions progressed and the total reward accumulated (i.e., effect of reward devaluation). The relative impact of delay and effort on error rates was reasonably stable within subjects. Thus, within the monkey population there seems to be a significant dichotomy in the sensitivity governing whether working is more costly than waiting, possibly arising from a constitutional or genetic trait. C1 [Minamimoto, Takafumi; Hori, Yukiko] Natl Inst Radiol Sci, Mol Imaging Ctr, Dept Mol Neuroimaging, Chiba 260, Japan. [Minamimoto, Takafumi; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Minamimoto, Takafumi] Japan Sci & Technol Agcy JST, PRESTO, Saitama, Japan. RP Minamimoto, T (reprint author), Natl Inst Radiol Sci, Mol Imaging Ctr, Dept Mol Neuroimaging, Chiba 260, Japan. EM minamoto@nirs.go.jp RI Minamimoto, Takafumi/D-6610-2012 OI Minamimoto, Takafumi/0000-0003-4305-0174 FU Ministry of Education, Culture, Sports, Science and Technology, MEXT Japan [KAKENHI 21012005, 23011006]; PRESTO/JST; National Institute of Mental Health; JSPS FX This research was supported by a Grant-in-Aid for Scientific Research on Priority Areas, from the Ministry of Education, Culture, Sports, Science and Technology, MEXT Japan (KAKENHI 21012005, 23011006 to TM), PRESTO/JST (to TM), and Intramural Research Program of the National Institute of Mental Health (to BJR). TM was partly supported by JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 1 Z9 1 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e48434 DI 10.1371/journal.pone.0048434 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800061 PM 23144881 ER PT J AU Ryan, PE Kales, SC Yadavalli, R Nau, MM Zhang, H Lipkowitz, S AF Ryan, Philip E. Kales, Stephen C. Yadavalli, Rajgopal Nau, Marion M. Zhang, Han Lipkowitz, Stanley TI Cbl-c Ubiquitin Ligase Activity Is Increased via the Interaction of Its RING Finger Domain with a LIM Domain of the Paxillin Homolog, Hic 5 SO PLOS ONE LA English DT Article ID GROWTH-FACTOR RECEPTOR; CONFORMATIONAL-CHANGE; POSSIBLE INVOLVEMENT; CONJUGATING ENZYME; ADHESION KINASE; FOCAL ADHESIONS; PROTEIN HIC-5; ACTIVATION; SENESCENCE; COMPLEX AB Cbl proteins (Cbl, Cbl-b and Cbl-c) are ubiquitin ligases that are critical regulators of tyrosine kinase signaling. In this study we identify a new Cbl-c interacting protein, Hydrogen peroxide Induced Construct 5 (Hic-5). The two proteins interact through a novel interaction mediated by the RING finger of Cbl-c and the LIM2 domain of Hic-5. Further, this interaction is mediated and dependent on specific zinc coordinating complexes within the RING finger and LIM domain. Binding of Hic-5 to Cbl-c leads to an increase in the ubiquitin ligase activity of Cbl-c once Cbl-c has been activated by Src phosphorylation or through an activating phosphomimetic mutation. In addition, co-transfection of Hic-5 with Cbl-c leads to an increase in Cblc mediated ubiquitination of the EGFR. These data suggest that Hic-5 enhances Cbl-c ubiquitin ligase activity once Cbl-c has been phosphorylated and activated. Interactions between heterologous RING fingers have been shown to activate E3s. This is the first demonstration of enhancement of ubiquitin ligase activity of a RING finger ubiquitin ligase by the direct interaction of a LIM zinc coordinating domain. C1 [Ryan, Philip E.; Kales, Stephen C.; Yadavalli, Rajgopal; Nau, Marion M.; Zhang, Han; Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ryan, Philip E.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. RP Lipkowitz, S (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lipkowis@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 5 Z9 8 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e49428 DI 10.1371/journal.pone.0049428 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800258 PM 23145173 ER PT J AU Snyder, JS Ferrante, SC Cameron, HA AF Snyder, Jason S. Ferrante, Sarah C. Cameron, Heather A. TI Late Maturation of Adult-Born Neurons in the Temporal Dentate Gyrus SO PLOS ONE LA English DT Article ID GENERATED GRANULE CELLS; HIPPOCAMPAL NEUROGENESIS; VENTRAL HIPPOCAMPUS; ENTORHINAL CORTEX; RAT HIPPOCAMPUS; FOS EXPRESSION; SPATIAL MEMORY; TOTAL NUMBER; WATER MAZE; BEHAVIOR AB Hippocampal function varies along its septotemporal axis, with the septal (dorsal) pole more frequently involved in spatial learning and memory and the temporal (ventral) pole playing a greater role in emotional behaviors. One feature that varies across these subregions is adult neurogenesis. New neurons are more numerous in the septal hippocampus but are more active in the temporal hippocampus during water maze training. However, many other aspects of adult neurogenesis remain unexplored in the context of septal versus temporal subregions. In addition, the dentate gyrus contains another functionally important anatomical division along the transverse axis, with the suprapyramidal blade showing greater experience-related activity than the infrapyramidal blade. Here we ask whether new neurons differ in their rates of survival and maturation along the septotemporal and transverse axes. We found that neurogenesis is initially higher in the infrapyramidal than suprapyramidal blade, but these cells are less likely to survive, resulting in similar densities of neurons in the two blades by four weeks. Across the septotemporal axis, neurogenesis was higher in septal than temporal pole, while the survival rate of new neurons did not differ. Maturation was assessed by immunostaining for the neuronal marker, NeuN, which increases in expression level with maturation, and for the immediate-early gene, Arc, which suggests a neuron is capable of undergoing activity-dependent synaptic plasticity. Maturation occurred approximately 1-2 weeks earlier in the septal pole than in the temporal pole. This suggests that septal neurons may contribute to function sooner; however, the prolonged maturation of new temporal neurons may endow them with a longer window of plasticity during which their functions could be distinct from those of the mature granule cell population. These data point to subregional differences in new neuron maturation and suggest that changes in neurogenesis could alter different hippocampus-dependent behaviors with different time courses. C1 [Snyder, Jason S.; Ferrante, Sarah C.; Cameron, Heather A.] NIMH, Unit Neuroplast, NIH, Bethesda, MD 20892 USA. RP Snyder, JS (reprint author), Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. EM jasonscottsnyder@psych.ubc.ca RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Snyder, Jason/0000-0002-5509-0272 FU National Institutes of Health, National Institute of Mental Health [1ZIAMH002784] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health, 1ZIAMH002784. