FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Blumen, SC Drory, VE Sadeh, M El-Ad, B Soimu, U Groozman, GB Bouchard, JP Goldfarb, LG AF Blumen, Sergiu C. Drory, Vivian E. Sadeh, Menachem El-Ad, Baruch Soimu, Uri Groozman, Galina B. Bouchard, Jean-Pierre Goldfarb, Lev G. TI Mutational analysis of glycyl-tRNA synthetase (GARS) gene in Hirayama disease SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Hirayama's disease; GARS gene; distal spinal muscular atrophy; dSMA-V ID JUVENILE MUSCULAR-ATROPHY; DISTAL UPPER EXTREMITY; MYELOPATHY AB Sporadic juvenile muscular atrophy of the distal upper extremity or Hirayama's disease (HD) and autosomal dominant motor distal neuronopathy/axonopathy (CMT2D/dSMA-V), produced by glycyl-tRNA synthetase (GARS) gene mutations, share some clinical features including: young age of onset, predilection for the distal upper extremity, asymmetry, sparing of proximal muscles and unusual cold sensitivity. However, incomplete penetrance of GARS gene mutations may account for apparently non-familial cases. In order to inquire whether GARS gene mutations are associated with HD we studied seven patients fulfilling the clinical and electrodiagnostic criteria for HD. All patients underwent MRI of cervical spine that excluded compressive myelopathy in neutral position and intramedullary pathology. Each patient was tested for the presence of mutations in GARS by sequencing all coding exons amplified from genomic DNA. No pathogenic mutations were found, excluding the role of GARS gene as a possible factor in the aetiology of HD in this cohort.The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of non-smoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental development index (MDI). Genes known to play important roles in the metabolic activation or detoxification of PAHs were selected. Genetic variations in these genes could influence susceptibility to adverse effects of PAHs in polluted air. We explored the effects of interactions between prenatal PAH exposure and 21 polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among 547 newborns and 806 mothers from three different ethnic groups. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene. C1 [Perera, Frederica P.] Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA. [Wang, Shuang; Li, Zhigang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Chanock, Stephen] NCI, Bethesda, MD 20892 USA. [Jedrychowski, Wieslaw] Jagiellonian Univ, Coll Med, Dept Epidemiol & Prevent Med, Krakow, Poland. RP Perera, FP (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, 100 Haven Ave,25F,Tower 3, New York, NY 10032 USA. EM fpp1@columbia.edu FU National Institute of Environmental Health Sciences [P01 009600, R01 ES08977, R01 ES111158, R01 ES012468, ES09089]; U.S. Environmental Protection Agency [R827027, R8260901]; Herbert Irving Cancer Center; Gladys and Roland Harriman Foundation; New York Community Trust; [5P30 CA 13696-23] FX Support through grants P01 009600, R01 ES08977, R01 ES111158, R01 ES012468 and ES09089 from the National Institute of Environmental Health Sciences; grants R827027 and R8260901 from the U.S. Environmental Protection Agency; Herbert Irving Cancer Center; Core grant 5P30 CA 13696-23;Gladys and Roland Harriman Foundation; and the New York Community Trust is gratefully acknowledged. All authors declare no conflict of interest on this work. NR 39 TC 15 Z9 16 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2010 VL 74 BP 46 EP 56 DI 10.1111/j.1469-1809.2009.00550.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 533OY UT WOS:000272835300006 PM 19860743 ER PT J AU Pierson, TM AF Pierson, Tyler Mark TI Whole Exome Sequencing Identifies AFG3L2 Mutation in a Novel Recessive Progressive Myoclonic Epilepsy-Ataxia-Neuropathy Syndrome SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Child-Neurology-Society CY OCT 13-16, 2010 CL Providence, RI SP Child Neurol Soc C1 [Pierson, Tyler Mark] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2010 VL 68 IS 4 SU 14 BP S3 EP S3 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670CP UT WOS:000283398800010 ER PT J AU Arumugam, TV Phillips, TM Cheng, AW Morrell, CH Mattson, MP Wan, RQ AF Arumugam, Thiruma V. Phillips, Terry M. Cheng, Aiwu Morrell, Christopher H. Mattson, Mark P. Wan, Ruiqian TI Age and Energy Intake Interact to Modify Cell Stress Pathways and Stroke Outcome SO ANNALS OF NEUROLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; CEREBRAL-ARTERY OCCLUSION; ISCHEMIC BRAIN-INJURY; ENDOPLASMIC-RETICULUM STRESS; NEUROTROPHIC FACTOR; DIETARY RESTRICTION; GENE-EXPRESSION; CALORIC RESTRICTION; MOLECULAR-MECHANISMS; BEHAVIORAL DEFICITS AB Objective: Age and excessive energy intake/obesity are risk factors for cerebrovascular disease, but it is not known if and how these factors affect the extent of brain damage and outcome in ischemic stroke. We therefore determined the interactions of age and energy intake on the outcome of ischemic brain injury, and elucidated the underlying mechanisms. Methods: We utilized a novel microchip-based immunoaffinity capillary electrophoresis technology to measure a panel of neurotrophic factors, cytokines, and cellular stress resistance proteins in brain tissue samples from young, middle-aged, and old mice that had been maintained on control or energy-restricted diets prior to middle cerebral artery occlusion and reperfusion. Results: Mortality from focal ischemic stroke was increased with advancing age and reduced by an intermittent fasting (IF) diet. Brain damage and functional impairment were reduced by IF in young and middle-aged mice, but not in old mice. The basal and poststroke levels of neurotrophic factors (brain-derived neurotrophic factor and basic fibroblast growth factor), protein chaperones (heat shock protein 70 and glucose regulated protein 78), and the antioxidant enzyme heme oxygenase-1 were decreased, whereas levels of inflammatory cytokines were increased in the cerebral cortex and striatum of old mice compared with younger mice. IF coordinately increased levels of protective proteins and decreased inflammatory cytokines in young, but not in old mice. Interpretation: Reduction in dietary energy intake differentially modulates neurotrophic and inflammatory pathways to protect neurons against ischemic injury, and these beneficial effects of IF are compromised during aging, resulting in increased brain damage and poorer functional outcome. ANN NEUROL 2010;67:41-52 C1 [Arumugam, Thiruma V.; Cheng, Aiwu; Mattson, Mark P.; Wan, Ruiqian] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. [Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, Natl Inst Hlth, Bethesda, MD USA. [Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; wanru@grc.nia.nih.gov RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 FU National Institutes of Health FX This research was supported by the National Institute on Aging Intramural Research Program and the National Institute of Biomedical Imaging and Bioengineering Intramural Research Program of the National Institutes of Health. NR 61 TC 89 Z9 89 U1 3 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2010 VL 67 IS 1 BP 41 EP 52 DI 10.1002/ana.21798 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 564AE UT WOS:000275181900007 PM 20186857 ER PT J AU Magnani, JW Mazzini, MJ Sullivan, LM Williamson, M Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Mazzini, Michael J. Sullivan, Lisa M. Williamson, MaryAnn Ellinor, Patrick T. Benjamin, Emelia J. TI P-Wave Indices, Distribution and Quality Control Assessment (from the Framingham Heart Study) SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiogram; P waves; reproducibility; epidemiology ID PAROXYSMAL ATRIAL-FIBRILLATION; LEFT-VENTRICULAR HYPERTROPHY; YOUNG HEALTHY-MEN; INTERATRIAL BLOCK; DIASTOLIC DYSFUNCTION; OBESE SUBJECTS; SINUS RHYTHM; QT INTERVAL; WEIGHT-LOSS; DISPERSION AB Background: P-wave indices of maximum P-wave duration and P-wave dispersion have been examined in a broad array of cardiovascular and noncardiovascular disease states. The P-wave indices literature has been highly heterogeneous in measurement methodologies, described quality control metrics, and distribution of values. We therefore sought to determine the reproducibility of P-wave indices in a community-based cohort. Methods: P-wave indices were measured in sequential subjects enrolled in the Framingham Heart Study. Electrocardiograms were obtained at the 11th biennial visit of the Original Cohort (n = 250) and the initial visit of the Offspring Cohort (n = 252). We determined the mean P-wave durations, interlead correlations, and P-wave indices. We then chose 20 ECGs, 10 from each cohort, and assessed intrarater and interrater variability. Results: The maximum P-wave duration ranged from 71 to 162 ms with mean of 112 +/- 12 ms. The minimum P-wave duration ranged from 35 to 103 ms with mean of 65 +/- 10 ms. P-wave dispersion ranged from 12 to 82 ms. The mean P-wave dispersion was 48 +/- 12 ms (40-56). The intrarater intraclass correlation coefficient (ICC) was r = 0.80 for maximum P-wave duration and r = 0.82 for P-wave dispersion. The interrater ICC was 0.56 for maximum P-wave duration and 0.70 for P-wave dispersion. Conclusions: We demonstrated excellent intrarater reproducibility and fair interrater reproducibility for calculating P-wave indices. Reproducibility is frequently lacking in studies of P-wave indices, but is an essential component for the field's growth and epidemiologic contribution. Ann Noninvasive Electrocardiol 2010;15(1):77-84 C1 [Magnani, Jared W.; Mazzini, Michael J.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Framingham, MA 01702 USA. [Williamson, MaryAnn] Sch Publ Hlth, Div Med, Boston, MA USA. [Benjamin, Emelia J.] Sch Publ Hlth, Whitaker Cardiovasc Inst, Boston, MA USA. [Sullivan, Lisa M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Benjamin, Emelia J.] NHLBI, Framingham Study, Framingham, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med & Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028] FX This research was supported by an American Heart Association award 09FTF2190028. NR 48 TC 12 Z9 15 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JAN PY 2010 VL 15 IS 1 BP 77 EP 84 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 546OW UT WOS:000273821100012 PM 20146786 ER PT J AU Ivy, SP Takebe, N Jamieson, C O'Brien, CA AF Ivy, S. P. Takebe, N. Jamieson, C. O'Brien, C. A. TI EDUCATIONAL LECTURE: STEM CELLS IN SOLID TUMORS: THE CANCER STEM CELL HYPOTHESIS AND EMBRYONIC SIGNALING PATHWAYS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD ID ACUTE MYELOID-LEUKEMIA; BREAST-CANCER; PROSPECTIVE IDENTIFICATION; BRAIN-TUMORS; OLD IDEA; CARCINOMA; LINES; RESISTANCE; HIERARCHY; CULTURE C1 [Ivy, S. P.; Takebe, N.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. [Jamieson, C.] Moores UCSD Canc Ctr, Div Hematol Oncol, La Jolla, CA USA. [O'Brien, C. A.] Univ Hlth Network, Div Cell & Mol Biol, Toronto, ON, Canada. NR 41 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 11 EP 12 PG 2 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800009 ER PT J AU Luo, J AF Luo, J. TI IDENTIFYING CANCER CELL VULNERABILITY WITH SYNTHETIC LETHAL RNAI SCREEN SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Luo, J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 15 EP 15 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800019 ER PT J AU Rajan, A Kelly, RJ Gutierrez, M Kummar, S Yancey, MA Ji, J Zhang, Y Parchment, R Doroshow, J Giaccone, G AF Rajan, A. Kelly, R. J. Gutierrez, M. Kummar, S. Yancey, M. A. Ji, J. Zhang, Y. Parchment, R. Doroshow, J. Giaccone, G. TI PHASE I COMBINATION STUDY OF OLAPARIB (AZD2281; KU-0059436) AND CISPLATIN (C) PLUS GEMCITABINE (G) IN ADULTS WITH SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Rajan, A.; Kelly, R. J.; Gutierrez, M.; Kummar, S.; Yancey, M. A.; Doroshow, J.; Giaccone, G.] NCI, Bethesda, MD 20892 USA. [Ji, J.; Zhang, Y.; Parchment, R.] SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800023 ER PT J AU Das, BB Shiloh, Y Pommier, Y AF Das, B. B. Shiloh, Y. Pommier, Y. TI ATM AND/OR DNA-PK FACILITATES REPAIR OF TOPOISOMERASE I-ASSOCIATED BREAKS BY NOVEL PHOSPHORYLATION OF THE DNA REPAIR ENZYME TDP1 AT SER81 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Das, B. B.; Pommier, Y.] NCI, Bethesda, MD 20892 USA. [Shiloh, Y.] Tel Aviv Univ, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800026 ER PT J AU Duffy, A AF Duffy, A. TI AXITINIB IN PANCREATIC CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Duffy, A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800027 ER PT J AU Giaccone, G Rajan, A Crandon, S Gutierrez, M Jain, L Figg, WD Houk, BE Shnaidman, M Brega, N AF Giaccone, G. Rajan, A. Crandon, S. Gutierrez, M. Jain, L. Figg, W. D. Houk, B. E. Shnaidman, M. Brega, N. TI A PHASE 1 STUDY OF PF-04929113 (SNX5422), AN ORALLY BIOAVAILABLE HEAT SHOCK PROTEIN 90 (HSP90) INHIBITOR AFTER TWICE WEEKLY ADMINISTRATION IN PATIENTS WITH REFRACTORY SOLID TUMOR MALIGNANCIES AND LYMPHOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Giaccone, G.; Rajan, A.; Crandon, S.; Gutierrez, M.; Jain, L.; Figg, W. D.] NCI, Bethesda, MD 20892 USA. [Houk, B. E.; Shnaidman, M.; Brega, N.] Pfizer, La Jolla, CA USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800037 ER PT J AU Neckers, L AF Neckers, L. TI HSP90 AND CANCER: TARGETING A DYNAMIC CHAPERONE COMPLEX SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Neckers, L.] NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800036 ER PT J AU Bates, SE Piekarz, RL Frye, R Turner, ML Wright, JJ Robey, RW Zhan, Z Luchenko, V Figg, WD Gardner, ER Steinberg, SM Ling, A Jaffe, ES Stetler-Stevenson, M Fojo, AT AF Bates, S. E. Piekarz, R. L. Frye, R. Turner, M. L. Wright, J. J. Robey, R. W. Zhan, Z. Luchenko, V. Figg, W. D. Gardner, E. R. Steinberg, S. M. Ling, A. Jaffe, E. S. Stetler-Stevenson, M. Fojo, A. T. TI HDAC INHIBITORS IN LYMPHOMAS AND SOLID TUMORS: THINKING ABOUT DRUG RESISTANCE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Bates, S. E.; Piekarz, R. L.; Frye, R.; Turner, M. L.; Wright, J. J.; Robey, R. W.; Zhan, Z.; Luchenko, V.; Figg, W. D.; Gardner, E. R.; Steinberg, S. M.; Ling, A.; Jaffe, E. S.; Stetler-Stevenson, M.; Fojo, A. T.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800043 ER PT J AU Solier, S Pommier, Y AF Solier, S. Pommier, Y. TI THE APOPTOTIC RING: A NOVEL ENTITY WITH PHOSPHORYLATED HISTONES H2AX AND H2B, AND ACTIVATED DNA DAMAGE RESPONSE KINASES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Solier, S.; Pommier, Y.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 25 EP 26 PG 2 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800044 ER PT J AU Annunziata, CM AF Annunziata, C. M. TI NF-KAPPAB SIGNALING IN CANCER: DEREGULATION AND TARGETING SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Annunziata, C. M.] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800052 ER PT J AU Driscoll, J Gootenberg, J Amin, S Pelluru, D Avet-Loiseau, H Minville, S Anderson, K Munshi, N Annunziata, C AF Driscoll, J. Gootenberg, J. Amin, S. Pelluru, D. Avet-Loiseau, H. Minville, S. Anderson, K. Munshi, N. Annunziata, C. TI THE UBIQUITIN LIGASE RNF4 IS INDUCED IN MULTIPLE MYELOMA, PROMOTES BORTEZOMIB RESISTANCE AND INTEGRATES THE SUMOYLATION, UBIQUITINATION AND PROTEASOME PATHWAYS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Driscoll, J.; Gootenberg, J.; Annunziata, C.] NCI, NIH, Bethesda, MD 20892 USA. [Amin, S.; Pelluru, D.; Avet-Loiseau, H.; Anderson, K.; Munshi, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minville, S.] Hematol Lab, Nantes, France. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800050 ER PT J AU Zoppoli, GM Connelly, WJR Reinhold, C Jobson, A Solier, S Monks, A Shoemaker, R Pommier, Y AF Zoppoli, G. M. Connelly, W. J. R. Reinhold, C. Jobson, A. Solier, S. Monks, A. Shoemaker, R. Pommier, Y. TI CHK2 STATUS AND INSIGHTS INTO THE ACTIVITY OF ITS INHIBITOR PV1019 ACROSS THE 60 CELL LINES FROM THE NCI SCREEN SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Zoppoli, G. M.; Connelly, W. J. R.; Reinhold, C.; Jobson, A.; Solier, S.; Monks, A.; Shoemaker, R.] NIH, Bethesda, MD 20892 USA. [Pommier, Y.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 29 EP 29 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800054 ER PT J AU Tandle, A Gehlhaus, K Shankavaram, U Tofilon, P Caplen, N Camphausen, K AF Tandle, A. Gehlhaus, K. Shankavaram, U. Tofilon, P. Caplen, N. Camphausen, K. TI SCREENING OF SMALL INTERFERING RNA LIBRARY OF HUMAN KINASES FOR THE DISCOVERY OF SURVIVAL GENES AND NOVEL DRUG TARGETS FOR THE TREATMENT OF GLIOBLASTOMAS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Tandle, A.; Gehlhaus, K.; Shankavaram, U.; Caplen, N.; Camphausen, K.] NCI, NIH, Bethesda, MD 20892 USA. [Tofilon, P.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 31 EP 31 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800057 ER PT J AU Kim, YS Lee, S Kumar, V Alarcon, SV Lee, R Malhotra, SV Trepel, JB AF Kim, Y. S. Lee, S. Kumar, V. Alarcon, S. V. Lee, R. Malhotra, S. V. Trepel, J. B. TI SMALL MOLECULE INHIBITORS OF ANDROGEN RECEPTOR TRANSLOCATION AND FUNCTION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Kim, Y. S.; Lee, S.; Alarcon, S. V.; Lee, R.; Trepel, J. B.] NCI, NIH, Bethesda, MD 20892 USA. [Kumar, V.; Malhotra, S. V.] NCI, SAIC Frederick Inc, Lab Synthet Chem, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 32 EP 32 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800060 ER PT J AU Leo, E AF Leo, E. TI HISTONE DEACETYLASE INHIBITION SLOWS DOWN REPLICATION FORKS, ACTIVATES DORMANT ORIGINS AND INDUCES DNA DAMAGE IN CANCER CELLS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Leo, E.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 35 EP 35 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800069 ER PT J AU Teicher, B Kurtzberg, L Schmid, S Pommier, Y Lavoie, E Ewesuedo, R Roth, S Krumbholz, R Rouleau, C Bagley, R AF Teicher, B. Kurtzberg, L. Schmid, S. Pommier, Y. Lavoie, E. Ewesuedo, R. Roth, S. Krumbholz, R. Rouleau, C. Bagley, R. TI GENZ-644282, A NOVEL NON-CAMPTOTHECIN TOPOISOMERASE I (TOP1) INHIBITOR FOR CANCER TREATMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Teicher, B.; Kurtzberg, L.; Schmid, S.; Ewesuedo, R.; Roth, S.; Krumbholz, R.; Rouleau, C.; Bagley, R.] Genzyme Corp, Framingham, MA 01701 USA. [Pommier, Y.] NCI, Bethesda, MD 20892 USA. [Lavoie, E.] Rutgers State Univ, Piscataway, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 35 EP 35 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800068 ER PT J AU Capala, J Zileinski, R Lyakhov, I AF Capala, J. Zileinski, R. Lyakhov, I. TI AFFITOXIN - A NOVEL RECOMBINANT, HER2-SPECIFIC, ANTI-CANCER AGENT FOR TARGETED THERAPY OF HER2-POSITIVE TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Capala, J.; Zileinski, R.] NCI, NIH, Bethesda, MD 20892 USA. [Lyakhov, I.] NCI, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 36 EP 37 PG 2 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800073 ER PT J AU Kim, G Henning, R Yu, M Squires, J Houston, N Kohn, EC AF Kim, G. Henning, R. Yu, M. Squires, J. Houston, N. Kohn, E. C. TI L-ASPARAGINASE MODULATES INTERACTIONS WITHIN THE TUMOR MICROENVIRONMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Kim, G.; Henning, R.; Yu, M.; Squires, J.; Houston, N.; Kohn, E. C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 37 EP 37 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800074 ER PT J AU Hodge, J Farsaci, B Higgins, J Schlom, J AF Hodge, J. Farsaci, B. Higgins, J. Schlom, J. TI EFFECT OF A SMALL MOLECULE BCL-2 INHIBITOR ON IMMUNE FUNCTION AND USE WITH A RECOMBINANT VACCINE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Hodge, J.; Farsaci, B.; Higgins, J.; Schlom, J.] NCI, Bethesda, MD 20892 USA. RI Farsaci, Benedetto/L-9837-2014 OI Farsaci, Benedetto/0000-0001-8275-2561 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 39 EP 39 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800078 ER PT J AU Capala, J Kramer-Marek, G Kiesewetter, D AF Capala, J. Kramer-Marek, G. Kiesewetter, D. TI IN VIVO QUANTIFICATION OF CHANGES IN HER2 EXPRESSION FOLLOWING THERAPEUTIC INTERVENTION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Capala, J.; Kramer-Marek, G.] NCI, NIH, Bethesda, MD 20892 USA. [Kiesewetter, D.] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 40 EP 41 PG 2 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800084 ER PT J AU Linguraru, MG Wang, S Gautam, R Peterson, J Linehan, WM Summers, RM AF Linguraru, M. G. Wang, S. Gautam, R. Peterson, J. Linehan, W. M. Summers, R. M. TI IMAGING BIOMARKERS FOR COMPUTER-AIDED CLASSIFICATION OF RENAL CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Linguraru, M. G.; Wang, S.; Gautam, R.; Peterson, J.; Linehan, W. M.; Summers, R. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 40 EP 40 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800083 ER PT J AU Hassan, R Sharon, E Pastan, I AF Hassan, R. Sharon, E. Pastan, I. TI MESOTHELIN TARGETED CHEMO-IMMUNOTHERAPY FOR TREATMENT OF MALIGNANT MESOTHELIOMA AND LUNG ADENOCARCINOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Hassan, R.; Sharon, E.; Pastan, I.] NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 42 EP 42 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800087 ER PT J AU Kreitman, JR Tallman, M Robak, T Coutre, S Wilson, WH Stetler-Stevenson, M Noel, P Fitzgerald, DJP McDevitt, J Pastan, I AF Kreitman, J. R. Tallman, M. Robak, T. Coutre, S. Wilson, W. H. Stetler-Stevenson, M. Noel, P. Fitzgerald, D. J. P. McDevitt, J. Pastan, I. TI PHASE I TESTING OF ANTI-CD22 RECOMBINANT IMMUNOTOXIN CAT-8015 (HA22) IN RELAPSED OR REFRACTORY HAIRY CELL LEUKEMIA AND CHRONIC LYMPHOCYTIC LEUKEMIA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Kreitman, J. R.; Wilson, W. H.; Stetler-Stevenson, M.; Fitzgerald, D. J. P.; Pastan, I.] NCI, Bethesda, MD 20892 USA. [Tallman, M.] Northwestern Univ, Chicago, IL 60611 USA. [Robak, T.] Med Univ Lodz, Lodz, Poland. [Coutre, S.] Stanford Univ, Stanford, CA 94305 USA. [Noel, P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [McDevitt, J.] MedImmune LLC, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 42 EP 43 PG 2 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800089 ER PT J AU Rajan, A Berman, A Kelly, RJ Lopez-Chavez, A Dechowdhury, R Chen, H Giaccone, G AF Rajan, A. Berman, A. Kelly, R. J. Lopez-Chavez, A. Dechowdhury, R. Chen, H. Giaccone, G. TI PHASE II STUDY OF THE INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR (IGF-1R) ANTIBODY CIXUTUMUMAB (C) IN PATIENTS (PTS) WITH THYMOMA (T) AND THYMIC CARCINOMA (TC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Rajan, A.; Berman, A.; Kelly, R. J.; Lopez-Chavez, A.; Dechowdhury, R.; Chen, H.; Giaccone, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 44 EP 44 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800094 ER PT J AU Mahoney, M Smyrk, T Allen, ZK Heigh, R Schoen, R Levine, J Stoffel, E Chiorean, M Benya, R Sontag, S Weinberg, D Lawson, M Gostout, C Rodriguez, LM Limburg, P AF Mahoney, M. Smyrk, T. Allen, Ziegler K. Heigh, R. Schoen, R. Levine, J. Stoffel, E. Chiorean, M. Benya, R. Sontag, S. Weinberg, D. Lawson, M. Gostout, C. Rodriguez, L. M. Limburg, P. TI PROLIFERATION AND APOPTOSIS BIOMARKER MODULATION IN A PHASE II COLORECTAL (CRC) CHEMOPREVENTION TRIAL OF ATORVASTATIN, SULINDAC, OR OLIGOFRUCTOSE-ENRICHED INLULIN: A CANCER PREVENTION NETWORK (CPN) TRIAL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 12th World Congress on Gastrointestinal Cancer CY JUN 30-JUL 03, 2010 CL Barcelona, SPAIN C1 [Mahoney, M.; Smyrk, T.; Allen, Ziegler K.; Heigh, R.; Gostout, C.; Limburg, P.] Mayo Clin, Rochester, MN USA. [Schoen, R.] Univ Pittsburgh, Pittsburgh, PA USA. [Levine, J.] Univ Connecticut, Farmington, CT USA. [Stoffel, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chiorean, M.] Indiana Univ, Indianapolis, IN 46204 USA. [Benya, R.] Univ Illinois, Chicago, IL USA. [Sontag, S.] Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Weinberg, D.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Lawson, M.] Kaiser Permanente No Calif, Sacramento, CA USA. [Rodriguez, L. M.] NCI, Canc Prevent Div, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 6 BP 79 EP 79 PG 1 WC Oncology SC Oncology GA 634EU UT WOS:000280563300242 ER PT J AU Aragon-Ching, JB Dahut, WL AF Aragon-Ching, J. B. Dahut, W. L. TI About tyrosine kinase inhibitors (TKIs) in prostate cancer: where do we go from here? SO ANNALS OF ONCOLOGY LA English DT Letter ID PHASE-II; 2ND-LINE CHEMOTHERAPY; SORAFENIB; MITOXANTRONE; DOCETAXEL; TRIAL; MEN C1 [Aragon-Ching, J. B.] George Washington Univ, Med Ctr, Dept Med, Div Hematol Oncol, Washington, DC 20037 USA. [Dahut, W. L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Aragon-Ching, JB (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Hematol Oncol, Washington, DC 20037 USA. EM jaragonching@mfa.gwu.edu OI Aragon-Ching, Jeanny/0000-0002-6714-141X NR 14 TC 3 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2010 VL 21 IS 1 BP 183 EP 184 DI 10.1093/annonc/mdp467 PG 2 WC Oncology SC Oncology GA 534VA UT WOS:000272924300030 PM 19903718 ER PT J AU Ripley, RT Davis, JL Klapper, JA Mathur, A Kammula, U Royal, RE Yang, JC Sherry, RM Hughes, MS Libutti, SK White, DE Steinberg, SM Dudley, ME Rosenberg, SA Avital, I AF Ripley, R. Taylor Davis, Jeremy L. Klapper, Jacob A. Mathur, Aarti Kammula, Udai Royal, Richard E. Yang, James C. Sherry, Richard M. Hughes, Marybeth S. Libutti, Steven K. White, Donald E. Steinberg, Seth M. Dudley, Mark E. Rosenberg, Steven A. Avital, Itzhak TI Liver Resection for Metastatic Melanoma with Postoperative Tumor-Infiltrating Lymphocyte Therapy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID AMERICAN JOINT COMMITTEE; ADOPTIVE CELL TRANSFER; HEPATIC RESECTION; SYSTEMIC CHEMOTHERAPY; CANCER-IMMUNOTHERAPY; MALIGNANT-MELANOMA; SURGICAL RESECTION; COMPLETE RESPONSES AB Patients with metastatic melanoma to the liver (MML) have a median survival of 4 to 6 months. This study evaluated patients who underwent liver resection with intent to receive postoperative tumor-infiltrating lymphocyte (TIL) therapy. Retrospective analysis of a prospective database identified patients with MML who underwent liver resection from 1980 to 2008. A total of 539 patients had MML, and 39% (204 of 539) had tumor collected for TIL. A total of 17% (35 of 204) underwent liver resection for TIL. The 3-year overall survival was 53%. Lack of extrahepatic disease (P = .026), negative margin (P = .056), and single hepatic metastasis (P = .04) predicted survival after univariate analysis. Only lack of extrahepatic disease remained a significant predictor of survival after multivariate analysis (P = .043). A total of 31% (11 of 35) underwent complete resection without TIL, and 69% (24 of 35) underwent resection with synchronous intrahepatic and extrahepatic disease with intent to receive TIL. For 9 of 11 patients (2 of 11 excluded for gene therapy), 3-year survival was 80%. A total of 4 (44%) of 9 experienced recurrence, with a median disease-free survival of 1.2 years. For 24 patients (69%) with residual disease, 3-year survival was 51% (2 of 24 excluded for gene therapy). A total of 63% (15 of 24) received postoperative TIL (3-year survival 65%), and 29% (7 of 24) did not. A total of 40% (6 of 15) had disease that partially responded to TIL; the disease of 67% (4 of 6) had not progressed at median follow-up of 55 months (range, 42-197+ months). The seven patients who did not receive TIL had a median survival of 4.6 months. Resection of MML with TIL should be considered because it can result in prolonged survival in a highly selected group of patients. C1 [Ripley, R. Taylor; Davis, Jeremy L.; Klapper, Jacob A.; Mathur, Aarti; Kammula, Udai; Royal, Richard E.; Yang, James C.; Sherry, Richard M.; Hughes, Marybeth S.; Libutti, Steven K.; White, Donald E.; Dudley, Mark E.; Rosenberg, Steven A.; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Rockville, MD USA. RP Ripley, RT (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov FU National Institutes of Health National Cancer Institute FX National Institutes of Health National Cancer Institute, Intramural grant, provided support for the Surgery Branch, Immunotherapy Section. NR 28 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2010 VL 17 IS 1 BP 163 EP 170 DI 10.1245/s10434-009-0677-0 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 543OJ UT WOS:000273587700025 PM 19777192 ER PT J AU Krasna, MJ Gamliel, Z Burrows, WM Sonett, JR Kwong, KF Edelman, MJ Hausner, PF Doyle, LA DeYoung, C Suntharalingam, M AF Krasna, Mark J. Gamliel, Ziv Burrows, Whitney M. Sonett, Joshua R. Kwong, King F. Edelman, Martin J. Hausner, Petr F. Doyle, L. Austin DeYoung, Chad Suntharalingam, Mohan TI Pneumonectomy for Lung Cancer After Preoperative Concurrent Chemotherapy and High-Dose Radiation SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 01, 2006 CL Chicago, IL SP Soc Thorac Surg ID GROUP PHASE-II; PULMONARY RESECTION; SURGICAL RESECTION; STAGE-IIIA; NEOADJUVANT THERAPY; CHEST RADIOTHERAPY; INDUCTION THERAPY; TRIAL; SURVIVAL; COMPLICATIONS AB Background. We studied the clinical characteristics and outcomes of patients undergoing pneumonectomy after preoperative concurrent chemoradiation for non-small cell lung cancer. Methods. Clinical records of patients with non-small cell lung cancer who underwent pneumonectomy at our institution between 1995 and 2005 after preoperative concurrent chemoradiation were reviewed retrospectively. Results. Twenty-nine patients underwent pneumonectomy after preoperative concurrent chemoradiation. Of the 21 men and 8 women who were treated, 1 had stage IIB (T3N0M0) and the remainder had stage IIIA or IIIB non-small cell lung cancer. Mean patient age at surgery was 53.4 years. There were 15 right pneumonectomies, of which 2 were for pancoast tumors. All patients received concurrent preoperative chemoradiation. Mean total radiation dose was 61.1 Gy. All patients went on to have complete (R0) resection by pneumonectomy. Pathologic complete response was found in 16 patients (55.2%). All patients were discharged alive from the hospital after pneumonectomy. Median hospital length of stay was 5 days (mean 8.6). Ninety-day mortality after surgery was 3.4% (n = 1). Recurrences have been found in 11 patients (38%), including brain metastases (n = 6), bone metastases (n = 4), liver metastases (n = 2), and cervical lymph node metastases (n = 2). One patient had a contralateral new primary lung cancer develop 70 months after undergoing pneumonectomy. Estimated 5-year disease-free survival is 48%. Median survival time has not been reached. Conclusions. Pneumonectomy can be performed safely after preoperative concurrent chemoradiation, even with high-dose radiation. The frequency of disease recurrence in the brain underscores the need to evaluate the role of prophylactic cranial radiation in non-small cell lung cancer. C1 St Joseph Canc Inst, Towson, MD USA. Univ Maryland, Thorac Oncol Program, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Valley Hosp, Ridgewood, NJ USA. NIH, Bethesda, MD 20892 USA. RP Krasna, MJ (reprint author), St Joseph Med Ctr, Inst Canc, 7501 Osler Dr,Suite 104, Towson, MD 21204 USA. EM markkrasna@catholichealth.net NR 25 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2010 VL 89 IS 1 BP 200 EP 206 DI 10.1016/j.athoracsur.2009.08.069 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 535AU UT WOS:000272939700030 PM 20103235 ER PT S AU Bolton, EE Wang, YL Thiessen, PA Bryant, SH AF Bolton, Evan E. Wang, Yanli Thiessen, Paul A. Bryant, Stephen H. BE Wheeler, RA Spellmeyer, DC TI PubChem: Integrated Platform of Small Molecules and Biological Activities SO ANNUAL REPORTS IN COMPUTATIONAL CHEMISTRY, VOL 4 SE Annual Reports in Computational Chemistry LA English DT Article; Book Chapter ID DRUG DISCOVERY; DATABASE C1 [Bolton, Evan E.; Wang, Yanli; Thiessen, Paul A.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov NR 13 TC 361 Z9 365 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1574-1400 BN 978-0-08-093278-1 J9 ANN REP COMP CHEM PY 2010 VL 4 BP 217 EP 241 DI 10.1016/S1574-1400(08)00012-1 PG 25 WC Chemistry, Physical SC Chemistry GA BCT94 UT WOS:000311385500013 ER PT S AU Misra, RN AF Misra, Raj N. BE Macor, JE TI NIH Translational Programs for Assisting Pre-Clinical Drug Discovery and Development SO ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 45 SE Annual Reports in Medicinal Chemistry LA English DT Review; Book Chapter ID DEPSIPEPTIDE C1 NCI, NIH, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Misra, RN (reprint author), NCI, NIH, Dev Therapeut Program, 6130 Execut Blvd,FPN Suite 8032, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-7743 BN 978-0-12-380902-5 J9 ANNU REP MED CHEM JI Annu. Rep. Med. Chem. PY 2010 VL 45 BP 361 EP 377 DI 10.1016/S0065-7743(10)45022-8 PG 17 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BSB42 UT WOS:000284075300022 ER PT S AU Yang, W AF Yang, Wei BE Rees, DC Dill, KA Williamson, JR TI Lessons Learned from UvrD Helicase: Mechanism for Directional Movement SO ANNUAL REVIEW OF BIOPHYSICS, VOL 39 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE motor-track-load; mechanochemical coupling; ATPase; spiral movement; step size; inchworm; hand-over-hand ID SINGLE-STRANDED-DNA; REPLICATIVE HEXAMERIC HELICASE; MICROTUBULE-KINESIN ATPASE; COLI REP PROTEIN; HAND-OVER-HAND; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; PCRA HELICASE; STRUCTURAL BASIS; STEP-SIZE AB How do molecular motors convert chemical energy to mechanical work? Helicases and nucleic acids offer simple motor systems for extensive biochemical and biophysical analyses. Atomic resolution structures of UvrD-like helicases complexed with DNA in the presence of AMPPNP, ADP.Pi, and Pi reveal several salient points that aid our understanding of mechanochemical coupling. Each ATPase cycle causes two motor domains to rotationally close and open. At a minimum, two motor-track contact points of alternating tight and loose attachment convert domain rotations to unidirectional movement. A motor is poised for action only when fully in contact with its track and, if applicable, working against a load. The orientation of domain rotation relative to the track determines whether the movement is linear, spiral, or circular. Motors powered by ATPases likely deliver each power stroke in two parts, before and after ATP hydrolysis. Implications of these findings for analyzing hexameric helicase, F(1)F(0) ATPase, and kinesin are discussed. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS [ZIA DK036119-16] NR 113 TC 14 Z9 14 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1839-0 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2010 VL 39 BP 367 EP 385 DI 10.1146/annurev.biophys.093008.131415 PG 19 WC Biophysics SC Biophysics GA BPJ16 UT WOS:000278959400019 PM 20192763 ER PT S AU Lippincott-Schwartz, J Phair, RD AF Lippincott-Schwartz, Jennifer Phair, Robert D. BE Rees, DC Dill, KA Williamson, JR TI Lipids and Cholesterol as Regulators of Traffic in the Endomembrane System SO ANNUAL REVIEW OF BIOPHYSICS, VOL 39 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE sphingolipids; microdomains; Golgi; secretion; endocytosis partitioning; modeling ID ELEMENT-BINDING PROTEINS; TRANS-GOLGI NETWORK; PLASMA-MEMBRANE; LIVING CELLS; BREFELDIN-A; ENDOPLASMIC-RETICULUM; SECRETORY CARGO; SEC7 DOMAIN; ER-EXPORT; COMPLEX AB The endomembrane system of eukaryotic cells uses membrane-enclosed carriers to move diverse macromolecules among different membrane-bound compartments, a requirement for cells to secrete and take up molecules from their environment. Two recycling pathways-biosynthetic and endocytic, each with specific lipid components make up this system, with the Golgi apparatus mediating transport between the two. Here, we integrate lipid-based mechanisms into the description of this system. A partitioning model of the Golgi apparatus is discussed as a working hypothesis to explain how membrane lipids and proteins that are segregated based on lateral lipid partitioning support the unique composition of the biosynthetic and endocytic recycling pathways in the face of constant trafficking of molecular constituents. We further discuss how computational modeling can allow for interpretation of experimental findings and provide mechanistic insight into these important cellular pathways. C1 [Lippincott-Schwartz, Jennifer] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Phair, Robert D.] Integrat Bioinformat Inc, Los Altos, CA 94024 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov; rphair@integrativebioinformatics.com FU Intramural NIH HHS [ZIA HD001609-17]; NIGMS NIH HHS [R01 GM079305, R01 GM079305-04] NR 93 TC 60 Z9 60 U1 0 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1839-0 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2010 VL 39 BP 559 EP 578 DI 10.1146/annurev.biophys.093008.131357 PG 20 WC Biophysics SC Biophysics GA BPJ16 UT WOS:000278959400028 PM 20192772 ER PT S AU Raychaudhuri, S Prinz, WA AF Raychaudhuri, Sumana Prinz, William A. BE Schekman, R Goldstein, L Lehmann, R TI The Diverse Functions of Oxysterol-Binding Proteins SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE cholesterol; sterol; phosphoinositides; signaling; lipid transport; membranes; membrane contact sites; lipid transport proteins ID YEAST SACCHAROMYCES-CEREVISIAE; PLECKSTRIN HOMOLOGY DOMAIN; COENZYME-A REDUCTASE; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; PHOSPHATIDYLINOSITOL 4-PHOSPHATE; GOLGI-COMPLEX; PIECEMEAL MICROAUTOPHAGY; PHOSPHOLIPID-BINDING; VESICULAR TRANSPORT AB Oxysterol-binding protein (OSBP)-related proteins (ORPs) are lipid-binding proteins that are conserved from yeast to humans. They are implicated in many cellular processes including signaling, vesicular trafficking, lipid metabolism, and nonvesicular sterol transport. All ORPs contain an OSBP-related domain (ORD) that has a hydrophobic pocket that binds a single sterol. ORDs also contain additional membrane-binding surfaces, some of which bind phosphoinositides and may regulate sterol binding. Studies in yeast suggest that ORPs function as sterol transporters, perhaps in regions where organelle membranes are closely apposed. Yeast ORPs also participate in vesicular trafficking, although their role is unclear. In mammalian cells, some ORPs function as sterol sensors that regulate the assembly of protein complexes in response to changes in cholesterol levels. This review will summarize recent advances in our understanding of how ORPs bind lipids and membranes and how they function in diverse cellular processes. C1 [Raychaudhuri, Sumana; Prinz, William A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Raychaudhuri, S (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov OI Raychaudhuri, Sumana/0000-0002-3164-0057 FU Intramural NIH HHS [ZIA DK060004-10] NR 92 TC 83 Z9 84 U1 0 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3126-9 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2010 VL 26 BP 157 EP 177 DI 10.1146/annurev.cellbio.042308.113334 PG 21 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BSL42 UT WOS:000284856700007 PM 19575662 ER PT S AU Gardel, ML Schneider, IC Aratyn-Schaus, Y Waterman, CM AF Gardel, Margaret L. Schneider, Ian C. Aratyn-Schaus, Yvonne Waterman, Clare M. BE Schekman, R Goldstein, L Lehmann, R TI Mechanical Integration of Actin and Adhesion Dynamics in Cell Migration SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE F-actin cytoskeleton; adhesion maturation; traction force; adhesion strength; focal adhesion ID FLUORESCENT SPECKLE MICROSCOPY; EARLY MOLECULAR EVENTS; MYOSIN-II MOTOR; STRESS FIBERS; FOCAL ADHESIONS; INTEGRIN ACTIVATION; MATRIX ADHESIONS; TRACTION FORCES; ARP2/3 COMPLEX; LEADING-EDGE AB Directed cell migration is a physical process that requires dramatic changes in cell shape and adhesion to the extracellular matrix. For efficient movement, these processes must be spatiotemporally coordinated. To a large degree, the morphological changes and physical forces that occur during migration are generated by a dynamic filamentous actin (F-actin) cytoskeleton. Adhesion is regulated by dynamic assemblies of structural and signaling proteins that couple the F-actin cytoskeleton to the extracellular matrix. Here, we review current knowledge of the dynamic organization of the F-actin cytoskeleton in cell migration and the regulation of focal adhesion assembly and disassembly with an emphasis on how mechanical and biochemical signaling between these two systems regulate the coordination of physical processes in cell migration. C1 [Gardel, Margaret L.; Aratyn-Schaus, Yvonne] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Gardel, Margaret L.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA. [Schneider, Ian C.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA. [Schneider, Ian C.] Iowa State Univ, Dept Chem & Biol Engn, Ames, IA 50011 USA. [Schneider, Ian C.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA. [Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. RP Gardel, ML (reprint author), Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. EM gardel@uchicago.edu; watermancm@nhlbi.nih.gov RI Gardel, Margaret/D-1703-2012; OI Waterman, Clare/0000-0001-6142-6775; Schneider, Ian/0000-0002-4414-3842 FU NCCDPHP CDC HHS [DP10D00354]; NIH HHS [DP1 OD003354, DP1 OD003354-01, DP1 OD003354-02, DP1 OD003354-03, DP1 OD003354-04] NR 163 TC 302 Z9 304 U1 15 U2 126 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3126-9 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2010 VL 26 BP 315 EP 333 DI 10.1146/annurev.cellbio.011209.122036 PG 19 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BSL42 UT WOS:000284856700013 PM 19575647 ER PT S AU Melani, M Weinstein, BM AF Melani, Mariana Weinstein, Brant M. BE Schekman, R Goldstein, L Lehmann, R TI Common Factors Regulating Patterning of the Nervous and Vascular Systems SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE angiogenesis; axon guidance; guidance cues; guidance receptors ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; AXON GUIDANCE; TUMOR ANGIOGENESIS; C-ELEGANS; CARDIOVASCULAR DEVELOPMENT; NEUROTROPHIN RECEPTOR; NETRIN RECEPTOR; SEMAPHORIN-III; MUTANT MICE AB The vascular and the nervous systems of vertebrates share many features with similar and often overlapping anatomy. The parallels between these two systems extend to the molecular level, where recent work has identified ever-increasing similarities between the molecular mechanisms employed in the specification, differentiation, and patterning of both systems. This review discusses some of the most recent literature on this subject, with particular emphasis on the roles that the Ephrin, Semaphorin, Netrin, and Slit signaling pathways play in vascular development. C1 [Melani, Mariana; Weinstein, Brant M.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Melani, M (reprint author), NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. EM bw96w@nih.gov RI Xiao, Yang/B-5668-2012 FU Intramural NIH HHS NR 146 TC 38 Z9 40 U1 0 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3126-9 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2010 VL 26 BP 639 EP 665 DI 10.1146/annurev.cellbio.093008.093324 PG 27 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BSL42 UT WOS:000284856700025 PM 19575651 ER PT S AU Thomason, MK Storz, G AF Thomason, Maureen Kiley Storz, Gisela BE Campbell, A Lichten, M Schupbach, G TI Bacterial Antisense RNAs: How Many Are There, and What Are They Doing? SO ANNUAL REVIEW OF GENETICS, VOL 44 SE Annual Review of Genetics LA English DT Review; Book Chapter DE small RNA; gene regulation; transcription interference; mRNA stability ID COLE1 PLASMID REPLICATION; CLOSTRIDIUM-ACETOBUTYLICUM FERMENTATIONS; ANABAENA-SP PCC-7120; HOK MESSENGER-RNA; ESCHERICHIA-COLI; TARGET RNA; GENE-EXPRESSION; STAPHYLOCOCCUS-AUREUS; DOWN-REGULATION; NONCODING RNAS AB Antisense RNAs encoded on the DNA strand opposite another gene have the potential to form extensive base-pairing interactions with the corresponding sense RNA. Unlike other smaller regulatory RNAs in bacteria, antisense RNAs range in size from tens to thousands of nucleotides. The numbers of antisense RNAs reported for different bacteria vary extensively, but hundreds have been suggested in some species. If all of these reported antisense RNAs are expressed at levels sufficient to regulate the genes encoded opposite them, antisense RNAs could significantly impact gene expression in bacteria. Here, we review the evidence for these RNA regulators and describe what is known about the functions and mechanisms of action for some of these RNAs. Important considerations for future research as well as potential applications are also discussed. C1 [Thomason, Maureen Kiley; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Thomason, Maureen Kiley] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cell Biol, Washington, DC 20007 USA. RP Thomason, MK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM kileyma@mail.nih.gov; storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS [ZIA HD001608-18, ZIA HD001608-19] NR 124 TC 149 Z9 152 U1 1 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1244-2 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2010 VL 44 BP 167 EP 188 DI 10.1146/annurev-genet-102209-163523 PG 22 WC Genetics & Heredity SC Genetics & Heredity GA BSX32 UT WOS:000286042600008 PM 20707673 ER PT S AU Parker, HG Shearin, AL Ostrander, EA AF Parker, Heidi G. Shearin, Abigail L. Ostrander, Elaine A. BE Campbell, A Lichten, M Schupbach, G TI Man's Best Friend Becomes Biology's Best in Show: Genome Analyses in the Domestic Dog SO ANNUAL REVIEW OF GENETICS, VOL 44 SE Annual Review of Genetics LA English DT Review; Book Chapter DE GWAS; linkage disequilibrium; genomics; canine; domestication; complex traits ID DUCHENNE MUSCULAR-DYSTROPHY; NEURONAL CEROID-LIPOFUSCINOSIS; VON-WILLEBRANDS-DISEASE; HORMONE-RECEPTOR GENE; ENGLISH-SETTER DOGS; COAT COLOR; LINKAGE DISEQUILIBRIUM; CONE DEGENERATION; GOLDEN-RETRIEVER; CANINE GENOME AB In the last five years, canine genetics has gone from map construction to complex disease deconstruction. The availability of a draft canine genome sequence, dense marker chips, and an understanding of the genome architecture has changed the types of studies canine geneticists can undertake. There is now a clear recognition that the dog system offers the opportunity to understand the genetics of both simple and complex traits, including those associated with morphology, disease susceptibility, and behavior. In this review, we summarize recent findings regarding canine domestication and review new information on the organization of the canine genome. We discuss studies aimed at finding genes controlling morphological phenotypes and provide examples of the way such paradigms may be applied to studies of behavior. We also discuss the many ways in which the clog has illuminated our understanding of human disease and conclude with a discussion on where the field is likely headed in the next five years. C1 [Parker, Heidi G.; Shearin, Abigail L.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Shearin, Abigail L.] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. RP Parker, HG (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z99 HG999999] NR 169 TC 70 Z9 73 U1 16 U2 98 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1244-2 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2010 VL 44 BP 309 EP 336 DI 10.1146/annurev-genet-102808-115200 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA BSX32 UT WOS:000286042600014 PM 21047261 ER PT S AU Winkler, CA Nelson, GW Smith, MW AF Winkler, Cheryl A. Nelson, George W. Smith, Michael W. BE Chakravarti, A Green, E TI Admixture Mapping Comes of Age SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 11 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE mapping by admixture linkage disequilibrium; risk loci; genetic mapping; hidden Markov chain; health disparities ID NUCLEOTIDE-POLYMORPHISM PANEL; NUTRITION EXAMINATION SURVEY; DISEASE-GENE DISCOVERY; LINKAGE DISEQUILIBRIUM; AFRICAN-AMERICAN; POPULATION-STRUCTURE; ADMIXED POPULATIONS; BREAST-CANCER; MEXICAN-AMERICANS; PROSTATE-CANCER AB Admixture mapping is based on the hypothesis that differences in disease rates between populations are due in part to frequency differences in disease-causing genetic variants. In admixed populations, these genetic variants occur more often on chromosome segments inherited from the ancestral population with the higher disease variant frequency. A genome scan for disease association requires only enough markers to identify the ancestral chromosome segments; for recently admixed populations, such as African Americans, 1,500-2,500 ancestry-informative markers (ATMs) are sufficient. The method was proposed over 50 years ago, but the AIM panels and statistical methods required have only recently become available. Since the first admixture scan in 2005, the genetic bases for a range of diseases/traits have been identified by admixture mapping. Here, we provide a historical perspective, review AIM panels and software packages, and discuss recent successes and unexpected insights into human diseases that exhibit disparate rates across human populations. C1 [Winkler, Cheryl A.; Nelson, George W.] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. [Smith, Michael W.] NCI Frederick, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Winkler, CA (reprint author), NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. EM winklerc@mail.nih.gov RI Smith, Michael/B-5341-2012 NR 86 TC 94 Z9 96 U1 0 U2 30 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3711-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2010 VL 11 BP 65 EP 89 DI 10.1146/annurev-genom-082509-141523 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA BRG14 UT WOS:000282662200004 PM 20594047 ER PT S AU McBride, CM Wade, CH Kaphingst, KA AF McBride, Colleen M. Wade, Christopher H. Kaphingst, Kimberly A. BE Chakravarti, A Green, E TI Consumers' Views of Direct-to-Consumer Genetic Information SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 11 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE genetic testing; health communication; genetic competency; translational research; decision making; health behavior ID NONPOLYPOSIS COLORECTAL-CANCER; MANAGED CARE ORGANIZATION; BREAST-OVARIAN CANCER; UNITED-STATES; SCREENING PRACTICES; MARKETING CAMPAIGN; RISK COMMUNICATION; ALZHEIMER-DISEASE; HEALTH BEHAVIOR; SUSCEPTIBILITY AB In this report, we describe the evolution and types of genetic information provided directly to consumers, discuss potential advantages and disadvantages of these products, and review research evaluating consumer responses to direct-to-consumer (DTC) genetic testing. The available evidence to date has focused on predictive tests and does not suggest that individuals, health care providers, or health care systems have been harmed by a DTC provision of genetic information. An understanding of consumer responses to susceptibility tests has lagged behind. The Multiplex Initiative is presented as a case study of research to understand consumers' responses to DTC susceptibility tests. Three priority areas are recommended for accelerated research activities to inform public policy regarding DTC genetic information: (a) exploring consumer's long-term responses to DTC genetic testing on a comprehensive set of outcomes, (b) evaluating optimal services to support decision making about genetic testing, and (c) evaluating best practices in promoting genetic competencies among health providers. C1 [McBride, Colleen M.; Wade, Christopher H.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Kaphingst, Kimberly A.] Washington Univ, Hlth Commun Res Lab, St Louis, MO 63112 USA. RP McBride, CM (reprint author), NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov; wadec@mail.nih.gov; kkaphingst@gwbmail.wustl.edu FU Intramural NIH HHS; NCI NIH HHS [U19 CA 079689] NR 99 TC 39 Z9 39 U1 5 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3711-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2010 VL 11 BP 427 EP 446 DI 10.1146/annurev-genom-082509-141604 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA BRG14 UT WOS:000282662200018 PM 20690815 ER PT S AU Mascola, JR Montefiori, DC AF Mascola, John R. Montefiori, David C. BE Paul, WE Littman, DR Yokoyama, WM TI The Role of Antibodies in HIV Vaccines SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 28 SE Annual Review of Immunology LA English DT Review; Book Chapter DE envelope glycoprotein; neutralizing antibodies; vaccine design ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; AUTOLOGOUS NEUTRALIZING ANTIBODY; HUMORAL IMMUNE-RESPONSES; ENVELOPE GLYCOPROTEIN COMPLEX; GP160 RECOMBINANT VACCINIA; CROSS-CLADE NEUTRALIZATION; PROXIMAL EXTERNAL REGION; 2ND HYPERVARIABLE REGION; HIV-1/SIV CHIMERIC VIRUS AB Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of host cells or that limit early events cif viral dissemination. Such antibodies must target the surface envelope glycoproteins of HIV-1, which are highly variable in sequence and structure. The first subunit vaccines to enter clinical trails were safe and immunogenic but unable to elicit antibodies that neutralized most circulating strains of HALL However, potent virus neutralizing antibodies (NAbs) can develop during the course of HIV-1 infection, and this is the type of antibody response that researchers seek to generate with a vaccine. Thus, current vaccine design efforts have focused on a more detailed understanding of these broadly neutralizing antibodies and their epitopes to inform the design of improved vaccines. C1 [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jmascola@nih.gov; monte@duke.edu NR 242 TC 256 Z9 261 U1 6 U2 47 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3028-6 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2010 VL 28 BP 413 EP 444 DI 10.1146/annurev-immunol-030409-101256 PG 32 WC Immunology SC Immunology GA BOR04 UT WOS:000277363600017 PM 20192810 ER PT S AU Zhu, JF Yamane, H Paul, WE AF Zhu, Jinfang Yamane, Hidehiro Paul, William E. BE Paul, WE Littman, DR Yokoyama, WM TI Differentiation of Effector CD4 T Cell Populations SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 28 SE Annual Review of Immunology LA English DT Review; Book Chapter DE CD4 effector T cells; regulatory T cells; T cell differentiation; cytokines; transcription factors; human diseases ID FOLLICULAR-HELPER-CELLS; NF-KAPPA-B; TRANSCRIPTION FACTOR FOXP3; IFN-GAMMA PRODUCTION; HYPER-IGE SYNDROME; INTERFERON-REGULATORY FACTOR-4; LOCUS-CONTROL REGION; NONRECEPTOR TYROSINE KINASE; ARYL-HYDROCARBON RECEPTOR; CYTOKINE GENE-EXPRESSION AB CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation. C1 [Zhu, Jinfang; Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov; hyamane@niaid.nih.gov; wpaul@niaid.nih.gov; wpaul@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012; jia, xu/A-8386-2016 FU Intramural NIH HHS [Z99 AI999999] NR 310 TC 957 Z9 1003 U1 29 U2 210 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3028-6 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2010 VL 28 BP 445 EP 489 DI 10.1146/annurev-immunol-030409-101212 PG 45 WC Immunology SC Immunology GA BOR04 UT WOS:000277363600018 PM 20192806 ER PT S AU Major, EO AF Major, Eugene O. TI Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE demyelination; viral latency and reactivation; cell tropism factors; immune system dysfunction; biological therapies for autoimmune diseases ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC PROGENITOR CELLS; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; JC VIRUS; NUCLEOTIDE-SEQUENCES; ANTIBODY NATALIZUMAB; CEREBROSPINAL-FLUID; PROLONGED SURVIVAL; HUMAN POLYOMAVIRUS AB Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the white matter of the human brain caused by lytic infection of oligodendrocytes with the human polyomavirus JCV Although the majority of PML cases occur in severely immune-suppressed individuals, with HIV-1 infection as the predominant factor, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies that modulate immune system functions. Monoclonal antibodies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri (R) for multiple sclerosis and Crohn's disease) or LFA-1 (efalizumab; Raptiva (R) for severe forms of plaque psoriasis) to prevent extravasation of inflammatory T cells into tissues, or target the cell surface marker CD20 (rituximab; Rituxan (R) for hematologic malignancies and rheumatoid arthritis) to deplete peripheral circulating B cells, have all been associated with PML. The link between the effects of these therapies on the immune system and the occurrence of PML has prompted investigations oil JCV sites of latency in the bone marrow, the migration of bone marrow derived cells into the circulation, and intracellular virus entry into the brain. C1 NINDS, Lab Mol Med & Neurosci, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, Div Intramural Res, NIH, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX The author has no conflicts and receives all laboratory support as a Senior Investigator of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 57 TC 224 Z9 226 U1 4 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0561-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 35 EP 47 DI 10.1146/annurev.med.080708.082655 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600003 PM 19719397 ER PT S AU Hazra, R Siberry, GK Mofenson, LM AF Hazra, Rohan Siberry, George K. Mofenson, Lynne M. TI Growing Up with HIV: Children, Adolescents, and Young Adults with Perinatally Acquired HIV Infection SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE human immunodeficiency virus; mother-to-child transmission; pediatric HIV infection; highly active antiretroviral therapy; metabolic complications ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MINERAL DENSITY; TENOFOVIR DISOPROXIL FUMARATE; OPTIMIZED BACKGROUND REGIMEN; QUALITY-OF-LIFE; UNITED-STATES; RISK-FACTORS; INSULIN-RESISTANCE; VIRAL LOAD AB Tremendous success in the prevention and treatment of pediatric HIV in high-resource countries has changed the face of the epidemic. A perinatally HIV-infected child now faces a chronic disease rather than a progressive, fatal one. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. These include maintaining adherence to long-term, likely life-long therapy; selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations and the lack of pharmacokinetic and safety data in children; and overcoming extensive drug resistance in multi-drug-experienced children. Pediatric HIV care now focuses on morbidity related to long-term HIV infection and its treatment. Survival into adulthood of perinatally HIV-infected youth in high-resource countries encourages expansion of pediatric treatment programs in low-resource countries, where most HIV-infected children live, and provides important lessons about how the epidemic changes with increasing access to antiretroviral therapy for children. C1 [Hazra, Rohan; Siberry, George K.; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Hazra, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. EM hazrar@mail.nih.gov; siberryg@mail.nih.gov; LM65D@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 90 TC 90 Z9 91 U1 2 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0561-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 169 EP 185 DI 10.1146/annurev.med.050108.151127 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600012 PM 19622036 ER PT J AU Linehan, WM Bratslavsky, G Pinto, PA Schmidt, LS Neckers, L Bottaro, DP Srinivasan, R AF Linehan, W. Marston Bratslavsky, Gennady Pinto, Peter A. Schmidt, Laura S. Neckers, Len Bottaro, Donald P. Srinivasan, Ramaprasad TI Molecular Diagnosis and Therapy of Kidney Cancer SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE kidney neoplasms; VHL; MET; BHD; TSC1; TSC2; fumarate hydratase succinate dehydrogenase ID RENAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; PARENCHYMAL SPARING SURGERY; TUMOR-SUPPRESSOR GENE; TUBEROUS SCLEROSIS COMPLEX; HIPPEL-LINDAU-DISEASE; ROBOTIC PARTIAL NEPHRECTOMY; ENDOTHELIAL GROWTH-FACTOR; CARBONIC-ANHYDRASE-IX; HEREDITARY LEIOMYOMATOSIS AB Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each having a different histology, following a different clinical course, responding differently to therapy, and caused by a different gene. Study of the genes underlying kidney cancer has revealed that it is fundamentally a metabolic disorder. Understanding the genetic basis of cancer of the kidney has significant implications for diagnosis and management of this disease. VHL is the gene for clear cell kidney cancer. The VHL protein forms a complex that targets the hypoxia-inducible factors for ubiquitin-mediated degradation. Knowledge of this pathway provided the foundation for the development of novel therapeutic approaches now approved for treatment of this disease. MET is the gene for the hereditary form of type I papillary renal carcinoma and is mutated in a subset of sporadic type I Papillary kidney cancers. Clinical trials are currently ongoing with agents targeting the tyrosine kinase domain of MET in sporadic and hereditary forms of papillary kidney cancer. BHD is the gene for the hereditary type of chromophobe kidney cancer. It is thought to be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. Hereditary leiomyomatosis renal cell carcinoma, a hereditary form of type 2 papillary renal carcinoma, is caused by inactivation of a Krebs cycle enzyme due to mutation. Knowledge of these kidney cancer gene pathways has enabled new approaches in the management of this disease and has provided the foundation for the development of targeted therapeutics. C1 [Linehan, W. Marston; Bratslavsky, Gennady; Pinto, Peter A.; Schmidt, Laura S.; Neckers, Len; Bottaro, Donald P.; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Schmidt, Laura S.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM WML@nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU National Institutes of Health [HHSN261200800001E]; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Set-vices, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors acknowledge outstanding editorial and graphics support by Georgia Shaw and Masaya Baba, MD, PhD. NR 94 TC 82 Z9 84 U1 1 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 329 EP 343 DI 10.1146/annurev.med.042808.171650 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600022 PM 20059341 ER PT S AU Schiller, JT Lowy, DR AF Schiller, John T. Lowy, Douglas R. BE Gottesman, S Harwood, CS TI Vaccines to Prevent Infections by Oncoviruses SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 64, 2010 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE HBV; HPV; HCV; KSHV; EBV; HTLV ID EPSTEIN-BARR-VIRUS; HEPATITIS-C-VIRUS; T-CELL LEUKEMIA; HUMAN-PAPILLOMAVIRUS INFECTIONS; SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; B-VIRUS; HEPATOCELLULAR-CARCINOMA; PARTICLE VACCINE; KAPOSIS-SARCOMA AB It has been estimated that viruses are etiological agents in approximately 12% of human cancers Most of these cancers can be attributed to infections by human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), and Kaposi's sarcoma associated herpesvirus (KSHV) Prophylactic vaccines against other pathogenic viruses have an excellent record as public health interventions in teams of safety, effectiveness, and ability to reach economically disadvantaged populations These considerations should prompt efforts to develop and implement vaccines against oncoviruses Safe and effective HBV and HPV vaccines, based on virus-like particles, are commercially available, and the major focus is now on vaccine delivery, especially to low-resource settings HCV and EBV vaccines are under active development, but few clinical trials have been conducted, and none of the candidate vaccines has proven to be sufficiently effective to warrant commercialization Efforts to develop KSHV vaccines have been more limited C1 [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 86 TC 39 Z9 40 U1 3 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1164-3 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2010 VL 64 BP 23 EP 41 DI 10.1146/annurev.micro.112408.134019 PG 19 WC Microbiology SC Microbiology GA BSA47 UT WOS:000284030600002 PM 20420520 ER PT S AU Noinaj, N Guillier, M Barnard, TJ Buchanan, SK AF Noinaj, Nicholas Guillier, Maude Barnard, Travis J. Buchanan, Susan K. BE Gottesman, S Harwood, CS TI TonB-Dependent Transporters: Regulation, Structure, and Function SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 64, 2010 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE outer membrane protein; siderophore; active transport; signal transduction ID OUTER-MEMBRANE RECEPTOR; PERIPLASMIC SIGNALING DOMAIN; COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; PSEUDOMONAS-AERUGINOSA; IRON TRANSPORT; COBALAMIN TRANSPORTER; R-DOMAIN; TRANSCRIPTION INITIATION AB TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that bind and transport ferric chelates, called siderophores, as well as vitamin B(12), nickel complexes, and carbohydrates The transport process requires energy in the form of proton motive force and a complex of three inner membrane proteins, TonB-ExbB-ExbD, to transduce this energy to the outer membrane The siderophore substrates range in complexity from simple small molecules such as citrate to large proteins such as serum transferrin and hemoglobin Because iron uptake is vital for almost all bacteria, expression of TBDTs is regulated in a number of ways that include metal-dependent regulators, sigma/anti-sigma factor systems, small RNAs, and even a riboswitch In recent years, many new structures of TBDTs have been solved in various states, resulting in a more complete understanding of siderophore selectivity and binding, signal transduction across the outer membrane, and interaction with the TonB-ExbB-ExbD complex However, the transport mechanism is still unclear In this review, we summarize recent progress in understanding regulation, structure, and function in TBDTs and questions remaining to be answered C1 [Noinaj, Nicholas; Barnard, Travis J.; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Guillier, Maude] CNRS, Inst Biol Physicochim, UPR 9073, F-75005 Paris, France. RP Noinaj, N (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 90 TC 218 Z9 220 U1 6 U2 79 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1164-3 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2010 VL 64 BP 43 EP 60 DI 10.1146/annurev.micro.112408.134247 PG 18 WC Microbiology SC Microbiology GA BSA47 UT WOS:000284030600003 PM 20420522 ER PT S AU Otto, M AF Otto, Michael BE Gottesman, S Harwood, CS TI Basis of Virulence in Community-Associated Methicillin-Resistant Staphylococcus aureus SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 64, 2010 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE MRSA; community-associated infections; Panton-Valentine leukocidin ID PANTON-VALENTINE LEUKOCIDIN; CATABOLIC MOBILE ELEMENT; CASSETTE CHROMOSOME MEC; SOFT-TISSUE INFECTIONS; ALPHA-TOXIN; MOLECULAR EPIDEMIOLOGY; UNITED-STATES; POLYMORPHONUCLEAR LEUKOCYTES; NECROTIZING PNEUMONIA; HUMAN NEUTROPHILS AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are causing a severe pandemic of mainly skin and soft tissue and occasionally fatal infections The basis of their success is the combination of methicillin resistance at low fitness cost and high virulence Investigation of the virulence potential of CA-MRSA, a key prerequisite for the development of anti-CA-MRSA therapeutics, has focused on strain USA300, which is responsible for the most serious CA-MRSA epidemic seen in the United States Current data indicate that in this strain virulence evolved via increased expression of core-genome-encoded virulence determinants, such as alpha-toxin and phenol-soluble modulins, and acquisition of the phage-encoded Panton-Valentine leukocidin (PVL) genes All these toxins impact disease progression in animal models of USA300 infection In contrast, the basis of virulence in other CA-MRSA epidemics, v, Inch also include PVL-negative strains, is poorly understood C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 134 TC 215 Z9 223 U1 7 U2 56 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1164-3 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2010 VL 64 BP 143 EP 162 DI 10.1146/annurev.micro.112408.134309 PG 20 WC Microbiology SC Microbiology GA BSA47 UT WOS:000284030600008 PM 20825344 ER PT S AU Forbes, CE Grafman, J AF Forbes, Chad E. Grafman, Jordan BE Hyman, SE TI The Role of the Human Prefrontal Cortex in Social Cognition and Moral Judgment SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 33 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE implicit and explicit social cognitive and moral judgment processing; frontal lobes; neural function; social cognitive neuroscience; structured event complex theory ID ANTERIOR CINGULATE CORTEX; HIGH-FUNCTIONING AUTISM; NEURAL FOUNDATIONS; ELECTION OUTCOMES; ASPERGER-SYNDROME; EVENT KNOWLEDGE; IN-GROUP; BRAIN; SELF; IMPLICIT AB Results from functional magnetic resonance imaging and lesion studies indicate that the prefrontal cortex (PFC) is essential for successful navigation through a complex social world inundated with intricate norms and moral values. This review examines regions of the PFC that are critical for implicit and explicit social cognitive and moral judgment processing. Considerable overlap between regions active when individuals engage in social cognition or assess moral appropriateness of behaviors is evident, underscoring the similarity between social cognitive and moral judgment processes in general. Findings are interpreted within the framework of structured event complex theory, providing a broad organizing perspective for how activity in PFC neural networks facilitates social cognition and moral judgment. We emphasize the dynamic flexibility in neural circuits involved in both implicit and explicit processing and discuss the likelihood that neural regions thought to uniquely underlie both processes heavily interact in response to different contextual primes. C1 [Forbes, Chad E.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. EM forbesce@cc.nih.gov; GrafmanJ@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS NR 112 TC 100 Z9 104 U1 4 U2 45 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2433-9 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2010 VL 33 BP 299 EP 324 DI 10.1146/annurev-neuro-060909-153230 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BRP46 UT WOS:000283330200014 PM 20350167 ER PT S AU Phang, JM Liu, W Zabirnyk, O AF Phang, James M. Liu, Wei Zabirnyk, Olga BE Cousins, RJ TI Proline Metabolism and Microenvironmental Stress SO ANNUAL REVIEW OF NUTRITION, VOL 30 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE cancer; collagen; bioenergetics; tumor suppressor; microRNA; oxLDL ID ACTIVATED-RECEPTOR-GAMMA; CANCER STEM-CELLS; DELTA(1)-PYRROLINE-5-CARBOXYLATE SYNTHASE; EXTRACELLULAR-MATRIX; PYRROLINE-5-CARBOXYLATE REDUCTASE; PROLIDASE ACTIVITY; COLLAGEN-METABOLISM; ENZYMATIC-SYNTHESIS; REDUCED ORNITHINE; INDUCED APOPTOSIS AB Proline, the only proteinogenic secondary amino acid, is metabolized by its own family of enzymes responding to metabolic stress and participating in metabolic signaling. Collagen in extracellular matrix, connective tissue, and bone is an abundant reservoir for prolific. Matrix metalloproteinases degrading collagen are activated during stress to make proline available, and proline oxidase, the first enzyme in proline degradation, is induced by p53, peroxisome proliferator-activated receptor gamma (PPAR gamma) and its ligands, and by AMP-activated protein kinase downregulating mTOR. Metabolism of prolific generates electrons to produce ROS and initiates a variety of downstream effects, including blockade of the cell cycle, autophagy, and apoptosis. The electrons can also enter the electron transport chain to produce adenosine triphosphate for survival under nutrient stress. Pyrroline-5-carboxylate, the product of prolific oxidation, is recycled back to proline with redox transfers or is sequentially converted to glutamate and alpha-ketoglutarate. The latter augments the prolyl hydroxylation of hypoxia-inducible factor-1 alpha and its proteasomal degradation. These effects of proline oxidase, as well as its decreased levels in tumors, support its role as a tumor suppressor. The mechanism for its decrease is mediated by a specific microRNA. The metabolic signaling by prolific oxidase between oxidized low-density lipoproteins and autophagy provides a functional link between obesity and increased cancer risk. C1 [Phang, James M.; Liu, Wei; Zabirnyk, Olga] NCI, Metab & Canc Susceptibil Sect, Lab Comparat Carcinogenesis, Ctr Canc Res, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Lab Comparat Carcinogenesis, Ctr Canc Res, Frederick, MD 21702 USA. EM phangj@mail.nih.gov RI liu, wei /E-7340-2012 FU Intramural NIH HHS; PHS HHS [HHSN27612080001] NR 118 TC 74 Z9 76 U1 2 U2 32 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2830-6 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2010 VL 30 BP 441 EP 463 DI 10.1146/annurev.nutr.012809.104638 PG 23 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BRN63 UT WOS:000283182500021 PM 20415579 ER PT S AU Young, BC Levine, RJ Karumanchi, SA AF Young, Brett C. Levine, Richard J. Karumanchi, S. Ananth TI Pathogenesis of Preeclampsia SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE hypertension; pregnancy; sFltl; placenta; ischemia ID ENDOTHELIAL-GROWTH-FACTOR; ELEVATED LIVER-ENZYMES; FACTOR RECEPTOR-1; TYROSINE KINASE-1; SOLUBLE ENDOGLIN; ANGIOTENSIN-II; GESTATIONAL HYPERTENSION; PREGNANT-WOMEN; TROPHOBLAST DIFFERENTIATION; AGONISTIC AUTOANTIBODIES AB Preeclampsia is a systemic syndrome that occurs in 3 to 5% of pregnant women and classically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. The only known cure is delivery of the placenta. Recent discoveries, however, have led to important advances in understanding the Pathogenesis of the condition. Placental antiangiogenic factors are upregulated and disrupt the maternal endothelium. This change in the normal angiogenic balance toward an antiangiogenic state can result in hypertension, proteinuria, glomerular endotheliosis, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and cerebral edema-the clinical signs of preeclampsia and eclampsia. The regulation of these antiangiogenic factors in the placenta is unknown. The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease. C1 [Young, Brett C.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Young, Brett C.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02215 USA. RP Young, BC (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU Intramural NIH HHS NR 118 TC 243 Z9 264 U1 7 U2 45 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4305-7 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2010 VL 5 BP 173 EP 192 DI 10.1146/annurev-pathol-121808-102149 PG 20 WC Pathology SC Pathology GA 562DU UT WOS:000275030400008 PM 20078220 ER PT S AU Patterson, G Davidson, M Manley, S Lippincott-Schwartz, J AF Patterson, George Davidson, Michael Manley, Suliana Lippincott-Schwartz, Jennifer BE Leone, SR Cremer, PS Groves, JT Johnson, MA Richmond, G TI Superresolution Imaging using Single-Molecule Localization SO ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 61 SE Annual Review of Physical Chemistry LA English DT Review; Book Chapter DE superresolution microscopy; single molecule; PALM; STORM; FPALM; diffraction limit; photoactivation; photoactivatable fluorescent protein; fluorescence imaging ID GREEN FLUORESCENT PROTEIN; STRUCTURED-ILLUMINATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; HAND-OVER-HAND; LIVING CELLS; DIFFRACTION-LIMIT; QUANTUM DOTS; IN-VIVO; 3-DIMENSIONAL SUPERRESOLUTION; LIVE CELLS AB Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (similar to 10-20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule-based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. C1 [Patterson, George] Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bethesda, MD 20892 USA. [Davidson, Michael] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Davidson, Michael] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. [Manley, Suliana] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. [Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Patterson, G (reprint author), Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov RI Manley, Suliana/D-3818-2012 OI Manley, Suliana/0000-0002-4755-4778 FU Intramural NIH HHS [Z01 HD001609-15] NR 83 TC 267 Z9 271 U1 17 U2 171 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-426X BN 978-0-8243-1061-5 J9 ANNU REV PHYS CHEM JI Annu. Rev. Phys. Chem. PY 2010 VL 61 BP 345 EP 367 DI 10.1146/annurev.physchem.012809.103444 PG 23 WC Chemistry, Physical SC Chemistry GA BOX60 UT WOS:000277960500017 PM 20055680 ER PT S AU Garantziotis, S Schwartz, DA AF Garantziotis, Stavros Schwartz, David A. BE Fielding, JE Brownson, RC Green, LW TI Ecogenomics of Respiratory Diseases of Public Health Significance SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 31 SE Annual Review of Public Health LA English DT Review; Book Chapter DE asthma; COPD; pulmonary fibrosis; respiratory infection; gene-environment interactions ID MANNOSE-BINDING LECTIN; IDIOPATHIC PULMONARY-FIBROSIS; GENE-ENVIRONMENT INTERACTIONS; COMMUNITY-ACQUIRED PNEUMONIA; VIRUS-INFECTION; SEPTIC SHOCK; LUNG-DISEASE; PNEUMOCOCCAL INFECTION; OCCUPATIONAL-EXPOSURE; HISTONE DEACETYLASE AB Gene-environment interactions are the indisputable cause of most respiratory diseases. However, we still have very limited understanding of the mechanisms that guide these interactions. Although the conceptual approaches to environmental genomics were established several decades ago, the tools are only now available to better define the mechanisms that underlie the interactions among these important etiological features ()flung disease. In this article, we summarize recent insights in the environmental genomics (ecogenomics) of common nonmalignant respiratory diseases (asthma, COPD, pulmonary fibrosis, and respiratory infections), describe the framework of gene-environment interactions that inform the pathogenesis of respiratory diseases, and propose future research directions that will help translate scientific advances into public health gains. C1 [Garantziotis, Stavros] Natl Inst Environm Hlth Sci, Clin Res Program, Res Triangle Pk, NC 27709 USA. [Garantziotis, Stavros] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Schwartz, David A.] Natl Jewish Hlth, Div Pulm & Crit Care Med, Denver, CO 80206 USA. [Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA. RP Garantziotis, S (reprint author), Natl Inst Environm Hlth Sci, Clin Res Program, Res Triangle Pk, NC 27709 USA. EM Garantziotis@niehs.nih.gov; SchwartzD@NJHealth.org RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS [Z01 ES102605-01, ZIA ES102605-02, ZIA ES102605-03, ZIA ES102605-04] NR 100 TC 5 Z9 5 U1 0 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2731-6 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2010 VL 31 BP 37 EP 51 DI 10.1146/annurev.publhealth.012809.103633 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BOX22 UT WOS:000277908800004 PM 20070197 ER PT S AU McBride, CM Koehly, LM Sanderson, SC Kaphingst, KA AF McBride, Colleen M. Koehly, Laura M. Sanderson, Saskia C. Kaphingst, Kimberly A. BE Fielding, JE Brownson, RC Green, LW TI The Behavioral Response to Personalized Genetic Information: Will Genetic Risk Profiles Motivate Individuals and Families to Choose More Healthful Behaviors? SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 31 SE Annual Review of Public Health LA English DT Review; Book Chapter DE genomics; behavior change; common disease; social networks; literacy ID NONPOLYPOSIS COLORECTAL-CANCER; SICKLE-CELL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; AFRICAN-AMERICAN SMOKERS; PSYCHOLOGICAL IMPACT; SMOKING-CESSATION; SCREENING PRACTICES; ENDOMETRIAL CANCER; SOCIAL NETWORK; SUSCEPTIBILITY AB This report describes the use of information emerging from genetic discovery to motivate risk-reducing health behaviors. Most research to date has evaluated the effects of information related to rare genetic variants on screening behaviors, in which genetic risk feedback has been associated consistently with improved screening adherence. The limited research with common genetic variants suggests that genetic information, when based on single-gene variants with low-risk probabilities, has little impact on behavior. The effect on behavioral outcomes of more realistic testing scenarios in which genetic risk is based on numerous genetic variants is largely unexplored. Little attention has been directed to matching genetic information to the literacy levels of target audiences. Another promising area for research is consideration of using genetic information to identify risk shared within kinship networks and to expand the influence of behavior change beyond the individual. C1 [McBride, Colleen M.; Koehly, Laura M.; Kaphingst, Kimberly A.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Sanderson, Saskia C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. RP McBride, CM (reprint author), NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov; koehlyl@mail.nih.gov; saskia.sanderson@mssm.edu; kkaphing@mail.nih.gov NR 83 TC 107 Z9 107 U1 4 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2731-6 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2010 VL 31 BP 89 EP 103 DI 10.1146/annurev.publhealth.012809.103532 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BOX22 UT WOS:000277908800007 PM 20070198 ER PT S AU Colditz, GA Taylor, PR AF Colditz, Graham A. Taylor, Philip R. BE Fielding, JE Brownson, RC Green, LW TI Prevention Trials: Their Place in How We Understand the Value of Prevention Strategies SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 31 SE Annual Review of Public Health LA English DT Review; Book Chapter DE durability; adherence; bias; behavior modification; drugs; intention-to-treat ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; ESTROGEN PLUS PROGESTIN; DESIGN AFFECTS OUTCOMES; BOWEL PROJECT P-1; CANCER PREVENTION; COLORECTAL ADENOMAS; BETA-CAROTENE; PUBLIC-HEALTH AB Several key factors bear on the interpretation of prevention trials and observational studies that inform prevention strategies. These factors include the underlying disease process and aspects of the intervention: sustainability of behavior change, the time course of the intervention within the disease process, dose and duration of exposure needed to effect risk reduction, durability of the impact of intervention, and methodological problems in implementing and interpreting randomized trials and observational studies to evaluate prevention strategies. The question asked through an intent-to-treat analysis of a randomized controlled trial (RCT) differs from that in the observational setting. Furthermore, the long duration necessary to conduct prevention trials and the resulting lack of adherence to therapy can bias results toward the null. A broader range of approaches to evaluate prevention interventions and programs with improved knowledge synthesis and translation to public health practice will speed our progress toward achieving public health and prevention of chronic diseases. C1 [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Colditz, GA (reprint author), Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. EM colditzg@wustl.edu; ptaylor@mail.nih.gov RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [P30 CA091842] NR 80 TC 4 Z9 4 U1 1 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2731-6 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2010 VL 31 BP 105 EP 120 DI 10.1146/annurev.publhealth.121208.131051 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BOX22 UT WOS:000277908800008 PM 20070190 ER PT S AU Macvanin, M Hughes, D AF Macvanin, Mirjana Hughes, Diarmaid BE Gillespie, SH McHugh, TD TI Assays of Sensitivity of Antibiotic-Resistant Bacteria to Hydrogen Peroxide and Measurement of Catalase Activity SO ANTIBIOTIC RESISTANCE PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Antibiotic resistance; Fitness cost; Reactive oxygen species; Hydrogen peroxide; Catalase; Salmonella typhimurium ID ENTERICA SEROVAR TYPHIMURIUM; ESCHERICHIA-COLI-B; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; HYDROPEROXIDASE-II; GENE-PRODUCT; RESPONSES; STRESS; PURIFICATION; MACROPHAGES AB Bacteria, in common with other organisms that take advantage of aerobic respiration, generate and accumulate reactive oxygen species (ROS) that damage DNA, fatty acids, and proteins. In addition, intracellular pathogens like Salmonella enterica are exposed to an oxidate burst produced by host macrophages. The relative ability of aerobically growing bacteria to withstand oxidative stress and eliminate ROS has a large impact of their fitness in vitro and in vivo. Methods arc described here to measure the viability and relative fitness or bacteria in the presence of hydrogen peroxide. A protocol for the determination of catalase activity, an important part of the ROS detoxification process, is also described. C1 [Macvanin, Mirjana] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hughes, Diarmaid] Uppsala Univ, Dept Cell & Mol Biol, Microbiol Programme, Uppsala, Sweden. RP Macvanin, M (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Hughes, Diarmaid/A-9487-2014 OI Hughes, Diarmaid/0000-0002-7456-9182 NR 26 TC 4 Z9 4 U1 2 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-278-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 642 BP 95 EP 103 DI 10.1007/978-1-60327-279-7_7 D2 10.1007/978-1-60327-279-7 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BOO68 UT WOS:000277155600007 PM 20401588 ER PT S AU Hughes, D Macvanin, M AF Hughes, Diarmaid Macvanin, Mirjana BE Gillespie, SH McHugh, TD TI Measurements of Heme Levels and Respiration Rate in Salmonella enterica Serovar Typhimurium SO ANTIBIOTIC RESISTANCE PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Antibiotic resistance; Fitness costs; Heme; Respiration; Salmonella typhimurium; Aminolevulinic acid (ALA) ID ACID-RESISTANT MUTANTS; RNA REDUCTASE HEMA; ESCHERICHIA-COLI; OXIDATIVE STRESS; DNA-DAMAGE; BIOSYNTHESIS; GENE; IDENTIFICATION; PROTEIN AB This chapter describes assays for the measurement of heme levels and the rate of respiration in bacteria. An assay of ALA supplementation is described, in which the effect of exogenous ALA in reversing sensitivity to hydrogen peroxide is an indication of a reduced flow through the heme biosynthesis pathway. A protocol for measurement of the relative amount of heme by a fluorescence assay, based on stripping the iron from the heme moiety, leaving a protoporphyrin molecule which fluoresces following excitation at 400 nm, is also provided. Finally, a method for the measurement of respiration (oxygen consumption) rate is provided. In this method, the respiration of the cell population is expressed as the specific respiration rate during one doubling time of the population. C1 [Hughes, Diarmaid] Uppsala Univ, Dept Cell & Mol Biol, Microbiol Programme, Uppsala, Sweden. [Macvanin, Mirjana] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hughes, D (reprint author), Uppsala Univ, Dept Cell & Mol Biol, Microbiol Programme, Uppsala, Sweden. RI Hughes, Diarmaid/A-9487-2014 OI Hughes, Diarmaid/0000-0002-7456-9182 NR 22 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-278-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 642 BP 105 EP 112 DI 10.1007/978-1-60327-279-7_8 D2 10.1007/978-1-60327-279-7 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BOO68 UT WOS:000277155600008 PM 20401589 ER PT B AU Pastan, I Ho, M AF Pastan, Ira Ho, Mitchell BE Kontermann, R Dubel, S TI Recombinant Immunotoxins for Treating Cancer SO ANTIBODY ENGINEERING, VOL 2, SECOND EDITION LA English DT Article; Book Chapter ID PHASE-I C1 [Pastan, Ira; Ho, Mitchell] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Ho, Mitchell/F-5059-2015 NR 8 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-3-642-01146-7 PY 2010 BP 127 EP 146 DI 10.1007/978-3-642-01147-4_10 D2 10.1007/978-3-642-01147-4 PG 20 WC Immunology SC Immunology GA BOZ47 UT WOS:000278106800010 ER PT J AU Luu, T Chow, W Lim, D Koczywas, M Frankel, P Cristea, M Margolin, K Doroshow, JH Somlo, G Gaur, S Yen, Y Morgan, RJ AF Luu, Thehang Chow, Warren Lim, Dean Koczywas, Marianna Frankel, Paul Cristea, Mihaela Margolin, Kim Doroshow, James H. Somlo, George Gaur, Shikha Yen, Yun Morgan, Robert J. TI Phase I Trial of Fixed-Dose Rate Gemcitabine in Combination with Bortezomib in Advanced Solid Tumors SO ANTICANCER RESEARCH LA English DT Article DE Bortezomib; fixed-dose rate gemcitabine; solid tumors; phase I ID PROTEASOME INHIBITOR PS-341; PANCREATIC-CANCER; RATE INFUSION; 2,2-DIFLUORODEOXYCYTIDINE; CYTOTOXICITY; METABOLISM; THERAPY; GROWTH; AGENTS; CELLS AB Background: Bortezomib demonstrates synergism with gemcitabine via a fixed-dose rate (FDR). The aim of this phase I trial in solid tumors was to establish the maximum tolerated dose (MTD) and safety data for this combination. Patients and Methods: Twenty-nine patients with a median age of 63 (range 36-84) years and median Karnofsky Performance Status of 90 (range 60-100) were enrolled and treated with bortezomib (1.0 or 1.3 mg/m(2)) on days 1, 4, 8 and 11 and FDR gemcitabine (750, 1,000, or 1,250 mg/m(2)) on days 1 and 8 of each 21-day cycle. Response vas evaluated every two cycles. Results: Dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia and grade 3 liver function test abnormalities. The MTD was bortezomib I mg/m2 and FDR gemcitabine 1,250 mg/m(2). The median number of cycles delivered was 3 (range 1-28). There was one partial response and six cases of stable disease. The median duration of response was 8.5 (range 3-20) months. Conclusion: FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity. C1 [Luu, Thehang; Chow, Warren; Lim, Dean; Koczywas, Marianna; Cristea, Mihaela; Margolin, Kim; Somlo, George; Gaur, Shikha; Yen, Yun; Morgan, Robert J.] City Hope Comprehens Canc, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Frankel, Paul] City Hope Comprehens Canc, Dept Biostat, Duarte, CA 91010 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Luu, T (reprint author), City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM tluu@coh.org NR 25 TC 3 Z9 3 U1 2 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN PY 2010 VL 30 IS 1 BP 167 EP 174 PG 8 WC Oncology SC Oncology GA 555TE UT WOS:000274537400022 PM 20150632 ER PT J AU Peterson, NB Trentham-Dietz, A Garcia-Closas, M Newcomb, PA Titus-Ernstoff, L Huang, YF Chanock, SJ Haines, JL Egan, KM AF Peterson, Neeraja B. Trentham-Dietz, Amy Garcia-Closas, Montserrat Newcomb, Polly A. Titus-Ernstoff, Linda Huang, Yifan Chanock, Stephen J. Haines, Jonathan L. Egan, Kathleen M. TI Association of COMT Haplotypes and Breast Cancer Risk in Caucasian Women SO ANTICANCER RESEARCH LA English DT Article DE Breast neoplasms; genetic polymorphism; epidemiology; estrogens; risk ID CATECHOL-O-METHYLTRANSFERASE; GENETIC-VARIATION; POLYMORPHISMS; METABOLISM; DNA AB Catechol-O-methyl transferase (COMT) is an important estrogen-metabolizing enzyme, and common genetic variants in this gene could affect breast cancer risk. We conducted a large population-based case control study in Massachusetts, New Hampshire, and Wisconsin to examine six strategically selected COMT haplotype-tagging (ht) single nucleotide polymorphism (SNPs), including the val158met polymorphism (rs4680), in relation to breast cancer risk. Analyses were based on 1,655 Caucasian women with invasive breast cancer and 1,470 Caucasian controls. None of the six individual SNPs were associated with breast cancer risk. The global test for haplotype associations was nonsignificant (p-value=0.097), although two uncommon haplotypes present in 6% of the study population showed statistically significant inverse associations with risk. These results suggest that, genetic variation in COMT has no significant association with breast cancer risk among Caucasian women. C1 [Peterson, Neeraja B.] Vanderbilt Univ, Dept Med, Med Ctr, Div Gen Internal Med & Publ Hlth,Sch Med, Nashville, TN 37232 USA. [Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Sch Med, Nashville, TN 37232 USA. [Trentham-Dietz, Amy; Newcomb, Polly A.