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 36 Z9 37 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 7 PY 2012 VL 7 IS 11 AR e48757 DI 10.1371/journal.pone.0048757 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048TK UT WOS:000311935800122 PM 23144957 ER PT J AU Matsubara, T Tanaka, N Krausz, KW Manna, SK Kang, DW Anderson, ER Luecke, H Patterson, AD Shah, YM Gonzalez, FJ AF Matsubara, Tsutomu Tanaka, Naoki Krausz, Kristopher W. Manna, Soumen K. Kang, Dong Wook Anderson, Erik R. Luecke, Hans Patterson, Andrew D. Shah, Yatrik M. Gonzalez, Frank J. TI Metabolomics Identifies an Inflammatory Cascade Involved in Dioxin- and Diet-Induced Steatohepatitis SO CELL METABOLISM LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; DEFICIENT MICE; DBA/2J MICE; INDUCTION; TOXICITY; TERATOGENESIS; DISRUPTION; MICROARRAY; EXPRESSION AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent environmentally toxic compounds. Serum metabolomics identified azelaic acid monoesters as significantly increased metabolites after TCDD treatment, due to downregulation of hepatic carboxylesterase 3 (CES3, also known as triglyceride hydrolase) expression in an arylhydrocarbon receptor (AhR)-dependent manner in mice. The decreased CES3 expression was accomplished by TODD-stimulated TGF beta-SMAD3 and IL6-STAT3 signaling, but not by direct AhR signaling. Methionine- and choline-deficient (MCD) diet-treated mice also showed enhanced serum azelaic acid monoester levels after attenuation of hepatic CES3 expression, while db/db mice did not, thus suggesting an association with steatohepatitis. Forced expression of CES3 reversed serum azelaic acid monoester/azelaic acid ratios and hepatic TGF beta mRNA levels in TCDD- and MCD diet-treated mice and ameliorated steatohepatitis induced by MCD diet. These results support the view that azelaic acid monoesters are possible indicators of TCDD exposure and steatohepatitis and suggest a link between CES3, TGF beta, and steatohepatitis. C1 [Matsubara, Tsutomu; Tanaka, Naoki; Krausz, Kristopher W.; Manna, Soumen K.; Patterson, Andrew D.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Anderson, Erik R.; Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol & Internal Med, Div Gastroenterol, Sch Med, Ann Arbor, MI 48109 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 FU National Cancer Institute Intramural Research Program, Center for Cancer Research; Japanese Society for the Promotion of Science FX This study was supported by the National Cancer Institute Intramural Research Program, Center for Cancer Research. We thank John Buckley and Linda Byrd for technical assistance (National Cancer Institute, NIH). Lalage Wakefield (National Cancer Institute, NIH) provided the SMAD3 expression vector and the SMAD3-binding luciferase vector, Arthur Hurwitz (National Cancer Institute, NIH) provided the STAT3 expression vector and the STAT3-binding luciferase vector, and Shioko Kimura (National Cancer Institute, NIH) furnished the CEBP alpha expression vector. T.M. was supported by a fellowship from the Japanese Society for the Promotion of Science. NR 24 TC 32 Z9 32 U1 3 U2 32 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 7 PY 2012 VL 16 IS 5 BP 634 EP 644 DI 10.1016/j.cmet.2012.10.006 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 046LE UT WOS:000311765700012 PM 23140643 ER PT J AU Bayeva, M Khechaduri, A Puig, S Chang, HC Patial, S Blackshear, PJ Ardehali, H AF Bayeva, Marina Khechaduri, Arineh Puig, Sergi Chang, Hsiang-Chun Patial, Sonika Blackshear, Perry J. Ardehali, Hossein TI mTOR Regulates Cellular Iron Homeostasis through Tristetraprolin SO CELL METABOLISM LA English DT Article ID MESSENGER-RNA DEGRADATION; SIGNALING PATHWAY; MAMMALIAN TARGET; DEFICIENCY; METABOLISM; PROTEIN; CELLS; SIROLIMUS; DISEASE; ALPHA AB Iron is an essential cofactor with unique redox properties. Iron-regulatory proteins 1 and 2 (IRP1/2) have been established as important regulators of cellular iron homeostasis, but little is known about the role of other pathways in this process. Here we report that the mammalian target of rapamycin (mTOR) regulates iron homeostasis by modulating transferrin receptor 1 (TfR1) stability and altering cellular iron flux. Mechanistic studies identify tristetraprolin (TTP), a protein involved in anti-inflammatory response, as the downstream target of mTOR that binds to and enhances degradation of TfR1 mRNA. We also show that TTP is strongly induced by iron chelation, promotes downregulation of iron-requiring genes in both mammalian and yeast cells, and modulates survival in low-iron states. Taken together, our data uncover a link between metabolic, inflammatory, and iron-regulatory pathways, and point toward the existence of a yeast-like TTP-mediated iron conservation program in mammals. C1 [Bayeva, Marina; Khechaduri, Arineh; Chang, Hsiang-Chun; Ardehali, Hossein] Northwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. [Puig, Sergi] CSIC, Inst Agroquim & Tecnol Alimentos, Dept Biotecnol, Valencia 46100, Spain. [Patial, Sonika; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Ardehali, H (reprint author), Northwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. EM h-ardehali@northwestern.edu RI Puig, Sergi/E-4788-2010 OI Puig, Sergi/0000-0002-1856-490X FU Northwestern University Flow Cytometry Facility; Cancer Center Support Grant [NCI CA060553]; American Heart Association [10PRE4430021]; NIH [K02 HL107448, R01 HL104181, P01 HL108795, R01 HL087149] FX We thank Dr. Seth A. Brooks for help with TTP RNA coIP experiments, Drs. Sarah Rice, Navdeep Chandel, and Elizabeth Leibold for the critical review of the manuscript, and Drs. William F.C. Rigby, M. Celeste Simon, and Tracey A. Rouault for their generous gifts of the human TTP antibody, ARNT KO MEFs, and IRP1 and 2 KO MEFs, respectively. This work was supported by the Northwestern University Flow Cytometry Facility and a Cancer Center Support Grant (NCI CA060553). M.B. and H.A. designed the research. M.B., A.K., and S.P. performed the experiments and data analysis. P.J.B and S.P. provided tools and reagents. M.B. wrote the manuscript, which all authors commented on. H.A. supervised the project. M.B. is supported by the American Heart Association 10PRE4430021. H.A. is supported by NIH grants K02 HL107448, R01 HL104181, P01 HL108795, and R01 HL087149. NR 39 TC 23 Z9 23 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 7 PY 2012 VL 16 IS 5 BP 645 EP 657 DI 10.1016/j.cmet.2012.10.001 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 046LE UT WOS:000311765700013 PM 23102618 ER PT J AU Low, LA Millecamps, M Seminowicz, DA Naso, L Thompson, SJ Stone, LS Bushnell, MC AF Low, Lucie A. Millecamps, Magali Seminowicz, David A. Naso, Lina Thompson, Scott J. Stone, Laura S. Bushnell, M. Catherine TI Nerve injury causes long-term attentional deficits in rats SO NEUROSCIENCE LETTERS LA English DT Article DE Neuropathic pain; Cognition; Rat; Chronic pain; Attention; Longitudinal study ID CHRONIC BACK-PAIN; PERIPHERAL NEUROPATHIC PAIN; CHRONIC INFLAMMATORY PAIN; TACTILE ALLODYNIA; BRAIN; MODEL; ANXIETY; AMYGDALA; BEHAVIOR; MORPHINE AB Human chronic pain sufferers frequently report problems with attention and concentration that affect daily functioning and quality of life. Chronic pain is also commonly associated with anxiety and depression. It is currently not known if the pain causes these co-morbidities, or if they are pre-disposing risk factors for the development of chronic pain. Animal studies suggest a possible causative effect of pain on cognition, but usually tests are conducted during acute ongoing pain when the pain may act as a distracter to normal cognitive and emotional processing. Here we examine long-term effects of nerve injury on cognitive functioning in a rat model, which contributes to better understanding of the relationship between cognitive impairment and chronic pain experience in human populations. This study investigated attentional capability, anxiety-like behavior and sensory functioning 6 months after spared nerve injury (SNI) surgery a time-point well beyond the acute pain phase and akin to decades of pain experience in humans. Male Long Evans rats subjected to nerve injury remained hypersensitive to sensory stimuli from the time of injury to the 6-month post-injury assessment. At 6 months they were impaired on a visual non-selective, non-sustained attention task and displayed anxiety-like behaviors in the elevated plus maze. These findings show that cognitive disturbances observed during acute pain persist for months in a rodent chronic pain model and suggest that cognitive alterations in chronic pain patients are at least partially caused by the chronic pain state. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Low, Lucie A.; Millecamps, Magali; Naso, Lina; Thompson, Scott J.; Stone, Laura S.; Bushnell, M. Catherine] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada. [Low, Lucie A.; Millecamps, Magali; Thompson, Scott J.; Stone, Laura S.; Bushnell, M. Catherine] McGill Univ, Fac Dent, Montreal, PQ, Canada. [Stone, Laura S.; Bushnell, M. Catherine] McGill Univ, Dept Anesthesia, Montreal, PQ, Canada. [Millecamps, Magali; Naso, Lina; Stone, Laura S.] McGill Univ, Montreal, PQ H3G 0G1, Canada. [Seminowicz, David A.] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA. [Low, Lucie A.; Thompson, Scott J.; Bushnell, M. Catherine] McGill Univ, Montreal, PQ H3A 0C7, Canada. RP Low, LA (reprint author), NIH, NCCAM, 10-CRC 4-1743,10 Ctr Dr, Bethesda, MD 20892 USA. EM lucie.low@mail.mcgill.ca RI Seminowicz, David/F-8732-2015; OI Seminowicz, David/0000-0003-3111-3756; Low, Lucie/0000-0001-6082-8625 FU Pfizer Canada FX This work was supported by a Neuropathic Pain Research grant from Pfizer Canada. NR 30 TC 19 Z9 19 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 7 PY 2012 VL 529 IS 2 BP 103 EP 107 DI 10.1016/j.neulet.2012.09.027 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 039RK UT WOS:000311264000001 PM 22999928 ER PT J AU Pitcher, D Goldhaber, T Duchaine, B Walsh, V Kanwisher, N AF Pitcher, David Goldhaber, Tanya Duchaine, Bradley Walsh, Vincent Kanwisher, Nancy TI Two Critical and Functionally Distinct Stages of Face and Body Perception SO JOURNAL OF NEUROSCIENCE LA English DT Article ID HUMAN VISUAL-CORTEX; HUMAN EXTRASTRIATE CORTEX; SURFACE-BASED ANALYSIS; OCCIPITOTEMPORAL CORTEX; MAGNETIC STIMULATION; DIRECTED ATTENTION; OCCIPITAL FACE; NEURAL BASIS; AREA; TIME AB Cortical regions that respond preferentially to particular object categories, such as faces and bodies, are essential for visual perception of these object categories. However, precisely when these regions play a causal role in recognition of their preferred categories is unclear. Here we addressed this question using transcranial magnetic stimulation (TMS). Across a series of experiments, TMS was delivered over the functionally localized right occipital face area (rOFA) or right extrastriate body area (rEBA) at different latencies, up to 150 ms, after stimulus onset while adult human participants performed delayed match-to-sample tasks on face and body stimuli. Results showed that TMS disrupted task performance during two temporally distinct time periods after stimulus onset, the first at 40/50 ms and the second at 100/110 ms. These two time periods exhibited functionally distinct patterns of impairment: TMS delivered during the early time period (at 40/50 ms) disrupted task performance for both preferred (faces at rOFA and bodies at rEBA) and nonpreferred (bodies at rOFA and faces at rEBA) categories. In contrast, TMS delivered during the later time period (at 100/110 ms) disrupted task performance for the preferred category only of each area (faces at rOFA and bodies at rEBA). These results indicate that category-selective cortical regions are critical for two functionally distinct stages of visual object recognition: an early, presumably preparatory stage that is not category selective occurring almost immediately after stimulus onset, followed by a later stage of category-specific perceptual processing. C1 [Pitcher, David; Goldhaber, Tanya; Kanwisher, Nancy] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Pitcher, David; Walsh, Vincent] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Duchaine, Bradley] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. RP Pitcher, D (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM david.pitcher@nih.gov FU National Institutes of Health [EY13455]; Biotechnology and Biological Sciences Research Council [BB/F022875/1] FX This work was supported by National Institutes of Health Grant EY13455 (N.K.) and Biotechnology and Biological Sciences Research Council Grant BB/F022875/1 (B. D. and V. W.). Thanks to Rebecca Lawson, Danny Dilks, Julie Golomb, and Ed Vul. NR 46 TC 27 Z9 27 U1 1 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 7 PY 2012 VL 32 IS 45 BP 15877 EP 15885 DI 10.1523/JNEUROSCI.2624-12.2012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 034AH UT WOS:000310842000022 PM 23136426 ER PT J AU Furl, N Hadj-Bouziane, F Liu, N Averbeck, BB Ungerleider, LG AF Furl, Nicholas Hadj-Bouziane, Fadila Liu, Ning Averbeck, Bruno B. Ungerleider, Leslie G. TI Dynamic and Static Facial Expressions Decoded from Motion-Sensitive Areas in the Macaque Monkey SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SUPERIOR TEMPORAL SULCUS; FACE-PROCESSING NETWORK; POLYSENSORY AREA; CONTRAST AGENT; IMPLIED MOTION; CORTEX; RECOGNITION; PERCEPTION; IDENTITY; FMRI AB Humans adeptly use visual motion to recognize socially relevant facial information. The macaque provides a model visual system for studying neural coding of expression movements, as its superior temporal sulcus (STS) possesses brain areas selective for faces and areas sensitive to visual motion. We used functional magnetic resonance imaging and facial stimuli to localize motion-sensitive areas [motion in faces (Mf) areas], which responded more to dynamic faces compared with static faces, and face-selective areas, which responded selectively to faces compared with objects and places. Using multivariate analysis, we found that information about both dynamic and static facial expressions could be robustly decoded from Mf areas. By contrast, face-selective areas exhibited relatively less facial expression information. Classifiers trained with expressions from one motion type (dynamic or static) showed poor generalization to the other motion type, suggesting that Mf areas employ separate and nonconfusable neural codes for dynamic and static presentations of the same expressions. We also show that some of the motion sensitivity elicited by facial stimuli was not specific to faces but could also be elicited by moving dots, particularly in fundus of the superior temporal and middle superior temporal polysensory/lower superior temporal areas, confirming their already well established low-level motion sensitivity. A different pattern was found in anterior STS, which responded more to dynamic than to static faces but was not sensitive to dot motion. Overall, we show that emotional expressions are mostly represented outside of face-selective cortex, in areas sensitive to motion. These regions may play a fundamental role in enhancing recognition of facial expression despite the complex stimulus changes associated with motion. C1 [Furl, Nicholas; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Hadj-Bouziane, Fadila; Liu, Ning; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Furl, N (reprint author), Med Res Council Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England. EM nick.furl@mrc-cbu.cam.ac.uk RI Hadj-Bouziane, Fadila/A-1180-2013; OI furl, nicholas/0000-0003-2488-1343 FU National Institute of Mental Health; United Kingdom Economic and Social Research Council [RES-062-23-2925] FX This work was supported by funding from the National Institute of Mental Health Intramural Research Program to N.F., B. A., F. H-B., N.L., and L. G. U and funding from