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Trentham-Dietz, Amy] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53726 USA. [Garcia-Closas, Montserrat; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20952 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Titus-Ernstoff, Linda] Norris Cotton Canc Ctr, Dartmouth Med Sch, Lebanon, NH 03756 USA. [Huang, Yifan; Egan, Kathleen M.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Tampa, FL 33612 USA. RP Peterson, NB (reprint author), Vanderbilt Univ, Dept Med, Med Ctr, Div Gen Internal Med & Publ Hlth,Sch Med, Suite 6108 Med Ctr E,North Tower, Nashville, TN 37232 USA. EM neeraja.peterson@vanderbilt.edu RI Haines, Jonathan/C-3374-2012; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [CA105197, CA47147, CA47305, CA69664, CA67338, CA67264] FX The Authors wish to thank the Study staff, tumor registrars, and all of the participants in the Collaborative Breast Cancer Study for their contributions to the research. This study was supported by grants CA105197. CA47147, CA47305. CA69664, CA67338, and CA67264, and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. We thank Louise Brinton (Division of Cancer Epidemiology and Genetics. National Cancer institute) for her contributions to the design of the Study and Pei Chao (IMS, Silver Spring, MD. USA) for her work oil data and sample management. NR 12 TC 7 Z9 7 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN PY 2010 VL 30 IS 1 BP 217 EP 220 PG 4 WC Oncology SC Oncology GA 555TE UT WOS:000274537400028 PM 20150638 ER PT J AU Buehler, PW D'Agnillo, F AF Buehler, Paul W. D'Agnillo, Felice TI Toxicological Consequences of Extracellular Hemoglobin: Biochemical and Physiological Perspectives SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID CROSS-LINKED HEMOGLOBIN; SICKLE-CELL-DISEASE; STROMA-FREE HEMOGLOBIN; INHALED NITRIC-OXIDE; EXPERIMENTAL INTRACEREBRAL HEMORRHAGE; EXPERIMENTAL SUBARACHNOID HEMORRHAGE; POLYMERIZED BOVINE HEMOGLOBIN; CULTURED ENDOTHELIAL-CELLS; MEDIATED OXIDATIVE INJURY; TRANSGENIC KNOCKOUT MICE AB Under normal physiology, human red blood cells (RBCs) demonstrate a circulating lifespan of similar to 100-120 days with efficient removal of senescent RBCs taking place via the reticuloendothelial system, spleen, and bone marrow phagocytosis. Within this time frame, hemoglobin (Hb) is effectively protected by efficient RBC enzymatic systems designed to allow for interaction between Hb and diffusible ligands while preventing direct contact between Hb and the external environment. Under normal resting conditions, the concentration of extracellular Hb in circulation is therefore minimal and controlled by specific plasma and cellular (monocyte/macrophage) binding proteins (haptoglobin) and receptors (CD163), respectively. However, during pathological conditions leading to hemolysis, extracellular Hb concentrations exceed normal plasma and cellular binding capacities, allowing Hb to become a biologically relevant vasoactive and redox active protein within the circulation and at extravascular sites. Under conditions of genetic, drug-induced, and autoimmune hemolytic anemias, large quantities of Hb are introduced into the circulation and often lead to acute renal failure and vascular dysfunction. Interestingly, the study of chemically modified Hb for use as oxygen therapeutics has allowed for some basic understanding of extracellular Hb toxicity, particularly in the absence of functional clearance mechanisms and in circulatory antioxidant depleted states. Antioxid. Redox Signal. 12, 275-291. C1 [Buehler, Paul W.; D'Agnillo, Felice] NIH, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res,FDA, Bethesda, MD 20892 USA. RP Buehler, PW (reprint author), NIH, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res,FDA, Campus 8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov FU CBER/FDA FX The work described was supported by a Critical Path Initiative award from CBER/FDA. We would like to thank Dr. Bindu Abraham for assistance in preparation of Fig. 3. NR 161 TC 44 Z9 45 U1 1 U2 19 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2010 VL 12 IS 2 BP 275 EP 291 DI 10.1089/ars.2009.2799 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 538JY UT WOS:000273181600009 PM 19659434 ER PT J AU Adamson, CS Freed, EO AF Adamson, Catherine S. Freed, Eric O. TI Novel approaches to inhibiting HIV-1 replication SO ANTIVIRAL RESEARCH LA English DT Review DE Virus entry; Virus assembly; Retrovirus; Drug resistance; HIV-1 drug therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; RIBONUCLEASE-H ACTIVITY; TYPE-1 GAG PRECURSOR; C-TERMINAL DOMAIN; B METHYL-ESTER; TRIM5-ALPHA RESTRICTION FACTOR; VIRION-ASSOCIATED CHOLESTEROL; SMALL-MOLECULE INHIBITION AB Considerable success has been achieved in the treatment of HIV-1 infection, and more than two-dozen antiretroviral drugs are available targeting several distinct steps in the viral replication cycle. However, resistance to these compounds emerges readily,even in the context of combination therapy. Drug toxicity, adverse drug-drug interactions, and accompanying poor patient adherence can also lead to treatment failure. These considerations make continued development of novel antiretroviral therapeutics necessary. In this article, we highlight a number of steps in the HIV-1 replication cycle that represent promising targets for drug discovery. These include lipid raft microdomains, the RNase H activity of the viral enzyme reverse transcriptase, uncoating of the viral core, host cell machinery involved in the integration of the viral DNA into host cell chromatin, virus assembly, maturation, and budding, and the functions of several viral accessory proteins. We discuss the relevant molecular and cell biology, and describe progress to date in developing inhibitors against these novel targets. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Published by Elsevier B.V. C1 [Adamson, Catherine S.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108,1050 Boyles St, Frederick, MD 21702 USA. EM efreed@nih.gov FU Intramural Research Program of the NIH; National Cancer Institute FX We thank Jason Rausch and members of the Freed laboratory for helpful discussions and critical review of the manuscript, and Kalyan Das for providing the RT structure. Research in our lab is Supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by the Intramural AIDS Targeted Antiviral Program. NR 362 TC 74 Z9 78 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 2010 VL 85 IS 1 SI SI BP 119 EP 141 DI 10.1016/j.antiviral.2009.09.009 PG 23 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 561LH UT WOS:000274978200010 PM 19782103 ER PT J AU Marcellin, P Liang, J AF Marcellin, Patrick Liang, Jake TI A personalized approach to optimize hepatitis B treatment in treatment-naive patients SO ANTIVIRAL THERAPY LA English DT Review ID TERM-FOLLOW-UP; TENOFOVIR DISOPROXIL FUMARATE; HBEAG-NEGATIVE PATIENTS; ADEFOVIR DIPIVOXIL; PEGINTERFERON ALPHA-2A; SUSTAINED RESPONSE; NUCLEOSIDE-NAIVE; HBSAG LOSS; VIRUS DNA; LAMIVUDINE AB In a treatment-naive patient with chronic hepatitis B, a personalized approach allows treatment efficacy to be optimized. Firstly, the selection of good candidates for therapy is crucial. Patients with chronic active hepatitis B - with relatively low levels of HBV DNA replication (<10(9) copies/ml) and relatively high alanine aminotransferase (ALT) levels - are good candidates for therapy. By contrast, patients with chronic hepatitis B in the immunotolerance phase, who have high levels of HBV DNA and persistently normal ALT levels, as well as inactive hepatitis B surface antigen (HBsAg) carriers with low HBV DNA and normal ALT levels do not have an indication for therapy as they are poor responders. Secondly, the characteristics or the patient (for example, gender, age, immune status, general health status and comorbidities), the characteristics of the liver disease (for example, presence of cirrhosis and liver function) and the characteristics of the virus (for example, genotype) are important when assessing the chance of success and when choosing the best therapeutic strategy (nucleoside/nucleotide analogue or interferon). Thirdly, during therapy, the antiviral effect - assessed by decrease in HBV DNA level - allows an individualized response-guided approach. In addition, quantification of HBsAg after 3-6 months of interferon therapy appears to be a good predictor of sustained virological response after treatment and HBsAg clearance. Continuing interferon therapy until week 48 is justified in patients with a significant decrease in HBsAg. Ongoing and future studies will provide useful information regarding prolonging interferon therapy beyond 48 weeks in some patients in order to increase efficacy, and also regarding the role of combination therapy with interferon and potent nucleoside/nucleotide analogues, such as entecavir or tenofovir disoproxil fumarate. C1 [Marcellin, Patrick] Hop Beaujon, AP HP, Serv Hepatol, Clichy, France. [Marcellin, Patrick] Univ Denis Diderot Paris7, INSERM, U773, CRB3, Clichy, France. [Liang, Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Marcellin, P (reprint author), Hop Beaujon, AP HP, Serv Hepatol, Clichy, France. EM patrick.marcellin@bjn.aphp.fr FU F Hoffmann-La Roche (Basel, Switzerland) FX Editorial support was provided by Liesje Thomas at Elements Communications and was funded by F Hoffmann-La Roche (Basel, Switzerland). NR 42 TC 8 Z9 9 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 3 BP 53 EP 59 DI 10.3851/IMP1624 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 657CS UT WOS:000282390400007 PM 21041904 ER PT J AU Nakata, H Kruhlak, M Kamata, W Ogata-Aoki, H Li, JF Maeda, K Ghosh, AK Mitsuya, H AF Nakata, Hirotomo Kruhlak, Michael Kamata, Wakako Ogata-Aoki, Hiromi Li, Jianfeng Maeda, Kenji Ghosh, Arun K. Mitsuya, Hiroaki TI Effects of CC chemokine receptor 5 (CCR5) inhibitors on the dynamics of CCR5 and CC-chemokine-CCR5 interactions SO ANTIVIRAL THERAPY LA English DT Article ID R5 HIV-1 INFECTION; SMALL-MOLECULE; CORECEPTOR CCR5; MIP-1 ALPHA; ANTAGONIST; RANTES; ENTRY; MARAVIROC; FUSION; POTENT AB Background: This study aimed to examine how CC chemokine receptor 5 (CCR5) inhibitors (aplaviroc [APL], TAK779 and maraviroc [MVC]) interact with CCR5 and affect its dynamics and physiological CC-chemokine-CCR5 interactions. Methods: A yellow fluorescent protein (YFP)-tagged CCR5-expressing U373-MAGI cell line was generated and a stable CCR5-expressing clonal population, (YFP)CCR5-UM16, was prepared. (YFP)CCR5-UM16 cells were exposed to RANTES, macrophage inflammatory protein (MIP)-1 alpha or MIP-1 beta (all 100 ng/ml) with or without CCR5 inhibitors and (YFP)CCR5 internalization was visualized with real-time by laser scanning confocal microscopy. The mobility of (YFP)CCR5 was also examined in the presence of CCR5 inhibitors with fluorescence recovery after photobleaching (FRAP) imaging. Results: Following the addition of each CC chemokine, intracellular fluorescence intensity increased whereas membranous fluorescence decreased, signifying (YFP)CCR5 internalization. All three CCR5 inhibitors failed to induce (YFP)CCR5 internalization. All three CCR5 inhibitors blocked the CC-chemokine-induced internalization at a high concentration of 1 mu M; however, the ratio of APL concentration that blocked RANTES-induced internalization by 50% over APL concentration that blocked HIV type-1 (HIV-1) replication by 50% was 16.4, indicating that APL permits CC-chemokine-induced internalization to a much greater extent compared with TAK779 and MVC, having ratios of 1.1 and 0.9, respectively. The examination of (YFP)CCR5 mobility with FRAP imaging revealed that (YFP)CCR5 continuously underwent rapid redistribution, which none of the three inhibitors blocked. Conclusions: The finding that APL moderately blocked the RANTES-triggered (YFP)CCR5 internalization despite the highly potent anti-HIV-1 activity of APL strongly suggests that development of CCR5 inhibitors, which do not overly inhibit physiological CC-chemokine-CCR5 interactions, is practically feasible. C1 [Nakata, Hirotomo; Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Nakata, Hirotomo; Kamata, Wakako; Ogata-Aoki, Hiromi; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 860, Japan. [Nakata, Hirotomo; Kamata, Wakako; Ogata-Aoki, Hiromi; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 860, Japan. [Kruhlak, Michael] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Li, Jianfeng; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Li, Jianfeng; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hm21q@nih.gov RI Li, Jianfeng/F-5057-2014 OI Li, Jianfeng/0000-0002-8838-3872 FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; National Institutes of Health [GM53386]; Ministry of Education, Culture, Sports, Science and Technology [Monbu-Kagakusho], Japan; Ministry of Health, Welfare, and Labor of Japan; Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Reemerging Infectious Diseases FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and in part by a grant for global education and research center aiming at the control of AIDS (Global Center of Excellence, supported by the Ministry of Education, Culture, Sports, Science and Technology [Monbu-Kagakusho], Japan; HM), Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan (HM), and a grant to the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Reemerging Infectious Diseases (Renkei Jigyo; Number 78, Kumamoto University) of Monbu-Kagakusho (HM), and by a grant from the National Institutes of Health (GM53386; AKG). NR 43 TC 2 Z9 2 U1 0 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 3 BP 321 EP 331 DI 10.3851/IMP1529 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 609PZ UT WOS:000278670800005 PM 20516552 ER PT J AU Mofenson, LM AF Mofenson, Lynne M. TI Antiretroviral drugs to prevent breastfeeding HIV transmission SO ANTIVIRAL THERAPY LA English DT Review ID TO-CHILD TRANSMISSION; LATE POSTNATAL TRANSMISSION; EXTENDED-DOSE NEVIRAPINE; DAR-ES-SALAAM; INFECTED WOMEN; PREMATURE DELIVERY; UNITED-KINGDOM; VIRAL LOAD; THERAPY; INFANTS AB Observational studies and randomized clinical trials demonstrating that antiretroviral prophylaxis of the breastfeeding infant or triple-drug antiretroviral prophylaxis of the lactating mother can significantly affect the risk of postnatal transmission of HIV via breast milk have recently become available. In resource-limited countries, breastfeeding is a cornerstone of infant survival. While shortening the duration of breastfeeding by HIV-infected women reduces postnatal HIV transmission, increasing data suggest this may also decrease overall infant survival. Thus, there is a crucial need for interventions to allow safer and more prolonged breastfeeding. This paper will critically review the results of studies of postnatal antiretroviral prophylaxis to prevent breast milk HIV transmission. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. RP Mofenson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 49 TC 34 Z9 34 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 BP 537 EP 553 DI 10.3851/IMP1574 PG 17 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800001 PM 20587847 ER PT J AU Delviks-Frankenberry, KA Lengruber, RB Santos, AF Soares, MA Kearney, M Maldarelli, F Coffin, JM Pathak, VK AF Delviks-Frankenberry, K. A. Lengruber, R. B. Santos, A. F. Soares, M. A. Kearney, M. Maldarelli, F. Coffin, J. M. Pathak, V. K. TI Enhanced NRTI and NNRTI resistance is associated with mutations in the HIV-1 reverse transcriptase connection subdomain of subtype C patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Delviks-Frankenberry, K. A.; Kearney, M.; Maldarelli, F.; Coffin, J. M.; Pathak, V. K.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Lengruber, R. B.; Santos, A. F.; Soares, M. A.] Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A78 EP A78 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300068 ER PT J AU Delviks-Frankenberry, KA Lengruber, RB Santos, AF Soares, MA Kearney, M Maldarelli, F Coffin, JM Pathak, VK AF Delviks-Frankenberry, K. A. Lengruber, R. B. Santos, A. F. Soares, M. A. Kearney, M. Maldarelli, F. Coffin, J. M. Pathak, V. K. TI Enhanced NRTI and NNRTI resistance is associated with mutations in the HIV-1 reverse transcriptase connection subdomain of subtype C patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Delviks-Frankenberry, K. A.; Kearney, M.; Maldarelli, F.; Coffin, J. M.; Pathak, V. K.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Lengruber, R. B.; Santos, A. F.; Soares, M. A.] Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 64 BP A78 EP A78 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800083 ER PT J AU Galli, A Nikolaitchik, O Chen, J Kearney, M Pathak, VK Maldarelli, F Coffin, J Hu, WS AF Galli, A. Nikolaitchik, O. Chen, J. Kearney, M. Pathak, V. K. Maldarelli, F. Coffin, J. Hu, W-S TI Factors affecting the emergence of intersubtype recombinants in HIV-1 population SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Galli, A.; Nikolaitchik, O.; Chen, J.; Kearney, M.; Pathak, V. K.; Maldarelli, F.; Coffin, J.; Hu, W-S] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A40 EP A40 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300036 ER PT J AU Galli, A Nikolattchik, O Chen, J Kearney, M Pathak, VK Maldarelli, F Coffin, J Hu, WS AF Galli, A. Nikolattchik, O. Chen, J. Kearney, M. Pathak, V. K. Maldarelli, F. Coffin, J. Hu, W-S TI Factors affecting the emergence of intersubtype recombinants in HIV-1 population SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Galli, A.; Nikolattchik, O.; Chen, J.; Kearney, M.; Pathak, V. K.; Maldarelli, F.; Coffin, J.; Hu, W-S] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 32 BP A40 EP A40 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800051 ER PT J AU Josefsson, L Palmer, S Casazza, J Ambrozak, D Kearney, M Shao, W O'Shea, A Heytens, L Rehm, C Mellors, J Albert, J Coffin, J Maldarelli, F AF Josefsson, L. Palmer, S. Casazza, J. Ambrozak, D. Kearney, M. Shao, W. O'Shea, A. Heytens, L. Rehm, C. Mellors, J. Albert, J. Coffin, J. Maldarelli, F. TI Analysis of HIV DNA molecules in paired peripheral blood and lymph node tissue samples from chronically infected patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Josefsson, L.; Palmer, S.; Albert, J.] Swedish Inst Infect Dis Control, Solna, Sweden. [Josefsson, L.; Palmer, S.; Albert, J.] Karolinska Inst, Solna, Sweden. [Josefsson, L.; Palmer, S.; Kearney, M.; Shao, W.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Casazza, J.; Ambrozak, D.; O'Shea, A.; Heytens, L.; Rehm, C.] NIAID, NIH, Bethesda, MD 20892 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A41 EP A41 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300037 ER PT J AU Josefsson, L Palmer, S Casazza, J Ambrozak, D Kearney, M Shao, W O'Shea, A Heytens, L Rehm, C Mellors, J Albert, J Coffin, J Maldarelli, F AF Josefsson, L. Palmer, S. Casazza, J. Ambrozak, D. Kearney, M. Shao, W. O'Shea, A. Heytens, L. Rehm, C. Mellors, J. Albert, J. Coffin, J. Maldarelli, F. TI Analysis of HIV DNA molecules in paired peripheral blood and lymph node tissue samples from chronically infected patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Josefsson, L.; Palmer, S.; Albert, J.] Swedish Inst Infect Dis Control, Solna, Sweden. [Josefsson, L.; Palmer, S.; Albert, J.] Karolinska Inst, Solna, Sweden. [Casazza, J.; Ambrozak, D.; O'Shea, A.; Heytens, L.; Rehm, C.] NIAID, NIH, Bethesda, MD 20892 USA. [Josefsson, L.; Palmer, S.; Kearney, M.; Shao, W.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 33 BP A41 EP A41 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800052 ER PT J AU Kearney, M Spindler, J Shao, W Stephens, R O'Shea, A Rehm, C Poethke, C Mellors, JW Coffin, JM Maldarelli, F AF Kearney, M. Spindler, J. Shao, W. Stephens, R. O'Shea, A. Rehm, C. Poethke, C. Mellors, J. W. Coffin, J. M. Maldarelli, F. TI Rebound HIV-1 viraemia after cessation of long-term suppressive antiretroviral therapy has low genetic diversity and little divergence from pre-therapy virus populations SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Kearney, M.; Spindler, J.; Poethke, C.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Shao, W.; Stephens, R.] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [O'Shea, A.; Rehm, C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mellors, J. W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A46 EP A46 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300042 ER PT J AU Kearney, M Spindler, J Shao, W Stephens, R O'Shea, A Rehm, C Poethke, C Mellors, JW Coffin, JM Maldarelli, F AF Kearney, M. Spindler, J. Shao, W. Stephens, R. O'Shea, A. Rehm, C. Poethke, C. Mellors, J. W. Coffin, J. M. Maldarelli, F. TI Rebound HIV-1 viraemia after cessation of long-term suppressive antiretroviral therapy has low genetic diversity and little divergence from pre-therapy virus populations SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Kearney, M.; Spindler, J.; Poethke, C.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Shao, W.; Stephens, R.] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [O'Shea, A.; Rehm, C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mellors, J. W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 38 BP A46 EP A46 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800057 ER PT J AU Kovari, IC Yedidi, RS Martin, PD Liu, Z AF Kovari, I. C. Yedidi, R. S. Martin, P. D. Liu, Z. TI Conformational rigidity of the multidrug-resistant HIV-1 protease revealed by modelling studies with the Gag-capsid protein SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Kovari, I. C.; Martin, P. D.; Liu, Z.] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI USA. [Yedidi, R. S.] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 68 BP A82 EP A82 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800087 ER PT J AU Kovari, LC Yedidi, RS Martin, PD Liu, Z AF Kovari, L. C. Yedidi, R. S. Martin, P. D. Liu, Z. TI Conformational rigidity of the multidrug-resistant HIV-1 protease revealed by modelling studies with the Gag-capsid protein SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Kovari, L. C.; Martin, P. D.; Liu, Z.] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI USA. [Yedidi, R. S.] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RI Liu, Zhigang/A-2003-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A82 EP A82 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300072 ER PT J AU Maldarelli, F Shao, W Dewar, R Rehman, T Kearney, M Rehn, C Metcalf, J Kottilil, S Mellors, J Coffin, J AF Maldarelli, F. Shao, W. Dewar, R. Rehman, T. Kearney, M. Rehn, C. Metcalf, J. Kottilil, S. Mellors, J. Coffin, J. TI New bioinformatic algorithm to identify recent HIV-1 infection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Maldarelli, F.; Kearney, M.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Shao, W.] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [Dewar, R.; Rehman, T.] NCI, Collaborat Clin Resource Branch, SAIC Frederick, Frederick, MD 21701 USA. [Rehn, C.; Metcalf, J.] NIAID, Clin Res Sect, NIH, Bethesda, MD 20892 USA. [Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mellors, J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A97 EP A97 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300084 ER PT J AU Maldarelli, F Shao, W Dewar, R Rehman, T Kearney, M Rehm, C Metcalf, J Kottilil, S Mellors, J Coffin, J AF Maldarelli, F. Shao, W. Dewar, R. Rehman, T. Kearney, M. Rehm, C. Metcalf, J. Kottilil, S. Mellors, J. Coffin, J. TI New bioinformatic algorithm to identify recent HIV-1 infection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Maldarelli, F.; Kearney, M.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Shao, W.] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [Dewar, R.; Rehman, T.] NCI, Collaborat Clin Resource Branch, SAIC Frederick, Frederick, MD 21701 USA. [Rehm, C.; Metcalf, J.] NIAID, Clin Res Sect, NIH, Bethesda, MD 20892 USA. [Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mellors, J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 80 BP A97 EP A97 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800099 ER PT J AU Marchand, B Kirby, KA Sietsema, D Kodama, EN Mitsuya, H Parniak, MA Sarafianos, SG AF Marchand, B. Kirby, K. A. Sietsema, D. Kodama, E. N. Mitsuya, H. Parniak, M. A. Sarafianos, S. G. TI The crystal structure of EFdA-resistant HIV-1 reverse transcriptase reveals structural changes in the polymerase active site SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Marchand, B.; Kirby, K. A.; Sietsema, D.; Sarafianos, S. G.] Univ Missouri, Columbia, MO USA. [Kodama, E. N.] Tohoku Univ, Sendai, Miyagi 980, Japan. [Mitsuya, H.] Kumamoto Univ, Kumamoto, Japan. [Mitsuya, H.] NIH, Bethesda, MD 20892 USA. [Parniak, M. A.] Univ Pittsburgh, Pittsburgh, PA USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A10 EP A10 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300006 ER PT J AU Marchand, B Kirby, KA Sietsema, D Kodama, EN Mitsuya, H Parmak, MA Sarafianos, SG AF Marchand, B. Kirby, K. A. Sietsema, D. Kodama, E. N. Mitsuya, H. Parmak, M. A. Sarafianos, S. G. TI The crystal structure of EFdA-resistant HIV-1 reverse transcriptase reveals structural changes in the polymerase active site SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Marchand, B.; Kirby, K. A.; Sietsema, D.; Sarafianos, S. G.] Univ Missouri, Columbia, MO USA. [Kodama, E. N.] Tohoku Univ, Sendai, Miyagi 980, Japan. [Mitsuya, H.] Kumamoto Univ, Kumamoto, Japan. [Mitsuya, H.] NIH, Bethesda, MD 20892 USA. [Parmak, M. A.] Univ Pittsburgh, Pittsburgh, PA USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 2 BP A10 EP A10 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800021 ER PT J AU Mens, H Kearney, M Wiegand, A Schonning, K Gerstoft, J Obel, N Maldarelli, F Mellors, JW Benfield, T Coffin, JM AF Mens, H. Kearney, M. Wiegand, A. Schonning, K. Gerstoft, J. Obel, N. Maldarelli, F. Mellors, J. W. Benfield, T. Coffin, J. M. TI Genetic analyses suggest functional differences in the nature of persistent viraemia between HIV-1 elite controllers and therapy exposed controllers SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Mens, H.; Benfield, T.] Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. [Mens, H.; Benfield, T.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Mens, H.; Kearney, M.; Wiegand, A.; Maldarelli, F.; Coffin, J. M.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Schonning, K.] Copenhagen Univ Hosp, Dept Clin Microbiol, Hvidovre, Denmark. [Gerstoft, J.; Obel, N.] Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark. [Mellors, J. W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A171 EP A171 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300140 ER PT J AU Mens, H Kearney, M Wiegand, A Schonning, K Gerstoft, J Obel, N Maldarelli, F Mellors, JW Benfield, T Coffin, JM AF Mens, H. Kearney, M. Wiegand, A. Schonning, K. Gerstoft, J. Obel, N. Maldarelli, F. Mellors, J. W. Benfield, T. Coffin, J. M. TI Genetic analyses suggest functional differences in the nature of persistent viraemia between HIV-1 elite controllers and therapy exposed controllers SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Mens, H.; Benfield, T.] Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. [Mens, H.; Benfield, T.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Mens, H.; Kearney, M.; Wiegand, A.; Maldarelli, F.; Coffin, J. M.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Schonning, K.] Copenhagen Univ Hosp, Dept Clin Microbiol, Hvidovre, Denmark. [Gerstoft, J.; Obel, N.] Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark. [Mellors, J. W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 136 BP A171 EP A171 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800155 ER PT J AU Mulligan, K Stephensen, CB Van Loan, MD Hazra, R Bethel, J Rutledge, BN Pan, CG Flynn, PM Lujan-Zilberman, J Kiser, JJ Baker, AM Liu, NX Kapogiannis, BG Worrell, C Wilson, CM Havens, PL AF Mulligan, K. Stephensen, C. B. Van Loan, M. D. Hazra, R. Bethel, J. Rutledge, B. N. Pan, C. G. Flynn, P. M. Lujan-Zilberman, J. Kiser, J. J. Baker, A. M. Liu, N. X. Kapogiannis, B. G. Worrell, C. Wilson, C. M. Havens, P. L. TI Evidence of renal tubular impairment and increased bone turnover in HIV-infected adolescents and young adults on tenofovir-containing combination antiretroviral therapy (cART): baseline results of Adolescent Trials Network (ATN) study 063 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Mulligan, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stephensen, C. B.; Van Loan, M. D.] Univ Calif Davis, USDA Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Hazra, R.; Kapogiannis, B. G.; Worrell, C.] Eunice Kennedy Shriver NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. [Bethel, J.; Rutledge, B. N.; Liu, N. X.] WESTAT Corp, Bethesda, MD USA. [Pan, C. G.; Havens, P. L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Flynn, P. M.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Lujan-Zilberman, J.] Univ S Florida, Coll Med, Tampa, FL USA. [Kiser, J. J.] Univ Colorado Denver, Aurora, CO USA. [Baker, A. M.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Wilson, C. M.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 8 BP A18 EP A19 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KN UT WOS:000287431200037 ER PT J AU Mulligan, K Stephensen, CB Van Loan, MD Hazra, R Bethel, J Rutledge, BN Pan, CG Flynn, PM Lujan-Zilberman, J Kiser, JJ Baker, AM Liu, NX Kapogiannis, BG Worrell, C Wilson, CM Havens, PL AF Mulligan, K. Stephensen, C. B. Van Loan, M. D. Hazra, R. Bethel, J. Rutledge, B. N. Pan, C. G. Flynn, P. M. Lujan-Zilberman, J. Kiser, J. J. Baker, A. M. Liu, N. X. Kapogiannis, B. G. Worrell, C. Wilson, C. M. Havens, P. L. TI Evidence of renal tubular impairment and increased bone turnover in HIV-infected adolescents and young adults on tewnofovir-containing combination antiretroviral therapy (cART): baseline results of Adolescent Trials Network (ATN) study 063 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Mulligan, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stephensen, C. B.; Van Loan, M. D.] Univ Calif Davis, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Hazra, R.; Worrell, C.] Eunice Kennedy Shriver NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. [Bethel, J.; Rutledge, B. N.; Liu, N. X.] WESTAT Corp, Bethesda, MD USA. [Pan, C. G.; Havens, P. L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Flynn, P. M.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Lujan-Zilberman, J.] Univ S Florida, Coll Med, Tampa, FL USA. [Kiser, J. J.] Univ Colorado Denver, Aurora, CO USA. [Baker, A. M.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Wilson, C. M.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 4 BP A18 EP A19 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KQ UT WOS:000287431500023 ER PT J AU Shao, W Boltz, VF Spindler, JE Kearney, M Maldarelli, F Mellors, JW Stewart, C Volfovsky, N Levitsky, A Stephens, RM Coffin, JM AF Shao, W. Boltz, V. F. Spindler, J. E. Kearney, M. Maldarelli, F. Mellors, J. W. Stewart, C. Volfovsky, N. Levitsky, A. Stephens, R. M. Coffin, J. M. TI Reduced PCR-based recombination for HIV-1 drug resistance mutation linkage determination by 454 pyrosequencing SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Shao, W.; Volfovsky, N.; Levitsky, A.; Stephens, R. M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. [Boltz, V. F.; Spindler, J. E.; Kearney, M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Mellors, J. W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Stewart, C.] NCI, LMT, SAIC Frederick, Frederick, MD 21701 USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A33 EP A33 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300029 ER PT J AU Shao, W Boltz, VF Spindler, JE Kearney, M Maldarelli, F Mellors, JW Stewart, C Volfovsky, N Levitsky, A Stephens, RM Coffin, JM AF Shao, W. Boltz, V. F. Spindler, J. E. Kearney, M. Maldarelli, F. Mellors, J. W. Stewart, C. Volfovsky, N. Levitsky, A. Stephens, R. M. Coffin, J. M. TI Reduced PCR-based recombination for HIV-1 drug resistance mutation linkage determination by 454 pyrosequencing SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Shao, W.; Volfovsky, N.; Levitsky, A.; Stephens, R. M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. [Boltz, V. F.; Spindler, J. E.; Kearney, M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Mellors, J. W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Stewart, C.] NCI, SAIC Frederick, LMT, Frederick, MD 21701 USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 25 BP A33 EP A33 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800044 ER PT J AU Sims, A Frank, L Cross, R Clauss, S Dimock, D Purdy, J Jacoub, I Hazra, R Hadigan, C Sable, C AF Sims, A. Frank, L. Cross, R. Clauss, S. Dimock, D. Purdy, J. Jacoub, I. Hazra, R. Hadigan, C. Sable, C. TI Abnormal cardiac strain in children and young adults with HIV acquired in early life SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Sims, A.; Frank, L.; Cross, R.; Clauss, S.; Sable, C.] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. [Dimock, D.; Purdy, J.; Jacoub, I.; Hazra, R.; Hadigan, C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 8 BP A16 EP A17 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KN UT WOS:000287431200035 ER PT J AU Sims, A Frank, L Cross, R Clauss, S Dimock, D Purdy, J Jacoub, I Hazra, R Hadigan, C Sable, C AF Sims, A. Frank, L. Cross, R. Clauss, S. Dimock, D. Purdy, J. Jacoub, I. Hazra, R. Hadigan, C. Sable, C. TI Abnormal cardiac strain in children and young adults with HIV acquired in early life SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Sims, A.; Frank, L.; Cross, R.; Clauss, S.; Sable, C.] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. [Dimock, D.; Purdy, J.; Jacoub, I.; Hazra, R.; Hadigan, C.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 4 BP A16 EP A17 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KQ UT WOS:000287431500021 ER PT J AU Sutin, AR Costa, PT Wethington, E Eaton, W AF Sutin, Angelina R. Costa, Paul T., Jr. Wethington, Elaine Eaton, William TI Perceptions of stressful life events as turning points are associated with self-rated health and psychological distress SO ANXIETY STRESS AND COPING LA English DT Article DE turning points; lesson learned; life story; physical health; psychological distress; stressful life event ID EPIDEMIOLOGIC CATCHMENT-AREA; FOLLOW-UP; DEFINING MEMORIES; MIDLIFE ADULTS; BREAST-CANCER; IDENTITY; MORTALITY; NARRATIVES; THINGS; SPAN AB We test the hypothesis that changes in physical and psychological health are associated with construals of stressful life events. At two points in time, approximately 10 years apart, participants (n = 1038) rated their physical health and psychological distress. At the second assessment, participants also reported their most stressful life event since the first assessment and indicated whether they considered the event a turning point and/or lesson learned. Lower self-ratings of health and higher ratings of psychological distress, controlling for baseline health and distress, and relevant demographic factors, were associated with perceiving the stressful life event as a turning point, particularly a negative turning point. The two health measures were primarily unrelated to lessons learned. How individuals construe the most stressful events in their lives are associated with changes in self-rated health and distress. C1 [Sutin, Angelina R.; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Wethington, Elaine] Cornell Univ, Dept Human Dev & Sociol, Ithaca, NY USA. [Eaton, William] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA026652]; NIMH NIH HHS [MH 47447, K23 MH064543, MH 50616, MH64543, R01 MH047447, R01 MH050616] NR 37 TC 5 Z9 7 U1 2 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2010 VL 23 IS 5 BP 479 EP 492 DI 10.1080/10615800903552015 PG 14 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 638IS UT WOS:000280888100001 PM 20099168 ER PT J AU Davis, JC Su, HC AF Davis, Jeremiah C. Su, Helen C. BE Preedy, VR TI Human Genetic Defects in Apoptosis Pathways and Processes SO APOPTOSIS SE Modern Insights into Disease from Molecules to Man LA English DT Article; Book Chapter ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; DENDRITIC CELL APOPTOSIS; FAS LIGAND; T-CELLS; MUTATIONS; LYMPHOCYTE; RECEPTOR; DISEASE; PATIENT; MAINTENANCE AB Research within the last two decades has revealed a complex and critical system of programmed cell death (PCD) in immune cells that helps maintain immunological homeostasis. Our understanding of apoptosis in normal immune function has been greatly informed by the study of rare patient phenotypes and the animal models they resemble (Sneller et al. 1992). Genetic defects uncovered in patients with Autoimmune Lymphoproliferative Syndrome (ALPS) or other conditions of lymphocyte accumulation and autoimmunity illustrate the importance of cell extrinsic apoptosis signals communicated by death receptors (DR), as well as cell intrinsic signals that function through mitochondrial pathways. Patient studies continue to yield new insights. Connections between traditional PCD components like caspase-8 and known growth and proliferation signals such as NF-kappa B have recently emerged (Su et al. 2005). Many clinical features remain unexplained, including the variable clinical penetrance seen in ALPS and the unpredictable manifestation of autoimmune disease. Solving these puzzles may allow us to manipulate apoptotic pathways to treat a wide range of diseases. C1 [Davis, Jeremiah C.; Su, Helen C.] NIAID, Human Immunol Dis Unit, Lab Host Defenses, NIH, Bethesda, MD 20892 USA. RP Su, HC (reprint author), NIAID, Human Immunol Dis Unit, Lab Host Defenses, NIH, Bldg 10 CRC,Room 5W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Jeremiah.Davis@nih.gov; hsu@niaid.nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 NR 32 TC 0 Z9 0 U1 0 U2 0 PU SCIENCE PUBLISHERS INC PI ENFIELD PA MAY ST, PO BOX 699, ENFIELD, NH 03748 USA BN 978-1-57808-583-5 J9 MOD INSIGHTS DIS MOL JI Mod. Insights Dis. Mol. Man PY 2010 BP 19 EP 36 DI 10.1201/9781439845431-4 D2 10.1201/9781439845431 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Pathology SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Pathology GA BTO67 UT WOS:000287577000003 ER PT B AU Kuwano, Y Gallouzi, IE Gorospe, M AF Kuwano, Yuki Gallouzi, Imed-Eddine Gorospe, Myriam BE Cecconi, F DAmelio, M TI Role of the RNA-Binding Protein HuR in Apoptosis and Apoptosome Function SO APOPTOSOME: AN UP-AND-COMING THERAPEUTICAL TOOL LA English DT Article; Book Chapter DE mRNA stability; translational control; post-transcriptional gene regulation; ribonucleoprotein complex ID TARGET MESSENGER-RNAS; BREAST-CANCER CELLS; PROTHYMOSIN-ALPHA; CYTOCHROME-C; NUCLEAR IMPORT; TRANSLATIONAL CONTROL; TRANSCRIPTION FACTORS; MEDIATED APOPTOSIS; OXIDATIVE STRESS; INHIBITOR P27 AB In response to damaging agents, cells alter gene expression patterns through transcriptional and post-transcriptional mechanisms. Among the major post-transcriptional regulators of gene expression is the RNA-binding protein HuR, which stabilizes or regulates the translation of target mRNAs. HuR function is modulated by stress-causing agents including oxidants, genotoxins, inflammatory stimuli, and nutrient deprivation. By influencing the expression of target mRNAs and protein ligands, HuR has been shown to influence cellular function in multiple ways, including by modulating apoptosis. In this chapter, we describe the dual influence of HuR on programmed cell death. In response to moderate, repairable stress, HuR was found to bind numerous mRNAs encoding inhibitors of apoptosis and apoptosome activity (e.g., prothymosin alpha, Bcl-2, Mcl-1, SIRT1, cyclins, HIF-1 alpha, p21) and elevated their expression. In several instances, these proteins were demonstrated effectors of HuR pro-survival actions. By contrast, in response to irreparable stress, HuR was reported to promote apoptosis through its association with protein ligand pp32/PHAPI, a potent activator of the apoptosome. HuR can also modulate the expression of pro-apoptotic proteins such as p53, c-myc, and P27(Kip1), but their involvement in HuR-triggered apoptosis remains to be studied. In sum, the association of HuR with specific mRNAs and proteins can either promote or inhibit cell death. We describe how these seemingly antagonistic functions of HuR on apoptosis are regulated and we discuss how HuR function is integrated in the overall homeostatic program of the cell. C1 [Kuwano, Yuki; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Gallouzi, Imed-Eddine] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Box 12,251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov NR 104 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-3414-4 PY 2010 BP 203 EP 220 DI 10.1007/978-90-481-3415-1_10 D2 10.1007/978-90-481-3415-1 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BNG50 UT WOS:000274505400010 ER PT J AU Peng, J Lau, ST Chao, C Dai, JY Chan, HLW Luo, HS Zhu, BP Zhou, QF Shung, KK AF Peng, J. Lau, S. T. Chao, C. Dai, J. Y. Chan, H. L. W. Luo, H. S. Zhu, B. P. Zhou, Q. F. Shung, K. K. TI PMN-PT single crystal thick films on silicon substrate for high-frequency micromachined ultrasonic transducers SO APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING LA English DT Article ID MEDICAL IMAGING APPLICATIONS; ARRAY AB In this work, a novel high-frequency ultrasonic transducer structure is realized by using PMNPT-on-silicon technology and silicon micromachining. To prepare the single crystalline PMNPT-on-silicon wafers, a hybrid processing method involving wafer bonding, mechanical lapping and wet chemical thinning is successfully developed. In the transducer structure, the active element is fixed within the stainless steel needle housing. The measured center frequency and -6 dB bandwidth of the transducer are 35 MHz and 34%, respectively. Owing to the superior electromechanical coupling coefficient (k (t) ) and high piezoelectric constant (d (33)) of PMNPT film, the transducer shows a good energy conversion performance with a very low insertion loss down to 8.3 dB at the center frequency. C1 [Peng, J.; Lau, S. T.; Chao, C.; Dai, J. Y.; Chan, H. L. W.] Hong Kong Polytech Univ, Dept Appl Phys, Hong Kong, Hong Kong, Peoples R China. [Zhu, B. P.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Zhu, B. P.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Luo, H. S.] Chinese Acad Sci, State Key Lab High Performance Ceram & Superfine, Shanghai Inst Ceram, Shanghai 201800, Peoples R China. [Peng, J.; Lau, S. T.; Chao, C.; Dai, J. Y.; Chan, H. L. W.] Hong Kong Polytech Univ, Mat Res Ctr, Hong Kong, Hong Kong, Peoples R China. RP Dai, JY (reprint author), Hong Kong Polytech Univ, Dept Appl Phys, Hong Kong, Hong Kong, Peoples R China. EM apdaijy@inet.polyu.edu.hk RI Lau, Sien-Ting/B-6091-2013; Dai, Jiyan/I-7098-2013; CHAN, Helen Lai Wa/B-5633-2014 OI Dai, Jiyan/0000-0002-7720-8032; CHAN, Helen Lai Wa/0000-0002-8508-3049 FU Hong Kong Innovative Technology Council [K-ZP21]; Hong Kong Polytechnic University; NIH [P41-EB2182] FX This work was supported by the Hong Kong Innovative Technology Council ( Project No. K-ZP21), the Centre for Smart Materials of the Hong Kong Polytechnic University, NIH Grant No. P41-EB2182. NR 18 TC 9 Z9 9 U1 3 U2 37 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0947-8396 J9 APPL PHYS A-MATER JI Appl. Phys. A-Mater. Sci. Process. PD JAN PY 2010 VL 98 IS 1 BP 233 EP 237 DI 10.1007/s00339-009-5381-1 PG 5 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA 521TS UT WOS:000271947800027 ER PT J AU Maholmes, V Lomonaco, CG AF Maholmes, Valerie Lomonaco, Carmela G. BE Maholmes, V Lomonaco, CG TI Applied Research in Child and Adolescent Development A Practical Guide Conclusion and Future Directions SO APPLIED RESEARCH IN CHILD AND ADOLESCENT DEVELOPMENT: A PRACTICAL GUIDE LA English DT Editorial Material; Book Chapter C1 [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Brookline, MA USA. RP Maholmes, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Brookline, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-85418-1 PY 2010 BP 303 EP 307 PG 5 WC Psychology, Developmental SC Psychology GA BUQ17 UT WOS:000290025200015 ER PT J AU Makarova, KS Koonin, EV AF Makarova, Kira S. Koonin, Eugene V. TI Archaeal Ubiquitin-Like Proteins: Functional Versatility and Putative Ancestral Involvement in tRNA Modification Revealed by Comparative Genomic Analysis SO ARCHAEA-AN INTERNATIONAL MICROBIOLOGICAL JOURNAL LA English DT Article ID ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; MOLYBDOPTERIN SYNTHASE; THIAMIN BIOSYNTHESIS; STRUCTURE PREDICTION; CRYSTAL-STRUCTURE; SULFUR TRANSFER; KEOPS COMPLEX; PROTEASOME; ACTIVATION AB The recent discovery of protein modification by SAMPs, ubiquitin-like (Ubl) proteins from the archaeon Haloferax volcanii, prompted a comprehensive comparative-genomic analysis of archaeal Ubl protein genes and the genes for enzymes thought to be functionally associated with Ubl proteins. This analysis showed that most archaea encode members of two major groups of Ubl proteins with the beta-grasp fold, the ThiS and MoaD families, and indicated that the ThiS family genes are rarely linked to genes for thiamine or Mo/W cofactor metabolism enzymes but instead are most often associated with genes for enzymes of tRNA modification. Therefore it is hypothesized that the ancestral function of the archaeal Ubl proteins is sulfur insertion into modified nucleotides in tRNAs, an activity analogous to that of the URM1 protein in eukaryotes. Together with additional, previously described genomic associations, these findings indicate that systems for protein quality control operating at different levels, including tRNA modification that controls translation fidelity, protein ubiquitination that regulates protein degradation, and, possibly, mRNA degradation by the exosome, are functionally and evolutionarily linked. C1 [Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Department of Health and Human Services of the USA (National Library of Medicine) FX The authors thank Valerie de Crecy-Lagard and Julie Maupin-Furlow for helpful discussions. The authors' research is supported by the intramural funds of the Department of Health and Human Services of the USA (National Library of Medicine). NR 65 TC 16 Z9 16 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1472-3646 J9 ARCHAEA JI Archaea PY 2010 AR 710303 DI 10.1155/2010/710303 PG 10 WC Microbiology SC Microbiology GA 740JY UT WOS:000288790500001 ER PT J AU Sakakibara, N Kasiviswanathan, R Kelman, Z AF Sakakibara, Nozomi Kasiviswanathan, Rajesh Kelman, Zvi TI Different Residues on the Surface of the Methanothermobacter thermautotrophicus MCM Helicase Interact with Single- and Double-Stranded DNA SO ARCHAEA-AN INTERNATIONAL MICROBIOLOGICAL JOURNAL LA English DT Article ID MINICHROMOSOME MAINTENANCE PROTEIN; THERMOAUTOTROPHICUM DELTA-H; BIOCHEMICAL-CHARACTERIZATION; SULFOLOBUS-SOLFATARICUS; CONSERVED LOOP; ARCHAEAL; INSIGHTS; BINDING; DOMAIN AB The minichromosome maintenance (MCM) complex is thought to function as the replicative helicase in archaea, separating the two strands of chromosomal DNA during replication. The catalytic activity resides within the C-terminal region of the MCM protein, while the N-terminal portion plays an important role in DNA binding and protein multimerization. An alignment of MCM homologues from several archaeal species revealed a number of conserved amino acids. Here several of the conserved residues located on the surface of the helicase have been mutated and their roles in MCM functions determined. It was found that some mutations result in increased affinity for ssDNA while the affinity for dsDNA is decreased. Other mutants exhibit the opposite effect. Thus, the data suggest that these conserved surface residues may participate in MCM-DNA interactions. C1 [Sakakibara, Nozomi; Kasiviswanathan, Rajesh] Univ Maryland, Ctr Adv Res Biotechnol, Inst Biotechnol, Rockville, MD 20850 USA. [Sakakibara, Nozomi] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Kasiviswanathan, Rajesh] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Kelman, Zvi] Univ Maryland, Dept Mol Genet & Cell Biol, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. RP Sakakibara, N (reprint author), Univ Maryland, Ctr Adv Res Biotechnol, Inst Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM sakakibaran@niaid.nih.gov RI Kasiviswanathan, Rajesh/D-2744-2012 FU NSF [MCB-0815646] FX The authors would like to thank Dr. Lori Kelman for her comments on the paper. This work was supported by a Grant from the NSF (MCB-0815646) awarded to Z. Kelman. NR 28 TC 1 Z9 1 U1 1 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1472-3646 J9 ARCHAEA JI Archaea PY 2010 AR 505693 DI 10.1155/2010/505693 PG 8 WC Microbiology SC Microbiology GA 740JQ UT WOS:000288789300001 ER PT J AU Weeraratna, AT Houben, R O'Connell, MP Becker, JC AF Weeraratna, Ashani T. Houben, Roland O'Connell, Michael P. Becker, Juergen C. TI Lack of Wnt5A Expression in Merkel Cell Carcinoma SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 [Weeraratna, Ashani T.; O'Connell, Michael P.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Houben, Roland; Becker, Juergen C.] Univ Hosp Wurzburg, Dept Dermatol, Wurzburg, Germany. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, 251 Bayview Blvd,Ste 100,Room 08C226, Baltimore, MD 21224 USA. EM weerarat@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999, ] NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2010 VL 146 IS 1 BP 88 EP 89 PG 2 WC Dermatology SC Dermatology GA 544WX UT WOS:000273692000018 PM 20083703 ER PT J AU Romitti, PA Watanabe-Galloway, S Budelier, WT Lynch, CF Puzhankara, S Wong-Gibbons, D Hoppin, JA Alavanja, MCR AF Romitti, Paul A. Watanabe-Galloway, Shinobu Budelier, William T. Lynch, Charles F. Puzhankara, Soman Wong-Gibbons, Donna Hoppin, Jane A. Alavanja, Michael C. R. TI Identification of Iowa Live Births in the Agricultural Health Study SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE children; occupational exposures; pesticides; pregnancy; prospective cohort ID PESTICIDE APPLICATORS; EXPOSURE; RISK; CHILDREN; COHORT; CRYPTORCHIDISM; PARTICIPANTS; PREGNANCY; RECORDS; ISSUES AB In the Agricultural Health Study, information on participant live births was largely provided by female partners of male private applicators. At the Iowa site, such information was available for 13,599 (42.9%) of 31,707 applicators. To improve identification of live births among Iowa participants, we used a probabilistic and deterministic approach to link available demographic data from 31,707 households and information on live births from 13,599 households with 1,014,916 Iowa birth certificates. Record linkage identified 16,611 (93.7%) of 17,719 reported live births and 17,883 additional live births, most (14,411 or 80.6%) not reported due to nonresponse by female partners. This record linkage produced an expanded cohort of live-born children among Iowa participants, which will facilitate improved study of the effects of agricultural exposures, including pesticides, on selected birth outcomes and childhood disease. C1 [Romitti, Paul A.; Budelier, William T.; Lynch, Charles F.; Puzhankara, Soman; Wong-Gibbons, Donna] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. [Watanabe-Galloway, Shinobu] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Epidemiol, Omaha, NE USA. [Hoppin, Jane A.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Alavanja, Michael C. R.] Natl Canc Inst, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Romitti, PA (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, 200 Hawkins Dr,C21E-GH, Iowa City, IA 52242 USA. EM paul-romitti@uiowa.edu FU Centers for Disease Control and Prevention [U50/CCU 713238, U01DD000492]; University of Iowa Center for Health Effects of Environmental Contamination [18018259]; National Institutes of Health; National Cancer Institute; National Institute of Environmental Health Sciences FX The grant sponsors for this study are the Centers for Disease Control and Prevention (U50/CCU 713238, U01DD000492) and The University of Iowa Center for Health Effects of Environmental Contamination (18018259). The Agricultural Health Study was funded by the intramural research programs of the National Institutes of Health, National Cancer Institute, and the National Institute of Environmental Health Sciences. NR 27 TC 4 Z9 4 U1 1 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 1933-8244 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PY 2010 VL 65 IS 3 BP 154 EP 162 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 645BH UT WOS:000281425400007 PM 20705576 ER PT J AU Beesdo, K Pine, DS Lieb, R Wittchen, HU AF Beesdo, Katja Pine, Daniel S. Lieb, Roselind Wittchen, Hans-Ulrich TI Incidence and Risk Patterns of Anxiety and Depressive Disorders and Categorization of Generalized Anxiety Disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; COMMON MENTAL-DISORDERS; DSM-IV ANXIETY; PROSPECTIVE-LONGITUDINAL COMMUNITY; PARTLY DIFFERENT ENVIRONMENTS; EARLY DEVELOPMENTAL-STAGES; PARENTAL REARING BEHAVIOR; MAJOR DEPRESSION; SURVEY REPLICATION AB Context: Controversy surrounds the diagnostic categorization of generalized anxiety disorder (GAD). Objectives: To examine the incidence, comorbidity, and risk patterns for anxiety and depressive disorders and to test whether developmental features of GAD more strongly support a view of this condition as a depressive as opposed to an anxiety disorder. Design: Face-to-face, 10-year prospective longitudinal and family study with as many as 4 assessment waves. The DSM-IV Munich Composite International Diagnostic Interview was administered by clinically trained interviewers. Setting: Munich, Germany. Participants: A community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34 years at last follow-up. Main Outcome Measures: Cumulative incidence of GAD, other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic disorder), and depressive disorders (major depressive disorder, and dysthymia). Results: Longitudinal associations between GAD and depressive disorders are not stronger than those between GAD and anxiety disorders or between other anxiety and depressive disorders. Survival analyses reveal that the factors associated with GAD overlap more strongly with those specific to anxiety disorders than those specific to depressive disorders. In addition, GAD differs from anxiety and depressive disorders with regard to family climate and personality profiles. Conclusions: Anxiety and depressive disorders appear to differ with regard to risk constellations and temporal longitudinal patterns, and GAD is a heterogeneous disorder that is, overall, more closely related to other anxiety disorders than to depressive disorders. More work is needed to elucidate the potentially unique aspects of pathways and mechanisms involved in the etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by cross-sectional features and diagnostic comorbidity patterns, minimizes the importance of longitudinal data on risk factors and symptom trajectories. Arch Gen Psychiatry. 2010; 67(1):47-57 C1 [Beesdo, Katja; Wittchen, Hans-Ulrich] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Lieb, Roselind; Wittchen, Hans-Ulrich] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Lieb, Roselind] Univ Basel, Inst Psychol Epidemiol & Hlth Psychol, CH-4003 Basel, Switzerland. RP Beesdo, K (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Chemnitzer St 46, D-01187 Dresden, Germany. EM Katja.Beesdo@tu-dresden.de RI Beesdo-Baum, Katja/A-5793-2012; Wittchen, Hans-Ulrich/A-8507-2014 FU German Federal Ministry of Education and Research [01EB9405/6, 01EB 9901/6, EB01016200, 01EB0140, 01EB0440]; Deutsche Forschungsgemeinschaft [LA1148/1-1, WI2246/1-1, WI709/7-1, WI 709/8-1] FX This work is part of the EDSP study, which is funded by grants 01EB9405/6, 01EB 9901/6, EB01016200, 01EB0140, and 01EB0440 from the German Federal Ministry of Education and Research. The field work and analyses were also supported in part by grants LA1148/1-1, WI2246/1-1, WI709/7-1, and WI 709/8-1 from the Deutsche Forschungsgemeinschaft. NR 125 TC 141 Z9 143 U1 9 U2 61 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2010 VL 67 IS 1 BP 47 EP 57 PG 11 WC Psychiatry SC Psychiatry GA 539NX UT WOS:000273262800006 PM 20048222 ER PT J AU Thambisetty, M Beason-Held, L An, Y Kraut, MA Resnick, SM AF Thambisetty, Madhav Beason-Held, Lori An, Yang Kraut, Michael A. Resnick, Susan M. TI APOE epsilon 4 Genotype and Longitudinal Changes in Cerebral Blood Flow in Normal Aging SO ARCHIVES OF NEUROLOGY LA English DT Article ID E ALLELE EPSILON-4; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; YOUNG INDIVIDUALS; COGNITIVE DECLINE; ELDERLY SUBJECTS; BRAIN ATROPHY; RISK; GENE; HIPPOCAMPAL AB Objective: To study differences in longitudinal changes in regional cerebral blood flow (rCBF) between apolipoprotein E (APOE) epsilon 4 carriers and noncarriers in non-demented older adults from the Baltimore Longitudinal Study of Aging using positron emission tomography in order to determine whether there are regionally specific longitudinal changes in rCBF in APOE epsilon 4 carriers that might be related to its well-established role as a genetic risk factor for Alzheimer disease. Design, Setting, and Participants: Using oxygen 15 ([(15)O])-labeled water positron emission tomography and voxel-based analysis, we compared changes in rCBF over an 8-year period between 29 nondemented APOE epsilon 4 carriers and 65 noncarriers older than 55 years. Serial neuropsychological data were collected for all participants. Results: Widespread differences were observed in longitudinal change in rCBF between epsilon 4 carriers and noncarriers. The predominant pattern was greater rCBF decline in epsilon 4 carriers. These differences were observed in the frontal, parietal, and temporal cortices. The affected brain regions were those especially vulnerable to pathological changes in Alzheimer disease. Both epsilon 4 carriers and noncarriers remained free of clinical diagnoses of dementia or mild cognitive impairment during the course of the study. Conclusions: Our findings suggest that APOE epsilon 4-mediated risk for Alzheimer disease is associated with widespread decline in rCBF over time that precedes the onset of dementia. Accelerated rates of decline in brain function in APOE epsilon 4 carriers may contribute to an increased risk for Alzheimer disease and a younger age at onset. C1 [Thambisetty, Madhav; Beason-Held, Lori; Resnick, Susan M.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [An, Yang] Johns Hopkins Univ, Sch Med, MedStar Res Inst, Baltimore, MD USA. [Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Thambisetty, M (reprint author), NIA, Lab Personal & Cognit, NIH, 251 Bayview Blvd,4B-311, Baltimore, MD 21224 USA. EM thambisetty@mail.nih.gov FU Intramural Research Program, National Institute on Aging, National Institutes of Health [N01-AG-3-2124]; MedStar Research Institute FX This work was supported in part by research and development contract N01-AG-3-2124 from the Intramural Research Program, National Institute on Aging, National Institutes of Health and by a research and development contract with MedStar Research Institute. NR 28 TC 50 Z9 51 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2010 VL 67 IS 1 BP 93 EP 98 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 542YQ UT WOS:000273535700013 PM 20065135 ER PT J AU Yeh, S Forooghian, F Wong, WT Faia, LJ Cukras, C Lew, JC Wroblewski, K Weichel, ED Meyerle, CB Sen, HN Chew, EY Nussenblatt, RB AF Yeh, Steven Forooghian, Farzin Wong, Wai T. Faia, Lisa J. Cukras, Catherine Lew, Julie C. Wroblewski, Keith Weichel, Eric D. Meyerle, Catherine B. Sen, Hatice Nida Chew, Emily Y. Nussenblatt, Robert B. TI Fundus Autofluorescence Imaging of the White Dot Syndromes SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCCULT OUTER RETINOPATHY; RELENTLESS PLACOID CHORIORETINITIS; RETINAL-PIGMENT EPITHELIUM; SERPIGINOUS CHOROIDITIS; MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; PROGRESSION; LIPOFUSCIN; ENTITY AB Objective: To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). Methods: Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. Results: Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P<.001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P<.001). Conclusions: Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs. C1 [Yeh, Steven; Forooghian, Farzin; Wong, Wai T.; Faia, Lisa J.; Cukras, Catherine; Lew, Julie C.; Wroblewski, Keith; Weichel, Eric D.; Meyerle, Catherine B.; Sen, Hatice Nida; Chew, Emily Y.; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Wroblewski, Keith; Weichel, Eric D.] Walter Reed Army Med Ctr, Dept Ophthalmol, Washington, DC 20307 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,10N-112, Bethesda, MD 20892 USA. EM DrBob@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute; National Institutes of Health; Heed Ophthalmic Foundation FX This study was supported in part by Intramural Funding of the National Eye Institute, National Institutes of Health, and the Heed Ophthalmic Foundation (Dr Yeh). NR 28 TC 29 Z9 31 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2010 VL 128 IS 1 BP 46 EP 56 DI 10.1001/archophthalmol.2009.368 PG 11 WC Ophthalmology SC Ophthalmology GA 542XO UT WOS:000273532800006 PM 20065216 ER PT J AU Tobian, AAR Gray, RH Quinn, TC AF Tobian, Aaron A. R. Gray, Ronald H. Quinn, Thomas C. TI Male Circumcision for the Prevention of Acquisition and Transmission of Sexually Transmitted Infections The Case for Neonatal Circumcision SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Review ID HUMAN-PAPILLOMAVIRUS INFECTION; RANDOMIZED CONTROLLED-TRIAL; ADULT MALE CIRCUMCISION; HIV-INFECTION; FEMALE PARTNERS; UNITED-STATES; CHLAMYDIA-TRACHOMATIS; NEWBORN CIRCUMCISION; BACTERIAL VAGINOSIS; CERVICAL-CANCER AB The American Academy of Pediatrics (AAP) male circumcision policy states that while there are potential medical benefits of newborn male circumcision, the data are insufficient to recommend routine neonatal circumcision. Since 2005, however, 3 randomized trials have evaluated male circumcision for prevention of sexually transmitted infections. The trials found that circumcision decreases human immunodeficiency virus acquisition by 53% to 60%, herpes simplex virus type 2 acquisition by 28% to 34%, and human papillomavirus prevalence by 32% to 35% in men. Among female partners of circumcised men, bacterial vaginosis was reduced by 40%, and Trichomonas vaginalis infection was reduced by 48%. Genital ulcer disease was also reduced among males and their female partners. These findings are also supported by observational studies conducted in the United States. The AAP policy has a major impact on neonatal circumcision in the United States. This review evaluates the recent data that support revision of the AAP policy to fully reflect the evidence of long-term health benefits of male circumcision. Arch Pediatr Adolesc Med. 2010; 164(1):78-84 C1 [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA. EM tquinn@jhmi.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Dr Quinn is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 75 TC 70 Z9 76 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 2010 VL 164 IS 1 BP 78 EP 84 PG 7 WC Pediatrics SC Pediatrics GA 539NY UT WOS:000273262900011 PM 20048246 ER PT J AU Brown, JM Chung, S Sawyer, JK Degirolamo, C Alger, HM Nguyen, TM Zhu, XW Duong, MN Brown, AL Lord, C Shah, R Davis, MA Kelley, K Wilson, MD Madenspacher, J Fessler, MB Parks, JS Rudel, LL AF Brown, J. Mark Chung, Soonkyu Sawyer, Janet K. Degirolamo, Chiara Alger, Heather M. Nguyen, Tam M. Zhu, Xuewei Duong, My-Ngan Brown, Amanda L. Lord, Caleb Shah, Ramesh Davis, Matthew A. Kelley, Kathryn Wilson, Martha D. Madenspacher, Jennifer Fessler, Michael B. Parks, John S. Rudel, Lawrence L. TI Combined Therapy of Dietary Fish Oil and Stearoyl-CoA Desaturase 1 Inhibition Prevents the Metabolic Syndrome and Atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE saturated fat; fish oil; atherosclerosis; inflammation; metabolic syndrome ID POLYUNSATURATED FATTY-ACIDS; TOLL-LIKE RECEPTOR-4; INSULIN-RESISTANCE; DEFICIENCY PROTECTS; HEPATIC STEATOSIS; TRANSGENIC MICE; INDUCED OBESITY; SATURATED FAT; MODULATION; GENE AB Background-Stearoyl-CoA desaturase 1 (SCD1) is a critical regulator of energy metabolism and inflammation. We have previously reported that inhibition of SCD1 in hyperlipidemic mice fed a saturated fatty acid (SFA)-enriched diet prevented development of the metabolic syndrome, yet surprisingly promoted severe atherosclerosis. In this study we tested whether dietary fish oil supplementation could prevent the accelerated atherosclerosis caused by SCD1 inhibition. Methods and Results-LDLr(-/-), ApoB(100/100) mice were fed diets enriched in saturated fat or fish oil in conjunction with antisense oligonucleotide (ASO) treatment to inhibit SCD1. As previously reported, in SFA-fed mice, SCD1 inhibition dramatically protected against development of the metabolic syndrome, yet promoted atherosclerosis. In contrast, in mice fed fish oil, SCD1 inhibition did not result in augmented macrophage inflammatory response or severe atherosclerosis. In fact, the combined therapy of dietary fish oil and SCD1 ASO treatment effectively prevented both the metabolic syndrome and atherosclerosis. Conclusions-SCD1 ASO treatment in conjunction with dietary fish oil supplementation is an effective combination therapy to comprehensively combat the metabolic syndrome and atherosclerosis in mice. (Arterioscler Thromb Vasc Biol. 2010;30:24-30.) C1 [Brown, J. Mark; Chung, Soonkyu; Sawyer, Janet K.; Degirolamo, Chiara; Nguyen, Tam M.; Zhu, Xuewei; Lord, Caleb; Shah, Ramesh; Davis, Matthew A.; Kelley, Kathryn; Wilson, Martha D.; Parks, John S.; Rudel, Lawrence L.] Wake Forest Univ, Sch Med, Dept Pathol, Sect Lipid Sci, Winston Salem, NC 27157 USA. [Alger, Heather M.] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. [Brown, Amanda L.] Wake Forest Univ, Sch Med, Dept Mol Med, Winston Salem, NC 27157 USA. [Duong, My-Ngan] Cleveland Clin, Dept Cell Biol, Cleveland, OH USA. [Madenspacher, Jennifer; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Rudel, LL (reprint author), Wake Forest Univ, Sch Med, Dept Pathol, Sect Lipid Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM lrudel@wfubmc.edu FU National Center for Complimentary and Alternative Medicine [NCCAM-P50AT002782]; National Institutes of Health [NIH-P01HL49373, R01-HL094525, 1K99HL096166-01]; American Heart Association [0625400U, 0825445E, 09POST2250225]; Howard Hughes Medical Institute FX This work was supported by grants from the National Center for Complimentary and Alternative Medicine (NCCAM-P50AT002782 to L. L. R. and J. S. P.), the National Institutes of Health (NIH-P01HL49373 to L. L. R. and J. S. P. R01-HL094525 to J. S. P., and 1K99HL096166-01 to J. M. B.), the American Heart Association (AHA postdoctoral fellowships #0625400U to J. M. B, #0825445E to S. C., and #09POST2250225 to X. Z.), and Howard Hughes Medical Institute (Gilliam Fellowship to T. M. N.). NR 56 TC 32 Z9 34 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2010 VL 30 IS 1 BP 24 EP U63 DI 10.1161/ATVBAHA.109.198036 PG 25 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 533KL UT WOS:000272822400009 PM 19834103 ER PT J AU Higashi-Kuwata, N Jinnin, M Makino, T Fukushima, S Inoue, Y Muchemwa, FC Yonemura, Y Komohara, Y Takeya, M Mitsuya, H Ihn, H AF Higashi-Kuwata, Nobuyo Jinnin, Masatoshi Makino, Takamitsu Fukushima, Satoshi Inoue, Yuji Muchemwa, Faith C. Yonemura, Yuji Komohara, Yoshihiro Takeya, Motohiro Mitsuya, Hiroaki Ihn, Hironobu TI Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; GENE-EXPRESSION; CIRCULATING MONOCYTES; SCAVENGER RECEPTORS; SERUM-LEVELS; POLARIZATION; CELLS; SCLERODERMA; DIFFERENTIATION; PATHOGENESIS AB Introduction: Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis (SSc). To analyze the assembly of the monocyte/macrophage population, we evaluated the expression of CD163 and CD204 and various activated macrophage markers, in the inflammatory cells of the skin and in the peripheral blood mononuclear cells (PBMCs) derived from patients with SSc. Methods: Skin biopsy specimens from 6 healthy controls and 10 SSc patients (7 limited cutaneous SSc and 3 diffuse cutaneous SSc) were analyzed by immunohistochemistry using monoclonal antibody against CD68 (pan-macrophage marker), CD163 and CD204. Surface and/or intracellular protein expression of CD14 (marker for monocyte lineage), CD163 and CD204 was analysed by flow cytometry in PBMCs from 16 healthy controls and 41 SSc patients (26 limited cutaneous SSc and 15 diffuse cutaneous SSc). Statistical analysis was carried out using Mann-Whitney U test for comparison of means. Results: In the skin from SSc patients, the number of CD163(+) cells or CD204(+) cells between the collagen fibers was significantly larger than that in healthy controls. Flow cytometry showed that the population of CD14(+) cells was significantly greater in PBMCs from SSc patients than that in healthy controls. Further analysis of CD14(+) cells in SSc patients revealed higher expression of CD163 and the presence of two unique peaks in the CD204 histogram. Additionally, we found that the CD163(+) cells belong to CD14(bright)CD204(+) population. Conclusions: This is the first report indicating CD163(+) or CD204(+) activated macrophages may be one of the potential fibrogenic regulators in the SSc skin. Furthermore, this study suggests a portion of PBMCs in SSc patients abnormally differentiates into CD14(bright)CD163(+)CD204(+) subset. The subset specific to SSc may play an important role in the pathogenesis of this disease, as the source of CD163(+) or CD204(+) macrophages in the skin. C1 [Higashi-Kuwata, Nobuyo; Jinnin, Masatoshi; Makino, Takamitsu; Fukushima, Satoshi; Inoue, Yuji; Muchemwa, Faith C.; Ihn, Hironobu] Kumamoto Univ, Fac Life Sci, Dept Dermatol & Plast & Reconstruct Surg, Kumamoto 8608556, Japan. [Yonemura, Yuji] Kumamoto Univ, Fac Life Sci, Dept Blood Transfus Med & Cell Therapy, Kumamoto 8608556, Japan. [Komohara, Yoshihiro; Takeya, Motohiro] Kumamoto Univ, Fac Life Sci, Dept Cell Pathol, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Fac Life Sci, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Jinnin, M (reprint author), Kumamoto Univ, Fac Life Sci, Dept Dermatol & Plast & Reconstruct Surg, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM mjin@kumamoto-u.ac.jp NR 32 TC 53 Z9 54 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 4 AR R128 DI 10.1186/ar3066 PG 10 WC Rheumatology SC Rheumatology GA 675PB UT WOS:000283841500003 PM 20602758 ER PT J AU Hinze, CH Fall, N Thornton, S Mo, JQ Aronow, BJ Layh-Schmitt, G Griffin, TA Thompson, SD Colbert, RA Glass, DN Barnes, MG Grom, AA AF Hinze, Claas H. Fall, Ndate Thornton, Sherry Mo, Jun Q. Aronow, Bruce J. Layh-Schmitt, GerlinDe Griffin, Thomas A. Thompson, Susan D. Colbert, Robert A. Glass, David N. Barnes, Michael G. Grom, Alexei A. TI Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID MACROPHAGE ACTIVATION SYNDROME; SERUM INTERLEUKIN-6 LEVELS; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; RHEUMATOID-ARTHRITIS; JOINT INVOLVEMENT; PERIPHERAL-BLOOD; IN-VITRO; ANEMIA; DIFFERENTIATION; PROFILES AB Introduction: Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene-expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared with related conditions. Methods: The 199 patients with JIA (23 sJIA and 176 non-sJIA) and 38 controls were studied. PBMCs were isolated and analyzed for multiple surface antigens with flow cytometry and for gene-expression profiles. The proportions of different PBMC subpopulations were compared among sJIA, non-sJIA patients, and controls and subsequently correlated with the strength of the erythropoiesis signature. Additional gene-expression data from patients with familial hemophagocytic lymphohistiocytosis (FHLH) and from a published sJIA cohort were analyzed to determine whether the erythropoiesis signature was present. Results: Patients with sJIA had significantly increased proportions of immature cell populations, including CD34(+) cells, correlating highly with the strength of the erythropoiesis signature. The erythropoiesis signature strongly overlapped with the gene-expression pattern in purified immature erythroid precursors. The expansion of immature cells was most prominently seen in patients with sJIA and anemia, even in the absence of reticulocytosis. Patients with non-sJIA and anemia did not exhibit the erythropoiesis signature. The erythropoiesis signature was found to be prominent in patients with FHLH and in a published cohort of patients with active sJIA, but not in patients with inactive sJIA. Conclusions: An erythropoiesis signature in active sJIA is associated with the expansion of CD34(+) cells, also is seen in some patients with FHLH and infection, and may be an indicator of ineffective erythropoiesis and hemophagocytosis due to hypercytokinemia. C1 [Hinze, Claas H.; Fall, Ndate; Thornton, Sherry; Layh-Schmitt, GerlinDe; Griffin, Thomas A.; Thompson, Susan D.; Colbert, Robert A.; Glass, David N.; Barnes, Michael G.; Grom, Alexei A.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA. [Mo, Jun Q.] Cincinnati Childrens Hosp Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. [Aronow, Bruce J.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA. [Hinze, Claas H.] Childrens Natl Med Ctr, Div Rheumatol, Washington, DC 20010 USA. [Layh-Schmitt, GerlinDe; Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hinze, CH (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM claas.hinze@gmail.com OI Hinze, Claas/0000-0001-9247-4729 FU NIH [P01 AR 048929, AR047784] FX The authors thank Drs. David D. Sherry (Children's Hospital of Philadelphia), Norman Ilowite and Beth Gottlieb (Schneider's Children's Hospital), and Judyann Olson (Medical College of Wisconsin) for data and sample collection. This work was supported by the NIH (Project Program Grant P01 AR 048929 and grant AR047784). NR 40 TC 21 Z9 23 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 3 AR R123 DI 10.1186/ar3061 PG 13 WC Rheumatology SC Rheumatology GA 629VJ UT WOS:000280227900068 PM 20576155 ER PT J AU Nguyen, CQ Yin, HE Lee, BH Carcamo, WC Chiorini, JA Peck, AB AF Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Carcamo, Wendy C. Chiorini, John A. Peck, Ammon B. TI Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like disease using adenovirus-mediated gene transfer SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SYNDROME (SJS)-LIKE DISEASE; NONOBESE DIABETIC MOUSE; T-HELPER-CELLS; SALIVARY-GLANDS; AUTOIMMUNE EXOCRINOPATHY; MURINE MODEL; NOD MICE; TGF-BETA; INFLAMMATION; T(H)17 AB Introduction: Sjogren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding T(H)17 cell populations that secrete predominantly interleukin (IL)-17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL-17A on the development and onset of SS. Methods: Adenovirus serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8 weeks of age or between 15 and 17 weeks of age. The mice were characterized for SS phenotypes. Results: Disease profiling indicated that SS-non-susceptible C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS-like disease profile, including the appearance of lymphocytic foci, increased cytokine levels, changes in antinuclear antibody profiles, and temporal loss of saliva flow. Conclusions: Induction of SS pathology by IL-17A in SS-non-susceptible mice strongly suggests that IL-17A is an important inflammatory cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be effective in preventing glandular dysfunction. C1 [Nguyen, Cuong Q.] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. [Nguyen, Cuong Q.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Nguyen, Cuong Q.; Lee, Byung Ha; Carcamo, Wendy C.; Peck, Ammon B.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. [Nguyen, Cuong Q.; Peck, Ammon B.] Univ Florida, Coll Dent, Ctr Orphan Autoimmune Disorders, Gainesville, FL 32610 USA. [Yin, Hongen; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Peck, Ammon B.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. RP Nguyen, CQ (reprint author), Eli & Edythe L Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM Nguyen@pathology.ufl.edu FU University of Florida; NIDCR [K99DE018958]; NIAID [R21AI081952]; Sjogren's Syndrome Foundation; Center for Orphan Autoimmune Disorders; NIH, NIDCR FX The authors would like to thank Dr. Jay K. Kolls and Dr. Julie Bindas (Children's Hospital of Pittsburgh) for generously providing the Ad5-LacZ and Ad5-IL17A vectors and Dr. Phil Cohen for his critical reading of the manuscript and helpful suggestions. We greatly appreciate the assistance of Dr. Craig Meyers and Dr. Nicholas Muzyczka for the use of the microscope. Publication of this article was funded in part by the University of Florida Open-Access publishing Fund.; This work was supported by PHS grants K99DE018958 (CQN) from NIDCR, R21AI081952 (ABP) from NIAID and funds from the Sjogren's Syndrome Foundation and Center for Orphan Autoimmune Disorders. HY and JAC were supported by an NIH, NIDCR intramural research grant. NR 41 TC 44 Z9 50 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 6 AR R220 DI 10.1186/ar3207 PG 11 WC Rheumatology SC Rheumatology GA 723OQ UT WOS:000287517000030 PM 21182786 ER PT J AU Tektonidou, MG Ward, MM AF Tektonidou, Maria G. Ward, Michael M. TI Validity of clinical associations of biomarkers in translational research studies: the case of systemic autoimmune diseases SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SURROGATE END-POINTS; LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION; PERIPHERAL-BLOOD; INTERFERON; VALIDATION; MARKERS; ISSUES; TESTS AB Introduction: Validity of biomarkers may be affected if studies do not include certain features in their design. We evaluated whether translational research studies of potential biomarkers incorporated design features important for valid clinical associations. Methods: We searched 10 journals for translational studies in six systemic autoimmune diseases published in 2004 through 2009. We included studies that reported associations between laboratory markers and the presence of disease, measures of disease activity, or prognosis. We examined the following design features: age, sex, and race matching; control for effects of treatment on expression of the biomarker; inclusion of patients with both early and late disease, or both active and inactive disease; longitudinal or cross-sectional design; and use of validated activity and damage measures. Results: Among 170 articles, 156 articles examined potential biomarkers for diagnosis, 37 for disease activity assessment, and nine for prognosis; 67 were studies of rheumatoid arthritis (RA); 48, of systemic lupus erythematosus; and 41, of other diseases. Gene-expression profiles were the most commonly examined potential biomarkers (n = 51). Fewer than one half of studies incorporated study-design features important for valid clinical associations. Only 47.4% of studies of biomarkers for diagnosis had groups that were age-matched, 45.5% were sex-matched, and 35.3% controlled for treatment. Studies that examined biomarkers in histologic samples and studies of RA were less likely to include important design features. Conclusions: Fewer than one half of translational studies of potential biomarkers incorporated design features needed for valid interpretation of clinical associations. Attention to these features could reduce false-positive and false-negative associations. C1 [Tektonidou, Maria G.; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Tektonidou, Maria G.] Natl Univ Athens, Sch Med, Dept Internal Med 1, Athens 11527, Greece. [Tektonidou, Maria G.] Euroclin Hosp, Athens 11521, Greece. RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 25 TC 9 Z9 10 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 5 AR R179 DI 10.1186/ar3143 PG 10 WC Rheumatology SC Rheumatology GA 685JV UT WOS:000284625900029 PM 20875104 ER PT J AU Nishikawa, T Matsuzawa, Y Suematsu, S Saito, J Omura, M Kino, T AF Nishikawa, Tetsuo Matsuzawa, Yoko Suematsu, Sachiko Saito, Jun Omura, Masao Kino, Tomoshige TI Effect of atorvastatin on aldosterone production induced by glucose, LDL or angiotensin II in human renal mesangial cells SO ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH LA English DT Article DE Aldosterone; Angiotensin II type I receptor; Atorvastatin; CAS 134523-03-8; CYP11B2; Mesangial cells ID MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; OXIDATIVE STRESS; STATINS; DISEASE; RAT; KIDNEY; HYPERTENSION; PROTEINURIA; EXPRESSION AB Nephropathy is a major complication of diabetes mellitus, thus development of rational therapeutic means is critical for improving public health. It was previously reported that human mesangial cells locally produced aldosterone, a steroid hormone that plays an important role in the development of diabetic nephropathy. The present experiments clarified the effect of glucose, LDL and angiotensin II, the molecules frequently elevated in patients with diabetic nephropathy, on aldosterone production in human primary mesangial cells. These cells expressed the CYP11B2 mRNA, a rate-limiting enzyme in the aldosterone biosynthesis. LDL and angiotensin II stimulated CYP11B2 mRNA expression in these cells, while a high concentration of glucose, angiotensin II and/or LDL increased aldosterone production. Importantly, atorvastatin (CAS 134523-03-8), an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor, strongly suppressed their effects on aldosterone production. Atorvastatin also suppressed positive effects of these compounds on the mRNA expression of the angiotensin II receptor type 1, thus atorvastatin exerted its negative effect in part through changing expression of this receptor. Since elevated levels of glucose and LDL, and increased action of the renin-angiotensin-aldosterone system is known to participate in the progression of diabetic nephropathy, it is speculated that the mesangial endocrine system that produces aldosterone locally is a promising therapeutic target for diabetic nephropathy where HMG-CoA reductase inhibitors provide a beneficial effect. C1 [Nishikawa, Tetsuo] Yokohama Rosai Hosp, Dept Med, Kohoku Ku, Yokohama, Kanagawa 2220036, Japan. [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Nishikawa, T (reprint author), Yokohama Rosai Hosp, Dept Med, Kohoku Ku, 3211 Kozukue Cho, Yokohama, Kanagawa 2220036, Japan. EM tetsuon@yokohamah.rofuku.go.jp FU Ministry of Public Health and Labor FX The present study was supported by a Grant-in-Aid for Scientific Research "Adrenal Disorders" provided from the Ministry of Public Health and Labor. NR 32 TC 7 Z9 7 U1 0 U2 0 PU ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN PI AULENDORF PA BANDELSTOCKWEG 20, POSTFACH 1255, D-88322 AULENDORF, GERMANY SN 0004-4172 J9 ARZNEIMITTEL-FORSCH JI Arzneimittelforschung PY 2010 VL 60 IS 7 BP 445 EP 451 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 633HZ UT WOS:000280493800006 PM 20712135 ER PT J AU Yanatatsaneeji, P Kitkumthorn, N Dhammawipark, C Rabalert, J Patel, V Mutirangura, A AF Yanatatsaneeji, Pattamawadee Kitkumthorn, Nakarin Dhammawipark, Chutintorn Rabalert, Jierada Patel, Vyomesh Mutirangura, Apiwat TI Codon72 Polymorphism in the P53 Tumor Suppressor Gene in Oral Lichen Planus Lesions in a Thai Population SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Oral lichen planus; polymorphism; p53 codon 72; apoptosis ID OPEN-ANGLE GLAUCOMA; CERVICAL-CANCER; LUNG-CANCER; EXPRESSION; APOPTOSIS; RISK; ASSOCIATION; FAS; GENOTYPE; ARGININE AB Background: Oral lichen planus (OLP) is a T-cell mediated autoimmune disease in which autocytotoxic CD8+ T cells (CTLs) trigger apoptosis of oral epithelial cells. Activated CTLs can produce Fas ligand and by binding to Fas lead to apoptosis. This Fas pathway and the action of p53 tumour suppressor gene are important in producing apoptosis. Current data demonstrate a link between these two factors at the transcriptional level. Objective: The purpose of this study was to investigate the p53 polymorphism at codon 72 which results in encoding of either proline or arginine. Methods: Our study used 97 OLP cases and 94 control blood samples from non-OLP individuals and performed PCR-RFLP. Results: Compared to control individuals, we found a significant increase in occurrence in OLP patients of the proline encoding cytosine allele (adjusted odd ratio (95% CI)=2.29 (1.42-3.70) and p=0.001). In addition, in individuals with the non-erosive type of OLP, the same situation was evident (OR=2.29, 95% CI (1.38-3.78), p=0.001). Furthermore, we noted a significantly higher prevalence of homozygosity [OR=3.17, 95% CI(1.58-7.25), p=0.001) for the p53 pro allele in the OLP group, which indicates a recessive mode of inheritance. Conclusion: Our data suggest a strong association between the pro/pro genotype and OLP, and that the process of apoptosis, in which p53 plays a role, is a factor in OLP pathogenesis. C1 [Yanatatsaneeji, Pattamawadee; Dhammawipark, Chutintorn; Rabalert, Jierada] Chulalongkorn Univ, Fac Sci, Dept Bot, Bangkok 10330, Thailand. [Kitkumthorn, Nakarin] Mahidol Univ, Fac Dent, Dept Oral Pathol, Bangkok 10700, Thailand. [Patel, Vyomesh] Natl Inst Craniofacial & Dent Res, NIH, Bethesda, MD USA. [Mutirangura, Apiwat] Chulalongkorn Univ, Fac Med, Dept Anat, Ctr Excellence Mol Genet Canc & Human Dis, Bangkok 10330, Thailand. RP Yanatatsaneeji, P (reprint author), Chulalongkorn Univ, Fac Sci, Dept Bot, Bangkok 10330, Thailand. EM simbj@mahidol.ac.th RI Mutirangura, Apiwat /C-8197-2009 FU Centre of Excellence in Molecular Genetics of Cancer and Human, Department of Anatomy, Faculty of Medicine, Chulalongkorn University [MRG 5180006]; Faculty of Science, Chulalongkorn University FX The authors are grateful to Mr. Dusit Bumalee for his excellent technical assistance. In addition, we are grateful to Dr. Paddi Lund, BDS; FRACDS for kindly revising the manuscript. This work was supported by Centre of Excellence in Molecular Genetics of Cancer and Human, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, TRF-MRG young scientific researcher grant No. MRG 5180006 and TRF senior research scholar grant and Research Funds from the Faculty of Science, Chulalongkorn University. NR 34 TC 2 Z9 2 U1 0 U2 1 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI NAGOYA PA 4-84 JOTO-CHO, KITA-KU, NAGOYA, 462-0831, JAPAN SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2010 VL 11 IS 4 BP 1137 EP 1141 PG 5 WC Oncology SC Oncology GA 699CY UT WOS:000285642700052 PM 21133638 ER PT J AU Ferrucci, LM Daniel, CR Kapur, K Chadha, P Shetty, H Graubard, BI George, PS Osborne, W Yurgalevitch, S Devasenapathy, N Chatterjee, N Prabhakaran, D Gupta, PC Mathew, A Sinha, R AF Ferrucci, Leah M. Daniel, Carrie R. Kapur, Kavita Chadha, Puneet Shetty, Hemali Graubard, Barry I. George, Preethi S. Osborne, Whitney Yurgalevitch, Susan Devasenapathy, Niveditha Chatterjee, Nilanjan Prabhakaran, Dorairaj Gupta, Prakash C. Mathew, Aleyamma Sinha, Rashmi TI Measurement of Spices and Seasonings in India: Opportunities for Cancer Epidemiology and Prevention SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE India; diet; spices; cooking oils; cancer prevention ID ISCHEMIC-HEART-DISEASE; N-3 FATTY-ACIDS; SOUTH-INDIA; CARDIOVASCULAR-DISEASE; ORGANOSULFUR COMPOUNDS; COLORECTAL-CARCINOMA; PROSPECTIVE COHORT; ALLIUM VEGETABLES; DIETARY-INTAKE; COSTA-RICA AB Bioactive components of many foods added during cooking have potential antioxidant, anti-inflammatory, antimicrobial, antibacterial and chemopreventive properties. However, epidemiologic studies generally do not collect detailed information on these items, which include spices, chilies, coconuts, garlic, onions, and oils. Since India has some of the highest spice consumption in the world, we developed a computer-based food preparer questionnaire to estimate per capita consumption of 19 spices, chilies, coconuts, garlic, onions, and 13 cooking oils among 3,625 participants in the India Health Study, a multicenter pilot study in three regions of India. We observed notable regional differences in consumption of spices, chilies, coconut, garlic, and onions. In Trivandrum, over 95 percent of the participants consumed 12 different spices, while in New Delhi and Mumbai, 95 percent of participants consumed only four and five spices, respectively. Cooking oil use also varied, as ghee was most common in New Delhi (96.8%) followed by mustard seed oil (78.0%), while in Trivandrum the primary oil was coconut (88.5%) and in Mumbai it was peanut (68.5%). There was some variation in consumption by education, income, and religion. Using a novel method for assessing food items primarly added during cooking, we successfully estimated per capita consumption within an epidemiologic study. Based on basic science research and suggestive ecologic level data on cancer incidence and spice consumption, improving epidemiologic assessment of these potentially chemopreventive food items may enhance our understanding of diet and cancer risk. C1 [Ferrucci, Leah M.; Daniel, Carrie R.; Graubard, Barry I.; Osborne, Whitney; Chatterjee, Nilanjan; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Kapur, Kavita] Steno Diabet Control, Gentofte, Denmark. [Chadha, Puneet; Devasenapathy, Niveditha; Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India. [Shetty, Hemali; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India. [George, Preethi S.; Mathew, Aleyamma] Reg Canc Ctr, Trivandrum 695011, Kerala, India. [Yurgalevitch, Susan] WESTAT Corp, Rockville, MD 20850 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. EM sinhar@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS [ZIA CP010194-04] NR 57 TC 9 Z9 10 U1 0 U2 10 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2010 VL 11 IS 6 BP 1621 EP 1629 PG 9 WC Oncology SC Oncology GA 772EM UT WOS:000291216400031 PM 21338207 ER PT J AU Mason, A Lee, SH Lee, R AF Mason, Andrew Lee, Sang-Hyop Lee, Ronald BE Kawai, M Lee, JW Petri, PA TI Will demographic change undermine Asia's growth prospects? SO ASIAN REGIONALISM IN THE WORLD ECONOMY: ENGINE FOR DYNAMISM AND STABILITY LA English DT Article; Book Chapter ID DEVELOPING-COUNTRIES; ECONOMIC-GROWTH; REMITTANCES; LONGEVITY; TAIWAN C1 [Mason, Andrew; Lee, Sang-Hyop] Univ Hawaii Manoa, Honolulu, HI 96822 USA. [Mason, Andrew; Lee, Sang-Hyop] East West Ctr, Honolulu, HI 96848 USA. [Mason, Andrew] Natl Transfer Account Project, Berkeley, CA USA. [Lee, Ronald] Univ Michigan, Dept Econ, Ann Arbor, MI 48109 USA. [Lee, Ronald] Univ Michigan, Ctr Populat Studies, Ann Arbor, MI 48109 USA. [Lee, Ronald] NIH, Populat & Social Sci Study Sect, Bethesda, MD USA. [Lee, Ronald] Natl Advisory Council Aging, Bethesda, MD USA. [Lee, Ronald] Univ Calif Berkeley, Ctr Econ & Demog Aging, Berkeley, CA USA. RP Mason, A (reprint author), Univ Hawaii Manoa, Honolulu, HI 96822 USA. NR 59 TC 2 Z9 2 U1 0 U2 0 PU EDWARD ELGAR PUBLISHING LTD PI CHELTENHAM PA GLENSANDA HOUSE, MONTPELLIER PARADE, CHELTENHAM GL50 1UA, GLOS, ENGLAND BN 978-1-84844-854-4 PY 2010 BP 70 EP 121 PG 52 WC Economics SC Business & Economics GA BZB77 UT WOS:000301058200003 ER PT J AU Cheng, AW Hou, Y Mattson, MP AF Cheng, Aiwu Hou, Yan Mattson, Mark P. TI Mitochondria and neuroplasticity SO ASN NEURO LA English DT Review DE neural progenitor cell; mitochondria biogenesis; mitochondria fission and fusion ID AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; TRANSCRIPTIONAL COACTIVATOR PGC-1; IMPAIRED SYNAPTIC PLASTICITY; TRAUMATIC BRAIN-INJURY; NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; STEM-CELLS; HUNTINGTONS-DISEASE AB The production of neurons from neural progenitor cells, the growth of axons and dendrites and the formation and reorganization of synapses are examples of neuroplasticity. These processes are regulated by cell-autonomous and intercellular (paracrine and endocrine) programs that mediate responses of neural cells to environmental input. Mitochondria are highly mobile and move within and between subcellular compartments involved in neuroplasticity (synaptic terminals, dendrites, cell body and the axon). By generating energy (ATP and NAD(+)), and regulating subcellular Ca2+ and redox homoeostasis, mitochondria may play important roles in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodelling. Particularly intriguing is emerging data suggesting that mitochondria emit molecular signals (e. g. reactive oxygen species, proteins and lipid mediators) that can act locally or travel to distant targets including the nucleus. Disturbances in mitochondrial functions and signalling may play roles in impaired neuroplasticity and neuronal degeneration in Alzheimer's disease, Parkinson's disease, psychiatric disorders and stroke. C1 [Cheng, Aiwu; Hou, Yan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Cheng, AW (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM chengai@mail.nih.gov; mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 157 TC 97 Z9 103 U1 3 U2 26 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2010 VL 2 IS 5 BP 243 EP 256 AR e00045 DI 10.1042/AN20100019 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 731FM UT WOS:000288091700001 PM 20957078 ER PT S AU Ghosh, AK Chapsal, BD Mitsuya, H AF Ghosh, Arun K. Chapsal, Bruno D. Mitsuya, Hiroaki BE Ghosh, AK TI Darunavir, a New PI with Dual Mechanism: From a Novel Drug Design Concept to New Hope Against Drug-Resistant HIV SO ASPARTIC ACID PROTEASES AS THERAPEUTIC TARGETS SE Methods and Principles in Medicinal Chemistry LA English DT Article; Book Chapter ID VIRUS TYPE-1 PROTEASE; TREATMENT-EXPERIENCED PATIENTS; ONCE-DAILY DARUNAVIR/RITONAVIR; HIGH-AFFINITY P-2-LIGANDS; PLACEBO-CONTROLLED TRIAL; LOW-DOSE RITONAVIR; 2 BINDING-SITES; HIV-1-INFECTED PATIENTS; CRYSTAL-STRUCTURE; TREATMENT-NAIVE C1 [Ghosh, Arun K.; Chapsal, Bruno D.