the United Kingdom Economic and Social Research Council (RES-062-23-2925) to N.F. We are grateful to our colleagues at the National Institute of Mental Health: Fern Baldwin and Lucas Glover for their help in training the animals; Jennifer Frihauf and Kathleen Hansen for their help with stimulus preparation; Ziad Saad and Maria Barsky for their help with data analysis; Frank Ye, Charles Zhu, Neal Phelps, and Wenming Luh for their assistance during scanning, and George Dold, David Ide, and Tom Talbot for technical assistance. Editorial assistance for the article was provided by the National Institutes of Health Fellows Editorial Board. NR 56 TC 15 Z9 15 U1 3 U2 30 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 7 PY 2012 VL 32 IS 45 BP 15952 EP 15962 DI 10.1523/JNEUROSCI.1992-12.2012 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 034AH UT WOS:000310842000029 PM 23136433 ER PT J AU Li, M Craigie, R AF Li, Min Craigie, Robert TI Retroviral Intasomes: Progress and Questions SO STRUCTURE LA English DT Editorial Material ID DNA STRAND TRANSFER; INTEGRATION; MECHANISM C1 [Li, Min; Craigie, Robert] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov FU Intramural NIH HHS [ZIA DK036169-07] NR 9 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 7 PY 2012 VL 20 IS 11 BP 1804 EP 1805 DI 10.1016/j.str.2012.10.004 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 034GR UT WOS:000310861400004 PM 23141692 ER PT J AU Freudenthal, BD Beard, WA Wilson, SH AF Freudenthal, Bret D. Beard, William A. Wilson, Samuel H. TI Structures of dNTP Intermediate States during DNA Polymerase Active Site Assembly SO STRUCTURE LA English DT Article ID BASE EXCISION-REPAIR; METAL-IONS; GASTRIC-CANCER; BETA STRUCTURE; MECHANISM; FIDELITY; DISCRIMINATION; CONFORMATION; COMPLEXES; EXTENSION AB DNA polymerase and substrate conformational changes are essential for high-fidelity DNA synthesis. Structures of DNA polymerase (pol) beta in complex with DNA show the enzyme in an "open" conformation. Subsequent to binding the nucleotide, the polymerase "closes" around the nascent base pair with two metals positioned for chemistry. However, structures of substrate/active site intermediates prior to closure are lacking. By destabilizing the closed complex, we determined unique ternary complex structures of pol beta with correct and incorrect incoming nucleotides bound to the open conformation. These structures reveal that Watson-Crick hydrogen bonding is assessed upon initial complex formation. Importantly, nucleotide-bound states representing intermediate metal coordination states occur with active site assembly. The correct, but not incorrect, nucleotide maintains Watson-Crick hydrogen bonds during interconversion of these states. These structures indicate that the triphosphate of the incoming nucleotide undergoes rearrangement prior to closure, providing an opportunity to deter misinsertion and increase fidelity. C1 [Freudenthal, Bret D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Lab Struct Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES050158, Z01-ES050161]; National Institutes of Health [1U19CA105010] FX We thank Drs. R.E. London, L.C. Pedersen, and V.K. Batra for critical reading of the manuscript and Dr. C.E. McKenna for the alpha,beta-difluoromethylene dCTP analog. This research was supported by Research Project Numbers Z01-ES050158 and Z01-ES050161 to S.H.W. in the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences and was in association with the National Institutes of Health Grant 1U19CA105010. B.D.F., W.A.B., and S.H.W. designed the research; B.D.F., W.A.B., and S.H.W. analyzed data; B.D.F. performed research; and B.D.F., W.A.B., and S.H.W. wrote the paper. NR 37 TC 18 Z9 18 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD NOV 7 PY 2012 VL 20 IS 11 BP 1829 EP 1837 DI 10.1016/j.str.2012.08.008 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 034GR UT WOS:000310861400008 PM 22959623 ER PT J AU Daviglus, ML Talavera, GA Aviles-Santa, ML Allison, M Cai, J Criqui, MH Gellman, M Giachello, AL Gouskova, N Kaplan, RC LaVange, L Penedo, F Perreira, K Pirzada, A Schneiderman, N Wassertheil-Smoller, S Sorlie, PD Stamler, J AF Daviglus, Martha L. Talavera, Gregory A. Aviles-Santa, M. Larissa Allison, Matthew Cai, Jianwen Criqui, Michael H. Gellman, Marc Giachello, Aida L. Gouskova, Natalia Kaplan, Robert C. LaVange, Lisa Penedo, Frank Perreira, Krista Pirzada, Amber Schneiderman, Neil Wassertheil-Smoller, Sylvia Sorlie, Paul D. Stamler, Jeremiah TI Prevalence of Major Cardiovascular Risk Factors and Cardiovascular Diseases Among Hispanic/Latino Individuals of Diverse Backgrounds in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NUTRITION EXAMINATION SURVEY; CORONARY HEART-DISEASE; MEXICAN-AMERICANS; MYOCARDIAL-INFARCTION; NATIONAL-HEALTH; LATIN-AMERICAN; PUERTO-RICANS; ACCULTURATION; ADULTS; HYPERTENSION AB Context Major cardiovascular diseases (CVDs) are leading causes of mortality among US Hispanic and Latino individuals. Comprehensive data are limited regarding the prevalence of CVD risk factors in this population and relations of these traits to socioeconomic status (SES) and acculturation. Objectives To describe prevalence of major CVD risk factors and CVD (coronary heart disease [CHD] and stroke) among US Hispanic/Latino individuals of different backgrounds, examine relationships of SES and acculturation with CVD risk profiles and CVD, and assess cross-sectional associations of CVD risk factors with CVD. Design, Setting, and Participants Multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos including individuals of Cuban(n=2201), Dominican (n=1400), Mexican (n=6232), Puerto Rican (n=2590), Central American (n=1634), and South American backgrounds(n=1022) aged 18 to 74 years. Analyses involved 15 079 participants with complete data enrolled between March 2008 and June 2011. Main Outcome Measures Adverse CVD risk factors defined using national guidelines for hypercholesterolemia, hypertension, obesity, diabetes, and smoking. Prevalence of CHD and stroke were ascertained from self-reported data. Results Age-standardized prevalence of CVD risk factors varied by Hispanic/Latino background; obesity and current smoking rates were highest among Puerto Rican participants (for men, 40.9% and 34.7%; for women, 51.4% and 31.7%, respectively); hypercholesterolemia prevalence was highest among Central American men (54.9%) and Puerto Rican women (41.0%). Large proportions of participants (80% of men, 71% of women) had at least 1 risk factor. Age-and sex-adjusted prevalence of 3 or more risk factors was highest in Puerto Rican participants (25.0%) and significantly higher (P<.001) among participants with less education (16.1%), those who were US-born (18.5%), those who had lived in the United States 10 years or longer (15.7%), and those who preferred English (17.9%). Overall, self-reported CHD and stroke prevalence were low (4.2% and 2.0% in men; 2.4% and 1.2% in women, respectively). In multivariate-adjusted models, hypertension and smoking were directly associated with CHD in both sexes as were hypercholesterolemia and obesity in women and diabetes in men (odds ratios [ORs], 1.5-2.2). For stroke, associations were positive with hypertension in both sexes, diabetes in men, and smoking in women (ORs, 1.7-2.6). Conclusion Among US Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and women had adverse major risk factors; prevalence of adverse CVD risk profiles was higher among participants with Puerto Rican background, lower SES, and higher levels of acculturation. C1 [Daviglus, Martha L.] Univ Illinois, Inst Minor Hlth Res, Dept Med, Gen Internal Med Sect, Chicago, IL 60612 USA. [Talavera, Gregory A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Aviles-Santa, M. Larissa; Sorlie, Paul D.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Allison, Matthew; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Cai, Jianwen; Gouskova, Natalia; LaVange, Lisa; Perreira, Krista] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Gellman, Marc; Schneiderman, Neil] Univ Miami, Dept Psychol, Behav Med Res Ctr, Miami, FL USA. [Daviglus, Martha L.; Giachello, Aida L.; Pirzada, Amber; Stamler, Jeremiah] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Penedo, Frank] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Kaplan, Robert C.; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Daviglus, ML (reprint author), Univ Illinois, Inst Minor Hlth Res, Dept Med, Gen Internal Med Sect, 1819 W Polk St,Ste 246, Chicago, IL 60612 USA. EM daviglus@uic.edu OI Gouskova, Natalia/0000-0001-7488-5014; Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233, N01-HC65234, N01-HC65235, N01-HC65236, N01-HC65237]; National Center on Minority Health and Health Disparities; National Institute on Deafness and Other Communications Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; Office of Dietary Supplements FX The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes, centers, or offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Center on Minority Health and Health Disparities, the National Institute on Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. NR 35 TC 194 Z9 198 U1 6 U2 32 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2012 VL 308 IS 17 BP 1775 EP 1784 DI 10.1001/jama.2012.14517 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 032NR UT WOS:000310726500024 PM 23117778 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Time for a Creative Transformation of Epidemiology in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID BLOOD INSTITUTE; NATIONAL HEART; LUNG C1 NHLBI, Off Director, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Off Director, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 16 TC 30 Z9 30 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2012 VL 308 IS 17 BP 1804 EP 1805 DI 10.1001/jama.2012.14838 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 032NR UT WOS:000310726500028 PM 23117782 ER PT J AU Towers, S Chowell, G AF Towers, S. Chowell, G. TI Impact of weekday social contact patterns on the modeling of influenza transmission, and determination of the influenza latent period SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE Epidemic model; Weekday contact patterns; Influenza latent period; Influenza incubation period; Pandemic influenza model ID PANDEMIC INFLUENZA; A H1N1; INFECTIOUS-DISEASES; UNITED-STATES; SIR MODEL; SCHOOL; SEASONALITY; OUTBREAK; PREDICT; CLOSURE AB Human social contact patterns show marked day-of-week variations, with a higher frequency of contacts occurring during weekdays when children are in school, and adults are in contact with co-workers, than typically occur on weekends. Using epidemic modeling, we show that using the average of social contacts during the week in the model yields virtually identical predictions of epidemic final size and the timing of the epidemic incidence peak as a model that incorporates weekday social contact patterns. This is true of models with a constant weekly average contact rate throughout the year, and also of models that assume seasonality of transmission. Our modeling studies reveal, however, that weekday social contact patterns can produce substantial weekday variations in an influenza incidence curve, and the pattern of variation is sensitive to the influenza latent period. The possible observability of weekday patterns in daily influenza incidence data opens up an interesting avenue of further inquiry that can shed light on the latent period of pandemic influenza. The duration of the latent period must be known with precision in order to design effective disease intervention strategies, such as use of antivirals. For a hypothetical influenza pandemic, we thus perform a simulation study to determine the number of cases needed to observe the weekday variation pattern in influenza epidemic incidence data. Our studies suggest that these patterns should be observable at 95% confidence in daily influenza hospitalization data from large cities over 75% of the time. Using 2009 A(H1N1) daily case data recorded by a large hospital in Santiago, Chile, we show that significant weekday incidence patterns are evident. From these weekday incidence patterns, we estimate the latent period of influenza to be [0.04, 0.60] days (95% CI). This method for determination of the influenza latent period in a community setting is novel, and unique in its approach. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Towers, S.] Purdue Univ, W Lafayette, IN 47907 USA. [Towers, S.; Chowell, G.] Arizona State Univ, Tempe, AZ USA. [Chowell, G.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Towers, S (reprint author), Purdue Univ, W Lafayette, IN 47907 USA. EM stowers@purdue.edu RI Chowell, Gerardo/F-5038-2012 OI Chowell, Gerardo/0000-0003-2194-2251 FU NSF [DMS-1022758]; Fogarty International Center, NIH FX This research is partially supported by NSF grant DMS-1022758 (ST) and by the Fogarty International Center, NIH (GC). NR 46 TC 8 Z9 8 U1 3 U2 17 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 EI 1095-8541 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 7 PY 2012 VL 312 BP 87 EP 95 DI 10.1016/j.jtbi.2012.07.023 PG 9 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 014KB UT WOS:000309373400009 PM 22871362 ER PT J AU Abdeladhim, M Jochim, RC Ben Ahmed, M Zhioua, E Chelbi, I Cherni, S Louzir, H Ribeiro, JMC Valenzuela, JG AF Abdeladhim, Maha Jochim, Ryan C. Ben Ahmed, Melika Zhioua, Elyes Chelbi, Ifhem Cherni, Saifedine Louzir, Hechmi Ribeiro, Jose M. C. Valenzuela, Jesus G. TI Updating the Salivary Gland Transcriptome of Phlebotomus papatasi (Tunisian Strain): The Search for Sand Fly-Secreted Immunogenic Proteins for Humans SO PLOS ONE LA English DT Article ID GLOSSINA-MORSITANS-MORSITANS; DELAYED-TYPE HYPERSENSITIVITY; LUTZOMYIA-LONGIPALPIS; CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; CIMEX-LECTULARIUS; ANTIBODY-RESPONSE; IMMUNE-RESPONSE; TSETSE-FLY; BED BUG AB Introduction: Sand fly saliva plays an important role in both blood feeding and outcome of Leishmania infection. A cellular immune response against a Phlebotomus papatasi salivary protein was shown to protect rodents against Leishmania major infection. In humans, P. papatasi salivary proteins induce a systemic cellular immune response as well as a specific antisaliva humoral immune response, making these salivary proteins attractive targets as markers of exposure for this Leishmania vector. Surprisingly, the repertoire of salivary proteins reported for P. papatasi-a model sand fly for Leishmania-vector-host molecular interactions-is very limited compared with other sand fly species. We hypothesize that a more comprehensive study of the transcripts present in the salivary glands of P. papatasi will provide better knowledge of the repertoire of proteins of this important vector and will aid in selection of potential immunogenic proteins for humans and of those proteins that are highly conserved between different sand fly strains. Methods and Findings: A cDNA library from P. papatasi (Tunisian strain) salivary glands was constructed, and randomly selected transcripts were sequenced and analyzed. The most abundant transcripts encoding secreted proteins were identified and compared with previously reported sequences. Importantly, we identified salivary proteins not described before in this sand fly species. Conclusions: Comparative analysis between the salivary proteins of P. papatasi from Tunisia and Israel strains shows a high level of identity, suggesting these proteins as potential common targets for markers of vector exposure or inducers of cellular immune responses in humans for different geographic areas. C1 [Jochim, Ryan C.