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Mitsuya, Hiroaki] NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Expt Retrovirol Sect, Bethesda, MD 20892 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA. NR 107 TC 4 Z9 4 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY SN 1865-0562 BN 978-3-527-31811-7 J9 METH PRIN MED CHEM PY 2010 VL 45 BP 205 EP 243 D2 10.1002/9783527630943 PG 39 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BA6WV UT WOS:000337297200010 ER PT S AU Mitsuya, H Ghosh, AK AF Mitsuya, Hiroaki Ghosh, Arun K. BE Ghosh, AK TI Development of HIV-1 Protease Inhibitors, Antiretroviral Resistance, and Current Challenges of HIV/AIDS Management SO ASPARTIC ACID PROTEASES AS THERAPEUTIC TARGETS SE Methods and Principles in Medicinal Chemistry LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOLUTION CRYSTAL-STRUCTURES; DRUG-RESISTANCE; TYPE-1 PROTEASE; ACTIVE-SITE; THERAPY; SELECTION; VARIANTS; DESIGN; MUTATIONS C1 [Mitsuya, Hiroaki] NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Expt Retrovirol Sect, Bethesda, MD 20892 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Expt Retrovirol Sect, Bldg 10,Room 5A11,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 2 Z9 2 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY SN 1865-0562 BN 978-3-527-31811-7 J9 METH PRIN MED CHEM PY 2010 VL 45 BP 245 EP 262 D2 10.1002/9783527630943 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BA6WV UT WOS:000337297200011 ER PT B AU Groll, AH Roilides, E Walsh, TJ AF Groll, Andreas H. Roilides, Emmanuel Walsh, Thomas J. BE Pasqualotto, AC TI Invasive Aspergillosis in Paediatric Patients SO ASPERGILLOSIS: FROM DIAGNOSIS TO PREVENTION LA English DT Article; Book Chapter DE Aspergillosis; Children; Diagnosis; Epidemiology; Neonates; Prevention; Treatment ID HEMATOPOIETIC STEM-CELL; CHRONIC GRANULOMATOUS-DISEASE; LIPOSOMAL AMPHOTERICIN-B; CENTRAL-NERVOUS-SYSTEM; MULTICENTER RETROSPECTIVE ANALYSIS; PRIMARY CUTANEOUS ASPERGILLOSIS; MARROW TRANSPLANT RECIPIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CENTER EXPERIENCE; CRITICALLY-ILL PATIENTS AB Invasive aspergillosis is an important cause of infectious morbidity and mortality in children with innate or acquired deficiencies in phagocytic host defences and anatomical barriers. Similar to adults, it most commonly affects the lung, and remains difficult to diagnose. Prognosis depends on early recognition, prompt institution of appropriate treatment and restoration of host defences. Paediatric patients represent a distinct population in regard to clinical presentation and epidemiology, and in particular, the utility of diagnostic tools such as the serum galactomannan ELISA and high resolution computed tomography scan imaging. The disposition of antifungal agents with clinical efficacy against invasive aspergillosis is different, resulting in different dosages across age groups and differential therapeutic algorithms due to the lack of either published clinical experience or a paediatric dosage as in the setting of antifungal prophylaxis. This chapter reviews presentation and epidemiology of invasive aspergillosis, in neonates, children and adolescents and discusses the value of currents diagnostics as well as options for treatment and prevention in these distinct Populations. C1 [Groll, Andreas H.] Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. [Groll, Andreas H.] Univ Childrens Hosp, Dept Pediat Hematol Oncol, Munster, Germany. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54006 Thessaloniki, Greece. RP Groll, AH (reprint author), Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. EM grollan@ukmuenster.de; roilides@med.auth.gr; walsht@mail.nih.gov NR 117 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2407-7 PY 2010 BP 461 EP 483 DI 10.1007/978-90-481-2408-4_28 PG 23 WC Dermatology; Mycology SC Dermatology; Mycology GA BMJ13 UT WOS:000272541500028 ER PT J AU Lenker, JA Fuhrer, MJ Jutai, JW Demers, L Scherer, MJ DeRuyter, F AF Lenker, James A. Fuhrer, Marcus J. Jutai, Jeffrey W. Demers, Louise Scherer, Marcia J. DeRuyter, Frank TI Treatment Theory, Intervention Specification, and Treatment Fidelity in Assistive Technology Outcomes Research SO ASSISTIVE TECHNOLOGY LA English DT Article DE assistive technology; evidence-based practice; outcomes research; treatment fidelity; treatment specification; treatment theory ID DEVICE OUTCOMES; HEALTH BEHAVIOR; CLINICAL-TRIALS; OLDER-ADULTS; BLACK-BOX; REHABILITATION; CARE; TAXONOMY; DISABILITIES; CHALLENGES AB Recent reports in the rehabilitation literature have suggested that treatment theory, intervention specification, and treatment fidelity have important implications for the design, results, and interpretation of outcomes research. At the same time, there has been relatively little discussion of how these concepts bear on the quality of assistive technology (AT) outcomes research. This article describes treatment theory, intervention specification, and treatment fidelity as interconnected facets of AT outcome studies that fundamentally affect the interpretation of their findings. The discussion of each is elucidated using case examples drawn from the AT outcomes research literature. Recommendations are offered for strengthening these components of AT outcomes research. C1 [Lenker, James A.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Rehabil Sci, Buffalo, NY 14214 USA. [Fuhrer, Marcus J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Jutai, Jeffrey W.] Univ Ottawa, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada. [Demers, Louise] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada. [Scherer, Marcia J.] Inst Matching Person & Technol, Webster, NY USA. [DeRuyter, Frank] Duke Univ, Med Ctr, Dept Surg, Div Speech Pathol & Audiol, Durham, NC 27710 USA. RP Lenker, JA (reprint author), SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Rehabil Sci, 515 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. EM lenker@buffalo.edu OI Scherer, Marcia/0000-0001-8374-6526; Jutai, Jeffrey/0000-0002-7294-1323 NR 66 TC 13 Z9 13 U1 1 U2 4 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2010 VL 22 IS 3 BP 129 EP 138 DI 10.1080/10400430903519910 PG 10 WC Rehabilitation SC Rehabilitation GA 803YX UT WOS:000293620200001 PM 20939422 ER PT B AU Ortega, AN Koinis-Mitchell, D Gergen, PJ AF Ortega, Alexander N. Koinis-Mitchell, Daphne Gergen, Peter J. BE Harver, A Kotses, H TI Asthma in Minority Populations SO ASTHMA, HEALTH AND SOCIETY: A PUBLIC HEALTH PERSPECTIVE LA English DT Article; Book Chapter ID INNER-CITY CHILDREN; PUERTO-RICAN CHILDREN; AFRICAN-AMERICAN CHILDREN; RANDOMIZED CLINICAL-TRIAL; HEALTH-CARE USE; CHILDHOOD ASTHMA; UNITED-STATES; EMERGENCY-DEPARTMENT; PANIC DISORDER; ENVIRONMENTAL INTERVENTION C1 [Ortega, Alexander N.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Ortega, Alexander N.] Univ Calif Los Angeles, Inst Social Res, Los Angeles, CA 90095 USA. [Koinis-Mitchell, Daphne] Brown Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI USA. [Gergen, Peter J.] NIAID, NIH, Atlanta, GA USA. RP Ortega, AN (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, 2134 Rolfe Hall, Los Angeles, CA 90095 USA. EM aortega@ucla.edu NR 127 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-78284-3 PY 2010 BP 263 EP 276 DI 10.1007/978-0-387-78285-0_16 D2 10.1007/978-0-387-78285-0 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA BNH62 UT WOS:000274571400016 ER PT J AU Selvin, E Najjar, SS Cornish, TC Halushka, MK AF Selvin, Elizabeth Najjar, Samer S. Cornish, Toby C. Halushka, Marc K. TI A comprehensive histopathological evaluation of vascular medial fibrosis: Insights into the pathophysiology of arterial stiffening SO ATHEROSCLEROSIS LA English DT Article DE Arteriosclerosis; Fibrosis; Image analysis; Tissue microarrays ID PULSE-WAVE VELOCITY; AGE-RELATED-CHANGES; AORTIC STIFFNESS; INDEPENDENT PREDICTOR; CARDIOVASCULAR RISK; BLOOD-PRESSURE; ATHEROSCLEROSIS; HYPERTENSION; CARDIOLOGY; SURVIVAL AB Objective: Medial vascular fibrosis contributes to arterial stiffening and reduced compliance, increasing the risk of cardiovascular events. We undertook the first comprehensive histopathologic study of medium-to-large caliber blood vessels (carotid, coronary, dorsalis pedis, internal mammary, iliac, mesenteric, pulmonary, and renal arteries) in 100 autopsy subjects to characterize medial fibrosis in relation to cardiovascular risk factors. Methods and results: Masson Trichrome staining of vascular tissue microarrays (TMAs) was digitally analyzed to determine the percent fibrosis (% collagen) of over 700 vascular segments. The percent fibrosis of the tunica media was strongly correlated within subjects across all systemic blood vessels (average r = 0.53), suggesting that fibrosis is a global process independent of the predilection of the vessel towards the development of atherosclerosis. Hypertension, diabetes, age and poor renal function were significantly associated with increased systemic vascular fibrosis (p <= 0.03). By multivariable analysis, only poor renal function (p = 0.003) was an independent predictor of higher levels of fibrosis. Finally, in a subset of 13 individuals we observed a significant correlation between pre-mortem pulse pressure and systemic vascular fibrosis (p < 0.001). Conclusions: This study demonstrates that vascular fibrosis is a global process associated with diseases of aging and elevated pulse pressures. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol & Med, Baltimore, MD USA. [Cornish, Toby C.; Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA. [Najjar, Samer S.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Halushka, MK (reprint author), Ross Bldg,RM 632L,720 Rutland Ave, Baltimore, MD 21205 USA. EM mhalush1@jhmi.edu RI Cornish, Toby/A-4394-2015; OI Cornish, Toby/0000-0002-1902-2109; Halushka, Marc/0000-0002-7112-7389 FU American Diabetes Association [1-05-JF-20]; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK076595]; National Institutes of Health/National Institute on Aging FX This study was supported by a junior faculty award from the American Diabetes Association (1-05-JF-20 to MKH), by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK076595 to ES) and supported in part by the Intramural Research Program of the National Institutes of Health/National Institute on Aging. NR 30 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2010 VL 208 IS 1 BP 69 EP 74 DI 10.1016/j.atherosclerosis.2009.06.025 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543IF UT WOS:000273567300014 PM 19632677 ER PT J AU Giallauria, F Cirillo, P Lucci, R Pacileo, M D'Agostino, M Maietta, P Vitelli, A Chiariello, M Vigorito, C AF Giallauria, Francesco Cirillo, Plinio Lucci, Rosa Pacileo, Mario D'Agostino, Mariantonietta Maietta, Paola Vitelli, Alessandra Chiariello, Massimo Vigorito, Carlo TI Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction SO ATHEROSCLEROSIS LA English DT Article DE High mobility group box-1; Autonomic dysfunction; Heart rate recovery; Cardiac remodeling; Myocardial infarction; Left ventricular remodeling ID HEART-RATE RECOVERY; GLYCATION END-PRODUCTS; HIGH-MOBILITY-GROUP-BOX-1 PROTEIN; CARDIAC REHABILITATION; INFLAMMATORY RESPONSE; CLINICAL-IMPLICATIONS; DIABETIC-NEUROPATHY; TREADMILL EXERCISE; MORTALITY; DISEASE AB Background: High mobility group box-1 (HMGB1) protein, a critical mediator of inflammatory processes, is a novel predictor of adverse post-infarction clinical outcomes, being involved in the healing process after MI. Heart rate recovery (HRR), a marker of autonomic function defined as the fall in heart rate during the first minute after exercise, is a powerful predictor of mortality in post-infarction patients. The present study was designed to test the hypothesis that HMGB1 is associated with autonomic dysfunction in post-infarction patients. Methods: Sixty-seven consecutive patients ( mean age 59.3 years, 84% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise and HMGB1 assay. Results: HMGB1 levels were inversely correlated with peak oxygen consumption (VO(2peak)) (r = -0.449, P < 0.001), with left ventricular ejection fraction (LVEF) (r = -0.360, P = 0.003), and with HRR (r = -0.387, P < 0.001). In a linear regression analysis adjusted for multiple confounders, we found a significant inverse association between HMGB1 levels and HRR independent of age, gender, body mass index, VO(2peak), slope of increase in ventilation over carbon dioxide output (VE/VCO(2slope)), and presence of diabetes (beta = -0.377, P = 0.034). Conclusions: This study provided the first evidence for a significant association between increased HMGB1 levels and autonomic dysfunction expressed by post-exercise slower HRR in post-infarction patients. The prognostic implication of such association needs to be explored as well as whether HMGB1 could represent a valid marker for risk stratification either during the acute phase or long-term after MI. (c) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Giallauria, Francesco; Lucci, Rosa; D'Agostino, Mariantonietta; Vitelli, Alessandra; Vigorito, Carlo] Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med Cardiovasc & Immunol Sci, I-80131 Naples, NA, Italy. [Giallauria, Francesco] Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, NIA, Baltimore, MD 21225 USA. [Cirillo, Plinio; Pacileo, Mario; Maietta, Paola; Chiariello, Massimo] Univ Naples Federico 2, Dept Clin Med Cardiovasc & Immunol Sci, Div Cardiol, I-80131 Naples, NA, Italy. RP Giallauria, F (reprint author), Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med Cardiovasc & Immunol Sci, Via Pansini 5, I-80131 Naples, NA, Italy. EM giallauria@libero.it RI Giallauria, Francesco/B-5681-2013; OI Giallauria, Francesco/0000-0003-4119-9397; CIRILLO, Plinio/0000-0001-7818-4952 FU University of Naples "Federico II"; NIH, National Institute on Aging FX This research was supported by University of Naples "Federico II" and in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 41 TC 13 Z9 15 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2010 VL 208 IS 1 BP 280 EP 284 DI 10.1016/j.atherosclerosis.2009.07.025 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 543IF UT WOS:000273567300047 PM 19651408 ER PT B AU Lewis, DEA Lee, SJ Adhya, S AF Lewis, Dale E. A. Lee, Sang Jun Adhya, Sankar BE Dame, RT Dorman, CJ TI Role of HU in Regulation of gal Promoters SO BACTERIAL CHROMATIN LA English DT Article; Book Chapter DE Anti-parallel DNA Looping; Atomic Force Microscopy; gal Operon; GalR; HU ID PROTEIN DNA COMPLEXES; HISTONE-LIKE PROTEINS; RNA-POLYMERASE CONTACT; SITE-SPECIFIC BINDING; ESCHERICHIA-COLI; LAC REPRESSOR; GALACTOSE OPERON; CRYSTAL-STRUCTURE; CYCLIC-AMP; TRANSPOSITION INTERMEDIATE AB HU is one of the histone-like DNA binding proteins, which are involved in maintaining the nucleoid structure in bacteria. HU has also been shown to participate in transcriptional regulation of specific promoters. In this chapter, we provide an overview of the mechanism of HU action in the transcriptional regulation of the two promoters of the gal operon in E. coli by providing results of genetic, biophysical and biochemical experiments both in vivo and in vitro. C1 [Lewis, Dale E. A.; Lee, Sang Jun; Adhya, Sankar] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM adhyas@mail.nih.gov NR 96 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-3472-4 PY 2010 BP 395 EP 417 DI 10.1007/978-90-481-3473-1_17 D2 10.1007/978-90-481-3473-1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BNM34 UT WOS:000274942100017 ER PT S AU Merikangas, KR Swanson, SA AF Merikangas, Kathleen Ries Swanson, Sonja Alsemgeest BE Stein, MB Steckler, T TI Comorbidity in Anxiety Disorders SO BEHAVIORAL NEUROBIOLOGY OF ANXIETY AND ITS TREATMENT SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Comorbidity; Anxiety disorders; NCS-R; Epidemiology; Family studies; Medical conditions ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MAJOR DEPRESSIVE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; CORONARY-HEART-DISEASE; SUBSTANCE USE DISORDERS; HIGH-SCHOOL-STUDENTS; MENTAL-DISORDERS; PANIC-ATTACKS; CO-MORBIDITY AB Ever since Feinstein coined the term "comorbidity", referring to the presence of any additional coexisting ailment in a patient with a particular index disease (J Chronic Dis 23:455-468, 1970), aspects of the phenomenon have been extensively studied. The aims of this chapter are: (1) to summarize the evidence of psychiatric comorbidity in anxiety disorders from adult population-based studies; (2) to present findings from the National Comorbidity Survey Replication (NCS-R); (3) to summarize evidence of psychiatric comorbidity in anxiety disorders from child and adolescent population-based samples; (4) to provide a summary of evidence on comorbidity from family and genetic studies; and (5) to examine patterns of comorbidity between anxiety disorders and medical conditions. Throughout each of these aims, implications of the comorbidity are explored, including whether these patterns reflect a need for redefining the disorders or rather an etiologic or even causal path. C1 [Merikangas, Kathleen Ries; Swanson, Sonja Alsemgeest] NIMH, Genet Epidemiol Res Branch, Mood & Anxiety Disorders Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Merikangas, Kathleen Ries] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Mood & Anxiety Disorders Program, US Dept HHS,NIH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM Kathleen.Merikangas@nih.gov NR 120 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-02911-0 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2010 VL 2 BP 37 EP 59 DI 10.1007/7854_2009_32 D2 10.1007/978-3-642-02912-7 PG 23 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BPM17 UT WOS:000279232700003 PM 21309105 ER PT S AU Rabin, CR Siegel, SJ AF Rabin, Cara R. Siegel, Steven J. BE Swerdlow, NR TI Antipsychotic Dosing and Drug Delivery SO BEHAVIORAL NEUROBIOLOGY OF SCHIZOPHRENIA AND ITS TREATMENT SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Schizophrenia; Medication; Dopamine; D2; Depot; Delivery ID ABA TRIBLOCK COPOLYMERS; SCHIZOPHRENIC-PATIENTS; MEDICATION ADHERENCE; RECEPTOR OCCUPANCY; IN-VITRO; SUBCUTANEOUS IMPLANTATION; PHARMACOLOGICAL-TREATMENT; ATYPICAL ANTIPSYCHOTICS; ALVEOLAR MACROPHAGES; PROLACTIN RESPONSES AB This chapter addresses the current state of affairs regarding proposed mechanism of action for antipsychotic medications and how this mechanism relates to dosing and delivery strategies. The initial portion describes the history of antipsychotic medication, including key discoveries that contribute to the dopamine hypothesis of schizophrenia and provide evidence that dopamine D-2 receptor antagonism remains the most copasetic explanation for both determination of dose and degree of efficacy for current antipsychotic medications. Early observations regarding the unique properties of clozapine and how those observations led to the misconception and misnomer of atypicality are also discussed. Subsequent sections relate the dosing of available medications using chlorpromazine equivalents, with a discussion of non-D-2-related mechanisms to antipsychotic effects. The balance of the chapter explores the temporal pattern of receptor occupancy as a key determinant of antipsychotic effectiveness, noting that continuous infusion would present the optimal method of treatment. In addition to the pharmacodynamic benefits of continuous long-term delivery systems, the incidence, causes, and clinical consequences of poor adherence are addressed. These observations are then discussed in the context of clinical studies and meta-analyses, demonstrating superiority of long-term depot preparations over oral administration. However, despite overwhelming evidence in favor of long-term delivery systems, few options are available to provide such ideal medication delivery profiles. Barriers to creating traditional depot preparations for a large number of antipsychotic agents, as well as efforts to address these limitations with polymer-based microspheres are described. The potential extension of current formulations to very long-term delivery implants using biodegradable and nonbiodegradable platforms is then described. Benefits as well as limitations of such systems are discussed with respect to clinical and ethical issues as well as a brief description of potential regulatory and logistic barriers to developing better delivery options. In summary, this chapter describes the basis for relating the dose of all existing antipsychotic medications to dopamine D-2 receptor affinity and the potential contribution of continuous occupancy to enhanced efficacy through superior biological effects and improved adherence. C1 [Siegel, Steven J.] Univ Penn, Dept Psychiat, Translat Neurosci Program, Philadelphia, PA 19104 USA. [Rabin, Cara R.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Siegel, SJ (reprint author), Univ Penn, Dept Psychiat, Translat Neurosci Program, 125 So 31st St, Philadelphia, PA 19104 USA. EM cara.rabin@gmail.com; siegels@mail.med.upenn.edu OI Siegel, Steven/0000-0001-8058-9713 NR 136 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-13716-7 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2010 VL 4 BP 141 EP 177 DI 10.1007/7854_2010_46 D2 10.1007/978-3-642-13717-4 PG 37 WC Neurosciences SC Neurosciences & Neurology GA BQY42 UT WOS:000282104600006 PM 21312400 ER PT J AU Riley, WT Mihm, P Behar, A Morin, CM AF Riley, William T. Mihm, Patricia Behar, Albert Morin, Charles M. TI A Computer Device to Deliver Behavioral Interventions for Insomnia SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID SELF-HELP TREATMENT; SLEEP ASSESSMENT DEVICE; RESTRICTION; GUIDANCE AB An automated program for delivering stimulus control and sleep restriction strategies was developed and implemented on a hand held computer and compared to a self-help manual program in 90 chronic primary insomnia participants at 6 and 12 weeks. The computerized program was generally well accepted and utilized. No significant differences between conditions were found on questionnaire and sleep diary measures,but subsequent exploratory analyses revealed greater percentages of participants in the computer condition compared to the self-help condition who were classified as without clinically significant insomnia at 6 weeks based on Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) criteria. Further research is needed on the efficacy of computerized behavioral approaches for insomnia,but the results of this study indicate that computerized delivery of stimulus control and sleep restriction is feasible and sufficiently promising to warrant further study. C1 [Riley, William T.] NHLBI, Bethesda, MD 20892 USA. [Mihm, Patricia; Behar, Albert] Personal Improvement Comp Syst Inc, Reston, VA USA. [Morin, Charles M.] Univ Laval, Dept Psychol, Quebec City, PQ, Canada. RP Riley, WT (reprint author), NHLBI, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM wiriley@mail.nih.gov RI Morin, Charles/G-1021-2011 FU SBIR [HL065893]; NHLBI FX This project was supported by an SBIR Grant No. HL065893 from NHLBI when the first author was an employee of Personal Improvement Computer Systems, Inc. NR 28 TC 11 Z9 12 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1540-2002 EI 1540-2010 J9 BEHAV SLEEP MED JI Behav. Sleep Med. PY 2010 VL 8 IS 1 BP 2 EP 15 DI 10.1080/15402000903425314 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 548SV UT WOS:000273987500001 PM 20043245 ER PT J AU Howlader, N Altekruse, SF Edwards, BK AF Howlader, Nadia Altekruse, Sean F. Edwards, Brenda K. BE Milner, JA Romagnolo, DF TI Monitoring the Burden of Cancer in the United States SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cancer; burden; surveillance; incidence; mortality; survival; prevalence ID RESULTS SEER PROGRAM; BREAST-CANCER; LUNG-CANCER; PROSTATE-CANCER; RATES; MORTALITY; TRENDS; PREVALENCE; WOMEN; EPIDEMIOLOGY C1 [Howlader, Nadia; Altekruse, Sean F.; Edwards, Brenda K.] NCI, Surveillance Res Program, Bethesda, MD 20892 USA. RP Howlader, N (reprint author), NCI, Surveillance Res Program, Bethesda, MD 20892 USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 3 EP 23 DI 10.1007/978-1-60761-627-6_1 D2 10.1007/978-1-60761-627-6 PG 21 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400001 ER PT J AU Milner, JA Romagnolo, DF AF Milner, John A. Romagnolo, Donato F. BE Milner, JA Romagnolo, DF TI Cancer Biology and Nutrigenomics SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Nutrigenomics; cancer biology; multistage carcinogenesis; bioactive compounds; molecular targets; prevention ID ESTROGEN-RESPONSIVE GENES; CUSTOMIZED DNA MICROARRAY; NF-KAPPA-B; BREAST-CANCER; CELL-LINES; HISTONE MODIFICATIONS; PREMENOPAUSAL WOMEN; PROSTATE-CANCER; PROMOTER HYPERMETHYLATION; MAMMOGRAPHIC DENSITIES C1 [Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. [Romagnolo, Donato F.] Univ Arizona, Dept Nutr Sci, Tucson, AZ USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. NR 101 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 25 EP 43 DI 10.1007/978-1-60761-627-6_2 D2 10.1007/978-1-60761-627-6 PG 19 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400002 ER PT J AU Davis, CD AF Davis, Cindy D. BE Milner, JA Romagnolo, DF TI Cellular Cancer Processes and Their Molecular Targets for Nutritional Preemption of Cancer SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cell proliferation; apoptosis; inflammation; immunity; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; RESVERATROL-INDUCED APOPTOSIS; BIOACTIVE FOOD COMPONENTS; PROSTATE-CANCER; CYCLE ARREST; POTENTIAL TARGET; IMMUNE-SYSTEM; KAPPA-B; EPIGALLOCATECHIN GALLATE; CHEMOPREVENTIVE AGENTS C1 NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. NR 125 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 45 EP 70 DI 10.1007/978-1-60761-627-6_3 D2 10.1007/978-1-60761-627-6 PG 26 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400003 ER PT J AU Ross, SA AF Ross, Sharon A. BE Milner, JA Romagnolo, DF TI Diet and Epigenetics SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Bioactive food components; diet; DNA methylation; histone; polycomb repressive complex; microRNA; epigenetics ID TUMOR-SUPPRESSOR GENES; PROSTATE-CANCER CELLS; INCREASES HISTONE ACETYLATION; DNA METHYLATION; DIALLYL DISULFIDE; RAT-LIVER; CHROMATIN MODIFICATION; TRANSPOSABLE ELEMENTS; COLORECTAL-CANCER; BMI-1 ONCOPROTEIN C1 NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ross, SA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 100 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 101 EP 123 DI 10.1007/978-1-60761-627-6_5 D2 10.1007/978-1-60761-627-6 PG 23 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400005 ER PT J AU Lof, M Olivo-Marston, S Hilakivi-Clarke, L AF Lof, Marie Olivo-Marston, Susan Hilakivi-Clarke, Leena BE Milner, JA Romagnolo, DF TI n-6 Polyunsaturated Fatty Acids and Cancer SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Dietary n-3 PUFA; n-6 PUFA; inflammation; cancer; cardiovascular diseases ID ACTIVATED-RECEPTOR-GAMMA; POSTMENOPAUSAL BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR SECRETION; PREPUBERTAL LOW-FAT; DIETARY-FAT; PROSTAGLANDIN E-2; MAMMARY CARCINOGENESIS; BIRTH-WEIGHT; PPAR-GAMMA C1 [Lof, Marie] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Olivo-Marston, Susan] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div,NIH, Bethesda, MD 20892 USA. [Hilakivi-Clarke, Leena] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Lof, M (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. NR 201 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 275 EP 307 DI 10.1007/978-1-60761-627-6_14 D2 10.1007/978-1-60761-627-6 PG 33 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400014 ER PT J AU Milner, JA AF Milner, John A. BE Milner, JA Romagnolo, DF TI Garlic and Cancer Prevention SO BIOACTIVE COMPOUNDS AND CANCER SE Nutrition and Health Series LA English DT Article; Book Chapter DE Garlic; allyl sulfur; antioxidant; carcinogenesis; proliferation; apoptosis; angiogenesis ID DRUG-METABOLIZING-ENZYMES; P34(CDC2) KINASE-ACTIVITY; ESCHERICHIA-COLI O157-H7; VEIN ENDOTHELIAL-CELLS; ALLYL SULFUR-COMPOUNDS; DIALLYL DISULFIDE; ORGANOSULFUR COMPOUNDS; ALLIUM-SATIVUM; PROSTATE-CANCER; IN-VIVO C1 NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. NR 141 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-626-9 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 567 EP 588 DI 10.1007/978-1-60761-627-6_24 D2 10.1007/978-1-60761-627-6 PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BPI49 UT WOS:000278922400024 ER PT J AU Dosemeci, A Jaffe, H AF Dosemeci, Ayse Jaffe, Howard TI Regulation of phosphorylation at the postsynaptic density during different activity states of Ca2+/calmodulin-dependent protein kinase II SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE PSD; CaMKII; SAPAP; GKAP; Shank; iTRAQ ID LONG-TERM POTENTIATION; AUTOPHOSPHORYLATION SITE; CA-2+ CALMODULIN; IDENTIFICATION; BINDING; DOMAIN; SPINOPHILIN; EXPRESSION; RECEPTORS; SYNAPSES AB Ca2+/calmodulin-dependent protein kinase II (CaMKII), the most abundant kinase at the postsynaptic density (PSD), is expected to be involved in activity-induced regulation of synaptic properties CaMKII is activated when it binds calmodulin in the presence of Ca2+ and, once autophosphorylated on T-286/7, remains active in the absence of Ca2+ (autonomous form). In the present study we used a quantitative mass spectrometric strategy (iTRAQ) to identify sites on PSD components phosphorylated upon CaMKII activation Phosphorylation in isolated PSDs was monitored under conditions where CaMKII is (1) mostly inactive (basal state), (2) active in the presence of Ca2+, and (3) active in the absence of Ca2+. The quantification strategy was validated through confirmation of previously described autophosphorylation characteristics of CaMKII. The effectiveness of phosphorylation of major PSD components by the activated CaMKII in the presence and absence of Ca2+ varied. Most notably, autonomous activity in the absence of Ca2+ was more effective in the phosphorylation of three residues on SynGAP Several PSD scaffold proteins were phosphorylated upon activation of CaMKII. The strategy adopted allowed the identification, for the first time, of CaMKII-regulated sites on SAPAPs and Shanks, including three conserved serine residues near the C-termini of SAPAP1, SAPAP2, and SAPAP3. Involvement of CaMKII in the phosphorylation of PSD scaffold proteins suggests a role in activity-induced structural re-organization of the PSD. Published by Elsevier Inc. C1 [Dosemeci, Ayse] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. [Jaffe, Howard] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Dosemeci, A (reprint author), NINDS, Neurobiol Lab, NIH, 9000 Rockville Pike,NIH Bldg 49,3A52, Bethesda, MD 20892 USA. FU NIH/NINDS FX This work was supported by the intramural research program at NIH/NINDS We Would like to thank Dr. Thomas Reese for support and discussion. NR 26 TC 22 Z9 22 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2010 VL 391 IS 1 BP 78 EP 84 DI 10.1016/j.bbrc.2009.10.167 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500015 PM 19896464 ER PT J AU Saito, T Sasaki, CY Rezanka, LJ Ghosh, P Longo, DL AF Saito, T. Sasaki, C. Y. Rezanka, L. J. Ghosh, P. Longo, D. L. TI p52-independent nuclear translocation of RelB promotes LPS-induced attachment SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE LPS; SCLC; NF-kappa B; p65; p52; RelB; Cellular attachment; beta 1 integrin ID NF-KAPPA-B; TOLL-LIKE RECEPTORS; TRANSCRIPTIONAL ACTIVITY; MYELOMA CELLS; CANCER-CELLS; TUMOR; GROWTH; LIPOPOLYSACCHARIDE; ACTIVATION; PATHWAY AB The NF-kappa B signaling pathways have a critical role in the development and progression of various cancers In this study. we demonstrated that the small Cell lung cancer cell line (SCLC) H69 expressed a unique NF-kappa B profile as compared to other cancer cell lines The p105/p50, p100/p52, c-Rel, and RelB protein and mRNA transcripts were absent in H69 cells but these cells expressed RelA/p65 The activation of H69 cells by lipopolysaccharide (LPS) resulted in the induction of RelB and p100 expression The treatment also induced the nuclear translocation of RelB without the processing of p100 to p52 Furthermore, LPS-induced beta 1 integrin expression and Cellular attachment through an NF-kappa B-dependent mechanism Blocking RelB expression prevented the increase in the expression of beta 1 integrin and the attachment of H69 Taken together, the results Suggest that RelB was responsible for the LPS-mediated attachment and may play an important role in the progression of some cancers Published by Elsevier Inc C1 [Saito, T.; Sasaki, C. Y.; Rezanka, L. J.; Ghosh, P.; Longo, D. L.] NIA, Immunol Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Sasaki, CY (reprint author), NIA, Immunol Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. FU National Institutes of Health, National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 34 TC 8 Z9 8 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 JAN 1 PY 2010 VL 391 IS 1 BP 235 EP 241 DI 10.1016/j.bbrc.2009.11.039 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500043 PM 19903458 ER PT J AU Nagineni, CN Kommineni, VK William, A Hooks, JJ Detrick, B AF Nagineni, Chandrasekharam N. Kommineni, Vijay K. William, Abitha Hooks, John J. Detrick, Barbara TI IL-11 expression in retinal and corneal cells is regulated by interferon-gamma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IL-11; IFN-gamma; TNF-alpha; IL-1; TGF-beta; Retina; Cornea ID PIGMENT EPITHELIAL-CELLS; INTERLEUKIN-11; CYTOKINE; BETA; TRANSPLANTATION AB Interleukin-11 (IL-11) is an anti-apoptotic. anti-inflammatory cytokine with hematopoietic potential The expression and protective actions of IL-11 have not been explored in the eye The expression of IL-11 in primary cultures of human retinal pigment epithelial (HRPE) and human corneal fibroblast (HCRF) cells were evaluated in these studies. Constitutive secretion of IL-11 was not observed in either HRPE or HCRF TNF-alpha + IL-1 induced IL-11 secretion and this production was inhibited by NF kappa B pathway inhibitors. IFN-gamma significantly inhibited TNF-alpha and IL-1 induced IL-11 secretion and inhibitors of JAK-STAT pathway reversed this inhibition TGF-beta induced IL-11 secretion that was blocked by TGF-beta receptor 1 inhibitor but not by IFN-gamma RT-PCR analysis confirmed the effects of IL-1, TNF-alpha, IFN-gamma and TGF-beta on IL-11 secretion at mRNA levels. Our results demonstrate that IL-11 is dramatically up regulated in retina and cornea cells and that IFN-gamma is a physiological inhibitor of IL-11 expression (C) 2009 Published by Elsevier Inc C1 [Hooks, John J.] NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 7,Room 200,7 Mem Dr, Bethesda, MD 20892 USA. FU National Eye Institute, National Institutes of Health FX This research was supported (in part) by the Intramural Research Program of the National Eye Institute, National Institutes of Health. NR 24 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2010 VL 391 IS 1 BP 287 EP 292 DI 10.1016/j.bbrc.2009.11.051 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500052 PM 19913506 ER PT J AU Li, HG Huang, PL Zhang, DW Sun, YT Chen, HC Zhang, J Huang, PL Kong, XP Lee-Huang, S AF Li, Hui-Guang Huang, Philip L. Zhang, Dawei Sun, Yongtao Chen, Hao-Chia Zhang, John Huang, Paul L. Kong, Xiang-Peng Lee-Huang, Sylvia TI A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AIDS; HIV-1; Antiviral; Anti-tumor; Adenosine glycosidase; Plant protein ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; MAP30; INHIBITION; BINDING; GAP-31; AGENTS; TRICHOSANTHIN; EXPRESSION; MECHANISM AB We report here the high-resolution atomic Structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third. GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA. (C) 2009 Elsevier Inc. All rights reserved. C1 [Li, Hui-Guang; Zhang, Dawei; Sun, Yongtao; Kong, Xiang-Peng; Lee-Huang, Sylvia] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. [Huang, Philip L.] Amer Biosci, Boston, MA 02114 USA. [Chen, Hao-Chia] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. [Zhang, John] NYU, Dept Chem, New York, NY 10003 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. RI Zhang, Dawei/C-5981-2008; OI Lee-Huang, Sylvia/0000-0003-3302-241X; Kong, Xiang-Peng/0000-0001-5773-2681 FU JT Research; National Center for Complementary and Alternative Medicine (NCCAM) [R01-AT01383]; National Institute of Allergy and Infectious Diseases (NIAID), NIH [R01-A131343] FX We thank staff members at X-ray beamlines X12B and X26C of NSLS and 19D of APS for assistance with data collections. This work was supported in part by a JT Research Grant to S.L -H. and X.PK S.L.-H. also acknowledges the support of research Grant R01-AT01383 from the National Center for Complementary and Alternative Medicine (NCCAM) and Grant R01-A131343 from the National Institute of Allergy and Infectious Diseases (NIAID), NIH. NR 23 TC 11 Z9 12 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 JAN 1 PY 2010 VL 391 IS 1 BP 340 EP 345 DI 10.1016/j.bbrc.2009.11.060 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500061 PM 19913503 ER PT J AU Adriaansen, J Zheng, CY Perez, P Baum, BJ AF Adriaansen, Janik Zheng, Changyu Perez, Paola Baum, Bruce J. TI Production and sorting of transgenic, modified human parathyroid hormone in vivo in rat salivary glands SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE PTH; Polarized epithelium; Secretion; Sorting; Salivary gland; Gene transfer ID PREPROPARATHYROID HORMONE; SUBMANDIBULAR-GLANDS; SIGNAL SEQUENCE; GROWTH-HORMONE; SECRETION; PROTEIN; EXPRESSION; PATHWAYS AB Polarized salivary epithelial cells can sort secretory proteins towards either the basolateral or apical pole Transaenic human parathyroid hormone (hPTH) exclusively sorts apically in rat submandibular glands To help understand this specific process we modified the hPTH cDNA sequence and delivered the cDNAs to glands in vivo using adenoviral (Ad) vectors The Ad vectors encoded (1) the native form of hPTH (Ad.pre-pro-hPTH1-84), (2) the native sequence, but with the pro-segment deleted (Ad.pre-hPTH1-84), and (3) a sequence containing the pre-segment followed by the first 34 amino acids of hPTH (Ad.pre-hPTH1-34). MYTH production and sorting were studied after two days. All constructs were effectively transcribed in targeted glands. However, the pre-hPTH1-84 modification led to reduced hPTH secretion and production, while no immunoreactive MYTH resulted from pre-hPTH1-34 cDNA infusion The pre-hPTH1-84 modification had no effect on apical sorting These in vivo results show that the signal responsible for hPTH's apical sorting does not reside in the pro-segment and that deleting both the prosegment and the carboxyl-terminal region severely impairs post-translational processing of hPTH. Published by Elsevier Inc. C1 [Adriaansen, Janik; Zheng, Changyu; Perez, Paola; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N113, Bethesda, MD 20892 USA. FU Division of Intramural Research of the National Institute of Dental and Craniofacial Research FX This research was supported by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research NR 22 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2010 VL 391 IS 1 BP 768 EP 772 DI 10.1016/j.bbrc.2009.11.135 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500134 PM 19944067 ER PT J AU Abdelmegeed, MA Moon, KH Chen, C Gonzalez, FJ Song, BJ AF Abdelmegeed, Mohamed A. Moon, Kwan-Hoon Chen, Chi Gonzalez, Frank J. Song, Byoung-Joon TI Role of cytochrome P450 2E1 in protein nitration and ubiquitin-mediated degradation during acetaminophen toxicity SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Liver toxicity; Acetaminophen; CYP2E1; Nitrotyrosine; Ubiquitin; Superoxide dismutase ID NITRIC-OXIDE SYNTHASE; ALCOHOLIC FATTY LIVER; INDUCED HEPATOTOXICITY; COVALENT BINDING; IMMUNOHISTOCHEMICAL LOCALIZATION; PEROXYNITRITE FORMATION; SUPEROXIDE-DISMUTASE; REACTIVE OXYGEN; HEPATOMA-CELLS; MOUSE-LIVER AB It is well established that following a toxic dose of acetaminophen (APAP), nitrotyrosine protein adducts (3-NT). a hallmark of peroxynitrate production, were colocalized with necrotic hepatic centrilobular regions where cytochrome P450 2E1 (CYP2E1) is highly expressed, suggesting that 3-NT formation may be essential in APAP-mediated toxicity. This Study was aimed at investigating the relationship between CYP2E1 and nitration (3-NT formation) followed by ubiquitin-mediated degradation of proteins in wildtype and Cyp2e1-null mice exposed to APAP (200 and 400 mg/kg) for 4 and 24 h Markedly increased centrilobular liver necrosis and 3-NT formation were only observed in APAP-exposed wild-type mice in a dose- and time-dependent manner. confirming an important role for CYP2E1 in APAP biotransformation and toxicity However, the pattern of 3-NT protein adducts. not accompanied by concurrent activation of nitric oxide synthase (NOS), was similar to that of protein ubiquitination. Immunoblot analysis further revealed that immunoprecipitated nitrated proteins were ubiquitinated in APAP-exposed wild-type mice, confirming the fact that nitrated proteins are more Susceptible than the native proteins for ubiquitin-dependent degradation, resulting in shorter half-lives. For instance, cytosolic Superoxide dismutase (SOD1) levels were clearly decreased and immunoprecipitated SOD1 was nitrated and ubiquitinated, likely leading to its accelerated degradation in APAP-exposed wild-type mice These data suggest that CYP2E I appears to play a key role in 3-NT formation, protein degradation, and liver damage, which is independent of NOS, and that decreased levels of many proteins in the wild-type mice (compared with Cyp2e1-null mice) likely contribute to APAP-relatec toxicity Published by Elsevier Inc C1 [Abdelmegeed, Mohamed A.; Moon, Kwan-Hoon; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Chen, Chi; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Research Program of National Institute on Alcohol Abuse and Alcoholism We are thankful to Dr. Klaus Gawrisch for Supporting this Study. NR 58 TC 38 Z9 41 U1 2 U2 5 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 JAN 1 PY 2010 VL 79 IS 1 BP 57 EP 66 DI 10.1016/j.bcp.2009.07.016 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 516OM UT WOS:000271551900007 PM 19660437 ER PT J AU Bustin, M AF Bustin, Michael TI High Mobility Group Proteins Preface SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Editorial Material ID GROUP CHROMOSOMAL-PROTEINS; HMGA C1 NCI, NIH, Bethesda, MD 20892 USA. RP Bustin, M (reprint author), NCI, NIH, Bldg 37,Room 3122,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 1 EP 2 DI 10.1016/j.bbagrm.2010.01.006 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500001 PM 20123064 ER PT J AU Postnikov, Y Bustin, M AF Postnikov, Yuri Bustin, Michael TI Regulation of chromatin structure and function By HMGN proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE High Mobility Group Protein; Chromatin; Nucleosomes; Histories; Epigenesis ID NUCLEOSOMAL BINDING-PROTEIN; GROUP CHROMOSOMAL-PROTEINS; MOBILITY-GROUP PROTEINS; HISTONE H3; INTRINSIC DISORDER; LIVING CELLS; DNA-DAMAGE; HMG-17; TRANSCRIPTION; EXPRESSION AB High mobility group nucleosome-binding (HMGN) proteins are architectural non-histone chromosomal proteins that bind to nucleosomes and modulate the structure and function of chromatin. The interaction of HMGN proteins with nucleosomes is dynamic and the proteins compete with the linker histone HI chromatin-binding sites. HMGNs reduce the H1-mediated compaction of the chromatin fiber and facilitate the targeting of regulatory factors to chromatin. They modulate the cellular epigenetic profile, affect gene expression and impact the biological processes such as development and the cellular response to environmental and hormonal signals. Here we review the role of HMGN in chromatin structure, the link between HMGN proteins and histone modifications, and discuss the consequence of this link on nuclear processes and cellular phenotype. Published by Elsevier B.V. C1 [Postnikov, Yuri; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Postnikov, Y (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM Yupo@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU NCI, NIH FX We acknowledge NIH Fellows Editorial Board for help with editing the manuscript. The research of the laboratory is supported by CCR, the intramural research program of NCI, NIH. NR 72 TC 35 Z9 35 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 62 EP 68 DI 10.1016/j.bbagrm.2009.11.016 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500008 PM 19948260 ER PT J AU Furusawa, T Cherukuri, S AF Furusawa, Takashi Cherukuri, Srujana TI Developmental function of HMGN proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE HMGN protein; Chromatin; Embryogenesis; Differentiation ID NUCLEOSOMAL-BINDING-PROTEIN; CHROMOSOMAL-PROTEINS; MOUSE DEVELOPMENT; HISTONE H1; IN-VIVO; EXPRESSION; CHROMATIN; TRANSCRIPTION; DIFFERENTIATION; ACTIVATION AB High mobility group N (HMGN) proteins are the only nuclear proteins known to specifically recognize the generic structure of the 147-bp nucleosome core particle. Both in vitro and in vivo experiments demonstrate that HMGN proteins are involved in epigenetic regulation by modulating chromatin structure and levels of posttranslational modifications of nucleosomal histones. Expression of HMGN proteins is developmentally regulated, and the loss or overexpression of these Proteins can lead to developmental abnormalities. This review will focus on the role and on the possible molecular mechanism whereby HMGN proteins affect cellular differentiation and development. Published by Elsevier B.V. C1 [Furusawa, Takashi; Cherukuri, Srujana] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Furusawa, T (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bldg 37,Room 3122,9000 Rockville Pike, Bethesda, MD 20892 USA. EM furusawt@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 44 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 69 EP 73 DI 10.1016/j.bbagrm.2009.11.011 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500009 PM 20123069 ER PT J AU Gerlitz, G AF Gerlitz, Gabi TI HMGNs, DNA repair and cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE HMGN proteins; Nucleotide excision repair; Transcription coupled repair; Double-strand breaks; DNA damage response; Histone H1 ID CHROMOSOMAL-PROTEIN HMGN1; DOUBLE-STRAND BREAKS; NUCLEOTIDE EXCISION-REPAIR; INVASION-INHIBITING FACTOR-2; NUCLEOSOMAL-BINDING-PROTEIN; DAMAGE RESPONSE; HISTONE H1; TUMOR-CELLS; IN-VIVO; CHROMATIN INTERACTIONS AB DNA lesions threaten the integrity of the genome and are a major factor in cancer formation and progression. Eukaryotic DNA is organized in nucleosome-based higher order structures, which form the chromatin fiber. In recent years, considerable knowledge has been gained on the importance of chromatin dynamics for the cellular response to DNA damage and for the ability to repair DNA lesions. High Mobility Group N1 (HMGN1) protein is an emerging factor that is important for chromatin alterations in response to DNA damage originated from both ultra violet light (UV) and ionizing irradiation (IR). HMGN1 is a member in the HMGN family of chromatin architectural proteins. HMGNs bind directly to nucleosomes and modulate the structure of the chromatin fiber in a highly dynamic manner. This review focuses mainly on the roles of HMGN1 in the cellular response pathways to different types of DNA lesions and in transcriptional regulation of cancer-related genes. In addition, emerging roles for HMGN5 in cancer progression and for HMGN2 as a potential tool in cancer therapy will be discussed. Published by Elsevier B.V. C1 NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gerlitz, G (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bldg 37,Room 3122,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gerlitzg@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This study was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH. I would like to thank M. Bustin (NCI), the NIH Fellows Editorial Board, R. Artzi-Gerlitz and V. Walker (NIH library) for constructive comments on the manuscript. NR 74 TC 25 Z9 25 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 80 EP 85 DI 10.1016/j.bbagrm.2009.10.007 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500011 PM 20004154 ER PT J AU Rochman, M Malicet, C Bustin, M AF Rochman, Mark Malicet, Cedric Bustin, Michael TI HMGN5/NSBP1: A new member of the HMGN protein family that affects chromatin structure and function SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE HMGN5; NSBP1; Chromatin; Linker histone H1; Transcription; Nucleosome ID NUCLEOSOMAL-BINDING-PROTEIN; GROUP CHROMOSOMAL-PROTEINS; HISTONE H1; GENE-EXPRESSION; PROTHYMOSIN-ALPHA; LIVING CELLS; MOBILITY; DYNAMICS; DIFFERENTIATION; MOUSE AB The dynamic nature of the chromatin fiber provides the structural and functional flexibility required for the accurate transcriptional responses to various stimuli. In living cells, structural proteins such as the linker histone Hi and the high mobility group (HMG) proteins continuously modulate the local and global architecture of the chromatin fiber and affect the binding of regulatory factors to their nucleosomal targets. HMGN proteins specifically bind to the nucleosome core particle through a highly conserved "nucleosomal binding domain" (NBD) and reduce chromatin compaction. HMGN5 (NSBP1), a new member of the HMGN protein family, is ubiquitously expressed in mouse and human tissues. Similar to other HMGNs, HMGN5 is a nuclear protein which binds to nucleosomes via NBD, unfolds chromatin, and affects transcription. This protein remains mainly uncharacterized and its biological function is unknown. In this review, we describe the structure of the HMGN5 gene and the known properties of the HMGN5 protein. We present recent findings related to the expression pattern of the protein during development, the mechanism of HMGN5 action on chromatin, and discuss the possible role of HMGN5 in pathological and physiological processes. Published by Elsevier B.V. C1 [Rochman, Mark; Malicet, Cedric; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Rochman, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 3122, Bethesda, MD 20892 USA. EM rochmanm@mail.nih.gov RI Bustin, Michael/G-6155-2015 FU NIH, National Cancer Institute (NCI) FX This project was supported by the Intramural Research Program of NIH, National Cancer Institute (NCI). We thank The Fellows Editorial Board for editorial assistance. NR 69 TC 34 Z9 34 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 86 EP 92 DI 10.1016/j.bbagrm.2009.09.012 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500012 PM 20123071 ER PT J AU Liu, Y Prasad, R Wilson, SH AF Liu, Yuan Prasad, Rajendra Wilson, Samuel H. TI HMGB1: Roles in base excision repair and related function SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE HMGB1; DNA binding; DNA bending; Base excision repair; AP endonuclease; FEN1; Trinucleotide repeat expansion ID MOBILITY-GROUP PROTEINS; DNA-POLYMERASE-BETA; GROUP CHROMOSOMAL-PROTEINS; IN-VITRO; V(D)J RECOMBINATION; MISMATCH REPAIR; CISPLATIN; CHROMATIN; DOMAIN; ENDONUCLEASE-1 AB High mobility group box 1 (HMGB1) is a nonhistone architectural protein that is involved in many biological processes including chromatin remodeling, transcription, cell signaling of inflammation, DNA damage repair and others. Recent studies have identified the cross-link of HMGB1 with a DNA base excision repair intermediate indicating that this Protein is involved in base excision repair (BER) pathway. Further characterization of the roles of HMGB1 in BER demonstrates that the protein acts as a cofactor to regulate BER sub-pathways by inhibiting single-nucleotide BER and stimulating long-patch BER through modulating the activities of base excision repair enzymes. Directing of base lesion repair to the long-patch sub-pathway can result in trinucleotide repeat instability suggesting an important role of HMGB1 in modulating genome stability. Published by Elsevier B.V. C1 [Liu, Yuan; Prasad, Rajendra; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health [Z01-ES010158]; NIEHS [Z01-ES050159] FX We thank William A. Beard for discussion and assistance with structural analysis of HMGB1. This work is supported by National Institutes of Health Research Projects Z01-ES010158 and Z01-ES050159 from the NIEHS Intramural Research Program. NR 58 TC 42 Z9 44 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 119 EP 130 DI 10.1016/j.bbagrm.2009.11.008 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500016 PM 20123074 ER PT J AU Yang, D Tewary, P de la Rosa, G Wei, F Oppenheim, JJ AF Yang, De Tewary, Poonam de la Rosa, Gonzalo Wei, Feng Oppenheim, Joost J. TI The alarmin functions of high-mobility group proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE High-mobility group protein; Alarmin; Dendritic cells; Immune response ID GROUP BOX-1 PROTEIN; EOSINOPHIL-DERIVED NEUROTOXIN; DNA-BINDING CYTOKINE; END-PRODUCTS RAGE; DENDRITIC CELLS; HIGH-MOBILITY-GROUP-BOX-1 PROTEIN; IMMUNE-RESPONSES; CHROMATIN PROTEIN; HMGB1 RELEASE; TISSUE-DAMAGE AB High-mobility group (HIVIG) proteins are non-histone nuclear proteins that bind nucleosomes and regulate chromosome architecture and gene transcription. Over the past decade, numerous studies have established that some HMG proteins can be released extracellularly and demonstrate distinct extracellular biological activities. Here, we will give a brief overview of HIVIG proteins and highlight their participation in innate/inflammatory and adaptive immune responses. They have the activities of alarmins, which are endogenous mediators that are rapidly released in response to danger signals initiated by infection and/or tissue damage and are capable of activating innate and adaptive immunity by promoting the recruitment and activation of antigen-presenting cells (APCs). (C) 2009 Published by Elsevier B.V. C1 [Yang, De; Tewary, Poonam; de la Rosa, Gonzalo; Wei, Feng; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Yang, De] SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM oppenhei@ncifcrf.gov RI Wei, Feng/E-2806-2015 OI Wei, Feng/0000-0002-4797-449X NR 116 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN-FEB PY 2010 VL 1799 IS 1-2 SI SI BP 157 EP 163 DI 10.1016/j.bbagrm.2009.11.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 559YL UT WOS:000274868500020 PM 20123077 ER PT J AU Ohlsson, R Lobanenkov, V Klenova, E AF Ohlsson, Rolf Lobanenkov, Victor Klenova, Elena TI Does CTCF mediate between nuclear organization and gene expression? SO BIOESSAYS LA English DT Review DE chromatin; epigenetics; gene expression; higher order structure ID INSULATOR PROTEIN CTCF; IMPRINTING CONTROL REGION; CCCTC-BINDING FACTOR; ENHANCER-BLOCKING ACTIVITY; THYROID-HORMONE RECEPTOR; METHYLATION-FREE DOMAINS; BETA-GLOBIN INSULATOR; CANCER-TESTIS GENE; CHIP-SEQ DATA; C-MYC GENE AB The multifunctional zinc-finger protein CCCTC-binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three-dimensional position in the nucleus, apparently responding to a "code" in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of genome functions. However, the molecular basis of these interactions still remains elusive and is a subject of intense debate. Here we discuss the nature of CTCF-DNA interactions, the CTCF-binding specificity to its binding sites and the relationship between CTCF and chromatin, and we examine data linking CTCF with gene regulation in the three-dimensional nuclear space. We discuss why these features render CTCF a very strong candidate for the role and propose a unifying model, the "CTCF code," explaining the mechanistic basis of how the information encrypted in DNA may be interpreted by CTCF into diverse nuclear functions. C1 [Ohlsson, Rolf] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden. [Lobanenkov, Victor] NIAID, Mol Pathol Sect, Immunopathol Lab, NIH,LIP, Rockville, MD 20852 USA. [Klenova, Elena] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. RP Ohlsson, R (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Nobels Vag 16,Box 280, SE-17177 Stockholm, Sweden. EM Rolf.Ohlsson@ki.se; VLOBANENKOV@niaid.nih.gov; klenovae@essex.ac.uk OI Lobanenkov, Victor/0000-0001-6665-3635 FU Swedish Science Research Council; Swedish Cancer Research Foundation; Swedish Pediatric Cancer Foundation; Lundberg Foundation; HEROIC; ChILL; NIAID/NIH; Medical Research Council, UK; Breast Cancer Campaign, UK; Breast Cancer Research Trust, UK; University of Essex, UK; Colchester Hospital University NHS Foundation Trust, UK FX We sincerely apologize to our colleagues in the field for not being able to cite many relevant original papers due to space limitation. Valuable advice from Dr. A. Gondor and Mr. P Vince is gratefully acknowledged. This work was supported by the Swedish Science Research Council (RO), the Swedish Cancer Research Foundation (RO), the Swedish Pediatric Cancer Foundation (RO), the Lundberg Foundation (RO) as well as HEROIC and ChILL (EU integrated projects, RO), and in part funded by intramural research program of NIAID/NIH (VL), Medical Research Council, UK (EK), Breast Cancer Campaign, UK (EK), Breast Cancer Research Trust, UK (EK), University of Essex, UK (EK), and Colchester Hospital University NHS Foundation Trust, UK (EK). NR 125 TC 96 Z9 97 U1 3 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2010 VL 32 IS 1 BP 37 EP 50 DI 10.1002/bies.200900118 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 542PL UT WOS:000273506800007 PM 20020479 ER PT J AU Ma, SG Zhang, YW Huang, J Han, XS Holford, T Lan, Q Rothman, N Boyle, P Zheng, TZ AF Ma, Shuangge Zhang, Yawei Huang, Jian Han, Xuesong Holford, Theodore Lan, Qing Rothman, Nathaniel Boyle, Peter Zheng, Tongzhang TI Identification of non-Hodgkin's lymphoma prognosis signatures using the CTGDR method SO BIOINFORMATICS LA English DT Article ID FOLLICULAR LYMPHOMA; MICROARRAY DATA; POLYMORPHISMS; SUSCEPTIBILITY; REGRESSION; SELECTION; SURVIVAL; LASSO; GENES; RISK AB Motivation: Although NHL (non-Hodgkin's lymphoma) is the fifth leading cause of cancer incidence and mortality in the USA, it remains poorly understood and is largely incurable. Biomedical studies have shown that genomic variations, measured with SNPs (single nucleotide polymorphisms) in genes, may have independent predictive power for disease-free survival in NHL patients beyond clinical measurements. Results: We apply the CTGDR (clustering threshold gradient directed regularization) method to genetic association studies using SNPs, analyze data from an association study of NHL and identify prognosis signatures to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common subtypes of NHL. With the CTGDR method, we are able to account for the joint effects of multiple genes/SNPs, whereas most existing studies are single-marker based. In addition, we are able to account for the 'gene and SNP-within-gene' hierarchical structure and identify not only predictive genes but also predictive SNPs within identified genes. In contrast, existing studies are limited to either gene or SNP identification, but not both. We propose using resampling methods to evaluate the predictive power and reproducibility of identified genes and SNPs. Simulation study and data analysis suggest satisfactory performance of the CTGDR method. C1 [Ma, Shuangge; Zhang, Yawei; Han, Xuesong; Holford, Theodore; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA. [Huang, Jian] Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA. [Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Boyle, Peter] Int Prevent Res Inst, Lyon, France. RP Ma, SG (reprint author), Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA. EM shuangge.ma@yale.edu RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU National Institutes of Health [LM009754, CA120988, CA62006, 1D43TW008323-01, 1D43TW007864-01]; National Science Foundation [DMS0805670, DMS0904181]; Yale Cancer Center [22067A] FX National Institutes of Health (LM009754, CA120988 and CA62006); National Science Foundation (DMS0805670 and DMS0904181); Yale Cancer Center (Hull Argall & Anna Grant 22067A); National Institutes of Health (Fogarty training grants 1D43TW008323-01 and 1D43TW007864-01). NR 15 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2010 VL 26 IS 1 BP 15 EP 21 DI 10.1093/bioinformatics/btp604 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 537MD UT WOS:000273116100003 PM 19850755 ER PT J AU Zheng, J Zhang, D Przytycki, PF Zielinski, R Capala, J Przytycka, TM AF Zheng, Jie Zhang, David Przytycki, Pawel F. Zielinski, Rafal Capala, Jacek Przytycka, Teresa M. TI SimBoolNet-a Cytoscape plugin for dynamic simulation of signaling networks SO BIOINFORMATICS LA English DT Article AB SimBoolNet is an open source Cytoscape plugin that simulates the dynamics of signaling transduction using Boolean networks. Given a user-specified level of stimulation to signal receptors, SimBoolNet simulates the response of downstream molecules and visualizes with animation and records the dynamic changes of the network. It can be used to generate hypotheses and facilitate experimental studies about causal relations and crosstalk among cellular signaling pathways. C1 [Zheng, Jie; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Zhang, David] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. [Przytycki, Pawel F.] Columbia Univ, Columbia Coll, New York, NY USA. [Zielinski, Rafal; Capala, Jacek] NCI, NIH, Bethesda, MD 20892 USA. RP Zheng, J (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM zhengj@ncbi.nlm.nih.gov; przytyck@ncbi.nlm.nih.gov RI Zheng, Jie/C-1356-2011 OI Zheng, Jie/0000-0001-6774-9786 FU National Institutes of Health; National Library of Medicine; National Cancer Institute; Center for Cancer Research FX Intramural Research Program of the National Institutes of Health (in part); National Library of Medicine (in part); National Cancer Institute, Center for Cancer Research (in part). NR 6 TC 25 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2010 VL 26 IS 1 BP 141 EP 142 DI 10.1093/bioinformatics/btp617 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 537MD UT WOS:000273116100026 PM 19887508 ER PT S AU Ehler, M Rajapakse, V Zeeberg, B Brooks, B Brown, J Czaja, W Bonner, RF AF Ehler, Martin Rajapakse, Vinodh Zeeberg, Barry Brooks, Brian Brown, Jacob Czaja, Wojciech Bonner, Robert F. BE Borodovsky, M Gogarten, JP Przytycka, TM Rajasekaran, S TI Analysis of Temporal-spatial Co-variation within Gene Expression Microarray Data in an Organogenesis Model SO BIOINFORMATICS RESEARCH AND APPLICATIONS, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 6th International Symposium on Bioinformatics Research and Applications CY MAY 23-26, 2010 CL Univ Connecticut, Storrs, CT HO Univ Connecticut DE laser capture microdissection; microarray; organogenesis; gene regulatory network; clustering ID LASER CAPTURE MICRODISSECTION; ONTOLOGY; TOOL; RETINA AB The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. We used a novel clustering method based on Laplacian Eigenmaps, a nonlinear dimension reduction method, to analyze microarray data from laser capture microdissected (LCM) cells at the site and developmental stages (days 10.5 to 12.5) of optic fissure closure. Our new method provided greater biological specificity than classical clustering algorithms in terms of identifying more biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates. This new methodology builds on the advantages of LCM to isolate pure phenotypic populations within complex tissues and allows improved ability to identify critical gene products expressed at lower copy number. The combination of LCM of embryonic organs, gene expression microarrays, and extracting spatial and temporal co-variations appear to be a powerful approach to understanding the gene regulatory networks that specify mammalian organogenesis. C1 [Ehler, Martin; Bonner, Robert F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Med Biophys, Bethesda, MD 20892 USA. [Ehler, Martin; Rajapakse, Vinodh; Czaja, Wojciech] Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA. [Zeeberg, Barry] NIH, NCI, Mol Pharmacol Lab, Gen & Bioinformat Grp, Bethesda, MD 20892 USA. [Brooks, Brian; Brown, Jacob] NIH, NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Ehler, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Med Biophys, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 FU Intramural Research Program of NICHD/NIH; NSF; NGA [HM15820810009]; ONR [N000140910144] FX The research was funded by the Intramural Research Program of NICHD/NIH, by NSF (CBET0854233), by NGA (HM15820810009), and by ONR (N000140910144) NR 22 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-13077-9 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2010 VL 6053 BP 38 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BQE19 UT WOS:000280765100004 ER PT S AU Ovcharenko, I AF Ovcharenko, Ivan BE Borodovsky, M Gogarten, JP Przytycka, TM Rajasekaran, S TI Structure of Proximal and Distant Regulatory Elements in the Human Genome SO BIOINFORMATICS RESEARCH AND APPLICATIONS, PROCEEDINGS SE LECTURE NOTES IN BIOINFORMATICS LA English DT Proceedings Paper CT 6th International Symposium on Bioinformatics Research and Applications CY MAY 23-26, 2010 CL Univ Connecticut, Storrs, CT HO Univ Connecticut C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20896 USA. RP Ovcharenko, I (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20896 USA. EM ovcharen@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-13077-9 J9 LECT N BIOINFORMAT PY 2010 VL 6053 BP 125 EP 125 PG 1 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BQE19 UT WOS:000280765100012 ER PT J AU Liao, W Mantini, D Zhang, ZQ Pan, ZY Ding, JR Gong, QY Yang, YH Chen, HF AF Liao, Wei Mantini, Dante Zhang, Zhiqiang Pan, Zhengyong Ding, Jurong Gong, Qiyong Yang, Yihong Chen, Huafu TI Evaluating the effective connectivity of resting state networks using conditional Granger causality SO BIOLOGICAL CYBERNETICS LA English DT Article DE Resting state networks; Effective connectivity; Independent component analysis; Conditional Granger causality analysis ID INDEPENDENT COMPONENT ANALYSIS; MEDIAL PREFRONTAL CORTEX; HUMAN AUDITORY-CORTEX; FUNCTIONAL MRI DATA; HUMAN BRAIN; DEFAULT-MODE; NEURAL-NETWORKS; GLOBAL SIGNAL; LOW-FREQUENCY; MOTOR CORTEX AB The human brain has been documented to be spatially organized in a finite set of specific coherent patterns, namely resting state networks (RSNs). The interactions among RSNs, being potentially dynamic and directional, may not be adequately captured by simple correlation or anticorrelation. In order to evaluate the possible effective connectivity within those RSNs, we applied a conditional Granger causality analysis (CGCA) to the RSNs retrieved by independent component analysis (ICA) from resting state functional magnetic resonance imaging (fMRI) data. Our analysis provided evidence for specific causal influences among the detected RSNs: default-mode, dorsal attention, core, central-executive, self-referential, somatosensory, visual, and auditory networks. In particular, we identified that self-referential and default-mode networks (DMNs) play distinct and crucial roles in the human brain functional architecture. Specifically, the former RSN exerted the strongest causal influence over the other RSNs, revealing a top-down modulation of self-referential mental activity (SRN) over sensory and cognitive processing. In quite contrast, the latter RSN was profoundly affected by the other RSNs, which may underlie an integration of information from primary function and higher level cognition networks, consistent with previous task-related studies. Overall, our results revealed the causal influences among these RSNs at different processing levels, and supplied information for a deeper understanding of the brain network dynamics. C1 [Liao, Wei; Pan, Zhengyong; Ding, Jurong; Chen, Huafu] Univ Elect Sci & Technol China, Minist Educ, Sch Life Sci & Technol, Key Lab Neuroinformat, Chengdu 610054, Peoples R China. [Mantini, Dante] Univ G DAnnunzio, Inst Adv Biomed Technol, Chieti, Italy. [Mantini, Dante] Univ G DAnnunzio, Dept Clin Sci & Bioimaging, Chieti, Italy. [Mantini, Dante] Katholieke Univ Leuven, Sch Med, Lab Neuropsychophysiol, Louvain, Belgium. [Zhang, Zhiqiang] Nanjing Univ, Coll Med, Dept Med Imaging, Nanjing Jinling Hosp,Clin Sch, Nanjing 210002, Peoples R China. [Gong, Qiyong] Sichuan Univ, W China Sch Med, W China Hosp, Huaxi MR Res Ctr HMRRC,Dept Radiol, Chengdu 610042, Peoples R China. [Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RP Chen, HF (reprint author), Univ Elect Sci & Technol China, Minist Educ, Sch Life Sci & Technol, Key Lab Neuroinformat, Chengdu 610054, Peoples R China. EM chenhf@uestc.edu.cn RI Mantini, Dante/H-3061-2011; Mantini, Dante/D-6989-2014 OI Mantini, Dante/0000-0001-6485-5559 FU Natural Science Foundation of China [90820006, 30770590, 30470510, 30800264]; 863 Program [2008AA02Z408]; key research project of science and technology of MOE [107097]; Flanders Research Foundation (FWO); Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute of Health (NIH), USA FX This study was supported by grants from the Natural Science Foundation of China (90820006, 30770590, 30470510, and 30800264); the 863 Program (2008AA02Z408); and the key research project of science and technology of MOE (107097). DM was partly supported by the Flanders Research Foundation (FWO). YY was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institute of Health (NIH), USA. NR 80 TC 78 Z9 87 U1 6 U2 32 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD JAN PY 2010 VL 102 IS 1 BP 57 EP 69 DI 10.1007/s00422-009-0350-5 PG 13 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 540CU UT WOS:000273309200005 PM 19937337 ER PT B AU Huang, Y Zheng, J Przytycka, TM AF Huang, Yang Zheng, Jie Przytycka, Teresa M. BE Chen, JY Lonardi, S TI Discovery of Regulatory Mechanisms from Gene Expression Variation by eQTL Analysis SO Biological Data Mining SE Chapman & Hall-CRC Data Mining and Knowledge Discovery Series LA English DT Article; Book Chapter ID QUANTITATIVE TRAIT LOCI; INTEGRATIVE GENOMICS APPROACH; TRANSCRIPTION FACTORS; NETWORK INFERENCE; WIDE ASSOCIATION; LINKAGE ANALYSIS; MODEL SELECTION; MULTIPLE LOCI; YEAST; ARABIDOPSIS C1 [Huang, Yang; Zheng, Jie; Przytycka, Teresa M.] NIH, Bethesda, MD 20892 USA. RP Huang, Y (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 64 TC 2 Z9 2 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-8684-3; 978-1-4200-8684-3 J9 CH CRC DATA MIN KNOW PY 2010 BP 205 EP 228 PG 24 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BC5KW UT WOS:000353353300011 ER PT J AU Enoch, MA Hodgkinson, CA Yuan, QP Shen, PH Goldman, D Roy, A AF Enoch, Mary-Anne Hodgkinson, Colin A. Yuan, Qiaoping Shen, Pei-Hong Goldman, David Roy, Alec TI The Influence of GABRA2, Childhood Trauma, and Their Interaction on Alcohol, Heroin, and Cocaine Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; childhood adversity; CTQ; gene-environment interaction; haplotype analyses; polysubstance dependence ID NATIONAL EPIDEMIOLOGIC SURVEY; VENTRAL TEGMENTAL AREA; SUBUNIT MESSENGER-RNAS; GABA(A) RECEPTORS; DRUG-DEPENDENCE; LINKAGE DISEQUILIBRIUM; ALPHA-2 SUBUNIT; UNITED-STATES; OPIATE REWARD; ADULT RATS AB Background: The GABRA2 gene has been implicated in addiction. Early life stress has been shown to alter GABRA2 expression in adult rodents. We hypothesized that childhood trauma, GABRA2 variation, and their interaction would influence addiction vulnerability. Methods: African-American men were recruited for this study: 577 patients with lifetime DSM-IV single and comorbid diagnoses of alcohol, cocaine, and heroin dependence, and 255 control subjects. The Childhood Trauma Questionnaire (CTQ) was administered. Ten GABRA2 haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped. Results: We found that exposure to childhood trauma predicted substance dependence (p < .0001). Polysubstance dependence was associated with the highest CTQ scores (p < .0001). The African Americans had four common haplotypes (frequency:.11-.30) within the distal haplotype block: two that correspond to the Caucasian and Asian yin-yang haplotypes, and two not found in other ethnic groups. One of the unique haplotypes predicted heroin addiction, whereas the other haplotype was more common in control subjects and seemed to confer resilience to addiction after exposure to severe childhood trauma. The yin-yang haplotypes had no effects. Moreover, the intron 2 SNP rs11503014, not located in any haplotype block and potentially implicated in exon splicing, was independently associated with addiction, specifically heroin addiction (p < .005). Childhood trauma interacted with rs11503014 variation to influence addiction vulnerability, particularly to cocaine (p < .005). Conclusions: Our results suggest that at least in African-American men, childhood trauma, GABRA2 variation, and their interaction play a role in risk-resilience for substance dependence. C1 [Enoch, Mary-Anne] NIAAA, Neurogenet Lab, NIH, DICBR,LNG, Bethesda, MD 20892 USA. [Roy, Alec] New Jersey VA Hlth Care Syst, Dept Vet Affairs, Psychiat Serv, E Orange, NJ USA. RP Enoch, MA (reprint author), NIAAA, Neurogenet Lab, NIH, DICBR,LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH); National Institute of Drug Abuse, NIH [R01 DA 10336-02] FX This research was supported by the Intramural Research Program of The National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), and inpart by Grant R01 DA 10336-02 to AR from the National Institute of Drug Abuse, NIH. NR 61 TC 63 Z9 65 U1 4 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2010 VL 67 IS 1 BP 20 EP 27 DI 10.1016/j.biopsych.2009.08.019 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 533XH UT WOS:000272858600003 PM 19833324 ER PT J AU Barr, CS Chen, SA Schwandt, ML Lindell, SG Sun, H Suomi, SJ Heilig, M AF Barr, Christina S. Chen, Scott A. Schwandt, Melanie L. Lindell, Stephen G. Sun, Hui Suomi, Stephen J. Heilig, Markus TI Suppression of Alcohol Preference by Naltrexone in the Rhesus Macaque: A Critical Role of Genetic Variation at the mu-Opioid Receptor Gene Locus SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alcoholism; family history; naltrexone; opioids ID SINGLE-NUCLEOTIDE POLYMORPHISM; FUNCTIONAL POLYMORPHISM; DEPENDENCE; ASSOCIATION; OPRM1; VARIANTS AB Background: The role of a nonsynonymous A118G polymorphism of the human mu-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions. Methods: Twenty-one rhesus macaques (13 female rhesus macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied during 1-hour sessions for preference between an a Spartame-sweetened alcohol solution (8.4%vol/vol) and a nonalcoholic control fluid in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design. Results: Mixed-model analysis of variance controlling for baseline and sex showed a highly significant (p = .003) interaction between genotype and treatment. Post hoc analysis showed that vehicle-treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p = .001). Following naltrexone administration, 77G carriers decreased their preference (p = .002) and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment and, in fact, showed a trend-level increase of preference following naltrexone. Conclusions: These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone. C1 [Barr, Christina S.; Chen, Scott A.; Schwandt, Melanie L.; Lindell, Stephen G.; Sun, Hui; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, NICHD, Bethesda, MD USA. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Child Health and Haman Development (NICHD) FX This work was supported by the intramural research programs of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute of Child Health and Haman Development (NICHD). NR 20 TC 34 Z9 34 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2010 VL 67 IS 1 BP 78 EP 80 DI 10.1016/j.biopsych.2009.07.026 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 533XH UT WOS:000272858600011 PM 19748082 ER PT J AU Klein, HG AF Klein, Harvey G. TI How safe is blood, really? SO BIOLOGICALS LA English DT Article DE Transfusion; Blood safety; Transfusion risks ID CELL TRANSFUSION; CARDIAC-SURGERY; CRITICALLY-ILL; UNITED-STATES; FRESH BLOOD; RISK; MORTALITY; DISEASE; SUBSTITUTES; INFECTIONS AB Blood is safer than it has ever been, however the progression of transfusion from dangerous intervention to reliable supportive care been non-linear. Disparities resulting from geography, economy, and social class persist Some risks are known, others are unknown but predictable, and still others may be totally unpredictable. Among the known risks are infectious and immunologic events that can be calculated per unit of blood transfused. These risks vary by component. Among the unknown risks are the potential for emerging pathogens transmitted by blood and for processing or storage lesions to result in short or long-term toxicity. National registries provide some reassurance that transfusion may not affect mortality significantly beyond the first few weeks after administration. Nevertheless, transmission of novel pathogens, repeated allogeneic stimulation, and infusion of cytokines or chemokmes may have unrecognized consequences. Blood safety can be effected dramatically with small investment in developing countries. In the developed world, technologies such as pathogen inactivation, antigen camouflage, component substitutes, or cell expansion promise relatively small advances in safety at substantial cost No strategy guarantees zero-risk. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. NR 45 TC 29 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JAN PY 2010 VL 38 IS 1 BP 100 EP 104 DI 10.1016/j.biologicals.2009.10.008 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 580CX UT WOS:000276425600021 PM 20074975 ER PT J AU Knezevic, I Stacey, G Petricciani, J Sheets, R AF Knezevic, I. Stacey, G. Petricciani, J. Sheets, R. CA WHO Study Group Cell Substrates TI Evaluation of cell substrates for the production of biologicals: Revision of WHO recommendations Report of the WHO Study Group on Cell Substrates for the Production of Biologicals, 22-23 April 2009, Bethesda, USA SO BIOLOGICALS LA English DT Article AB Evaluating cell substrates for producing vaccines and other biologicals is one of the critical aspects in assuring quality and safety of these products. As part of its mission in setting standards for biological products. WHO provides recommendations for manufacturing and evaluating biologicals. Regular updates of the guidance documents are important to manufacturers and regulators worldwide. WHO Expert Committee on Biological Standardization (ECBS) identified a need for revising the requirements for cell substrates (WHO TRS 878, annex 1). In response, WHO established a Study Group (SG) in 2006 that prepared an updated set of recommendations for using cell substrates for the production of biologicals. A summary of the proposed changes that the SG made in 2007 is available at WHO web site (http.//www.who.int/biologicals/publications/meetings/areasivaccinesicells/en/index.html). Draft revised recommendations were circulated to regulators, manufacturers and other experts for comments in April 2009. The SG held its third meeting on 22-23 April 2009 to review progress in the revision and to propose further improvements In addition, the experts discussed the need for reference preparations, reference cell banks, and standardization of testing methodologies. The SG proposed clarifications of the rationale for in vivo testing as well as the potential for applying new methods for in vitro testing for detecting microbial agents In line with this, WHO should conduct review of the current manufacturers' practice in using tests for microbial agents and interpreting these results Additionally. WHO should take a lead in developing an International Standard for nucleic acid amplification test (NAT) for detecting mycoplasma contamination in cell substrates. WHO Collaborating Centers will lead this initiative, involving other relevant institutions in this area Finally, advice on the replacement of the WHO Vero reference cell bank 10-87 with respect to the source of cells and re-characterization of the bank was provided. The intended use of the replacement cell bank would be the same as for the current cell bank, which is to serve as a source of well-characterized cells for establishing master cell banks for the production of biologicals The SG will report outcomes of its discussion to the ECBS at its next meeting in October 2009 for further considerations and advice regarding the proposed course of action. C1 [Knezevic, I.] WHO, Dept Immunizat Vaccines & Biol, Qual Safety & Stand Team, CH-1211 Geneva, Switzerland. [Stacey, G.] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. [Sheets, R.] NIAID, NIH, Bethesda, MD 20892 USA. RP Knezevic, I (reprint author), WHO, Dept Immunizat Vaccines & Biol, Qual Safety & Stand Team, Ave Appia, CH-1211 Geneva, Switzerland. EM knezevici@who.int FU NIAID; IABS FX Financial and technical support of NIAID and IABS in organizing the Workshop on Microbial Agents in Animal Cells on 20-21 April 2009 is gratefully acknowledged. Review of current approaches and recent developments in the detection of microbial contaminants of animal cells facilitated the discussion of cell substrates in the SG meeting. NR 5 TC 16 Z9 16 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JAN PY 2010 VL 38 IS 1 BP 162 EP 169 DI 10.1016/j.biologicals.2009.08.019 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 580CX UT WOS:000276425600030 PM 19818645 ER PT S AU Evans, GW Kim, P AF Evans, Gary W. Kim, Pilyoung BE Adler, NE Stewart, J TI Multiple risk exposure as a potential explanatory mechanism for the socioeconomic status-health gradient SO BIOLOGY OF DISADVANTAGE: SOCIOECONOMIC STATUS AND HEALTH SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE multiple risk; cumulative risk; SES; health; poverty ID STRESSFUL LIFE EVENTS; CORONARY-HEART-DISEASE; CUMULATIVE RISK; PSYCHOLOGICAL DISTRESS; PSYCHOSOCIAL FACTORS; ENVIRONMENTAL RISK; SOCIOEMOTIONAL ADJUSTMENT; ACADEMIC ADJUSTMENT; CHILDHOOD POVERTY; EARLY ADOLESCENCE AB The social patterning of disease and mortality provokes a search for explanation. One potential underlying explanation for socioeconomic status (SES) gradients in health is exposure to multiple risk factors. Income and class tend to sort individuals into different settings that are often accompanied by systematic differences in environmental quality. Housing and neighborhood quality, pollutants and toxins, crowding and congestion, and noise exposure all vary with SES. Persons lower in SES also experience more adverse interpersonal relationships with family members, friends, supervisors, and community members. Furthermore, exposure to these multiple risk factors is associated with worse health outcomes. Thus, the convergence of exposure to multiple physical and psychosocial risk factors accompanying disadvantage may account for a portion of SES gradients in health in both childhood and adulthood. C1 [Evans, Gary W.] Cornell Univ, Ithaca, NY 14853 USA. [Kim, Pilyoung] NIMH, Bethesda, MD 20892 USA. RP Evans, GW (reprint author), Cornell Univ, 3M2061 Martha Van Rensselaer Hall, Ithaca, NY 14853 USA. EM gwe1@cornell.edu NR 72 TC 98 Z9 101 U1 7 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-770-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1186 BP 174 EP 189 DI 10.1111/j.1749-6632.2009.05336.x PG 16 WC Public, Environmental & Occupational Health; Multidisciplinary Sciences SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BOX21 UT WOS:000277908000010 PM 20201873 ER PT J AU Ghanayem, BI Bai, R Kissling, GE Travlos, G Hoffler, U AF Ghanayem, Burhan I. Bai, Re Kissling, Grace E. Travlos, Greg Hoffler, Undi TI Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity SO BIOLOGY OF REPRODUCTION LA English DT Article DE acrylamide; diet-induced obesity; dominant lethal mutations; hyperinsulinemia; insulin; leptin; male mice infertility ID BODY-MASS INDEX; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; CYTOCHROME-P450 2E1; FEMALE REPRODUCTION; ADAPTER PROTEIN; CREM ACTIVATOR; LIVER-INJURY; IN-VIVO; LEPTIN AB The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity. C1 [Ghanayem, Burhan I.; Bai, Re; Hoffler, Undi] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Travlos, Greg] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Pharmacol Lab, NIH, POB 12233,MD B3-10,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov FU Intramural NIH HHS NR 65 TC 51 Z9 64 U1 2 U2 16 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2010 VL 82 IS 1 BP 96 EP 104 DI 10.1095/biolreprod.109.078915 PG 9 WC Reproductive Biology SC Reproductive Biology GA 533TG UT WOS:000272847600011 PM 19696015 ER PT J AU Danshina, PV Geyer, CB Dai, QS Goulding, EH Willis, WD Kitto, GB McCarrey, JR Eddy, EM O'Brien, DA AF Danshina, Polina V. Geyer, Christopher B. Dai, Qunsheng Goulding, Eugenia H. Willis, William D. Kitto, G. Barrie McCarrey, John R. Eddy, E. M. O'Brien, Deborah A. TI Phosphoglycerate Kinase 2 (PGK2) Is Essential for Sperm Function and Male Fertility in Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE gene targeting; glycolysis; male fertility; spermatogenesis; sperm metabolism; sperm motility ID MOUSE SPERMATOGENIC CELLS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE-S; IMMUNOHISTOCHEMICAL LOCALIZATION; CRYSTAL-STRUCTURE; ACYL PHOSPHATASE; ROUND SPERMATIDS; FIBROUS SHEATH; MALE GERMLINE; TESTIS; GENE AB Phosphoglycerate kinase 2 (PGK2), an isozyme that catalyzes the first ATP-generating step in the glycolytic pathway, is encoded by an autosomal retrogene that is expressed only during spermatogenesis. It replaces the ubiquitously expressed phosphoglycerate kinase 1 (PGK1) isozyme following repression of Pgk1 transcription by meiotic sex chromosome inactivation during meiotic prophase and by postmeiotic sex chromatin during spermiogenesis. The targeted disruption of Pgk2 by homologous recombination eliminates PGK activity in sperm and severely impairs male fertility, but does not block spermatogenesis. Mating behavior, reproductive organ weights ( testis, excurrent ducts, and seminal vesicles), testis histology, sperm counts, and sperm ultrastructure were indistinguishable between Pgk2(-/-) and wild-type mice. However, sperm motility and ATP levels were markedly reduced in males lacking PGK2. These defects in sperm function were slightly less severe than observed in males lacking glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS), the isozyme that catalyzes the step preceding PGK2 in the sperm glycolytic pathway. Unlike Gapdhs(-/-) males, the Pgk2(-/-) males also sired occasional pups. Alternative pathways that bypass the PGK step of glycolysis exist. We determined that one of these bypass enzymes, acylphosphatase, is active in mouse sperm, perhaps contributing to phenotypic differences between mice lacking GAPDHS or PGK2. This study determined that PGK2 is not required for the completion of spermatogenesis, but is essential for sperm motility and male fertility. In addition to confirming the importance of the glycolytic pathway for sperm function, distinctive phenotypic characteristics of Pgk2(-/-) mice may provide further insights into the regulation of sperm metabolism. C1 [Danshina, Polina V.; O'Brien, Deborah A.] Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Danshina, Polina V.; O'Brien, Deborah A.] Univ N Carolina, Sch Med, Labs Reprod Biol, Chapel Hill, NC 27599 USA. [O'Brien, Deborah A.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA. [Geyer, Christopher B.; Dai, Qunsheng; Goulding, Eugenia H.; Willis, William D.; Eddy, E. M.] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. [Kitto, G. Barrie] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA. [McCarrey, John R.] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. RP O'Brien, DA (reprint author), Univ N Carolina, Sch Med, Dept Cell & Dev Biol, CB 7090, Chapel Hill, NC 27599 USA. EM dao@med.unc.edu FU National Institutes of Health (NIH) [U01 HD45982, R01 HD46637]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by National Institutes of Health (NIH) grants U01 HD45982 (D.A.O.) and R01 HD46637 (J.R.M.) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development NR 57 TC 67 Z9 69 U1 1 U2 14 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2010 VL 82 IS 1 BP 136 EP 145 DI 10.1095/biolreprod.109.079699 PG 10 WC Reproductive Biology SC Reproductive Biology GA 533TG UT WOS:000272847600016 PM 19759366 ER PT J AU Straszewski-Chavez, SL Abrahams, VM Aldo, PB Romero, R Mor, G AF Straszewski-Chavez, Shawn L. Abrahams, Vikki M. Aldo, Paula B. Romero, Roberto Mor, Gil TI AKT Controls Human First Trimester Trophoblast Cell Sensitivity to FAS-Mediated Apoptosis by Regulating XIAP Expression SO BIOLOGY OF REPRODUCTION LA English DT Article DE AKT; apoptosis; FAS; PIK3; placenta; pregnancy; trophoblast; XIAP ID X-LINKED INHIBITOR; PROTEIN-KINASE CK2; GROWTH-FACTOR; LIGAND EXPRESSION; PLACENTAL FAS; CANCER-CELLS; PHOSPHORYLATION; ACTIVATION; SURVIVAL; PATHWAY AB The PIK3/AKT pathway plays an important role in both the inhibition of the apoptotic cascade and the promotion of cell growth and proliferation. Multiple apoptosis-related targets of phosphatidylinositide 3-kinase (PIK3) and protein kinase B (AKT) have been identified, including the antiapoptotic protein XIAP. By phosphorylating XIAP, AKT was previously shown to prevent the ubiquitinization and degradation of XIAP. First-trimester trophoblast cells express high levels of XIAP, which protects them from certain apoptotic stimuli. In this study, we determine that the inhibition of the PIK3/AKT pathway induces XIAP inactivation and the activation of caspase 3 in first-trimester trophoblast cells. Using a specific AKT inhibitor and a XIAP mutant construct, which mimics the AKT phosphorylated form of XIAP, we also demonstrate that these effects are dependent on the phosphorylation of XIAP by AKT. Finally, we show that the selective inhibition of AKT renders normally resistant first-trimester trophoblast cells sensitive to FAS-mediated apoptosis by regulating XIAP expression. Our findings may provide a link between AKT, XIAP, and the regulation of the FAS apoptotic cascade in first-trimester trophoblast cells and contribute to our current knowledge of the molecular mechanisms mediating normal trophoblast physiology during pregnancy. C1 [Mor, Gil] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. [Straszewski-Chavez, Shawn L.] Yale Univ, Sch Med, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,LSOG 305A, New Haven, CT 06520 USA. EM Gil.Mor@yale.edu FU Perinatology Research Branch; Division of Intramural Research; National Institute of Child Health and Human Development; National Institutes of Health, Department of Health and Human Services FX Supported in part by the Perinatology Research Branch, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 40 TC 8 Z9 8 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2010 VL 82 IS 1 BP 146 EP 152 DI 10.1095/biolreprod.109.078972 PG 7 WC Reproductive Biology SC Reproductive Biology GA 533TG UT WOS:000272847600017 PM 19726736 ER PT J AU Geyer, C Anderson, AJ Eddy, M AF Geyer, Chris Anderson, Amy J. Eddy, Mitch TI The Rhox13 Gene Is Expressed in Premeiotic Germ Cells in Both Sexes and Its Translation Is Regulated in the Testis by NANOS2 SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Geyer, Chris; Anderson, Amy J.; Eddy, Mitch] NIEHS NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 69 BP 65 EP 65 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300064 ER PT J AU Fan, HY Liu, ZL Johnson, PF Richards, JS AF Fan, Heng-Yu Liu, Zhilin Johnson, Peter F. Richards, JoAnne S. TI CCAAT/Enhancer Binding Protein (C/EBP)-alpha and -beta Are Essential for Ovulation and Luteinization by Regulating the Expression of Novel Target Genes SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 Baylor Coll Med, Houston, TX 77030 USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 151 BP 83 EP 83 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300143 ER PT J AU Winuthayanon, W Hewitt, SC Orvis, GD Behringer, RR Korach, KS AF Winuthayanon, Wipawee Hewitt, Sylvia Curtis Orvis, Grant D. Behringer, Richard R. Korach, Kenneth S. TI Selective Ablation of ER alpha in Uterine Epithelia Alters Uterine Estrogen Responses SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 167 BP 87 EP 87 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300158 ER PT J AU Newbold, RR AF Newbold, Retha R. TI Developmental Effects of Environmental Estrogens on Subsequent Fertility and Ovarian Function SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Newbold, Retha R.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 208 BP 96 EP 96 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300197 ER PT J AU Kim, B Kan, R Anguish, L Nelson, LM Coonrod, SA AF Kim, Boram Kan, Rui Anguish, Lynne Nelson, Lawrence M. Coonrod, Scott A. TI Role for MATER in Cytoplasmic Lattice Formation in Murine Oocytes SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 Cornell Univ, Ithaca, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 328 BP 122 EP 122 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300305 ER PT J AU Clement, T Inselman, A Willis, W Goulding, E Eddy, M AF Clement, Tracy Inselman, Amy Willis, William Goulding, Eugenia Eddy, Mitch TI Cyclin Dependant Kinase 1 (Cdk1) is Required for Male Meiotic Progression and Male Fertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Clement, Tracy; Inselman, Amy; Willis, William; Goulding, Eugenia; Eddy, Mitch] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 506 BP 160 EP 160 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300470 ER PT J AU Burkart, A Baibakov, B Gauthier, L Dean, J AF Burkart, Anna Baibakov, Boris Gauthier, Lyn Dean, Jurrien TI Potential Role of a Cortical-Granule Metalloprotease in the Post-Fertilization Block to Polyspermy. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Burkart, Anna; Baibakov, Boris; Gauthier, Lyn; Dean, Jurrien] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 557 BP 170 EP 170 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300514 ER PT B AU Speakman, J AF Speakman, John BE Ochs, MF Casagrande, JT Davuluri, RV TI The caBIG (R) Clinical Trials Suite SO BIOMEDICAL INFORMATICS FOR CANCER RESEARCH LA English DT Article; Book Chapter AB As part of its Cancer Biomedical Informatics Grid (caBIG (R)) program and its overall commitment to drive the reengineering of the clinical research enterprise, the National Cancer Institute has developed the caBIG (R) Clinical Trials Suite. The Suite is a free, stable, supported collection of open-source software tools for clinical trials management, developed in response to the expressed need of the biomedical research community and deployable either as one or more standalone components or as an integrated Suite. It is also a reference implementation of the caBIG (R) enterprise architecture paradigm of modular, interoperable software components. This chapter gives an overview of the context within which the Suite was envisaged and developed, describes the functionality and availability of the Suite and gives an overview of the enterprise architecture of which the Suite is intended to serve as a reference implementation. C1 NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. RP Speakman, J (reprint author), NCI, Ctr Biomed Informat & Informat Technol, 2115 E Jefferson St,Suite 6000, Rockville, MD 20852 USA. EM speakmaj@mail.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5712-2 PY 2010 BP 203 EP 213 DI 10.1007/978-1-4419-5714-6_10 D2 10.1007/978-1-4419-5714-6 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology GA BOO43 UT WOS:000277148600010 ER PT B AU Klemm, J Basu, A Fore, I Floratos, A Komatsoulis, G AF Klemm, Juli Basu, Anand Fore, Ian Floratos, Aris Komatsoulis, George BE Ochs, MF Casagrande, JT Davuluri, RV TI The caBIG (R) Life Sciences Distribution SO BIOMEDICAL INFORMATICS FOR CANCER RESEARCH LA English DT Article; Book Chapter ID MICROARRAY DATA; IMPLEMENTATION; ARCHITECTURE; NETWORKS; ONTOLOGY; CONTEXT; MIAME; TOOL AB caBIG (R) is a virtual network of organizations developing and adopting interoperable databases and analytical tools to facilitate translational cancer research (von Eschenbach and Buetow 2007). It is an open-source, open-access program, and all the tools and resources are freely available to the research community. The National Cancer Institute is developing resources to assist enterprise-wide adoption of the caBIG (R) tools. To this end, we have bundled mature software tools together to facilitate easy adoption and installation. The Life Sciences Distribution (LSD) is comprised of tools to support the continuum of translational research: caArray, for the management and annotation of microarray data; caTissue, to support the collection, annotation, and distribution of biospecimens; the Clinical Trials Object Data System, for the sharing of clinical trials information; the National Biomedical Imaging Archive, for annotation, storage, and sharing of in vivo images; cancer Genome Wide Association Studies, for publishing and mining data from GWAS studies; and geWorkbench, supporting the integrated analysis and annotation of expression and sequence data. All the LSD tools are connected to caGrid (Saltz et al. 2006), which makes it possible for the databases at multiple institutions to be interconnected to support data sharing and integration. More information on the LSD suite of products, including installation packages, user and installation guides, and links to exemplar installations can be found at http://ncicb.nci.nih.gov/NCICB/tools/lsd. C1 [Klemm, Juli; Basu, Anand; Fore, Ian; Komatsoulis, George] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. [Floratos, Aris] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. RP Klemm, J (reprint author), NCI, Ctr Biomed Informat & Informat Technol, 2115 E Jefferson St,Suite 6000, Rockville, MD 20852 USA. EM klemmj@mail.nih.gov OI Komatsoulis, George/0000-0001-6967-7085 NR 17 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5712-2 PY 2010 BP 253 EP 266 DI 10.1007/978-1-4419-5714-6_14 D2 10.1007/978-1-4419-5714-6 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology GA BOO43 UT WOS:000277148600014 ER PT J AU Iyer, MR Lee, YS Deschamps, JR Rothman, RB Dersch, CM Jacobson, AE Rice, KC AF Iyer, Malliga R. Lee, Yong Sok Deschamps, Jeffrey R. Rothman, Richard B. Dersch, Christina M. Jacobson, Arthur E. Rice, Kenner C. TI Probes for narcotic receptor mediated phenomena. 40. N-Substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Synthesis; Opioid receptor binding; N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols; Oxide-bridged phenylmorphans; Geometry optimization; Superposition ID OXIDE-BRIDGED PHENYLMORPHANS; PHENETHYL ANALOGS; IN-VITRO; AFFINITY; ISOMERS; 5-(META-HYDROXYPHENYL)MORPHAN; MORPHINE; AGONISTS AB A series of N-substituted rac-cis-4a-ethyl-1,2,3,4,4a, 9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols have been prepared using a simple synthetic route previously designed for synthesis of related cis-2-methyl-4a-alkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols. The new phenolic compounds, where the aromatic hydroxy moiety is situated ortho to the oxygen atom in the oxide-bridged ring, do not interact as well as the pyridin-6-ols with opioid receptors. The N-para-fluorophenethyl derivative had the highest mu-opioid receptor affinity of the examined compounds (K(i) = 0.35 mu M). Published by Elsevier Ltd. C1 [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lee, Yong Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, CIT,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. [Rothman, Richard B.; Dersch, Christina M.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA. EM kr21f@nih.gov OI Deschamps, Jeffrey/0000-0001-5845-0010 FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [Y1-DA6002, Y01 DA006002] NR 27 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2010 VL 18 IS 1 BP 91 EP 99 DI 10.1016/j.bmc.2009.11.022 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 534JJ UT WOS:000272892100010 PM 20005115 ER PT J AU Weidlich, IE Dexheimer, T Marchand, C Antony, S Pommier, Y Nicklaus, MC AF Weidlich, Iwona E. Dexheimer, Thomas Marchand, Christophe Antony, Smitha Pommier, Yves Nicklaus, Marc C. TI Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by virtual screening using ligand-based pharmacophores SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Human tyrosyl-DNA phosphodiesterase; Tdp1; Inhibitors; Small molecule docking; Drug design; Virtual screening ID PHOSPHODIESTERASE TDP1; CRYSTAL-STRUCTURE; COMPLEXES; VANADATE; IDENTIFICATION; MECHANISM; PATHWAYS; BINDING; PEPTIDE; SITES AB Human tyrosyl-DNA phosphodiesterase (hTdp1) inhibitors have become a major area of drug research and structure-based design since they have been shown to work synergistically with camptothecin (CPT) and selectively in cancer cells. The pharmacophore features of 14 hTdp1 inhibitors were used as a filter to screen the ChemNavigator iResearch Library of about 27 million purchasable samples. Docking of the inhibitors and hits obtained from virtual screening was performed into a structural model of hTdp1 based on a high resolution X-ray crystal structure of human Tdp1 in complex with vanadate, DNA and a human topoisomerase I (TopI)-derived peptide (PDB code: 1NOP). A total of 46 compounds matching the three-dimensional arrangement of the pharmacophoric features were assayed. Using a high-throughput screening assay, we have identified an 1H-indol-3-yl-acetic acid derivative as a potent Tdp1 inhibitor with an IC(50) value of 7.94 mu M. The obtained novel chemotype may provide a new scaffold for developing inhibitors of Tdp1. (C) 2009 Published by Elsevier Ltd. C1 [Weidlich, Iwona E.; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Dexheimer, Thomas; Marchand, Christophe; Antony, Smitha; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Nicklaus, MC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. EM iweidlic@helix.nih.gov; mn1@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU Intramural NIH HHS [ZIC BC010639-07] NR 28 TC 13 Z9 13 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2010 VL 18 IS 1 BP 182 EP 189 DI 10.1016/j.bmc.2009.11.008 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 534JJ UT WOS:000272892100021 PM 19963390 ER PT J AU Patel, SA Rajale, T O'Briena, E Burkhart, DJ Nelson, JK Twamley, B Blumenfeld, A Szabon-Watola, MI Gerdes, JM Bridges, RJ Natale, NR AF Patel, Sarjubhai A. Rajale, Trideep O'BrienA, Erin Burkhart, David J. Nelson, Jared K. Twamley, Brendan Blumenfeld, Alex Szabon-Watola, Monika I. Gerdes, John M. Bridges, Richard J. Natale, Nicholas R. TI Isoxazole analogues bind the System x(c)(-) transporter: Structure-activity relationship and pharmacophore model SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Isoxazole; System x(c)(-); Transporter; Pharmacophore; Structure-activity relationship ID CYSTINE-GLUTAMATE EXCHANGE; PRIMARY BRAIN-TUMORS; GLIOMA-CELLS; AMINO-ACID; EXTRACELLULAR GLUTAMATE; ANTINOCICEPTIVE AGENTS; IN-VIVO; INHIBITORS; RELEASE; MECHANISM AB Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System x(c)(-). Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System x(c)(-), the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y = Y' = 3,5-(CF3)(2), which both inhibited glutamate uptake by the System x(c)(-) transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Patel, Sarjubhai A.; Rajale, Trideep; O'BrienA, Erin; Szabon-Watola, Monika I.; Gerdes, John M.; Bridges, Richard J.; Natale, Nicholas R.] Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. [Rajale, Trideep; Burkhart, David J.; Nelson, Jared K.; Twamley, Brendan; Blumenfeld, Alex; Szabon-Watola, Monika I.; Natale, Nicholas R.] Univ Idaho, Dept Chem, Moscow, ID 83844 USA. RP Natale, NR (reprint author), Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. EM Nicholas.natale@umontana.edu FU NCRR NIH HHS [P20 RR015583, P20 RR015583-105624, P20RR015583]; NINDS NIH HHS [NS038444, NS30570, R01 NS030570, R01 NS030570-12, R15 NS038444, R15 NS038444-04] NR 49 TC 17 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2010 VL 18 IS 1 BP 202 EP 213 DI 10.1016/j.bmc.2009.11.001 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 534JJ UT WOS:000272892100023 PM 19932968 ER PT J AU Liu, F Stephen, AG Waheed, AA Freed, EO Fisher, RJ Burke, TR AF Liu, Fa Stephen, Andrew G. Waheed, Abdul A. Freed, Eric O. Fisher, Robert J. Burke, Terrence R., Jr. TI Application of ring-closing metathesis macrocyclization to the development of Tsg101-binding antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Macrocycle; Ring-closing metathesis; Peptide mimic; Peptide; Solid-phase synthesis ID EXPEDITED LIBRARY SYNTHESIS; HYDROGEN-BOND SURROGATE; METABOLIC STABILITY; CYCLIC-PEPTIDES; ALPHA-HELIX; STABILIZATION; CYCLIZATION; PROTEINS; PEPTOIDS; DOMAINS AB HIV-1 viral budding involves binding of the viral Gag(p6) protein to the ubiquitin E2 variant domain of the human tumor susceptibility gene 101 protein (Tsg101). Recognition of p6 by Tsg101 is mediated in part by a proline-rich motif that contains the sequence 'Pro-Thr-Ala-Pro' ('PTAP'). Using the p6-derived 9-mer sequence 'PEPTAPPEE', we had previously improved peptide binding affinity by employing N-alkylglycine ('peptoid') residues. The current study applies ring-closing metathesis macrocyclization strategies to Tsg101-binding peptide-peptoid hybrids as an approach to stabilize binding conformations and to observe the effects of such macrocyclization on Tsg101-binding affinity and bioavailability. Published by Elsevier Ltd. C1 [Liu, Fa; Burke, Terrence R., Jr.] Natl Canc Inst Frederick, Med Chem Lab, Ctr Canc Res, Natl Inst Hlth Frederick, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick Inc, Prot Chem Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA. [Waheed, Abdul A.; Freed, Eric O.] Natl Canc Inst Frederick, HIV Drug Resistance Program, Natl Inst Hlth Frederick, Frederick, MD 21702 USA. RP Liu, F (reprint author), Natl Canc Inst Frederick, Med Chem Lab, Ctr Canc Res, Natl Inst Hlth Frederick, Frederick, MD 21702 USA. EM liuf@ncifcrf.gov; tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU NIH [N01-CO-12400]; Center for Cancer Research; NCI-Frederick; National Cancer Institute FX This Work was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick and the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. NR 35 TC 7 Z9 7 U1 0 U2 8 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 JAN 1 PY 2010 VL 20 IS 1 BP 318 EP 321 DI 10.1016/j.bmcl.2009.10.105 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 534ZG UT WOS:000272935600070 PM 19914066 ER PT J AU Wang, HF Byun, Y Barinka, C Pullambhatla, M Bhang, HEC Fox, JJ Lubkowski, J Mease, RC Pomper, MG AF Wang, Haofan Byun, Youngjoo Barinka, Cyril Pullambhatla, Mrudula Bhang, Hyo-eun C. Fox, James J. Lubkowski, Jacek Mease, Ronnie C. Pomper, Martin G. TI Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure-activity relationship studies SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE PSMA; Glutamate carboxypeptidase II; Molecular imaging; Radiopharmaceutical; SPECT ID GLUTAMATE-CARBOXYPEPTIDASE-II; NAAG PEPTIDASE INHIBITORS; ISCHEMIC BRAIN-INJURY; MEMBRANE ANTIGEN; PROSTATE-CANCER; N-ACETYLASPARTYLGLUTAMATE; MONOCLONAL-ANTIBODIES; MODELS; SCHIZOPHRENIA; NEUROPATHY AB We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure-activity relationship studies of the P1' site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with K(i) values below 20 nM. Among them, compound 32d (K(i) = 11 nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1' pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wang, Haofan; Byun, Youngjoo; Pullambhatla, Mrudula; Fox, James J.; Mease, Ronnie C.; Pomper, Martin G.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21231 USA. [Barinka, Cyril; Lubkowski, Jacek] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Bhang, Hyo-eun C.; Pomper, Martin G.] Johns Hopkins Med Inst, Dept Pharmacol & Mol Sci, Baltimore, MD 21231 USA. RP Pomper, MG (reprint author), Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21231 USA. EM mpomper@jhmi.edu RI Barinka, Cyril/G-9803-2014 FU National Institutes of Health [MH080580, CA092871]; U.S. Department of Energy [W-31-109-Eng38]; National Cancer Institute, Center for Cancer Research FX The authors are grateful for financial support from National Institutes of Health Grants MH080580 and CA092871 to M. G. P. The use of the Advanced Photon Source was supported by the U.S. Department of Energy (W-31-109-Eng38). J.L. and C. B. acknowledge financial support from the National Cancer Institute, Center for Cancer Research. NR 33 TC 38 Z9 38 U1 0 U2 8 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 JAN 1 PY 2010 VL 20 IS 1 BP 392 EP 397 DI 10.1016/j.bmcl.2009.10.061 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 534ZG UT WOS:000272935600088 PM 19897367 ER PT J AU Frolov, VA Bashkirov, PV Akimov, SA Zimmerberg, J AF Frolov, Vadim A. Bashkirov, Pavel V. Akimov, Sergei A. Zimmerberg, Joshua TI Membrane Curvature and Fission By Dynamin: Mechanics, Dynamics and Partners SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Frolov, Vadim A.; Bashkirov, Pavel V.; Akimov, Sergei A.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Bashkirov, Pavel V.; Akimov, Sergei A.] RAS, AN Frumkin Inst Phys Chem & Electrochem, Moscow 117901, Russia. RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 0 TC 0 Z9 0 U1 1 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 2A EP 2A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000011 ER PT J AU Capone, R Mustata, M Jang, H Ramachandran, S Nussinov, R Lal, R AF Capone, Ricardo Mustata, Mirela Jang, Hyunbum Ramachandran, Srinivasan Nussinov, Ruth Lal, Ratneshwar TI Protegrin-1 (PG-1), An Antimicrobial Peptide Forms Ion Channels: Atomic Force Microscopy, Channel Conductance, and Molecular Dynamics Simulation Study SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Capone, Ricardo; Mustata, Mirela; Ramachandran, Srinivasan; Lal, Ratneshwar] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Jang, Hyunbum; Nussinov, Ruth] NCI, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 9A EP 10A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000050 ER PT J AU Harada, BT Liu, SX Le Grice, SFJ Zhuang, XW AF Harada, Bryan T. Liu, Shixin Le Grice, Stuart F. J. Zhuang, Xiaowei TI Dynamics of the HIV Reverse Transcription Initiation Complex SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Harada, Bryan T.; Liu, Shixin; Zhuang, Xiaowei] Harvard Univ, Cambridge, MA 02138 USA. [Le Grice, Stuart F. J.] NCI, Frederick, MD 21701 USA. [Zhuang, Xiaowei] Howard Hughes Med Inst, Cambridge, MA USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 12A EP 12A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000064 ER PT J AU Kobrinsky, E Duong, S Sheydina, A Soldatov, N AF Kobrinsky, Evgeny Duong, Sonny Sheydina, Anna Soldatov, Nikolai TI Calcium Channel-Activated CREB-Dependent Excitation-Transcription Coupling: Microdomain Organization and Frequency-Dependent Regulation Revealed By Wavelet Analysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kobrinsky, Evgeny; Duong, Sonny; Sheydina, Anna; Soldatov, Nikolai] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 15A EP 15A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000078 ER PT J AU Bennett, MP Greeley, LA Mitchell, DC AF Bennett, Michael P. Greeley, Laura A. Mitchell, Drake C. TI Hydrophobic Mismatch Modulates the Kinetics of G Protein Binding and Receptor Conformation Change SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bennett, Michael P.] NIAAA, Bethesda, MD USA. [Greeley, Laura A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Mitchell, Drake C.] Portland State Univ, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 21A EP 21A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000109 ER PT J AU Maltsev, AV Maltsev, VA Mikheev, M Maltseva, LA Sirenko, SG Lakatta, EG Stern, MD AF Maltsev, Anna V. Maltsev, Victor A. Mikheev, Maxim Maltseva, Larissa A. Sirenko, Syevda G. Lakatta, Edward G. Stern, Michael D. TI Emergence of Local Ca Oscillators in Cardiac Pacemaker Cells: 2d Ca Dynamics Measurements, An Analytical Theory, and Complex Systems Numerical Modeling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Maltsev, Anna V.; Maltsev, Victor A.; Mikheev, Maxim; Lakatta, Edward G.; Stern, Michael D.] NIA, IRP, NIH, Baltimore, MD 21224 USA. [Maltseva, Larissa A.; Sirenko, Syevda G.] MedStar Res Inst, Baltimore, MD USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 21A EP 21A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000111 ER PT J AU Soubias, O Mitchell, DC Gawrisch, K AF Soubias, Olivier Mitchell, Drake C. Gawrisch, Klaus TI Functional Consequences of Lipid-Mediated Interaction Between Rhodopsin Molecules SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Soubias, Olivier; Gawrisch, Klaus] NIH, Rockville, MD USA. [Mitchell, Drake C.] Portland State Univ, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 21A EP 21A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000108 ER PT J AU Liu, J Nussinov, R AF Liu, Jin Nussinov, Ruth TI Conformational Control of Ubiquitination in the Cullin-Ring E3 Ligase Machinery SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Liu, Jin; Nussinov, Ruth] NCI, SAIC Frederick, Frederick, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 26A EP 27A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000140 ER PT J AU Chung, HS Gopich, IV Louis, JM McHale, K Cellmer, T Eaton, WA AF Chung, Hoi Sung Gopich, Irina V. Louis, John M. McHale, Kevin Cellmer, Troy Eaton, William A. TI Photon-By-Photon Analysis of Single Molecule Fluorescence Trajectories of a Fast Folding Protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chung, Hoi Sung; Gopich, Irina V.; Louis, John M.; McHale, Kevin; Cellmer, Troy; Eaton, William A.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 29A EP 30A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000155 ER PT J AU Zhao, HY Schuck, P AF Zhao, Huaying Schuck, Peter TI Determining Thermodynamic Parameters of Protein Interactions By Global Analysis of Data From Multiple Techniques SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Zhao, Huaying; Schuck, Peter] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 61A EP 61A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000323 ER PT J AU Jin, J Bai, L Johnson, DS Fulbright, RM Kireeva, ML Kashlev, M Wang, MD AF Jin, Jing Bai, Lu Johnson, Daniel S. Fulbright, Robert M. Kireeva, Maria L. Kashlev, Mikhail Wang, Michelle D. TI Synergistic Action of RNA Polymerases in Overcoming the Nucleosomal Barrier SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Jin, Jing; Fulbright, Robert M.] Cornell Univ, Ithaca, NY USA. [Bai, Lu; Johnson, Daniel S.] Rockefeller Univ, New York, NY 10021 USA. [Kireeva, Maria L.; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Wang, Michelle D.] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 67A EP 67A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000357 ER PT J AU Wall, ME Markowitz, DA Rosner, JL Martin, RG AF Wall, Michael E. Markowitz, David A. Rosner, Judah L. Martin, Robert G. TI Model of Transcriptional Activation By MarA in Escherichia Coli SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wall, Michael E.; Markowitz, David A.] Los Alamos Natl Lab, Los Alamos, NM USA. [Rosner, Judah L.; Martin, Robert G.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 70A EP 70A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000369 ER PT J AU Rouzina, I Qualley, D Wu, TY Iwatani, Y Geertsema, H Chan, D Hertz, A Williams, MC Levin, J Musier-Forsyth, K AF Rouzina, Ioulia Qualley, Dominic Wu, Tiyun Iwatani, Yasumasa Geertsema, Hylkje Chan, Denise Hertz, Amber Williams, Mark C. Levin, Judith Musier-Forsyth, Karin TI Nucleic Acid Interaction Kinetics of APOBEC3G Investigated Using Ensemble and Single Molecule Methods SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Rouzina, Ioulia] Univ Minnesota, Minneapolis, MN USA. [Qualley, Dominic; Musier-Forsyth, Karin] Ohio State Univ, Columbus, OH 43210 USA. [Wu, Tiyun; Hertz, Amber; Levin, Judith] NIH, Bethesda, MD 20892 USA. [Iwatani, Yasumasa] Natl Hosp Org Nagoya Med Ctr, Nagoya, Aichi, Japan. [Geertsema, Hylkje; Williams, Mark C.] Northeastern Univ, Boston, MA 02115 USA. [Chan, Denise] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 72A EP 72A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000379 ER PT J AU Mohanty, JG Barodka, V Berkowitz, DE Rifkind, JM AF Mohanty, Joy G. Barodka, Viachaslau Berkowitz, Dan E. Rifkind, Joseph M. TI Intracellular Calcium Mediated Stiffness of Red Blood Cells Is Reversed By Hypoxic Pre-Incubation With Nitrite Ions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Mohanty, Joy G.; Rifkind, Joseph M.] NIA, Baltimore, MD 21224 USA. [Barodka, Viachaslau; Berkowitz, Dan E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 77A EP 77A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000408 ER PT J AU Contreras, JE Limon, A Lopez-Rodriguez, A AF Contreras, Jorge E. Limon, Agenor Lopez-Rodriguez, Angelica TI Gating by Voltage and Ca2+ in Human Connexin (cx26) Hemichannels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Contreras, Jorge E.; Lopez-Rodriguez, Angelica] NIH, Bethesda, MD 20892 USA. [Contreras, Jorge E.; Limon, Agenor; Lopez-Rodriguez, Angelica] MBL, Grass Lab, Woods Hole, MA USA. [Limon, Agenor] Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 92A EP 92A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000488 ER PT J AU Smyth, JT Petranka, JG Boyles, RR DeHaven, WI Fukushima, M Johnson, KL Williams, JG Putney, JW AF Smyth, Jeremy T. Petranka, John G. Boyles, Rebecca R. DeHaven, Wayne I. Fukushima, Miwako Johnson, Katina L. Williams, Jason G. Putney, James W. TI Phosphorylation of STIM1 Underlies Suppression of Store-Operated Calcium Entry During Mitosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Smyth, Jeremy T.; Petranka, John G.; Boyles, Rebecca R.; DeHaven, Wayne I.; Fukushima, Miwako; Johnson, Katina L.; Williams, Jason G.; Putney, James W.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 97A EP 98A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000513 ER PT J AU Yang, DM Lyashkov, A Yue, L Lakatta, EG AF Yang, Dongmei Lyashkov, Alexey Yue, Li Lakatta, Edward G. TI A Reduction of Spontaneous Beating Rate of Adult Rabbit Pacemaker Cells in Culture is Reversed by RGS2 Overexpression, Gi Inhibition or beta-Ar Stimulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yang, Dongmei; Lyashkov, Alexey; Yue, Li; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 98A EP 99A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000518 ER PT J AU Vinogradova, TM Lakatta, EG AF Vinogradova, Tatiana M. Lakatta, Edward G. TI Spontaneous Beating of Rabbit Sinoatrial Node Cells Requires Basal Protein Kinase C Activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 99A EP 99A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000519 ER PT J AU Lyashkov, AE Vinogradova, TM Lakatta, EG Maltsev, VA AF Lyashkov, Alexey E. Vinogradova, Tatiana M. Lakatta, Edward G. Maltsev, Victor A. TI Ignition Point: A Novel Parameter of Sinoatrial Nodal Cell (SANC) Diastolic Depolarization (DD) Reports the Onset of Spontaneous Local Subsarcolemmal Ca Release (LCR) and Predicts Cycle Length SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lyashkov, Alexey E.; Vinogradova, Tatiana M.; Lakatta, Edward G.; Maltsev, Victor A.] NIA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 103A EP 103A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001013 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI A Novel Quantitative Explanation of G Protein-Coupled Receptor Modulation of Sinoatrial Cell Automaticity Via Interactions of Ca Clock and Membrane Voltage Clock SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 103A EP 103A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001012 ER PT J AU Arce, FMT Jang, H Nussinov, R Lal, R AF Arce, Fernando M. Teran Jang, Hyunbum Nussinov, Ruth Lal, Ratnesh TI Real-Time Afm Imaging of Surface-Induced Oligomerization of the Non-Amyloidogenic P3 Peptide: Implications for Membrane Insertion and Ion Channel Formation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Arce, Fernando M. Teran; Lal, Ratnesh] Univ Chicago, Chicago, IL 60637 USA. [Jang, Hyunbum; Nussinov, Ruth] NCI, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 110A EP 110A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001047 ER PT J AU Bosmans, F Puopolo, M Martin-Eauclaire, MF Bean, BP Swartz, KJ AF Bosmans, Frank Puopolo, Michelino Martin-Eauclaire, Marie-France Bean, Bruce P. Swartz, Kenton J. TI Defining the Voltage Sensor Properties and Pharmacology of Nav1.9 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bosmans, Frank; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA. [Puopolo, Michelino; Bean, Bruce P.] Harvard Univ, Sch Med, Boston, MA USA. [Martin-Eauclaire, Marie-France] CNRS, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 115A EP 115A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001070 ER PT J AU Feng, HZ Chen, M Weinstein, LS Jin, JP AF Feng, Hanzhong Chen, Min Weinstein, Lee S. Jin, J. P. TI Fast-To-Slow Fiber Type Switch Increases Fatigue Resistance as a Compensatory Adaptation In Gs alpha-Deficient Soleus Muscle SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Feng, Hanzhong; Jin, J. P.] Wayne State Univ, Dept Physiol, Detroit, MI USA. [Chen, Min; Weinstein, Lee S.] NIH, Metab Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 149A EP 149A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001238 ER PT J AU Qiu, XY Setlow, P Rau, DC Parsegian, VA AF Qiu, Xiangyun Setlow, Peter Rau, Donald C. Parsegian, V. Adrian TI Examples of X-Ray Scattering Studies of Biological Systems under Extreme Conditions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Qiu, Xiangyun; Rau, Donald C.; Parsegian, V. Adrian] NIH, Bethesda, MD 20892 USA. [Setlow, Peter] Univ Connecticut, Ctr Hlth, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 160A EP 160A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001298 ER PT J AU Combs, CA Smirnov, A Chess, D McGavern, D Luger-Hammer, M Knutson, JR Balaban, RS AF Combs, Christian A. Smirnov, Aleksandr Chess, David McGavern, Dorian Luger-Hammer, Merav Knutson, Jay R. Balaban, Robert S. TI Optimizing Multi-Photon Fluorescence Microscopy Light Collection from Living Tissue by Non-Contact Total Emission Detection (TEDII) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Combs, Christian A.; Smirnov, Aleksandr; Chess, David; McGavern, Dorian; Luger-Hammer, Merav; Knutson, Jay R.; Balaban, Robert S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 180A EP 180A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001401 ER PT J AU Paik, DH Seol, Y Halsey, W Perkins, TT AF Paik, Daniel H. Seol, Yeonee Halsey, Wayne Perkins, Thomas T. TI Integrating a High-Force Optical Trap with Gold Nanoposts and a Robust Gold-DNA Bond SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Paik, Daniel H.; Halsey, Wayne; Perkins, Thomas T.] Univ Colorado, JILA, Boulder, CO 80309 USA. [Seol, Yeonee] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 183A EP 184A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001419 ER PT J AU Dimitriadis, EK Heymann, JB Steven, AC Gellert, M Yang, W AF Dimitriadis, Emilios K. Heymann, J. Bernard Steven, Alasdair C. Gellert, Martin Yang, Wei TI Organization of RAG1/2 and RSS DNA in the Post-Cleavage Complex SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD USA. [Gellert, Martin; Yang, Wei] NIDDK, NIH, Bethesda, MD USA. [Heymann, J. Bernard; Steven, Alasdair C.] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 189A EP 189A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001451 ER PT J AU Kotova, S Lafer, EM Smith, PD Nossal, R Jin, AJ AF Kotova, Svetlana Lafer, Eileen M. Smith, Paul D. Nossal, Ralph Jin, Albert J. TI AFM and SMFS of Clathrin Triskelia under Fluid SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kotova, Svetlana; Smith, Paul D.; Jin, Albert J.] NIBIB, NIH, Bethesda, MD USA. [Lafer, Eileen M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Nossal, Ralph] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 190A EP 191A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001457 ER PT J AU Kotova, S Jimenez-Movilla, M Dimitriadis, EK Dean, J AF Kotova, Svetlana Jimenez-Movilla, Maria Dimitriadis, Emilios K. Dean, Jurrien TI Inhomogeneous Morphology and Elasticity of Mouse Oocyte Zona Pellucida Pre- And Post-Fertilization SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kotova, Svetlana; Dimitriadis, Emilios K.] NIBIB, LBPS, NIH, Bethesda, MD USA. [Jimenez-Movilla, Maria; Dean, Jurrien] NIDDK, LCDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 193A EP 193A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001468 ER PT J AU Rostovtseva, TK Sheldon, K Bezrukov, SM AF Rostovtseva, Tatiana K. Sheldon, Kely Bezrukov, Sergey M. TI Using VDAC-Tubulin Interaction to Assess VDAC Orientation in the Mitochondrial Membrane SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Rostovtseva, Tatiana K.; Sheldon, Kely; Bezrukov, Sergey M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 207A EP 208A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002036 ER PT J AU Lowe, AR Siegel, JJ Kalab, P Siu, M Weis, K Liphardt, JT AF Lowe, Alan R. Siegel, Jake J. Kalab, Petr Siu, Merek Weis, Karsten Liphardt, Jan T. TI Selectivity Mechanism of the Nuclear Pore Complex Characterized by Single Cargo Tracking SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lowe, Alan R.; Weis, Karsten; Liphardt, Jan T.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Siegel, Jake J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Kalab, Petr] NCI, Bethesda, MD 20892 USA. [Siu, Merek] Illumina Inc, Hayward, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 209A EP 209A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002043 ER PT J AU Kanchanawong, P Shtengle, G Ramko, EB Davidson, MW Hess, HF Waterman, C AF Kanchanawong, Pakorn Shtengle, Gleb Ramko, Erika B. Davidson, Michael W. Hess, Harald F. Waterman, Clare TI Nanoscale Protein Architecture of Focal Adhesions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kanchanawong, Pakorn; Waterman, Clare] NHLBI, NIH, Bethesda, MD 20892 USA. [Shtengle, Gleb; Hess, Harald F.] Janelia Farm HHMI, Ashburn, VA USA. [Ramko, Erika B.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL USA. NR 0 TC 1 Z9 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 211A EP 211A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002052 ER PT J AU Milac, AL Anishkin, A Fatakia, SN Chow, CC Sukharev, S Guy, RH AF Milac, Adina L. Anishkin, Andriy Fatakia, Sarosh N. Chow, Carson C. Sukharev, Sergei Guy, Robert H. TI Structural Models of Two-Pore-Domain Potassium Channels Focus on TREK SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Milac, Adina L.; Guy, Robert H.] NCI, NIH, Bethesda, MD 20892 USA. [Anishkin, Andriy; Sukharev, Sergei] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [Fatakia, Sarosh N.; Chow, Carson C.] NIDDK, NIH, Bethesda, MD USA. RI Milac, Adina/C-1070-2011 OI Milac, Adina/0000-0003-1845-4281 NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 228A EP 228A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002137 ER PT J AU Oke, O Sakamoto, T Forgacs, E Knight, P Stan, B Sellers, J White, HD Trinick, J AF Oke, Olusola Sakamoto, Takeshi Forgacs, Eva Knight, Peter Stan, Burgess Sellers, James White, Howard D. Trinick, John TI Myosin 5A Walking Mechanism: The Structural Basis of Slow ADP Dissociatin from the Lead Head SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Oke, Olusola; Knight, Peter; Stan, Burgess; Trinick, John] Univ Leeds, Leeds, W Yorkshire, England. [Sakamoto, Takeshi] Wayne State Univ, Detroit, MI USA. [Forgacs, Eva; White, Howard D.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Sellers, James] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 229A EP 229A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002142 ER PT J AU Michelman-Ribeiro, A Mazza, D Rosales, T Stasevich, TJ Boukari, H Rishi, V Vinson, C Knutson, JR McNally, JG AF Michelman-Ribeiro, Ariel Mazza, Davide Rosales, Tilman Stasevich, Timothy J. Boukari, Hacene Rishi, Vikas Vinson, Charles Knutson, Jay R. McNally, James G. TI Measurement of Protein Binding Rates in Live Cells with FCS SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Michelman-Ribeiro, Ariel] NIST, Gaithersburg, MD 20899 USA. [Mazza, Davide; Rosales, Tilman; Stasevich, Timothy J.; Boukari, Hacene; Rishi, Vikas; Vinson, Charles; Knutson, Jay R.; McNally, James G.] NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 234A EP 234A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002167 ER PT J AU Lountos, G Tropea, J Cherry, S Waugh, D AF Lountos, George Tropea, Joseph Cherry, Scott Waugh, David TI Overproduction, Purification and Structure Determination of Human Dual Specificity Phosphatase 14 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lountos, George; Tropea, Joseph; Cherry, Scott; Waugh, David] NCI, Frederick, MD 21701 USA. RI Lountos, George/B-3983-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 247A EP 247A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002238 ER PT J AU Cormier, C Chin, J LaBaer, J AF Cormier, Catherine Chin, Jean LaBaer, Joshua TI Protein Structure Initiative Material Repository (PSI-MR): A Resource of Structural Genomics Plasmids for the Biological Community SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Cormier, Catherine; LaBaer, Joshua] Arizona State Univ, Tempe, AZ USA. [Chin, Jean] NIGMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 250A EP 250A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002255 ER PT J AU Preusch, PC Basavappa, R Chin, J Edmonds, C Smith, W Lewis, C AF Preusch, Peter C. Basavappa, Ravi Chin, Jean Edmonds, Charles Smith, Ward Lewis, Catherine TI NIGMS PSI: Biology Initiative High-Throughput-Enabled Structural Biology SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Preusch, Peter C.; Basavappa, Ravi; Chin, Jean; Edmonds, Charles; Smith, Ward; Lewis, Catherine] Nat Inst Gen Med Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 250A EP 250A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002257 ER PT J AU Liu, XY Kopkalli, Y Smirnov, AV Rosales, T Hawkins, ME Knutson, JR Davenport, L AF Liu, Xiuyi Kopkalli, Yasemin Smirnov, Aleksandr V. Rosales, Tilman Hawkins, Mary E. Knutson, Jay R. Davenport, Lesley TI Local Dynamic Studies of Guanine Residues within the Human Telomeric DNA G-Quadruplexed Conformation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Liu, Xiuyi; Kopkalli, Yasemin; Davenport, Lesley] CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. [Liu, Xiuyi; Davenport, Lesley] CUNY, Grad Ctr, New York, NY USA. [Smirnov, Aleksandr V.; Rosales, Tilman; Knutson, Jay R.] NIH, Heart Lung & Blood Inst, Bethesda, MD 20892 USA. [Hawkins, Mary E.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 265A EP 265A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002337 ER PT J AU DeRouchey, J Rau, DC Parsegian, A AF DeRouchey, Jason Rau, Don C. Parsegian, Adrian TI Understanding DNA Condensation: From Simple Ions to Complex Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [DeRouchey, Jason; Rau, Don C.; Parsegian, Adrian] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 269A EP 269A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002356 ER PT J AU Gurnev, PA Podgornik, R Cohen, JA Bezrukov, SM Parsegian, VA AF Gurnev, Philip A. Podgornik, Rudolf Cohen, Joel A. Bezrukov, Sergey M. Parsegian, V. Adrian TI Molecules Pushing Molecules: Dynamic Consequences of Crowding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Gurnev, Philip A.; Bezrukov, Sergey M.] NICHHD, Bethesda, MD 20892 USA. [Podgornik, Rudolf] Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 61000, Slovenia. [Podgornik, Rudolf] Jozef Stefan Inst, Dept Theoret Phys, Ljubljana, Slovenia. [Cohen, Joel A.] Univ Pacific, Dept Physiol, AA Dugoni Sch Dent, San Francisco, CA USA. [Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 274A EP 274A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002383 ER PT J AU Klauda, JB Venable, RM Pastor, RW AF Klauda, Jeffery B. Venable, Richard M. Pastor, Richard W. TI A Modified Lipid Force Field for Charmm: Development and Application to Single-Celled Organism Membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Klauda, Jeffery B.] Univ Maryland, College Pk, MD 20742 USA. [Venable, Richard M.; Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 282A EP 282A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002430 ER PT J AU Kimura, T Yeliseev, AA Vukoti, K Gawrisch, K AF Kimura, Tomohiro Yeliseev, Alexei A. Vukoti, Krishna Gawrisch, Klaus TI Influence of Membrane Composition on Function of Human Peripheral Cannabinoid Receptor CB2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kimura, Tomohiro; Yeliseev, Alexei A.; Vukoti, Krishna; Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 90034 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 290A EP 290A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002468 ER PT J AU Soubias, O Kimura, T Gaede, HC Yeliseev, AA Gawrisch, K AF Soubias, Olivier Kimura, Tomohiro Gaede, Holly C. Yeliseev, Alexei A. Gawrisch, Klaus TI Anodic Aluminum Oxide Nanopores as Substrate for Functional and Structural Studies on G Protein-Coupled Membrane Receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Soubias, Olivier; Kimura, Tomohiro; Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, SNMR, LMBB, NIH, Bethesda, MD 90034 USA. [Gaede, Holly C.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. RI Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 0 TC 0 Z9 0 U1 2 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 292A EP 292A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002476 ER PT J AU Arispe, N Durell, SR Shafrir, Y Guy, HR AF Arispe, Nelson Durell, Stewart R. Shafrir, Yinon Guy, H. R. TI Polyhistidine Peptide Inhibitor of the A beta Calcium Channel Potently Blocks the A beta-Induced Calcium Response in Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Arispe, Nelson] USUHS, Uniformed Serv Univ Sch Med, Bethesda, MD USA. [Durell, Stewart R.; Shafrir, Yinon; Guy, H. R.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 293A EP 293A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002479 ER PT J AU Sirenko, S Vinogradova, TM Jones, LR Maltsev, V Lakatta, EG AF Sirenko, Syevda Vinogradova, Tatiana M. Jones, Larry R. Maltsev, Victor Lakatta, Edward G. TI Synchronization of Spontaneous Stochastic RyR Activation in Ventricular Myocytes (VM) by Camp or Disengagement of Phospholambam (PLB) From SERCA2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sirenko, Syevda; Vinogradova, Tatiana M.; Maltsev, Victor; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. [Sirenko, Syevda] MedStar Res Inst, Baltimore, MD USA. [Jones, Larry R.] Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 296A EP 296A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762002496 ER PT J AU Ivanov, V Mizuuchi, K AF Ivanov, Vassili Mizuuchi, Kiyoshi TI A Zoo of Dynamic Pattern Formation by Bacterial Cell Division Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Ivanov, Vassili; Mizuuchi, Kiyoshi] NIDDK, NIH, Bethesda, MD USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 304A EP 304A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003020 ER PT J AU Krepkiy, D Swartz, KJ AF Krepkiy, Dmitriy Swartz, Kenton J. TI Conformational Changes in Potassium Channel Voltage-Sensing Domains Reconstituted into Different Lipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Krepkiy, Dmitriy; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 315A EP 315A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003073 ER PT J AU Milescu, M Bosmans, F Swartz, KJ AF Milescu, Mirela Bosmans, Frank Swartz, Kenton J. TI Interactions Between Lipids and Voltage Sensor Paddles Detected with Tarantula Toxins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Milescu, Mirela; Bosmans, Frank; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 315A EP 315A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003072 ER PT J AU Maksaev, G Liu, NL Guy, HR Sukharev, S AF Maksaev, Grigori Liu, Naili Guy, H. Robert Sukharev, Sergei TI Deletion Analysis of the Mechanosensitive TREK-1 Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Maksaev, Grigori; Liu, Naili; Sukharev, Sergei] Univ Maryland, College Pk, MD 20742 USA. [Guy, H. Robert] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 324A EP 324A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003115 ER PT J AU Chen, J Contreras, JE Lau, AY Jogini, V Roux, B Holmgren, M AF Chen, Jin Contreras, Jorge E. Lau, Albert Y. Jogini, Vishwanath Roux, Benoit Holmgren, Miguel TI Voltage Profile along the Permeation Pathway of an Open Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chen, Jin; Contreras, Jorge E.; Holmgren, Miguel] NINDS, Bethesda, MD 20892 USA. [Lau, Albert Y.; Jogini, Vishwanath; Roux, Benoit] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 330A EP 330A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003147 ER PT J AU Alcaraz, A Garcia-Gimenez, E Aguilella, VM Nestorovich, EM Bezrukov, SM AF Alcaraz, Antonio Garcia-Gimenez, Elena Aguilella, Vicente M. Nestorovich, Ekaterina M. Bezrukov, Sergey M. TI Increased Salt Concentration Promotes Negative Cooperativity in OmpF Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Alcaraz, Antonio; Garcia-Gimenez, Elena; Aguilella, Vicente M.] Univ Jaume 1, Castellon de La Plana, Spain. [Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] NICHD, PPB, NIH, Bethesda, MD USA. RI Aguilella, Vicente/B-7592-2008; Alcaraz, Antonio/F-8498-2016 OI Aguilella, Vicente/0000-0002-2420-2649; NR 0 TC 0 Z9 0 U1 2 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 332A EP 332A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003159 ER PT J AU Kalia, J Swartz, KJ AF Kalia, Jeet Swartz, Kenton J. TI Exploring Structural Relationships between TRP and Kv Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kalia, Jeet; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 340A EP 340A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003198 ER PT J AU Sackett, DL AF Sackett, Dan L. TI Tubulin is an Amphiphilic Protein Whose Interaction With Membranes is Regulated by its Charged Carboxy-Terminal Tails SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sackett, Dan L.] NICHD, NIH, Bethesda, MD USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 363A EP 363A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003309 ER PT J AU Csordas, G Varnai, P Golenar, T Roy, S Purkins, G Balla, T Hajnoczky, G AF Csordas, Gyoergy Varnai, Peter Golenar, Tuende Roy, Swati Purkins, George Balla, Tamas Hajnoczky, Gyoergy TI Imaging Interorganelle Contacts and Local Calcium Dynamics at the ER-Mitochondrial Interface SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Csordas, Gyoergy; Golenar, Tuende; Roy, Swati; Purkins, George; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Varnai, Peter] Semmelweis Univ, H-1085 Budapest, Hungary. [Balla, Tamas] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 380A EP 380A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003396 ER PT J AU Wu, XW Zhang, PJ Khursigara, CM Subramaniam, S Brooks, BR AF Wu, Xiongwu Zhang, Peijun Khursigara, Cezar M. Subramaniam, Sriram Brooks, Bernard R. TI Electron Tomography and Molecular Modeling Study of Chemoreceptor Organization SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wu, Xiongwu; Zhang, Peijun; Khursigara, Cezar M.; Subramaniam, Sriram; Brooks, Bernard R.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 382A EP 382A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003406 ER PT J AU Lerner, MG Pastor, RW AF Lerner, Michael G. Pastor, Richard W. TI Membrane Diffusion of Tethered DPPC and Tethered PIP3-Bound Protein Systems SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lerner, Michael G.; Pastor, Richard W.] NHLBI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 384A EP 384A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003417 ER PT J AU Le, SY Kim, T Shapiro, BA AF Le, Shu-Yun Kim, Taejin Shapiro, Bruce A. TI Computational Design of an RNA Nanoparticle Consisting of a Three-Way Junction and pre-miRNAs SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Le, Shu-Yun; Kim, Taejin; Shapiro, Bruce A.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 402A EP 403A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004005 ER PT J AU Brown, PH AF Brown, Patrick H. TI Size Distributions of Quantum Dots and Colloidal Gold Nanoparticles Using Analytical Ultracentrifugation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Brown, Patrick H.] NIBIB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 408A EP 408A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004032 ER PT J AU Sirenko, S Yaeger, D Vinogradova, TM Li, Y Vaniv, Y Zahanich, I Spurgeon, H Maltsev, V Lakatta, EG AF Sirenko, Syevda Yaeger, Dan Vinogradova, Tatiana M. Li, Yue Vaniv, Yael Zahanich, Ihor Spurgeon, Harold Maltsev, Victor Lakatta, Edward. G. TI Cardiac Glycoside Chronotropic and Arrhythmogenic Effects in Sinoatrial Nodal Pacemaker Cells (SANC) Occur Along a Continuum of Electrochemical Gradients of Na+ (E-Na) and Ca2+ (E-Ca) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sirenko, Syevda; Yaeger, Dan; Vinogradova, Tatiana M.; Li, Yue; Vaniv, Yael; Zahanich, Ihor; Spurgeon, Harold; Maltsev, Victor; Lakatta, Edward. G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Sirenko, Syevda] MedStar Res Inst, Baltimore, MD USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 412A EP 412A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004054 ER PT J AU Rosales, T Liu, XY Kopkalli, Y Davenport, L Hawkins, M Knutson, JR AF Rosales, Tilman Liu, Xiuyi Kopkalli, Yasemin Davenport, Lesley Hawkins, Mary Knutson, Jay R. TI G-Quadruplex Folding Observed by two Photon Fluorescence Correlation Spectroscopy and Dual Time Scale SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Rosales, Tilman; Knutson, Jay R.] NHLBI, NIH, LMB, OSS, Bethesda, MD 20892 USA. [Liu, Xiuyi; Kopkalli, Yasemin; Davenport, Lesley] CUNY, Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA. [Hawkins, Mary] NCI, NIH, POB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 414A EP 414A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004062 ER PT J AU Xia, D Savarino, SJ Bullitt, E AF Xia, Di Savarino, Stephen J. Bullitt, Esther TI Structure and Assembly of CFA/I pili from Enterotoxigenic Escherichia Coli That Cause Traveler's Diarrhea SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Xia, Di] NCI, Bethesda, MD 20892 USA. [Savarino, Stephen J.] Naval Med Res Ctr, Silver Spring, MD USA. [Bullitt, Esther] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 417A EP 417A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004078 ER PT J AU Lizunov, VA Stenkula, KG Cushman, SW Zimmerberg, J AF Lizunov, Vladimir A. Stenkula, Karin G. Cushman, Samuel W. Zimmerberg, Joshua TI Selective Exocytosis and Spatiotemporal Regulation of Protein Recycling at the Plasma Membrane SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lizunov, Vladimir A.; Zimmerberg, Joshua] NICHD, NIH, Bethesda, MD USA. [Stenkula, Karin G.; Cushman, Samuel W.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 439A EP 439A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004193 ER PT J AU Tai, CH Sam, V Gibrat, JF Munson, P Lee, B Garnier, J AF Tai, Chin-Hsien Sam, Vichetra Gibrat, Jean-Francois Munson, Peter Lee, Byungkook Garnier, Jean TI Using Structure Recurrence to Define Protein Domains SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Tai, Chin-Hsien; Lee, Byungkook] NCI, NIH, Bethesda, MD 20892 USA. [Sam, Vichetra; Munson, Peter] NIH, CIT, Bethesda, MD 20892 USA. [Gibrat, Jean-Francois; Garnier, Jean] INRA, Jouy En Josas, France. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 454A EP 454A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004275 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Polymorphism in Alzheimer A beta Amyloid Organization: Insight into A beta Aggregation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Miller, Yifat] NCI, NIH, Frederick, MD 21701 USA. [Ma, Buyong; Nussinov, Ruth] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 457A EP 457A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004289 ER PT J AU Jang, H Arce, FT Capone, R Ramachandran, S Lal, R Nussinov, R AF Jang, Hyunbum Arce, Fernando Teran Capone, Ricardo Ramachandran, Srinivasan Lal, Ratnesh Nussinov, Ruth TI Modeling Ion-Permeable beta-Amyloid (A beta) Barrels in the Lipid Bilayer SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. [Arce, Fernando Teran; Capone, Ricardo; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 459A EP 459A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004297 ER PT J AU Pfefferkorn, C AF Pfefferkorn, Candace TI Fluorescent Probes of Membrane-Bound alpha-Synuclein: Insights into the Role of Membranes in Aggregation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Pfefferkorn, Candace] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 459A EP 459A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004299 ER PT J AU Pabit, SA Li, L Meisburger, SP Lamb, JS Qiu, XY Pollack, L AF Pabit, Suzette A. Li, Li Meisburger, Steve P. Lamb, Jessica S. Qiu, Xiangyun Pollack, Lois TI The Role of Helix Topology and Counterion Distributions in RNA Interactions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Pabit, Suzette A.; Li, Li; Meisburger, Steve P.; Pollack, Lois] Cornell Univ, Ithaca, NY USA. [Lamb, Jessica S.; Qiu, Xiangyun] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 471A EP 471A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004366 ER PT J AU Mateja, A Szlachcic, A Downing, M Dobosz, M Mariappan, M Hegde, RS Keenan, RJ AF Mateja, Agnieszka Szlachcic, Anna Downing, Maureen Dobosz, Malgorzata Mariappan, Malaiyalam Hegde, Ramanujan S. Keenan, Robert J. TI Tail-Anchored Membrane Protein Recognition by Get3 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Mateja, Agnieszka; Szlachcic, Anna; Downing, Maureen; Dobosz, Malgorzata; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Mariappan, Malaiyalam; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 498A EP 498A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004509 ER PT J AU Sinha, G Dimitriadis, EK Iwasa, KH AF Sinha, Ghanshyam Dimitriadis, Emilios K. Iwasa, Kuni H. TI AFM Images of Outer Hair Cells' Lateral Plasma Membrane: An Auto-correlation Function Analysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sinha, Ghanshyam; Dimitriadis, Emilios K.; Iwasa, Kuni H.] NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 508A EP 508A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005033 ER PT J AU Sul, B Iwasa, KH AF Sul, Bora Iwasa, Kuni H. TI Effect of Having Two Identical Channels Per Tip-Link in Hair Bundles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sul, Bora; Iwasa, Kuni H.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 509A EP 509A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005036 ER PT J AU Kumar, J Mayer, ML AF Kumar, Janesh Mayer, Mark L. TI Crystal Structure of KA2-Subtype Ionotropic Glutamate Receptor Amino Terminal Domain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kumar, Janesh; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 524A EP 524A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005108 ER PT J AU Spivak, CE Doyle, ME AF Spivak, Charles E. Doyle, Maire E. TI Effects of Cannabinoids on Ion Channels of Pancreatic Beta Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Spivak, Charles E.] NIDA, IRP, Baltimore, MD USA. [Doyle, Maire E.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 535A EP 535A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005161 ER PT J AU Goh, HZ Broccio, M Shenoy, S Heinrich, F Mindell, JA Losche, M AF Goh, Haw-Zan Broccio, Matteo Shenoy, Sidd Heinrich, Frank Mindell, Joseph A. Loesche, Mathias TI Functional Incorporation of KcsA into Tethered Lipid Bilayer Membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Goh, Haw-Zan; Broccio, Matteo; Shenoy, Sidd; Heinrich, Frank; Loesche, Mathias] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. [Heinrich, Frank; Loesche, Mathias] NIST, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Mindell, Joseph A.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 537A EP 537A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005171 ER PT J AU Kanchanawong, P Hou, JH Zajac, AL Aguet, F Davidson, MW Danuser, G Jaqaman, K Waterman, CM AF Kanchanawong, Pakorn Hou, Jennifer H. Zajac, Allison L. Aguet, Francois Davidson, Michael W. Danuser, Gaudenz Jaqaman, Khuloud Waterman, Clare M. TI Analysis of Single Integrin Behavior in Living Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kanchanawong, Pakorn; Waterman, Clare M.] NHLBI, Bethesda, MD 20892 USA. [Hou, Jennifer H.] Harvard Univ, Cambridge, MA 02138 USA. [Zajac, Allison L.] Univ Penn, Philadelphia, PA 19104 USA. [Aguet, Francois; Danuser, Gaudenz; Jaqaman, Khuloud] Harvard Univ, Sch Med, Boston, MA USA. [Davidson, Michael W.] Florida State Univ, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 558A EP 558A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005278 ER PT J AU Nagy, A Takagi, Y Homsher, EE Hong, DKT Kovacs, M Sellers, J AF Nagy, Attila Takagi, Yasuharu Homsher, Earl E. Hong, Davin K. T. Kovacs, Mihaly Sellers, James TI Kinetic Characterization of Non-Muscle Myosin IIB Single-Headed Heavy Meromyosin on Single Molecule Level with Optical Tweezers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Nagy, Attila; Takagi, Yasuharu; Sellers, James] NHLBI, NIH, LMP, Bethesda, MD 20892 USA. [Homsher, Earl E.] Univ Calif Los Angeles, Dept Physiol, NIH, Los Angeles, CA 90024 USA. [Hong, Davin K. T.] ABT Software, Washington Dc, DC USA. [Kovacs, Mihaly] Eotvos Lorand Univ, Dept Biochem, Budapest, Hungary. RI Kovacs, Mihaly/A-6841-2011 NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 561A EP 561A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005292 ER PT J AU Huck, D Sellers, J Sakamoto, T AF Huck, Daniel Sellers, Jim Sakamoto, Takeshi TI Flexibility of Stepping Manner of Myosin V and X Processive Movement on 2D Actin Structures SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Huck, Daniel; Sakamoto, Takeshi] Wayne State Univ, Detroit, MI USA. [Sellers, Jim] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 563A EP 563A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005305 ER PT J AU Knight, PJ Baboolal, TG Sakamoto, T Forgacs, E White, HD Jackson, SM Takagi, Y Farrow, RE Molloy, JE Sellers, JR Peckham, M AF Knight, Peter J. Baboolal, Thomas G. Sakamoto, Takeshi Forgacs, Eva White, Howard D. Jackson, Scott M. Takagi, Yasuharu Farrow, Rachel E. Molloy, Justin E. Sellers, James R. Peckham, Michelle TI Mechanical and Kinetic Properties of a Myosin 5-SAH Chimera SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Knight, Peter J.; Baboolal, Thomas G.; Jackson, Scott M.; Peckham, Michelle] Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England. [Sakamoto, Takeshi] Wayne State Univ, Dept Phys & Astron, Detroit, MI 48202 USA. [Forgacs, Eva; White, Howard D.] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23501 USA. [Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Farrow, Rachel E.; Molloy, Justin E.] MRC NIMR, Div Phys Biochem, London, England. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 563A EP 564A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005306 ER PT J AU Lee, H Pastor, RW AF Lee, Hwankyu Pastor, Richard W. TI Coarse-Grained Molecular Dynamics Simulations of Pegylated Lipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lee, Hwankyu; Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 569A EP 569A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005340 ER PT J AU Yun, SJ Guy, HR AF Yun, Sijung Guy, H. Robert TI Discrete Molecular Dynamics as a Tool to Test Soluble Protein Models SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yun, Sijung; Guy, H. Robert] NCI, Bethesday, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 570A EP 570A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005344 ER PT J AU Nguyen, TA Koushik, SV Blank, PS Vogel, SS AF Nguyen, Tuan A. Koushik, Srinagesh V. Blank, Paul S. Vogel, Steven S. TI Irregular Excess Energy Transfer Observed with a Cerulean Donor and Multiple Venus FRET Acceptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Nguyen, Tuan A.; Koushik, Srinagesh V.; Vogel, Steven S.] NIAAA, NIH, Rockville, MD 20852 USA. [Blank, Paul S.] NICHD, NIH, Bethesda, MD USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 584A EP 585A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005425 ER PT J AU Yavlovich, A Singh, A Jang, H Nussinov, R Puri, A Blumenthal, R AF Yavlovich, Amichai Singh, Alok Jang, Hyunbum Nussinov, Ruth Puri, Anu Blumenthal, Robert TI Light-Induced Permeability Changes in Liposomes Containing Photo-Polymerizable Phospholipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yavlovich, Amichai; Jang, Hyunbum; Nussinov, Ruth; Puri, Anu; Blumenthal, Robert] NCI, NIH, Frederick, MD 21701 USA. [Singh, Alok] Naval Res Lab, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 602A EP 602A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006002 ER PT J AU Chaudhry, C Plested, AJR Schuck, P Mayer, ML AF Chaudhry, Charu Plested, Andrew J. R. Schuck, Peter Mayer, Mark L. TI Energetics of Allosteric ion Binding to a Ligand-Gated ion Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chaudhry, Charu; Mayer, Mark L.] NICHD, NIH, Bethesda, MD USA. [Plested, Andrew J. R.] Leibniz Inst Mol Pharmacol, Berlin, Germany. [Schuck, Peter] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 610A EP 610A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006045 ER PT J AU Li, MF Kawate, T Silberberg, SD Swartz, KJ AF Li, Mufeng Kawate, Toshimitsu Silberberg, Shai D. Swartz, Kenton J. TI Structure Rearrangement of the Pore in P2X Receptors During Gating SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Li, Mufeng; Kawate, Toshimitsu; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 610A EP 610A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006047 ER PT J AU Lippincott-Schwartz, J Manley, S Burnette, D Gillette, J Patterson, G AF Lippincott-Schwartz, Jennifer Manley, Suliana Burnette, Dylan Gillette, Jennifer Patterson, George TI PALM-Based Super-Resolution Imaging and its Applications SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lippincott-Schwartz, Jennifer; Manley, Suliana; Burnette, Dylan; Gillette, Jennifer; Patterson, George] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 619A EP 619A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006094 ER PT J AU Kimura, T Vukoti, K Lynch, DL Hurst, DP Grossfield, A Pitman, MC Reggio, PH Yeliseev, AA Gawrisch, K AF Kimura, Tomohiro Vukoti, Krishna Lynch, Diane L. Hurst, Dow P. Grossfield, Alan Pitman, Michael C. Reggio, Patricia H. Yeliseev, Alexei A. Gawrisch, Klaus TI Secondary-Structure Analysis of Human Peripheral Cannabinoid Receptor CB2 Based on Solid-State C-13-, N-15-MAS NMR and Molecular Dynamics Simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kimura, Tomohiro; Vukoti, Krishna; Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 90034 USA. [Lynch, Diane L.; Hurst, Dow P.; Reggio, Patricia H.] Univ N Carolina, Greensboro, NC 27412 USA. [Grossfield, Alan] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Pitman, Michael C.] IBM Thomas J Watson Res Ctr, Yorktown Hts, NY USA. NR 0 TC 1 Z9 1 U1 2 U2 4 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 625A EP 625A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006126 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Polymophism of A-Beta1-42 Peptide Oligomer - Membrane Interactions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Ma, Buyong; Nussinov, Ruth] NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 650A EP 650A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006259 ER PT J AU Forbes, JG Wang, K AF Forbes, Jeffrey G. Wang, Kuan TI Disorderness Profile of Scaffolding Proteins as a Predictor of Supramolecular Architecture: Titin and Nebulin Profiles Correlate with the Sarcomere Proportion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Forbes, Jeffrey G.; Wang, Kuan] NIAMS, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 652A EP 652A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006269 ER PT J AU Li, L Pabbit, SA Meisburger, SP Lamb, JS Pollack, L AF Li, Li Pabbit, Suzette A. Meisburger, Stephen P. Lamb, Jessica S. Pollack, Lois TI Measuring DNA Condensation Driven by Cobalt Hexamine SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Li, Li; Pabbit, Suzette A.; Meisburger, Stephen P.; Pollack, Lois] Cornell Univ, Ithaca, NY USA. [Lamb, Jessica S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 657A EP 657A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006298 ER PT J AU Hardin, AH Liou, GF Osheroff, N Neuman, KC AF Hardin, Ashley H. Liou, Grace F. Osheroff, Neil Neuman, Keir C. TI Determining the Role DNA of Bending in Topology Simplification by Type II Topoisomerases SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hardin, Ashley H.; Liou, Grace F.; Neuman, Keir C.] NIH, Bethesda, MD 20892 USA. [Osheroff, Neil] Vanderbilt Univ, Nashville, TN 37235 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 660A EP 660A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006315 ER PT J AU Seol, Y Gentry, AC Osheroff, N Neuman, KC AF Seol, Yeonee Gentry, Amanda C. Osheroff, Neil Neuman, Keir C. TI Single-Molecule Study of Human Topoisomerase II SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Seol, Yeonee; Neuman, Keir C.] NIH, Bethesda, MD 20892 USA. [Gentry, Amanda C.; Osheroff, Neil] Vanderbilt Univ, Nashville, TN 37235 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 660A EP 660A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006316 ER PT J AU Wang, F Wu, H Li, JL McCauley, MJ Jones, C Datta, SA Rein, A Gorelick, RJ Rouzina, I Musier-Forsyth, K Williams, MC AF Wang, Fei Wu, Hao Li, Jialin McCauley, Micah J. Jones, Christopher Datta, Siddhartha A. Rein, Alan Gorelick, Robert J. Rouzina, Ioulia Musier-Forsyth, Karin Williams, Mark C. TI Nucleic Acid Interaction Kinetics Modulate the Chaperone Activity of Retroviral Nucleocapsid and Gag Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wang, Fei; Wu, Hao; Li, Jialin; McCauley, Micah J.; Williams, Mark C.] Northeastern Univ, Boston, MA 02115 USA. [Jones, Christopher; Musier-Forsyth, Karin] Ohio State Univ, Columbus, OH 43210 USA. [Datta, Siddhartha A.; Rein, Alan] NCI, Frederick, MD 21701 USA. [Gorelick, Robert J.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Rouzina, Ioulia] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 662A EP 662A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006327 ER PT J AU Wang, HW Finzi, L Lewis, DAE Dunlap, DD AF Wang, Haowei Finzi, Laura Lewis, Dale A. E. Dunlap, David D. TI AFM Studies of DNA Loops Secured by Lambda Repressor Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Wang, Haowei] Emory Univ, Atlanta, GA 30322 USA. [Finzi, Laura] Emory Univ Sch, Atlanta, GA USA. [Lewis, Dale A. E.] NIH, Bethesda, MD 20892 USA. [Dunlap, David D.] Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 662A EP 662A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006324 ER PT J AU Dieudonne, DJ Gurnev, PA Rogozea, AL Ray, BD Petrache, HI AF Dieudonne, Dino J. Gurnev, Philip A. Rogozea, Adriana L. Ray, Bruce D. Petrache, Horia I. TI Physical Properties of the Lipid Diphytanoyl Phosphatidylcholine (DPhPc) used for Ion Channel Measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Dieudonne, Dino J.; Rogozea, Adriana L.; Ray, Bruce D.; Petrache, Horia I.] Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. [Gurnev, Philip A.] NIH, Bethesda, MD 20892 USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 667A EP 668A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006355 ER PT J AU Evseev, A Bashkirov, P AF Evseev, Alexey Bashkirov, Pavel TI Fission of Membrane Nanotubes Caused by Osmotic Stress SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Evseev, Alexey; Bashkirov, Pavel] RAS, Frumkin Inst Phys Chem & Electrochem, Moscow 117901, Russia. [Bashkirov, Pavel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 672A EP 672A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006381 ER PT J AU Yang, ST Chernomordik, L Melikov, K AF Yang, Sung-Tae Chernomordik, Leonid Melikov, Kamran TI Fusion Between Intraluminal Vesicles of Late Endosomes as a Possible Mechanism of Endosomal Escape by Cell-Penetrating Peptides SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yang, Sung-Tae; Chernomordik, Leonid; Melikov, Kamran] NICHD, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 672A EP 672A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006380 ER PT J AU Koushik, SV Fernando, J Henry, CN Puhl, L Vogel, SS AF Koushik, Srinagesh V. Fernando, Jose Henry, Covian-Nares Puhl, L., III Vogel, Steven S. TI A Role for Dysferlin and Agatoxin Sensitive Calcium Channels in the Calcium-Triggered Secretion of ATP Following Plasma Membrane Wounding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Koushik, Srinagesh V.; Fernando, Jose; Henry, Covian-Nares; Puhl, L., III; Vogel, Steven S.] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 680A EP 680A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006420 ER PT J AU Francis, D Cafiso, DS Mindell, JA AF Francis, Derek Cafiso, David S. Mindell, Joseph A. TI Detection of Substrate-Dependent Conformational Changes in HP1 of the Glutamate Transporter GltPH SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Francis, Derek; Mindell, Joseph A.] NIH, Bethesda, MD 20892 USA. [Cafiso, David S.] Univ Virginia, Charolettesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 686A EP 686A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006446 ER PT J AU Golebiewska, UP Kay, J Grinstein, S Im, W Pastor, R Scarlata, S McLaughlin, S AF Golebiewska, Urszula P. Kay, Jason Grinstein, Sergio Im, Wonpil Pastor, Richard Scarlata, Suzanne McLaughlin, Stuart TI Don't Fence Me in: Evidence for a 'fence' that Impedes the Diffusion of PIP2 Into and Out of Nascent Phagosomes in Macrophages SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Golebiewska, Urszula P.; Scarlata, Suzanne; McLaughlin, Stuart] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Golebiewska, Urszula P.] CUNY Queensborough Community Coll, Bayside, NY USA. [Kay, Jason; Grinstein, Sergio] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA. [Pastor, Richard] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 688A EP 688A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006455 ER PT J AU Im, W McLaughlin, S Pastor, RW AF Im, Wonpil McLaughlin, Stuart Pastor, Richard W. TI Hard to Fence You in: Computational Approaches to Explore the Hypothesis that Actin Filaments Impede PIP2 Diffusion in Membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Im, Wonpil] Univ Kansas, Lawrence, KS 66045 USA. [McLaughlin, Stuart] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Pastor, Richard W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 688A EP 688A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006456 ER PT J AU Lao, QZ Kobrinsky, E Soldatov, N AF Lao, Qi Zong Kobrinsky, Evgeny Soldatov, Nikolai TI Oligomerization of Ca-v beta Subunits is an Essential Correlate of Ca2+ Channel Activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lao, Qi Zong; Kobrinsky, Evgeny; Soldatov, Nikolai] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 694A EP 694A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006489 ER PT J AU Tomic, M Yan, ZH Li, S Sherman, A Stojilkovic, SS AF Tomic, Melanija Yan, Zonghe Li, Suo Sherman, Arthur Stojilkovic, Stanko S. TI P2X7 Receptor-Mediated Disruption of the Plasma Membrane and Endoplasmic Reticulum Morphology and Cell Survival SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Tomic, Melanija; Yan, Zonghe; Li, Suo; Stojilkovic, Stanko S.] NICHD, NIH, Bethesda, MD USA. [Sherman, Arthur] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 701A EP 702A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006524 ER PT J AU Kawate, T Li, MF Silberberg, SD Swartz, KJ AF Kawate, Toshimitsu Li, Mufeng Silberberg, Shai D. Swartz, Kenton J. TI Identifying the Ion Access Pathway to the Transmembrane Pore in P2X Receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kawate, Toshimitsu; Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 702A EP 702A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762006526 ER PT J AU Dellisanti, CD Hanson, SM Chen, L Czajkowski, C AF Dellisanti, Cosma D. Hanson, Sonya M. Chen, Lin Czajkowski, Cynthia TI Packing of the Extracellular Domain Hydrophobic Core is Evolutionarily Optimized to Facilitate Pentameric Ligand-Gated Ion Channel Activation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Dellisanti, Cosma D.; Czajkowski, Cynthia] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA. [Hanson, Sonya M.] NINDS, Mol Physiol & Biophys Sect, Bethesda, MD 20892 USA. [Chen, Lin] Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 703A EP 703A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007003 ER PT J AU Lopez-Rodriguez, A Holmgren, M AF Lopez-Rodriguez, Angelica Holmgren, Miguel TI Transferring S3-S4 Motif from Kv Channels to the CNG Channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Lopez-Rodriguez, Angelica; Holmgren, Miguel] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 707A EP 707A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007022 ER PT J AU Cammarato, A Alayari, NN Gucek, M Reedy, MC Rucker, J Van Eyk, JE Cole, RN O'Rourke, B Bodmer, R Bernstein, SI Foster, DB AF Cammarato, Anthony Alayari, Nakissa N. Gucek, Marjan Reedy, Mary C. Rucker, Jasma Van Eyk, Jennifer E. Cole, Robert N. O'Rourke, Brian Bodmer, Rolf Bernstein, Sanford I. Foster, D. Brian TI A Systems Biology Approach to Restrictive Cardiomyopathy in Drosophila SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Cammarato, Anthony; Alayari, Nakissa N.; Bernstein, Sanford I.] San Diego State Univ, San Diego, CA 92182 USA. [Cammarato, Anthony; Alayari, Nakissa N.; Bodmer, Rolf] Burnham Inst Med Res, La Jolla, CA USA. [Gucek, Marjan] NIH, Bethesda, MD 20892 USA. [Reedy, Mary C.] Duke Univ, Med Ctr, Durham, NC USA. [Rucker, Jasma; Van Eyk, Jennifer E.; Cole, Robert N.; O'Rourke, Brian; Foster, D. Brian] Johns Hopkins Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 717A EP 718A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007074 ER PT J AU Crawford, G Lu, SJ Dore, J Horowits, R AF Crawford, Garland Lu, Shajia Dore, Justin Horowits, Robert TI Cardiac Specific Overexpression of N-RAP in Transgenic Mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Crawford, Garland; Lu, Shajia; Dore, Justin; Horowits, Robert] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 718A EP 719A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007075 ER PT J AU Haithcock, J Pinder, JC Nagy, A Stafford, W Cartwright, S Belknap, B Sellers, JR White, HD Forgacs, E AF Haithcock, Jessica Pinder, Jennifer C. Nagy, Attila Stafford, Walter Cartwright, Suzanne Belknap, Betty Sellers, James R. White, Howard D. Forgacs, Eva TI Mouse Myosinviia is a Monomeric, "slow" Motor with an Intermediate Duty Ratio SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Haithcock, Jessica; Cartwright, Suzanne; Belknap, Betty; White, Howard D.; Forgacs, Eva] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Pinder, Jennifer C.] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. [Nagy, Attila; Sellers, James R.] NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA. [Stafford, Walter] Boston Biomed Res Inst, Analyt Ultracentrifugat Res Lab, Watertown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 724A EP 725A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007109 ER PT J AU Siththanandan, V Kengyel, A Takagi, Y Forgacs, E Hong, D Sellers, J AF Siththanandan, Verl Kengyel, Andras Takagi, Yasuharu Forgacs, Eva Hong, Davin Sellers, James TI A Comparison of Mechanical Properties of Drosophila and Mouse Myosin 7a SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Siththanandan, Verl; Takagi, Yasuharu; Sellers, James] NIH, Bethesda, MD 20892 USA. [Kengyel, Andras] Univ Pecs, Pecs, Hungary. [Forgacs, Eva] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Hong, Davin] Summit Comp, Washington, DC USA. NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 725A EP 725A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007110 ER PT J AU Kanchanawong, P Shtengle, G Ramko, EB Davidson, MW Hess, HF Waterman, C AF Kanchanawong, Pakorn Shtengle, Gleb Ramko, Erika B. Davidson, Michael W. Hess, Harald F. Waterman, Clare TI Nanoscale Protein Architecture of Focal Adhesions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kanchanawong, Pakorn; Waterman, Clare] NHLBI, NIH, Bethesda, MD 20892 USA. [Shtengle, Gleb; Hess, Harald F.] Janelia Farm HHMI, Ashburn, VA USA. [Ramko, Erika B.; Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 729A EP 729A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007132 ER PT J AU Yaniv, Y Juhaszova, M Lyashkov, AE Spurgeon, HA Sollott, SJ Lakatta, EG AF Yaniv, Yael Juhaszova, Magdalena Lyashkov, Alexey E. Spurgeon, Harold A. Sollott, Steven J. Lakatta, Edward G. TI Cardiac Pacemaker Cells Uniquely Match ATP Supply to Demand SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E.; Spurgeon, Harold A.; Sollott, Steven J.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA. RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 NR 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 734A EP 734A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007162 ER PT J AU Sheldon, KL Bezrukov, SM Rostovtseva, TK AF Sheldon, Kely L. Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI VDAC Phosphorylation Regulates Interaction with Tubulin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sheldon, Kely L.; Bezrukov, Sergey M.; Rostovtseva, Tatiana K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 735A EP 735A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007166 ER PT J AU Sarkar, SK Marmer, B Goldberg, G Neuman, KC AF Sarkar, Susanta K. Marmer, Barry Goldberg, Gregory Neuman, Keir C. TI Single Molecule Study of the Motion of Matrix Metalloprotease MMP1 on Type I Collagen Fiber Shows Proteolysis Driven Hindered Biased Diffusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Sarkar, Susanta K.; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Marmer, Barry; Goldberg, Gregory] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Marmer, Barry; Goldberg, Gregory] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA. RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 0 TC 0 Z9 0 U1 1 U2 3 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 752A EP 753A PG 2 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007255 ER PT J AU Kasprzak, WK Bindewald, E Kim, TJ Stephen, A Fisher, R Shapiro, BA AF Kasprzak, Wojciech K. Bindewald, Eckart Kim, Tae-Jin Stephen, Andrew Fisher, Robert Shapiro, Bruce A. TI Evaluation of Selected Kissing-Loops as Building Blocks in RNA Nano Design SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kasprzak, Wojciech K.; Bindewald, Eckart; Stephen, Andrew; Fisher, Robert] SAIC Frederick Inc, Frederick, MD USA. [Kim, Tae-Jin; Shapiro, Bruce A.] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 758A EP 758A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007284 ER PT J AU Kim, T Marquez, VE Shapiro, BA AF Kim, Taejin Marquez, Victor E. Shapiro, Bruce A. TI Characterization of RNA Nano Design Structures by Steered Molecular Dynamics Simulations Approach SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kim, Taejin; Marquez, Victor E.; Shapiro, Bruce A.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2010 VL 98 IS 3 SU 1 BP 758A EP 758A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007285 ER PT J AU Miller, M AF Miller, Maria TI The Early Years of Retroviral Protease Crystal Structures SO BIOPOLYMERS LA English DT Article DE retroviral protease; crystal structure; chemical protein synthesis; HIV-1 PR; MVT-101; substrate-based inhibitor ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOTAL CHEMICAL-SYNTHESIS; SYNTHESIZED HIV-1 PROTEASE; MOLECULAR-DYNAMICS SIMULATION; HEXAPEPTIDE INHIBITOR; ASPARTIC PROTEINASES; ENZYMATIC-ACTIVITY; TYPE-1 PROTEASE; CLEAVAGE SITE; RESOLUTION AB Soon after its discovery, the attempts to develop anti-AIDS therapeutics focused on the retroviral protease (PR)-an enzyme used by lentiviruses to process the precursor polypeptide into mature viral proteins. An urgent need for the three-dimensional structure of PR to guide rational drug design prompted efforts to produce milligram quantities of this enzyme. However, only minute amounts of PR were present in the HIV-1 and HIV-2 viruses, and initial attempts to express this protein in bacteria were not successful. This review describes X-ray crystallographic studies of the retroviral proteases carried out at NCI-Frederick in the late 1980s and early 1990s and puts into perspective the crucial role that the total protein chemical synthesis played in unraveling the structure, mechanism of action, and inhibition of HIV-1 PR. Notably, the first fully correct structure of HIV-1 PR and the first cocrystal structure of its complex with an inhibitor (a substrate-derived, reduced isostere hexapeptide MVT-101) were determined using chemically synthesized protein. Most importantly, these sets of coordinates were made freely available to the research community and were used worldwide to solve X-ray structures of HIV-1 PR complexes with an array of inhibitors and set in motion a variety of theoretical studies. Publication of the structure of chemically synthesized HIV-1 PR complexed with MVT-101 preceded only by six years the approval of the first PR inhibitor as an anti-AIDS drug. (C) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 521-529, 2010. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Miller, M (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM mariami@mail.nih.gov RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 FU NIH, National Cancer Institute, Center for Cancer Research FX Contract grant sponsor: NIH, National Cancer Institute, Center for Cancer Research NR 48 TC 9 Z9 9 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2010 VL 94 IS 4 SI SI BP 521 EP 529 DI 10.1002/bip.21387 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 619RL UT WOS:000279447700019 PM 20593466 ER PT J AU Vaught, J Baust, JG Heacox, AE Riegman, P Betsou, F Mazur, P Baust, JM Stacey, G Barnes, M AF Vaught, Jim Baust, John G. Heacox, Albert E. Riegman, Peter Betsou, Fay Mazur, Peter Baust, John M. Stacey, Glyn Barnes, Michael TI What Are Three Actionable Strategies to Improve Quality in Biomedical Research SO BIOPRESERVATION AND BIOBANKING LA English DT Article C1 [Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Baust, John G.] SUNY Binghamton, Inst Biomed Technol, Binghamton, NY 13902 USA. [Heacox, Albert E.] CryoLife Inc, Res & Dev, Kennesaw, GA 30144 USA. [Riegman, Peter] Erasmus MC, Erasmus MC Tissue Bank, Dept Pathol, NL-300 DR Rotterdam, Netherlands. [Riegman, Peter] Erasmus MC, European Human Frozen Tumor Tissue Bank Tubafrost, Dept Pathol, NL-300 DR Rotterdam, Netherlands. [Riegman, Peter] Erasmus MC, ISBER, Dept Pathol, NL-300 DR Rotterdam, Netherlands. [Betsou, Fay] Integrated Biobank Luxembourg, L-1210 Luxembourg, Luxembourg. [Mazur, Peter] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA. [Baust, John M.] CPSI Biotech, Owego, NY 13827 USA. [Stacey, Glyn] UK Stem Cell Bank, Potters Bar EN6 3QG, Herts, England. [Barnes, Michael] Cincinnati Childrens Hosp, Cincinnati Biobank, Cincinnati, OH 45229 USA. RP Vaught, J (reprint author), NCI, Off Biorepositories & Biospecimen Res, 11400 Rockville Pike, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov; JGBaust@binghamton.edu; Heacox.al@cryolife.com; p.riegman@erasmusmc.nl; Fay.Betsou@ibbl.lu; pmazur@utk.edu; JMBaust@cpsibiotech.com; Glyn.Stacey@nibsc.hpa.org.uk; Michael.Barnes@cchmc.org NR 0 TC 3 Z9 3 U1 0 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PY 2010 VL 8 IS 3 BP 121 EP 125 DI 10.1089/bio.2010.8315 PG 5 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 660PD UT WOS:000282654600002 PM 24836479 ER PT J AU She, DW Li, Y Zhang, H Graubard, BI Li, ZH AF She, Dewei Li, Yan Zhang, Hong Graubard, Barry I. Li, Zhaohai TI Trend tests for genetic association using population-based cross-sectional complex survey data SO BIOSTATISTICS LA English DT Article DE Complex sampling; F-version of Rao-Scott second-order correction; Quasi-score test; Survey data; Trend test ID SAMPLE-SIZE; CONTINGENCY-TABLES; SCORE TESTS; POWER; POLYMORPHISMS; PROPORTIONS; STATISTICS; GENOTYPES; MARKERS AB Genetic data collected from surveys such as the Third National Health and Nutrition Examination Survey (NHANES III) enable researchers to investigate the association between wide varieties of health factors and genetic variation for the US population. Tests for trend in disease with increasing number of alleles have been developed for simple random samples. However, surveys such as the NHANES III have complex sample designs involving multistage cluster sampling and sample weighting. These types of sample designs can affect Type I error and power properties of statistical tests based on simple random samples. In order to address these issues, we have derived tests of trend based on Wald and quasi-score statistics, with and without assuming a genetic model, that account for the complex sampling design. The finite-sample properties of the proposed test procedures are evaluated via Monte Carlo simulation studies. We make recommendations about the choice of the test statistic depending on whether or not the underlying genetic model is known. Proposed test statistics are applied to NHANES III data to test for associations between the locus ADRB2 (rs1042713) and obesity, between VDR (rs2239185) and high blood lead level, and between TGFB1 (rs1982073) and asthma. C1 [She, Dewei; Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [She, Dewei] EMMES Corp, Rockville, MD 20850 USA. [Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA. [Zhang, Hong] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. [Zhang, Hong; Li, Zhaohai] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. RP Li, ZH (reprint author), George Washington Univ, Dept Stat, Washington, DC 20052 USA. EM zli@gwu.edu NR 21 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2010 VL 11 IS 1 BP 48 EP 56 DI 10.1093/biostatistics/kxp035 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 534VM UT WOS:000272925500004 PM 19745160 ER PT J AU Tang, LL Liu, AY AF Tang, Liansheng Larry Liu, Aiyi TI Sample size recalculation in sequential diagnostic trials SO BIOSTATISTICS LA English DT Article DE Diagnostic accuracy; Error spending function; ROC; Sensitivity; Specificity ID CLINICAL-TRIALS; ACCURACY; DESIGN AB Before a comparative diagnostic trial is carried out, maximum sample sizes for the diseased group and the nondiseased group need to be obtained to achieve a nominal power to detect a meaningful difference in diagnostic accuracy. Sample size calculation depends on the variance of the statistic of interest, which is the difference between receiver operating characteristic summary measures of 2 medical diagnostic tests. To obtain an appropriate value for the variance, one often has to assume an arbitrary parametric model and the associated parameter values for the 2 groups of subjects under 2 tests to be compared. It becomes more tedious to do so when the same subject undergoes 2 different tests because the correlation is then involved in modeling the test outcomes. The calculated variance based on incorrectly specified parametric models may be smaller than the true one, which will subsequently result in smaller maximum sample sizes, leaving the study underpowered. In this paper, we develop a nonparametric adaptive method for comparative diagnostic trials to update the sample sizes using interim data, while allowing early stopping during interim analyses. We show that the proposed method maintains the nominal power and type I error rate through theoretical proofs and simulation studies. C1 [Tang, Liansheng Larry] George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth Human, Biostat & Bioinformat Branch, NIH, Rockville, MD 20852 USA. RP Tang, LL (reprint author), George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. EM ltang1@gmu.edu OI Liu, Aiyi/0000-0002-6618-5082 FU National Institute of Child Health and Human Development, National Institutes of Health FX Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health to A. L. NR 17 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2010 VL 11 IS 1 BP 151 EP 163 DI 10.1093/biostatistics/kxp044 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 534VM UT WOS:000272925500012 PM 19822693 ER PT J AU Flegel, WA AF Flegel, Willy A. TI Rare gems: null phenotypes of blood groups SO BLOOD TRANSFUSION LA English DT Editorial Material ID JK(A-B-) PHENOTYPE; UREA LYSIS; GROUP GENE; ALLELES; POPULATIONS; FREQUENCY; CELLS C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Flegel, WA (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C711 MSC 1184,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 12 TC 6 Z9 6 U1 0 U2 1 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD JAN PY 2010 VL 8 IS 1 BP 2 EP 4 DI 10.2450/2009.0133-09 PG 3 WC Hematology SC Hematology GA 687VH UT WOS:000284805800002 PM 20104271 ER PT J AU Drummond, MB Kirk, GD Ricketts, EP McCormack, MC Hague, JC McDyer, JF Mehta, SH Engels, EA Wise, RA Merlo, CA AF Drummond, M. Bradley Kirk, Gregory D. Ricketts, Erin P. McCormack, Meredith C. Hague, J. Christian McDyer, John F. Mehta, Shruti H. Engels, Eric A. Wise, Robert A. Merlo, Christian A. TI Cross sectional analysis of respiratory symptoms in an injection drug user cohort: the impact of obstructive lung disease and HIV SO BMC PULMONARY MEDICINE LA English DT Article AB Background: Injection drug use is associated with an increased risk of human immunodeficiency virus (HIV) infection and with obstructive lung diseases (OLD). Understanding how HIV and OLD may impact respiratory symptoms among injection drug users (IDUs) is important to adequately care for this high-risk population. We characterized the independent and joint effects of HIV and OLD on respiratory symptoms of a cohort of inner-city IDUs. Methods: Demographics, risk behavior and spirometric measurements were collected from a cross-sectional analysis of the Acquired Immunodeficiency Syndrome Link to the IntraVenous Experience study, an observational cohort of IDUs followed in Baltimore, MD since 1988. Participants completed a modified American Thoracic Society respiratory questionnaire and the Medical Research Council (MRC) dyspnea score to assess respiratory symptoms of cough, phlegm, wheezing and dyspnea. Results: Of 974 participants, 835 (86%) were current smokers and 288 (29.6%) were HIV-infected. The prevalence of OLD (FEV1/FVC <= 0.70) was 15.5%, and did not differ by HIV status. OLD, but not HIV, was associated with increased frequency of reported respiratory symptoms. There was a combined effect of OLD and HIV on worsening of MRC scores. OLD and HIV were independently associated with an increased odds of reporting an MRC >= 2 (OR 1.83 [95% CI 1.23-2.73] and 1.50 [95% CI 1.08-2.09], respectively). COPD, but not HIV, was independently associated with reporting an MRC >= 3 (OR 2.25 [95% CI 1.43-3.54] and 1.29 [95% CI 0.87-1.91], respectively). Conclusions: While HIV does not worsen cough, phlegm or wheezing, HIV significantly increases moderate but not severe dyspnea in individuals of similar OLD status. Incorporating the MRC score into routine evaluation of IDUs at risk for OLD and HIV provides better assessment than cough, phlegm and wheezing alone. C1 [Drummond, M. Bradley; Kirk, Gregory D.; McCormack, Meredith C.; McDyer, John F.; Engels, Eric A.; Wise, Robert A.; Merlo, Christian A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kirk, Gregory D.; Ricketts, Erin P.; Hague, J. Christian; Mehta, Shruti H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Drummond, MB (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. EM mdrummo3@jhmi.edu OI Wise, Robert/0000-0002-8353-2349 FU NIH [RO1s HL090483, DA04334, DA12568]; Institute for Clinical and Translational Research (KL2) Mentored Career Development Award from the National Institutes of Health; National Cancer Institute FX This study was funded in part by grants from the NIH (RO1s HL090483, DA04334 and DA12568). MBD is supported by an Institute for Clinical and Translational Research (KL2) Mentored Career Development Award from the National Institutes of Health. EAE is supported by the Intramural Research Program of the National Cancer Institute. NR 43 TC 14 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PY 2010 VL 10 AR 27 DI 10.1186/1471-2466-10-27 PG 9 WC Respiratory System SC Respiratory System GA V27DA UT WOS:000208592700027 PM 20459792 ER PT J AU Zaalberg, TB AF Zaalberg, Thijs Brocades TI The Aftermath of Somalia, Rwanda and Srebrenica: Parallels and Differences SO BMGN-THE LOW COUNTRIES HISTORICAL REVIEW LA Dutch DT Article AB The Aftermath of Somalia, Rwanda and Srebrenica: Parallels and Differences Christ Klep has written an impressive and highly accessible thesis on the aftermath of three unsuccessful peace operations. By using a bold comparative approach and an ambitious tone of enquiry he places the traumatic Dutch Srebrenica experience in the context of two broadly similar processes of finger-pointing and evading responsibility in Canada and Belgium following their respective interventions in Somalia and Rwanda. He thus exposes many fascinating parallels, yet the historian Klep pays little attention to the differences between his case studies. This is regrettable, as this would have strengthened rather than weakened his otherwise compelling argument. The Somali case in particular differs from 'Srebrenica' and 'Rwanda', since the murders perpetrated by Canadian soldiers horrific as they may have been and the subsequent cover-up in no way constituted a defining moment in the collapsing international mission as a whole. Unlike the genocides in Rwanda and Srebrenica the death of the two Somalis was the result of a purely national Canadian failure, which helps explain why the Somalia Inquiry could identify guilty compatriots far more decisively than, for example, the Netherlands Institute for War Documentation (NIOD) in its Srebrenica report. C1 NIMH, Bethesda, MD 20892 USA. RP Zaalberg, TB (reprint author), NIMH, Bethesda, MD 20892 USA. EM tw.brocades.zaalberg@mindef.nl NR 1 TC 0 Z9 0 U1 1 U2 7 PU KONINKLIJK NEDERLANDS HISTORISCH GENOOTSCHAP PI HAGUE PA PO BOX 90406, HAGUE, 2509 LK, NETHERLANDS SN 0165-0505 J9 BMGN JI BMGN-LCHR PY 2010 VL 125 IS 1 BP 39 EP 47 PG 9 WC History SC History GA 864DQ UT WOS:000298217600004 ER PT S AU Wolkow, CA AF Wolkow, Catherine A. BE Mobbs, CV Hof, PR TI New Haystacks Reveal New Needles: Using Caenorhabditis elegans to Identify Novel Targets for Ameliorating Body Composition Changes during Human Aging SO BODY COMPOSITION AND AGING SE Interdisciplinary Topics in Gerontology LA English DT Article; Book Chapter ID HEAT-SHOCK FACTOR; C-ELEGANS; LIFE-SPAN; RECEPTOR NHR-49; LONGEVITY; FAT; AUTOPHAGY; METABOLISM; EXPRESSION; SARCOPENIA AB Dramatic changes in body composition accompany aging in humans, particularly with respect to adiposity and the musculature. People accumulate fat as they age and lose muscle mass and strength. Caenorhabditis elegans nematodes are small, hermaphroditic soil nematodes that offer a flexible model for studying genetic pathways regulating body composition in humans. While there are significant physiological differences between worms and people, many of the genetic pathways relevant to human lipid and muscle homeostasis are present in worms. Initial studies indicate that adiposity increases in C. elegans during aging, as occurs in humans. Furthermore, substantial evidence demonstrates age-related loss of muscle mass in worms. Possible mechanisms for these changes in C. elegans are presented. Recent studies have highlighted neuroendocrine and environmental signals regulating C. elegans fat metabolism. Potential dysfunction of these pathways during aging could affect overall fat accumulation. By contrast, muscle decline in aging worms results from accumulated damage and 'wear-and-tear' over life span. However, neuroendocrine pathways also regulate muscle mass in response to food availability. Such pathways might provide useful therapeutic approaches for combating muscle loss during aging. From this chapter, readers will develop a deeper understanding of the ways that C. elegans can be used for mechanistic gerontological studies. Copyright (C) 2010 S. Karger AG, Basel C1 NIA, Neurosci Lab, IRP, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, IRP, NIH,Biomed Res Ctr, Suite 05C222,251 Bayview Blvd, Baltimore, MD 21224 USA. EM wolkowca@mail.nih.gov FU Intramural NIH HHS [ZIA AG000323-01, ] NR 52 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0074-1132 BN 978-3-8055-9521-6 J9 INTERD TOP GERONTOL JI Interdiscipl.Top.Gerontol. PY 2010 VL 37 BP 84 EP 93 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA BQT14 UT WOS:000281774200006 PM 20703057 ER PT B AU Kim, SG Bandettini, PA AF Kim, Seong-Gi Bandettini, Peter A. BE Faro, SH Mohamed, FB TI Principles of Functional MRI SO BOLD FMRI: A GUIDE TO FUNCTIONAL IMAGING FOR NEUROSCIENTISTS LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE IMAGE; RECOVERY FAIR TECHNIQUE; HUMAN BRAIN ACTIVATION; TIME-RESOLVED FMRI; WEIGHTED SPIN-ECHO; HIGH-RESOLUTION; SIGNAL CHANGES; BOLD FMRI; IN-VIVO C1 [Kim, Seong-Gi] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15260 USA. [Kim, Seong-Gi] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Kim, SG (reprint author), Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15260 USA. NR 72 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1328-9 PY 2010 BP 3 EP 22 DI 10.1007/978-1-4419-1329-6_1 D2 10.1007/978-1-4419-1329-6 PG 20 WC Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BQB96 UT WOS:000280603400001 ER PT B AU Regard, JB Mak, KK Gordon, JA Yang, YZ AF Regard, Jean B. Mak, Kingston K. Gordon, Joshua A. Yang, Yingzi BE Bronner, F FarachCarson, MC Roach, HI TI Hedgehog Signaling in Growth Plate and Bone Development SO BONE AND DEVELOPMENT SE Topics in Bone Biology LA English DT Article; Book Chapter ID INTRAFLAGELLAR TRANSPORT PROTEINS; BRACHYDACTYLY TYPE A1; HUMAN SONIC HEDGEHOG; LEMLI-OPITZ-SYNDROME; DEVELOPING LIMB BUD; INDIAN-HEDGEHOG; CHONDROCYTE DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; CRANIOFACIAL MORPHOGENESIS; CHOLESTEROL-BIOSYNTHESIS C1 [Regard, Jean B.; Mak, Kingston K.; Gordon, Joshua A.; Yang, Yingzi] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Regard, JB (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 122 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-84882-821-6 J9 TOP BONE BIOL PY 2010 VL 6 BP 65 EP 80 DI 10.1007/978-1-84882-822-3_4 D2 10.1007/978-1-84882-822-3 PG 16 WC Endocrinology & Metabolism; Medicine, General & Internal; Medicine, Research & Experimental; Orthopedics SC Endocrinology & Metabolism; General & Internal Medicine; Research & Experimental Medicine; Orthopedics GA BOK29 UT WOS:000276889800004 ER PT J AU Singh, AK Chen, J Calado, R Sowers, A Mitchell, JB Barrett, AJ AF Singh, A. K. Chen, J. Calado, R. Sowers, A. Mitchell, J. B. Barrett, A. J. TI TBI with lung dose reduction does not improve hematopoietic cell homing to BM during allogeneic transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE TBI; lung shielding; dose reduced; BID; stem cell homing ID TOTAL-BODY IRRADIATION; BONE-MARROW-TRANSPLANTATION; PULMONARY-FUNCTION TESTS; STEM-CELLS; PERIPHERAL-BLOOD; PROGENITOR CELLS; CONDITIONING REGIMEN; APLASTIC-ANEMIA; ENGRAFTMENT; CYCLOPHOSPHAMIDE AB To determine the effects of TBI dose, fractionation and lung shielding on hematopoietic stem cell homing to the BM, BM cells were extracted from tibiae and femurs of B6-green fluorescent protein (GFP) mice and transplanted into B6 mice. Recipient mice had either: (i) no radiation, (ii) single-dose TBI at 13.6 Gy, (iii) single-dose TBI at 13.6 Gy with reduced lung exposure to 0.4 Gy by shielding, (iv) split-dose TBI at 12 Gy to twice per day over 4 days or (v) split-dose TBI at 12 Gy to twice per day over 4 days with reduced lung exposure to 0.36 Gy by shielding. The last radiation exposure preceded tail vein injection by 4-6 h. Mice were killed after 18 h. The homing of GFP-positive, lineage-negative cells was not significantly improved in any irradiated group compared with control. The homing of GFP-positive, lineage-negative, Kit-positive cells was significantly worse in all irradiated groups. TBI does not improve the homing of lineage-negative donor BM cells to the recipient marrow. The homing of lineage-negative, Kit-positive donor BM cells was significantly worse following TBI, with or without lung dose reduction. Bone Marrow Transplantation (2010) 45, 25-30; doi: 10.1038/bmt.2009.121; published online 15 June 2009 C1 [Singh, A. K.] Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. [Chen, J.; Calado, R.; Barrett, A. J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Sowers, A.; Mitchell, J. B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), Roswell Pk Canc Inst, Dept Radiat Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM anurag.singh@roswellpark.org RI Calado, Rodrigo/G-2619-2011 FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 39 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2010 VL 45 IS 1 BP 25 EP 30 DI 10.1038/bmt.2009.121 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 543PZ UT WOS:000273592000004 PM 19525987 ER PT S AU Leker, RR Mezey, E AF Leker, Ronen R. Mezey, Eva BE Arnason, BG TI Neural and Non-Neural Stem Cells as Novel Therapeutic Modalities for Brain Injury SO BRAIN AND HOST DEFENSE SE Neuroimmune Biology LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; BONE-MARROW-CELLS; LEUKEMIA INHIBITORY FACTOR; FIBROBLAST-GROWTH-FACTOR; ADULT-RAT HIPPOCAMPUS; HUMAN CEREBRAL-CORTEX; RADIAL GLIAL-CELLS; DENTATE GYRUS; SUBVENTRICULAR ZONE; PRECURSOR CELLS C1 [Leker, Ronen R.] Hebrew Univ Jerusalem, Hadassah Med Ctr, Cerebrovasc Serv, Dept Neurol, Jerusalem, Israel. [Leker, Ronen R.] Hebrew Univ Jerusalem, Hadassah Med Ctr, Periz & Chantal Sheinberg Cerebrovasc Res Lab, Dept Neurol, Jerusalem, Israel. [Mezey, Eva] NIDCR, NIH, CSDB, Bethesda, MD USA. RP Leker, RR (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Cerebrovasc Serv, Dept Neurol, Jerusalem, Israel. NR 114 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-7443 BN 978-0-44-453545-0 J9 NEUROIMMUNE PY 2010 VL 9 BP 59 EP 66 PG 8 WC Immunology; Clinical Neurology SC Immunology; Neurosciences & Neurology GA BCP74 UT WOS:000310976500007 ER PT J AU Hutchinson, MR Zhang, YN Shridhar, M Evans, JH Buchanan, MM Zhao, TX Slivka, PF Coats, BD Rezvani, N Wieseler, J Hughes, TS Landgraf, KE Chan, S Fong, S Phipps, S Falke, JJ Leinwand, LA Maier, SF Yin, H Rice, KC Watkins, LR AF Hutchinson, Mark R. Zhang, Yingning Shridhar, Mitesh Evans, John H. Buchanan, Madison M. Zhao, Tina X. Slivka, Peter F. Coats, Benjamen D. Rezvani, Niloofar Wieseler, Julie Hughes, Travis S. Landgraf, Kyle E. Chan, Stefanie Fong, Stephanie Phipps, Simon Falke, Joseph J. Leinwand, Leslie A. Maier, Steven F. Yin, Hang Rice, Kenner C. Watkins, Linda R. TI Evidence that opioids may have toll-like receptor 4 and MD-2 effects SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Toll-like receptor 4; Knockout; Opioid; Analgesia; Dependence; Glia; Microglia ID MORPHINE ANTINOCICEPTIVE TOLERANCE; NECROSIS-FACTOR-ALPHA; MOUSE SPINAL-CORD; PROINFLAMMATORY CYTOKINES; DEXTRO-MORPHINE; LEVO-MORPHINE; KNOCKOUT MICE; ANALGESIA; MICROGLIA; LIPOPOLYSACCHARIDE AB Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically-employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LIPS binding pocket of MD-2 rather than TLR4. An in silica to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling. (C) 2009 Elsevier Inc. All rights reserved. C1 [Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Ctr Neurosci, Boulder, CO 80309 USA. [Hutchinson, Mark R.; Zhang, Yingning; Shridhar, Mitesh; Coats, Benjamen D.; Rezvani, Niloofar; Wieseler, Julie; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Hutchinson, Mark R.; Chan, Stefanie; Fong, Stephanie] Univ Adelaide, Dept Pharmacol, Adelaide, SA, Australia. [Shridhar, Mitesh; Evans, John H.; Buchanan, Madison M.; Zhao, Tina X.; Slivka, Peter F.; Landgraf, Kyle E.; Falke, Joseph J.; Yin, Hang] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Hughes, Travis S.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Phipps, Simon; Leinwand, Leslie A.] Newcastle Univ, Div Biomed Sci, CARD, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA. RP Watkins, LR (reprint author), Univ Colorado, Dept Psychol & Neurosci, Ctr Neurosci, Campus Box 345, Boulder, CO 80309 USA. EM linda.watkins@colorado.edu RI Phipps, Simon/F-9170-2010; Hutchinson, Mark/G-4147-2014; YIN, HANG/O-2097-2014; OI Phipps, Simon/0000-0002-7388-3612; Hutchinson, Mark/0000-0003-2154-5950; YIN, HANG/0000-0002-9762-4818; LEINWAND, LESLIE/0000-0003-1470-4810 FU International Association for the Study of Pain; American Australian Association Merck Company Foundation; National Health and Medical Research Council [ID 465423]; NIH [DA015642, DA017670, DA024044, DE017782, T32 GM-065103]; Council on Research and Creative Work at the University of Colorado at Boulder; Kimmel Foundation [SKF-08-101]; University of Colorado at Boulder [T32 GM-065103] FX This work was supported by an International Association for the Study of Pain International Collaborative grant, American Australian Association Merck Company Foundation Fellowship, National Health and Medical Research Council CJ Martin Fellowship (ID 465423; M.R.H.) and NIH Grants DA015642, DA017670, DA024044, DE017782, T32 GM-065103, and DE017782. This work was partially supported by the by the NIH Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. H.Y. thanks the Council on Research and Creative Work at the University of Colorado at Boulder and the Kimmel Foundation (SKF-08-101) for financial support of the work. M.S., TXZ. and M.M.B. are grateful for HHMI undergraduate grants for biomedical research provided by the Undergraduate Research Opportunities Program at the University of Colorado at Boulder. P.F.S. thanks for the University of Colorado Pre-doctoral Training program in Molecular Biophysics (T32 GM-065103). We thank Avigen (Alameda, CA, USA) for the gift of the HEK293-TLR4 cell line and AV411. Thanks to the Akira Research group, Osaka University, Osaka, Japan for permission to use the TLR4 knockout mice. NR 54 TC 177 Z9 182 U1 3 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2010 VL 24 IS 1 BP 83 EP 95 DI 10.1016/j.bbi.2009.08.004 PG 13 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 531OE UT WOS:000272676400012 PM 19679181 ER PT S AU Spatz, M AF Spatz, Maria BE Czernicki, Z Baethmann, A Ito, U Katayama, Y Kuroiwa, T Mendelow, D TI Past and Recent BBB Studies with Particular Emphasis on Changes in Ischemic Brain Edema Dedicated to the memory of Dr. Igor Klatzo SO BRAIN EDEMA XIV SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 14th International Symposium on Brain Edema and Brain Tissue Injury CY JUN 11-14, 2008 CL Warsaw, POLAND DE Blood-brain barrier (BBB); neurovascular unit; ischemia; brain edema ID FOCAL CEREBRAL-ISCHEMIA; ENDOTHELIAL-CELLS; BARRIER; EXPRESSION; PERMEABILITY; AQUAPORIN-4; INJURY; STROKE; 2-AG AB The blood-brain barrier (BBB) functions to protect the environment of the brain through endothelial cells and their interactions with other cells and components of the cerebral vasculature and the brain parenchyma. Alterations in the BBB as a result of injuries (i.e., brain ischemia and traumatic brain injury) play a crucial role in the pathophysiological response. The following is a brief review of the BBB and the mechanisms by which its cellular elements participate in barrier disruptions such as those associated with ischemia and resulting brain edema formation. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. EM maria.spatz@med.navy.mil NR 27 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-98758-2 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2010 VL 106 BP 21 EP 27 DI 10.1007/978-3-211-98811-4_3 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA BNL75 UT WOS:000274867500003 PM 19812915 ER PT B AU Salvadore, G Machado-Vieira, R Manji, HK AF Salvadore, Giacomo Machado-Vieira, Rodrigo Manji, Husseini K. BE Ritsner, MS TI Neuroprotective Agents in Mood Disorders: Pathophysiological and Therapeutic Implications SO BRAIN PROTECTION IN SCHIZOPHRENIA, MOOD AND COGNITIVE DISORDERS LA English DT Article; Book Chapter ID PROTON-MAGNETIC-RESONANCE; MAJOR DEPRESSIVE DISORDER; DORSOLATERAL PREFRONTAL CORTEX; GAMMA-AMINOBUTYRIC-ACID; GLYCOGEN-SYNTHASE KINASE-3; VOXEL-BASED MORPHOMETRY; N-ACETYL-ASPARTATE; BIPOLAR-I DISORDER; GRAY-MATTER VOLUME; ANTERIOR CINGULATE CORTEX AB Drug development for mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) has undergone an important paradigm shift in the last decade due to our expanding knowledge of the pathophysiology and treatment of these illnesses. While previous research focused exclusively on abnormalities of the monoaminergic neurotransmitter systems, more recent preclinical and clinical studies have emphasized the role of impaired neuroplasticity and cellular resilience in mood disorders. Also informing our thinking for drug development are the neurotrophic/neuroprotective properties associated with several agents currently used as treatments for mood disorders-including antidepressants, mood stabilizers, atypical antipsychotics, and a number of experimental agents currently under investigation. Many of these agents share some potent neurotrophic and neuroprotective properties, exert significant effects on signaling pathways that regulate cellular plasticity, and are believed to act directly on some of the core pathophysiological mechanisms underlying these devastating illnesses. In this chapter, we discuss how drugs that modulate signaling pathways involved in regulating cell survival and cell death target some of the core pathophysiological mechanisms of BPD and MDD, with a particular emphasis on brain imaging and neuropathological abnormalities in mood disorders. Cellular and molecular mechanisms of action of agents with neurotrophic and neuroplastic properties are also discussed, with a special focus on the mood stabilizers lithium and valproate. C1 [Salvadore, Giacomo; Machado-Vieira, Rodrigo; Manji, Husseini K.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil. RP Salvadore, G (reprint author), NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. EM salvadoreg@mail.nih.gov; machadovieirar@mail.nih.gov; manji@nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 195 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-8552-8 PY 2010 BP 417 EP 449 DI 10.1007/978-90-481-8553-5_14 D2 10.1007/978-90-481-8553-5 PG 33 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BQD33 UT WOS:000280733000014 ER PT J AU Esquenazi, D Bussoloti, I Carvalho, MDD de Barros, FS AF Esquenazi, David Bussoloti Filho, Ivo da Costa Carvalho, Maria da Gloria de Barros, Fernando Souza TI The frequency of human papillomavirus findings in normal oral mucosa of healthy people by PCR SO BRAZILIAN JOURNAL OF OTORHINOLARYNGOLOGY LA English DT Article DE mouth; papillomavirus infections; mouth mucosa ID POLYMERASE-CHAIN-REACTION; SOUTHERN BLOT HYBRIDIZATION; SQUAMOUS-CELL CARCINOMAS; NATURAL-HISTORY; HPV INFECTIONS; RISK; DNA; PREVALENCE; TYPE-16; CANCER AB The human papillomavirus (HPV) is a DNA virus, which belongs to papillomaviridae family, being of low and high risk, which infect the skin and mucous membranes and can induce benign and malign tumor formation. In the oral mucosa they have been associated with oral papilloma, focal epithelial hyperplasia, leucoplakia and oral neoplasia. Aim: to study the frequency of HPV finding in oral mucosa of normal people. Materials and methods: Prospective study, cross-sectional cohort. One hundred volunteers, young adults, healthy, aged between 20 and 31 years, university students with no history, no complains, without oral or oropharyngeal lesions. They were submitted to a questionnaire with questions regarding HPV infection epidemiology. The samples were harvested by brushing and analyzed by PCR. Results: The results were negative for HPV in all samples. Conclusion: It seems we had high social and economical class individuals, with nutrition rich in carotenoyds and vitamin C, low smoking and alcohol consumption and heterosexual habits with predominant monogamy and regular use of condoms. C1 [Esquenazi, David; de Barros, Fernando Souza] Univ Fed Rio de Janeiro, Sch Med, Sci Initiat Program, BR-21941 Rio De Janeiro, Brazil. [Esquenazi, David; Bussoloti Filho, Ivo] Santa Casa Sao Paulo Med Sci Sch, Sao Paulo, Brazil. [Bussoloti Filho, Ivo] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. [da Costa Carvalho, Maria da Gloria] NIH, Bethesda, MD 20892 USA. [da Costa Carvalho, Maria da Gloria] Univ Fed Rio de Janeiro, Inst Biophys, Lab CCF, BR-21941 Rio De Janeiro, Brazil. RP Esquenazi, D (reprint author), Univ Fed Rio de Janeiro, Sch Med, Sci Initiat Program, BR-21941 Rio De Janeiro, Brazil. OI carvalho, maria da gloria/0000-0001-5890-8095 NR 50 TC 19 Z9 20 U1 0 U2 1 PU ASSOC BRASILEIRA OTORRINOLARINGOLOGIA & CIRURGIA CERVICOFACIAL PI SAO PAULO PA AV INDIANOPOLOS 740, MOEMA, SAO PAULO, SP 04062-001, BRAZIL SN 1808-8694 EI 1808-8686 J9 BRAZ J OTORHINOLAR JI Braz. J. Otorhinolaryngol. PD JAN-FEB PY 2010 VL 76 IS 1 BP 78 EP 84 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 803GO UT WOS:000293570000013 PM 20339693 ER PT B AU Chowdhury, N Swain, SM AF Chowdhury, Nabila Swain, Sandra M. BE Tan, AR TI Management of HER2-Positive Metastatic Breast Cancer: Standard and New Approaches SO BREAST CANCER SE Emerging Cancer Therapeutics LA English DT Article; Book Chapter DE HER2 human epidermal growth factor receptor 2; MBC metastatic breast cancer; Trastuzumab; Neratinib; T-DM1 Trastuzumab DM1 ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; TRASTUZUMAB RESISTANCE; NERATINIB HKI-272; THERAPY; PLUS; PACLITAXEL; EFFICACY; HER2 AB Overexpression of the human epidermal growth factor receptor 2 (HER2, ErbB2) is a negative prognostic factor associated with increased recurrence and shorter survival in breast cancer. Trastuzumab is the first modern targeted therapy specifically designed for the treatment of HER2-positive breast cancer. Although trastuzumab-based therapy has changed the treatment paradigm of HER2-positive metastatic breast cancer, most patients eventually develop progressive disease. This review discusses the advances being made in the management of HER2-positive metastatic breast cancer, with a special focus on trastuzumab resistance, treatments after progression on trastuzumab, and newer biological agents that may provide further therapeutic options for these patients. C1 [Chowdhury, Nabila; Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Chowdhury, Nabila] NCI, NIH, Bethesda, MD 20892 USA. [Swain, Sandra M.] Georgetown Univ, Washington, DC USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St, Washington, DC 20010 USA. EM sandra.m.swain@medstar.net NR 52 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-14-7 J9 EMERG CANCER THER PY 2010 VL 1 IS 3 BP 577 EP 588 DI 10.5003/2151-4194.1.3.577 PG 12 WC Oncology SC Oncology GA BSV94 UT WOS:000285941900011 ER PT J AU Harvie, M Pegington, M Cuzick, J Frystyk, J Flyvbjerg, A Jebb, S Mattson, M Howell, A AF Harvie, M. Pegington, M. Cuzick, J. Frystyk, J. Flyvbjerg, A. Jebb, S. Mattson, M. Howell, A. TI Effect of intermittent versus continuous energy restriction on weight loss and breast cancer risk biomarkers SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT Conference on Breast Cancer Research CY MAY 18, 2010 CL London, ENGLAND C1 [Harvie, M.; Pegington, M.; Howell, A.] Genesis Prevent Ctr, Manchester, Lancs, England. [Cuzick, J.] Wolfson Inst, Dept Epidemiol & Stat, London, England. [Frystyk, J.; Flyvbjerg, A.] Aarhus Univ, Med Res Labs, Aarhus, Denmark. [Jebb, S.] MRC, Human Nutr Res Grp, Cambridge, England. [Mattson, M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 SU 1 BP S9 EP S10 AR P28 DI 10.1186/bcr2525 PG 2 WC Oncology SC Oncology GA 708OF UT WOS:000286371800035 ER PT J AU Mendez-Catala, CF Vostrov, A Pugacheva, E Ito, Y Docquier, F Chernukhin, I Farrar, D Kita, GX Murrell, A Lobanankov, V Klenova, E AF Mendez-Catala, C. F. Vostrov, A. Pugacheva, E. Ito, Y. Docquier, F. Chernukhin, I. Farrar, D. Kita, G-X Murrell, A. Lobanankov, V. Klenova, E. TI Regulation of the apoptotic genes in breast cancer cells by the transcription factor CTCF SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT Conference on Breast Cancer Research CY MAY 18, 2010 CL London, ENGLAND C1 [Mendez-Catala, C. F.; Chernukhin, I.; Farrar, D.; Kita, G-X; Klenova, E.] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. [Vostrov, A.; Pugacheva, E.; Lobanankov, V.] NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD USA. [Ito, Y.; Murrell, A.] Li Ka Shing Ctr, CRUK Cambridge Res Inst, Cambridge, England. [Docquier, F.] Anglia Ruskin Univ, Helen Rollason Res Lab, Chelmsford, Essex, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 SU 1 BP S5 EP S5 AR P12 DI 10.1186/bcr2509 PG 1 WC Oncology SC Oncology GA 708OF UT WOS:000286371800019 ER PT J AU Arason, A Gunnarsson, H Johannesdottir, G Jonasson, K Bendahl, PO Gillanders, EM Agnarsson, BA Jonsson, G Pylkas, K Mustonen, A Heikkinen, T Aittomaki, K Blomqvist, C Melin, B Johannsson, OTH Moller, P Winqvist, R Nevanlinna, H Borg, A Barkardottir, RB AF Arason, Adalgeir Gunnarsson, Haukur Johannesdottir, Gudrun Jonasson, Kristjan Bendahl, Par-Ola Gillanders, Elizabeth M. Agnarsson, Bjarni A. Jonsson, Goran Pylkas, Katri Mustonen, Aki Heikkinen, Tuomas Aittomaki, Kristiina Blomqvist, Carl Melin, Beatrice Johannsson, Oskar T. H. Moller, Pal Winqvist, Robert Nevanlinna, Heli Borg, Ake Barkardottir, Rosa B. TI Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families SO BREAST CANCER RESEARCH LA English DT Article ID WILD-TYPE CHROMOSOME; OVARIAN-CANCER; SUSCEPTIBILITY LOCUS; GENE; POPULATION; BRCA1; PREVALENCE; MUTATIONS; PENETRANCE; DELETIONS AB Introduction: A significant proportion of high-risk breast cancer families are not explained by mutations in known genes. Recent genome-wide searches (GWS) have not revealed any single major locus reminiscent of BRCA1 and BRCA2, indicating that still unidentified genes may explain relatively few families each or interact in a way obscure to linkage analyses. This has drawn attention to possible benefits of studying populations where genetic heterogeneity might be reduced. We thus performed a GWS for linkage on nine Icelandic multiple-case non-BRCA1/2 families of desirable size for mapping highly penetrant loci. To follow up suggestive loci, an additional 13 families from other Nordic countries were genotyped for selected markers. Methods: GWS was performed using 811 microsatellite markers providing about five centiMorgan (cM) resolution. Multipoint logarithm of odds (LOD) scores were calculated using parametric and nonparametric methods. For selected markers and cases, tumour tissue was compared to normal tissue to look for allelic loss indicative of a tumour suppressor gene. Results: The three highest signals were located at chromosomes 6q, 2p and 14q. One family contributed suggestive LOD scores (LOD 2.63 to 3.03, dominant model) at all these regions, without consistent evidence of a tumour suppressor gene. Haplotypes in nine affected family members mapped the loci to 2p23.2 to p21, 6q14.2 to q23.2 and 14q21.3 to q24.3. No evidence of a highly penetrant locus was found among the remaining families. The heterogeneity LOD (HLOD) at the 6q, 2p and 14q loci in all families was 3.27, 1.66 and 1.24, respectively. The subset of 13 Nordic families showed supportive HLODs at chromosome 6q (ranging from 0.34 to 1.37 by country subset). The 2p and 14q loci overlap with regions indicated by large families in previous GWS studies of breast cancer. Conclusions: Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction. C1 [Arason, Adalgeir; Gunnarsson, Haukur; Johannesdottir, Gudrun; Agnarsson, Bjarni A.; Barkardottir, Rosa B.] Landspitali LSH, Dept Pathol, IS-101 Reykjavik, Iceland. [Arason, Adalgeir; Agnarsson, Bjarni A.; Johannsson, Oskar T. H.; Barkardottir, Rosa B.] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Jonasson, Kristjan] Univ Iceland, Fac Engn & Nat Sci, IS-107 Reykjavik, Iceland. [Bendahl, Par-Ola; Jonsson, Goran; Borg, Ake] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden. [Gillanders, Elizabeth M.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. [Pylkas, Katri; Mustonen, Aki; Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet, SF-90220 Oulu, Finland. [Pylkas, Katri; Mustonen, Aki; Winqvist, Robert] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, SF-90220 Oulu, Finland. [Heikkinen, Tuomas; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki 00029, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00029, Finland. [Melin, Beatrice] Umea Univ, Dept Radiat Sci, S-90185 Umea, Sweden. [Johannsson, Oskar T. H.] Landspitali LSH, Dept Oncol, IS-101 Reykjavik, Iceland. [Moller, Pal] Oslo Univ Hosp, Sect Inherited Canc, N-0310 Oslo, Norway. RP Arason, A (reprint author), Landspitali LSH, Dept Pathol, IS-101 Reykjavik, Iceland. EM adalgeir@landspitali.is OI Arason, Adalgeir/0000-0003-0480-886X; Nevanlinna, Heli/0000-0002-0916-2976 FU Icelandic Research Fund; Nordic Cancer Union; Landspitali University Hospital; Memorial Fund of Bergthora Magnusdottir and Jakob Bjarnason; Icelandic association: "Walking for Breast Cancer Research"; Swedish Cancer Society; Helsinki University Central Hospital; Academy of Finland; Finnish Cancer Society; Sigrid Juselius Foundation; Finnish Cancer Foundation; University of Finland; Oulu University Hospital FX We thank the patients and their family members whose contribution made this work possible. We gratefully acknowledge the staff at the Department of Pathology, Landspitali-University Hospital for providing pathological information and tissue samples, the Genetic Committee of the University of Iceland for pedigree information and Valgardur Egilsson, Landspitali-University Hospital who provided extended pedigree information on family 70234, the Finnish, Icelandic, Norwegian and Swedish Cancer Registry for information on cancer data, and the staff at Landspitali-University Hospital and the Service Center at Noatun for help with blood sampling. Financial support was provided by the Icelandic Research Fund, the Nordic Cancer Union, the Landspitali University Hospital Research Fund, the Memorial Fund of Bergthora Magnusdottir and Jakob Bjarnason, the Icelandic association: "Walking for Breast Cancer Research", the Swedish Cancer Society, the Helsinki University Central Hospital Research Fund, Academy of Finland, the Finnish Cancer Society, the Sigrid Juselius Foundation, the Finnish Cancer Foundation, the University of Finland and the Oulu University Hospital. NR 36 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 4 AR R50 DI 10.1186/bcr2608 PG 10 WC Oncology SC Oncology GA 697HO UT WOS:000285504100006 PM 20637093 ER PT J AU Bussard, KM Boulanger, CA Kittrell, FS Behbod, F Medina, D Smith, GH AF Bussard, Karen M. Boulanger, Corinne A. Kittrell, Frances S. Behbod, Fariba Medina, Daniel Smith, Gilbert H. TI Immortalized, premalignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA SO BREAST CANCER RESEARCH LA English DT Article ID RESTING HUMAN-BREAST; STEM-CELLS; MAMMARY-GLAND; IN-VIVO; SELECTIVE SEGREGATION; MOUSE; STRANDS; COSEGREGATION; EXPRESSION; MORPHOGENESIS AB Introduction: During selective segregation of DNA, a cell asymmetrically divides and retains its template DNA. Asymmetric division yields daughter cells whose genome reflects that of the parents, simultaneously protecting the parental cell from genetic errors that may occur during DNA replication. We hypothesized that long-lived epithelial cells are present in immortal, premalignant cell populations, undergo asymmetric division, retain their template DNA strands, and cycle both during allometric growth and during pregnancy. Methods: The glands of 3-week-old immune-competent Balb/C female mice were used intact or cleared of host epithelium and implanted with ductal-limited, lobule-limited, or alveolar-ductal progenitor cells derived from COMMA-D1 pre-malignant epithelial cells. 5-Bromo-2-deoxyuridine (5-BrdU) was administered to identify those cells that retain their template DNA. Nulliparous mice were then either injected with [(3)H]-thymidine ((3)H-TdR) to distinguish 5-BrdU label-retaining cells that enter the cell cycle and euthanized, or mated, injected with (3)H-TdR, and euthanized at various days after coitus. Sections were stained for estrogen receptor-alpha (ER-alpha) or progesterone receptor (PR) with immunohistochemistry. Cells labeled with both 5-BrdU and (3)H-TdR were indicative of label-retaining epithelial cells (LRECs). Results: Cells that retained a 5-BrdU label and cells labeled with [(3)H]-thymidine were found in all mice and were typically detected along the branching epithelium of mature mouse mammary glands. Cells containing double-labeled nuclei (LRECs) were found in the intact mammary glands of both pregnant and nulliparous mice, and in mammary glands implanted with premalignant cells. Double-labeled cells ((3)H-TdR/5-BrdU) represent a small portion of cells in the mammary gland that cycle and retain their template DNA (5-BrdU). Some label-retaining cells were also ER-alpha or PR positive. LRECs distributed their second label ((3)H-TdR) to daughter cells, and this effect persisted during pregnancy. LRECs, and small focal hyperplasia, were found in all immortalized premalignant mammary-implant groups. Conclusions: The results indicate that a subpopulation of long-lived, label-retaining epithelial cells (LRECs) is present in immortal premalignant cell populations. These LRECs persist during pregnancy, retain their original DNA, and a small percentage express ER-alpha and PR. We speculate that LRECs in premalignant hyperplasia represent the long-lived (memory) cells that maintain these populations indefinitely. C1 [Bussard, Karen M.; Boulanger, Corinne A.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. [Kittrell, Frances S.; Medina, Daniel] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. [Behbod, Fariba] Univ Kansas, Dept Pathol & Lab Med, Med Ctr, Kansas City, KS 66160 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bldg 37,Room 1112,37 Convent Dr, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU Center for Cancer Research NCI, NIH FX The authors acknowledge the technical assistance of Gayle DeSalvo and SAIC, Frederick Cancer Research Center, in preparation of the animals, their tissues, autoradiography, and immunohistochemistry. The intramural research program of the Center for Cancer Research NCI, NIH, supported this work. NR 26 TC 10 Z9 10 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 5 AR R86 DI 10.1186/bcr2754 PG 13 WC Oncology SC Oncology GA 697IG UT WOS:000285506100021 PM 20964820 ER PT J AU Dorgan, JF Stanczyk, FZ Kahle, LL Brinton, LA AF Dorgan, Joanne F. Stanczyk, Frank Z. Kahle, Lisa L. Brinton, Louise A. TI Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk SO BREAST CANCER RESEARCH LA English DT Article ID ANTI-MULLERIAN HORMONE; POSTMENOPAUSAL WOMEN; REPRODUCTIVE-AGE; MENSTRUAL-CYCLE; ANDROGEN LEVELS; ESTROGEN; TRANSITION; AROMATASE; MENOPAUSE AB Introduction: Breast cancer is frequently a hormonally dependent cancer, and associations of circulating estrogens and androgens with subsequent breast cancer risk are well established in postmenopausal women. Associations of serum estrogens and androgens with breast cancer risk in premenopausal women are less well studied. The objective of this study was to determine whether estradiol and testosterone levels in serum collected before menopause are associated with subsequent breast cancer risk. Methods: We conducted a prospective case-control study of 266 participants who were registered in the Columbia, Missouri, Serum Bank and not using exogenous hormones at the time of blood collection. Each of 98 in situ or invasive breast cancer cases with prediagnostic serum collected before menopause was matched to two controls by age, date, menstrual cycle day, and time of day of blood collection. Estradiol and testosterone concentrations were quantified by using specific radioimmunoassays, and sex hormone-binding globulin (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of the non-SHBG bound hormone fractions. Data were analyzed by using conditional logistic regression. All tests of statistical significance were two-sided. Results: Serum testosterone was strongly and significantly associated with breast cancer risk. The relative odds (OR) for increasing quartiles of total testosterone were 1.0, 2.1 (95% confidence interval (CI) 0.9 to 4.8), 1.5 (95% CI, 0.6 to 3.4), and 3.3 (95% CI, 1.5 to 7.5, P-trend = 0.006). Comparable ORs for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0, 1.7 (95% CI, 0.7 to 4.2), 1.7 (95% CI, 0.7 to 4.0), and 4.2 (95% CI, 1.6 to 10.9, P-trend = 0.002). Total and non-SHBG-bound estradiol were not associated with breast cancer, but extreme variation in levels across the menstrual cycle coupled with relatively small numbers, particularly for analyses stratified by cycle phase, limited the power to detect associations. Conclusions: Results suggest that premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer. C1 [Dorgan, Joanne F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kahle, Lisa L.] Informat Management Serv Inc, Rockville, MD 20852 USA. [Brinton, Louise A.] NCI, Rockville, MD 20852 USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM joanne.dorgan@fccc.edu RI Perez , Claudio Alejandro/F-8310-2010; Brinton, Louise/G-7486-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Brinton, Louise/0000-0003-3853-8562 FU U.S. Department of Defense [BC062367]; National Institutes of Health [P30CA006927] FX We thank all of the participants in the Columbia, MO, Serum Bank. Funding was provided by the U.S. Department of Defense (BC062367 to JFD), the National Institutes of Health (P30CA006927), and by the National Institutes of Health intramural research program. NR 33 TC 27 Z9 29 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 6 AR R98 DI 10.1186/bcr2779 PG 8 WC Oncology SC Oncology GA 739WJ UT WOS:000288751500009 PM 21087481 ER PT J AU Ghabach, B Anderson, WF Curtis, RE Huycke, MM Lavigne, JA Dores, GM AF Ghabach, Bassam Anderson, William F. Curtis, Rochelle E. Huycke, Mark M. Lavigne, Jackie A. Dores, Graca M. TI Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study SO BREAST CANCER RESEARCH LA English DT Article ID C-KIT; PROLIFERATIVE ACTIVITY; ESTROGEN-RECEPTORS; SALIVARY-GLAND; CANCER; EXPRESSION; TUMOR; PATTERNS; METASTASIS; PREVALENCE AB Introduction: Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC incidence, relative survival, and associated cancer risk in the United States. Methods: Using data from the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), and relative survival for breast-ACC, and standardized incidence ratios (SIRs) for other cancers. Results: Overall 338 women (IR = 0.92/1 million person-years) were diagnosed with breast-ACC during 1977 to 2006. Blacks had 39% lower IRs than Whites (IRR = 0.61, 95% confidence interval = 0.37 to 0.96), and IRs remained constant over the 30-year period. Ninety-five percent of cases presented with localized stage (n = 320; IR = 0.87), and the highest IRs were observed for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative tumors (IR = 0.56). Like other typically ER-negative tumors, age-specific IRs increased until midlife and then plateaued. Five-year, 10-year, and 15-year relative survival was 98.1%, 94.9%, and 91.4%, respectively. The risk of female breast cancer was not increased following (SIR = 0.89, 95% confidence interval = 0.43 to 1.64) or preceding (SIR = 0.71, 95% confidence interval = 0.28 to 1.46) breast-ACC. Similarly, no association was observed for breast-ACC and risk of all other cancers combined, solid tumors, or lymphohematopoietic malignancies. Conclusions: Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and lend credence to the apparent heterogeneity of basal-like breast cancers. C1 [Ghabach, Bassam; Huycke, Mark M.; Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv 111, Oklahoma City, OK 73104 USA. [Ghabach, Bassam; Huycke, Mark M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Anderson, William F.; Curtis, Rochelle E.; Lavigne, Jackie A.; Dores, Graca M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ghabach, B (reprint author), Dept Vet Affairs Med Ctr, Med Serv 111, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM bassam-ghabach@ouhsc.edu FU Department of Veterans Affairs Medical Center in Oklahoma City, OK, USA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA FX The present work was supported by the Department of Veterans Affairs Medical Center in Oklahoma City, OK, USA (to BG, MMH, GMD) and the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA (to WFA, REC, JAL, GMD). The sponsors did not directly participate in the study design, data analysis or interpretation, or preparation of the manuscript. The sponsors approved the submission of the manuscript for publication. NR 68 TC 40 Z9 47 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 4 AR R54 DI 10.1186/bcr2613 PG 9 WC Oncology SC Oncology GA 697HO UT WOS:000285504100010 PM 20653964 ER PT J AU Kohn, EA Du, ZJ Sato, M van Schyndle, CMH Welsh, MA Yang, YA Stuelten, CH Tang, BW Ju, WJ Bottinger, EP Wakefield, LM AF Kohn, Ethan A. Du, Zhijun Sato, Misako van Schyndle, Catherine M. H. Welsh, Michael A. Yang, Yu-an Stuelten, Christina H. Tang, Binwu Ju, Wenjun Bottinger, Erwin P. Wakefield, Lalage M. TI A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGF beta signaling in the mammary gland SO BREAST CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; MESENCHYMAL TRANSITION; TARGETED DISRUPTION; GENE-EXPRESSION; SMAD2; MOUSE; CANCER; MICE; DIFFERENTIATION; PROGRESSION AB Introduction: Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference-based knockdown approaches to fully ablate gene function. Here we describe a method for the generation of conditionally immortalized mammary epithelial cells with defined genetic defects, and we show how such cells can be used to investigate complex signal transduction processes using the transforming growth factor beta (TGF beta)/Smad pathway as an example. Methods: We intercrossed the previously described H-2Kb-tsA58 transgenic mouse (Immortomouse), which expresses a temperature-sensitive mutant of the simian virus-40 large T-antigen (tsTAg), with mice of differing Smad genotypes. Conditionally immortalized mammary epithelial cell cultures were derived from the virgin mammary glands of offspring of these crosses and were used to assess the Smad dependency of different biological responses to TGF beta. Results: IMECs could be propagated indefinitely at permissive temperatures and had a stable epithelial phenotype, resembling primary mammary epithelial cells with respect to several criteria, including responsiveness to TGF beta. Using this panel of cells, we demonstrated that Smad3, but not Smad2, is necessary for TGF beta-induced apoptotic, growth inhibitory and epithelial-to-mesenchymal transition responses, whereas either Smad2 or Smad3 can support TGF beta-induced invasion as long as a threshold level of total Smad is exceeded. Conclusions: The present work demonstrates the practicality and utility of generating conditionally immortalized mammary epithelial cell lines from genetically modified Immortomice for detailed investigation of complex signaling pathways in the mammary epithelium. C1 [Kohn, Ethan A.; Du, Zhijun; Sato, Misako; van Schyndle, Catherine M. H.; Welsh, Michael A.; Yang, Yu-an; Stuelten, Christina H.; Tang, Binwu; Wakefield, Lalage M.] Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Ju, Wenjun] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Bottinger, Erwin P.] Mt Sinai Sch Med, Div Nephrol, Dept Med, Charles R Bronfman Inst Personalized Med, New York, NY 10029 USA. RP Wakefield, LM (reprint author), Natl Canc Inst, Lab Canc Biol & Genet, Ctr Canc Res, 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM lw34g@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research [Z01 BC 005785] FX The authors acknowledge the expert assistance of Mario Anzano, Anthony Vieira and Hao Du in the Animal Core, and of Mengge Shan for western blots. They thank the members of the Cancer Biology of TGF beta Section and Dr Li Yang for helpful discussions and critical reading of the manuscript. The present research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research Z01 BC 005785 (LMW). NR 43 TC 13 Z9 14 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 5 AR R83 DI 10.1186/bcr2728 PG 16 WC Oncology SC Oncology GA 697IG UT WOS:000285506100018 PM 20942910 ER PT J AU McHenry, PR Sears, JC Herrick, MP Chang, P Heckman-Stoddard, BM Rybarczyk, M Chodosh, LA Gunther, EJ Hilsenbeck, SG Rosen, JM Vargo-Gogola, T AF McHenry, Peter R. Sears, James C. Herrick, Matthew P. Chang, Peggy Heckman-Stoddard, Brandy M. Rybarczyk, Megan Chodosh, Lewis A. Gunther, Edward J. Hilsenbeck, Susan G. Rosen, Jeffrey M. Vargo-Gogola, Tracy TI P190B RhoGAP has pro-tumorigenic functions during MMTV-Neu mammary tumorigenesis and metastasis SO BREAST CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; C-NEU; DUCTAL MORPHOGENESIS; ERK PHOSPHORYLATION; SIGNALING PATHWAYS; OXIDATIVE STRESS; EPITHELIAL-CELLS; KINASE-ACTIVITY; GTPASES; TRANSFORMATION AB Introduction: Rho GTPases are overexpressed and hyperactivated in human breast cancers. Deficiency of p190B RhoGAP, a major inhibitor of the Rho GTPases, inhibits mouse mammary tumor virus long terminal repeat (MMTV)-Neu/ErbB2 mammary tumor formation and progression in part through effects within the stromal environment, suggesting that p190B function is pro-tumorigenic. To further investigate the potential pro-tumorigenic actions of p190B, we examined the effects of exogenous p190B expression within the mammary epithelium on MMTV-Neu tumor formation and progression. Methods: Tetracycline (tet)-regulatable p190B transgenic mice were bred to MMTV-Neu mice, and the effects of exogenous p190B expression on tumor latency, multiplicity, growth rates, angiogenesis, and metastasis were examined. The effects of exogenous p190B expression on cell-matrix adhesion and invasion were tested using non-transformed primary mammary epithelial cells (MECs). Rho GTPase activity, oxidative stress as an indicator of reactive oxygen species (ROS) production, and downstream signaling pathways were analyzed. Results: Altered p190B expression resulted in a two-fold increase in tumor multiplicity and a three-fold increase in metastases compared to control mice indicating that exogenous p190B expression in the mammary epithelium promotes MMTV-Neu mammary tumor formation and progression. Interestingly, non-transformed primary MECs expressing exogenous p190B displayed increased adhesion to laminin and type IV collagen and formed invasive structures in a three-dimensional culture assay. Ras related C3 botulinum toxin 1 (Rac1)-GTP levels were elevated in p190B transgenic tumors whereas Ras homologous A (RhoA) and cell division cycle 42 (Cdc42)-GTP levels were not significantly altered. Rac1 activity affects production of ROS, which regulate transformation, metastasis, and oxidative stress. Protein carbonylation, which is indicative of oxidative stress, was elevated 1.75-fold in p190B transgenic tumors as compared to control tumors suggesting that exogenous p190B expression may affect Rac1-dependent ROS production. Conclusions: These studies indicate that paradoxically, p190B RhoGAP, a major inhibitor of the Rho GTPases in vitro, has pro-tumorigenic functions that enhance MMTV-Neu induced mammary tumor formation and metastasis. Furthermore, exogenous p190B expression enhances cell adhesion and invasion, which may facilitate metastasis. Rac1 activity and oxidative stress are elevated in tumors expressing exogenous p190B suggesting that p190B may promote tumorigenesis through a Rac1/ROS dependent mechanism. C1 [McHenry, Peter R.; Sears, James C.; Chang, Peggy; Rybarczyk, Megan; Vargo-Gogola, Tracy] Indiana Univ, Dept Biochem & Mol Biol, Sch Med, South Bend, IN 46617 USA. [Heckman-Stoddard, Brandy M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Herrick, Matthew P.; Rosen, Jeffrey M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Chodosh, Lewis A.] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA. [Gunther, Edward J.] Penn State Milton S Hershey Med Ctr, Dept Med, Hershey, PA 17033 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Vargo-Gogola, T (reprint author), Indiana Univ, Dept Biochem & Mol Biol, Sch Med, 1234 Notre Dame Ave, South Bend, IN 46617 USA. EM vargo-gogola.1@nd.edu OI Sears, James/0000-0003-2918-2429 FU NCI [R00CA127361]; [CA030195-22] FX These studies were funded by grants CA030195-22 to JMR and NCI Howard Temin Pathway to Independence Award R00CA127361 to TV-G. The authors thank Shirley Small for help with animal husbandry and colony management and Maria Gonzalez-Rimbau and Camilo Mohar for technical support. NR 54 TC 12 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 5 AR R73 DI 10.1186/bcr2643 PG 16 WC Oncology SC Oncology GA 697IG UT WOS:000285506100008 PM 20860838 ER PT J AU Milne, RL Gaudet, MM Spurdle, AB Fasching, PA Couch, FJ Benitez, J Perez, JIA Zamora, MP Malats, N Silva, ID Gibson, LJ Fletcher, O Johnson, N Anton-Culver, H Ziogas, A Figueroa, J Brinton, L Sherman, ME Lissowska, J Hopper, JL Dite, GS Apicella, C Southey, MC Sigurdson, AJ Linet, MS Schonfeld, SJ Freedman, DM Mannermaa, A Kosma, VM Kataja, V Auvinen, P Andrulis, IL Glendon, G Knight, JA Weerasooriya, N Cox, A Reed, MWR Cross, SS Dunning, AM Ahmed, S Shah, M Brauch, H Ko, YD Bruning, T Lambrechts, D Reumers, J Smeets, A Wang-Gohrke, S Hall, P Czene, K Liu, JJ Irwanto, AK Chenevix-Trench, G Holland, H Giles, GG Baglietto, L Severi, G Bojensen, SE Nordestgaard, BG Flyger, H John, EM West, DW Whittemore, AS Vachon, C Olson, JE Fredericksen, Z Kosel, M Hein, R Vrieling, A Flesch-Janys, D Heinz, J Beckmann, MW Heusinger, K Ekici, AB Haeberle, L Humphreys, MK Morrison, J Easton, DF Pharoah, PD Garcia-Closas, M Goode, EL Chang-Claude, J AF Milne, Roger L. Gaudet, Mia M. Spurdle, Amanda B. Fasching, Peter A. Couch, Fergus J. Benitez, Javier Arias Perez, Jose Ignacio Pilar Zamora, M. Malats, Nuria dos Santos Silva, Isabel Gibson, Lorna J. Fletcher, Olivia Johnson, Nichola Anton-Culver, Hoda Ziogas, Argyrios Figueroa, Jonine Brinton, Louise Sherman, Mark E. Lissowska, Jolanta Hopper, John L. Dite, Gillian S. Apicella, Carmel Southey, Melissa C. Sigurdson, Alice J. Linet, Martha S. Schonfeld, Sara J. Freedman, D. Michal Mannermaa, Arto Kosma, Veli-Matti Kataja, Vesa Auvinen, Paeivi Andrulis, Irene L. Glendon, Gord Knight, Julia A. Weerasooriya, Nayana Cox, Angela Reed, Malcolm W. R. Cross, Simon S. Dunning, Alison M. Ahmed, Shahana Shah, Mitul Brauch, Hiltrud Ko, Yon-Dschun Bruening, Thomas Lambrechts, Diether Reumers, Joke Smeets, Ann Wang-Gohrke, Shan Hall, Per Czene, Kamila Liu, Jianjun Irwanto, Astrid K. Chenevix-Trench, Georgia Holland, Helene Giles, Graham G. Baglietto, Laura Severi, Gianluca Bojensen, Stig E. Nordestgaard, Borge G. Flyger, Henrik John, Esther M. West, Dee W. Whittemore, Alice S. Vachon, Celine Olson, Janet E. Fredericksen, Zachary Kosel, Matthew Hein, Rebecca Vrieling, Alina Flesch-Janys, Dieter Heinz, Judith Beckmann, Matthias W. Heusinger, Katharina Ekici, Arif B. Haeberle, Lothar Humphreys, Manjeet K. Morrison, Jonathan Easton, Doug F. Pharoah, Paul D. Garcia-Closas, Montserrat Goode, Ellen L. Chang-Claude, Jenny CA GENICA Network KConFab AOCS TI Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study SO BREAST CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; OVARIAN-CANCER; CONFER SUSCEPTIBILITY; FAMILY REGISTRY; RECEPTOR; BRCA1; CHEK2-ASTERISK-1100DELC; MUTATIONS; GENOTYPE AB Introduction: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. Methods: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. Results: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. Conclusions: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified. C1 [Milne, Roger L.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Human Canc Genet Programme, Madrid 28029, Spain. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Dept Obstet & Gynecol, Dept Womens Hlth, New York, NY 10461 USA. [Spurdle, Amanda B.; Chenevix-Trench, Georgia; Holland, Helene] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Benitez, Javier] CNIO, Human Genet Grp, Human Canc Genet Programme, Madrid 28029, Spain. [Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo 33012, Spain. [Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid 28046, Spain. [dos Santos Silva, Isabel; Gibson, Lorna J.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England. [Fletcher, Olivia; Johnson, Nichola] Breakthrough Breast Canc Res Ctr, Inst Canc Res, London SW36JB, England. [Anton-Culver, Hoda; Ziogas, Argyrios] UC Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA. [Figueroa, Jonine; Brinton, Louise; Sherman, Mark E.; Garcia-Closas, Montserrat] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Sigurdson, Alice J.; Linet, Martha S.; Schonfeld, Sara J.; Freedman, D. Michal] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Mannermaa, Arto; Kosma, Veli-Matti] Univ Eastern Finland, Dept Pathol, Inst Clin Med, Kuopio 70210, Finland. [Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti] Bioctr Kuopio, Kuopio 70211, Finland. [Kataja, Vesa; Auvinen, Paeivi] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Vaasa 65130, Finland. [Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G IX5, Canada. [Andrulis, Irene L.; Glendon, Gord; Weerasooriya, Nayana] Ontario Canc Genet Network, Canc Care Ontario, Toronto, ON M5G 2C1, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med, Toronto, ON M5S 1A8, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Pathobiol, Toronto, ON M5S 1A8, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada. [Cox, Angela] Univ Sheffield, Sch Med, Dept Oncol, Inst Canc Studies,Western Bank, Sheffield S10 2TN, S Yorkshire, England. [Reed, Malcolm W. R.] Univ Sheffield, Sch Med, Dept Oncol, Acad Unit Surg Oncol,Western Bank, Sheffield S10 2TN, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Sch Med, Dept Neurosci, Acad Unit Pathol,Western Bank, Sheffield S10 2TN, S Yorkshire, England. [Dunning, Alison M.; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.; Garcia-Closas, Montserrat] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge CB1 8RN, England. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70367 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany. [Bruening, Thomas] Inst Prevent & Occupat Med German Social Accid In, D-44789 Bochum, Germany. Deutsch Krebsforschungszentrum DFKZ, D-69120 Heidelberg, Germany. [GENICA Network] Univ Bonn, Fac Med, Inst Pathol, D-53113 Bonn, Germany. [Lambrechts, Diether; Reumers, Joke] VIB & KULeuven, VRC, B-3000 Louvain, Belgium. [Smeets, Ann] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Leuven, Belgium. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89075 Ulm, Germany. [Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Liu, Jianjun; Irwanto, Astrid K.] Genome Inst Singapore, Singapore 138672, Singapore. [KConFab] Kathleen Cuningham Fdn, Peter MacCallum Canc Ctr, Consortium Res Familial Breast Canc, Melbourne, Vic 3002, Australia. [AOCS] Australian Ovarian Canc Study Grp, Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Bojensen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik] Copenhagen Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. [Bojensen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. [John, Esther M.; West, Dee W.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [John, Esther M.; West, Dee W.; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Vachon, Celine; Olson, Janet E.; Fredericksen, Zachary; Kosel, Matthew; Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Hein, Rebecca; Vrieling, Alina; Chang-Claude, Jenny] German Canc Res Ctr DFKZ, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Flesch-Janys, Dieter; Heinz, Judith] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Beckmann, Matthias W.; Heusinger, Katharina; Haeberle, Lothar] Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Ekici, Arif B.] Friedrich Alexander Univ Erlangen Nuremberg, Inst Human Genet, D-91054 Erlangen, Germany. [Humphreys, Manjeet K.; Morrison, Jonathan; Easton, Doug F.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. RP Milne, RL (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Human Canc Genet Programme, Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM rmilne@cnio.es RI Knight, Julia/A-6843-2012; Verdrengh, Evelien/H-4571-2012; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Malats, Nuria/H-7041-2015; Vrieling, Alina/A-2725-2016; Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Spurdle, Amanda/A-4978-2011 OI Cross, Simon/0000-0003-2044-1754; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Malats, Nuria/0000-0003-2538-3784; Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Dite, Gillian/0000-0002-2448-2548; Czene, Kamila/0000-0002-3233-5695; Spurdle, Amanda/0000-0003-1337-7897 FU NHMRC [251533, 209057, 504711]; National Breast Cancer Foundation; Cancer Australia [628333]; European Community [223175 (HEALTH-F2-2009-223175)]; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra Cancer; Fondo de Investigacion Santiario [PI081583, PI081120]; Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer Institute, Department of Health and Human Services, USA; National Institutes of Health, National Cancer Institute [CA-58860, CA-92044]; Lon V Smith Foundation [LVS-39420]; United States National Cancer Institute, National Institutes of Health (NIH) [RFA-CA-06-503]; Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; Kuopio University Hospital; Vaasa Central Hospital; Academy of Finland; Finnish Cancer Foundation; Yorkshire Cancer Research; Breast Cancer Campaign; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation of Medical Research, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ) Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; European Union [LSHC-CT-2003-503297]; Stichting tegen Kanker [232-2008]; Deutsche Krebshilfe e. V. [70492, 70-2892-BR I]; state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm [P. 685]; Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council Tasmania; Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Copenhagen University Hospital; Herlev Hospital; NIH [CA122340, CA116201]; Hamburg Cancer Society; German Cancer Research Center; University Hospital of Erlangen; Dr. Mildred Scheel Foundation of the Deutsche Krebshilfe; Agency for Science, Technology and Research of Singapore (A*STAR); NIH; Susan G. Komen Breast Cancer Foundation FX We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and members of the administrative staff who have enabled this work to be carried out. In particular, we thank: Charo Alonso, Toni Picornell, David Pisano, Eduardo Andres, Eva Barroso, Inaki De Blas Mendez and Primitiva Menendez (CNIO-BCS); Eileen Williams and Elaine Ryder-Mills (BBCS); Stephen Chanock (PBCS; National Cancer Institute, USA), Neonila Szeszenia-Dabrowska and Beata Peplonska (PBCS; Nofer Institute of Occupational Medicine, Lodz, Poland), Witold Zatonski (PBCS; M. Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland), Pei Chao and Michael Stagner (PBCS; Information Management Services, Sliver Spring MD, USA); Margaret McCredie (ABCFS); Jerry Reid (USRT; American Registry of Radiologic Technologists), Laura Bowen (USRT), Diane Kampa and Allison Iwan (USRT; University of Minnesota); Helena Kemilainen, Aija Parkkinen and Eija Myohanen (KBCP); Helen Cramp, Dan Connley, Sue Higham, Ian Brock, Saba Balasubramanian and Graeme Elliott (SBCS); Christina Justenhoven, Ute Hamann, Christian Baisch, Hans-Peter Fischer, Beate Pesch, Volker Harth and Sylvia Rabstein (GENICA); Gilian Peuteman, Dominiek Smeets, Sofie Van Soest and Kathleen Corthouts (LMBC); Ursula Eilber, Belinda Kaspereit and Tanya Koehler (GESBC); Heather Thorne, Eveline Niedermayr and the Family Cancer Clinics (kConFab), the kConFab team and the kConFab Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333); D Bowtell, G Chenevix-Trench, A deFazio, D Gertig, A Green, P Webb (AOCS Management Group); Mary Karaus, Catie Erding and Xianshu Wang (MCBCS); Tracy Slanger, Elke Mutschelknauss, S. Behrens, R. Birr, W. Busch, U. Eilber, B. Kaspereit, N. Knese, K. Smit and the pathology institutes (MARIE); the SEARCH team, Caroline Baynes, Craig Luccarini and Don Conroy (SEARCH).; Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175). The CNIO-BCS work was partly funded by the Red Tematica de Investigacion Cooperativa en Cancer, the Asociacion Espanola Contra Cancer and grants from the Fondo de Investigacion Santiario (PI081583 to RLM and PI081120 to JB). The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The UCIBCS is supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The ABCFS, NC-BCFR and OFBCR work was supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. JLH is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The USRT study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. The KBCP is supported by EVO funds from Kuopio University Hospital and Vaasa Central Hospital, and grants from the Academy of Finland and the Finnish Cancer Foundation. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The GENICA Network was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation of Medical Research, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The LMBC is supported by European Union Framework Programme 6 Project LSHC-CT-2003-503297 (the Cancerdegradome) and by the 'Stichting tegen Kanker' (232-2008). The GESBC was supported by the Deutsche Krebshilfe e. V. (70492), with genotyping partly funded by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P. 685).; The kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Autralia, and the Cancer Foundation of Western Australia. Financial support to the AOCS was provided by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia. ABS and GCT are Senior and Senior Principal Research Fellows, respectively, of the NHMRC. The MCCS was funded by grants from the NHMRC (251533, 209057, 504711) and was further supported by infrastructure provided by The Cancer Council Victoria. The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Copenhagen University Hospital, Herlev Hospital. The MCBCS was supported by NIH grant CA122340 and the NIH breast cancer specialized program of research excellence (CA116201). The MARIE study was supported by the Deutsche Krebshilfe e. V., grant number 70-2892-BR I, the Hamburg Cancer Society and the German Cancer Research Center. The BBCC was partly funded by the ELAN Program of the University Hospital of Erlangen. P. A. F. was funded by the Dr. Mildred Scheel Foundation of the Deutsche Krebshilfe. SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the NIH and the Susan G. Komen Breast Cancer Foundation. The Breast Cancer Association Consortium and SEARCH are funded by grants from Cancer Research UK. DFE is a Cancer Research UK Principal Research Fellow. None of these funding bodies had any role in the analysis or interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication. NR 50 TC 57 Z9 57 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 6 AR R110 DI 10.1186/bcr2797 PG 11 WC Oncology SC Oncology GA 739WJ UT WOS:000288751500021 PM 21194473 ER PT J AU Wishart, GC Azzato, EM Greenberg, DC Rashbass, J Kearins, O Lawrence, G Caldas, C Pharoah, PDP AF Wishart, Gordon C. Azzato, Elizabeth M. Greenberg, David C. Rashbass, Jem Kearins, Olive Lawrence, Gill Caldas, Carlos Pharoah, Paul D. P. TI PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer (vol 12, R1, 2010) SO BREAST CANCER RESEARCH LA English DT Correction C1 [Wishart, Gordon C.; Caldas, Carlos] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England. [Azzato, Elizabeth M.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Azzato, Elizabeth M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Greenberg, David C.; Rashbass, Jem] ECRIC, Unit C, Cambridge CB22 3AD, England. [Kearins, Olive; Lawrence, Gill] Univ Birmingham, W Midlands Canc Intelligence Unit, Birmingham B15 2TT, W Midlands, England. [Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England. [Caldas, Carlos] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Funct Breast Canc Genom Lab, Cambridge CB2 0RE, England. [Wishart, Gordon C.; Caldas, Carlos] Addenbrookes Hosp, Cambridge Biomed Res Ctr, NIHR, Cambridge CB2 2QQ, England. RP Wishart, GC (reprint author), Addenbrookes Hosp, Cambridge Breast Unit, Hills Rd, Cambridge CB2 2QQ, England. EM gordon.wishart@addenbrookes.nhs.uk NR 1 TC 2 Z9 2 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 2 AR 401 DI 10.1186/bcr2480 PG 2 WC Oncology SC Oncology GA 622AT UT WOS:000279631100008 ER PT J AU Wishart, GC Azzato, EM Greenberg, DC Rashbass, J Kearins, O Lawrence, G Caldas, C Pharoah, PDP AF Wishart, Gordon C. Azzato, Elizabeth M. Greenberg, David C. Rashbass, Jem Kearins, Olive Lawrence, Gill Caldas, Carlos Pharoah, Paul D. P. TI PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID RANDOMIZED-TRIALS; INDEX; ADJUVANT; PROGRAM AB Introduction: The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. Methods: Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation. Results: Differences in overall actual and predicted mortality were < 1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were < 1% at eight years for ECRIC (12.9% vs. 13.5%) and < 1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). Conclusions: We have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort. C1 [Wishart, Gordon C.; Caldas, Carlos] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England. [Azzato, Elizabeth M.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Azzato, Elizabeth M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Greenberg, David C.; Rashbass, Jem] ECRIC, Unit C, Cambridge CB22 3AD, England. [Kearins, Olive; Lawrence, Gill] Univ Birmingham, W Midlands Canc Intelligence Unit, Birmingham B15 2TT, W Midlands, England. [Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England. [Caldas, Carlos] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Funct Breast Canc Genom Lab, Cambridge CB2 0RE, England. [Wishart, Gordon C.; Caldas, Carlos] Addenbrookes Hosp, Cambridge Biomed Res Ctr, NIHR, Cambridge CB2 2QQ, England. RP Wishart, GC (reprint author), Addenbrookes Hosp, Cambridge Breast Unit, Hills Rd, Cambridge CB2 2QQ, England. EM gordon.wishart@addenbrookes.nhs.uk RI Caldas, Carlos/A-7543-2008 FU Pfizer Limited; Cambridge NIHR Biomedical Research Centre; National Cancer Institute; NIH FX This project was funded by an unrestricted educational grant from Pfizer Limited. Pfizer Limited had no involvement in the data collection, analysis, data interpretation, writing of the manuscript or the decision to submit this paper for publication. GCW & CC receive research funding from the Cambridge NIHR Biomedical Research Centre. PDPP is a Senior Clinical Research Fellow of Cancer Research UK. EMA is supported by the National Cancer Institute and the NIH-Cambridge Graduate Partnership Program. NR 15 TC 49 Z9 49 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 1 AR R1 DI 10.1186/bcr2464 PG 10 WC Oncology SC Oncology GA 587JD UT WOS:000276986300007 PM 20053270 ER PT J AU de Azambuja, E McCaskill-Stevens, W Francis, P Quinaux, E Crown, JPA Vicente, M Giuliani, R Nordenskjold, B Gutierez, J Andersson, M Vila, MM Jakesz, R Demol, J Dewar, J Santoro, A Lluch, A Olsen, S Gelber, RD Leo, A Piccart-Gebhart, M AF de Azambuja, Evandro McCaskill-Stevens, Worta Francis, Prudence Quinaux, Emmanuel Crown, John P. A. Vicente, Malou Giuliani, Rosa Nordenskjold, Bo Gutierez, Jorge Andersson, Michael Vila, Mireia Margeli Jakesz, Raimund Demol, Jan Dewar, Joanna Santoro, Armando Lluch, Ana Olsen, Steven Gelber, Richard D. Di Leo, Angelo Piccart-Gebhart, Martine TI The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Obesity; BMI; Adjuvant chemotherapy; Docetaxel; Node-positive ID COLON-CANCER; OBESITY; ESTROGEN; OUTCOMES; PROGNOSIS; WEIGHT; METAANALYSIS; RECURRENCE; WOMEN AB Background: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. Patients and methods: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI a parts per thousand yen 30 kg/mA(2). Results: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for non-obese and 70.0% for obese patients (HR 1.20; P = 0.041). In a multivariate model, obesity remained an independent prognostic factor for OS and DFS. Conclusions: In this study, obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed. C1 [de Azambuja, Evandro; Piccart-Gebhart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Piccart-Gebhart, Martine] ULB, B-1000 Brussels, Belgium. [McCaskill-Stevens, Worta] NCI, NIH, Bethesda, MD 20892 USA. [Francis, Prudence] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence] St Vincents Hosp, Australian New Zealand Breast Canc Trials Grp, Melbourne, Vic, Australia. [Francis, Prudence] Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Francis, Prudence] Int Breast Canc Study Grp, Bern, Switzerland. [Quinaux, Emmanuel] Int Inst Drug Dev, Louvain, Belgium. [Crown, John P. A.] St Vincents Hosp, Dublin 4, Ireland. [Vicente, Malou] Br EAST Data Ctr, Brussels, Belgium. [Giuliani, Rosa] S Camillo Forlanini Hosp, Med Oncol Unit, Rome, Italy. [Nordenskjold, Bo] Univ Sjukhuset, Linkoping, Sweden. [Gutierez, Jorge] Clin Las Condes, Santiago, Chile. [Andersson, Michael] Copenhagen Univ Hosp, Rigshosp, Finsen Ctr, Dept Oncol, Copenhagen, Denmark. [Vila, Mireia Margeli] Hosp Badalona Germans Trias & Pujol, Badalona, Spain. [Jakesz, Raimund] Univ Vienna, Gen Hosp, Vienna, Austria. [Demol, Jan] Heilig Hart Ziekenhuis, Roeselare, Belgium. [Dewar, Joanna] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Santoro, Armando] Ist Clin Humanitas, Rozzano, Italy. [Lluch, Ana] Hosp Clin Univ, Valencia, Spain. [Olsen, Steven] Sanofi Aventis, Paris, France. [Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Di Leo, Angelo] Hosp Prato, Sandro Pitigliani Med Oncol Unit, Prato, Italy. RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 125, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Francis, Prudence/J-4003-2012 FU National Health and Medical Research Council [100925, 351164] FX We thank the patients, physicians, nurses and data managers who participated in BIG 02-98 and the staff at the central offices of the cooperative groups. The following cooperative groups participated: Breast European Adjuvant Studies Team, International Breast Cancer Study Group (including Australian New Zealand Breast Cancer Trials Group), Irish Clinical Oncology Research Group, Grupo Espanol de Investigacion en Cancer de Mama, Danish Breast Cancer Cooperative Group, Swedish Breast Cancer Group, Austrian Breast and Colorectal Cancer Study Group and Grupo Oncologico Cooperative Chileno De Investigacion. The BIG 02-98 trial was supported by the National Health and Medical Research Council (project grants 100925 and 351164 to Australian New Zealand Breast Cancer Trials Group). NR 31 TC 65 Z9 66 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2010 VL 119 IS 1 BP 145 EP 153 DI 10.1007/s10549-009-0512-0 PG 9 WC Oncology SC Oncology GA 530CL UT WOS:000272566400016 PM 19731015 ER PT J AU Brinton, LA Carreon, JD Gierach, GL McGlynn, KA Gridley, G AF Brinton, Louise A. Carreon, J. Daniel Gierach, Gretchen L. McGlynn, Katherine A. Gridley, Gloria TI Etiologic factors for male breast cancer in the US Veterans Affairs medical care system database SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Male breast cancer; Medical history; Hormonal factors ID LIFE-STYLE FACTORS; RISK-FACTORS; PROSTATE-CANCER; UNITED-STATES; KLINEFELTERS-SYNDROME; SERUM ANDROGENS; MEN; EPIDEMIOLOGY; SEX; POPULATION AB The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case-control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969-1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18-100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05-1.60), obesity (1.98, 1.55-2.54), orchitis/epididymitis (1.84, 1.10-3.08), Klinefelter syndrome (29.64, 12.26-71.68), and gynecomastia (5.86, 3.74-9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59-7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81-41.62), gynecomastia (5.08, 3.21-8.03), obesity (1.91, 1.50-2.44), and orchitis/epididymitis (1.80, 1.08-3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors. C1 [Brinton, Louise A.; Carreon, J. Daniel; Gierach, Gretchen L.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. [Gridley, Gloria] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Room 5018, Rockville, MD 20852 USA. EM Brinton@nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU National Cancer Institute, National Institutes of Health FX This study was supported in part by funds from the intramural program of the National Cancer Institute, National Institutes of Health. We are indebted to Eric Boyd of IMS in Rockville, MD for assistance with computer programming. NR 42 TC 26 Z9 28 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2010 VL 119 IS 1 BP 185 EP 192 DI 10.1007/s10549-009-0379-0 PG 8 WC Oncology SC Oncology GA 530CL UT WOS:000272566400021 PM 19330525 ER PT J AU Przytycka, TM Singh, M Slonim, DK AF Przytycka, Teresa M. Singh, Mona Slonim, Donna K. TI Toward the dynamic interactome: it's about time SO BRIEFINGS IN BIOINFORMATICS LA English DT Review DE network analysis; network dynamics; interaction networks; systems biology ID PROTEIN-INTERACTION NETWORKS; TRANSCRIPTIONAL REGULATORY NETWORK; INTEGRATIVE GENOMICS APPROACH; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; INTERACTION MAP; SIGNALING PATHWAYS; DNA INTERACTIONS; IN-VIVO AB Dynamic molecular interactions play a central role in regulating the functioning of cells and organisms. The availability of experimentally determined large-scale cellular networks, along with other high-throughput experimental data sets that provide snapshots of biological systems at different times and conditions, is increasingly helpful in elucidating interaction dynamics. Here we review the beginnings of a new subfield within computational biology, one focused on the global inference and analysis of the dynamic interactome. This burgeoning research area, which entails a shift from static to dynamic network analysis, promises to be a major step forward in our ability to model and reason about cellular function and behavior. C1 [Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Res Grp Algorithms & Graph Theory Computat & Syst, Bethesda, MD 20814 USA. [Slonim, Donna K.] Tufts Univ, Dept Comp Sci, Medford, MA 02155 USA. [Slonim, Donna K.] Tufts Univ, Dept Pathol, Sch Med, Medford, MA 02155 USA. [Singh, Mona] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA. [Singh, Mona] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Res Grp Algorithms & Graph Theory Computat & Syst, 8000 Rockville Pike, Bethesda, MD 20814 USA. EM przytyck@ncbi.nlm.nih.gov FU National Institutes of Health [GM076275, LM009411, HD058880]; National Library of Medicine; National Science Foundation [CCF-0542187]; National Institutes of Health Center of Excellence [P50 GM071508] FX Intramural Research Program of the National Institutes of Health and National Library of Medicine (to T. M. P.); National Science Foundation grant CCF-0542187, National Institutes of Health grant GM076275 and National Institutes of Health Center of Excellence grant P50 GM071508 (M. S.); National Institutes of Health grants LM009411 and HD058880 (to D. K. S.). NR 180 TC 103 Z9 105 U1 5 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JAN PY 2010 VL 11 IS 1 BP 15 EP 29 DI 10.1093/bib/bbp057 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 547DS UT WOS:000273866500003 PM 20061351 ER PT J AU Bogner, C Dechow, T Ringshausen, I Wagner, M Oelsner, M Lutzny, G Licht, T Peschel, C Pastan, I Kreitman, RJ Decker, T AF Bogner, Christian Dechow, Tobias Ringshausen, Ingo Wagner, Michaela Oelsner, Madlen Lutzny, Gloria Licht, Thomas Peschel, Christian Pastan, Ira Kreitman, Robert J. Decker, Thomas TI Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl-2 expression SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE apoptosis; Bcl-2; lymphoma drugs; non-Hodgkin lymphoma; drug resistance ID CHRONIC LYMPHOPROLIFERATIVE DISORDERS; CHRONIC LYMPHOCYTIC-LEUKEMIA; RECOMBINANT IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; CYCLIN D1; COMPLETE RESPONSES; HODGKINS LYMPHOMA; IN-VIVO; RITUXIMAB; THERAPY AB P>Mantle cell lymphoma (MCL) is an incurable mature B cell proliferation, combining the unfavourable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL has an even worse prognosis and new treatment options are clearly needed. We analysed the effects of BL22, an immunotoxin composed of the Fv portion of an anti- CD22 antibody fused to a 38-kDa Pseudomonas exotoxin-A fragment on four MCL cell lines as well as on primary cells of four MCL patients. Apoptosis induction by BL22 was much more pronounced in MCL cell lines with low Bcl-2 expression (NCEB-1, JeKo-1 and JVM-2) compared to Granta-519 cells with high Bcl-2 expression. While the expression of the antiapoptotic protein Mcl-1 declined (NCEB-1, Granta-519), Bcl-2 levels remained unchanged in Granta-519 cells. However transfection of BCL2 cDNA into NCEB-1, JeKo-1 and JVM-2 cells significantly reduced BL22-mediated toxicity. Accordingly we examined the effects of Bcl-2 inactivation in Granta-519 cells using siRNA. Indeed, apoptosis induction was strongly enhanced in Granta-519 cells with silenced Bcl-2. Our results were confirmed in freshly isolated MCL-cells from patients with leukaemic MCL. We conclude that Bcl-2 expression is important for mediating resistance against the immunotoxin BL22 in MCL cells. C1 [Bogner, Christian; Dechow, Tobias; Ringshausen, Ingo; Wagner, Michaela; Oelsner, Madlen; Lutzny, Gloria; Peschel, Christian; Decker, Thomas] Tech Univ Munich, Dept Med 3, D-81675 Munich, Germany. [Licht, Thomas] Klin Oberstaufen, Oberstaufen, Germany. [Decker, Thomas] Onkol Ravensburg, Ravensburg, Germany. [Pastan, Ira; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bogner, C (reprint author), Tech Univ Munich, Dept Med 3, Ismaninger Str 15, D-81675 Munich, Germany. EM christian.bogner@lrz.tu-muenchen.de FU Jose Carreras Leukaemia fund [R05/17] FX This work was supported by the research grant R05/17 DJCLS from the Jose Carreras Leukaemia fund. NR 46 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2010 VL 148 IS 1 BP 99 EP 109 DI 10.1111/j.1365-2141.2009.07939.x PG 11 WC Hematology SC Hematology GA 533ZB UT WOS:000272864000010 PM 19821820 ER PT J AU Bates, SE Zhan, ZR Steadman, K Obrzut, T Luchenko, V Frye, R Robey, RW Turner, M Gardner, ER Figg, WD Steinberg, SM Ling, A Fojo, T To, KW Piekarz, RL AF Bates, Susan E. Zhan, Zhirong Steadman, Kenneth Obrzut, Tomasz Luchenko, Victoria Frye, Robin Robey, Robert W. Turner, Maria Gardner, Erin R. Figg, William D. Steinberg, Seth M. Ling, Alex Fojo, Tito To, Kin Wah Piekarz, Richard L. TI Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE histone deacetylase inhibitor; romidepsin; p-glycoprotein; fetal haemoglobin; T-cell lymphoma ID HISTONE DEACETYLASE INHIBITOR; ADVANCED SOLID TUMORS; SUBEROYLANILIDE HYDROXAMIC ACID; COLON-CANCER CELLS; DEPSIPEPTIDE FR901228; GENE-EXPRESSION; DIFFERENTIATING AGENTS; MYELOID-LEUKEMIA; FETAL-HEMOGLOBIN; DOWN-REGULATION AB P>Romidepsin has shown promise in the treatment of T-cell lymphomas, and so we evaluated molecular endpoints gathered from 61 patients enrolled on a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma at the National Institutes of Health. The endpoints included histone H3 acetylation and ABCB1 gene expression in peripheral blood mononuclear cells (PBMCs); ABCB1 gene expression in tumour biopsy samples; and blood fetal haemoglobin levels (HbF), all of which were increased following romidepsin treatment. The fold increase in histone acetylation in PBMCs at 24 h was weakly to moderately well correlated with the pharmacokinetic parameters C(max) and area under the curve (AUC)(last) (rho = 0 center dot 37, P = 0 center dot 03 and rho = 0 center dot 36, P = 0 center dot 03 respectively) and inversely associated with clearance (rho = -0 center dot 44; P = 0 center dot 03). Histone acetylation in PBMCs at 24 h was associated with response (P = 0 center dot 026) as was the increase in fetal haemoglobin (P = 0 center dot 014); this latter association may be due to the longer on-study duration for patients with disease response. Together, these results suggest that pharmacokinetics may be an important determinant of response to histone deacetylase inhibitors (HDIs) - the association with histone acetylation in PBMCs at 24 h is consistent with a hypothesis that potent HDIs are needed for a critical threshold of drug exposure and durable activity. C1 [Bates, Susan E.; Zhan, Zhirong; Steadman, Kenneth; Obrzut, Tomasz; Luchenko, Victoria; Frye, Robin; Robey, Robert W.; Fojo, Tito; To, Kin Wah; Piekarz, Richard L.] NIH, Med Oncol Branch, Bethesda, MD 20892 USA. [Turner, Maria] NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI Frederick, SAIC Frederick, Clin Pharmacol Program, Frederick, MD USA. [Figg, William D.] NIH, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Ling, Alex] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NIH, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI Figg Sr, William/M-2411-2016; Steadman, Kenneth/J-3883-2013; To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research FX We appreciate the contributions of Dr Wilfried Stein, Susan Booher, Christiane da Silva and Julian Bahr to this work. We also extend our gratitude to the patients enrolled on the clinical trial. This project has been 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 US Government. This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 52 TC 43 Z9 45 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2010 VL 148 IS 2 BP 256 EP 267 DI 10.1111/j.1365-2141.2009.07954.x PG 12 WC Hematology SC Hematology GA 534GJ UT WOS:000272884100008 PM 19874311 ER PT S AU Lenfant, C AF Lenfant, Claude BE Abman, SH TI Bronchopulmonary Dysplasia Introduction SO BRONCHOPULMONARY DYSPLASIA SE Lung Biology in Health and Disease LA English DT Editorial Material; Book Chapter C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 0362-3181 BN 978-1-4200-7692-9; 978-1-4200-7691-2 J9 LUNG BIOL HEALTH DIS PY 2010 VL 240 BP VII EP VIII PG 2 WC Respiratory System SC Respiratory System GA BC5UE UT WOS:000353576400001 ER PT S AU Armstrong, DL Erxleben, C White, JA AF Armstrong, David L. Erxleben, Christian White, Jody A. BE Whitaker, M TI Patch Clamp Methods for Studying Calcium Channels SO CALCIUM IN LIVING CELLS SE Methods in Cell Biology LA English DT Review; Book Chapter ID CELLS AB The patch clamp technique, which was introduced by Neher and Sakmann and their colleagues in 1981, has allowed electrophysiologists to record ion channel activity from most mammalian cell types. When well-established precautions are taken to minimize electrical and mechanical fluctuations, current transients as small as 0.5 pA and as brief as 0.5 ms can be measured reliably in cell-attached patches of plasma membrane with a polished glass pipette when it forms a giga-ohm seal with the membrane. In many cases, this is sufficient to watch individual channel proteins open and close repeatedly in real time on metabolically intact cells. No other technique currently provides a more precise or detailed view of the function and regulation of calcium channel gating. If antibiotics are added to the pipette to permeabilize the membrane underneath to small monovalent cations, thereby allowing the entire cell to be voltage-clamped without disrupting its contents, the integrated activity of all the calcium channels in the surface membrane can be measured. C1 [Armstrong, David L.; Erxleben, Christian; White, Jody A.] Natl Inst Environm Hlth Sci, Membrane Signaling Grp, Neurobiol Lab, NIH, Durham, NC USA. RP Armstrong, DL (reprint author), Natl Inst Environm Hlth Sci, Membrane Signaling Grp, Neurobiol Lab, NIH, Durham, NC USA. FU Intramural NIH HHS; NIEHS NIH HHS [Z01-ES080043] NR 16 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374841-6 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 99 BP 183 EP 197 DI 10.1016/S0091-679X(10)99007-9 PG 15 WC Cell Biology SC Cell Biology GA BSI00 UT WOS:000284504900007 PM 21035687 ER PT J AU Sosnovtsev, SV AF Sosnovtsev, Stanislav V. BE Hansman, GS Jiang, XJ Green, KY TI Proteolytic Cleavage and Viral Proteins SO CALICIVIRUSES: MOLECULAR AND CELLULAR VIROLOGY LA English DT Article; Book Chapter ID HEMORRHAGIC-DISEASE VIRUS; DEPENDENT RNA-POLYMERASE; RAY CRYSTALLOGRAPHIC STRUCTURE; CALICIVIRUS-INFECTED CELLS; COMPLETE NUCLEOTIDE-SEQUENCE; NOROVIRUS 3C-LIKE PROTEASE; NORWALK-LIKE VIRUSES; AMINO-ACID-RESIDUES; FELINE CALICIVIRUS; CAPSID PROTEIN AB Caliciviruses are icosahedral non-enveloped viruses with a positive-sense single-stranded RNA genome that does not exceed 8.6 kb. Despite its small size, the virus genome encodes a number of non-structural proteins that successfully facilitate and regulate mechanisms required for efficient virus amplification. Although caliciviruses show significant genetic diversity, they share a common protein expression strategy. Recent findings have shown that the non-structural proteins of caliciviruses are produced by autocatalytic cleavage of a polyprotein encoded by ORF1 of the virus genome. A single virus protease structurally similar to a class of viral chymotrypsin-like cysteine proteases mediates these cleavages, and in some caliciviruses, adds to a release of the virus capsid protein. The temporal regulation of viral protein synthesis relies on the specificity of the protease and may be modulated by additional viral and cellular factors. The proteolytic processing results not only in the synthesis of the mature virus proteins, but also their precursors, whose functions have yet to be determined. Almost all calicivirus proteins have been identified as components of the virus replication complexes; however, their roles in replication are not entirely understood and remain an active and crucial target of calicivirus research. C1 NIAID, Norovirus Gastroenteritis Unit, NIH, Bethesda, MD 20892 USA. RP Sosnovtsev, SV (reprint author), NIAID, Norovirus Gastroenteritis Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ss216m@nih.gov NR 147 TC 4 Z9 5 U1 0 U2 5 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-63-9 PY 2010 BP 65 EP 94 PG 30 WC Biochemistry & Molecular Biology; Virology SC Biochemistry & Molecular Biology; Virology GA BPS08 UT WOS:000279759600004 ER PT J AU Messaoudi, I Young, JE Colman, RJ Handy, AM Roth, GS Ingram, DK Mattison, JA AF Messaoudi, Ilhem Young, Jennifer E. Colman, Ricki J. Handy, April M. Roth, George S. Ingram, Donald K. Mattison, Julie A. BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Aging and the Effect of Calorie Restriction in Rhesus Monkeys SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID AGE-RELATED DECLINE; T-CELL SENESCENCE; MACAQUES MACACA-MULATTA; BLOOD MONONUCLEAR-CELLS; DIETARY RESTRICTION; IMMUNE-SYSTEM; PERIPHERAL-BLOOD; VISUAL-DISCRIMINATION; BEHAVIORAL DEFICITS; CYTOKINE PRODUCTION C1 [Young, Jennifer E.; Handy, April M.; Mattison, Julie A.] NIA, Intramural Res Program, Lab Expt Gerontol, NIH, Poolesville, MD 20837 USA. [Colman, Ricki J.