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Abdeladhim, Maha; Ben Ahmed, Melika; Louzir, Hechmi] Pasteur Inst Tunis, Lab Transmiss Control & Immunobiol Infect Dis, Tunis, Tunisia. [Ben Ahmed, Melika; Louzir, Hechmi] Tunis El Manar Univ, Fac Med Tunis, Tunis, Tunisia. [Zhioua, Elyes; Chelbi, Ifhem; Cherni, Saifedine] Pasteur Inst Tunis, Lab Vector Ecol, Tunis, Tunisia. [Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM jvalenzuela@niaid.nih.gov RI Jochim, Ryan/C-6756-2013; Ribeiro, Jose/J-7011-2015 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID) FX The study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 16 Z9 16 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e47347 DI 10.1371/journal.pone.0047347 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300007 PM 23139741 ER PT J AU Baysan, M Bozdag, S Cam, MC Kotliarova, S Ahn, S Walling, J Killian, JK Stevenson, H Meltzer, P Fine, HA AF Baysan, Mehmet Bozdag, Serdar Cam, Margaret C. Kotliarova, Svetlana Ahn, Susie Walling, Jennifer Killian, Jonathan K. Stevenson, Holly Meltzer, Paul Fine, Howard A. TI G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data SO PLOS ONE LA English DT Article ID VALIDATION; MICROARRAY; SUBTYPES AB Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data. C1 [Baysan, Mehmet; Cam, Margaret C.; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Bozdag, Serdar] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53233 USA. [Killian, Jonathan K.; Stevenson, Holly; Meltzer, Paul] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Fine, Howard A.] NYU, Inst Canc, Langone Med Ctr, New York, NY USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. EM Howard.Fine@nyumc.org FU National Institutes of Health Intramural Research Program FX This study was funded through the National Institutes of Health Intramural Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 10 Z9 10 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e47839 DI 10.1371/journal.pone.0047839 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300013 PM 23139755 ER PT J AU Khaibullina, A Kenyon, N Guptill, V Quezado, MM Wang, L Koziol, D Wesley, R Moya, PR Zhang, ZJ Saha, A Mukherjee, AB Quezado, ZMN AF Khaibullina, Alfia Kenyon, Nicholas Guptill, Virginia Quezado, Martha M. Wang, Li Koziol, Deloris Wesley, Robert Moya, Pablo R. Zhang, Zhongjian Saha, Arjun Mukherjee, Anil B. Quezado, Zenaide M. N. TI In a Model of Batten Disease, Palmitoyl Protein Thioesterase-1 Deficiency Is Associated with Brown Adipose Tissue and Thermoregulation Abnormalities SO PLOS ONE LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; ENERGY-METABOLISM; NONSHIVERING THERMOGENESIS; ACTIVATION; MICE; INCL; NEURODEGENERATION; APOPTOSIS; UCP1; FAT AB Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha), and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1 alpha and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1 alpha and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets) compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of neurodegenerative diseases that are linked to alterations in peripheral metabolic processes. In addition, extrapolating these findings clinically, impaired thermoregulation and hypothermia are potential risks in patients with INCL. C1 [Khaibullina, Alfia; Kenyon, Nicholas; Wang, Li; Quezado, Zenaide M. N.] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA. [Guptill, Virginia; Quezado, Zenaide M. N.] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Quezado, Martha M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Koziol, Deloris; Wesley, Robert] NIH, Biostat & Clin Epidemiol Serv, Off Director, Ctr Clin, Bethesda, MD USA. [Moya, Pablo R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Zhongjian; Saha, Arjun; Mukherjee, Anil B.] NICHHD, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA. EM zquezado@cnmc.org RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural Research Program of the National Institutes of Health, NIH Clinical Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC FX This research was supported by the Intramural Research Program of the National Institutes of Health, NIH Clinical Center, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, and the The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 1 Z9 1 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e48733 DI 10.1371/journal.pone.0048733 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300053 PM 23139814 ER PT J AU Langlais, KK Brown, JL Kassis, JA AF Langlais, Kristofor K. Brown, J. Lesley Kassis, Judith A. TI Polycomb Group Proteins Bind an engrailed PRE in Both the "ON" and "OFF" Transcriptional States of engrailed SO PLOS ONE LA English DT Article ID DROSOPHILA BITHORAX COMPLEX; GROUP RESPONSE ELEMENTS; CUBITUS-INTERRUPTUS; CELLULAR MEMORY; PCG PROTEINS; GENOME-WIDE; MELANOGASTER; MECHANISMS; EXPRESSION; GENES AB Polycomb group (PcG) and trithorax Group (trxG) proteins maintain the "OFF" and "ON" transcriptional states of HOX genes and other targets by modulation of chromatin structure. In Drosophila, PcG proteins are bound to DNA fragments called Polycomb group response elements (PREs). The prevalent model holds that PcG proteins bind PREs only in cells where the target gene is "OFF". Another model posits that transcription through PREs disrupts associated PcG complexes, contributing to the establishment of the "ON" transcriptional state. We tested these two models at the PcG target gene engrailed. engrailed exists in a gene complex with invected, which together have 4 well-characterized PREs. Our data show that these PREs are not transcribed in embryos or larvae. We also examined whether PcG proteins are bound to an engrailed PRE in cells where engrailed is transcribed. By FLAG-tagging PcG proteins and expressing them specifically where engrailed is "ON" or "OFF", we determined that components of three major PcG protein complexes are present at an engrailed PRE in both the "ON" and "OFF" transcriptional states in larval tissues. These results show that PcG binding per se does not determine the transcriptional state of engrailed. C1 [Langlais, Kristofor K.; Brown, J. Lesley; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM jkassis@mail.nih.gov FU Intramural Research Program of the NIH/NICHD FX This research was supported by the Intramural Research Program of the NIH/NICHD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 9 Z9 9 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e48765 DI 10.1371/journal.pone.0048765 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300056 PM 23139817 ER PT J AU Rothfuchs, AG Roffe, E Gibson, A Cheever, AW Ezekowitz, RAB Takahashi, K Steindel, M Sher, A Bafica, A AF Rothfuchs, Antonio Gigliotti Roffe, Ester Gibson, Amanda Cheever, Allen W. Ezekowitz, R. Alan B. Takahashi, Kazue Steindel, Mario Sher, Alan Bafica, Andre TI Mannose-Binding Lectin Regulates Host Resistance and Pathology during Experimental Infection with Trypanosoma cruzi SO PLOS ONE LA English DT Article ID CHAGAS-DISEASE; MAMMALIAN-CELLS; DEFICIENT MICE; PROTEIN; TISSUE; SERUM; SUSCEPTIBILITY; AMASTIGOTES; CARDIOMYOPATHY; RECOGNITION AB Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas' disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. In this study we employed MBL-/- mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas' disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL-/- mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL-/- mice. Importantly, MBL-/- mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. C1 [Rothfuchs, Antonio Gigliotti; Gibson, Amanda; Cheever, Allen W.