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Messaoudi, Ilhem] Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Div Pathobiol & Immunol, Beaverton, OR 97006 USA. [Roth, George S.] GeroScience, Pylesville, MD 21132 USA. [Ingram, Donald K.] Louisiana State Univ, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. RP Mattison, JA (reprint author), NIA, Intramural Res Program, Lab Expt Gerontol, NIH, Poolesville, MD 20837 USA. EM mattisonj@mail.nih.gov NR 119 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 55 EP 78 DI 10.1007/978-90-481-8556-6_4 D2 10.1007/978-90-481-8556-6 PG 24 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100004 ER PT J AU Poirier, L de Cabo, R Zou, SG AF Poirier, Luc de Cabo, Rafael Zou, Sige BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Dietary Restriction and Aging in Drosophila Melanogaster SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID EXTENDS LIFE-SPAN; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; FRUIT-FLY; SACCHAROMYCES-CEREVISIAE; MEDIATES LONGEVITY; SIGNALING PATHWAY; COUNTING CALORIES; OXIDATIVE STRESS; C-ELEGANS C1 [de Cabo, Rafael; Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM decabora@mail.nih.gov; zous@grc.nia.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 89 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 79 EP 95 DI 10.1007/978-90-481-8556-6_5 D2 10.1007/978-90-481-8556-6 PG 17 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100005 ER PT J AU Wei, M Madia, F de Cabo, R Longo, VD AF Wei, Min Madia, Federica de Cabo, Rafael Longo, Valter D. BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Aging and Dietary Restriction: The Yeast Paradigm SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID LIFE-SPAN EXTENSION; SMALL-MOLECULE ACTIVATORS; SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; GENE-EXPRESSION; PROTEIN-KINASE; STRESS RESISTANCE; INCREASED RESPIRATION; OXIDATIVE DAMAGE; NADH METABOLISM C1 [Wei, Min; Madia, Federica; Longo, Valter D.] Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Davis Sch Gerontol, Los Angeles, CA 90089 USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Longo, VD (reprint author), Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Davis Sch Gerontol, Los Angeles, CA 90089 USA. EM decabora@mail.nih.gov; vlongo@usc.edu RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693; Wei, Min/0000-0002-2649-9271 NR 108 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 97 EP 109 DI 10.1007/978-90-481-8556-6_6 D2 10.1007/978-90-481-8556-6 PG 13 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100006 ER PT J AU Spangler, EL Long, J Kelley-Bell, B Miller, M Minor, RK de Cabo, R AF Spangler, Edward L. Long, Jeffrey Kelley-Bell, Bennett Miller, Marshall Minor, Robin K. de Cabo, Rafael BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Will Calorie Restriction Stave Off Age-Related Brain Dysfunction, Specifically to Learning and Memory? A Review and Critique of the Rodent Literature SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID LIFELONG DIET RESTRICTION; MAZE PERFORMANCE; NEURODEGENERATIVE DISORDERS; MOLECULAR MECHANISMS; SYNAPTIC PLASTICITY; RECEPTOR SUBUNITS; FOOD RESTRICTION; SPATIAL MEMORY; NMDA RECEPTOR; RATS C1 [Minor, Robin K.; de Cabo, Rafael] NIA, Aging Metab & Nutr Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP de Cabo, R (reprint author), NIA, Aging Metab & Nutr Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM decabora@mail.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 64 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 177 EP 190 DI 10.1007/978-90-481-8556-6_10 D2 10.1007/978-90-481-8556-6 PG 14 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100010 ER PT J AU Le Couteur, DG Sinclair, DA Cogger, VC McMahon, AC Warren, A Everitt, AV Lebel, M de Cabo, R AF Le Couteur, David G. Sinclair, David A. Cogger, Victoria C. McMahon, Aisling C. Warren, Alessandra Everitt, Arthur V. Lebel, Michel de Cabo, Rafael BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI The Aging Liver and the Effects of Long Term Caloric Restriction SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID AGE-RELATED-CHANGES; MITOCHONDRIAL OXIDATIVE STRESS; RAT SKELETAL-MUSCLE; DRUG-METABOLIZING ENZYMES; SMALL-MOLECULE ACTIVATORS; GENE-EXPRESSION PROFILE; MALE FISCHER-344 RATS; OLD RATS; ENDOTHELIAL-CELLS; MOUSE-LIVER C1 [Le Couteur, David G.; Cogger, Victoria C.; McMahon, Aisling C.; Warren, Alessandra] Univ Sydney, Concord RG Hosp, Ctr Educ & Res Ageing, ANZAC Res Inst, Sydney, NSW 2006, Australia. [Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Glenn Labs Aging Res, Boston, MA 02115 USA. [Everitt, Arthur V.] Univ Sydney, Concord RG Hosp, Ctr Educ & Res Ageing, Concord, NSW 2139, Australia. [Everitt, Arthur V.] Univ Sydney, Sch Med Sci, Discipline Physiol, Sydney, NSW 2006, Australia. [Lebel, Michel] Univ Laval, Hop Hotel Dieu Quebec, Ctr Rech Cancerol, Quebec City, PQ, Canada. [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Le Couteur, DG (reprint author), Univ Sydney, Concord RG Hosp, Ctr Educ & Res Ageing, ANZAC Res Inst, Sydney, NSW 2006, Australia. EM david.lecouteur@sydney.edu.au; arthureveritt42@bigpond.com; decabora@mail.nih.gov; arthureveritt42@bigpond.com RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 196 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 191 EP 216 DI 10.1007/978-90-481-8556-6_11 D2 10.1007/978-90-481-8556-6 PG 26 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100011 ER PT J AU Csiszar, A de Cabo, R Ungvari, Z AF Csiszar, Anna de Cabo, Rafael Ungvari, Zoltan BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Caloric Restriction and Cardiovascular Disease SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID GROWTH-FACTOR-I; NF-KAPPA-B; MITOCHONDRIAL H2O2 PRODUCTION; SKELETAL-MUSCLE MITOCHONDRIA; VASCULAR OXIDATIVE STRESS; OXYGEN SPECIES PRODUCTION; ACTIVATED PROTEIN-KINASE; LOWERS BLOOD-GLUCOSE; C-REACTIVE PROTEIN; ENOS-KNOCKOUT MICE C1 [Csiszar, Anna; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Ungvari, Z (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA. EM decabora@mail.nih.gov; zoltan_ungvari@ouhsc.cdu RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 114 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 263 EP 277 DI 10.1007/978-90-481-8556-6_15 D2 10.1007/978-90-481-8556-6 PG 15 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100015 ER PT J AU Minor, RK Anson, RM de Cabo, R AF Minor, Robin K. Anson, R. Michael de Cabo, Rafael BE Everitt, AV Rattan, SIS LeCouteur, DG DeCabo, R TI Calorie Restriction and Cancer: An Update SO CALORIE RESTRICTION, AGING AND LONGEVITY LA English DT Article; Book Chapter ID DIETARY ENERGY RESTRICTION; LIFE-SPAN; MAMMARY CARCINOGENESIS; SKIN CARCINOGENESIS; OXIDATIVE STRESS; RHESUS-MONKEYS; MICE; TUMORIGENESIS; INHIBITION; PREVENTION C1 [Minor, Robin K.; Anson, R. Michael; de Cabo, Rafael] NIA, Aging Metab & Nutr Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP de Cabo, R (reprint author), NIA, Aging Metab & Nutr Unit, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM decabora@mail.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 45 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-8555-9 PY 2010 BP 301 EP 309 DI 10.1007/978-90-481-8556-6_17 D2 10.1007/978-90-481-8556-6 PG 9 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA BOY67 UT WOS:000278069100017 ER PT J AU Jonasch, E Corn, P Pagliaro, LC Warneke, CL Johnson, MM Tamboli, P Ng, C Aparicio, A Ashe, RG Wright, JJ Tannir, NM AF Jonasch, Eric Corn, Paul Pagliaro, Lance C. Warneke, Carla L. Johnson, Marcella M. Tamboli, Pheroze Ng, Chaan Aparicio, Ana Ashe, Robynne G. Wright, John J. Tannir, Nizar M. TI Upfront, Randomized, Phase 2 Trial of Sorafenib Versus Sorafenib and Low-Dose Interferon Alfa in Patients With Advanced Renal Cell Carcinoma Clinical and Biomarker Analysis SO CANCER LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol DE hypoxia-inducible factor alpha; phosphorylated protein kinase B; receptor tyrosine kinases; vascular endothelial growth factor receptor; renal cell carcinoma; sorafenib; interferon; resistance; biomarkers ID II TRIAL; GROWTH-FACTOR; 1ST-LINE TREATMENT; CANCER; PATHWAY; BEVACIZUMAB; GEMCITABINE; COMBINATION; INHIBITION; ACTIVATION AB BACKGROUND: The objective of this study was to independently evaluate the objective response rate of sorafenib and sorafenib plus low-dose interferon-alfa 2b (IFN) as frontline therapy in patients with metastatic renal cell carcinoma (mRCC). METHODS: Untreated patients with clear cell mRCC were randomized to receive sorafenib 400 mg orally twice daily or sorafenib 400 mg orally twice daily plus subcutaneous IFN 0.5 million U (MU) twice daily. Primary endpoints included the objective response rate (ORR) and safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the predictive value of tumor tissue biomarkers. RESULTS: Eighty patients were enrolled. The median follow-up was 19.7 months (range, 0-34.2 months). The ORR was 30% (95% confidence interval [CI], 16.6%-46.5%) in the sorafenib arm and 25% (95% CI, 12.7%-41.2%) in the combination arm. The median PFS was 7.39 months in the sorafenib-alone arm (95% Cl, 5.52-9.20 months) and 7.56 months in the sorafenib plus IFN arm (95% Cl, 5.19-11.07 months), The median OS was 27.04 months in the combination arm (95% Cl, from 22.31 to not attained) and was not reached in the sorafenib arm. Toxicities were comparable in both arms. In a multivariate model, increased phosphorylated protein kinase B (pAKT) levels were associated with poorer PFS (hazard ratio, 1.04; 95% Cl, 1.00-1.08; P = .0411) and OS (hazard ratio, 1.15; 95% Cl, 1.02-1.29; P = .0173). CONCLUSIONS: The addition of low-dose IFN to sorafenib resulted in efficacy outcomes that were comparable to those achieved with sorafenib monotherapy. The current results indicated that pAKT levels may predict for clinical outcome, but further mechanistic study is required. Cancer 2010;116:57-65. (C) 2010 American Cancer Society. C1 [Jonasch, Eric; Corn, Paul; Pagliaro, Lance C.; Aparicio, Ana; Ashe, Robynne G.; Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Warneke, Carla L.; Johnson, Marcella M.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Tamboli, Pheroze] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Ng, Chaan] Dept Diagnost Radiol, Houston, TX 77030 USA. [Wright, John J.] NIH, Invest Drug Branch, Rockville, MD USA. RP Jonasch, E (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, 1515 Holcombe Blvd,Unit 1374, Houston, TX 77030 USA. EM ejonasch@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 34 TC 68 Z9 68 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2010 VL 116 IS 1 BP 57 EP 65 DI 10.1002/cncr.24685 PG 9 WC Oncology SC Oncology GA 547DA UT WOS:000273864600009 PM 19862815 ER PT B AU Ballard-Barbash, R Berrigan, D Potischman, N Dowling, E AF Ballard-Barbash, Rachel Berrigan, David Potischman, Nancy Dowling, Emily BE Berger, NA TI Obesity and Cancer Epidemiology SO CANCER AND ENERGY BALANCE, EPIDEMIOLOGY AND OVERVIEW SE Energy Balance and Cancer LA English DT Article; Book Chapter ID BODY-MASS INDEX; EPITHELIAL OVARIAN-CANCER; RENAL-CELL CARCINOMA; RECREATIONAL PHYSICAL-ACTIVITY; POSTMENOPAUSAL BREAST-CANCER; GASTRIC BYPASS-SURGERY; MILLION NORWEGIAN MEN; NON-HODGKINS-LYMPHOMA; LARGE US COHORT; PROSTATE-CANCER AB Evidence has expanded extensively in the past two decades on the association between body mass index (BMI) and other measures of body composition and weight gain with many cancers. Evidence is convincing for obesity as a risk factor for cancers of the esophagus, pancreas, colon and rectum, postmenopausal breast, endometrium, kidney, and thyroid and as probable for cancer of the gallbladder. Although not yet definitive, research is expanding rapidly for a number of other rare cancers and suggests associations for obesity and cancers of the ovary and liver and for several types of lymphoid and hematological malignancies. Associations between obesity and lung and head and neck cancers are confounded by tobacco use. An important shift in research has been the effort to examine the combined effect of overweight/obesity, physical inactivity, and poor diet. Generally, studies that have examined these combinations of factors have found much greater increases in risk among people who have these adverse health profiles. A number of mechanisms are being explored related to obesity and cancer, including changes in sex hormones, insulin-related growth factors, inflammation, immune function, and other growth factors. Data on racial/ethnic groups other than non-Hispanic whites and Asians are limited for most cancers, but suggest there may be some differences in BMI and cancer associations in some subgroups. The continued global epidemics of obesity and diabetes mellitus are likely to contribute to global increases in a number of obesity-related cancers. C1 [Ballard-Barbash, Rachel; Potischman, Nancy; Dowling, Emily] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM barbashr@mail.nih.gov; berrigad@mail.nih.org; nancy.potischman@nih.gov; emily.dowling@nih.gov NR 178 TC 10 Z9 10 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5514-2 J9 ENERG BALANCE CANCER JI Energy Balance Canc. PY 2010 VL 1 BP 1 EP 44 DI 10.1007/978-1-4419-5515-9_1 D2 10.1007/978-1-4419-5515-9 PG 44 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BRP52 UT WOS:000283332100002 ER PT B AU Xu, WH Matthews, CE AF Xu, Wanghong Matthews, Charles E. BE Berger, NA TI Obesity and Cancer in Asia SO CANCER AND ENERGY BALANCE, EPIDEMIOLOGY AND OVERVIEW SE Energy Balance and Cancer LA English DT Article; Book Chapter ID BODY-MASS-INDEX; POSTMENOPAUSAL BREAST-CANCER; HEALTH-INSURANCE-CORPORATION; SQUAMOUS-CELL CARCINOMA; RISK-FACTORS; GASTRIC CARDIA; NUTRITION TRANSITION; PHYSICAL-ACTIVITY; ENDOMETRIAL CANCER; INSULIN-RESISTANCE AB Obesity has emerged as a major public health challenge for both developed and developing countries. Like more developed countries where obesity represents an increasingly important risk factor for many cancers [1, 2], numerous studies conducted in Asian countries suggest that long-term positive energy balance that leads to elevated adiposity also contributes to the development of many chronic diseases, including the burden associated with a number of different cancer types [3-12]. While the biological mechanisms linking elevated adiposity to cancer do not appear to be markedly different in these populations, there are several unique features of the obesity-cancer association in Asia that are important to understand in relation to cancer prevention and control. First, given the population size and age structure of the larger countries in Asia, the impact of these countries on the worldwide cancer burden is now substantial and in future years will only increase. Second, there are differences in the body size and composition of Asian as compared to Caucasian adults that translate to important differences in association between obesity and cancer, relative to findings from studies conducted among Caucasian adults in the West. In this chapter we will focus on several of these features through review of the epidemiologic evidence available from selected countries in East (e.g., China, Japan, Korea, and Singapore) and Southern Asia (e.g., India, Pakistan). C1 [Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Xu, Wanghong] Fudan Univ, Dept Epidemiol, Sch Publ Hlth, Shanghai 200433, Peoples R China. RP Matthews, CE (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. EM wanghong.xu@fudan.edu.cn; charles.matthews2@nih.gov NR 137 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5514-2 J9 ENERG BALANCE CANCER JI Energy Balance Canc. PY 2010 VL 1 BP 65 EP 86 DI 10.1007/978-1-4419-5515-9_3 D2 10.1007/978-1-4419-5515-9 PG 22 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BRP52 UT WOS:000283332100004 ER PT B AU Berrigan, D McKinnon, R Dunton, G Huang, L Ballard-Barbash, R AF Berrigan, David McKinnon, Robin Dunton, Genevieve Huang, Lan Ballard-Barbash, Rachel BE Berger, NA TI Geographic and Contextual Effects on Energy Balance-Related Behaviors and Cancer SO CANCER AND ENERGY BALANCE, EPIDEMIOLOGY AND OVERVIEW SE Energy Balance and Cancer LA English DT Article; Book Chapter ID LOW-FAT MILK; CHILDRENS PHYSICAL-ACTIVITY; RESIDENTIAL SELF-SELECTION; FRANCISCO BAY AREA; BUILT ENVIRONMENT; UNITED-STATES; NEIGHBORHOOD CHARACTERISTICS; COLORECTAL-CANCER; TRAVEL BEHAVIOR; FOOD DESERTS AB This chapter concerns the analysis of geographic and contextual effects on health behaviors related to energy balance, such as diet, weight, and physical activity. We adopt a broad definition of the environment to include not just ambient exposures to toxins, meteorological conditions, or other traditional foci of environmental sciences but also the built, economic, social, and policy aspects of the environment. The chapter includes a selective review of research in this area concerning urban sprawl and obesity, built environment and physical activity, social context and energy balance, and the food environment. We then focus on ongoing challenges to advances in the analysis of contextual effects, including discussion of confounding self-selection as a barrier to causal inference, variable selection and spatial scan statistics, and the general problem of incorporating maps into research on health behavior variables. Experimental and longitudinal designs have not been applied extensively in this field and are required to examine causal associations and to quantify which types of interventions are likely to have the largest effect in specific situations. C1 [Berrigan, David] NCI, Div Canc Control & Populat Sci, NIH, Appl Res Program, Bethesda, MD 20892 USA. [Dunton, Genevieve] Univ So Calif, Dept Prevent Med, Inst Hlth Promot & Dis Prevent Res, Los Angeles, CA 90089 USA. [Huang, Lan] Univ Calif Irvine, Irvine, CA USA. [McKinnon, Robin] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. RP Berrigan, D (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Appl Res Program, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM berrigad@mail.nih.gov; robin.mckinnon@nih.gov; dunton@usc.edu; lanhuang@uci.edu; barbashr@mail.nih.gov NR 169 TC 0 Z9 0 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5514-2 J9 ENERG BALANCE CANCER JI Energy Balance Canc. PY 2010 VL 1 BP 267 EP 297 DI 10.1007/978-1-4419-5515-9_10 D2 10.1007/978-1-4419-5515-9 PG 31 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BRP52 UT WOS:000283332100011 ER PT J AU Cho, EH Whipple, RA Matrone, MA Balzer, EM Martin, SS AF Cho, Edward H. Whipple, Rebecca A. Matrone, Michael A. Balzer, Eric M. Martin, Stuart S. TI Delocalization of gamma-tubulin due to increased solubility in human breast cancer cell lines SO CANCER BIOLOGY & THERAPY LA English DT Article DE gamma-tubulin; centrosomes; microtubule nucleation; breast cancer; solubility ID SYK TYROSINE KINASE; DEPENDENT MICROTUBULE NUCLEATION; CENTROSOME AMPLIFICATION; CHROMOSOMAL INSTABILITY; MULTIDRUG-RESISTANCE; ORGANIZING CENTERS; TISSUE-SECTIONS; BRCA1; EXPRESSION; PROGRESSION AB The centrosome is the major organelle responsible for the nucleation and organization of microtubules into arrays. Recent studies demonstrate that microtubules can nucleate outside the centrosome. The molecular mechanisms controlling acentrosomal microtubule nucleation are currently poorly defined, and the function of this type of microtubule regulation in tumor cell biology is particularly unclear. since microtubule nucleation is initiated by the gamma-tubulin protein, we examined the regulation of gamma-tubulin in a panel of human breast tumor cell lines, ranging from non-tumorigenic to highly aggressive. We have identified a more dispersive subcellular localization of gamma-tubulin in aggressive breast cancer cell lines, while gamma-tubulin localization remains largely centrosomal in non-aggressive cell lines. Delocalization of gamma-tubulin occurs independently from changes in protein expression and is therefore regulated at the post-translational level. subcellular fractionation revealed that tumor cell lines show an aberrantly increased release of gamma-tubulin into a soluble cytoplasmic fraction, with the most dramatic changes observed in tumor cell lines of greater aggressiveness. extraction of soluble gamma-tubulin revealed acentrosomal incorporation of gamma-tubulin in cytoplasmic microtubules and along cell junctions. Moreover, acentrosomal delocalization of gamma-tubulin yielded resistance to colchicine-mediated microtubule collapse. These findings support a model where the solubility of gamma-tubulin can be altered through post-translational modification and provides a new mechanism for microtubule dysregulation in breast cancer. Gamma-tubulin that is delocalized from the centrosome can still clearly be incorporated into filaments, and defines a novel mechanism for tumor cells to develop resistance to microtubule-targeted chemotherapies. C1 [Cho, Edward H.; Whipple, Rebecca A.; Matrone, Michael A.; Balzer, Eric M.; Martin, Stuart S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cho, Edward H.; Matrone, Michael A.; Balzer, Eric M.; Martin, Stuart S.] Marlene & Stewart Greenebaum NCI Canc Ctr, Grad Program Life Sci, Dept Physiol, Baltimore, MD USA. RP Martin, SS (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. EM ssmartin@som.umaryland.edu RI Cho, Edward/B-3727-2012 OI Cho, Edward/0000-0002-0278-334X FU USA Medical Research and Materiel Command [BC083126, BC061047]; National Cancer Institute [1R01CA124704-01]; State of Maryland Department of Health and Mental Hygiene [CH 649 CRF] FX This work is supported by a predoctoral fellowship (BC083126) from the USA Medical Research and Materiel Command (to E.H.C.), 1R01CA124704-01 from the National Cancer Institute (to S.S.M.), a Breast Cancer Idea Award (BC061047) from the USA Medical Research and Materiel Command (to S.S.M.) and a Cigarette Restitution Fund Cancer Research Grant (CH 649 CRF) from the State of Maryland Department of Health and Mental Hygiene. NR 51 TC 7 Z9 8 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN 1 PY 2010 VL 9 IS 1 BP 66 EP 76 PG 11 WC Oncology SC Oncology GA 556GR UT WOS:000274578800012 PM 20009567 ER PT J AU Ali-Fehmi, R Chatterjee, M Ionan, A Levin, NK Arabi, H Bandyopadhyay, S Shah, JP Bryant, CS Hewitt, SM O'Rand, MG Alekseev, OM Morris, R Munkarah, A Abrams, J Tainsky, MA AF Ali-Fehmi, Rouba Chatterjee, Madhumita Ionan, Alexei Levin, Nancy K. Arabi, Haitham Bandyopadhyay, Sudeshna Shah, Jay P. Bryant, Christopher S. Hewitt, Stephen M. O'Rand, Michael G. Alekseev, Oleg M. Morris, Robert Munkarah, Adnan Abrams, Judith Tainsky, Michael A. TI Analysis of the expression of human tumor antigens in ovarian cancer tissues SO CANCER BIOMARKERS LA English DT Article DE Ovarian cancer; phage display; tissue biomarker; humoral immune response; tissue microarray ID BREAST-CANCER; IMMUNE-RESPONSE; CELL-CYCLE; PROTEIN; HER-2/NEU; GENES; CARCINOMAS; ANTIBODIES; MUTATION; COMPLEX AB Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression. C1 [Ali-Fehmi, Rouba; Arabi, Haitham; Bandyopadhyay, Sudeshna; Tainsky, Michael A.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Chatterjee, Madhumita; Ionan, Alexei; Levin, Nancy K.; Tainsky, Michael A.] Wayne State Univ, Karmanos Canc Inst, Program Mol Biol & Human Genet, Detroit, MI 48201 USA. [Ali-Fehmi, Rouba; Shah, Jay P.; Bryant, Christopher S.; Morris, Robert; Munkarah, Adnan] Wayne State Univ, Sch Med, Div Gynecol Oncol, Detroit, MI 48201 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [O'Rand, Michael G.; Alekseev, Oleg M.] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Abrams, Judith] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. RP Tainsky, MA (reprint author), Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. EM tainskym@karmanos.org OI Arabi, Haitham/0000-0001-7605-3852; Hewitt, Stephen/0000-0001-8283-1788 FU National Institutes of Health (NIH) [R21/R33-CA100740, U01-117748]; The Michigan Life Science Corridor Fund [085P300470]; Eunice Kennedy Shriver NICHD [U54 (HD35041)] FX We acknowledge Natalie Victor Shirley for coordinating the tissue samples, the Karmanos Cancer Institute Gynecologic Oncology support staff for assisting in identifying eligible cases and consenting them to the study and the Gynecologic Oncology Group Tissue Bank (GOG), which is funded by the National Cancer Institute. We thank Barbara Pruetz for performing immunohistochemical staining for all the biomarkers in tissue sections obtained from OVCA patients. This project was supported by funds from the Gail Purtan Ovarian Cancer Research Fund, and by grants from National Institutes of Health (NIH), R21/R33-CA100740 and U01-117748, and The Michigan Life Science Corridor Fund (085P300470). Production of anti-NASP antibodies was funded by a grant to MGO from the Eunice Kennedy Shriver NICHD cooperative agreement [U54 (HD35041)] as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. NR 49 TC 16 Z9 16 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2010 VL 6 IS 1 BP 33 EP 48 DI 10.3233/CBM-2009-0117 PG 16 WC Oncology SC Oncology GA 556PQ UT WOS:000274603900004 PM 20164540 ER PT J AU Baird, CL Fischer, CJ Pefaur, NB Miller, KD Kagan, J Srivastava, S Rodland, KD AF Baird, Cheryl L. Fischer, Christopher J. Pefaur, Noah B. Miller, Keith D. Kagan, Jacob Srivastava, Sudhir Rodland, Karin D. TI Developing recombinant antibodies for biomarker detection SO CANCER BIOMARKERS LA English DT Article DE Yeast surface display; phage display; affinity maturation; recombinant immune library; recombinant non-immune library; directed molecular evolution ID YEAST SURFACE-DISPLAY; AFFINITY HUMAN-ANTIBODIES; DIRECTED EVOLUTION; BOTULINUM NEUROTOXIN; MOLECULAR EVOLUTION; RANDOM MUTAGENESIS; LIBRARIES; PHAGE; MATURATION; ANTIGEN AB Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (e. g., yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (< 10 nM) more quickly than other methods. Non-immune libraries provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays. C1 [Baird, Cheryl L.; Miller, Keith D.; Rodland, Karin D.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Fischer, Christopher J.] Chris Fischer LLC, Pasco, WA USA. [Pefaur, Noah B.] Novo Nordisk Inflammat Res Ctr, Dept Target Discovery & Validat, Seattle, WA USA. [Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Baird, CL (reprint author), Pacific NW Natl Lab, Richland, WA 99352 USA. EM cheryl.baird@pnl.gov RI Baird, Cheryl/F-6569-2011 FU National Cancer Institute [Y1-CN-5014]; United States Department of Energy (LaboratoryDirected Research and Development) FX This work was supported by the Early Detection Research Network of the National Cancer Institute by cooperative agreement Y1-CN-5014 and by the United States Department of Energy (LaboratoryDirected Research and Development). NR 44 TC 2 Z9 2 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2010 VL 6 IS 5-6 BP 271 EP 279 DI 10.3233/CBM-2009-0144 PG 9 WC Oncology SC Oncology GA 661SY UT WOS:000282749600005 PM 20938087 ER PT J AU Mirabello, L Garcia-Closas, M Cawthon, R Lissowska, J Brinton, LA Peplonska, B Sherman, ME Savage, SA AF Mirabello, Lisa Garcia-Closas, Montserrat Cawthon, Richard Lissowska, Jolanta Brinton, Louise A. Peplonska, Beata Sherman, Mark E. Savage, Sharon A. TI Leukocyte telomere length in a population-based case-control study of ovarian cancer: a pilot study SO CANCER CAUSES & CONTROL LA English DT Article DE Ovarian cancer; Telomere length; Case-control study; Epidemiology ID PREDISPOSITION FACTOR; RISK; DYSFUNCTION; CHEMOTHERAPY; CARCINOMA AB Telomeres are structures at chromosome ends that contribute to maintaining genomic integrity. Telomere shortening with repeated cell divisions may lead to genomic instability and carcinogenesis. Studies suggest that shorter telomeres in constitutional DNA are associated with bladder, breast, lung, and renal cancer. Ovarian cancer tissues also have shortened telomeres and increased telomerase activity, suggesting that telomere abnormalities may be related to ovarian cancer. We investigated leukocyte telomere length in 99 women with serous ovarian adenocarcinoma and 100 age-matched cancer-free controls enrolled in a population-based case-control study. Cases tended to have shorter telomeres than controls (P (wilcoxon) = 0.002). Compared to subjects with telomere lengths in the longest tertile, those in the middle and shortest tertiles showed respective age-adjusted odds ratios (95% confidence intervals) of 2.69 (1.23-5.88) and 3.39 (1.54-7.46) (P (trend) = 0.002). Strongest associations were found for subjects with poorly differentiated carcinomas (OR = 4.89, 95% CI 1.93-12.34). This study shows that short leukocyte telomeres are associated with serous ovarian adenocarcinoma. These findings should be confirmed in large, prospective studies. C1 [Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Mirabello, Lisa; Garcia-Closas, Montserrat; Brinton, Louise A.; Sherman, Mark E.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cawthon, Richard] Univ Utah, Dept Human Genet, Salt Lake City, UT 84132 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Room 7018,6120 Execut Blvd, Rockville, MD 20892 USA. EM savagesh@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Savage, Sharon/B-9747-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Savage, Sharon/0000-0001-6006-0740; Lissowska, Jolanta/0000-0003-2695-5799 FU NIH [CA82838]; National Cancer Institute; Division of Cancer Epidemiology and Genetics; Center for Cancer Research; American Cancer Society [RSG-00-061-04-CCE] FX We are grateful to Drs. Mark H. Greene and Phuong Mai of the National Cancer Institute for helpful comments. We thank Neonila Szeszenia-Dabrowska from the Nofer Institute of Occupational Medicine, Lodz, Poland and Witold Zatonski from the Sklodowska-Curie Institute of Oncology and Cancer Center, Warsaw, Poland for their contributions to the study design and conduct; Anita Soni (Westat, Rockville, MD) for her work on study management for the Polish ovarian cancer study; Pei Chao (IMS, Silver Spring, MD) for her work on data and sample management; and physicians, nurses, interviewers and study participants for their efforts during field work. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Center for Cancer Research; National Institutes of Health (grant CA82838); and American Cancer Society (Grant RSG-00-061-04-CCE). NR 26 TC 42 Z9 42 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2010 VL 21 IS 1 BP 77 EP 82 DI 10.1007/s10552-009-9436-6 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543FB UT WOS:000273555400009 PM 19784860 ER PT J AU Coombs, NJ Cronin, KA Taylor, RJ Freedman, AN Boyages, J AF Coombs, Nathan J. Cronin, Kathleen A. Taylor, Richard J. Freedman, Andrew N. Boyages, John TI The impact of changes in hormone therapy on breast cancer incidence in the US population SO CANCER CAUSES & CONTROL LA English DT Article DE Breast neoplasms; Hormone replacement therapy; Incidence; Epidemiology ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; INITIATIVE RANDOMIZED-TRIAL; REPLACEMENT THERAPY; UNITED-STATES; RISK; MAMMOGRAPHY AB This study combines population changes in hormone therapy (HT) use with reported relative risks to estimate directly the impact of reductions in HT use on US breast cancer incidence. Using breast cancer incidence rates and prevalence estimates of HT use, the breast cancer incidence in HT users and non-users was derived. Attributable fraction calculations used risk data from the Million Women Survey (MWS), Collins' meta-analysis (CMA), and the initial or later data from the Women's Health Initiative (WHI) study. Between 2000 and 2005, HT use fell from 25.0 to 11.3%. The reported breast cancer incidence (in women aged 40-79) fell 8.8%. Derived incidence rates among non-users of HT remained unchanged (MWS or later WHI data) or slightly lower (initial WHI and CMA data), suggesting reductions in incidence are almost entirely (MWS or later WHI data) or partially (initial WHI or CMA data) due to reduced HT use. Changes in reported breast cancer incidence may be partially or largely explained by changes in HT use in the US population. C1 [Coombs, Nathan J.; Boyages, John] NSW Breast Canc Inst, Sydney, NSW, Australia. [Coombs, Nathan J.] Great Western Hosp, Swindon, Wilts, England. [Cronin, Kathleen A.; Freedman, Andrew N.] NCI, Bethesda, MD 20892 USA. [Taylor, Richard J.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia. [Taylor, Richard J.] Univ New S Wales, Sch Publ Hlth & Community Med, Sydney, NSW 2052, Australia. RP Boyages, J (reprint author), NSW Breast Canc Inst, Sydney, NSW, Australia. EM terrigalb@gmail.com; john.boyages@bci.org.au NR 30 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2010 VL 21 IS 1 BP 83 EP 90 DI 10.1007/s10552-009-9437-5 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543FB UT WOS:000273555400010 PM 19795215 ER PT J AU Kilfoy, BA Zheng, TZ Lan, Q Han, XS Holford, T Hein, DW Qin, Q Leaderer, B Morton, LM Yeager, M Boyle, P Zhao, P Chanock, S Rothman, N Zhang, YW AF Kilfoy, Briseis A. Zheng, Tongzhang Lan, Qing Han, Xuesong Holford, Theodore Hein, David W. Qin, Qin Leaderer, Brian Morton, Lindsay M. Yeager, Meredith Boyle, Peter Zhao, Ping Chanock, Stephen Rothman, Nathaniel Zhang, Yawei TI Genetic variation in N-acetyltransferases 1 and 2, cigarette smoking, and risk of non-Hodgkin lymphoma SO CANCER CAUSES & CONTROL LA English DT Article DE Non-Hodgkin lymphoma; NAT1; NAT2; Smoking; Single nucleotide polymorphisms ID NAT2 SLOW ACETYLATION; UNITED-STATES; BLADDER-CANCER; BREAST-CANCER; MULTIPLE-MYELOMA; TOBACCO-SMOKE; EPIDEMIOLOGY; POLYMORPHISMS; WOMEN; SUSCEPTIBILITY AB Cigarette smoke contains many carcinogens that are metabolically activated through xenobiotic metabolism by phase I and II enzymes, including N-acetyltransferases 1 and 2 (NAT1 and NAT2). We investigated non-Hodgkin lymphoma risk in general and by subtype in relation to NAT1 and NAT2 genotypes and cigarette smoking in a population-based case-control study in Connecticut. Of the 535 controls, 53.1% reported ever smoking, and of the 461 cases, 55.7% reported ever smoking. We found a two-fold increased risk of T-cell lymphoma among those possessing the NAT1*10 genotype compared to those with other NAT1 genotypes; including an OR of 2.0 (95% CI: 1.0-2.4) for those heterozygous or homozygous for NAT1*10 genotypes. Rapid acetylator NAT2 phenotype increased the risk of both T-cell lymphoma (OR = 3.2; 95% CI: 1.1-9.5) and marginal zone lymphoma (OR = 3.0; 95% CI: 1.0-8.7), though these results were based on a small number of cases. When smoking status and risk of NHL was stratified by NAT1 and NAT2 genotypes, an increased risk of NHL overall was observed in current (OR = 1.7; 95% CI: 1.2-2.4) smokers without the NAT1*10 genotype but not among smokers with the NAT1*10 genotype (p-interaction < 0.01). No association between history of cigarette smoking and risk of NHL overall was observed with any NAT2 genotype. Our results present modest evidence that acetylation rate is associated with risk of NHL for specific subtypes and that the NAT1*10 genotype is an "at-risk" allele. Additionally, our results suggest that the relationship between NHL and smoking status may be modified by common genetic variation in NAT1 but not NAT2. We conclude that these findings require replication in larger studies and ultimately in pooled analyses. C1 [Kilfoy, Briseis A.; Lan, Qing; Morton, Lindsay M.; Yeager, Meredith; Chanock, Stephen; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Kilfoy, Briseis A.; Zheng, Tongzhang; Han, Xuesong; Holford, Theodore; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Hein, David W.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Hein, David W.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Qin, Qin] Univ So Maine, Ctr Toxicol & Environm Hlth, Portland, ME 04103 USA. [Boyle, Peter] Int Agcy Res Canc, F-69372 Lyon, France. [Zhao, Ping] Natl Canc Inst, Beijing, Peoples R China. RP Kilfoy, BA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. EM kilfoyb@mail.nih.gov; yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Hein, David/A-9707-2008; Boyle, Peter/A-4380-2014; Morton, Lindsay/B-5234-2015 OI Boyle, Peter/0000-0001-6251-0610; Morton, Lindsay/0000-0001-9767-2310 FU National Cancer Institute (NCI) [CA62006]; National Institutes of Health (NIH), NCI [1D43TW007864-01, 1D43TW008323-01] FX This project is supported by grant CA62006 from the National Cancer Institute (NCI), the Intramural Research Program of the National Institutes of Health (NIH), NCI, and Fogarty training grants 1D43TW007864-01 and 1D43TW008323-01 from NIH. NR 47 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2010 VL 21 IS 1 BP 127 EP 133 DI 10.1007/s10552-009-9442-8 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543FB UT WOS:000273555400015 PM 19809881 ER PT J AU Laiyemo, AO Kamangar, F Marcus, PM Taylor, PR Virtamo, J Albanes, D Stolzenberg-Solomon, RZ AF Laiyemo, Adeyinka O. Kamangar, Farin Marcus, Pamela M. Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius Stolzenberg-Solomon, Rachael Z. TI Atrophic gastritis and the risk of incident colorectal cancer SO CANCER CAUSES & CONTROL LA English DT Article DE Serum pepsinogen; Atrophic gastritis; Colorectal cancer ID PROTON-PUMP INHIBITOR; HELICOBACTER-PYLORI; DIETARY FACTORS; BETA-CAROTENE; SERUM GASTRIN; PEPSINOGEN-I; MALE SMOKERS; FOLLOW-UP; NEOPLASIA; COLON AB Previous studies evaluating whether risk factors for gastric cancer are also associated with colorectal cancer (CRC) have shown inconsistent results. We prospectively examined the association of atrophic gastritis, a pre-malignant condition for gastric cancer and long-term sequelae common to many exposure factors, and the risk of incident CRC. A total of 20,928 Finnish male smokers, aged 50-69, who were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) had serum pepsinogen I (SPGI) levels measured. Participants with low SPGI levels (< 25 mu g/l; n = 1,665) were invited for gastroscopy. Of these, 1,059 (63.6%) participants underwent gastroscopy and atrophic gastritis was histologically confirmed in 1,006 (95.0%) participants. We used Cox proportional hazards regression to evaluate the risk of incident CRC. During a mean follow-up of 11.3 years (236,258 person-years), 425 incident CRCs were diagnosed. The incidence rates were 1.82, 1.48, and 1.82 per 1,000 person-years of follow-up for participants with normal SPGI (a parts per thousand yen25 mu g/l), low SPGI, and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal SPGI, there was no increased risk of CRC among subjects with low SPGI (Adjusted Hazard Ratio (HR) = 0.71; 95% CI: 0.47-1.05) and among those with histologically confirmed atrophic gastritis (Adjusted HR = 0.86; 95% CI: 0.55-1.34). Atrophic gastritis is not associated with an increased risk of colorectal cancer among male smokers. C1 [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.; Marcus, Pamela M.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Kamangar, Farin; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. RP Laiyemo, AO (reprint author), NCI, Canc Prevent Fellowship Program, Biometry Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3131, Bethesda, MD 20892 USA. EM laiyemoa@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Institutes of Health, Division of Cancer Epidemiology and Genetics; National Cancer Institute; Division of Cancer Prevention, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and the Division of Cancer Prevention, National Institutes of Health, Department of Health and Human Services. The funding agency had a role in the design and reporting of the study and in the decision to submit the manuscript for publication and approved the final version of the manuscript. NR 34 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2010 VL 21 IS 1 BP 163 EP 170 DI 10.1007/s10552-009-9446-4 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543FB UT WOS:000273555400019 PM 19838812 ER PT J AU Kummar, S Gutierrez, ME Gardner, ER Figg, WD Melillo, G Dancey, J Sausville, EA Conley, BA Murgo, AJ Doroshow, JH AF Kummar, Shivaani Gutierrez, Martin E. Gardner, Erin R. Figg, William D. Melillo, Giovanni Dancey, Janet Sausville, Edward A. Conley, Barbara A. Murgo, Anthony J. Doroshow, James H. TI A phase I trial of UCN-01 and prednisone in patients with refractory solid tumors and lymphomas SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Cyclin-dependent kinase inhibitor; Protein kinase C; Phase I; Combination chemotherapy; UCN-01; Prednisone ID PROTEIN-KINASE-C; INHIBITOR 7-HYDROXYSTAUROSPORINE; CLINICAL-PHARMACOLOGY; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY; CELL LINES; CANCER; COMBINATION; CONSORTIUM; CISPLATIN AB UCN-01 potently inhibits protein kinase C, phosphatidylinositide-dependent kinase-1, and checkpoint kinase 1, which are involved in regulating cell cycle progression. We designed a phase I study to determine the maximum tolerated dose (MTD) of UCN-01 with prednisone in patients with advanced malignancies. UCN-01 was administered as a continuous intravenous infusion over 72 h in cycle 1 and 36 h in subsequent cycles. Prednisone was given orally at 60 mg/m(2) per day for five consecutive days within each 28-day cycle. Standard dose escalation was employed, and MTD was defined as the dose at which no more than one of six patients experienced a dose-limiting toxicity (DLT). Plasma pharmacokinetics of UCN-01 were assessed. Fifteen patients received a total of 55 courses of treatment. The MTD and the recommended phase II dose of UCN-01 in this combination is 72 mg/m(2) total dose over 72 h for cycle 1 followed by 36 mg/m(2) per cycle over 36 h. All patients experienced hyperglycemia but responded to insulin treatment. Hypophosphatemia was a DLT in two patients. There were no cumulative toxicities. No objective responses were observed, but five patients had stable disease, including two patients with lymphoid malignancies who had prolonged disease stabilizations. UCN-01 has a long terminal half-life and low clearance; there was wide inter-patient variability in peak concentrations. UCN-01 can be safely administered in combination with prednisone without unacceptable toxicity. The prolonged stable disease in two patients with lymphoid malignancies is a proof of principle for the evaluation of cyclin-dependent kinase inhibitors in oncology. C1 [Kummar, Shivaani; Gutierrez, Martin E.; Figg, William D.; Conley, Barbara A.; Murgo, Anthony J.; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Dancey, Janet; Sausville, Edward A.; Murgo, Anthony J.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Gardner, Erin R.; Melillo, Giovanni] Sci Applicat Int Corp Frederick Inc, NCI, Frederick, MD USA. RP Kummar, S (reprint author), NCI, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Center for Cancer Research FX This paper was written with support from the Division of Cancer Treatment and Diagnosis and the Center for Cancer Research of the National Cancer Institute. This project has been funded 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 US Government. This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We would like to thank Gina Uhlenbrauck, SAIC-Frederick, Inc. for editorial assistance in the preparation of this manuscript. NR 28 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2010 VL 65 IS 2 BP 383 EP 389 DI 10.1007/s00280-009-1154-y PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 521TW UT WOS:000271948300021 PM 19894051 ER PT J AU Prentice, RL Huang, Y Hinds, DA Peters, U Cox, DR Beilharz, E Chlebowski, RT Rossouw, JE Caan, B Ballinger, DG AF Prentice, Ross L. Huang, Ying Hinds, David A. Peters, Ulrike Cox, David R. Beilharz, Erica Chlebowski, Rowan T. Rossouw, Jacques E. Caan, Bette Ballinger, Dennis G. TI Variation in the FGFR2 Gene and the Effect of a Low-Fat Dietary Pattern on Invasive Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; MODIFICATION TRIAL; SUSCEPTIBILITY; RISK; TRANSCRIPTION; DESIGN; CELLS; YY1 AB Background: The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects. Methods: All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype. Results: Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P >= 0.18). However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (>= 36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1., and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41.], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors. Conclusion: Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene. Cancer Epidemiol Biomarkers Prev; 19(1); 74-9. (C)2010 AACR. C1 [Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Hinds, David A.; Cox, David R.; Beilharz, Erica; Ballinger, Dennis G.] Perlegen Sci Inc, Mountain View, CA USA. [Chlebowski, Rowan T.] Harbor Univ Calif, Los Angeles Res & Educ Inst, Torrance, CA USA. [Rossouw, Jacques E.] NIH, Bethesda, MD 20892 USA. [Caan, Bette] Kaiser Permanente Div Res, Oakland, CA USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. EM rprentic@fhcrc.org FU National Heart, Lung, and Blood Institute, NIH; U.S. Department of Health and Human Services [HHSN268200764314C, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, 44221]; National Cancer Institute [CA53996] FX National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services (contracts HHSN268200764314C, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, and 44221). Clinical Trials Registration: ClinicalTrials.gov identifier: NCT00000611. R.L. Prentice was partially supported by grant CA53996 from the National Cancer Institute. NR 21 TC 14 Z9 16 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 74 EP 79 DI 10.1158/1055-9965.EPI-09-0663 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700009 PM 20056625 ER PT J AU Zhang, LP Tang, XJ Rothman, N Vermeulen, R Ji, ZY Shen, M Qiu, CY Guo, WH Liu, SW Reiss, B Freeman, LB Ge, YC Hubbard, AE Hua, M Blair, A Galvan, N Ruan, XL Alter, BP Xin, KX Li, SH Moore, LE Kim, S Xie, YX Hayes, RB Azuma, M Hauptmann, M Xiong, J Stewart, P Li, LY Rappaport, SM Huang, HL Fraumeni, JF Smith, MT Lan, Q AF Zhang, Luoping Tang, Xiaojiang Rothman, Nathaniel Vermeulen, Roel Ji, Zhiying Shen, Min Qiu, Chuangyi Guo, Weihong Liu, Songwang Reiss, Boris Freeman, Laura Beane Ge, Yichen Hubbard, Alan E. Hua, Ming Blair, Aaron Galvan, Noe Ruan, Xiaolin Alter, Blanche P. Xin, Kerry X. Li, Senhua Moore, Lee E. Kim, Sungkyoon Xie, Yuxuan Hayes, Richard B. Azuma, Mariko Hauptmann, Michael Xiong, Jun Stewart, Patricia Li, Laiyu Rappaport, Stephen M. Huang, Hanlin Fraumeni, Joseph F., Jr. Smith, Martyn T. Lan, Qing TI Occupational Exposure to Formaldehyde, Hematotoxicity, and Leukemia-Specific Chromosome Changes in Cultured Myeloid Progenitor Cells SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LYMPHOHEMATOPOIETIC MALIGNANCIES; INHALATION EXPOSURE; WORKERS; MORTALITY; BENZENE; BLOOD; LYMPHOCYTES; EMBALMERS; RATS AB There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing, and other industries. Epidemiologic studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on the ability of formaldehyde to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a mariner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures. Cancer Epidemiol Biomarkers Prev, 19(1); 80-8. (C)2010 AACR. C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Zhang, Luoping; Ji, Zhiying; Guo, Weihong; Hubbard, Alan E.; Galvan, Noe; Xin, Kerry X.; Azuma, Mariko; Rappaport, Stephen M.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Hua, Ming; Ruan, Xiaolin; Li, Senhua; Xie, Yuxuan; Li, Laiyu; Huang, Hanlin] Guangdong Poisoning Control Ctr, Guangzhou, Guangdong, Peoples R China. [Vermeulen, Roel; Reiss, Boris] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Liu, Songwang] Qiaotou Hosp, Dongguan, Peoples R China. [Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Dongguan, Guangdong, Peoples R China. [Kim, Sungkyoon; Rappaport, Stephen M.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Room 8010, Rockville, MD 20852 USA. EM luoping@berkeley.edu; qingl@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; Beane Freeman, Laura/C-4468-2015; OI Vermeulen, Roel/0000-0003-4082-8163; Beane Freeman, Laura/0000-0003-1294-4124; Hayes, Richard/0000-0002-0918-661X FU NIH (National Cancer Institute); National Institute of Environmental Health Sciences [R01ES017452, P42ES004705]; Northern California Center for Occupational and Environmental Health; Department of Science and Technology of Guangdong Province, China [2007A050100004] FX This study was supported in part by the Intramural Research Program of the NIH (National Cancer Institute) and by the National Institute of Environmental Health Sciences grants R01ES017452 (L. Zhang) and P42ES004705 (M.T. Smith). Additional support was provided by the Northern California Center for Occupational and Environmental Health and Department of Science and Technology of Guangdong Province, China, grant 2007A050100004. NR 54 TC 68 Z9 72 U1 1 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 80 EP 88 DI 10.1158/1055-9965.EPI-09-0762 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700010 PM 20056626 ER PT J AU Reichman, ME Altekruse, S Li, CI Chen, VW Deapen, D Potts, M Wu, XC Morrell, D Hafterson, J Phipps, AI Harlan, LC Ries, LG Edwards, BK AF Reichman, Marsha E. Altekruse, Sean Li, Christopher I. Chen, Vivien W. Deapen, Dennis Potts, Mary Wu, Xiao-Cheng Morrell, Donna Hafterson, Jennifer Phipps, Amanda I. Harlan, Linda C. Ries, Lynn G. Edwards, Brenda K. TI Feasibility Study for Collection of HER2 Data by National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program Central Cancer Registries SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR RECEPTOR-2; INVASIVE BREAST-CANCER; AMPLIFICATION; ESTROGEN; WOMEN AB The clinical importance of human epidermal growth factor receptor-2 (HER2) in breast cancer is now clearly established, given that expression of this tumor marker is used to guide therapy and as a prognostic indicator. Despite its now routine evaluation in breast cancer patients, population-based data are lacking because information on HER2 status is not routinely collected in the majority of population-based cancer registries. We assessed the feasibility of collecting HER2 data and its completeness in three registries in the Surveillance Epidemiology and End Results (SEER) Program. Among a sample of invasive first primary breast cancer patients diagnosed between June and December 2007, HER2 tests had been done on 96.5% (n = 522), and test results were available for 95.2% (n = 515) of patients. The majority of HER2 tests were performed by immunohistochemistry alone (50.9%), 35.3% by both immunohistochemistry and fluorescence in situ hybridization (FISH), and 11.8% of tests by FISH alone. As a result of these findings, SEER registries will collect HER2 data on all invasive breast cancer patients as an optional data element for those diagnosed in 2009 and HER2 will likely be a required data element for these patients in 2010. Cancer Epidemiol Biomarkers Prev; 19(1); 144-7, (C)2010 AACR. C1 [Reichman, Marsha E.; Altekruse, Sean; Ries, Lynn G.; Edwards, Brenda K.] NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Rockville, MD 20852 USA. [Harlan, Linda C.] NCI, DCCPS, Appl Res Program, Rockville, MD 20852 USA. [Li, Christopher I.; Potts, Mary; Hafterson, Jennifer; Phipps, Amanda I.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chen, Vivien W.; Wu, Xiao-Cheng] Louisiana Tumor Registry, New Orleans, LA USA. [Deapen, Dennis; Morrell, Donna] Los Angeles Surveillance Epidemiol & End Results, Los Angeles, CA USA. RP Reichman, ME (reprint author), NCI, Div Canc Control & Populat Sci, Surveillance Res Program, 6130 Execut Blvd,Suite 6138, Rockville, MD 20852 USA. EM ReichmaM@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 144 EP 147 DI 10.1158/1055-9965.EPI-09-0807 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700017 PM 20056633 ER PT J AU Xue, XN Gange, SJ Zhong, Y Burk, RD Minkoff, H Massad, LS Watts, DH Kuniholm, MH Anastos, K Levine, AM Fazzari, M D'Souza, G Plankey, M Palefsky, JM Strickler, HD AF Xue, Xiaonan Gange, Stephen J. Zhong, Ye Burk, Robert D. Minkoff, Howard Massad, L. Stewart Watts, D. Heather Kuniholm, Mark H. Anastos, Kathryn Levine, Alexandra M. Fazzari, Melissa D'Souza, Gypsyamber Plankey, Michael Palefsky, Joel M. Strickler, Howard D. TI Marginal and Mixed-Effects Models in the Analysis of Human Papillomavirus Natural History Data SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENERALIZED ESTIMATING EQUATIONS; LONGITUDINAL DATA-ANALYSIS; CORRELATED BINARY DATA; COMMON OUTCOMES; RELATIVE RISK; WOMEN; INFECTION; COHORT; REGRESSION; DESIGN AB Human papillomavirus (HPV) natural history has several characteristics that, at least from a statistical perspective, are not often encountered elsewhere in infectious disease and cancer research. There are, for example, multiple HPV types, and infection by each HPV type may be considered separate events. Although concurrent infections are common, the prevalence, incidence, and duration/persistence of each individual HPV can be separately measured. However, repeated measures involving the same subject tend to be correlated. The probability of detecting any given HPV type, for example, is greater among individuals who are currently positive for at least one other HPV type. Serial testing for HPV over time represents a second form of repeated measures. Statistical inferences that fail to take these correlations into account would be invalid. However, methods that do not use all the data would be inefficient. Marginal and mixed-effects models can address these issues but are not frequently used in HPV research. The current Study provides an overview of these methods and then uses HPV data from a cohort of HIV-positive women to illustrate how they may be applied, and compare their results. The findings show the greater efficiency of these models compared with standard logistic regression and Cox models. Because mixed-effects models estimate subject-specific associations, they sometimes gave much higher effect estimates than marginal models, which estimate population-averaged associations. Overall, the results show that marginal and mixed-effects models are efficient for studying HPV natural history but also highlight the importance of understanding how these models differ. Cancer Epidemiol Bioniarkers Prev; 19(1); 159-69. (C)2010 AACR. C1 [Xue, Xiaonan] Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Gange, Stephen J.; D'Souza, Gypsyamber] Johns Hopkins Univ, Baltimore, MD USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Minkoff, Howard] SUNY Downstate, Brooklyn, NY USA. [Massad, L. Stewart] So Illinois Univ, Sch Med, Springfield, IL USA. [Watts, D. Heather] NICHHD, NIH, Bethesda, MD 20892 USA. [Levine, Alexandra M.] Univ So Calif, Los Angeles, CA USA. [Plankey, Michael] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Palefsky, Joel M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Xue, XN (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1308, Bronx, NY 10461 USA. EM xiaonan.xue@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute on Drug Abuse [U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, U01-AI-42590]; National Institute of Child Health and Human Development [U01-HD-32632]; National Center for Research Resources [M01-RR-00071, M01-RR-00079, M01-RR-00083]; [R01-CA-085178] FX HPV DNA testing is funded through R01-CA-085178. All specimens and other data in this study were collected by the WIHS Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (Kathryn Anastos, M.D.); Brooklyn, NY (Howard Minkoff, M.D.); Washington, DC, Metropolitan Consortium (Mary Young, M.D.); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt, M.D.); Los Angeles County/Southern California Consortium (Alexandra M. Levine, M.D.); Chicago Consortium (Mardge Cohen, M.D.); and Data Coordinating Center (Stephen J. Gange, Ph.D.). The WIHS is funded by the National Institute of Allergy and Infectious Diseases with supplemental funding from the National Cancer Institute and the National Institute on Drug Abuse (U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590). Funding is also provided by the National Institute of Child Health and Human Development (U01-HD-32632) and the National Center for Research Resources (M01-RR-00071, M01-RR-00079, and M01-RR-00083). NR 29 TC 50 Z9 50 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 159 EP 169 DI 10.1158/1055-9965.EPI-09-0546 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700019 PM 20056635 ER PT J AU Doherty, JA Rossing, MA Cushing-Haugen, KL Chen, C Van Den Berg, DJ Wu, AH Pike, MC Ness, RB Moysich, K Chenevix-Trench, G Beesley, J Webb, PM Chang-Claude, J Wang-Gohrke, S Goodman, MT Lurie, G Thompson, PJ Carney, ME Hogdall, E Kjaer, SK Hogdall, C Goode, EL Cunningham, JM Fridley, BL Vierkant, RA Berchuck, A Moorman, PG Schildkraut, JM Palmieri, RT Cramer, DW Terry, KL Yang, HP Garcia-Closas, M Chanock, S Lissowska, J Song, HL Pharoah, PDP Shah, M Perkins, B McGuire, V Whittemore, AS Di Cioccio, RA Gentry-Maharaj, A Menon, U Gayther, SA Ramus, SJ Ziogas, A Brewster, W Anton-Culver, H Pearce, CL AF Doherty, Jennifer A. Rossing, Mary Anne Cushing-Haugen, Kara L. Chen, Chu Van Den Berg, David J. Wu, Anna H. Pike, Malcolm C. Ness, Roberta B. Moysich, Kirsten Chenevix-Trench, Georgia Beesley, Jonathan Webb, Penelope M. Chang-Claude, Jenny Wang-Gohrke, Shan Goodman, Marc T. Lurie, Galina Thompson, Pamela J. Carney, Michael E. Hogdall, Estrid Kjaer, Susanne Kruger Hogdall, Claus Goode, Ellen L. Cunningham, Julie M. Fridley, Brooke L. Vierkant, Robert A. Berchuck, Andrew Moorman, Patricia G. Schildkraut, Joellen M. Palmieri, Rachel T. Cramer, Daniel W. Terry, Kathryn L. Yang, Hannah P. Garcia-Closas, Montserrat Chanock, Stephen Lissowska, Jolanta Song, Honglin Pharoah, Paul D. P. Shah, Mitul Perkins, Barbara McGuire, Valerie Whittemore, Alice S. Di Cioccio, Richard A. Gentry-Maharaj, Aleksandra Menon, Usha Gayther, Simon A. Ramus, Susan J. Ziogas, Argyrios Brewster, Wendy Anton-Culver, Hoda Pearce, Celeste Leigh CA Australian Ovarian Canc Study Mana Australian Canc Study Ovarian Canc Ovarian Canc Assoc Consortium TI ESR1/SYNE1 Polymorphism and Invasive Epithelial Ovarian Cancer Risk: An Ovarian Cancer Association Consortium Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; CANDIDATE SNPS; BREAST; MUTATIONS; SYNE-1 AB We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1. (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.0061. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope I (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be down-regulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 Studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95% Cl, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid Subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer. Cancer Epidemiol Biomarkers Prev; 190); 245-50. (C) 2010 AACR. C1 [Doherty, Jennifer A.; Rossing, Mary Anne; Cushing-Haugen, Kara L.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. [Van Den Berg, David J.; Wu, Anna H.; Pike, Malcolm C.; Pearce, Celeste Leigh] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Moysich, Kirsten; Di Cioccio, Richard A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Australian Canc Study Ovarian Canc] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Goodman, Marc T.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Hogdall, Claus] Rigshosp, Juliane Marie Ctr, Dept Gynecol & Obstet, DK-2100 Copenhagen, Denmark. [Goode, Ellen L.; Cunningham, Julie M.; Fridley, Brooke L.; Vierkant, Robert A.] Mayo Clin, Coll Med, Rochester, MN USA. [Berchuck, Andrew; Moorman, Patricia G.; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Durham, NC USA. [Palmieri, Rachel T.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Yang, Hannah P.; Garcia-Closas, Montserrat; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lissowska, Jolanta] M Sklodowska Curie Inst Oncol & Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Song, Honglin; Pharoah, Paul D. P.; Shah, Mitul; Perkins, Barbara] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England. [McGuire, Valerie; Whittemore, Alice S.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.] UCL, Dept Gynaecol Oncol, EGA Inst Womens Hlth, London, England. [Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Australian Ovarian Canc Study Mana] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RP Doherty, JA (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol M4 C308, POB 19024, Seattle, WA 98109 USA. EM jdoherty@fhcrc.org RI Menon, Usha/C-4716-2008; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; Bowtell, David/H-1007-2016; OI Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Vierkant, Robert/0000-0001-6242-5221; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Webb, Penelope/0000-0003-0733-5930; Lissowska, Jolanta/0000-0003-2695-5799 FU Cancer Research UK [10124, , 10119, A10119, A10124]; Department of Health; Intramural NIH HHS; Medical Research Council [G0801875]; NCI NIH HHS [CA-58860, CA105009, CA112523, CA122443, CA14089, CA16056, CA54419, CA61132, CA63464, CA87538, N01 PC035137, N01 PC067010, N01-PC-35137, N01-PC67010, N01PC35137, P01 CA017054, P01 CA017054-310001, P01-CA17054, P30 CA014089, P30 CA014089-33, P30 CA016056, P30 CA016056-33, P50 CA105009, P50 CA105009-02, R01 CA054419, R01 CA054419-10, R01 CA058598, R01 CA058598-10, R01 CA058860, R01 CA063464, R01 CA063464-09, R01 CA076016, R01 CA076016-10, R01 CA087538, R01 CA087538-05, R01 CA095023, R01 CA095023-06, R01 CA112523, R01 CA112523-04, R01 CA122443, R01 CA122443-03, R01 CA61107, R01-CA-58598, R01-CA76016, R01CA095023, R03 CA113148, R03 CA113148-02, R03-CA113148, U01 CA058860, U01 CA058860-09, U01 CA063464, U01 CA069417, U01 CA069417-100002, U01 CA071966, U01 CA071966-05S2, U01 CA69417, U01 CA71966]; NHLBI NIH HHS [R01 HL090559, R01 HL090559-03, R01-HL090559] NR 15 TC 37 Z9 39 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 245 EP 250 DI 10.1158/1055-9965.EPI-09-0729 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700028 PM 20056644 ER PT J AU Langeberg, WJ Kwon, EM Koopmeiners, JS Ostrander, EA Stanford, JL AF Langeberg, Wendy J. Kwon, Erika M. Koopmeiners, Joseph S. Ostrander, Elaine A. Stanford, Janet L. TI Population-Based Study of the Association of Variants in Mismatch Repair Genes with Prostate Cancer Risk and Outcomes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MICROSATELLITE INSTABILITY; HIGH-FREQUENCY; EXPRESSION; DNA; ADENOCARCINOMA; HMSH2; POLYMORPHISMS; RECURRENCE; PHENOTYPE; DEFECTS AB Background: Mismatch repair (MMR) gene activity may be associated with prostate cancer risk and outcomes. This Study evaluated whether single nucleotide polymorphisms (SNP) in key MMR genes are related to prostate cancer outcomes. Methods: Data from two population-based case-control studies of prostate cancer among Caucasian and African-American men residing in King County, Washington were combined for this analysis. Cases (n = 1,458) were diagnosed with prostate cancer in 1993 to 1996 or 2002 to 2005 and were identified through the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Controls (n = 1,351) were age-matched to cases and were identified through random digit dialing. Logistic regression was used to assess the relationship between haplotype-tagging SNPs and prostate cancer risk and disease aggressiveness. Cox proportional hazards regression was used to assess the relationship between SNPs and prostate cancer recurrence and prostate cancer-specific death. Results: Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and 4 in PMS2. Among Caucasian men, one SNP in MLH1 (rs9852810) was associated with overall prostate cancer risk [odds ratio, 1.21; 95% confidence interval (95%, CI), 1.02, 1.44; P = 0.03], more aggressive prostate cancer (odds ratio, 1.49; 95% Cl, 1.15, 1.91; P < 0.01), and prostate cancer recurrence (hazard ratio, 1.83; 95% CI, 1.18, 2.86; P < 0.01), but not prostate cancer-specific mortality. A nonsynonymous coding SNP in MLH1, rs1799977 (1219V), was also found to be associated with more aggressive disease. These results did not remain significant after adjusting for multiple comparisons. Conclusion: This population-based case-control study provides evidence for a possible association with a gene variant in MLH1 in relation to the risk of overall prostate cancer, more aggressive disease, and prostate cancer recurrence, which warrants replication. Cancer Epidemiol Biomarkers Prev; 19(1); 258-64. (C)2010 AACR. C1 [Stanford, Janet L.] Univ Washington, Program Epidemiol, Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Langeberg, Wendy J.; Koopmeiners, Joseph S.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Seattle, WA 98109 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Stanford, JL (reprint author), Univ Washington, Program Epidemiol, Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, M4-B874,POB 19024, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1 CA056678, RO1 CA082664, RO1 CA092579, P50 CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Grants RO1 CA056678, RO1 CA082664, RO1 CA092579, and P50 CA097186 from the National Cancer Institute, with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 33 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 258 EP 264 DI 10.1158/1055-9965.EPI-09-0800 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700030 PM 20056646 ER PT J AU Fedirko, V Bostick, RM Long, Q Flanders, WD McCullough, ML Sidelnikov, E Daniel, CR Rutherford, RE Shaukat, A AF Fedirko, Veronika Bostick, Roberd M. Long, Qi Flanders, W. Dana McCullough, Marjorie L. Sidelnikov, Eduard Daniel, Carrie R. Rutherford, Robin E. Shaukat, Aasma TI Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; NORMAL COLON MUCOSA; POSTMENOPAUSAL WOMEN; DIETARY CALCIUM; ANTIOXIDANT EXPOSURES; BILE-ACIDS; CANCER; CARCINOGENESIS; ADENOMA; STRESS AB The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25%, (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 19(1); 280-91. (C) 2010 AACR. C1 [Fedirko, Veronika; Bostick, Roberd M.; Flanders, W. Dana; Sidelnikov, Eduard] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Long, Qi; Flanders, W. Dana] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Fedirko, Veronika; Bostick, Roberd M.; Long, Qi; Flanders, W. Dana; Sidelnikov, Eduard] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [McCullough, Marjorie L.] Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. [Rutherford, Robin E.] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA 30322 USA. [Daniel, Carrie R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Shaukat, Aasma] Univ Minnesota, Dept Med, GI Div, Minneapolis, MN 55455 USA. RP Bostick, RM (reprint author), Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM rmbosti@sph.emory.edu FU NIH [RO1 CA104637, R03 CA136113]; Georgia Cancer Coalition Distinguished Scholar Award; Franklin Foundation; Emory Graduate School FX National Cancer Institute, NIH grants RO1 CA104637 and R03 CA136113 and Georgia Cancer Coalition Distinguished Scholar Award (R.M. Bostick); Franklin Foundation; and Emory Graduate School supplemental research funds (V. Fedirko).; The National Cancer Institute, the Georgia Cancer Coalition, the Franklin Foundation, and the Emory Graduate School had no influence on the design of the study; the collection, analysis, and interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 54 TC 65 Z9 67 U1 3 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 280 EP 291 DI 10.1158/1055-9965.EPI-09-0448 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700033 PM 20056649 ER PT J AU Faupel-Badger, JM Fuhrman, BJ Xu, X Falk, RT Keefer, LK Veenstra, TD Hoover, RN Ziegler, RG AF Faupel-Badger, Jessica M. Fuhrman, Barbara J. Xu, Xia Falk, Roni T. Keefer, Larry K. Veenstra, Timothy D. Hoover, Robert N. Ziegler, Regina G. TI Comparison of Liquid Chromatography-Tandem Mass Spectrometry, RIA, and ELISA Methods for Measurement of Urinary Estrogens SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; ASIAN-AMERICAN WOMEN; POSTMENOPAUSAL WOMEN; ENDOGENOUS ESTROGENS; 2-HYDROXYESTRONE/16-ALPHA-HYDROXYESTRONE RATIO; METABOLITES; SERUM; 2-HYDROXYESTRONE; REPRODUCIBILITY; ASSAY AB Absolute and relative concentrations of estrogens and estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used for measuring estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of estrone, estradiol, and estriol measured by indirect RIA and of 2-hydroxyestrone and 16 alpha-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15 estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (r(s)) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (r(s) = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16 alpha-hydroxyestrone ratio, a putative biomarker of breast cancer risk, were moderately correlated in premenopausal women (r(s) = 0.6-0.7) but only weakly correlated in postmenopausal women (r(s) = 0.2). LC-MS/MS had higher intraclass correlation coefficients (>= 99.6%) and lower coefficients of variation (<= 9.4%) than ELISA (>= 97.2% and <= 14.2%) and RIA (>= 95.2% and <= 17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA estrogen metabolite measures may be problematic, especially at low estrogen metabolite levels characteristic of postmenopausal women. Cancer Epidemiol Biomarkers Prev; 19(1); 292-300. (C)2010 AACR. C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.; Fuhrman, Barbara J.; Hoover, Robert N.; Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. [Falk, Roni T.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Xu, Xia; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD USA. RP Faupel-Badger, JM (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, 6120 Execut Blvd,Suite 150E,MSC 7105, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Fuhrman, Barbara/0000-0002-1777-9888 FU National Cancer Institute; NIH [NO1-CO-12400] FX Intramural Research Program of the National Cancer Institute, NIH and National Cancer Institute, NIH contract NO1-CO-12400 and contract to SAIC-Frederick.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 33 TC 37 Z9 38 U1 1 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 292 EP 300 DI 10.1158/1055-9965.EPI-09-0643 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700034 PM 20056650 ER PT J AU Yang, Y Valera, VA Padilla-Nash, HM Sourbier, C Vocke, CD Vira, MA Abu-Asab, MS Bratslavsky, G Tsokos, M Merino, MJ Pinto, PA Srinivasan, R Ried, T Neckers, L Linehan, WM AF Yang, Youfeng Valera, Vladimir A. Padilla-Nash, Hesed M. Sourbier, Carole Vocke, Cathy D. Vira, Manish A. Abu-Asab, Mones S. Bratslavsky, Gennady Tsokos, Maria Merino, Maria J. Pinto, Peter A. Srinivasan, Ramaprasad Ried, Thomas Neckers, Len Linehan, W. Marston TI UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID CUTANEOUS LEIOMYOMAS; UTERINE LEIOMYOMAS; MAMMALIAN-CELLS; MUTATIONS; FAMILIES; GENE; TUMORS; TRANSLOCATION; SPECTRUM AB Energy deregulation and abnormalities of tumor cell metabolism are critical issues in understanding cancer. Hereditary leiomyomatosis renal cell carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme fumarate hydratase (FH), and one known to be highly metastatic and unusually lethal. There is considerable utility in establishing preclinical cell and xenograft models for study of disorders of energy metabolism, as well as in development of new therapeutic approaches targeting of tricarboxylic acid (TCA) cycle enzyme deficient human cancers. Here we describe a new immortalized cell line, UOK 262, derived from a patient having aggressive HLRCC-associated recurring kidney cancer. We investigated gene expression, chromosome profiles, efflux bioenergetic analysis, mitochondrial ultrastructure, FH catabolic activity, invasiveness, and optimal glucose requirements for in vitro growth. UOK 262 cells have an isochromosome 1q recurring chromosome abnormality, i(1)(q10), and exhibit compromised oxidative phosphorylation and in vitro dependence on anaerobic glycolysis consistent with the clinical manifestation of HLRCC. The cells also display glucose-dependent growth, an elevated rate of lactate efflux, and overexpression of the glucose transporter GLUT I and of lactate dehydrogenase A (LDHA). Mutant FH protein was present primarily in edematous mitochondria, but with catalytic activity nearly undetectable. UOK 262 xenografts retain the characteristics of HLRCC histopathology. Our findings indicate that the severe compromise of oxidative phosphorylation and rapid glycolytic flux in UOK 262 are an essential feature of this TCA cycle enzyme-deficient form of kidney cancer. This tumor model is the embodiment of the Warburg effect. UOK 262 provides a unique in vitro and in vivo preclinical model for studying the bioenergetics of the Warburg effect in human cancer. (C) 2010 Elsevier Inc. All rights reserved. C1 [Yang, Youfeng; Valera, Vladimir A.; Sourbier, Carole; Vocke, Cathy D.; Vira, Manish A.; Bratslavsky, Gennady; Pinto, Peter A.; Srinivasan, Ramaprasad; Neckers, Len; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Padilla-Nash, Hesed M.; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones S.; Tsokos, Maria; Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1107,Bldg 10 CRC,Room 1-5942, Bethesda, MD 20892 USA. EM wml@nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research. We thank Robert A. Worrell, PhD, for operative tissue procurement; Linda Stapleton-Barenboim, for preparation of the SKY probes; Guofeng Zhang, PhD, for processing electron microscopy thin sections and images acquisitions; Catherine Wells, for assistance with animal xenograft studies; and Georgia Shaw, for editorial support. NR 37 TC 64 Z9 64 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN 1 PY 2010 VL 196 IS 1 BP 45 EP 55 DI 10.1016/j.cancergencyto.2009.08.018 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 592QX UT WOS:000277395600007 PM 19963135 ER PT B AU Ren, L Khanna, C AF Ren, L. Khanna, C. BE ThomasTikhonenko, A TI Merlin/NF2 Tumor Suppressor and Ezrin-Radixin-Moesin (ERM) Proteins in Cancer Development and Progression SO CANCER GENOME AND TUMOR MICROENVIRONMENT LA English DT Article; Book Chapter ID MEMBRANE-MICROFILAMENT LINKER; MEDIATES CONTACT INHIBITION; MICROVILLAR CORE PROTEIN; EPIDERMAL-GROWTH-FACTOR; CELL-CELL CONTACTS; PLASMA-MEMBRANE; IMMUNOLOGICAL SYNAPSE; EPITHELIAL-CELLS; T-LYMPHOCYTES; GENE-PRODUCT C1 [Khanna, C.] NCI, Head Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Head Tumor & Metastasis Biol Sect, Pediat Oncol Branch, 37 Convent Dr,Suite 2144, Bethesda, MD 20892 USA. EM renl@mail.nih.gov; khannac@mail.nih.gov NR 139 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0710-3 PY 2010 BP 93 EP 115 DI 10.1007/978-1-4419-0711-0_5 PG 23 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BMV87 UT WOS:000273689100005 ER PT J AU Cereda, V Poole, DJ Palena, C Das, S Bera, TK Remondo, C Gulley, JL Arlen, PM Yokokawa, J Pastan, I Schlom, J Tsang, KY AF Cereda, Vittore Poole, Diane J. Palena, Claudia Das, Sudipto Bera, Tapan K. Remondo, Cinzia Gulley, James L. Arlen, Philip M. Yokokawa, Junko Pastan, Ira Schlom, Jeffrey Tsang, Kwong Y. TI New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE NGEP; Prostate cancer; T cell; Vaccine; Epitopes ID ANTIGEN-PRESENTING CELLS; MEMBRANE ANTIGEN; PROTEIN; PEPTIDE; VACCINE; LYMPHOCYTES; IDENTIFICATION; NGEP; MUTATIONS; THERAPY AB New gene expressed in prostate (NGEP) is a prostate-specific gene encoding either a small cytoplasmic protein (NGEP-S) or a larger polytopic membrane protein (NGEP-L). NGEP-L expression is detectable only in prostate cancer, benign prostatic hyperplasia and normal prostate. We have identified an HLA-A2 binding NGEP epitope (designated P703) which was used to generate T cell lines from several patients with localized and metastatic prostate cancer. These T cell lines were able to specifically lyse HLA-A2 and NGEP-expressing human tumor cells. NGEP-P703 tetramer binding assays demonstrated that metastatic prostate cancer patients had a higher frequency of NGEP-specific T cells when compared with healthy donors. Moreover, an increased frequency of NGEP-specific T cells was detected in the peripheral blood mononuclear cells of prostate cancer patients post-vaccination with a PSA-based vaccine, further indicating the immunogenicity of NGEP. These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer. C1 [Cereda, Vittore; Poole, Diane J.; Palena, Claudia; Remondo, Cinzia; Gulley, James L.; Arlen, Philip M.; Yokokawa, Junko; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Das, Sudipto; Bera, Tapan K.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU NCI, NIH FX The authors thank Bonnie Casey and Debra Weingarten for their editorial assistance in the preparation of this manuscript. This research was supported by the Intramural Research Program of the Center for Cancer Research, NCI, NIH. NR 34 TC 10 Z9 11 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2010 VL 59 IS 1 BP 63 EP 71 DI 10.1007/s00262-009-0723-6 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 507QH UT WOS:000270869000006 PM 19495750 ER PT J AU Danforth, DN AF Danforth, David N., Jr. TI Breast Cancer During Pregnancy A Comprehensive View SO CANCER JOURNAL LA English DT Editorial Material ID LYMPH-NODE BIOPSY; PROGNOSIS; SAFETY C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 4-5764, Bethesda, MD 20892 USA. EM david_danforth@nih.gov NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2010 VL 16 IS 1 BP 68 EP 69 DI 10.1097/PPO.0b013e3181d388e4 PG 2 WC Oncology SC Oncology GA 582EJ UT WOS:000276578600012 PM 20164694 ER PT S AU Powell, AC Paciotti, GF Libutti, SK AF Powell, Anathea C. Paciotti, Giulio F. Libutti, Steven K. BE Grobmyer, SR Moudgil, BM TI Colloidal Gold: A Novel Nanoparticle for Targeted Cancer Therapeutics SO CANCER NANOTECHNOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tumor necrosis factor; colloidal gold; colloidal gold nanoparticles; pegylated colloidal gold; tumor necrosis factor conjugated to colloidal gold ID TUMOR-NECROSIS-FACTOR; PHASE-II TRIAL; INTERFERON-GAMMA; CLINICAL-TRIAL; DRUG-DELIVERY; FACTOR-ALPHA; NANOTECHNOLOGY; MELANOMA; ANGIOGENESIS; PERMEABILITY AB Since their initial description in 1857, gold nanoparticles have been used extensively in the fields of diagnostics and therapeutics. Now, gold nanoparticles are engineered to target the delivery of potent anti-cancer therapeutics to solid tumors to improve either their safety or efficacy or both. Described in this chapter is the development of one such nanotherapeutic, termed CYT-6091, that targets the delivery of tumor necrosis factor alpha (TNF) to solid tumors. Outlined in the presentation is a discussion of nanoparticles and specifically colloidal gold, an historical review on the biology of TNF and its limited use in the clinic when administered systemically, and finally, how gold nanoparticles bound with TNF may improve the safety and efficacy profiles of TNF. C1 [Powell, Anathea C.; Libutti, Steven K.] NCI, Tumor Angiogenesis Sect, Surg Branch, Bethesda, MD 20892 USA. [Paciotti, Giulio F.] CytImmune Sci Inc, Rockville, MD USA. RP Powell, AC (reprint author), NCI, Tumor Angiogenesis Sect, Surg Branch, Bethesda, MD 20892 USA. NR 41 TC 28 Z9 30 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-608-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 624 BP 375 EP 384 DI 10.1007/978-1-60761-609-2_25 D2 10.1007/978-1-60761-609-2 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Oncology; Science & Technology - Other Topics GA BOG44 UT WOS:000276569600025 PM 20217609 ER PT B AU Fossa, SD Travis, LB Dahl, AA AF Fossa, Sophie D. Travis, Lois B. Dahl, Alv A. BE Laguna, MP Albers, P Bokemeyer, C Richie, JP TI Testicular Cancer: Late Effects of Treatment SO CANCER OF THE TESTIS LA English DT Article; Book Chapter ID LONG-TERM SURVIVORS; GERM-CELL TUMORS; QUALITY-OF-LIFE; CARCINOMA-IN-SITU; SECONDARY LEUKEMIA; SEXUAL FUNCTION; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; GONADAL-FUNCTION; HORMONAL STATUS C1 [Fossa, Sophie D.] Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Dept Clin Canc Res,Canc Clin, N-0027 Oslo, Norway. [Travis, Lois B.] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dahl, Alv A.] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Clin Canc Res, Oslo, Norway. RP Fossa, SD (reprint author), Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Dept Clin Canc Res,Canc Clin, N-0027 Oslo, Norway. NR 103 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84800-369-9 PY 2010 BP 275 EP 287 DI 10.1007/978-1-84800-370-5_20 D2 10.1007/978-1-84800-370-5 PG 13 WC Oncology; Surgery; Urology & Nephrology SC Oncology; Surgery; Urology & Nephrology GA BVA07 UT WOS:000290878900020 ER PT J AU Wang, W Srivastava, S AF Wang, Wendy Srivastava, Sudhir TI Strategic Approach to Validating Methylated Genes as Biomarkers for Breast Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID FINE-NEEDLE-ASPIRATION; PROMOTER HYPERMETHYLATION; DNA METHYLATION; RUNX3 GENE; RISK; WOMEN; EXPRESSION; PREDICTION; BENIGN; AGE AB Although the potential of biomarkers to aid in the early detection, diagnosis, prevention, and treatment of breast cancer is broadly recognized and numerous biomarker candidates have been reported in the literature, few molecular markers have been adopted into clinical use to date. To address this lack of translation of biomarkers from the bench to clinical practice, the Cancer Biomarkers Research Group in the Division of Cancer Prevention of the National Cancer Institute organized a meeting, "Strategic Discussion on Biomarkers for Breast Cancer," which was held at the Fred Hutchinson Cancer Research Center on September 14, 2008. Participants included industry leaders, basic and physician scientists, and National Cancer Institute program staff. The objectives of this strategic discussion were to define clinical uses and needed performance characteristics of biomarkers; to identify novel approaches to discover and validate breast cancer biomarkers, particularly those with improved chances of being clinically useful; and to identify candidate DNA methylation markers that could be taken forward for validation. Participants presented and recommended methylation biomarkers suitable for initiating collaborative projects to evaluate the markers for future clinical application. This commentary summarizes their discussions and recommendations and the rationale for initiating specific projects to validate DNA methylation biomarkers of breast cancer. Cancer Prev Res; 3(1); 16-24. (c) 2010 AACR. C1 [Wang, Wendy; Srivastava, Sudhir] US Natl Canc Inst, Canc Prevent Div, Canc Biomarkers Res Grp, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), US Natl Canc Inst, Canc Prevent Div, Canc Biomarkers Res Grp, 6130 Execut Blvd,Suite 3142, Rockville, MD 20852 USA. EM srivasts@mail.nih.gov NR 50 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 16 EP 24 DI 10.1158/1940-6207.CAPR-09-0098 PG 9 WC Oncology SC Oncology GA 539YK UT WOS:000273295500005 PM 20051369 ER PT J AU Tang, JY Aszterbaum, M Athar, M Barsanti, F Cappola, C Estevez, N Hebert, J Hwang, J Khaimskiy, Y Kim, A Lu, Y So, PL Tang, XW Kohn, MA McCulloch, CE Kopelovich, L Bickers, DR Epstein, EH AF Tang, Jean Y. Aszterbaum, Michelle Athar, Mohammad Barsanti, Franco Cappola, Carol Estevez, Nini Hebert, Jennifer Hwang, Jimmy Khaimskiy, Yefim Kim, Arianna Lu, Ying So, Po-Lin Tang, Xiuwei Kohn, Michael A. McCulloch, Charles E. Kopelovich, Levy Bickers, David R. Epstein, Ervin H., Jr. TI Basal Cell Carcinoma Chemoprevention with Nonsteroidal Anti-inflammatory Drugs in Genetically Predisposed PTCH1(+/-) Humans and Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; NONMELANOMA SKIN-CANCER; CYCLOOXYGENASE-2 INHIBITOR; CLINICAL-TRIAL; IONIZING-RADIATION; SULINDAC THERAPY; TUMOR-FORMATION; HAIRLESS MICE; RECTAL-CANCER; HUMAN HOMOLOG AB In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study of their efficacy in preventing the more common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition of cyclooxygenase (COX) enzymes in the skin of Ptch1(+/-) mice. We then assessed the effects of celecoxib on the development of BCCs in a 3-year, double-blinded, randomized clinical trial in 60 (PTCH1(+/-)) patients with the basal cell nevus syndrome. In Ptch1(+/-) mice, genetic deletion of COX1 or COX2 robustly decreased (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the human trial, we detected a trend for oral celecoxib reducing BCC burden in all subjects (P = 0.069). Considering only the 60% of patients with less severe disease (< 15 BCCs at study entry), celecoxib significantly reduced BCC number and burden: subjects receiving placebo had a 50% increase in BCC burden per year, whereas subjects in the celecoxib group had a 20% increase (P-difference = 0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1(+/-) mice and had a significant anti-BCC effect in humans with less severe disease. Cancer Prev Res; 3(1); 25-34. (c) 2010 AACR. C1 [Tang, Jean Y.; Aszterbaum, Michelle; Estevez, Nini; Hebert, Jennifer; Khaimskiy, Yefim; So, Po-Lin; Epstein, Ervin H., Jr.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. [Athar, Mohammad; Barsanti, Franco; Cappola, Carol; Kim, Arianna; Tang, Xiuwei; Bickers, David R.] Columbia Univ, Med Ctr, New York, NY USA. [Tang, Jean Y.] Stanford Univ, Stanford, CA 94305 USA. [Hwang, Jimmy; Lu, Ying; Kohn, Michael A.; McCulloch, Charles E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Athar, Mohammad] Univ Alabama, Birmingham, AL USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Epstein, EH (reprint author), Childrens Hosp, Oakland Res Inst, 5700 Martin Luther King,Jr Way, Oakland, CA 94609 USA. EM eepstein@chori.org FU NIH [CA81888, CN-95116]; NIH/National Center for Research Resources/Office of the Director University of California at San Francisco Clinical and Translational Science Institute [KL2 RR024130]; Mike Rainen Family Foundation; Patricia Hughes; Stanley Eisenberg; Merck; Pfizer; National Center for Research Resources [5 M01 RR-00079]; USPHS FX NIH grants CA81888 and CN-95116 (E.H. Epstein), NIH/National Center for Research Resources/Office of the Director University of California at San Francisco Clinical and Translational Science Institute grant KL2 RR024130 (J.Y. Tang), Mike Rainen Family Foundation, Patricia Hughes, and Stanley Eisenberg, Merck, and Pfizer through donations of drugs for human and mouse treatments. These studies were carried out in part in the Clinical and Translational Science Institute Clinical Research Center, Mt. Zion Hospital, University of California at San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, USPHS. NR 56 TC 40 Z9 40 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 25 EP 34 DI 10.1158/1940-6207.CAPR-09-0200 PG 10 WC Oncology SC Oncology GA 539YK UT WOS:000273295500006 PM 20051370 ER PT J AU Bailey, HH Kim, K Verma, AK Sielaff, K Larson, PO Snow, S Lenaghan, T Viner, JL Douglas, J Dreckschmidt, NE Hamielec, M Pomplun, M Sharata, HH Puchalsky, D Berg, ER Havighurst, TC Carbone, PP AF Bailey, Howard H. Kim, KyungMann Verma, Ajit K. Sielaff, Karen Larson, Paul O. Snow, Stephen Lenaghan, Theresa Viner, Jaye L. Douglas, Jeff Dreckschmidt, Nancy E. Hamielec, Mary Pomplun, Marcy Sharata, Harry H. Puchalsky, David Berg, Eric R. Havighurst, Thomas C. Carbone, Paul P. TI A Randomized, Double-Blind, Placebo-Controlled Phase 3 Skin Cancer Prevention Study of alpha-Difluoromethylornithine in Subjects with Previous History of Skin Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID BASAL-CELL CARCINOMA; ORNITHINE-DECARBOXYLASE ACTIVITY; CONTROLLED-TRIAL; CLINICAL-TRIAL; I CHEMOPREVENTION; POLYAMINE LEVELS; HUMAN PROSTATE; BETA-CAROTENE; INDUCTION; TISSUE AB Preclinical studies have shown that the inhibition of ornithine decarboxylase (ODC) by alpha-difluoromethylornithine (DFMO) and resultant decreases in tissue concentrations of polyamines (putrescine and spermidine) prevents neoplastic developments in many tissue types. Clinical studies of oral DFMO at 500 mg/m(2)/day revealed it to be safe and tolerable and resulted in significant inhibition of phorbol ester-induced skin ODC activity. Two hundred and ninety-one participants (mean age, 61 years; 60% male) with a history of prior nonmelanoma skin cancer (NMSC; mean, 4.5 skin cancers) were randomized to oral DFMO (500 mg/m(2)/day) or placebo for 4 to 5 years. There was a trend toward a history of more prior skin cancers in subjects randomized to placebo, but all other characteristics including sunscreen and nonsteroidal anti-inflammatory drug use were evenly distributed. Evaluation of 1,200 person-years of follow-up revealed a new NMSC rate of 0.5 events/person/year. The primary end point, new NMSCs, was not significantly different between subjects taking DFMO and placebo (260 versus 363 cancers, P = 0.069, two-sample t test). Evaluation of basal cell (BCC) and squamous cell cancers separately revealed very little difference in squamous cell cancer between treatment groups but a significant difference in new BCC (DFMO, 163 cancers; placebo, 243 cancers; expressed as event rate of 0.28 BCC/person/year versus 0.40 BCC/person/year, P = 0.03). Compliance with DFMO was > 90% and it seemed to be well tolerated with evidence of mild ototoxicity as measured by serial audiometric examination when compared with placebo subjects. The analysis of normal skin biopsies revealed a significant (P < 0.05) decrease in 12-0-tetradecanoylphorbol-13-acetate-induced ODCactivity (month 24, 36, and 48) and putrescine concentration (month 24 and 36 only) in DFMO subjects. Subjects with a history of skin cancer taking daily DFMO had an insignificant reduction (P = 0.069) in new NMSC that was predominantly due to a marked reduction in new BCC. Based on these data, the potential of DFMO, alone or in combination, to prevent skin cancers should be explored further. Cancer Prev Res; 3(1); 35-47. (c) 2010 AACR. C1 [Bailey, Howard H.; Kim, KyungMann; Verma, Ajit K.; Sielaff, Karen; Larson, Paul O.; Snow, Stephen; Lenaghan, Theresa; Douglas, Jeff; Dreckschmidt, Nancy E.; Hamielec, Mary; Pomplun, Marcy; Havighurst, Thomas C.; Carbone, Paul P.] Univ Wisconsin, Paul P Carbone Canc Ctr, Madison, WI 53706 USA. [Puchalsky, David; Berg, Eric R.] Meriter Clin, Madison, WI USA. [Viner, Jaye L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Bailey, HH (reprint author), K4-650 CSC,600 Highland Ave, Madison, WI 53792 USA. EM hhbailey@wisc.edu FU National Cancer Institute [R01 CA77158, U01 CA77158, P30 CA 14520]; National Center for Research Resources [UL1 RR025011] FX National Cancer Institute awards R01 CA77158, U01 CA77158, P30 CA 14520, and National Center for Research Resources award UL1 RR025011. NR 36 TC 52 Z9 53 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 35 EP 47 DI 10.1158/1940-6207.CAPR-09-0096 PG 13 WC Oncology SC Oncology GA 539YK UT WOS:000273295500007 PM 20051371 ER PT J AU Bellacosa, A Godwin, AK Peri, S Devarajan, K Caretti, E Vanderveer, L Bove, B Slater, C Zhou, Y Daly, M Howard, S Campbell, KS Nicolas, E Yeung, AT Clapper, ML Crowell, JA Lynch, HT Ross, E Kopelovich, L Knudson, AG AF Bellacosa, Alfonso Godwin, Andrew K. Peri, Suraj Devarajan, Karthik Caretti, Elena Vanderveer, Lisa Bove, Betsy Slater, Carolyn Zhou, Yan Daly, Mary Howard, Sharon Campbell, Kerry S. Nicolas, Emmanuelle Yeung, Anthony T. Clapper, Margie L. Crowell, James A. Lynch, Henry T. Ross, Eric Kopelovich, Levy Knudson, Alfred G. TI Altered Gene Expression in Morphologically Normal Epithelial Cells from Heterozygous Carriers of BRCA1 or BRCA2 Mutations SO CANCER PREVENTION RESEARCH LA English DT Article ID HERITABLE COLORECTAL-CANCER; DNA-DAMAGE RESPONSE; PROBE LEVEL DATA; BREAST-CANCER; OVARIAN-CANCER; MESSENGER-RNA; PROFILES; REPAIR; CYCLOOXYGENASE-1; IDENTIFICATION AB We hypothesized that cells bearing a single inherited "hit" in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. We report here on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations, which were validated independently by real-time reverse transcription-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers, including mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings show that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner; these detectable effects of "one hit" represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention. Cancer Prev Res; 3(1); 48-61. (c) 2010 AACR. C1 [Bellacosa, Alfonso] Fox Chase Canc Ctr, Epigenet & Progenitor Cells Program, Philadelphia, PA 19111 USA. [Bellacosa, Alfonso] Fox Chase Canc Ctr, Human Genet Program, Philadelphia, PA 19111 USA. [Godwin, Andrew K.; Vanderveer, Lisa; Bove, Betsy; Slater, Carolyn; Ross, Eric] Fox Chase Canc Ctr, Ovarian Canc Program, Philadelphia, PA 19111 USA. [Peri, Suraj; Devarajan, Karthik; Zhou, Yan; Ross, Eric] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Howard, Sharon; Campbell, Kerry S.; Nicolas, Emmanuelle] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. [Daly, Mary; Clapper, Margie L.] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 USA. [Crowell, James A.; Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Caretti, Elena; Yeung, Anthony T.; Knudson, Alfred G.] NCI, Div Populat Sci, Bethesda, MD 20892 USA. [Lynch, Henry T.] Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. [Bellacosa, Alfonso] Ist Regina Elena, Lab Dev Therapeut, I-00161 Rome, Italy. RP Bellacosa, A (reprint author), Fox Chase Canc Ctr, Epigenet & Progenitor Cells Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Alfonso.Bellacosa@fccc.edu FU NIH [N01 CN-95037, N01-CN-43309, P30 CA06927]; Ovarian Cancer Specialized Programs of Research Excellence at Fox Chase Cancer Center [P50 CA083638]; Commonwealth of Pennsylvania to the Fox Chase Cancer Center; Eileen Stein Jacoby Fund FX NIH contracts N01 CN-95037, N01-CN-43309, the Ovarian Cancer Specialized Programs of Research Excellence at Fox Chase Cancer Center (P50 CA083638), NIH grant P30 CA06927, an appropriation from the Commonwealth of Pennsylvania to the Fox Chase Cancer Center, and the Eileen Stein Jacoby Fund. NR 47 TC 34 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 48 EP 61 DI 10.1158/1940-6207.CAPR-09-0078 PG 14 WC Oncology SC Oncology GA 539YK UT WOS:000273295500008 PM 20051372 ER PT J AU Izzotti, A Calin, GA Steele, VE Cartiglia, C Longobardi, M Croce, CM De Flora, S AF Izzotti, Alberto Calin, George A. Steele, Vernon E. Cartiglia, Cristina Longobardi, Mariagrazia Croce, Carlo M. De Flora, Silvio TI Chemoprevention of Cigarette Smoke-Induced Alterations of MicroRNA Expression in Rat Lungs SO CANCER PREVENTION RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; GENE-EXPRESSION; DOWN-REGULATION; BREAST-CANCER; CYCLE ARREST; DNA-DAMAGE; P53; INHIBITION; APOPTOSIS; MECHANISM AB We previously showed that exposure to environmental cigarette smoke (ECS) for 28 days causes extensive downregulation of microRNA expression in the lungs of rats, resulting in the overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lungs of either ECS-free or ECS-exposed rats treated with the orally administered chemopreventive agents N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone, and phenethyl isothiocyanate (as single agents or in combinations). This is the first study of microRNA modulation by chemopreventive agents in nonmalignant tissues. Scatterplot, hierarchical cluster, and principal component analyses of microarray and quantitative PCR data showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, indicating potential safety. On the other hand, all of them attenuated ECS-induced alterations but to a variable extent and with different patterns, indicating potential preventive efficacy. The main ECS-altered functions that were modulated by chemopreventive agents included cell proliferation, apoptosis, differentiation, Ras activation, P53 functions, NF-kappa B pathway, transforming growth factor-related stress response, and angiogenesis. Some microRNAs known to be polymorphic in humans were downregulated by ECS and were protected by chemopreventive agents. This study provides proof-of-concept and validation of technology that we are further refining to screen and prioritize potential agents for continued development and to help elucidate their biological effects and mechanisms. Therefore, microRNA analysis may provide a new tool for predicting at early carcinogenesis stages both the potential safety and efficacy of cancer chemopreventive agents. Cancer Prev Res; 3(1); 62-72. (c) 2010 AACR. C1 [Izzotti, Alberto; Cartiglia, Cristina; Longobardi, Mariagrazia; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Calin, George A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Steele, Vernon E.] NCI, Rockville, MD USA. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU NIH [N01-CN-53301] FX NIH National Cancer Institute ( contract N01-CN-53301). NR 48 TC 56 Z9 59 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 62 EP 72 DI 10.1158/1940-6207.CAPR-09-0202 PG 11 WC Oncology SC Oncology GA 539YK UT WOS:000273295500009 PM 20051373 ER PT J AU McCormick, DL Phillips, JM Horn, TL Johnson, WD Steele, VE Lubet, RA AF McCormick, David L. Phillips, Jonathan M. Horn, Thomas L. Johnson, William D. Steele, Vernon E. Lubet, Ronald A. TI Overexpression of Cyclooxygenase-2 in Rat Oral Cancers and Prevention of Oral Carcinogenesis in Rats by Selective and Nonselective COX Inhibitors SO CANCER PREVENTION RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MAMMARY CARCINOGENESIS; CARDIOVASCULAR EVENTS; COLORECTAL-CANCER; CELECOXIB; ROFECOXIB; TRIAL; CHEMOPREVENTION; NAPROXEN; ASPIRIN AB Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO) show substantial overexpression of cyclooxygenase-2 (COX-2) when compared with adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase (LOX) nor 12-LOX is overexpressed in rat oral cancers. Two chemoprevention studies were done to test the resulting hypothesis that COX-2 is a useful target for oral cancer chemoprevention in the rat. In both studies, male F344 rats received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by administration of chemopreventive agents from week 10 until study termination at week 26. In the first study, groups of rats were fed basal diet (control), or basal diet supplemented with the selective COX-2 inhibitor celecoxib (500 or 1,500 mg/kg diet), the nonselective COX inhibitor piroxicam (50 or 150 mg/kg diet), or the 5-LOX inhibitor zileuton (2,000 mg/kg diet). In the second study, rats were fed basal diet (control) or basal diet supplemented with nitric oxide-naproxen (180 or 90 mg/kg diet), a nonselective COX inhibitor that shows reduced gastrointestinal toxicity. When compared with dietary controls, celecoxib decreased oral cancer incidence, cancer invasion score, and cancer-related mortality. Piroxicam decreased cancer-related mortality and cancer invasion score, whereas nitric oxide-naproxen decreased oral cancer incidence and cancer invasion score. By contrast, zileuton showed no chemopreventive activity by any parameter assessed. These data show that both selective and nonselective inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The chemopreventive activity of COX inhibitors may be linked to overexpression of their enzymatic target in incipient oral neoplasms. Cancer Prev Res; 3(1); 73-81. (c) 2010 AACR. C1 [McCormick, David L.; Phillips, Jonathan M.; Horn, Thomas L.; Johnson, William D.] IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. [Steele, Vernon E.; Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, 10 W 35th St, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU National Cancer Institute, Department of Health and Human Services [NO1-CN-85163, NO1-CN-05111, N01-CN-25113] FX NO1-CN-85163, NO1-CN-05111, and N01-CN-25113 from the National Cancer Institute, Department of Health and Human Services. NR 34 TC 20 Z9 22 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 73 EP 81 DI 10.1158/1940-6207.CAPR-09-0151 PG 9 WC Oncology SC Oncology GA 539YK UT WOS:000273295500010 PM 20051374 ER PT J AU Janakiram, NB Mohammed, A Zhang, YT Choi, CI Woodward, C Collin, P Steele, VE Rao, CV AF Janakiram, Naveena B. Mohammed, Altaf Zhang, Yuting Choi, Chang-In Woodward, Carl Collin, Peter Steele, Vernon E. Rao, Chinthalapally V. TI Chemopreventive Effects of Frondanol A5, a Cucumaria frondosa Extract, against Rat Colon Carcinogenesis and Inhibition of Human Colon Cancer Cell Growth SO CANCER PREVENTION RESEARCH LA English DT Article ID ABERRANT CRYPT FOCI; DNA-DAMAGE; CASPASE-2-INDUCED APOPTOSIS; NATURAL-PRODUCTS; ACTIVATION; ARREST; INACTIVATION; MITOCHONDRIA; REQUIREMENT; PREVENTION AB Sea cucumber extracts have been widely used to treat individuals with inflammatory conditions in East Asia. The present study has been designed to test potential colon cancer-preventive properties of Frondanol A5, a glycolipid extract from the sea cucumber, Cucumaria frondosa, using in vivo and in vitro models of colon cancer. Chemopreventive efficacy of Frondanol A5 was evaluated on azoxy-methane-induced rat colon carcinogenesis using colonic aberrant crypt foci (ACF) as efficacy marker. At 7 weeks of age, groups of rats (12 per group) were fed the AIN-76A diet, and ACFs were induced by azoxymethane (15 mg/kg body weight). Three days after azoxymethane treatment, rats were fed with the diets containing 0, 150, and 450 ppm of Frondanol A5 and continued on the diets for 8 weeks, at which time ACFs were evaluated. Expression levels of proliferating cell nuclear antigen and p21(WAF1/CIP1) were determined in ACFs. Further, Frondanol A5 (10-120 mu g/mL) was studied for its growth-inhibitory and apoptotic effects in the HCT-116 cell line. Dietary administration of 150 and 450 ppmof Frondanol A5 significantly suppressed azoxymethane-induced total colonic ACF formation, approximately 34% to 55% (P < 0.01 to P < 0.0001), and multicrypt aberrant foci (48-68.5%, P < 0.0001) in a dose-dependent manner. ACFs in rats treated with Frondanol A5 showed significant upregulation of p21(WAF1/CIP1) and downregulation of proliferating cell nuclear antigen compared with control group. Frondanol A5 showed growth inhibition at S and G(2)-M phase with a decrease in Cdc25c and an increase in p21(WAF1/CIP) with significant apoptosis associated with H2AX phosphorylation and caspase-2 cleavage in HCT116 cells. Overall, Frondanol A5 exhibits potential chemopreventive properties for colon carcinogenesis, which suggests further development of this sea cucumber extract. Cancer Prev Res; 3(1); 82-91. (c) 2010 AACR. C1 [Janakiram, Naveena B.; Mohammed, Altaf; Zhang, Yuting; Choi, Chang-In; Rao, Chinthalapally V.] Univ Oklahoma, Inst Canc, Hlth Sci Ctr, Dept Med,Hem Onc Sect, Oklahoma City, OK 73104 USA. [Woodward, Carl; Collin, Peter] Coastside Bio Resources, Stonington, ME USA. [Steele, Vernon E.] NCI, Canc Prevent Div, NIH, Rockville, MD USA. RP Rao, CV (reprint author), Univ Oklahoma, Inst Canc, Hlth Sci Ctr, Dept Med,Hem Onc Sect, 975 NE 10th St,BRC 1203, Oklahoma City, OK 73104 USA. EM cv-rao@ouhsc.edu FU National Cancer Institute [CN-N01-53300] FX National Cancer Institute CN-N01-53300. NR 45 TC 22 Z9 24 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 82 EP 91 DI 10.1158/1940-6207.CAPR-09-0112 PG 10 WC Oncology SC Oncology GA 539YK UT WOS:000273295500011 PM 20051375 ER PT J AU Thompson, PA Hsu, CH Green, S Stopeck, AT Johnson, K Alberts, DS Chow, HHS AF Thompson, Patricia A. Hsu, Chiu-Hsieh Green, Sylvan Stopeck, Alison T. Johnson, Karen Alberts, David S. Chow, H-H. Sherry TI Sulindac and Sulindac Metabolites in Nipple Aspirate Fluid and Effect on Drug Targets in a Phase I Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BREAST-CANCER RISK; PROSTAGLANDIN E-2 CONCENTRATIONS; POSTMENOPAUSAL WOMEN; ACTIVATED GENE; EXPRESSION; INHIBITORS; CELLS; COX-2; CYCLOOXYGENASE-2 AB Regular use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated with reduced risk of breast cancer. Sulindac, a nonselective NSAID with both cyclooxygenase-2-dependent and -independent activities, is a candidate for breast chemoprevention. We conducted a phase Ib trial in 30 women at increased risk for breast cancer to evaluate the breast tissue distribution of sulindac at two dose levels (150 mg daily and 150 mg twice daily for 6 weeks), using nipple aspirate fluid (NAF) as a surrogate of breast tissue drug exposure. We also explored the effect of sulindac on drug-induced biomarkers in NAF. We show that sulindac and its metabolites partition to human breast as measured by NAF levels. Sulindac intervention did not decrease 13,14-dihydro-15-keto prostaglandin A(2), a stable derivative of prostaglandin E(2), in NAF, but exposure was associated with a significant trend towards higher levels of growth differentiation factor 15 in NAF in women receiving 150 mg twice daily (P = 0.038). These results are the first to show partitioning of sulindac and metabolites to human breast tissue and the first evidence for a potential dose-dependent effect of sulindac on growth differentiation factor 15 levels in NAF. Cancer Prev Res; 3(1); 101-7. (c) 2010 AACR. C1 [Thompson, Patricia A.; Hsu, Chiu-Hsieh; Green, Sylvan; Stopeck, Alison T.; Alberts, David S.; Chow, H-H. Sherry] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Thompson, Patricia A.; Hsu, Chiu-Hsieh; Green, Sylvan] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA. [Johnson, Karen] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Thompson, PA (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA. EM pthompson@azcc.arizona.edu FU National Cancer Institute, Division of Cancer Prevention [N01CN35158] FX National Cancer Institute, Division of Cancer Prevention, contract no. N01CN35158. NR 24 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2010 VL 3 IS 1 BP 101 EP 107 DI 10.1158/1940-6207.CAPR-09-0120 PG 7 WC Oncology SC Oncology GA 539YK UT WOS:000273295500013 PM 20051377 ER PT J AU Wu, YJ Brodt, P Sun, H Mejia, W Novosyadlyy, R Nunez, N Chen, XL Mendoza, A Hong, SH Khanna, C Yakar, S AF Wu, Yingjie Brodt, Pnina Sun, Hui Mejia, Wilson Novosyadlyy, Ruslan Nunez, Nomeli Chen, Xiaoli Mendoza, Arnulfo Hong, Sung-Hyeok Khanna, Chand Yakar, Shoshana TI Insulin-Like Growth Factor-I Regulates the Liver Microenvironment in Obese Mice and Promotes Liver Metastasis SO CANCER RESEARCH LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; CELL-ADHESION MOLECULES; DIET-INDUCED OBESITY; CANCER-CELLS; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; TUMOR-GROWTH; INFLAMMATION; PROGRESSION; SENSITIVITY AB Among the mechanisms implicated in the tumor-promoting effects of obesity, signaling by insulin-like growth factor-I (IGF-I) and insulin has received considerable attention. However, the emerging realization that obesity is associated with chronic inflammation has prompted other consideration of how the IGF-I axis may participate in cancer progression. In the present study, we used two mouse models of chronic (LID) and inducible (iLID) igf-1 gene deficiency in the liver to investigate the role of IGF-I in regulating the host microenvironment and colorectal carcinoma growth and metastasis in obese mice. Obese mice had a heightened inflammatory response in the liver, which was abolished in mice with chronic IGF-I deficiency (LID). In control animals changes to the hepatic microenvironment associated with obesity sustained the presence of tumor cells in the liver and increased the incidence of hepatic metastases after intrasplenic/portal inoculation of colon carcinoma cells. These changes did not occur in LID mice with chlonic IGF-1 deficiency. In contrast, these changes occured in iLID mice with acute IGF-1 deficiency, in the same manner as the control animals, revealing a fundamental difference in the nature of the requirement for IGF-1 on tumor growth and metastasis. In the setting of obesity, our findings imply that IGF-1 is critical to activate and sustain an inflammatory response in the liver that is needed for hepatic metastasis, not only through direct, paracrine effect on tumor cell growth, but also through indirect effects involving the tumor microenvironment. Cancer Res; 70(1); 57-67. (C)2010 AACR. C1 [Wu, Yingjie; Sun, Hui; Mejia, Wilson; Novosyadlyy, Ruslan; Yakar, Shoshana] Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Brodt, Pnina] McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. [Brodt, Pnina] McGill Univ, Dept Med, Montreal, PQ H3A 2T5, Canada. [Nunez, Nomeli] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA. [Chen, Xiaoli] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN USA. [Mendoza, Arnulfo; Hong, Sung-Hyeok; Khanna, Chand] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yakar, S (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. EM shoshana.yakar@mssm.edu FU Canadian Institute for Health Research [MOP-81201] FX Canadian Institute for Health Research grant MOP-81201. NR 43 TC 49 Z9 52 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2010 VL 70 IS 1 BP 57 EP 67 DI 10.1158/0008-5472.CAN-09-2472 PG 11 WC Oncology SC Oncology GA 606EH UT WOS:000278404300009 PM 20048072 ER PT J AU Saini, V Shoemaker, RH AF Saini, Vaibhav Shoemaker, Robert H. TI Potential for therapeutic targeting of tumor stem cells SO CANCER SCIENCE LA English DT Review ID BREAST-CANCER CELLS; GENE-EXPRESSION; DRUG-RESISTANCE; IDENTIFICATION; GLIOBLASTOMA; MELANOMA; LRIG1; CHEMORESISTANCE; CHEMOTHERAPY; DEGRADATION AB Recent developments in isolation and characterization of tumor stem cells (TSCs) have opened new possibilities for developing TSC-targeted therapies. Extensive efforts have been made to ascertain markers of TSCs, including cell surface, enzymatic, gene expression profile, and functional markers. These markers and the technologies used to identify and isolate TSCs are discussed in this review. TSC characteristics, such as quiescence, multidrug resistance, enhanced DNA repair ability, and anti-apoptotic mechanisms, and various features of the in vivo niche, which may make them resistant to conventional therapy, are also discussed here. The increasing understanding of aberrantly expressed molecules and signaling pathways in TSCs may provide the foundation for design of therapeutic strategies for TSC ablation. (Cancer Sci 2009). C1 [Saini, Vaibhav; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. RP Shoemaker, RH (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. EM shoemakr@mail.nih.gov NR 51 TC 35 Z9 38 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JAN PY 2010 VL 101 IS 1 BP 16 EP 21 DI 10.1111/j.1349-7006.2009.01371.x PG 6 WC Oncology SC Oncology GA 530ZM UT WOS:000272631500003 PM 19860850 ER PT S AU Kuznetsov, SG Chang, SW Sharan, SK AF Kuznetsov, Sergey G. Chang, Suhwan Sharan, Shyam K. BE Webb, M TI Functional Analysis of Human BRCA2 Variants Using a Mouse Embryonic Stem Cell-Based Assay SO CANCER SUSCEPTIBILITY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Breast cancer; BRCA2; Variants of unknown clinical significance (VUS); Missense mutation; Mouse embryonic stem (ES) cells; Functional assay; DNA repair; Bacterial artificial chromosome; (BAG); HPRT7 minigene ID SEQUENCE VARIANTS; MUTATIONS; CULTURE; GENES; LINES; MICE AB We describe here a comprehensive and reliable assay to test the functional significance or variants of unknown clinical significance (VUS) identified in the human breast cancer susceptibility gene, BRCA2. lhc assay is based on the ability of human BRCA2 to complement the loss ofendogenous Rtya2 in mouse embryonic stem cells. The procedure involves generation of a desired mutation in BRCA2 present in a bacterial artificial chromosome (BAC) and the introduction of the BAG into ES cells engineered For the assay. These ES cells have one null and one conditional allele of Brca2. First, the effect of the BRCA2 variants on the viability of ES cells is tested by Cre-mediated deletion of the conditional allele. Subsequently, variants that result in viable ES cells are examined for their effect on known functions of BRCA2 using a variety of functional assays such as sensitivity to genotoxic agents, in vivo and in vitro proliferation, effecton homologous recombination and genomic stability. The method described herein allows for the analysis of three to five sequence variants within 2-3 months. This approach can also be used for functional analysis of variants identified in other human disease genes that result in a phenotype detectable in ES cells. C1 [Kuznetsov, Sergey G.; Chang, Suhwan; Sharan, Shyam K.] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Kuznetsov, Sergey G.] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. RP Kuznetsov, SG (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA. OI Kuznetsov, Sergey/0000-0002-5662-9700 NR 24 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-758-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 653 BP 259 EP 280 DI 10.1007/978-1-60761-759-4_16 D2 10.1007/978-1-60761-759-4 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BQW51 UT WOS:000282015000016 PM 20721749 ER PT J AU Schetter, AJ Heegaard, NHH Harris, CC AF Schetter, Aaron J. Heegaard, Niels H. H. Harris, Curtis C. TI Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways SO CARCINOGENESIS LA English DT Review ID NF-KAPPA-B; CELL LUNG-CANCER; HELICOBACTER-PYLORI INFECTION; CHRONIC LYMPHOCYTIC-LEUKEMIA; PREVENT COLORECTAL ADENOMAS; OXIDE SYNTHASE EXPRESSION; COLITIS-ASSOCIATED CANCER; TUMOR-SUPPRESSOR GENE; HUMAN BREAST-CANCER; NITRIC-OXIDE AB Chronic inflammation and infection are major causes of cancer. There are continued improvements to our understanding of the molecular connections between inflammation and cancer. Key mediators of inflammation-induced cancer include nuclear factor kappa B, reactive oxygen and nitrogen species, inflammatory cytokines, prostaglandins and specific microRNAs. The collective activity of these mediators is largely responsible for either a pro-tumorigenic or anti-tumorigenic inflammatory response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. As our understanding grows, inflammatory mediators will provide opportunities to develop novel diagnostic and therapeutic strategies. In this review, we provide a general overview of the connection between inflammation, microRNAs and cancer and highlight how our improved understanding of these connections may provide novel preventive, diagnostic and therapeutic strategies to reduce the health burden of cancer. C1 [Schetter, Aaron J.; Heegaard, Niels H. H.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Heegaard, Niels H. H.] Statens Serum Inst, Dept Clin Biochem & Immunol, DK-2300 Copenhagen, Denmark. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM harrisc@mail.nih.gov FU National Cancer Institute; C.C.H; Center for Cancer Research; National Institutes of Health; Division of Microbiology and Diagnostics; Statens Serum Institute, Denmark FX Intramural Research Program of the National Cancer Institute to A.J.S. and C.C.H.; Center for Cancer Research; National Institutes of Health; Division of Microbiology and Diagnostics to N.H.H.H.; Statens Serum Institute, Denmark. NR 184 TC 257 Z9 276 U1 4 U2 63 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2010 VL 31 IS 1 BP 37 EP 49 DI 10.1093/carcin/bgp272 PG 13 WC Oncology SC Oncology GA 542KW UT WOS:000273493100005 PM 19955394 ER PT J AU Chung, CC Magalhaes, WCS Gonzalez-Bosquet, J Chanock, SJ AF Chung, Charles C. Magalhaes, Wagner C. S. Gonzalez-Bosquet, Jesus Chanock, Stephen J. TI Genome-wide association studies in cancer-current and future directions SO CARCINOGENESIS LA English DT Review ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COPY-NUMBER VARIATION; IDIOPATHIC PULMONARY-FIBROSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; COMMON SEQUENCE VARIANTS; URINARY-BLADDER CANCER; RISK-ASSOCIATED LOCI; PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER AB Genome-wide association studies (GWAS) have emerged as an important tool for discovering regions of the genome that harbor genetic variants that confer risk for different types of cancers. The success of GWAS in the last 3 years is due to the convergence of new technologies that can genotype hundreds of thousands of single-nucleotide polymorphism markers together with comprehensive annotation of genetic variation. This approach has provided the opportunity to scan across the genome in a sufficiently large set of cases and controls without a set of prior hypotheses in search of susceptibility alleles with low effect sizes. Generally, the susceptibility alleles discovered thus far are common, namely, with a frequency in one or more population of > 10% and each allele confers a small contribution to the overall risk for the disease. For nearly all regions conclusively identified by GWAS, the per allele effect sizes estimated are < 1.3. Consequently, the findings of GWAS underscore the complex nature of cancer and have focused attention on a subset of the genetic variants that comprise the genomic architecture of each type of cancer, which already can differ substantially by the number of regions associated with specific types of cancer. For instance, in prostate cancer, there could be > 30 distinct regions harboring common susceptibility alleles identified by GWAS, whereas in lung cancer, a disease strongly driven by exposure to tobacco products, so far, only three regions have been conclusively established. To date, > 85 regions have been conclusively associated in over a dozen different cancers, yet no more than five regions have been associated with more than one distinct cancer type. GWAS are an important discovery tool that require extensive follow-up to map each region, investigate the biological mechanism underpinning the association and eventually test the optimal markers for assessing risk for a disease or its outcome, such as in pharmacogenomics, the study of the effect of genetic variation on pharmacological interventions. The success of GWAS has opened new horizons for exploration and highlighted the complex genomic architecture of disease susceptibility. C1 [Chung, Charles C.; Magalhaes, Wagner C. S.; Gonzalez-Bosquet, Jesus; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Magalhaes, Wagner C. S.] Univ Fed Minas Gerais, Dept Biol Geral, Inst Ciencias Biol, BR-31270910 Belo Horizonte, MG, Brazil. RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Magalhaes, Wagner/D-8822-2015 NR 152 TC 60 Z9 62 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2010 VL 31 IS 1 BP 111 EP 120 DI 10.1093/carcin/bgp273 PG 10 WC Oncology SC Oncology GA 542KW UT WOS:000273493100012 PM 19906782 ER PT J AU Jaquish, CE White, CC North, K Monda, K Heard-Costa, NL Lee, MHJ Johnson, AD Zillikens, M Harris, TB Smith, AV Gudnason, V Van Duijn, CM Janssens, ACJW Broer, L Hofman, A Uitterlinden, AG Feitosa, M Borecki, I Atwood, LA Dupuis, J Cupples, LA Fox, CS AF Jaquish, C. E. White, C. C. North, K. Monda, K. Heard-Costa, N. L. Lee, M. H. J. Johnson, A. D. Zillikens, M. Harris, T. B. Smith, A., V Gudnason, V Van Duijn, C. M. Janssens, A. C. J. W. Broer, L. Hofman, A. Uitterlinden, A. G. Feitosa, M. Borecki, I Atwood, L. A. Dupuis, J. Cupples, L. A. Fox, C. S. TI An Assessment of Genetic Effects on Body Weight Change during Adulthood SO CARDIOLOGY LA English DT Meeting Abstract C1 [Jaquish, C. E.] NHLBI, NIH, Bethesda, MD USA. [White, C. C.; Dupuis, J.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [North, K.; Monda, K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Heard-Costa, N. L.; Lee, M. H. J.; Atwood, L. A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Jaquish, C. E.; Johnson, A. D.; Fox, C. S.] NHLBI, Div Intramural Res, NHLBIs Framingham Heart Study, Framingham, MA USA. [Zillikens, M.; Van Duijn, C. M.; Janssens, A. C. J. W.; Broer, L.; Hofman, A.; Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Smith, A., V; Gudnason, V] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, V] Univ Iceland, Reykjavik, Iceland. [Van Duijn, C. M.] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Feitosa, M.; Borecki, I] Washington Univ, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. RI Johnson, Andrew/G-6520-2013; Gudnason, Vilmundur/K-6885-2015; Feitosa, Mary/K-8044-2012 OI Gudnason, Vilmundur/0000-0001-5696-0084; Feitosa, Mary/0000-0002-0933-2410 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 117 SU 1 BP 5 EP 6 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648BD UT WOS:000281664500012 ER PT J AU Elmariah, S O'Brien, KD Budoff, MJ Bluemke, DA Delaney, JAC Fuster, V Kronmal, RA Halperin, JL AF Elmariah, S. O'Brien, K. D. Budoff, M. J. Bluemke, D. A. Delaney, J. A. C. Fuster, V. Kronmal, R. A. Halperin, J. L. TI Relationship between Left Ventricular Mass and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis SO CARDIOLOGY LA English DT Meeting Abstract C1 [Elmariah, S.; Fuster, V.; Halperin, J. L.] Mt Sinai Sch Med, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA. [O'Brien, K. D.; Delaney, J. A. C.; Kronmal, R. A.] Univ Washington, Seattle, WA 98195 USA. [Budoff, M. J.] Harbor UCLA, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA. [Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Fuster, V.] Ctr Nacl Invest Cardiovasc, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 115 IS 4 BP 265 EP 265 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 584TD UT WOS:000276774900039 ER PT J AU Marini, JC Cabral, WA Barnes, AM AF Marini, Joan C. Cabral, Wayne A. Barnes, Aileen M. TI Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta SO CELL AND TISSUE RESEARCH LA English DT Review DE Recessive osteogenesis imperfecta; CRTAP; P3H1/LEPRE1; Prolyl 3-hydroxylation; Osteochondrodysplasia ID CARTILAGE-ASSOCIATED PROTEIN; CIS-TRANS-ISOMERASE; MEMBRANE-ASSOCIATED PROTEOGLYCAN; PROLYL 3-HYDROXYLASE; I PROCOLLAGEN; INTRACELLULAR RETENTION; COLLAGEN GLOMERULOPATHY; CDNA CLONING; TRIPLE-HELIX; ENZYME AB Classical osteogenesis imperfecta (OI) is a dominant genetic disorder of connective tissue caused by mutations in either of the two genes encoding type I collagen, COL1A1 and COL1A2. Recent investigations, however, have generated a new paradigm for OI incorporating many of the prototypical features that distinguish dominant and recessive conditions, within a type I collagen framework. We and others have shown that the long-sought cause of the recessive form of OI, first postulated in the Sillence classification, lies in defects in the genes encoding cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1/LEPRE1). Together with cyclophilin B (PPIB), CRTAP and P3H1 comprise the collagen prolyl 3-hydroxylation complex, which catalyzes a specific post-translational modification of types I, II, and V collagen, and may act as a general chaperone. Patients with mutations in CRTAP or LEPRE1 have a lethal to severe osteochondrodystrophy that overlaps with Sillence types II and III OI but has distinctive features. Infants with recessive OI have white sclerae, undertubulation of the long bones, gracile ribs without beading, and a small to normal head circumference. Those who survive to childhood or the teen years have severe growth deficiency and extreme bone fragility. Most causative mutations result in null alleles, with the absence or severe reduction of gene transcripts and proteins. As expected, 3-hydroxylation of the Pro986 residue is absent or severly reduced, but bone severity and survival length do not correlate with the extent of residual hydroxylation. Surprisingly, the collagen produced by cells with an absence of Pro986 hydroxylation has helical overmodification by lysyl hydroxylase and prolyl 4-hydroxylase, indicating that the folding of the collagen helix has been substantially delayed. C1 [Marini, Joan C.; Cabral, Wayne A.; Barnes, Aileen M.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Cabral, WA (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Rm 10-10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov; cabralw@mail.nih.gov FU Intramural NIH HHS [Z01 HD000408-24, Z01 HD008830-01, Z99 HD999999, ZIA HD000408-27] NR 61 TC 54 Z9 56 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2010 VL 339 IS 1 BP 59 EP 70 DI 10.1007/s00441-009-0872-0 PG 12 WC Cell Biology SC Cell Biology GA 548IF UT WOS:000273953300006 PM 19862557 ER PT S AU Danthi, P Guglielmi, KM Kirchner, E Mainou, B Stehle, T Dermody, TS AF Danthi, Pranav Guglielmi, Kristen M. Kirchner, Eva Mainou, Bernardo Stehle, Thilo Dermody, Terence S. BE Johnson, JE TI From Touchdown to Transcription: The Reovirus Cell Entry Pathway SO CELL ENTRY BY NON-ENVELOPED VIRUSES SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID JUNCTIONAL ADHESION MOLECULE; CAPSID PROTEIN MU-1; INFECTIOUS SUBVIRION PARTICLES; NF-KAPPA-B; MEMBRANE-PENETRATION PROTEIN; CENTRAL-NERVOUS-SYSTEM; CLATHRIN-COATED PITS; MAMMALIAN REOVIRUS; ATTACHMENT PROTEIN; SIALIC-ACID AB Mammalian orthoreoviruses (reoviruses) are prototype members of the Reoviridae family of nonenveloped viruses. Reoviruses contain ten double-stranded RNA gene segments enclosed in two concentric protein shells, outer capsid and core. These viruses serve as a versatile experimental system for studies of virus cell entry, innate immunity, and organ-specific disease. Reoviruses engage cells by binding to cell-surface carbohydrates and the immunoglobulin superfamily member, junctional adhesion molecule-A (JAM-A). JAM-A is a homodimer formed by extensive contacts between its N-terminal immunoglobulin-like domains. Reovirus attachment protein sigma 1 disrupts the JAM-A dimer, engaging a single JAM-A molecule by virtually the same interface used for JAM-A homodimerization. Following attachment to JAM-A and carbohydrate, reovirus internalization is promoted by beta 1 integrins, most likely via clathrin-dependent endocytosis. In the endocytic compartment, reovirus outer-capsid protein sigma 3 is removed by cathepsin proteases, which exposes the viral membrane-penetration protein, mu 1. Proteolytic processing and conformational rearrangements of mu 1 mediate endosomal membrane rupture and delivery of transcriptionally active reovirus core particles into the host cell cytoplasm. These events also allow the phi cleavage fragment of mu 1 to escape into the cytoplasm where it activates NF-kappa B and elicits apoptosis. This review will focus on mechanisms of reovirus cell entry and activation of innate immune response signaling pathways. C1 [Guglielmi, Kristen M.; Mainou, Bernardo; Stehle, Thilo; Dermody, Terence S.] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN 37232 USA. [Danthi, Pranav] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Guglielmi, Kristen M.; Dermody, Terence S.] Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA. [Guglielmi, Kristen M.; Mainou, Bernardo; Stehle, Thilo; Dermody, Terence S.] Vanderbilt Univ, Elizabeth B Lamb Ctr Pediat Res, Sch Med, MCN D7235, Nashville, TN 37232 USA. [Guglielmi, Kristen M.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Kirchner, Eva; Stehle, Thilo] Univ Tubingen, Interfak Inst Biochem, D-72076 Tubingen, Germany. RP Dermody, TS (reprint author), Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN 37232 USA. EM terry.dermody@vanderbilt.edu OI Mainou, Bernardo/0000-0002-7721-183X; Danthi, Pranav/0000-0001-6199-6022 FU NHLBI NIH HHS [T32 HL007751, T32 HL07751]; NIAID NIH HHS [F32 AI080108, R01 AI032539, R01 AI038296, R01 AI050080, R01 AI38296, R01 AI50080, R37 AI038296, R37 AI32539]; NIGMS NIH HHS [T32 GM08554, R01 GM067853, R01 GM67853, T32 GM008554] NR 155 TC 32 Z9 32 U1 0 U2 19 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-13331-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 343 BP 91 EP 119 DI 10.1007/82_2010_32 D2 10.1007/978-3-642-13332-9 PG 29 WC Immunology; Microbiology SC Immunology; Microbiology GA BQZ12 UT WOS:000282187600004 PM 20397070 ER PT J AU Zhu, JF Paul, WE AF Zhu, Jinfang Paul, William E. TI Heterogeneity and plasticity of T helper cells SO CELL RESEARCH LA English DT Review DE CD4; Tregs; T cell differentiation; transcription factors; cytokines ID GROWTH-FACTOR-BETA; LATENCY-ASSOCIATED PEPTIDE; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; IMMUNE-RESPONSES; IN-VIVO; AUTOIMMUNE ENCEPHALOMYELITIS; TH2 DIFFERENTIATION; LEISHMANIA-MAJOR; ORAL TOLERANCE AB CD4 T helper (Th) cells play critical roles in adaptive immune responses. They recruit and activate other immune cells including B cells, CD8 T cells, macrophages, mast cells, neutrophils, eosinophils and basophils. Based on their functions, their pattern of cytokine secretion and their expression of specific transcription factors, Th cells, differentiated from naive CD4 T cells, are classified into four major lineages, Th1, Th2, Th17 and T regulatory (Treg) cells, although other Th lineages may exist. Subsets of the same lineage may express different effector cytokines, reside at different locations or give rise to cells with different fates, whereas cells from different lineages may secrete common cytokines, such as IL-2, IL-9 and IL-10, resulting in massive heterogeneity of the Th cell population. In addition, the pattern of cytokine secretion may switch from that of one lineage toward another under certain circumstances, suggesting that Th cells are plastic. Tregs are also more heterogeneous and plastic than were originally thought. In this review, we summarize recent reports on heterogeneity and plasticity of Th cells, and discuss potential mechanisms and implications of such features that Th cells display. C1 [Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov; wpaul@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX This work is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. NR 77 TC 243 Z9 251 U1 1 U2 34 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JAN PY 2010 VL 20 IS 1 BP 4 EP 12 DI 10.1038/cr.2009.138 PG 9 WC Cell Biology SC Cell Biology GA 546DT UT WOS:000273790500002 PM 20010916 ER PT J AU Wan, FY Lenardo, MJ AF Wan, Fengyi Lenardo, Michael J. TI The nuclear signaling of NF-kappa B: current knowledge, new insights, and future perspectives SO CELL RESEARCH LA English DT Review DE RPS3; immunity; DNA binding ID DEPENDENT GENE-EXPRESSION; UBIQUITIN-LIGASE; TRANSCRIPTION FACTORS; ANTIGEN-RECEPTOR; TUMOR-SUPPRESSOR; BINDING SITES; CELL-SURVIVAL; P65 SUBUNIT; ACTIVATION; PROTEIN AB The nuclear factor-kappa B (NF-kappa B) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-kappa B is normally sequestered in the cytoplasm by a family of inhibitory proteins known as inhibitors of NF-kappa B (I kappa Bs). The signal pathways leading to the liberation and nuclear accumulation of NF-kappa B, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-kappa B must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-kappa B transcriptional activity. A non-Rel subunit of NF-kappa B, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-kappa B, including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-kappa B in the nucleus. Further insights into the nuclear events that govern NF-kappa B function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-kappa B-associated diseases. C1 [Wan, Fengyi; Lenardo, Michael J.] NIAID, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Wan, FY (reprint author), NIAID, Immunol Lab, Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. EM fwan@niaid.nih.gov FU NIH [1K99CA137171] FX We are grateful to our colleagues Andrew Snow, Amanda Weaver, and Michael Bern for critically reading the manuscript. We apologize to those who also made important contributions to the issues discussed and could not be cited due to space limit. The research in the authors' laboratory is supported by the Intramural Research Program of the NIAID, NIH. FW is a recipient of an NIH grant 1K99CA137171. NR 68 TC 139 Z9 160 U1 7 U2 30 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2010 VL 20 IS 1 BP 24 EP 33 DI 10.1038/cr.2009.137 PG 10 WC Cell Biology SC Cell Biology GA 546DT UT WOS:000273790500005 PM 19997086 ER PT J AU Airavaara, M Richie, C Castillo, PJ Chiocco, MJ Howard, DB Peranen, J Liu, C Fang, S Wang, Y Hoffer, BJ Harvey, BK AF Airavaara, M. Richie, C. Castillo, P. J. Chiocco, M. J. Howard, D. B. Peranen, J. Liu, C. Fang, S. Wang, Y. Hoffer, B. J. Harvey, B. K. TI Protective Effects of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Against lschemia and Endoplasmic Reticulum Stress SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 29-MAY 01, 2010 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Airavaara, M.; Richie, C.; Castillo, P. J.; Chiocco, M. J.; Howard, D. B.; Wang, Y.; Hoffer, B. J.; Harvey, B. K.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. [Peranen, J.] Univ Helsinki, Viikki Bioctr, Inst Biotechnol, Helsinki, Finland. [Liu, C.; Fang, S.] Univ Maryland, Inst Biotechnol, Baltimore, MD 21201 USA. RI Fang, Shengyun/H-3802-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 3 BP 330 EP 331 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 592ZB UT WOS:000277419400012 ER PT J AU Coggiano, M Dillon-Carter, O Chen, J Errico, S Freed, WJ AF Coggiano, M. Dillon-Carter, O. Chen, J. Errico, S. Freed, W. J. TI Rearrangements of Plasmid DNA in Rodent Mesencephalic Cell Lines Produced by Transfection SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 29-MAY 01, 2010 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Coggiano, M.; Dillon-Carter, O.; Chen, J.; Errico, S.; Freed, W. J.] Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 3 BP 335 EP 336 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 592ZB UT WOS:000277419400027 ER PT J AU Harvey, BK Airavaara, MT Hinzman, J Chiocco, MJ Shen, H Howard, DB Gerhardt, GA Hoffer, BJ Wang, Y AF Harvey, B. K. Airavaara, M. T. Hinzman, J. Chiocco, M. J. Shen, H. Howard, D. B. Gerhardt, G. A. Hoffer, B. J. Wang, Y. TI Overexpression of Glutamate Transporter (GLT1) by Adeno-Associated Viral Vector Reduces Extracellular Glutamate Overflow and Cerebral Infarction After Transient Middle Cerebral Artery Occlusion in Rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 29-MAY 01, 2010 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Harvey, B. K.; Airavaara, M. T.; Chiocco, M. J.; Shen, H.; Howard, D. B.; Hoffer, B. J.; Wang, Y.] Natl Inst Drug Abuse, Addict Res Ctr, Baltimore, MD 21224 USA. [Hinzman, J.; Gerhardt, G. A.] Univ Kentucky, Lexington, KY USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 3 BP 343 EP 343 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 592ZB UT WOS:000277419400047 ER PT J AU Hayakawa, J Hsieh, MM Anderson, DE Phang, O Uchida, N Washington, K Tisdale, JF AF Hayakawa, Jun Hsieh, Matthew M. Anderson, D. Eric Phang, Oswald Uchida, Naoya Washington, Kareem Tisdale, John F. TI The Assessment of Human Erythroid Output in NOD/SCID Mice Reconstituted With Human Hematopoietic Stem Cells SO CELL TRANSPLANTATION LA English DT Article DE NOD/LtSz-scid/IL2R gamma(null) mice; Erythropoiesis; Xenograft mouse model; Sickle cell; HbF; HbS; Hemoglobin switching; Lentiviral vector; GFP ID BLOOD CD34(+) CELLS; SCID IL2R-GAMMA(NULL) MICE; CORD-BLOOD; HEMOGLOBIN-SYNTHESIS; IN-VIVO; BETA-THALASSEMIA; EX-VIVO; PROLIFERATION; GENE; ERYTHROPOIESIS AB The third-generation NOD/LtSz-scid/IL2R gamma(null) (NOD/SCID IL2R gamma(null)) mouse represents a significantly improved xenograft model allowing high levels of human leukocyte engraftment over extended follow up. One remaining limitation of this mouse model, however, is the low level of circulating human erythrocytes. We established a practical ex vivo erythroid culture system of xenograft marrow progenitors to enrich for human erythroid progeny. At various time points after transplant, erythroid cells were easily assayed after 17 days of ex vivo culture of xenograft marrow, with nearly all nucleated cells of human origin and approximately 60% human GPA or CD71 positive. We then transplanted cord blood CD34(+) cells marked with a lentiviral vector encoding green fluorescent protein (GFP). Three months later, ex vivo culture of xenograft marrow progenitors showed 41.3% of the cultured erythroid cells were positive for GFP and human CD71, and 56.2% were positive for GFP and human GPA, similar to that of circulating leukocytes at the same time point. Next, G-CSF mobilized peripheral blood CD34(+) cells from a sickle cell trait subject were infused in this mouse model to determine if the hemoglobin pattern could be modeled. CD34(+) cells from the sickle cell trait subject engrafted equally compared to CD34(+) cells from normal subjects, establishing the sickle cell trait phenotype. Lastly, a comparison of adult-derived peripheral blood CD34(+) cells and cord blood-derived CD34(+) cells xenografted mice was made, and long term follow-up demonstrated a recapitulation of the fetal to adult hemoglobin switch. This approach should prove a useful tool for testing strategies for genetic manipulation of erythroid progeny and the study of hemoglobin switching. C1 [Hayakawa, Jun; Hsieh, Matthew M.; Phang, Oswald; Uchida, Naoya; Washington, Kareem; Tisdale, John F.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hayakawa, Jun; Hsieh, Matthew M.; Phang, Oswald; Uchida, Naoya; Washington, Kareem; Tisdale, John F.] Natl Inst Diabet & Digest & Kidney Disorders NIDD, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. [Anderson, D. Eric] Natl Inst Diabet & Digest & Kidney Disorders NIDD, Prote & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), 9000 Rockville Pike,Bldg 10,Room 9N112, Bethesda, MD 20892 USA. EM johntis@mail.nih.gov FU NIDDK at the NIH; NHLBI at the NIH FX This work was supported by the Intramural Research Program of NIDDK and NHLBI at the NIH. NR 32 TC 5 Z9 5 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 11 BP 1465 EP 1473 DI 10.3727/096368910X314161 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 704VY UT WOS:000286084900009 PM 21214970 ER PT J AU Mueller, MB Fischer, M Zellner, J Berner, A Dienstknecht, T Prantl, L Kujat, R Nerlich, M Tuan, RS Angele, P AF Mueller, Michael B. Fischer, Maria Zellner, Johannes Berner, Arne Dienstknecht, Thomas Prantl, Lukas Kujat, Richard Nerlich, Michael Tuan, Rocky S. Angele, Peter TI Hypertrophy in Mesenchymal Stem Cell Chondrogenesis: Effect of TGF-beta Isoforms and Chondrogenic Conditioning SO CELLS TISSUES ORGANS LA English DT Article DE Bone marrow stromal cell; Cartilage biology; Cartilage repair; Cell biology; Chondrogenic differentiation; Hypertrophy; Mesenchymal progenitor cell differentiation; Mesenchymal stem cells; Tissue engineering ID VITRO CARTILAGE FORMATION; BONE-MARROW; PROGENITOR CELLS; ENDOCHONDRAL OSSIFICATION; CHONDROCYTE MATURATION; MOLECULAR EVENTS; GENE-EXPRESSION; DIFFERENTIATION; CULTURE; GROWTH AB Induction of chondrogenesis in mesenchymal stem cells (MSCs) with TGF-beta leads to a hypertrophic phenotype. The hypertrophic maturation of the chondrocytes is dependent on the timed removal of TGF-beta and sensitive to hypertrophy-promoting agents in vitro. In this study, we have investigated whether TGF-beta 3, which has been shown to be more pro-chondrogenic compared to TGF-beta 1, similarly enhances terminal differentiation in an in vitro hypertrophy model of chondrogenically differentiating MSCs. In addition, we tested the impact of the time of chondrogenic conditioning on the enhancement of hypertrophy. MSCs were chondrogenically differentiated in pellet culture in medium containing TGF-beta 1 or TGF-beta 3. After 2 or 4 weeks, chondrogenic medium was switched to hypertrophy-inducing medium for 2 weeks. Aggregates were analyzed histologically and biochemically on days 14, 28 and 42. The switch to hypertrophy medium after 14 days induced hypertrophic cell morphology and significant increase in alkaline phosphatase activity compared to the chondrogenesis only control using both TGF-beta 1 and TGF-beta 3. After 28 days predifferentiation, differences between hypertrophic and control groups diminished compared to 14 days predifferentiation. In conclusion, chondrogenic conditioning with both TGF-beta isoforms similarly induced hypertrophy in our experiment and allowed the enhancement of the hypertrophic chondrocyte phenotype by hypertrophic medium. Enhancement of hypertrophy was seen more clearly after the shorter chondrogenic conditioning. Therefore, to utilize this experimental model as a tool to study hypertrophy in MSC chondrogenesis, a predifferentiation period of 14 days is recommended. Copyright (C) 2010 S. Karger AG, Basel C1 [Mueller, Michael B.; Fischer, Maria; Zellner, Johannes; Berner, Arne; Dienstknecht, Thomas; Prantl, Lukas; Kujat, Richard; Nerlich, Michael; Angele, Peter] Univ Regensburg, Ctr Med, Dept Trauma Surg, DE-93042 Regensburg, Germany. [Mueller, Michael B.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Pittsburgh, PA 15261 USA. RP Mueller, MB (reprint author), Univ Regensburg, Ctr Med, Dept Trauma Surg, Franz Josef Strauss Allee 11, DE-93042 Regensburg, Germany. EM michaelbmueller@web.de OI Zellner, Johannes/0000-0001-5385-9378 FU AO Research Fund [S-07-3M]; German Research Foundation [DFG; MU2318-1]; NIH [Z01 AR41131] FX This study was supported by AO Research Fund (S-07-3M), German Research Foundation (DFG; MU2318-1) and the NIH Intramural Research Program (Z01 AR41131). NR 30 TC 60 Z9 67 U1 0 U2 14 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2010 VL 192 IS 3 BP 158 EP 166 DI 10.1159/000313399 PG 9 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 641QK UT WOS:000281144600002 PM 20407224 ER PT J AU Facchinetti, MM Gandini, NA Fermento, ME Sterin-Speziale, NB Ji, YM Patel, V Gutkind, JS Rivadulla, MG Curino, AC AF Facchinetti, Maria M. Gandini, Norberto A. Fermento, Maria E. Sterin-Speziale, Norma B. Ji, Youngmi Patel, Vyomesh Gutkind, J. Silvio Rivadulla, Maria G. Curino, Alejandro C. TI The Expression of Sphingosine Kinase-1 in Head and Neck Carcinoma SO CELLS TISSUES ORGANS LA English DT Article DE Sphingosine kinase; Oral cancer; Sphingolipids; Tissue microarray ID SQUAMOUS-CELL CARCINOMA; MOLECULAR-CLONING; CANCER-CELLS; FUNCTIONAL-CHARACTERIZATION; P53-INDEPENDENT INDUCTION; TOPOISOMERASE-II; PLASMA-MEMBRANE; SPHINGOSINE-1-PHOSPHATE; APOPTOSIS; PHENOXODIOL AB Sphingosine kinase-1 (SPHK1) modulates the proliferation, apoptosis and differentiation of keratinocytes through the regulation of ceramide and sphingosine-1-phosphate levels. However, studies on the expression of SPHK1 in human head and neck squamous cell carcinoma (HNSCC) specimens are lacking. Therefore, the aim of the present work was to evaluate SPHK1 expression in human primary HNSCCs and to correlate the results with clinical and anatomopathological parameters. We investigated the expression of this protein by immunohistochemistry performed in tissue microarrays of HNSCC and in an independent cohort of 37 paraffin-embedded specimens. SPHK1 expression was further validated by real-time PCR performed on laser capture-microdissected tissue samples. The positive rate of SPHK1 protein in the cancerous tissues was significantly higher (74%) than that in the nontumor oral tissues (23%), and malignant tissues showed stronger immunoreactivity for SPHK1 than normal matching samples. These results were confirmed by real-time PCR quantification of SPHK1 mRNA. Interestingly, the positive expression of SPHK1 was associated with shorter patient survival time (Kaplan-Meier survival curves) and with the loss of p21 expression. Taken together, these results demonstrate that SPHK1 is upregulated in HNSCC and provide clues of the role SPHK1 might play in tumor progression. Copyright (c) 2010 S. Karger AG, Basel C1 [Facchinetti, Maria M.; Gandini, Norberto A.; Fermento, Maria E.; Curino, Alejandro C.] Consejo Nacl Invest Cient & Tecn, Lab Biol Basica Canc, Inst Invest Bioquim Bahia Blanca, INIBIBB, Bahia Blanca, Buenos Aires, Argentina. [Rivadulla, Maria G.] Serv Patol Hosp Municipal Dr Leonidas Lucero, Bahia Blanca, Buenos Aires, Argentina. [Sterin-Speziale, Norma B.] UBA, Lab Biol Celular & Histol, Fac Farm & Bioquim, Buenos Aires, DF, Argentina. [Ji, Youngmi] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Curino, AC (reprint author), Ctr Cient Tecnol Bahia Blanca, Inst Invest Bioquim Bahia Blanca INIBIBB, Lab Biol Basica Canc, Camino Carrindanga Km 7 CC 857, RA-8000 Bahia Blanca, Buenos Aires, Argentina. EM acurino@criba.edu.ar RI Gutkind, J. Silvio/A-1053-2009 FU Scientific Commission of Buenos Aires Province (CIC); Secretary of Science and Technology of the Universidad Nacional del Sur; CONICET FX This work was supported by grants from the Scientific Commission of Buenos Aires Province (CIC) and from the Secretary of Science and Technology of the Universidad Nacional del Sur. M.E.F. is the recipient of a fellowship from the CIC and A.G. from the CONICET. We thank Dr. Lina M. Obeid for generously sharing the polyclonal SPHK1 antibody with us. NR 63 TC 37 Z9 41 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2010 VL 192 IS 5 BP 314 EP 324 DI 10.1159/000318173 PG 11 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 666QL UT WOS:000283131500004 PM 20606403 ER PT J AU Wang, SM Fu, LJ Duan, XL Crooks, DR Yu, P Qian, ZM Di, XJ Li, J Rouault, TA Chang, YZ AF Wang, S. -M. Fu, L. -J. Duan, X. -L. Crooks, D. R. Yu, P. Qian, Z. -M. Di, X. -J. Li, J. Rouault, T. A. Chang, Y. -Z. TI Role of hepcidin in murine brain iron metabolism SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Hepcidin; Ferroportin1; Brain iron metabolism; Aging; Murine ID RESTLESS LEGS SYNDROME; DIVALENT METAL TRANSPORTER-1; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; NEURODEGENERATIVE DISORDERS; CERULOPLASMIN EXPRESSION; FERROXIDASE ACTIVITY; PEPTIDE HEPCIDIN; HORMONE HEPCIDIN; GENE-EXPRESSION AB Brain iron homeostasis is maintained by a balance of both iron uptake and release, and accumulating evidence has revealed that brain iron concentrations increase with aging. Hepcidin, an iron regulatory hormone produced by hepatocytes in response to inflammatory stimuli, iron, and hypoxia, has been shown to be the long-sought hormone responsible for the regulation of body iron balance and recycling in mammals. In this study, we report that hepcidin is widely expressed in the murine brain. In cerebral cortex, hippocampus and striatum, hepcidin mRNA levels increased with aging. Injection of hepcidin into the lateral cerebral ventricle resulted in decreased Fpn1 protein levels in cerebral cortex, hippocampus, and striatum. Additionally, treatment of primary cultured neurons with hepcidin caused decreased neuronal iron release and Fpn1 protein levels. Together, our data provide further evidence that hepcidin may be involved in the regulation of brain iron metabolism. C1 [Wang, S. -M.; Fu, L. -J.; Duan, X. -L.; Yu, P.; Qian, Z. -M.; Di, X. -J.; Li, J.; Chang, Y. -Z.] Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Hebei, Peoples R China. [Crooks, D. R.; Rouault, T. A.] NICHHD, Program Mol Med, Bethesda, MD 20892 USA. [Qian, Z. -M.] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Lab Iron Metab, Jiulong, Hong Kong, Peoples R China. RP Chang, YZ (reprint author), Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Hebei, Peoples R China. EM frankyzchang@yahoo.com.hk RI Qian , Zhong Ming/B-3089-2010 FU National Natural Sciences Foundation of China [30570957, 30871260]; Natural Science Foundation of Hebei Province [C2007000251] FX This work was supported by National Natural Sciences Foundation of China (30570957, 30871260) and Natural Science Foundation of Hebei Province (C2007000251). NR 53 TC 38 Z9 49 U1 0 U2 11 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2010 VL 67 IS 1 BP 123 EP 133 DI 10.1007/s00018-009-0167-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 540DB UT WOS:000273309900011 PM 19898775 ER PT J AU Kohler, ME Hallett, WHD Chen, QR Khan, J Johnson, BD Orentas, RJ AF Kohler, M. Eric Hallett, William H. D. Chen, Qing-Rong Khan, Javed Johnson, Bryon D. Orentas, Rimas J. TI Early expression of stem cell-associated genes within the CD8 compartment after treatment with a tumor vaccine SO CELLULAR IMMUNOLOGY LA English DT Article DE Cancer vaccines; Neuroblastoma; Tumor immunity; Cellular immunity; CD8; Gene expression profiling; Stem cells; GSEA ID IMMUNOLOGICAL SELF-TOLERANCE; CHRONIC VIRAL-INFECTION; REGULATORY T-CELLS; IN-VIVO; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSES; EFFECTOR-CELLS; MESSENGER-RNA; CUTTING EDGE; HELPER-CELLS AB Using a mouse neuroblastoma cell line, we have demonstrated that vaccination of tumor-free mice with a cell-based vaccine leads to productive immunity and resistance to tumor challenge, while vaccination of tumor-bearing mice does not. The T cell immunity induced by this vaccine, as measured by in vitro assays, is amplified by the depletion of Treg. Our goal is to understand this barrier to the development of protective cellular immunity. mRNA microarray analyses of CD8(+) T cells from nave or tumor-bearing mice undergoing vaccination were carried out with or without administering anti-CD25 antibody. Gene-expression pathway analysis revealed the presence of CD8(+) T cells expressing stem cell-associated genes early after induction of productive anti-tumor immunity in tumor-free mice, prior to any phenotypic changes, but not in tumor-bearing mice. These data demonstrate that early after the induction of productive immune response, cells within the CD8(+) T cell compartment adopt a stem cell-related genetic phenotype that correlates with increased anti-tumor function. Published by Elsevier Inc. C1 [Orentas, Rimas J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Kohler, M. Eric; Hallett, William H. D.; Johnson, Bryon D.] Med Coll Wisconsin, Dept Pediat, Hematol Oncol Sect, Milwaukee, WI 53226 USA. [Chen, Qing-Rong; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, NIH,Adv Technol Ctr, Gaithersburg, MD 20877 USA. RP Orentas, RJ (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,1W3840, Bethesda, MD 20892 USA. EM rimas.orentas@nih.gov FU National Cancer Institute [CA100030]; Northwestern Mutual Life Foundation, Milwaukee, WI; Midwest Athletes Against Childhood Cancer (MACC) Fund, Milwaukee, WI; Schield's Foundation, Milwaukee, WI FX The authors thank Weiqing Jing, Alexandra Liska-Baird, Laura McOlash, Katie Palen, James Weber, Mellissa Keller and Jamie Zernicke for outstanding technical assistance. The authors also thank Jill Gershan for helpful discussions involved in the generation of this manuscript. This publication has been funded all or in part by National Cancer Institute grant CA100030 (B.D.J., R.J.O.), Northwestern Mutual Life Foundation, Milwaukee, WI (M.E.K., R.J.O.), Midwest Athletes Against Childhood Cancer (MACC) Fund, Milwaukee, WI W.H.D.H., M.E.K., R.J.O.), and the Schield's Foundation, Milwaukee, WI (B.D.J., M.E.K., R.J.O.). Funding bodies have no input on data analysis and interpretation, manuscript submission, or publication decisions. NR 61 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2010 VL 265 IS 1 BP 65 EP 73 DI 10.1016/j.cellimm.2010.07.004 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 651RR UT WOS:000281945300011 PM 20692654 ER PT J AU Grabe, N Lahrmann, B Pommerencke, T Doeberitz, MV Reuschenbach, M Wentzensen, N AF Grabe, Niels Lahrmann, Bernd Pommerencke, Thora Doeberitz, Magnus von Knebel Reuschenbach, Miriam Wentzensen, Nicolas TI A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides SO CELLULAR ONCOLOGY LA English DT Article DE Virtual microscopy; internet; whole slide scanning; image processing; p16; cytology; cervical cancer ID HUMAN-PAPILLOMAVIRUS DNA; INTRAEPITHELIAL NEOPLASIA; CANCER; IMPLEMENTATION; VACCINATION; DIAGNOSIS; INTERNET; TRIAL; TESTS; CELLS AB Background: Although cytological screening for cervical precancers has led to a reduction of cervical cancer incidence worldwide it is a subjective and variable method with low single-test sensitivity. New biomarkers like p16 that specifically highlight abnormal cervical cells can improve cytology performance. Virtual microscopy offers an ideal platform for assisted evaluation and archiving of biomarker-stained slides. Methods: We first performed a quantitative analysis of p16-stained slides digitized with the Hamamatsu NDP slide scanner. From the results an automated algorithm was created to reliably detect cells, nuclei and p16-stained cells. The algorithm's performance was evaluated on two complete slides and tiles from 52 independent slides (11,628, 4094 and 25,619 cells/clusters, respectively). Results: We achieved excellent performance to discriminate unstained cells from nuclei and biomarker-stained cells. The automated algorithm showed a high overall and positive agreement (99.0-99.7% and 70.9-83.4%, respectively) with the gold standard and had a very high sensitivity (89.1-100.0%) and specificity (98.9-100.0%) to detect biomarker-stained cells. Conclusion: We implemented a virtual microscopy system allowing highly efficient automated prescreening and archiving of biomarker-stained slides. Based on the initial results, we will evaluate the performance of our system in large epidemiologic studies against disease endpoints. C1 [Grabe, Niels] BIOQUANT BQ10, Hamamatsu Tissue Imaging & Anal Ctr, TIGA, D-69120 Heidelberg, Germany. [Grabe, Niels; Lahrmann, Bernd; Pommerencke, Thora] Univ Heidelberg Hosp, Inst Med Biometry & Informat, Sect Med Informat, Heidelberg, Germany. [Doeberitz, Magnus von Knebel; Reuschenbach, Miriam; Wentzensen, Nicolas] Univ Heidelberg Hosp, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany. [Wentzensen, Nicolas] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Grabe, N (reprint author), BIOQUANT BQ10, Hamamatsu Tissue Imaging & Anal Ctr, TIGA, Neuenheimer Feld 267, D-69120 Heidelberg, Germany. EM niels.grabe@med.uni-heidelberg.de FU Intramural NIH HHS [ZIA CP010124-18] NR 23 TC 11 Z9 11 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 1-2 BP 109 EP 119 DI 10.3233/CLO-2009-0508 PG 11 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PQ UT WOS:000276461800010 PM 20208139 ER PT J AU Weber, A Chung, HJ Springer, E Heitzmann, D Warth, R AF Weber, Achim Chung, Hye-Jung Springer, Erik Heitzmann, Dirk Warth, Richard TI The TFIIH subunit p89 (XPB) localizes to the centrosome during mitosis SO CELLULAR ONCOLOGY LA English DT Article DE TFIIH; mitosis; centrosome ID AFFECT MICROTUBULE FUNCTION; RNA-POLYMERASE-I; XERODERMA-PIGMENTOSUM; INTERACTING GENES; EXCISION-REPAIR; TRANSCRIPTION; DROSOPHILA; MUTATIONS; PHOSPHORYLATION; PROGRESSION AB Background: The general transcription factor II H (TFIIH), comprised of a core complex and an associated CAK-complex, functions in transcription, DNA repair and cell cycle control. Mutations of the two largest subunits, p89 (XPB) and p80 (XPD), cause the hereditary cancer-prone syndrome xeroderma pigmentosum. Methods: The TFIIH subunit p89 was monitored during interphase and cell division by immunofluorescence staining, GFP-fusion constructs including deletions, live cell imaging and immuno-precipitations. Results: Here we demonstrate that during cell division, from prophase until telophase, the TFIIH core subunit p89, but not other subunits of TFIIH, associates with the centrosomes and the adjacent parts of the mitotic spindle. With overall constant levels throughout mitosis, p89 re-localizes to the newly formed nuclei by the end of mitosis. Furthermore, p89 interacts with the centrosomal protein.-tubulin. Truncations of p89 result in an abnormal subcellular distribution during interphase and abolished centrosomal association during mitosis. Conclusions: Our observations suggest a so far unappreciated role for p89 in cell cycle regulation, and may be the structural basis for a long known, but hitherto unexplained interaction between p89 and tubulin. C1 [Weber, Achim] Univ Zurich Hosp, Dept Pathol, Inst Surg Pathol, CH-8091 Zurich, Switzerland. [Chung, Hye-Jung] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Springer, Erik] Johannes Gutenberg Univ Mainz, Inst Pathol, D-6500 Mainz, Germany. [Heitzmann, Dirk; Warth, Richard] Univ Regensburg, Inst Pathol, Regensburg, Germany. [Heitzmann, Dirk] Univ Munster, Clin & Policlin Internal Med, Munster, Germany. RP Weber, A (reprint author), Univ Zurich Hosp, Dept Pathol, Inst Surg Pathol, Schmelzbergstr 12, CH-8091 Zurich, Switzerland. EM achim.weber@usz.ch RI Warth, Richard/N-7119-2014 OI Warth, Richard/0000-0001-6084-0659 FU Deutsche Forschungsgemeinschaft (DFG) [AW 2397/1-2]; USB AG, Switzerland FX We thank Dr. David L. Levens for support and helpful discussion. The expert assistance of Ines Tegtmeier and Dr. Elisa Romeo is gratefully acknowledged. This study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (AW 2397/1-2) and from an external sponsor, arranged by USB AG, Switzerland to A. Weber. NR 24 TC 8 Z9 8 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 1-2 BP 121 EP 130 DI 10.3233/CLO-2009-0509 PG 10 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PQ UT WOS:000276461800011 PM 20208140 ER PT J AU Ried, T Camps, J Emons, G Hummon, A Ghadimi, BM Habermann, J Heselmeyer-Haddad, K Auer, G Grade, M AF Ried, T. Camps, J. Emons, G. Hummon, A. Ghadimi, B. M. Habermann, J. Heselmeyer-Haddad, K. Auer, G. Grade, M. TI EXPLOITING THE GENOME AND TRANSCRIPTOME FOR INDIVIDUALIZED CANCER DIAGNOSIS AND TREATMENT STRATIFICATION SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Congress of the International-Society-for-Cellular-Oncology CY MAR 17-19, 2010 CL Dresden, GERMANY SP Int Soc Cellular Oncol C1 [Ried, T.; Camps, J.; Emons, G.; Hummon, A.; Ghadimi, B. M.; Habermann, J.; Heselmeyer-Haddad, K.; Auer, G.; Grade, M.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 3 BP 160 EP 160 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PR UT WOS:000276461900010 ER PT J AU Grade, M Hummon, AB Camps, J Emons, G Spitzner, M Gaedcke, J Hoermann, P Ebner, R Becker, H Difilippantonio, MJ Ghadimi, BM Beissbarth, T Caplen, NJ Ried, T AF Grade, M. Hummon, A. B. Camps, J. Emons, G. Spitzner, M. Gaedcke, J. Hoermann, P. Ebner, R. Becker, H. Difilippantonio, M. J. Ghadimi, B. M. Beissbarth, T. Caplen, N. J. Ried, T. TI A COMBINED FUNCTIONAL AND SYSTEMS BIOLOGY APPROACH IDENTIFIES COLORECTAL CANCER GENES AS NOVEL POTENTIAL THERAPEUTIC TARGETS SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Congress of the International-Society-for-Cellular-Oncology CY MAR 17-19, 2010 CL Dresden, GERMANY SP Int Soc Cellular Oncol C1 [Grade, M.; Emons, G.; Spitzner, M.; Gaedcke, J.; Becker, H.; Ghadimi, B. M.; Beissbarth, T.] Univ Gottingen, Univ Med, Dep Gen & Visceral Surg, Gottingen, Germany. [Grade, M.; Hummon, A. B.; Camps, J.; Hoermann, P.; Ebner, R.; Difilippantonio, M. J.; Ried, T.] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. [Caplen, N. J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RI Beissbarth, Tim/B-3129-2013 OI Beissbarth, Tim/0000-0001-6509-2143 NR 0 TC 0 Z9 0 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 3 BP 164 EP 165 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PR UT WOS:000276461900019 ER PT J AU Auer, G Roblick, UJ Ried, T Habermann, JK AF Auer, G. Roblick, U. J. Ried, T. Habermann, J. K. TI PREDICTION IN COLORECTAL CANCER USING PROTEOMICS SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Congress of the International-Society-for-Cellular-Oncology CY MAR 17-19, 2010 CL Dresden, GERMANY SP Int Soc Cellular Oncol C1 [Auer, G.; Roblick, U. J.; Habermann, J. K.] Karolinska Inst, KBC, Stockholm, Sweden. [Roblick, U. J.; Habermann, J. K.] Univ Clin Schleswig Holstein, Dept Surg, Surg Res Lab, Lubeck, Germany. [Ried, T.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 3 BP 172 EP 172 PG 1 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PR UT WOS:000276461900037 ER PT J AU Kendziorra, E Spitzner, M Emons, G Ahlborn, K Gaedcke, J Rave-Frank, M Beissbarth, T Becker, H Ghadimi, BM Ried, T Grade, M AF Kendziorra, E. Spitzner, M. Emons, G. Ahlborn, K. Gaedcke, J. Rave-Fraenk, M. Beissbarth, T. Becker, H. Ghadimi, B. M. Ried, T. Grade, M. TI RNAi-MEDIATED SILENCING OF TCF7L2 SENSITIZES COLORECTAL CANCER CELLS TO RADIATION SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT Congress of the International-Society-for-Cellular-Oncology CY MAR 17-19, 2010 CL Dresden, GERMANY SP Int Soc Cellular Oncol C1 [Kendziorra, E.; Spitzner, M.; Emons, G.; Ahlborn, K.; Gaedcke, J.; Rave-Fraenk, M.; Beissbarth, T.; Becker, H.; Ghadimi, B. M.; Grade, M.] Univ Med Ctr, Gottingen, Germany. [Ried, T.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Beissbarth, Tim/B-3129-2013 OI Beissbarth, Tim/0000-0001-6509-2143 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2010 VL 32 IS 3 BP 229 EP 230 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 580PR UT WOS:000276461900140 ER PT S AU Chenoweth, JG Tesar, PJ AF Chenoweth, Josh G. Tesar, Paul J. BE Ding, S TI Isolation and Maintenance of Mouse Epiblast Stem Cells SO CELLULAR PROGRAMMING AND REPROGRAMMING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Epiblast stem cells; Postimplantation epiblast; Egg cylinder; Pluripotency; Pou5f1 (Oct3/4) ID DERIVATION; EMBRYOS; LINE AB Epiblast stem cells (EpiSCs) are isolated from the postimplantation mouse embryo just after implantation but prior to gastrulation. EpiSCs are pluripotent and provide a tractable, in vitro system to study the processes that function during gastrulation to transition pluripotent cells to their differentiated derivatives. This chapter describes the methods for the isolation and maintenance of mouse EpiSCs. We also describe basic assays used to characterize new EpiSC lines. C1 [Chenoweth, Josh G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Tesar, Paul J.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. RP Chenoweth, JG (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Tesar, Paul/C-9848-2014 OI Tesar, Paul/0000-0003-1532-3155 NR 13 TC 19 Z9 19 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-690-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 636 BP 25 EP 44 DI 10.1007/978-1-60761-691-7_2 D2 10.1007/978-1-60761-691-7 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOK46 UT WOS:000276891700002 PM 20336514 ER PT J AU Sehm, B Perez, MA Xu, B Hidler, J Cohen, LG AF Sehm, B. Perez, M. A. Xu, B. Hidler, J. Cohen, L. G. TI Functional Neuroanatomy of Mirroring during a Unimanual Force Generation Task SO CEREBRAL CORTEX LA English DT Article DE caudal cingulate; fMRI; mirror EMG; primary motor cortex; supplementary motor area ID SUPPLEMENTARY MOTOR AREA; TRANSCRANIAL MAGNETIC STIMULATION; VENTRAL CINGULATE CORTEX; NEURONAL-ACTIVITY; HUMAN BRAIN; CORTICOSPINAL EXCITABILITY; VOLUNTARY CONTRACTIONS; BILATERAL INTERACTIONS; DYNAMIC ENVIRONMENT; PARKINSONS-DISEASE AB Performance of a unimanual motor task often induces involuntary mirror electromyographic (EMG) activity in the opposite, resting hand. In spite of the ubiquitous presence of mirroring, little is known regarding the underlying cortical contributions. Here, we used functional magnetic resonance imaging (fMRI) to study brain regions activated in association with parametric increases in right isometric wrist flexion force (10%, 20%, 30%, and 70%) in 12 healthy volunteers. During scanning, EMG activity was recorded bilaterally from flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BB), and triceps brachii (TB). Mirror EMG was observed in left FCR during 20%, 30%, and 70% of force. Left ECR, BB, and TB showed mirror EMG only at 70% of force. Increasing force was associated with a linear increase of blood-oxygen-level-dependent (BOLD) signal in bilateral primary motor cortex (M1), supplementary motor area (SMA), caudal cingulate, and cerebellum. Mirroring in the left FCR correlated with activity in bilateral M1, SMA, and the cerebellum. Overall, our results suggest that activity in these regions might reflect sensorimotor processes operating in association with mirroring and suggest caution when interpreting fMRI activity in studies that involve unilateral force generation tasks in the absence of simultaneous bilateral EMG/kinematics measurements. C1 [Sehm, B.; Perez, M. A.; Xu, B.; Cohen, L. G.] NINDS, Human Cort Physiol Sect & Stroke Neurorehabil, NIH, Bethesda, MD 20892 USA. [Sehm, B.] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, D-17487 Greifswald, Germany. [Hidler, J.] Catholic Univ, Dept Biomed Engn, Washington, DC 20064 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect & Stroke Neurorehabil, NIH, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov FU Intramural NIH HHS NR 68 TC 29 Z9 30 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2010 VL 20 IS 1 BP 34 EP 45 DI 10.1093/cercor/bhp075 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 531RH UT WOS:000272685000004 PM 19435709 ER PT J AU Hachinski, V Donnan, GA Gorelick, PB Hacke, W Cramer, SC Kaste, M Fisher, M Brainin, M Buchan, AM Lo, EH Skolnick, BE Furie, KL Hankey, GJ Kivipelto, M Morris, J Rothwell, PM Sacco, RL Smith, SC Wang, YL Bryer, A Ford, GA Iadecola, C Martins, SCO Saver, J Skvortsova, V Bayley, M Bednar, MM Duncan, P Enney, L Finklestein, S Jones, TA Kalra, L Kleim, J Nitkin, R Teasell, R Weiller, C Desai, B Goldberg, MP Heiss, WD Saarelma, O Schwamm, LH Shinohara, Y Trivedi, B Wahlgren, N Wong, LK Hakim, A Norrving, B Prudhomme, S Bornstein, NM Davis, SM Goldstein, LB Leys, D Tuomilehto, J AF Hachinski, Vladimir Donnan, Geoffrey A. Gorelick, Philip B. Hacke, Werner Cramer, Steven C. Kaste, Markku Fisher, Marc Brainin, Michael Buchan, Alastair M. Lo, Eng H. Skolnick, Brett E. Furie, Karen L. Hankey, Graeme J. Kivipelto, Miia Morris, John Rothwell, Peter M. Sacco, Ralph L. Smith, Sidney C., Jr. Wang, Yulun Bryer, Alan Ford, Gary A. Iadecola, Costantino Martins, Sheila C. O. Saver, Jeff Skvortsova, Veronika Bayley, Mark Bednar, Martin M. Duncan, Pamela Enney, Lori Finklestein, Seth Jones, Theresa A. Kalra, Lalit Kleim, Jeff Nitkin, Ralph Teasell, Robert Weiller, Cornelius Desai, Bhupat Goldberg, Mark P. Heiss, Wolf-Dieter Saarelma, Osmo Schwamm, Lee H. Shinohara, Yukito Trivedi, Bhargava Wahlgren, Nils Wong, Lawrence K. Hakim, Antoine Norrving, Bo Prudhomme, Stephen Bornstein, Natan M. Davis, Stephen M. Goldstein, Larry B. Leys, Didier Tuomilehto, Jaakko TI Stroke: Working toward a Prioritized World Agenda SO CEREBROVASCULAR DISEASES LA English DT Article DE Prevention; Rehabilitation; Stroke; Translational; Treatment ID RECOMMENDATIONS; VALIDATION; CENTERS; SCREEN AB Background and Purpose: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e. g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. Copyright (C) 2010 American Heart Association. Inc., S. Karger AG, Basel, and John Wiley & Sons, Inc. C1 [Hachinski, Vladimir] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON N6A 5A5, Canada. [Teasell, Robert] St Josephs Healthcare London, London, ON, Canada. [Bayley, Mark] Toronto Rehabil Inst, Toronto, ON, Canada. [Hakim, Antoine] Univ Ottawa, Canadian Stroke Network, Ottawa, ON, Canada. [Hakim, Antoine] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Donnan, Geoffrey A.] Florey Neurosci Inst, Carlton S Victoria, Australia. [Davis, Stephen M.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Davis, Stephen M.] Univ Melbourne, Melbourne, Vic, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Gorelick, Philip B.] Univ Illinois, Chicago, IL USA. [Trivedi, Bhargava] So Illinois Healthcare, Carbondale, IL USA. [Cramer, Steven C.] Univ Calif Irvine, Orange, CA 92668 USA. [Desai, Bhupat] Pomona Valley Hosp Med Ctr, Pomona, CA USA. [Wang, Yulun] InTouch Hlth, Goleta, CA USA. [Saver, Jeff] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lo, Eng H.; Furie, Karen L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Finklestein, Seth] Biotrofix Inc, Waltham, MA USA. [Skolnick, Brett E.] Novo Nordisk AS, Princeton, NJ USA. [Morris, John; Goldberg, Mark P.] Washington Univ, Sch Med, St Louis, MO USA. [Sacco, Ralph L.] Univ Miami, AHA, Miami, FL USA. [Kleim, Jeff] Univ Florida, Gainesville, FL USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Duncan, Pamela; Goldstein, Larry B.] Duke Univ, Durham, NC USA. [Enney, Lori] GlaxoSmithKline Inc, Durham, NC USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Iadecola, Costantino] Weill Cornell Med Coll, New York, NY USA. [Bednar, Martin M.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA. [Jones, Theresa A.] Univ Texas Austin, Austin, TX 78712 USA. [Nitkin, Ralph] NICHHD, Natl Ctr Med Rehabil, NIH, Rockville, MD USA. [Prudhomme, Stephen] Amer Heart Assoc, Dallas, TX USA. [Hacke, Werner] Univ Heidelberg, Heidelberg, Germany. [Weiller, Cornelius] Univ Freiburg, Freiburg, Germany. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany. [Kaste, Markku] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Saarelma, Osmo] Terveystalo Med Ctr, Helsinki, Finland. [Brainin, Michael] Univ Donau Univ Krems, Krems, Austria. [Buchan, Alastair M.] Univ Oxford, Oxford, England. [Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Ford, Gary A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Kalra, Lalit] Kings Coll London, London WC2R 2LS, England. [Wahlgren, Nils] Karolinska Inst, Stockholm, Sweden. [Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden. [Smith, Sidney C., Jr.] World Heart Federat, Geneva, Switzerland. [Bryer, Alan] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Bryer, Alan] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Martins, Sheila C. O.] Hosp Clin, Porto Alegre, RS, Brazil. [Skvortsova, Veronika] Russian State Res Stroke Inst, Moscow, Russia. [Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan. [Wong, Lawrence K.] Chinese Univ Hong Kong, Sha Tin, Hong Kong, Peoples R China. [Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Leys, Didier] Univ Lille Nord France, Lille, France. RP Hachinski, V (reprint author), Univ Western Ontario, Univ Hosp, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM Vladimir.Hachinski@lhsc.on.ca RI Skolnick, Brett/B-5140-2009; Buchan, Alastair/B-9095-2009; OI Buchan, Alastair/0000-0002-2918-5200; Norrving, Bo/0000-0002-8024-5096; Schwamm, Lee/0000-0003-0592-9145; Kivipelto, Miia/0000-0003-0992-3875; Donnan, Geoffrey/0000-0001-6324-3403; Saver, Jeffrey/0000-0001-9141-2251; Kaste, Markku/0000-0001-6557-6412 FU AHA/ASA; World Federation of Neurology; WSO; ESO; European Stroke Conference; Canadian Stroke Network; Heart & Stroke Foundation; Lippincott Williams Wilkins; National Institute of Neurological Disorders and Stroke FX We thank Gary Houser and his Stroke Group for expert help in organizing the Synergium. Warm thanks to Yvette Ballantyne and the AHA staff for help with the organization and registration for the Synergium. We thank the supporting organizations of the Synergium: AHA/ASA, World Federation of Neurology, WSO, ESO, European Stroke Conference, Canadian Stroke Network, Heart & Stroke Foundation Centre for Stroke Recovery, and Lippincott Williams & Wilkins. The views and conclusions of the synergium are that of the participants and contributors and not necessarily those of the supporting organizations.; The Synergium authors appreciate the input of Drs Walter Koroshetz and Petra Kaufmann as well as the financial support of the National Institute of Neurological Disorders and Stroke. NR 8 TC 14 Z9 14 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 2 BP 127 EP 147 DI 10.1159/000315099 PG 21 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XB UT WOS:000280461800004 PM 20516682 ER PT J AU Sanossian, N Starkman, S Eckstein, M Stratton, S Pratt, F Conwit, R Saver, JL AF Sanossian, Nerses Starkman, Sidney Eckstein, Mark Stratton, Samuel Pratt, Frank Conwit, Robin Saver, Jeffrey L. CA FAST-MAG Trail Investigators TI Intercontinental Elicitation of Informed Consent for Enrollment in Stroke Research SO CEREBROVASCULAR DISEASES LA English DT Article ID TRIALS C1 [Sanossian, Nerses] Univ So Calif, Dept Neurol, Stroke Ctr, Los Angeles, CA 90033 USA. [Eckstein, Mark] Univ So Calif, Dept Emergency Med, Stroke Ctr, Los Angeles, CA 90033 USA. [Starkman, Sidney; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Stratton, Samuel] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Pratt, Frank] Torrance Mem Med Ctr, Dept Emergency Med, Torrance, CA USA. [Conwit, Robin] NINDS, Bethesda, MD 20892 USA. RP Sanossian, N (reprint author), Univ So Calif, Dept Neurol, Stroke Ctr, 1100 N State St,Room A4E117, Los Angeles, CA 90033 USA. EM sanossia@yahoo.com OI Saver, Jeffrey/0000-0001-9141-2251 FU NIH-NINDS [U01 NS 44364] FX This work was supported by NIH-NINDS Award U01 NS 44364. The study was approved by the IRB of each of the 55 participating destination hospitals. NR 4 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 3 BP 323 EP 324 DI 10.1159/000319609 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XD UT WOS:000280462000015 PM 20664268 ER PT J AU Silva, GS Lima, FO Camargo, ECS Smith, WS Lev, MH Harris, GJ Halpern, EF Koroshetz, W Furie, KL AF Silva, Gisele S. Lima, Fabricio O. Camargo, Erica C. S. Smith, Wade S. Lev, Michael H. Harris, Gordon J. Halpern, Elkan F. Koroshetz, Walter Furie, Karen L. TI Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion SO CEREBROVASCULAR DISEASES LA English DT Article DE Sex differences; Ischemic stroke; CT angiography ID TISSUE-PLASMINOGEN ACTIVATOR; SEX-BASED DIFFERENCES; CARE; REGISTRY; WOMEN; TRIAL; MORTALITY AB Background: The reasons for gender disparities in stroke outcome remain unclear, and little is known about the value of acute neuroimaging characteristics in elucidating differential stroke outcomes between the sexes. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography (CTA) was performed in all patients within 24 h of symptom onset. CTA source images were used to evaluate lesion volume. The primary outcome measure was a modified Rankin scale (mRS) score >= 3 at 6 months. Results: We evaluated 676 consecutive patients (322 women). Women were older than men (p < 0.01), more frequently had a prestroke mRS >0 (p < 0.01), and had higher admission National Institutes of Health Stroke scale scores (p = 0.01). More women had intracranial artery occlusions than men (46 vs. 33.1%, p = 0.01), but there was no significant difference between ischemic lesion volumes (p = 0.21). Using multiple regression, female gender remained an independent predictor of poor mRS scores at 6 months (odds ratio 1.57; 95% confidence interval 1.02-2.36) after adjustment for clinical and imaging covariates. Conclusion: Compared with men, women are less likely to achieve independence after acute ischemic stroke. The disparity in stroke outcome is not explained by differences in ischemic lesion volume or the presence of intracranial artery occlusions. Copyright (C) 2010 S. Karger AG, Basel C1 [Silva, Gisele S.; Lima, Fabricio O.; Camargo, Erica C. S.; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lev, Michael H.; Harris, Gordon J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Silva, Gisele S.] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Silva, GS (reprint author), 741 Altino Arantes Ave,Apt 81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; National Institutes of Health [P50NS051343]; Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Lakeside Foundation FX Sources of funding: supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392 and National Institutes of Health grant P50NS051343. We gratefully acknowledge the support of the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation and the Lakeside Foundation. NR 32 TC 21 Z9 21 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 5 BP 470 EP 475 DI 10.1159/000317088 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 661TY UT WOS:000282752200006 PM 20733301 ER PT J AU Nyquist, P Zhang, JH De Graba, TJ AF Nyquist, Paul Zhang, Jianhua De Graba, Thomas J. TI The-928 G/C and-362 G/C Single-Nucleotide Polymorphisms in the Promoter of MCP-1: Increased Transcriptional Activity and Novel Binding Sites SO CEREBROVASCULAR DISEASES LA English DT Article DE Chemokines; Single-nucleotide polymorphisms; Genetics; Carotid stenosis ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPRESSION; RECEPTOR; GENE; ATHEROSCLEROSIS; ACTIVATION; THICKNESS; ELEMENT; MICE AB Background: The -928 guanine (G)/cytosine (C) and -362 G/C single-nucleotide polymorphisms (SNPs) in the proximal promoter region of the monocyte chemoattractant protein 1 gene have been associated with an increased risk for intimal medial thickness and carotid atherosclerosis, respectively. We characterized the transcriptional activity of these two SNPs in vitro and identified transcription factors that bind to them. Methods: The proximal promoter region spanning bases -2746 to +440 was sequenced in subjects with carotid atherosclerosis. Two SNPs consisting of C-for-G substitution at bases -928 and -362 were characterized. Each observed haplotype was inserted into a luciferase reporter and transfected into mammalian cells. Results: Stimulation with 12-O-tetradecanoylphorbol 13-acetate increased transcriptional activity of the -928 C plasmid ( p = 0.005). The basal transcription activities of the plasmids containing -928 C and -362 C were also increased ( p < 0.001 and p < 0.0001, respectively). Electrophoretic mobility shift assay ( EMSA) and DNA footprinting identified an Ah receptor nuclear translocator protein (ARNT) binding site at the -928 C SNP. EMSA data indicated signal transducers and activators of transcription ( STAT) binding at the -362 G SNP. A nuclear binding protein, poly(ADP-ribose) polymerase ( PARP) 1, was purified from the -928 C SNP site and identified by mass spectroscopy. Conclusion: The -928 C SNP and the -362 C SNP are associated with increased transcriptional activity in vitro, but the -362 G site is not. The -928 C SNP is associated with PARP-1 and ARNT binding, and the -362 G is associated with a STAT binding site. Copyright (C) 2009 S. Karger AG, Basel C1 [Nyquist, Paul] Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, Baltimore, MD 21217 USA. [Nyquist, Paul] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21217 USA. [Nyquist, Paul] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Baltimore, MD 21217 USA. [Nyquist, Paul] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 28217 USA. [Nyquist, Paul; De Graba, Thomas J.] Natl Naval Med Ctr, Dept Neurol, Bethesda, MD USA. [Nyquist, Paul; De Graba, Thomas J.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Nyquist, Paul; De Graba, Thomas J.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Zhang, Jianhua] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Nyquist, P (reprint author), Johns Hopkins Univ, Sch Med, Div Neurosci Crit Care, 600 N Wolfe St,Meyer 8-140, Baltimore, MD 21217 USA. EM pnyquis1@jhmi.edu NR 14 TC 10 Z9 10 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 29 IS 3 BP 242 EP 247 DI 10.1159/000267849 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 549VL UT WOS:000274082300006 PM 20029197 ER PT J AU Silva, GS Lima, FO Camargo, ECS Smith, WS Singhal, AB Greer, DM Ay, H Lev, MH Harris, GJ Halpern, EF Sonni, S Koroshetz, W Furie, KL AF Silva, Gisele S. Lima, Fabricio O. Camargo, Erica C. S. Smith, Wade S. Singhal, Aneesh B. Greer, David M. Ay, Hakan Lev, Michael H. Harris, Gordon J. Halpern, Elkan F. Sonni, Shruti Koroshetz, Walter Furie, Karen L. TI Wake-Up Stroke: Clinical and Neuroimaging Characteristics SO CEREBROVASCULAR DISEASES LA English DT Article DE Wake-up stroke; Computed tomography angiography; Computed tomography perfusion; Ischemic penumbra ID ACUTE ISCHEMIC-STROKE; PERFUSION COMPUTED-TOMOGRAPHY; INTRACEREBRAL HEMORRHAGE; THROMBOLYTIC THERAPY; SOURCE IMAGES; DIFFUSION; TRIAL; ONSET; MRI; CT AB Background: Approximately 25% of ischemic stroke patients awaken with neurological deficits. In these patients, in whom the time from symptom onset is uncertain, brain imaging is a potential strategy to characterize the ischemia duration and the presence of salvageable brain tissue. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography and CT perfusion (CTP) were performed in patients within 24 h of symptom onset. The patients were classified into 'known onset', 'indefinite onset but not on awakening' and 'wake-up stroke' groups. Results: Of 676 patients evaluated, 420 had known-onset strokes, 131 wake-up strokes and 125 strokes with an indefinite time of symptom onset. Ischemic lesion volumes were higher in patients with indefinite-onset strokes ( p = 0.04). The frequencies of CTP mismatch and of large-vessel intracranial occlusions were similar among the groups ( p = 0.9 and p = 0.2, respectively). Conclusion: The considerable prevalence of CTP mismatch and of intracranial artery occlusions in our patients with wake-up strokes suggests that arterial and perfusion imaging might be particularly important in this population. Revised indications for thrombolysis by using imaging-based protocols might offer these patients the prospect of receiving acute stroke treatment even without a clear time of symptom onset. Copyright (C) 2010 S. Karger AG, Basel C1 [Silva, Gisele S.; Lima, Fabricio O.; Camargo, Erica C. S.; Singhal, Aneesh B.; Greer, David M.; Sonni, Shruti; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ay, Hakan; Lev, Michael H.; Harris, Gordon J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA. [Silva, Gisele S.] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Silva, GS (reprint author), 741 Altino Arantes Ave Apt 81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU NIH [AHRQ R01 HS11392] FX This study was supported by NIH grant AHRQ R01 HS11392 (K.L.F.). NR 23 TC 45 Z9 45 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 29 IS 4 BP 336 EP 342 DI 10.1159/000278929 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 588DU UT WOS:000277048400004 PM 20130399 ER PT B AU Moss, B Bengali, Z Bisht, H Laliberte, JP Satheskumar, PS AF Moss, Bernard Bengali, Zain Bisht, Himani Laliberte, Jason P. Satheskumar, P. S. BE Shafferman, A Ordentlich, A Velan, B TI Poxvirus Entry into Host Cells SO CHALLENGE OF HIGHLY PATHOGENIC MICROORGANISMS: MECHANISMS OF VIRULENCE AND NOVEL MEDICAL COUNTERMEASURES LA English DT Proceedings Paper CT 46th Oholo Conference on the Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures CY OCT 25-29, 2009 CL Eilat, ISRAEL SP Israel Inst Biol Res DE Poxvirus; Membrane fusion; Endocytosis ID VACCINIA-VIRUS ENTRY; INTRACELLULAR MATURE VIRION; SERINE-PROTEASE INHIBITOR; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; FUSION COMPLEX; ESSENTIAL COMPONENT; APOPTOTIC MIMICRY; VIRAL MEMBRANE; A27L PROTEIN AB Vaccinia virus, the prototype member of the poxvirus family, assembles two related infectious forms: the mature virion (MV) and the enveloped virion (EV). The MV consists of a core surrounded by a lipoprotein membrane. The EV is essentially an MV with an additional antigenically distinct outer membrane that must be disrupted prior to or during entry. Entry of the MV occurs by fusion of the lipoprotein membrane with the plasma membrane or following endocytosis. Approximately 25 proteins are associated with the MV membrane. Of these, four have roles in cell attachment and twelve in entry and membrane fusion. The entry fusion proteins are conserved in all poxviruses and form a stable complex in the MV membrane. C1 [Moss, Bernard; Bengali, Zain; Bisht, Himani; Laliberte, Jason P.; Satheskumar, P. S.