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Roffe, Ester] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. [Ezekowitz, R. Alan B.; Takahashi, Kazue] Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rothfuchs, Antonio Gigliotti] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden. [Steindel, Mario; Bafica, Andre] Univ Fed Santa Catarina, Dept Microbiol Immunol & Parasitol, Florianopolis, SC, Brazil. RP Rothfuchs, AG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM antonio.rothfuchs@ki.se; andre.bafica@ufsc.br RI Rothfuchs, Antonio/F-5981-2013; Vacinas, Inct/J-9431-2013; Roffe, Ester/H-4688-2012 OI Rothfuchs, Antonio/0000-0001-6001-7240; FU Intramural Research Program of the NIAID; EU [FP7-MC-IRG-247684]; Swedish Society for Medicine FX This work was supported by the Intramural Research Program of the NIAID. AB and MS are CNPq senior research fellows. AGR is a recipient of a Marie Curie International Reintegration grant from the EU (FP7-MC-IRG-247684) and a project grant from the Swedish Society for Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 7 Z9 8 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2012 VL 7 IS 11 AR e47835 DI 10.1371/journal.pone.0047835 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040IE UT WOS:000311315300012 PM 23139754 ER PT J AU Fernandes, AM Fero, K Arrenberg, AB Bergeron, SA Driever, W Burgess, HA AF Fernandes, Antonio M. Fero, Kandice Arrenberg, Aristides B. Bergeron, Sadie A. Driever, Wolfgang Burgess, Harold A. TI Deep Brain Photoreceptors Control Light-Seeking Behavior in Zebrafish Larvae SO CURRENT BIOLOGY LA English DT Article ID EXTRARETINAL PHOTORECEPTORS; ABLATION; CELLS; HYPOTHALAMUS; PHYSIOLOGY; VISION; MICE; RAT AB Most vertebrates process visual information using elaborately structured photosensory tissues, including the eyes and pineal. However, there is strong evidence that other tissues can detect and respond to photic stimuli [1-3]. Many reports suggest that photosensitive elements exist within the brain itself and influence physiology and behavior; however, a long-standing puzzle has been the identity of the neurons and photoreceptor molecules involved [4, 5]. We tested whether light cues influence behavior in zebrafish larvae through deep brain photosensors. We found that larvae lacking eyes and pineal perform a simple light-seeking behavior triggered by loss of illumination ("dark photokinesis"). Neuroanatomical considerations prompted us to test orthopedia(otpa)-deficient fish, which show a profound reduction in dark photokinesis. Using targeted genetic ablations, we narrowed the photosensitive region to neurons in the preoptic area. Neurons in this region express several photoreceptive molecules, but expression of the melanopsin opn4a is selectively lost in otpa mutants, suggesting that opn4a mediates dark photokinesis. Our findings shed light on the identity and function of deep brain photoreceptors and suggest that otpa specifies an ancient population of sensory neurons that mediate behavioral responses to light. C1 [Fero, Kandice; Bergeron, Sadie A.; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. [Fernandes, Antonio M.; Arrenberg, Aristides B.; Driever, Wolfgang] Univ Freiburg, Dev Biol Unit, Fac Biol, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany. [Fernandes, Antonio M.; Arrenberg, Aristides B.; Driever, Wolfgang] Univ Freiburg, FRIAS Freiburg Inst Adv Studies, D-79104 Freiburg, Germany. RP Burgess, HA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. EM burgessha@mail.nih.gov RI Burgess, Harold/B-8474-2015; OI Burgess, Harold/0000-0003-1966-7801; Bergeron, Sadie/0000-0002-1238-8730 FU National Institute for Child Health and Human Development; German Research Foundation [DFG-SFB780-B6]; European Commission (FP7 DOPAMINET) FX We thank the Sanger Zebrafish Mutation Project for the otpbsa0115 allele, Alida Filippi for opn4a histological sections, Jochen Wittbrodt for chokhs399 fish, the European Zebrafish Resource Center and J. Maier for chokht25327 fish, Josh Bonkowsky for Tg(otpb.A:Gal4)zc67 fish, Erin Beddows and Mattanja Sonn for excellent technical support, the zebrafish community for sharing reagents, and H. Codore and S. Gotter for expert zebrafish care. This work was supported by the Intramural Research Program of the National Institute for Child Health and Human Development (to H.A.B.), the German Research Foundation (DFG-SFB780-B6 to W.D.), and the European Commission (FP7 DOPAMINET to W.D.). NR 35 TC 57 Z9 57 U1 3 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 6 PY 2012 VL 22 IS 21 BP 2042 EP 2047 DI 10.1016/j.cub.2012.08.016 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 036VK UT WOS:000311060200026 PM 23000151 ER PT J AU Zhao, HY Schuck, P AF Zhao, Huaying Schuck, Peter TI Global Multi-Method Analysis of Affinities and Cooperativity in Complex Systems of Macromolecular Interactions SO ANALYTICAL CHEMISTRY LA English DT Article ID ISOTHERMAL TITRATION CALORIMETRY; PROTEIN INTERACTIONS; KINETIC-DATA; BINDING; CELL AB Cooperativity, multisite, and multicomponent interactions are hallmarks of biological systems of interacting macromolecules. Their thermodynamic characterization is often very challenging due to the notoriously low information content of binding isotherms. We introduce a strategy for the global multimethod analysis of data from multiple techniques (GMMA) that exploits enhanced information content emerging from the mutual constraints of the simultaneous modeling of orthogonal observables from calorimetric, spectroscopic, hydrodynamic, biosensing, or other thermodynamic binding experiments. We describe new approaches to address statistical problems that arise in the analysis of dissimilar data sets. The GMMA approach can significantly increase the complexity of interacting systems that can be accurately thermodynamically characterized. C1 [Schuck, Peter] Natl Inst Biomed Imaging, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. Natl Inst Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA. EM Peter.Schuck@nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We thank Andrea Balbo for expert technical assistance with the protein purification. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 34 TC 17 Z9 17 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 6 PY 2012 VL 84 IS 21 BP 9513 EP 9519 DI 10.1021/ac302357w PG 7 WC Chemistry, Analytical SC Chemistry GA 031TG UT WOS:000310664600089 PM 23020071 ER PT J AU Keteyian, SJ Leifer, ES Houston-Miller, N Kraus, WE Brawner, CA O'Connor, CM Whellan, DJ Cooper, LS Fleg, JL Kitzman, DW Cohen-Solal, A Blumenthal, JA Rendall, DS Pina, IL AF Keteyian, Steven J. Leifer, Eric S. Houston-Miller, Nancy Kraus, William E. Brawner, Clinton A. O'Connor, Christopher M. Whellan, David J. Cooper, Lawton S. Fleg, Jerome L. Kitzman, Dalane W. Cohen-Solal, Alain Blumenthal, James A. Rendall, David S. Pina, Ileana L. CA HF-ACTION Investigators TI Relation Between Volume of Exercise and Clinical Outcomes in Patients With Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiac rehabilitation; dose response; exercise training ID RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR FUNCTION; CARDIAC REHABILITATION; HF-ACTION; ENDOTHELIAL DYSFUNCTION; SKELETAL-MUSCLE; METAANALYSIS; ACTIVATION; PREVENTION; MORBIDITY AB Objectives This study determined whether greater volumes of exercise were associated with greater reductions in clinical events. Background The HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial showed that among patients with heart failure (HF), regular exercise confers a modest reduction in the adjusted risk for all-cause mortality or hospitalization. Methods Patients randomized to the exercise training arm of HF-ACTION who were event-free at 3 months after randomization were included (n = 959). Median follow-up was 28.2 months. Clinical endpoints were all-cause mortality or hospitalization and cardiovascular mortality or HF hospitalization. Results A reverse J-shaped association was observed between exercise volume and adjusted clinical risk. On the basis of Cox regression, exercise volume was not a significant linear predictor but was a logarithmic predictor (p = 0.03) for all-cause mortality or hospitalization. For cardiovascular mortality or HF hospitalization, exercise volume was a significant (p = 0.001) linear and logarithmic predictor. Moderate exercise volumes of 3 to <5 metabolic equivalent (MET)-h and 5 to <7 MET-h per week were associated with reductions in subsequent risk that exceeded 30%. Exercise volume was positively associated with the change in peak oxygen uptake at 3 months (r = 0.10; p = 0.005). Conclusions In patients with chronic systolic HF, volume of exercise is associated with the risk for clinical events, with only moderate levels (3 to 7 MET-h per week) of exercise needed to observe a clinical benefit. Although further study is warranted to confirm the relationship between volume of exercise completed and clinical events, our findings support the use of regular exercise in the management of these patients. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437) (J Am Coll Cardiol 2012;60:1899-905) (C) 2012 by the American College of Cardiology Foundation C1 [Keteyian, Steven J.] Henry Ford Hosp, Dept Cardiovasc Med, Div Cardiovasc Med, Detroit, MI 48202 USA. [Leifer, Eric S.; Cooper, Lawton S.; Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Houston-Miller, Nancy] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Kraus, William E.; O'Connor, Christopher M.; Rendall, David S.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [O'Connor, Christopher M.; Whellan, David J.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Kitzman, Dalane W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Cohen-Solal, Alain] Hop Lariboisiere, APHP, Sci Mixt Res Unit S942, Fac Paris Diderot, F-75475 Paris, France. [Pina, Ileana L.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Keteyian, SJ (reprint author), Henry Ford Hosp, Dept Cardiovasc Med, Div Cardiovasc Med, 6525 2nd Ave, Detroit, MI 48202 USA. EM sketeyi1@hfhs.org OI Brawner, Clinton A./0000-0002-1705-6620; Kraus, William E/0000-0003-1930-9684 FU National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland; NIH; GE Healthcare; Amgen; Servier; Astra Zeneca; Menarini; Takeda; IPSEN Genzyme; Novartis; Sorin FX This work was supported by the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland. Dr. Keteyian received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen; and is a consultant to Janssen Research & Development and the Duke University Medical Center. Dr. Leifer is an employee of NHLBI. Dr. Kraus received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen. Dr. O'Connor received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen. Dr. Whellan received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen. Drs. Cooper and Fleg are employees of NHLBI. Dr. Kitzman received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen. Dr. Cohen-Solal received grants or funding from Servier, Astra Zeneca, Menarini, Takeda, Amgen, IPSEN Genzyme, GE Health Care, Novartis, and Sorin. Dr. Pi a received grants or funding, personal income for consulting, and honoraria from the NIH, GE Healthcare, and Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 38 TC 47 Z9 47 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 6 PY 2012 VL 60 IS 19 BP 1899 EP 1905 DI 10.1016/j.jacc.2012.08.958 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 027LB UT WOS:000310352600008 PM 23062530 ER PT J AU Nestorovich, EM Karginov, VA Berezhkovskii, AM Parsegian, VA Bezrukov, SM AF Nestorovich, Ekaterina M. Karginov, Vladimir A. Berezhkovskii, Alexander M. Parsegian, V. Adrian Bezrukov, Sergey M. TI Kinetics and thermodynamics of binding reactions as exemplified by anthrax toxin channel blockage with a cationic cyclodextrin derivative SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein-ligand binding; molecular docking ID DRUG DESIGN; TEMPERATURE; DEPENDENCE; STRENGTH; WATER; PORE AB The thermodynamics of binding reactions is usually studied in the framework of the linear van't Hoff analysis of the temperature dependence of the equilibrium constant. The logarithm of the equilibrium constant is plotted versus inverse temperature to discriminate between two terms: an enthalpic contribution that is linear in the inverse temperature, and a temperature-independent entropic contribution. When we apply this approach to a particular case-blockage of the anthrax PA(63) channel by a multicharged cyclodextrin derivative-we obtain a nearly linear behavior with a slope that is characterized by enthalpy of about 1 kcal/mol. In contrast, from blocker partitioning between the channel and the bulk, we estimate the depth of the potential well for the blocker in the channel to be at least 8 kcal/mol. To understand this apparent discrepancy, we use a simple model of particle interaction with the channel and show that this significant difference between the two estimates is due to the temperature dependence of the physical forces between the blocker and the channel. In particular, we demonstrate that if the major component of blocker-channel interaction is van der Waals interactions and/or Coulomb forces in water, the van't Hoff enthalpy of the binding reaction may be close to zero or even negative, including cases of relatively strong binding. The results are quite general and, therefore, of importance for studies of enzymatic reactions, rational drug design, small-molecule binding to proteins, protein-protein interactions, and protein folding, among others. C1 [Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Nestorovich, Ekaterina M.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [Karginov, Vladimir A.] Innovat Biol, Herndon, VA 20171 USA. [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Center for Information Technology FX We thank Donald Rau for fruitful discussions and reading the manuscript. This study was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Center for Information Technology. NR 27 TC 10 Z9 10 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2012 VL 109 IS 45 BP 18453 EP 18458 DI 10.1073/pnas.1208771109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038DZ UT WOS:000311156700051 PM 23100532 ER PT J AU Bartoshuk, LM Catalanotto, F Hoffman, H Logan, H Snyder, DJ AF Bartoshuk, Linda M. Catalanotto, Frank Hoffman, Howard Logan, Henrietta Snyder, Derek J. TI Taste damage (otitis