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 44 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-90-481-9053-9 PY 2010 BP 107 EP 113 DI 10.1007/978-90-481-9054-6_11 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA BGG65 UT WOS:000322847000011 ER PT J AU Xie, J Wang, JH Niu, G Huang, J Chen, K Li, XG Chen, XY AF Xie, Jin Wang, Jinhua Niu, Gang Huang, Jing Chen, Kai Li, Xingguo Chen, Xiaoyuan TI Human serum albumin coated iron oxide nanoparticles for efficient cell labeling SO CHEMICAL COMMUNICATIONS LA English DT Article ID MR CONTRAST AGENTS; CEREBRAL-ISCHEMIA; GLIAL RESPONSES; INFLAMMATION; MACROPHAGES; STROKE; MECHANISMS; LEUKOCYTES; THERAPY; TISSUE AB A novel dopamine-plus-HSA (human serum albumin) approach was developed to functionalize iron oxide nanoparticles (IONPs), yielding nanoconjugates that are highly efficient in labeling various types of cell lines, which was demonstrated by in vivo MR imaging on xenograft and focal cerebral ischemia models. C1 [Xie, Jin; Wang, Jinhua; Niu, Gang; Huang, Jing; Chen, Kai; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Wang, Jinhua] Nanchang Univ, Coll Med, Dept Radiol, Nanchang, Peoples R China. [Huang, Jing; Li, Xingguo] Beijing Univ, Dept Chem, Beijing 100871, Peoples R China. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,31-1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Xie, Jin/E-8193-2010 FU Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) FX This research was supported by Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). NR 22 TC 47 Z9 49 U1 0 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2010 VL 46 IS 3 BP 433 EP 435 DI 10.1039/b917195a PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 535TA UT WOS:000272992700021 PM 20066316 ER PT J AU Guo, K Berezin, MY Zheng, J Akers, W Lin, F Teng, B Vasalatiy, O Gandjbakhche, A Griffiths, GL Achilefu, S AF Guo, Kevin Berezin, Mikhail Y. Zheng, Jie Akers, Walter Lin, Franck Teng, Bao Vasalatiy, Olga Gandjbakhche, Amir Griffiths, Gary L. Achilefu, Samuel TI Near infrared-fluorescent and magnetic resonance imaging molecular probe with high T-1 relaxivity for in vivo multimodal imaging SO CHEMICAL COMMUNICATIONS LA English DT Article ID MRI CONTRAST AGENTS; HUMAN SERUM-ALBUMIN; GD-DTPA; RELAXATION; NANOPARTICLE; LIFETIME; DESIGN; MS-325 AB A new gadolinium chelating NIR fluorescent molecular probe increases T-1 relaxivity of water protons, facilitating combined optical and magnetic resonance imaging. C1 [Guo, Kevin; Berezin, Mikhail Y.; Zheng, Jie; Akers, Walter; Achilefu, Samuel] Washington Univ, Dept Radiol, St Louis, MO 63110 USA. [Lin, Franck; Achilefu, Samuel] Washington Univ, Dept Biomed Engn, St Louis, MO 63110 USA. [Teng, Bao; Vasalatiy, Olga; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA. [Gandjbakhche, Amir] Eunice Shriver NICHD, NIH, Bethesda, MD 20892 USA. [Achilefu, Samuel] Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Achilefu, S (reprint author), Washington Univ, Dept Radiol, St Louis, MO 63110 USA. EM achilefus@mir.wustl.edu RI Achilefu, Samuel/A-3681-2012; Berezin, Mikhail/B-4102-2009; OI Akers, Walter/0000-0002-9697-7654; Achilefu, Samuel/0000-0002-3133-6717 FU NIBIB, National Institutes of Health [R01 EB008111]; NCI, National Institutes of Health [R01 CA109754]; Eunice Shriver NICHD FX This study was funded in part by grants from the National Institutes of Health (NIBIB R01 EB008111 and NCI R01 CA109754), the NIH Roadmap for Medical Research as funding source for the IPDC, and the Intramural Research Program of Eunice Shriver NICHD. NR 27 TC 25 Z9 26 U1 1 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2010 VL 46 IS 21 BP 3705 EP 3707 DI 10.1039/c000536c PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 598JQ UT WOS:000277832600019 PM 20390151 ER PT J AU Biswas, D Deschamps, JR Keefer, LK Hrabie, JA AF Biswas, Debanjan Deschamps, Jeffrey R. Keefer, Larry K. Hrabie, Joseph A. TI Nitrogen-bound diazeniumdiolated amidines SO CHEMICAL COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE DONORS; FUNCTIONAL-GROUP; JS-K; CHEMISTRY; PRODRUGS; ANALOGS; CARBON; IONS AB In contrast to amidines bearing ionizable alpha-CH bonds, which react with nitric oxide (NO) to add diazeniumdiolate groups at their alpha-carbons, benzamidine forms an N-bound diazeniumdiolate that can be further derivatized at the other amidine nitrogen and/or the terminal oxygen to form caged NO compounds as potential NO prodrugs. C1 [Biswas, Debanjan; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Hrabie, Joseph A.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Biswas, D (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM biswasd@mail.nih.gov; hrabiej@mail.nih.gov RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Deschamps, Jeffrey/0000-0001-5845-0010 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute on Drug Abuse [Y1-DA6002]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Crystallographic studies were supported by the National Institute on Drug Abuse under contract Y1-DA6002. NR 17 TC 4 Z9 5 U1 1 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2010 VL 46 IS 31 BP 5799 EP 5801 DI 10.1039/c0cc00849d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 633PE UT WOS:000280514500052 PM 20589293 ER PT J AU Huang, J Xie, J Chen, K Bu, LH Lee, S Cheng, Z Li, XG Chen, XY AF Huang, Jing Xie, Jin Chen, Kai Bu, Lihong Lee, Seulki Cheng, Zhen Li, Xingguo Chen, Xiaoyuan TI HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging SO CHEMICAL COMMUNICATIONS LA English DT Article ID IRON-OXIDE NANOPARTICLES; MAGNETIC NANOPARTICLES; NANOCRYSTALS; ALBUMIN; CANCER; RGD AB We report in this Communication a facile, two-step surface modification strategy to achieve manganese oxide nanoparticles with prominent MRI T1 contrast. In a U87MG glioblastoma xenograft model, we confirmed that the particles can accumulate efficiently in tumor area to induce effective T1 signal alteration. C1 [Huang, Jing; Li, Xingguo] Peking Univ, Coll Chem & Mol Engn, BNLMS, Beijing 100871, Peoples R China. [Huang, Jing; Xie, Jin; Chen, Kai; Bu, Lihong; Lee, Seulki; Cheng, Zhen; Chen, Xiaoyuan] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Huang, Jing; Xie, Jin; Chen, Kai; Bu, Lihong; Lee, Seulki; Cheng, Zhen; Chen, Xiaoyuan] Stanford Univ, Bio X Program, Stanford, CA 94305 USA. [Xie, Jin; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Bu, Lihong] Harbin Med Coll, Hosp 4, Dept Radiol, Heilongjiang 150001, Peoples R China. RP Li, XG (reprint author), Peking Univ, Coll Chem & Mol Engn, BNLMS, Beijing 100871, Peoples R China. EM xgli@pku.edu.cn; shawn.chen@nih.gov RI Xie, Jin/E-8193-2010; Cheng, Zhen/K-2843-2012 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); MOST of China [2009CB939902, 2010CB631301] FX This research was supported by Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and MOST of China (No. 2009CB939902 and 2010CB631301). NR 19 TC 69 Z9 70 U1 2 U2 46 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2010 VL 46 IS 36 BP 6684 EP 6686 DI 10.1039/c0cc01041c PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 647FX UT WOS:000281604500010 PM 20730157 ER PT J AU Ravichandran, S AF Ravichandran, Sarangan TI Identifying the Common Binding Modes of Flavonoids to Cytochrome P450 3A4 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Ravichandran, Sarangan] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. EM sravi@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 54 BP 276 EP 277 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500085 ER PT J AU Pietsch, KE Yu, X Neels, JF Gong, JC Sturla, SJ AF Pietsch, Kathryn E. Yu, Xiang Neels, James F. Gong, Jiachang Sturla, Shana J. TI Chemical Aspects of Acylfulvene Bioactivation to a Cytotoxic Reactive Intermediate SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Pietsch, Kathryn E.; Neels, James F.; Gong, Jiachang; Sturla, Shana J.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. [Yu, Xiang] NCI, Cell & Canc Biol Branch, Natl Inst Hlth, Bethesda, MD 20814 USA. EM piet0123@umn.edu; yux@mail.nih.gov; sturl002@umn.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 61 BP 278 EP 278 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500092 ER PT J AU Sczepanski, J Jacobs, A Van Houten, B Greenberg, MM AF Sczepanski, Jonathan Jacobs, Aaron Van Houten, Bennett Greenberg, Marc M. TI Scope and Mechanism of Formation of Interstrand Cross-Links That Give Rise to Double Strand Breaks upon Nucleotide Excision Repair SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Sczepanski, Jonathan; Jacobs, Aaron; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. [Van Houten, Bennett] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM jons@jhu.edu; ajacobs@jhu.edu; vanhout1@niehs.nih.gov; mgreenberg@jhu.edu RI Sczepanski, Jonathan/N-8719-2015 OI Sczepanski, Jonathan/0000-0002-9275-2597 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 85 BP 284 EP 284 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500116 ER PT J AU Brooks, PJ AF Brooks, Phillip J. TI DNA Adducts Involved in Xeroderma Pigmentosum Neurologic Disease and in Alcohol-Related Carcinogenesis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Brooks, Phillip J.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. EM pjbrooks@dicbr.niaaa.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 101 BP 288 EP 288 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500132 ER PT J AU Garcia, J Barluenga, S Beebe, K Neckers, L Winssinger, N AF Garcia, Jose Barluenga, Sofia Beebe, Kristin Neckers, Len Winssinger, Nicolas TI Concise Modular Asymmetric Synthesis of Deguelin, Tephrosin and Investigation into Their Mode of Action SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE deguelin; Hsp90; natural products; tephrosin; total synthesis ID CANCER CHEMOPREVENTIVE ACTIVITY; SMALL-MOLECULE INHIBITORS; ORNITHINE-DECARBOXYLASE; OLEFIN METATHESIS; TARGETING HSP90; CHAPERONE HSP90; DL-DEGUELIN; ROTENOIDS; DISEASE; GELDANAMYCIN C1 [Garcia, Jose; Barluenga, Sofia; Winssinger, Nicolas] Univ Strasbourg, ISIS, UMR 7006, CNRS, F-67000 Strasbourg, France. [Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Winssinger, N (reprint author), Univ Strasbourg, ISIS, UMR 7006, CNRS, 8 Allee Gaspard Monge, F-67000 Strasbourg, France. RI Winssinger, Nicolas/B-6710-2017 OI Winssinger, Nicolas/0000-0003-1636-7766 FU Institut Universitaire de France (IUF) FX This work was supported in part by a grant from Institut Universitaire de France (IUF) We thank Sylvam Bianchi for preliminary work NR 56 TC 14 Z9 14 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PY 2010 VL 16 IS 32 BP 9767 EP 9771 DI 10.1002/chem.201001080 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 648JO UT WOS:000281689700011 PM 20572190 ER PT J AU Lee, YS Hodoscek, M Chun, JH Pike, VW AF Lee, Yong-Sok Hodoscek, Milan Chun, Joong-Hyun Pike, Victor W. TI Conformational Structure and Energetics of 2-Methylphenyl(2 '-methoxyphenyl)iodonium Chloride: Evidence for Solution Clusters SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE cluster compounds; dimerization; iodinium salts; inversion pathways; stereogenic iodine ID HETEROAROMATIC IODONIUM SALTS; POLYVALENT IODINE COMPOUNDS; REPLICA PATH METHOD; DIARYLIODONIUM-SALTS; DIPHENYLIODONIUM HALIDES; TRANSITION-STATES; AB-INITIO; CHEMISTRY; ION; DECOMPOSITION AB Diaryliodonium salts allow the efficient incorporation of cyclotron-produced [(18)F]fluoride ions into electron-rich and electron-deficient arenes to provide potential radiotracers for molecular imaging in vivo with positron emission tomography (PET). This process (ArI(+)Ar'+(18)F(-)-> Ar(18)F+Ar'I) is still not well understood mechanistically. To better understand this and similar reactions, it would be valuable to understand the structures of diaryliodonium salts in organic media, where the reactions are typically conducted. In this endeavor, the X-ray structure of a representative iodonium salt, 2-methylphenyl(2'-methoxyphenyl)iodonium chloride (1), was determined. Our X-ray structure analysis showed 1 to have the conformational M P dimer as the unit cell with hyper-valent iodine as a stereogenic center in each conformer. With the ab initio replica path method we constructed the inversion path between the two enantiomers of 1, thereby revealing two additional pairs of enantiomers that are likely to undergo fast interconversion in solution. Also LC-MS of 1 showed the presence of dimeric and tetrameric anion-bridged clusters in weak organic solution. This observation is consistent with the energetics of 1, both as monomeric and dimeric forms in MeCN, calculated at the B3LYP/DGDZVP level. These evidences of the existence of dimeric and higher order clusters of 1 in solution are relevant to achieve a deeper general understanding of the mechanism and outcome of reactions of diaryliodonium salts in organic media with nucleophiles, such as the [(18)F]fluoride ion. C1 [Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hodoscek, Milan] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hodoscek, Milan] Natl Inst Chem, Ljubljana, Slovenia. [Chun, Joong-Hyun; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lee, YS (reprint author), NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol,Dept Hlth & Human Serv, Bldg 12A,Room 2049, Bethesda, MD 20892 USA. EM leeys@mail.nih.gov FU National Institutes of Health (NIMH) FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIMH and CIT). We are grateful to Dr. S. Hassan (cm for discussion, and Dr. M. J. Panzner (University of Akron) for X-ray analysis of I. The quantum chemical study utilized PC/LINUX clusters at the Center for Molecular Modeling of the NIH (http://citmih.gov). We are also deeply grateful to Dr. H. U. Shetty (NIMH) for assistance with LC-MS. NR 38 TC 10 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PY 2010 VL 16 IS 34 BP 10418 EP 10423 DI 10.1002/chem.201000607 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 659AP UT WOS:000282539700020 PM 20632418 ER PT J AU Platt, AB Kuna, ST Field, SH Chen, Z Gupta, R Roche, DE Christie, JD Asch, DA AF Platt, Alec B. Kuna, Samuel T. Field, Samuel H. Chen, Zhen Gupta, Rajesh Roche, Dominic E. Christie, Jason D. Asch, David A. TI Adherence to Sleep Apnea Therapy and Use of Lipid-Lowering Drugs A Study of the Healthy-User Effect SO CHEST LA English DT Article ID POSITIVE AIRWAY PRESSURE; PLACEBO-CONTROLLED TRIAL; INDEPENDENT RISK-FACTOR; BLOOD-PRESSURE; CARDIOVASCULAR OUTCOMES; MEDICATION ADHERENCE; PRACTICE PARAMETERS; DAYTIME SLEEPINESS; FOLLOW-UP; CPAP USE AB Background: Evidence that continuous positive airway pressure (CPAP) reduces cardiovascular morbidity comes largely from observational studies. This association may be confounded if CPAP adherents are healthier in ways not measured by investigators. We assessed whether patients adhering to lipid-lowering medications were more adherent to CPAP. Methods: This was a retrospective cohort study undertaken at the Philadelphia Veterans Affairs (VA) Medical Center (2005-2006) of consecutive patients on lipid-lowering therapy newly initiating CPAP for obstructive sleep apnea. Adherence to medications dispensed via the VA closed-pharmacy system was measured as the proportion of days covered (>= 80% vs <80%) in the year prior to CPAP initiation. CPAP adherence was defined as >= 4 h/d of "mask-on" time, measured electronically daily during the first week of CPAP, We examined the association between medication adherence and CPAP adherence using multivariable logistic regression. Results: Complete data were available for 117 of 142 (81.5%) subjects. After adjustment for age, race, medical comorbidity, and sleep apnea-related clinical factors, subjects with low medication adherence demonstrated a 40.1% (95% CI, 30.0-51.0) probability of using CPAP >= 4 h/d compared with 55.2% (95% CI, 46.9-63.1) for subjects with adequate (>= 80%) medication adherence (adjusted for comparison, odds ratio (OR) = 1.8 [95% CI, 1.0-3.3], P = .04). Married patients were more adherent to medications and CPAP; inclusion of this factor reduced to nonsignificance the association of medication and CPAP adherence (OR = 1.6 [95% CI, 0.9-2.8], P = .12). Conclusion: Patients consistently refilling lipid-lowering medications were more adherent to CPAP, suggesting that differences in medication adherence or other health-promoting behaviors should be investigated in future nonrandomized, observational studies linking CPAP adherence and cardiovascular outcomes. CHEST 2010; 137(1).102-108 C1 [Platt, Alec B.; Kuna, Samuel T.; Field, Samuel H.; Roche, Dominic E.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Gupta, Rajesh] Philadelphia Vet Affairs Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA USA. [Kuna, Samuel T.; Christie, Jason D.; Asch, David A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Christie, Jason D.; Asch, David A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Platt, Alec B.] Reading Hosp Med Ctr, Reading, PA USA. [Field, Samuel H.] Univ N Carolina, FPG Child Dev Inst, Chapel Hill, NC USA. [Chen, Zhen] NICHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Platt, AB (reprint author), 2608 Keiser Blvd, Wyomissing, PA 19610 USA. EM alecplatt@gmail.com OI Asch, David/0000-0002-7970-286X FU Center for Health Equity Research and Promotion; Philadelphia VA Medical Center, Philadelphia, PA; National Institutes of Health [T-32 HL07713-14] FX This study was supported by grant funding to Dr Platt from Center for Health Equity Research and Promotion, Philadelphia VA Medical Center, Philadelphia, PA. Dr Platt was supported by a training grant from National Institutes of Health [Grant T-32 HL07713-14]. NR 51 TC 23 Z9 25 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2010 VL 137 IS 1 BP 102 EP 108 DI 10.1378/chest.09-0842 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 542DK UT WOS:000273471500019 PM 19820075 ER PT J AU Eum, SY Kong, JH Hong, MS Lee, YJ Kim, JH Hwang, SH Cho, SN Via, LE Barry, CE AF Eum, Seok-Yong Kong, Ji-Hye Hong, Min-Sun Lee, Ye-Jin Kim, Jin-Hee Hwang, Soo-Hee Cho, Sang-Nae Via, Laura E. Barry, Clifton E., III TI Neutrophils Are the Predominant Infected Phagocytic Cells in the Airways of Patients With Active Pulmonary TB SO CHEST LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; PERIPHERAL-BLOOD NEUTROPHILS; ALVEOLAR MACROPHAGES; GRANULOMA-FORMATION; IN-VITRO; MICE; ACTIVATION; RELEASE; HOST; CYTOKINES AB Background: The exact role of neutrophils in the pathogenesis of TB is poorly understood. Recent evidence suggests that neutrophils are not simply scavenging phagocytes in Mycobacterium tuberculosis (Mtb) infection. Methods: Three different types of clinical specimens from patients with active pulmonary TB who underwent lung surgery were examined: sputum, BAIL fluid, and cavity contents. Differential cell separation and quantification were performed for intracellular and extracellular bacteria, and bacterial length was measured using microscopy. Results: Neutrophils were more abundant than macrophages in sputum (86.6% +/- 2.2% vs 8.4% +/- 1.3%) and in BAL fluid (78.8% +/- 5.8% vs 11.8% +/- 4.1%). Inside the cavity, lymphocytes (41.3% +/- 11.2%) were the most abundant cell type, followed by neutrophils (38.8% +/- 9.4%) and macrophages (19.5% +/- 7.5%). More intracellular bacilli were found in neutrophils than macrophages in sputum (67.6% +/- 5.6% vs 25.2% +/- 6.5%), in BAL fluid (65.1% +/- 14.4% vs 28.3% +/- 11.6%), and in cavities (61.8% +/- 13.3% vs 23.9% +/- 9.3%). The lengths of Mtb were shortest in cavities (1.9 +/- 0.1 mu m), followed by in sputum (2.9 +/- 0.1 mu m) and in BAIL fluid (3.6 +/- 0.2 mu m). Conclusions: Our results show that neutrophils are the predominant cell types infected with AM in patients with TB and that these intracellular bacteria appear to replicate rapidly. These results are consistent with a role for neutrophils in providing a permissive site for a final burst of active replication of the bacilli prior to transmission. CHEST 2010; 137(1):122-128 C1 [Eum, Seok-Yong; Hong, Min-Sun; Lee, Ye-Jin] Int TB Res Ctr, Div Immunopathol & Cellular Immunol, Masan 631320, South Korea. [Kim, Jin-Hee; Hwang, Soo-Hee] Natl Masan TB Hosp, Masan, South Korea. [Cho, Sang-Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. [Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Eum, SY (reprint author), Int TB Res Ctr, Div Immunopathol & Cellular Immunol, 475-1 Gapo, Masan 631320, South Korea. EM syeumkr@gmail.com RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU National Institutes of Health, National Institute of Allergy and Infections Diseases [Z01 AI000783-11]; Bill and Melinda Gates Foundation; Wellcome Trust [37882] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infections Diseases (Z01 AI000783-11), and in part by a grant from the Bill and Melinda Gates Foundation and the Wellcome Trust through the Grand Challenges in Global Health Initiative (C.E.B. and S.-N.C.) Grant No. 37882 (Douglas Young, Imperial College, Principal Investigator). NR 45 TC 163 Z9 169 U1 2 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2010 VL 137 IS 1 BP 122 EP 128 DI 10.1378/chest.09-0903 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 542DK UT WOS:000273471500022 PM 19749004 ER PT J AU O'Neal, CR Brotman, LM Huang, KY Gouley, KK Kamboukos, D Calzada, EJ Pine, DS AF O'Neal, Colleen R. Brotman, Laurie Miller Huang, Keng-Yen Gouley, Kathleen Kiely Kamboukos, Dimitra Calzada, Esther J. Pine, Daniel S. TI Understanding Relations Among Early Family Environment, Cortisol Response, and Child Aggression via a Prevention Experiment SO CHILD DEVELOPMENT LA English DT Article ID CALLOUS-UNEMOTIONAL TRAITS; PITUITARY-ADRENAL AXIS; STRESS HORMONE LEVELS; SALIVARY CORTISOL; MATERNAL-CARE; ANTISOCIAL-BEHAVIOR; PHYSICAL AGGRESSION; PARENTING PRACTICES; CONDUCT PROBLEMS; HIGH-RISK AB This study examined relations among family environment, cortisol response, and behavior in the context of a randomized controlled trial with 92 children (M = 48 months) at risk for antisocial behavior. Previously, researchers reported an intervention effect on cortisol response in anticipation of a social challenge. The current study examined whether changes in cortisol response were related to later child aggression. Among lower warmth families, the intervention effect on aggression was largely mediated by the intervention effect on cortisol response. Although the intervention also resulted in significant benefits on child engaging behavior, cortisol response did not mediate this effect. These findings demonstrate meaningful associations between cortisol response and aggression among children at familial risk for antisocial behavior. C1 [O'Neal, Colleen R.; Brotman, Laurie Miller; Huang, Keng-Yen; Gouley, Kathleen Kiely; Kamboukos, Dimitra; Calzada, Esther J.] NYU, NYU Child Study Ctr, Sch Med, New York, NY 10016 USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RP O'Neal, CR (reprint author), NYU, NYU Child Study Ctr, Sch Med, 215 Lexington Ave,14th Floor, New York, NY 10016 USA. EM onealc01@nyumc.org; millel02@nyumc.org FU NIMH NIH HHS [R01 MH055188, R01 MH055188-04, R01 MH055188-05, R01 MH055188-06, R01 MH55188]; NIMHD NIH HHS [P60 MD000538-01] NR 78 TC 32 Z9 32 U1 3 U2 21 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2010 VL 81 IS 1 BP 290 EP 305 PG 16 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 552QM UT WOS:000274308300018 PM 20331668 ER PT S AU Hayashi, T Su, TP AF Hayashi, Teruo Su, Tsung-Ping BE Harris, JR TI Cholesterol at the Endoplasmic Reticulum: Roles of the Sigma-1 Receptor Chaperone and Implications thereof in Human Diseases SO CHOLESTEROL BINDING AND CHOLESTEROL TRANSPORT PROTEINS: STRUCTURE AND FUNCTION IN HEALTH AND DISEASE SE Subcellular Biochemistry LA English DT Article; Book Chapter DE Cholesterol; Steroid; Sigma-1 receptor chaperone; Endoplasmic retieulum; Mitochondria-associated ER membrane; Lipid raft; Detergent-resistant microdomain; Trophic factor ID LONG-TERM POTENTIATION; AMINO-ACID-RESIDUES; DOMAIN-LIKE-I; LIGAND-BINDING; LIPID RAFTS; STEROID-BINDING; SIGNAL-TRANSDUCTION; MEMBRANE-FRACTION; MOLECULAR-CLONING; PC12 CELLS AB Despite substantial data elucidating the roles of cholesterol in lipid rafts at the plasma membrane, the roles of cholesterol and related lipids in lipid raft microdomains at the level of subcellular membrane, such as the endoplasmic retieulum (ER) membrane, remain less understood. Growing evidence, however, begins to unveil the importance of cholesterol and lipids on the lipid raft at the ER membrane. A few ER proteins including the sigma-1 receptor chaperone were identified at lipid raft-like microdomains of the ER membrane. The sigma-1 receptor, which is highly expressed at a subdomain of ER membrane directly apposing mitochondria and known as the mitochondria-associated ER membrane or MAM, has been shown to associate with steroids as well as cholesterol. The sigma-1 receptor has been implicated in ER lipid metabolisms/transports, lipid raft reconstitution at the plasma membrane, trophic factor signalling, cellular differentiation, and cellular protection against p-amyloid-induced neurotoxicity. Recent studies on sigma-1 receptor chaperones and other ER proteins clearly suggest that cholesterol, in concert with those ER proteins, may regulate several important functions of the ER including folding, degradation, compartmentalization, and segregation of ER proteins, and the biosynthesis of sphingolipids. C1 [Hayashi, Teruo; Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,US Dept HHS,NIH, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,US Dept HHS,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM thayashi@intra.nida.nih.gov; TSU@intra.nida.nih.gov FU Intramural NIH HHS [ZIA DA000206-25] NR 82 TC 24 Z9 28 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0306-0225 BN 978-90-481-8621-1 J9 SUBCELL BIOCHEM JI Subcell. Biochem. PY 2010 VL 51 BP 381 EP 398 DI 10.1007/978-90-481-8622-8_13 D2 10.1007/978-90-481-8622-8 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BOH93 UT WOS:000276683800013 PM 20213551 ER PT J AU Pilotto, A Addante, F Franceschi, M Leandro, G Rengo, G D'Ambrosio, P Longo, MG Rengo, F Pellegrini, F Dallapiccola, B Ferrucci, L AF Pilotto, Alberto Addante, Filomena Franceschi, Marilisa Leandro, Gioacchino Rengo, Giuseppe D'Ambrosio, Piero Longo, Maria Grazia Rengo, Franco Pellegrini, Fabio Dallapiccola, Bruno Ferrucci, Luigi TI Multidimensional Prognostic Index Based on a Comprehensive Geriatric Assessment Predicts Short-Term Mortality in Older Patients With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; mortality; risk factors; Multidimensional Prognostic Index (MPI); prognosis ID ELDERLY-PATIENTS; RISK STRATIFICATION; VALIDATION; FRAILTY; CLASSIFICATION; DIAGNOSIS; OUTCOMES; PEOPLE; MODEL; STATE AB Background-Multidimensional impairment of older patients may influence the clinical outcome of diseases. The aim of this study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure. Methods and Results-In this prospective study with a 1-month follow-up, 376 patients aged 65 and older with a diagnosis of heart failure were enrolled. A standardized comprehensive geriatric assessment that included information on functional (activities of daily living and instrumental activities of daily living), cognitive (Short Portable Mental Status Questionnaire), and nutritional status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications, and social support network, was used to calculate the MPI for mortality using a previously validated algorithm. The New York Heart Association, the Enhanced Feedback for Effective Cardiac Treatment, and the Acute Decompensated Heart Failure National Registry regression model scores were also calculated. Higher MPI values were significantly associated with higher 30-day mortality, both in men (MPI-1, 2.8%; MPI-2, 15.3%; MPI-3, 47.4%; P=0.000) and women (MPI-1, 0%; MPI-2, 6.5%; MPI-3, 14.6%; P=0.011). The discrimination of the MPI was also good, with areas under the receiver operating characteristic curves (men: 0.83; 95% CI, 0.75 to 0.90; women: 0.80; 95% CI, 0.71 to 0.89) greater than receiver operating characteristic areas of New York Heart Association (men: 0.63; 95% CI, 0.57 to 0.69; P=0.015; women: 0.65; 95% CI, 0.55 to 0.75; P=0.064), Enhanced Feedback for Effective Cardiac Treatment (men: 0.69; 95% CI, 0.58 to 0.79; P=0.045; women: 0.71; 95% CI, 0.55 to 0.87; P=0.443), and Acute Decompensated Heart Failure National Registry scores (men: 0.65; 95% CI, 0.52 to 0.78; P=0.023; women: 0.67; 95% CI, 0.49 to 0.83, P=0.171). Conclusions-The MPI, calculated from information collected in a standardized comprehensive geriatric assessment, is useful to estimate the risk of 1-month mortality in older patients with heart failure. (Circ Heart Fail. 2010; 3: 14-20.) C1 [Pilotto, Alberto; Addante, Filomena; Franceschi, Marilisa; D'Ambrosio, Piero; Longo, Maria Grazia] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, I-71013 San Giovanni Rotondo, FG, Italy. [Pilotto, Alberto; Addante, Filomena; Franceschi, Marilisa; D'Ambrosio, Piero; Longo, Maria Grazia] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, I-71013 San Giovanni Rotondo, FG, Italy. [Leandro, Gioacchino] IRCCS Saverio De Bellis, Biostat & Gastroenterol Unit, Castellana Grotte, Italy. [Rengo, Giuseppe] Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA. [Rengo, Giuseppe; Rengo, Franco] Univ Naples Federico 2, Dept Internal Med Cardiovasc Sci & Immunol, Naples, Italy. [Pellegrini, Fabio] Biostat Unit, San Giovanni Rotondo, Italy. [Pellegrini, Fabio] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, CH, Italy. [Dallapiccola, Bruno] Casa Sollievo della Sofferenza Mendel Inst, Rome, Italy. [Dallapiccola, Bruno] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Pilotto, A (reprint author), IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, Viale Cappuccini 1, I-71013 San Giovanni Rotondo, FG, Italy. EM alberto.pilotto@operapadrepio.it RI Rengo, Giuseppe/K-4963-2016; Dallapiccola, Bruno/K-8692-2016 OI Rengo, Giuseppe/0000-0002-9701-0437; Leandro, Gioacchino/0000-0001-6624-4532; Dallapiccola, Bruno/0000-0002-5031-1013 FU Ministero della Salute (Italy); National Institute of Aging (Baltimore, Md) FX This work was supported by grants from Ministero della Salute (Italy), IRCCS Research Program 2006-2008, Line 2: "Malattie di rilevanza sociale," and by the Intramural Research Program of the National Institute of Aging (Baltimore, Md). NR 41 TC 57 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2010 VL 3 IS 1 BP 14 EP 20 DI 10.1161/CIRCHEARTFAILURE.109.865022 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 545MA UT WOS:000273735100004 PM 19850698 ER PT S AU Valle, BL Morin, PJ AF Valle, Blanca L. Morin, Patrice J. BE Yu, ASL TI Claudins in Cancer Biology SO CLAUDINS SE Current Topics in Membranes LA English DT Review; Book Chapter ID CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; SQUAMOUS-CELL CARCINOMA; TIGHT-JUNCTION PROTEINS; DIFFERENTIAL GENE-EXPRESSION; EPITHELIAL OVARIAN-CANCER; SEROUS PAPILLARY CARCINOMA; HUMAN COLORECTAL-CANCER; GROWTH-FACTOR RECEPTOR; LYMPH-NODE METASTASIS; CANINE KIDNEY-CELLS AB OVERVIEW Claudins are a family of 24 integral membrane proteins that have crucial roles in tight junction (TJ) formation and function (Krause et al., 2008; Lal-Nag & Morin, 2009; Tsukita & Furuse, 2000). The cellular TJ, located at the most apical area of the basolateral membrane of epithelial and endothelial cells, is a structure involved in maintenance of cell polarity and paracellular ion transport. Different tissues have different transport requirements, and it is believed that the different combinations of claudins in a given cell determines the tightness and selectivity of the TJ (Krause et al.; Van Itallie & Anderson, 2006), explaining the heterogeneity in claudin expression among different tissues. A large number of studies have now demonstrated that the expression of claudin proteins is frequently altered in several human malignancies. In this chapter, we review the changes in claudin expression observed in various cancers, their mechanisms of regulation, as well as the functional studies that may suggest a role for these proteins in cancer. Finally, we summarize the extensive literature suggesting that claudins may become useful markers for detection and diagnosis, as well as possible targets for therapy. C1 [Valle, Blanca L.; Morin, Patrice J.] NIA, Lab Cellular & Mol Biol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Valle, BL (reprint author), NIA, Lab Cellular & Mol Biol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. NR 235 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-381039-7 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2010 VL 65 BP 293 EP 333 DI 10.1016/S1063-5823(10)65013-2 PG 41 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BPZ47 UT WOS:000280437500013 ER PT J AU Saulsbury, FT Remmers, EF Aksentijevich, I AF Saulsbury, F. T. Remmers, E. F. Aksentijevich, I. TI A novel mutation in TNFRSF1A associated with overlapping features of tumour necrosis factor receptor-associated periodic syndrome and hyper-IgD syndrome SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE Tumour necrosis factor receptor; hyper-IgD; fever ID ENCODING MEVALONATE KINASE; FEVER SYNDROME; HYPERIMMUNOGLOBULINEMIA-D; TNF-RECEPTOR; SYNDROME TRAPS; SPECTRUM; GENE AB We describe a 10-year-old child with a novel mutation, c.352A>G/p.Thr118Ala (T89A) in the tumour necrosis factor receptor superfamily 1A (TNFRSF1A) gene. The patient presented with periodic fevers beginning at 2 years of age. He had overlapping clinical and laboratory features of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and hyper-IgD syndrome (HMS). This patient expands the clinical and genetic spectrum of TRAPS. C1 [Saulsbury, F. T.] Univ Virginia Hlth Syst, Dept Pediat, Div Immunol & Rheumatol, Charlottesville, VA 22908 USA. [Remmers, E. F.; Aksentijevich, I.] NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA. RP Saulsbury, FT (reprint author), Univ Virginia Hlth Syst, Dept Pediat, Div Immunol & Rheumatol, Box 800386, Charlottesville, VA 22908 USA. EM fts@virginia.edu FU Intramural NIH HHS NR 16 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JAN-FEB PY 2010 VL 28 IS 1 BP 94 EP 96 PG 3 WC Rheumatology SC Rheumatology GA 573DK UT WOS:000275888400019 PM 20346247 ER PT J AU Cui, C Carbis, R An, SJ Jang, H Czerkinsky, C Szu, SSC Clemens, JD AF Cui, Changfa Carbis, Rodney An, So Jung Jang, Hyun Czerkinsky, Cecil Szu, Shousun C. Clemens, John D. TI Physical and Chemical Characterization and Immunologic Properties of Salmonella enterica Serovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; CHILDREN YOUNGER; VI-ANTIGEN; VACCINE; FEVER; IMMUNOGENICITY; IMMUNIZATION; INFANTS; AGE; PERSISTENCE AB Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines. C1 [Cui, Changfa; Carbis, Rodney; An, So Jung; Jang, Hyun; Czerkinsky, Cecil; Clemens, John D.] Int Vaccine Inst, Seoul 151919, South Korea. [Szu, Shousun C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20854 USA. RP Cui, C (reprint author), 40 Boniface Dr, Rochester, NY 14620 USA. EM ccui@ivi.int RI CZERKINSKY, CECIL/G-6520-2015 FU governments of Korea, Kuwait, and Sweden; Disease of the Most Impoverished Program (DOMI); Bill and Melinda Gates Foundation FX The typhoid conjugate vaccine project is supported by the governments of Korea, Kuwait, and Sweden and by the Disease of the Most Impoverished Program (DOMI). The DOMI program is funded by the Bill and Melinda Gates Foundation. NR 56 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2010 VL 17 IS 1 BP 73 EP 79 DI 10.1128/CVI.00266-09 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539ED UT WOS:000273235500008 PM 19889941 ER PT J AU Bowen, RAR Hortin, GL Csako, G Otanez, OH Remaley, AT AF Bowen, Raffick A. R. Hortin, Glen L. Csako, Gyorgy Otanez, Oscar H. Remaley, Alan T. TI Impact of blood collection devices on clinical chemistry assays SO CLINICAL BIOCHEMISTRY LA English DT Review DE Blood collection devices; Surfactant; Interference; Clinical assay; Tube; Clinical chemistry; Preanalytical; Phlebotomy ID SERUM SEPARATOR TUBES; COAGULATION ACTIVATION MARKERS; IONIZED CALCIUM MEASUREMENTS; GEL BARRIER FORMATION; CENTRAL VENOUS LINES; SAMPLE STORAGE TIME; MACRO SOLID-PHASES; GLASS SYRINGES; WHOLE-BLOOD; MASS-SPECTROMETRY AB Blood collection devices interact with blood to alter blood composition, serum, or plasma fractions and in some cases adversely affect laboratory tests. Vascular access devices may release coating substances and exert shear forces that lyse cells. Blood-dissolving tube additives can affect blood constituent stability and analytical systems. Blood tube stoppers, stopper lubricants, tube walls, surfactants, clot activators, and separator gels may add materials, adsorb blood components, or interact with protein and cellular components. Thus, collection devices can be a major source of preanalytical error in laboratory testing. Device manufacturers, laboratory test vendors, and clinical laboratory personnel must understand these interactions as potential sources of error during preanalytical laboratory testing. Although the effects of endogenous blood substances have received attention, the effects of exogenous Substances on assay results have not been well described. This review will identify sources of exogenous substances in blood specimens and propose methods to minimize their impact on clinical chemistry assays. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Bowen, Raffick A. R.; Otanez, Oscar H.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Hortin, Glen L.] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32608 USA. [Csako, Gyorgy; Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Bowen, RAR (reprint author), Stanford Univ, Dept Pathol, 300 Pasteur Dr,Room H1507 B, Stanford, CA 94305 USA. EM rbowen@stanfordmed.org NR 317 TC 73 Z9 74 U1 4 U2 41 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD JAN PY 2010 VL 43 IS 1-2 BP 4 EP 25 DI 10.1016/j.clinbiochem.2009.10.001 PG 22 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 542SD UT WOS:000273514400002 PM 19822139 ER PT J AU Memmott, RM Dennis, PA AF Memmott, Regan M. Dennis, Phillip A. TI The Role of the Akt/mTOR Pathway in Tobacco Carcinogen-Induced Lung Tumorigenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; RECEPTOR SUBUNIT GENES; K-RAS MUTATIONS; A/J MICE; PROTEIN-KINASE; T-CELLS; SUSCEPTIBILITY LOCUS; 3-KINASE/AKT PATHWAY; MEDIATED ACTIVATION; NICOTINIC RECEPTOR AB Lung cancer is the leading cause of cancer-related death in the United States, and 85 to 90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mammalian target of rapamycin (mTOR) pathway that regulates cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco carcinogen-induced activation of Akt and mTOR. Preclinical studies show that inhibitors of the Akt/mTOR pathway inhibit tumor formation in mouse models of carcinogen-induced lung tumorigenesis. Some of these inhibitors will be highlighted, and their clinical potential for the treatment and prevention of lung cancer will be discussed. Clin Cancer Res; 16(1); 4-10. (C) 2010 AACR. C1 [Memmott, Regan M.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov FU Intramural NIH HHS [Z01 SC010292-09] NR 66 TC 31 Z9 33 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2010 VL 16 IS 1 BP 4 EP 10 DI 10.1158/1078-0432.CCR-09-0234 PG 7 WC Oncology SC Oncology GA 606EI UT WOS:000278404500002 PM 20028747 ER PT J AU Kimura, T Kuwata, T Ashimine, S Yamazaki, M Yamauchi, C Nagai, K Ikehara, A Feng, Y Dimitrov, DS Saito, S Ochiai, A AF Kimura, Taichi Kuwata, Takeshi Ashimine, Satoshi Yamazaki, Manabu Yamauchi, Chisako Nagai, Kanji Ikehara, Akashi Feng, Yang Dimitrov, Dimiter S. Saito, Seiichi Ochiai, Atsushi TI Targeting of Bone-Derived Insulin-Like Growth Factor-II by a Human Neutralizing Antibody Suppresses the Growth of Prostate Cancer Cells in a Human Bone Environment SO CLINICAL CANCER RESEARCH LA English DT Article ID COMBINED IMMUNODEFICIENT MICE; IGF-II; RECEPTOR; METASTASIS; EXPRESSION; BIOAVAILABILITY; BREAST; MATRIX AB Purpose: Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer. Experimental Design: We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells. Results: Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells. Conclusions: Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer. Clin Cancer Res; 16(1); 121-9. (C)2010 AACR. C1 [Kimura, Taichi; Kuwata, Takeshi; Ashimine, Satoshi; Yamazaki, Manabu; Yamauchi, Chisako; Ochiai, Atsushi] East Hosp, Natl Canc Ctr, Res Ctr Innovat Oncol, Div Pathol, Chiba 2778577, Japan. [Nagai, Kanji] East Hosp, Natl Canc Ctr, Div Thorac Oncol, Chiba 2778577, Japan. [Kimura, Taichi; Ashimine, Satoshi; Ikehara, Akashi; Saito, Seiichi] Univ Ryukyus, Fac Med, Dept Organ Oriented Med, Div Urol, Okinawa, Japan. [Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Ochiai, A (reprint author), East Hosp, Natl Canc Ctr, Res Ctr Innovat Oncol, Div Pathol, 6-5-1 Kashiwanoha, Chiba 2778577, Japan. EM aochiai@east.ncc.go.jp FU Ministry of Health and Welfare of Japan; Foundation for Promotion of Cancer Research in Japan; NIH, National Cancer Institute, Center for Cancer Research FX Grant-in-Aid for the Third-Term Comprehensive 10 Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan and Research Resident Fellowships from the Foundation for Promotion of Cancer Research in Japan (T. Kimura, S. Ashimine, M. Yamazaki, and C. Yamauchi). The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (Y. Feng and D.S. Dimitrov). NR 29 TC 19 Z9 20 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2010 VL 16 IS 1 BP 121 EP 129 DI 10.1158/1078-0432.CCR-09-0982 PG 9 WC Oncology SC Oncology GA 606EI UT WOS:000278404500013 PM 20028742 ER PT J AU Yoshizawa, A Fukuoka, J Shimizu, S Shilo, K Franks, TJ Hewitt, SM Fujii, T Cordon-Cardo, C Jen, J Travis, WD AF Yoshizawa, Akihiko Fukuoka, Junya Shimizu, Shigeki Shilo, Konstantin Franks, Teri J. Hewitt, Stephen M. Fujii, Takeshi Cordon-Cardo, Carlos Jen, Jin Travis, William D. TI Overexpression of Phospho-eIF4E Is Associated with Survival through AKT Pathway in Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ATYPICAL ADENOMATOUS HYPERPLASIA; FACTOR RECEPTOR MUTATION; TUBEROUS SCLEROSIS; MAMMALIAN TARGET; TRANSLATION INITIATION; TISSUE MICROARRAY; SIGNALING PATHWAY; EGFR MUTATIONS; FACTOR EIF-4E; CYCLIN D1 AB Purpose: The eukaryotic translation initiation factor complex 4E (eIF4E) is downstream in the mammalian target of rapamycin (mTOR) pathway. This study explored expression of eIF4E and its relationship with the PTEN/AKT and RAS/MEK/ERK pathways in non-small cell lung carcinoma (NSCLC). Experimental Design: The status of phosphorylated eIF4E (p-eIF4E), phosphorylated AKT (p-AKT), PTEN, phosphorylated tuberin (p-TSC2), phosphorylated mTOR (p-mTOR), phosphorylated S6 (p-S6), and phosphorylated Erk1/2 (p-Erk1/2) was studied using immunohistochemical analysis applied to a tissue microarray containing 300 NSCLCs. Staining results for each antibody were compared with clinical and pathologic features, and the relationship between staining results was explored. Results: Overexpression of p-eIF4E, p-AKT, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 in NSCLC was found in 39.9%, 78.8%, 5.1%, 46.7%, 27.1%, and 16.6% of tumors, respectively. The phenotype of p-eIF4E correlated positively with that of p-AKT, p-TSC2, and p-S6 (P < 0.001). Overall survival in NSCLC patients was significantly shorter in cases with overexpression of p-eIF4E and p-AKT alone and in combination (log-rank P < 0.001, each). Cases with underexpression of PTEN were limited (6.4%), and this phenotype did not correlate with any clinical variable. In cluster analysis, the p-AKT/p-mTOR/p-eIF4E/p-S6-positive group had significantly shorter survival compared with the survival of all cases (P < 0.001). Multivariate analysis showed that p-eIF4E overexpression is an independent prognostic factor for NSCLC (P = 0.004). Conclusions: This study shows that p-eIF4E expression in addition to p-AKT predicts poor prognosis in NSCLC. Moreover, the correlation between expression of p-eIF4E with p-AKT, as well as p-TSC2 and p-S6, indicates that eIF4E activation through the AKT pathway plays an important role in the progression of NSCLC. Clin Cancer Res; 16(1); 240-8. (C)2010 AACR. C1 [Yoshizawa, Akihiko; Shimizu, Shigeki; Travis, William D.] Columbia Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Cordon-Cardo, Carlos] Columbia Univ, Dept Pathol, New York, NY 10065 USA. [Fukuoka, Junya] Toyama Univ Hosp, Pathol Lab, Toyama, Japan. [Shimizu, Shigeki] Nagoya City Univ, Grad Sch Med Sci, Dept Clin Pathol Pathol 2, Nagoya, Aichi, Japan. [Shilo, Konstantin; Franks, Teri J.] AFIP, Dept Pulm & Mediastinal Pathol, Washington, DC USA. [Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Fujii, Takeshi] Toranomon Gen Hosp, Dept Pathol, Tokyo, Japan. [Yoshizawa, Akihiko] Kyoto Univ Hosp, Dept Diagnost Pathol, Kyoto 606, Japan. [Jen, Jin] Mayo Clin, Dept Pulm & Crit Care Med, Rochester, MN USA. RP Travis, WD (reprint author), Columbia Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM travisw@mskcc.org RI Shilo, Konstantin/E-4084-2011; Fujii, Takeshi/D-5877-2014; OI Fujii, Takeshi/0000-0001-7237-1183; Hewitt, Stephen/0000-0001-8283-1788; S, K/0000-0002-6702-3130 NR 49 TC 62 Z9 66 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2010 VL 16 IS 1 BP 240 EP 248 DI 10.1158/1078-0432.CCR-09-0986 PG 9 WC Oncology SC Oncology GA 606EI UT WOS:000278404500024 PM 20008839 ER PT J AU He, M Mangiameli, DP Kachala, S Hunter, K Gillespie, J Bian, XP Shen, HCJ Libutti, SK AF He, Mei Mangiameli, David P. Kachala, Stefan Hunter, Kent Gillespie, John Bian, Xiaopeng Shen, H. -C. Jennifer Libutti, Steven K. TI Expression Signature Developed from a Complex Series of Mouse Models Accurately Predicts Human Breast Cancer Survival SO CLINICAL CANCER RESEARCH LA English DT Article ID ORGAN MICROENVIRONMENT; HISTOLOGIC GRADE; METASTASIS; PROGNOSIS; THERAPY; PATHOGENESIS; LUNG; CELL AB Purpose: The capability of microarray platform to interrogate thousands of genes has led to the development of molecular diagnostic tools for cancer patients. Although large-scale comparative studies on clinical samples are often limited by the access of human tissues, expression profiling databases of various human cancer types are publicly available for researchers. Given that mouse models have been instrumental to our current understanding of cancer progression, we aimed to test the hypothesis that novel gene signatures possessing predictability in clinical outcome can be derived by coupling genomic analyses in mouse models of cancer with publicly available human cancer data sets. Experimental Design: We established a complex series of syngeneic metastatic animal models using a murine breast cancer cell line. Tumor RNA was hybridized on Affymetrix MouseGenome-430A2.0 Gene-Chips. With the use of Venn logic, gene signatures that represent metastatic competency were derived and tested against publicly available human breast and lung cancer data sets. Results: Survival analyses showed that the spontaneous metastasis gene signature was significantly associated with metastasis-free and overall survival (P < 0.0005). Consequently, the six-gene model was determined and showed statistical predictability in predicting survival in breast cancer patients. In addition, the model was able to stratify poor from good prognosis for lung cancer patients in most data sets analyzed. Conclusions: Together, our data support that novel gene signature derived from mouse models of cancer can be used for predicting human cancer outcome. Our approaches set precedence that similar strategies may be used to decipher novel gene signatures for clinical utility. Clin Cancer Res; 16(1); 249-59. (C)2010 AACR. C1 [Libutti, Steven K.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA. [He, Mei; Mangiameli, David P.; Shen, H. -C. Jennifer; Libutti, Steven K.] NCI, Tumor Angiogenesis Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. [Hunter, Kent] NCI, Metastasis Susceptibil Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Bian, Xiaopeng] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA. [Mangiameli, David P.] Columbia Univ, Coll Phys & Surg, Dept Surg, Div Surg Oncol, New York, NY USA. [Kachala, Stefan] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Surg, New York, NY USA. [Gillespie, John] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Libutti, SK (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Dept Surg, 4th Floor,Greene Med Arts Pavil,3400 Bainbridge A, Bronx, NY 10467 USA. EM slibutti@montefiore.org FU Intramural NIH HHS [Z01 SC010368-07] NR 24 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2010 VL 16 IS 1 BP 249 EP 259 DI 10.1158/1078-0432.CCR-09-1602 PG 11 WC Oncology SC Oncology GA 606EI UT WOS:000278404500025 PM 20028755 ER PT J AU Ascierto, M Worschech, A Pos, Z Rossano, F Ascierto, P Wang, E Marincola, F AF Ascierto, Maria Worschech, Andrea Pos, Zoltan Rossano, Fabio Ascierto, Paolo Wang, Ena Marincola, Francesco TI Variations of Vaccinia Virus' Replication in Melanoma and Lung Cell Lines Based on Different Expression of IFI6, and IFTMN2 and beta-microglobin SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Ascierto, Maria; Pos, Zoltan; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Worschech, Andrea] Genelox Corp, San Diego, CA USA. [Ascierto, Paolo] Fondaz G Pascale, NCI, Naples, Italy. [Rossano, Fabio] Univ Naples Federico 2, Naples, Italy. RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S65 EP S65 DI 10.1016/j.clim.2010.03.198 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700182 ER PT J AU Bax, H Kristosturyan, E Browne, S Ding, L Holland, S Sampaio, E AF Bax, Hannelore Kristosturyan, Ervand Browne, Sarah Ding, Li Holland, Steven Sampaio, Elizabeth TI STAT1:STAT3 Cross-regulation in Patients with Defective Interferon Gamma Signaling SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Bax, Hannelore; Kristosturyan, Ervand; Browne, Sarah; Ding, Li; Holland, Steven; Sampaio, Elizabeth] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S134 EP S134 DI 10.1016/j.clim.2010.03.404 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700388 ER PT J AU Bedognetti, D Zoppoli, G Zanardi, E Massucco, C Sertoli, MR Messina, M Siffredi, G Caltabiano, G Provinciali, N Blandini, P Sanguineti, S Ricci, F Zupo, S Schiavone, G Santamaria, S Marincola, F Uccellini, L Ansaldi, F De Maria, A AF Bedognetti, Davide Zoppoli, Gabriele Zanardi, Elisa Massucco, Carlotta Sertoli, Mario Roberto Messina, Marco Siffredi, Guido Caltabiano, Graziano Provinciali, Nicoletta Blandini, Pietro Sanguineti, Silvia Ricci, Francesco Zupo, Simonetta Schiavone, Giovanna Santamaria, Stefania Marincola, Francesco Uccellini, Lorenzo Ansaldi, Filippo De Maria, Andrea TI Prolonged Lack of Humoral Response to Influenza Vaccine Associated with a Persistent Depletion of B Memory Cells in Non Hodgkin's Lymphoma Patients Treated with Rituximab-containing lmmunochemotherapy SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Bedognetti, Davide; Zanardi, Elisa; Sertoli, Mario Roberto; Messina, Marco; Siffredi, Guido; Caltabiano, Graziano; Provinciali, Nicoletta; Blandini, Pietro; Ricci, Francesco; Schiavone, Giovanna; Santamaria, Stefania; Ansaldi, Filippo; De Maria, Andrea] Univ Genoa, Genoa, Italy. [Zoppoli, Gabriele; Sanguineti, Silvia; Marincola, Francesco; Uccellini, Lorenzo] NIH, Bethesda, MD 20892 USA. [Massucco, Carlotta; Zupo, Simonetta] Natl Inst Canc Res, Genoa, Italy. RI Bedognetti, Davide/A-9090-2012; de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S84 EP S84 DI 10.1016/j.clim.2010.03.252 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700236 ER PT J AU Biancotto, A Fuchs, C Pradeep, D McCoy, J AF Biancotto, Angelique Fuchs, Christopher Pradeep, Dagur McCoy, J. TI Complex Alterations in T Regulatory Cells Revealed by High Dimensional Flow Cytometry SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Biancotto, Angelique; Fuchs, Christopher; Pradeep, Dagur; McCoy, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S130 EP S130 DI 10.1016/j.clim.2010.03.391 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700375 ER PT J AU Damsker, J Luger, D Silver, P Iwakura, Y Chan, CC Caspi, R AF Damsker, Jesse Luger, Dror Silver, Phyllis Iwakura, Yoichiro Chan, Chi-Chao Caspi, Rachel TI Ocular Autoimmunity in the Face of a Combined Defect in Th1 and Th17 Effector Responses SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Damsker, Jesse; Luger, Dror; Silver, Phyllis; Chan, Chi-Chao; Caspi, Rachel] NIH, Bethesda, MD 20892 USA. [Iwakura, Yoichiro] Univ Tokyo, Tokyo, Japan. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S28 EP S29 DI 10.1016/j.clim.2010.03.088 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700072 ER PT J AU Deng, M Arias, M Ramaswamy, M Siegel, R AF Deng, Min Arias, Marco Ramaswamy, Madhu Siegel, Richard TI microRNA-181a: A Potential Regulator of Effector CD4+T Cell Phenotype SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Deng, Min; Arias, Marco; Ramaswamy, Madhu; Siegel, Richard] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S26 EP S26 DI 10.1016/j.clim.2010.03.083 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700067 ER PT J AU Elloumi, H Paulson, M Ding, L Gulbu, U Kristosturyan, E Bax, H Sampaio, E Holland, S AF Elloumi, Houda Paulson, Michelle Ding, Li Gulbu, Uzel Kristosturyan, Ervand Bax, Hannelore Sampaio, Elizabeth Holland, Steven TI Identification of a Novel STAT1 Dominant Negative Mutation Characterizes Decreased Activation in Response to Interferon Gamma SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Elloumi, Houda; Paulson, Michelle; Ding, Li; Gulbu, Uzel; Kristosturyan, Ervand; Bax, Hannelore; Sampaio, Elizabeth; Holland, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S139 EP S140 DI 10.1016/j.clim.2010.03.423 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700407 ER PT J AU Grant, C Duclos, S Moran-Paul, C Spain, L Arreaza-Rubin, G Guberski, D AF Grant, Christian Duclos, Shane Moran-Paul, Catherine Spain, Lisa Arreaza-Rubin, Guillermo Guberski, Dennis TI Development of Glucose Testing Protocols to Identify Pre-diabetic NOD Mice for Interventional Treatment SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Grant, Christian; Duclos, Shane; Moran-Paul, Catherine; Guberski, Dennis] Biomed Res Models Inc, Worcester, MA USA. [Spain, Lisa; Arreaza-Rubin, Guillermo] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S101 EP S101 DI 10.1016/j.clim.2010.03.302 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700286 ER PT J AU Grant, C Duclos, S Moran-Paul, C Spain, L Arreaza-Rubin, G Guberski, D AF Grant, Christian Duclos, Shane Moran-Paul, Catherine Spain, Lisa Arreaza-Rubin, Guillermo Guberski, Dennis TI Development of Protocols to Optimize Insulin Treatment of Type 1 Diabetes in NOD Mice SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Grant, Christian; Duclos, Shane; Moran-Paul, Catherine; Guberski, Dennis] Biomed Res Models Inc, Worcester, MA USA. [Spain, Lisa; Arreaza-Rubin, Guillermo] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S101 EP S101 DI 10.1016/j.clim.2010.03.304 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700288 ER PT J AU Karnelll, J Karnell, F Wilson, M Goldbach-Mansky, R Coyle, A Herbst, R Ettinger, R AF Karnelll, Jodi Karnell, Fredrick Wilson, Mildred Goldbach-Mansky, Raphaela Coyle, Anthony Herbst, Ronald Ettinger, Rachel TI Mycophenolic Acid Inhibits Primary B Cells but not Terminally Differentiated Plasma Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Karnelll, Jodi; Karnell, Fredrick; Coyle, Anthony; Herbst, Ronald; Ettinger, Rachel] MedImmune, Gaithersburg, MD USA. [Wilson, Mildred; Goldbach-Mansky, Raphaela] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S18 EP S18 DI 10.1016/j.clim.2010.03.058 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700042 ER PT J AU Katara, G Ansari, N Ramesh, V Salotra, P AF Katara, Gajendra Ansari, Nasim Ramesh, V. Salotra, Poonam TI Evidence for Accumulation of T Regulatory Cells in Lesion Tissue of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients: A Marker for Distinct Pathology SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Katara, Gajendra; Salotra, Poonam] Safdarjang Hosp, ICMR, Inst Pathol, New Delhi, India. [Ansari, Nasim] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S67 EP S68 DI 10.1016/j.clim.2010.03.206 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700190 ER PT J AU Pos, Z Thomas, J Selleri, S Spivey, T Wang, J Liu, H Worschech, A Sabatino, M Monaco, A Alter, H Falus, A Wang, E Marincola, F AF Pos, Zoltan Thomas, Jaime Selleri, Silvia Spivey, Tara Wang, Jeanne Liu, Hui Worschech, Andrea Sabatino, Marianna Monaco, Alessandro Alter, Harvey Falus, Andras Wang, Ena Marincola, Francesco TI The Impact of Race on Interferon-alpha Responsiveness: A Genome-wide Study SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Pos, Zoltan; Thomas, Jaime; Spivey, Tara; Liu, Hui; Sabatino, Marianna; Monaco, Alessandro; Alter, Harvey; Wang, Ena; Marincola, Francesco] Natl Inst Hlth, Bethesda, MD USA. [Selleri, Silvia] Ist Sci San Raffaele, Milan, Italy. [Wang, Jeanne] US FDA, Silver Spring, MD USA. [Worschech, Andrea] Univ Wurzburg, Wurzburg, Germany. [Falus, Andras] Semmelweis Univ, Budapest, Hungary. RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S45 EP S45 DI 10.1016/j.clim.2010.03.138 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700122 ER PT J AU Randall, K Lambe, T Johnson, A Kucharska, E Vinuesa, C Treanor, B Batista, F Chan, T Camidge, T Brink, R Cornall, R Goodnow, C AF Randall, Katrina Lambe, Teresa Johnson, Andy Kucharska, Edyta Vinuesa, Carola Treanor, Bebhinn Batista, Facundo Chan, Tyani Camidge, Tahra Brink, Robert Cornall, Richard Goodnow, Chris TI Immunodeficiency and Abnormal B Cell Synapse Formation due to DOCK8 Mutations in Mice SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Randall, Katrina] Canberra Hosp, Woden, ACT, Australia. [Lambe, Teresa; Cornall, Richard] Univ Oxford, Oxford, England. [Johnson, Andy] NIAID, NIH, Bethesda, DC USA. [Kucharska, Edyta; Vinuesa, Carola; Goodnow, Chris] Australian Natl Univ, Canberra, ACT, Australia. [Treanor, Bebhinn; Batista, Facundo] London Res Inst, London, England. [Chan, Tyani; Camidge, Tahra; Brink, Robert] Garvan Inst, Sydney, NSW, Australia. RI Lambe, Teresa/E-5733-2016 OI Lambe, Teresa/0000-0001-7711-897X NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S17 EP S17 DI 10.1016/j.clim.2010.03.055 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700039 ER PT J AU Sen, HN Liu, BY Wei, L Hu, MJ Jawad, S Chakrabarty, S Nussenblatt, R AF Sen, H. Nida Liu, Baoying Wei, Lai Hu, Mengjun Jawad, Shayma Chakrabarty, Sagarika Nussenblatt, Robert TI The Role of Double Negative T Cells in Uveitis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Sen, H. Nida; Liu, Baoying; Wei, Lai; Hu, Mengjun; Jawad, Shayma; Chakrabarty, Sagarika; Nussenblatt, Robert] Natl Inst Hlth, Bethesda, MD USA. RI Wei, Lai/D-1088-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S45 EP S45 DI 10.1016/j.clim.2010.03.137 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700121 ER PT J AU Song, YJ Meylan, F Botson, J Goldbach-Mansky, R Lee, D Siegel, R AF Song, Yun-Jeong Meylan, Francoise Botson, John Goldbach-Mansky, Raphaela Lee, David Siegel, Richard TI TL1A-DR3 Interactions are Important in Both Adaptive and Innate Immunity in Inflammatory Arthritis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Song, Yun-Jeong; Meylan, Francoise; Botson, John; Goldbach-Mansky, Raphaela; Siegel, Richard] NIH, Bethesda, MD 20892 USA. [Lee, David] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S88 EP S88 DI 10.1016/j.clim.2010.03.265 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700249 ER PT J AU Tran, D Bebris, L Shevach, E Illei, G AF Tran, Dat Bebris, Lolita Shevach, Ethan Illei, Gabor TI Efalizumab Down-regulates CD25 Expression on FOXP3(+) Regulatory T Cells and Exacerbates the Autoimmunity in Primary Sjogren's Syndrome SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Tran, Dat] Univ Texas Houston, Sch Med, Houston, TX USA. [Bebris, Lolita; Illei, Gabor] NIDCR, NIH, Bethesda, MD USA. [Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S58 EP S58 DI 10.1016/j.clim.2010.03.178 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700162 ER PT J AU Tran, D Thornton, A Shevach, E AF Tran, Dat Thornton, Angela Shevach, Ethan TI Helios is a Marker for Human Thymic-derived FOXP3+Regulatory T Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Tran, Dat] Univ Texas Houston, Sch Med, Houston, TX USA. [Thornton, Angela; Shevach, Ethan] NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S5 EP S5 DI 10.1016/j.clim.2010.03.020 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700004 ER PT J AU Yang, B Remmers, E Cosan, F Kirino, Y Ombrello, M O'Shea, J Gadina, M Kastner, D Gul, A AF Yang, Barbara Remmers, Elaine Cosan, Fulya Kirino, Yohei Ombrello, Michael O'Shea, John Gadina, Massimo Kastner, Daniel Gul, Ahmet TI Common Variants of the Class I Major Histocompatibility Complex, IL10, CPLX1, and IL23R Genes Predispose to Behcet's Disease in the Turkish Population SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Yang, Barbara; Remmers, Elaine; Kirino, Yohei; Ombrello, Michael; O'Shea, John; Gadina, Massimo; Kastner, Daniel] NIAMSD, NIH, Bethesda, MD 20892 USA. [Cosan, Fulya; Gul, Ahmet] Istanbul Univ, Istanbul, Turkey. NR 0 TC 0 Z9 0 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S11 EP S12 DI 10.1016/j.clim.2010.03.041 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700025 ER PT J AU Mulligan, K Harris, DR Monte, D Stoszek, S Emmanuel, P Hardin, DS Kapogiannis, BG Worrell, C Meyer, WA Sleasman, J Wilson, CM Aldrovandi, GM AF Mulligan, Kathleen Harris, D. Robert Monte, Dina Stoszek, Sonia Emmanuel, Patricia Hardin, Dana S. Kapogiannis, Bill G. Worrell, Carol Meyer, William A., III Sleasman, John Wilson, Craig M. Aldrovandi, Grace M. CA Adolescent Trials Network 021 Pro TI Obesity and Dyslipidemia in Behaviorally HIV-Infected Young Women: Adolescent Trials Network Study 021 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; METABOLIC SYNDROME; PHYSICAL-ACTIVITY; ANTIRETROVIRAL THERAPY; UNITED-STATES; SCIENTIFIC STATEMENT; INSULIN SENSITIVITY; FAT DISTRIBUTION AB Background. The goal of this study was to determine the nature and prevalence of abnormalities in lipids, glucose metabolism, and body composition in behaviorally human immunodeficiency virus (HIV)-infected young women and the relationship of these abnormalities to different classes of antiretroviral therapy regimens. Methods. We conducted a cross-sectional, multicenter study involving 173 behaviorally HIV-infected women aged 14-24 years and 61 HIV-seronegative control subjects. HIV-infected women were categorized as follows: antiretroviral therapy naive (n = 85), receiving a regimen containing a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 33), receiving a regimen containing a protease inhibitor (PI; n = 36), or receiving a regimen not containing an NNRTI or a PI (n = 19). Measurements included fasting lipid levels, glucose and insulin levels before and 2 hours after an oral glucose challenge, high-sensitivity C-reactive protein (hsCRP) levels, anthropometry, fat distribution (measured by dual energy X-ray absorptiometry), and antiretroviral therapy and medical histories. Race-adjusted results were compared across groups and within HIV-infected groups. Results. The median age of participants was 20 years. Of HIV-infected subjects, 77% were African American, 35% smoked cigarettes, and 32% reported exercising regularly. More than 40% had a body mass index >= 25. Triglycerides; total, high-density lipoprotein (HDL), and non-HDL cholesterol; and hsCRP levels differed significantly among groups, with higher levels being most common among those receiving antiretroviral therapy. Indices of glucose metabolism did not differ among groups. In general, cholesterol levels, hsCRP levels, and indices of glucose metabolism worsened as body mass index increased. Conclusions. Obesity, dyslipidemia, and inflammation were prominent among HIV-infected adolescent women and, coupled with other risk factors, may accelerate the lifetime risk of cardiovascular disease and other adverse events. These results underscore the need for a multifaceted approach to addressing risk reduction in this population. C1 [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Aldrovandi, Grace M.] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Harris, D. Robert; Monte, Dina; Stoszek, Sonia] WESTAT Corp, Rockville, MD 20850 USA. [Kapogiannis, Bill G.; Worrell, Carol] NICHHD, NIH, Bethesda, MD 20892 USA. [Meyer, William A., III] Quest Diagnost, Baltimore, MD USA. [Emmanuel, Patricia] Univ S Florida, Tampa, FL USA. [Sleasman, John] Univ S Florida, St Petersburg, FL 33701 USA. [Hardin, Dana S.] Ohio State Univ, Columbus, OH 43210 USA. [Wilson, Craig M.] Univ Alabama, Birmingham, AL USA. RP Mulligan, K (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Endocrinol, Bldg 30,Rm 3501K,1001 Potrero Ave, San Francisco, CA 94110 USA. EM kathleen.mulligan@ucsf.edu FU National Institutes of Health through the National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; National Institutes on Drug Abuse and Mental Health FX Adolescent Trials Network for HIV/AIDS Interventions from the National Institutes of Health (U01 HD 040533 and U01 HD 040474) through the National Institute of Child Health and Human Development (to B. G. K.), with supplemental funding from the National Institutes on Drug Abuse and Mental Health. NR 40 TC 17 Z9 17 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2010 VL 50 IS 1 BP 106 EP 114 DI 10.1086/648728 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539YO UT WOS:000273296500019 PM 19947855 ER PT J AU Chapman, AB Torres, VE Perrone, RD Steinman, TI Bae, KT Miller, JP Miskulin, DC Oskoui, FR Masoumi, A Hogan, MC Winklhofer, FT Braun, W Thompson, PA Meyers, CM Kelleher, C Schrier, RW AF Chapman, Arlene B. Torres, Vicente E. Perrone, Ronald D. Steinman, Theodore I. Bae, Kyongtae T. Miller, J. Philip Miskulin, Dana C. Oskoui, Frederic Rahbari Masoumi, Arnirali Hogan, Marie C. Winklhofer, Franz T. Braun, William Thompson, Paul A. Meyers, Catherine M. Kelleher, Cass Schrier, Robert W. TI The HALT Polycystic Kidney Disease Trials: Design and Implementation SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CONVERTING ENZYME-INHIBITION; RENIN-ANGIOTENSIN SYSTEM; BLOOD-PRESSURE CONTROL; II RECEPTOR BLOCKER; COMBINATION THERAPY; RENAL-DISEASE; ALDOSTERONE SYSTEM; VOLUME PROGRESSION; ENALAPRIL; CREATININE AB Background and objectives: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebocontrolled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m(2) were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACE monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m(2) compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. Results: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. Conclusions: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD. Clin J Am Soc Nephrol 5: 102-109, 2010. doi: 10.2215/CJN.04310709 C1 [Chapman, Arlene B.; Oskoui, Frederic Rahbari] Emory Univ, Sch Med, Atlanta, GA USA. [Torres, Vicente E.; Hogan, Marie C.] Mayo Coll Med, Rochester, MN USA. [Perrone, Ronald D.; Miskulin, Dana C.] Tufts Med Ctr, Boston, MA USA. [Steinman, Theodore I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bae, Kyongtae T.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Miller, J. Philip] Washington Univ, St Louis, MO USA. [Masoumi, Arnirali; Kelleher, Cass; Schrier, Robert W.] Univ Colorado, Aurora, CO USA. [Winklhofer, Franz T.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Braun, William] Cleveland Clin, Cleveland, OH 44106 USA. [Thompson, Paul A.] Univ S Dakota, Sioux Falls, SD USA. [Meyers, Catherine M.] NIDDK, NIH, Bethesda, MD USA. RP Chapman, AB (reprint author), 1364 Clifton Rd,Suite GG23, Atlanta, GA 30322 USA. EM Arlene_chapman@emory.org OI Miller, J Philip/0000-0003-4568-6846 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [DK62408, DK62401, DK62410, DK62402, DK62411]; NCRR GCRCs [RR000039, RR000051, RR00585, RR000054, RR23940]; NCRR CTSAs [RR025008, RR025780, RR024150, RR025752, RR024992]; The Polycystic Kidney Disease Foundation FX The HALT-PKD study is supported by cooperative agreements from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (DK62408, DK62401, DK62410, DK62402, and DK62411), the NCRR GCRCs at each institution (RR000039 Emory, RR000051 Colorado, RR00585 Mayo, RR000054 Tufts Medical Center, and RR23940 Kansas), and the NCRR CTSAs at each institution (RR025008 Emory, RR025780 Colorado, RR024150 Mayo, RR025752 Tufts, and RR024992 Washington University). Study medication for both trials was provided by Boehringer-Ingetheim Pharmaceuticals (telmisartan and matched placebo) and Merck & Co. (lisinopril). The Polycystic Kidney Disease Foundation provided financial support and recruitment assistance for the enrollment phase of HALT-PKD. The investigators thank Gigi Flynn and Robin Woltman and all of the clinical coordinators at each clinical site for their perseverance and hard work in implementing HALT-PKD. NR 45 TC 69 Z9 71 U1 3 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2010 VL 5 IS 1 BP 102 EP 109 DI 10.2215/CJN.04310709 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 545CN UT WOS:000273710200016 PM 20089507 ER PT J AU Beck, S Hallett, M AF Beck, S. Hallett, M. TI Surround inhibition is modulated by task difficulty SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Reaction time task; Motor evoked potentials; Transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; FOCAL HAND DYSTONIA; FRONTAL-CORTEX; INTERHEMISPHERIC INHIBITION; CORTICOSPINAL EXCITABILITY; INTRACORTICAL INHIBITION; VOLUNTARY MOVEMENT; EVOKED-POTENTIALS; REACTION-TIME AB Objective: The aim of this study was to further characterize surround inhibition (SI) in the primary motor cortex (M1) by comparing its magnitude and time course during a simple reaction time task (SRT) and a choice reaction time task (CRT). Methods: In both the SRT and the CRT, subjects performed the same right index finger flexion in response to an acoustic signal. For CRT, the alternative choice was a similar movement using the left index finger, as distinguished by a different tone. In both tasks, single pulse transcranial magnetic stimulation (TMS) was applied at rest, 75 ms (T1) and 25 ms before EMG onset (T2), and during the first peak of EMG (T3) in the right first dorsal interosseous muscle (FDI). Motor evoked potentials (MEPs) were recorded from both FDIs, which act as synergists in the task, and the right surrounding, relaxed abductor pollicis brevis muscle (APB). Results: For right hand movement, SI started earlier and was more pronounced for CRT compared to SRT. For left hand movement in the CRT, SI was similar to that of right hand movement. Conclusions: We conclude that SI occurs earlier and stronger with increasing task difficulty. Significance: The timing as well as the bilateral effect of the inhibition suggests that motor areas involved in motor planning, proximate to the motor cortex, contribute to the genesis of surround inhibition. Published by Elsevier Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Beck, S.; Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Beck, S.] Univ Freiburg, Dept Clin Neurol & Neurophysiol, D-7800 Freiburg, Germany. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10-7D37,10 Ctr Dr, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Deutsche Forschungsgemeinschaft (DFG) [BE-3792/1]; NINDS; S, NIH FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG, BE-3792/1) and by the Intramural Research Program of the NINDS, NIH. NR 40 TC 26 Z9 26 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JAN PY 2010 VL 121 IS 1 BP 98 EP 103 DI 10.1016/j.clinph.2009.09.010 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 556AC UT WOS:000274557500015 PM 19906559 ER PT J AU Sheehan, FT Derasari, A Fine, KM Brindle, TJ Alter, KE AF Sheehan, Frances T. Derasari, Aditya Fine, Kenneth M. Brindle, Timothy J. Alter, Katharine E. TI Q-angle and J-sign Indicative of Maltracking Subgroups in Patellofemoral Pain SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ANTERIOR KNEE PAIN; IN-VIVO; TIBIOFEMORAL KINEMATICS; PHYSICAL-EXAMINATION; PATELLAR TRACKING; ALIGNMENT; JOINT; WOMEN; INDIVIDUALS; RELIABILITY AB Mechanical factors related to patellofemoral pain syndrome and maltracking are poorly understood. Clinically, the Q-angle, J-sign,and lateral hypermobility commonly are used to evaluate patellar maltracking. However, these measures have yet to be correlated to specific three-dimensional patellofemoral displacements and rotations. Thus, we tested the hypotheses that increased Q-angle, lateral hypermobility, and J-sign correlate with three-dimensional patellofemoral displacements and rotations. We also determined whether multiple maltracking patterns can be discriminated, based on patellofemoral displacements and rotations. Three-dimensional patellofemoral motion data were acquired during active extension-flexion using dynamic MRI in 30 knees diagnosed with patellofemoral pain and at least one clinical sign of patellar maltracking (Q-angle, lateral hypermobility, or J-sign) and in 37 asymptomatic knees. Although the Q-angle is assumed to indicate lateral patellar subluxation, our data supported a correlation between the Q-angle and medial, not lateral, patellar displacement. We identified two distinct maltracking groups based on patellofemoral lateral-medial displacement, but the same groups could not be discriminated based on standard clinical measures (eg, Q-angle, lateral hypermobility, and J-sign). A more precise definition of abnormal three-dimensional patellofemoral motion, including identifying subgroups in the patellofemoral pain population, may allow more targeted and effective treatments. C1 [Sheehan, Frances T.; Brindle, Timothy J.; Alter, Katharine E.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Derasari, Aditya] Univ Miami, Dept Orthopaed, Miami, FL USA. [Fine, Kenneth M.] Orthopaed Ctr, Rockville, MD USA. [Brindle, Timothy J.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA. RP Sheehan, FT (reprint author), NIH, Dept Rehabil Med, Bldg 10 CRC,Room 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU Diagnostic Radiology Department at the National Institutes of Health FX We thank Ching-yi Shieh, PhD, and Elizabeth K. Rasch, PT, PhD, for support on the statistical analysis and Steven Stanhope, PhD, for guidance throughout the project. We also thank Bonnie Damaska, Jamie Fraunhaffer, Jere McLucas, Dr. Barry Boden, and the Diagnostic Radiology Department at the National Institutes of Health for their support and research time. NR 51 TC 18 Z9 18 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2010 VL 468 IS 1 BP 266 EP 275 DI 10.1007/s11999-009-0880-0 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 558SU UT WOS:000274767200039 PM 19430854 ER PT J AU Benjamin, DK Smith, PB Arrieta, A Castro, L Sanchez, PJ Kaufman, D Arnold, LJ Kovanda, LL Sawamoto, T Buell, DN Hope, WW Walsh, TJ AF Benjamin, D. K., Jr. Smith, P. B. Arrieta, A. Castro, L. Sanchez, P. J. Kaufman, D. Arnold, L. J. Kovanda, L. L. Sawamoto, T. Buell, D. N. Hope, W. W. Walsh, T. J. TI Safety and Pharmacokinetics of Repeat-Dose Micafungin in Young Infants SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ANTIFUNGAL-SURVEILLANCE-PROGRAM; LIPOSOMAL AMPHOTERICIN-B; BIRTH-WEIGHT INFANTS; IN-VITRO ACTIVITIES; DOUBLE-BLIND TRIAL; INVASIVE CANDIDIASIS; PEDIATRIC-PATIENTS; NEONATAL CANDIDEMIA; GLOBAL SURVEILLANCE; FUNGAL-INFECTIONS AB Given the risk of central nervous system infection, relatively high weight-based echinocandin dosages may be required for the successful treatment of invasive candidiasis and candidemia in young infants. This open-label study assessed the safety and pharmacokinetics (PK) of micafungin in 13 young infants (>48 h and <120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weight >= 1,000 and <1,000 g received 7 and 10 mg/kg/day, respectively, for a minimum of 4-5 days. In the 7-mg/kg/day group, the mean baseline weight and gestational age were 2,101 g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688 g and 25 weeks, respectively. The median pharmacokinetic values for the 7- and 10-mg/kg/day groups, respectively, were as follows: area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 258.1 and 291.2 mu g.h/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57 ml/min/kg; maximum plasma concentration, 23.3 and 24.9 mu g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8 ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage. C1 [Benjamin, D. K., Jr.; Smith, P. B.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Benjamin, D. K., Jr.; Smith, P. B.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Arrieta, A.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Castro, L.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Sanchez, P. J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kaufman, D.] Univ Virginia, Charlottesville, VA USA. [Arnold, L. J.; Kovanda, L. L.; Sawamoto, T.; Buell, D. N.] Astellas Pharma Global Dev, Deerfield, IL USA. [Hope, W. W.] Univ Manchester, Manchester, Lancs, England. [Walsh, T. J.] Natl Canc Inst, Bethesda, MD USA. RP Benjamin, DK (reprint author), Duke Univ, Dept Pediat, Durham, NC 27706 USA. EM danny.benjamin@duke.edu RI Smith, Phillip/I-5565-2014; OI Hope, William/0000-0001-6187-878X FU National Institute of Child Health and Human Development [1U10-HD45962-06, 1U10-HD046000-06]; Astellas Pharma Inc., Deerfield, IL FX This study was supported in part by the National Institute of Child Health and Human Development Pediatric Pharmacology Research Unit (grant 1U10-HD45962-06 to D.K.B. and grant 1U10-HD046000-06 to P.J.S.). Further funding for this study was provided by Astellas Pharma Inc., Deerfield, IL. Medical writing and editorial support was provided by Paul Hassan of Envision Pharma Ltd. and funded by Astellas Pharma Global Development Inc. Study site coordinators, including Luz Muniz of the University of Texas Southwestern Medical Center, are acknowledged for their valuable contributions. This study was presented, in part, at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 25-28 October 2008, abstract A-012, and at the Pediatric Academic Societies' Annual Meeting, Baltimore, MD, 2-5 May 2009, abstract 751040. NR 31 TC 54 Z9 56 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2010 VL 87 IS 1 BP 93 EP 99 DI 10.1038/clpt.2009.200 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 537VA UT WOS:000273141100023 PM 19890251 ER PT J AU Raben, N Baum, R Schreiner, C Takikita, S Plotz, P AF Raben, Nina Baum, Rebecca Schreiner, Cynthia Takikita, Shoichi Plotz, Paul TI Genetic Suppression of Autophagy Dramatically Enhances Enzyme Replacement Therapy in Murine Pompe Disease SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 3rd European Symposium on Steps Forward in Pompe Disease CY NOV 20-21, 2009 CL Munich, GERMANY ID SKELETAL-MUSCLE C1 [Raben, Nina; Baum, Rebecca; Schreiner, Cynthia; Takikita, Shoichi; Plotz, Paul] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov NR 6 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2010 VL 32 SU B BP S62 EP S62 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 568BB UT WOS:000275495400016 ER PT J AU Wanner, C Giannini, EH Mehta, AB Hilz, MJ Beck, M Bichet, DG Brady, RO West, M Germain, DP Waldek, S Clarke, JTR Mengel, E Strotmann, JM Warnock, DG Linhart, A AF Wanner, Christoph Giannini, Edward H. Mehta, Atul B. Hilz, Max J. Beck, Michael Bichet, Daniel G. Brady, Roscoe O. West, Michael Germain, Dominique P. Waldek, Stephen Clarke, Joe T. R. Mengel, Eugen Strotmann, Joerg M. Warnock, David G. Linhart, Ales TI A VALIDATED DISEASE SEVERITY SCORING SYSTEM FOR FABRY DISEASE SO CLINICAL THERAPEUTICS LA English DT Meeting Abstract CT 10th Annual European Round Table on Fabry Disease CY OCT 16-17, 2009 CL Prague, CZECH REPUBLIC C1 [Wanner, Christoph] Univ Wurzburg, Div Nephrol, Dept Med, Wurzburg, Germany. [Giannini, Edward H.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH USA. [Mehta, Atul B.] Royal Free Hosp, Dept Acad Haematol, London NW3 2QG, England. [Mehta, Atul B.] UCL, Sch Med, London W1N 8AA, England. [Hilz, Max J.] Univ Erlangen Nurnberg, Dept Neurol, D-8520 Erlangen, Germany. [Hilz, Max J.] NYU, Dept Neurol Med & Psychiat, New York, NY USA. [Beck, Michael; Mengel, Eugen] Univ Med Mainz, Ctr Pediat, Mainz, Germany. [Bichet, Daniel G.] Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, Canada. [Brady, Roscoe O.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [West, Michael] Dalhousie Univ, Dept Med, Div Nephrol, Halifax, NS, Canada. [Germain, Dominique P.] Univ Versailles St Quentin Yvelines, Hop Raymond Poincare, AP HP, Garches, France. [Germain, Dominique P.] Div Med Genet, Garches, France. [Waldek, Stephen] Salford Royal NHS Fdn Trust, Adult Inherited Metab Dis Dept Metab Dis, Manchester, Lancs, England. [Clarke, Joe T. R.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Clarke, Joe T. R.] Univ Toronto, Toronto, ON, Canada. [Clarke, Joe T. R.] Univ Sherbrooke, Serv Genet, Dept Pediat, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada. [Strotmann, Joerg M.] Univ Wurzburg, Dept Med 1, Ctr Cardiovasc Med, Wurzburg, Germany. [Warnock, David G.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Linhart, Ales] Charles Univ Prague, Dept Internal Med 2, Fac Med 1, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 3 U2 5 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2010 VL 32 SU C BP S108 EP S109 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 642LP UT WOS:000281215400024 ER PT J AU Falcao, RO Nacif, MS Liu, ST Bluemke, DA Rochitte, CE Marchiori, E AF Falcao, Ricardo Oliveira Nacif, Marcelo Souto Liu, Songtao Bluemke, David A. Rochitte, Carlos Eduardo Marchiori, Edson TI Anomalous origin of left coronary artery diagnosed by magnetic resonance imaging SO CLINICS LA English DT Letter ID WHITE-GARLAND SYNDROME; PULMONARY-ARTERY; TRUNK C1 [Falcao, Ricardo Oliveira] Plani Diagnost Med, Sao Jose Dos Campos, SP, Brazil. [Nacif, Marcelo Souto; Marchiori, Edson] Univ Fed Rio de Janeiro, Univ Fed Fluminense, Rio De Janeiro, Brazil. [Nacif, Marcelo Souto; Liu, Songtao; Bluemke, David A.] Natl Inst Hlth Clin Ctr, Dept Radiol & Imaging Sci, Bethesda, MD USA. [Nacif, Marcelo Souto] Johns Hopkins Sch Med, Dept Cardiol, Baltimore, MD USA. [Rochitte, Carlos Eduardo] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Cardiovasc MRI & CT,Inst Coracao InCor, Sao Paulo, Brazil. RP Falcao, RO (reprint author), Plani Diagnost Med, Sao Jose Dos Campos, SP, Brazil. EM msnacif@yahoo.com.br RI Marchiori, Edson/C-1205-2013; OI Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [ZIA EB000072-01, ZIA CL090019-01] NR 11 TC 1 Z9 2 U1 0 U2 0 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2010 VL 65 IS 11 BP 1215 EP 1216 DI 10.1590/S1807-59322010001100027 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 736JW UT WOS:000288492000027 PM 21243299 ER PT J AU Gualco, G Klumb, CE Barber, GN Weiss, LM Bacchi, CE AF Gualco, Gabriela Klumb, Claudete E. Barber, Glen N. Weiss, Lawrence M. Bacchi, Carlos E. TI Pediatric lymphomas in Brazil SO CLINICS LA English DT Article DE Lymphomas; Pediatric; Childhood; Adolescent; Brazil; Hodgkin Lymphoma; Epidemiology; Geographic Region ID B-CELL LYMPHOMA; EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; CLINICOPATHOLOGICAL FEATURES; CLINICAL-FEATURES; BURKITTS-LYMPHOMA; ONCOLOGY-GROUP; MALT LYMPHOMA; UNITED-STATES; CHILDREN AB OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%), followed by diffuse large B-cell lymphomas (24%). In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%), followed by peripheral T-cell lymphoma, then not otherwise specified (25%). In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions. C1 [Gualco, Gabriela; Bacchi, Carlos E.] Consultoria Patol, Sao Paulo, Brazil. [Weiss, Lawrence M.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Barber, Glen N.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Barber, Glen N.] Fogarty Int Ctr, Sylvester Canc Ctr, Miami, FL USA. [Klumb, Claudete E.] Inst Nacl Canc, Rio De Janeiro, Brazil. RP Gualco, G (reprint author), Consultoria Patol, Sao Paulo, Brazil. EM bacchi@conspat.com.br RI Inca, Inct/K-2204-2013; Klumb, Claudete/L-2682-2015 OI Klumb, Claudete/0000-0002-7672-1088 FU NIAID NIH HHS [P30 AI073961] NR 64 TC 11 Z9 10 U1 2 U2 3 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2010 VL 65 IS 12 BP 1267 EP 1278 DI 10.1590/S1807-59322010001200008 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 736KK UT WOS:000288493400008 PM 21340214 ER PT J AU Nacif, MS Mello, RAF Lacerda, OO Sibley, CT Machado, RA Marchiori, E AF Nacif, Marcelo Souto Mello, Ricardo A. F. Lacerda Junior, Orly O. Sibley, Christophe T. Machado, Renato A. Marchiori, Edson TI Double-chambered left ventricle in an adult: diagnosis by CMRI SO CLINICS LA English DT Letter ID MAGNETIC-RESONANCE C1 [Nacif, Marcelo Souto; Sibley, Christophe T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Nacif, Marcelo Souto] Johns Hopkins Sch Med, Baltimore, MD USA. [Mello, Ricardo A. F.] Univ Fed Espirito, Vitoria, ES, Brazil. [Lacerda Junior, Orly O.; Machado, Renato A.] UNIMED CIAS, Vitoria, ES, Brazil. [Marchiori, Edson] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. RP Nacif, MS (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM msnacif@gmail.com RI Marchiori, Edson/C-1205-2013; Sibley, Christopher/C-9900-2013 NR 12 TC 0 Z9 0 U1 0 U2 2 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2010 VL 65 IS 12 BP 1393 EP 1395 DI 10.1590/S1807-59322010001200028 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 736KK UT WOS:000288493400028 PM 21340234 ER PT J AU Hornyak, TJ AF Hornyak, Thomas J. TI Future Advances in Melanoma Research SO CLINICS IN PLASTIC SURGERY LA English DT Article DE Melanoma; Melanocyte; Nevus; Senescence; Oncogene; Cancer stem cell ID CONGENITAL MELANOCYTIC NEVI; ACUTE MYELOID-LEUKEMIA; MALIGNANT-MELANOMA; BRAF MUTATIONS; CELLULAR SENESCENCE; CUTANEOUS MELANOMA; PANCREATIC-CANCER; HIGH-FREQUENCY; N-RAS; CELLS AB The future of melanoma research is promising. Specific mechanisms leading to oncogenic transformation in melanoma development have been identified, and are likely to produce new targets for melanoma therapy. Also, advances in melanoma research will result from melanoma investigators co-opting approaches used to study other malignancies in which progress has been made more rapidly. Systematic roadblocks limiting advances in melanoma research relative to other malignancies are being addressed in a formal manner. The public and public officials are increasingly becoming aware of the need for more dedicated efforts to address the challenges of research on this malignancy. C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hornyak, TJ (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10-12N242, Bethesda, MD 20892 USA. EM hornyakt@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This activity was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 58 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD JAN PY 2010 VL 37 IS 1 BP 169 EP + DI 10.1016/j.cps.2009.07.005 PG 9 WC Surgery SC Surgery GA 592IB UT WOS:000277370900015 PM 19914467 ER PT J AU Ervin, AM Wojciechowski, R Schein, O AF Ervin, Ann-Margret Wojciechowski, Robert Schein, Oliver TI Punctal occlusion for dry eye syndrome SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID PROSPECTIVE RANDOMIZED-TRIAL; KERATOCONJUNCTIVITIS SICCA; SILICONE PLUGS; RISK-FACTORS; THERAPY; PREVALENCE; SYMPTOMS; EFFICACY; EPIDEMIOLOGY; MANAGEMENT AB Background Dry eye syndrome is a disorder of the tear film and is associated with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment in which the tear drainage system is blocked in order to aid in the preservation of natural tears on the ocular surface. Objectives The objective of this review was to assess the safety and efficacy of punctal plugs for the management of dry eye. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 6), MEDLINE (January 1950 to June 2010), EMBASE (January 1980 to June 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2010), the metaRegister of Controlled Trials (mRCT) (www. controlled-trials. com) and ClinicalTrials. gov (http://clinicaltrials. gov). We also searched the Science Citation Index-Expanded database and reference lists of included studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 21 June 2010. Selection criteria We included randomized and quasi-randomized controlled trials of collagen or silicone punctal plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry eye syndrome. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We contacted study investigators for additional information. Main results Seven randomized controlled trials including 305 participants (601 eyes) met the inclusion criteria and are summarized in this review. We did not perform meta-analysis due to appreciable variability in interventions and follow-up intervals. Although punctal plugs provided symptomatic improvement and clinical outcomes also improved frombaseline measures, few studies demonstrated a benefit of punctal plugs over the comparison intervention. Reported adverse effects included epiphora (overflow of tears), foreign body sensation, eye irritation, and spontaneous plug loss. Authors' conclusions This systematic review shows a relative scarcity of controlled clinical trials assessing the efficacy of punctal occlusion therapy in dry eye. Although the evidence is very limited, the data suggest that silicone plugs can provide symptomatic relief in severe dry eye. Moreover, temporary collagen plugs appear similarly effective to silicone plugs on a short-term basis. C1 [Ervin, Ann-Margret] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Wojciechowski, Robert] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Schein, Oliver] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Ervin, AM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,W5010, Baltimore, MD 21205 USA. EM aervin@jhsph.edu FU National Institutes of Health, USA; National Human Genome Research Institute, National Institutes of Health; National Eye Institute, National Institutes of Health, USA [N01-EY-2-1003, 1 U01 EY020522-01] FX Internal sources; National Human Genome Research Institute Intramural funds, National Institutes of Health, USA.; This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health; External sources; Contract N01-EY-2-1003 and Grant 1 U01 EY020522-01, National Eye Institute, National Institutes of Health, USA. NR 44 TC 14 Z9 14 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 9 AR CD006775 DI 10.1002/14651858.CD006775.pub2 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA 647PC UT WOS:000281629700011 PM 20824852 ER PT J AU Waters, AM Kokkoris, LL Mogg, K Bradley, BP Pine, DS AF Waters, Allison M. Kokkoris, Liza L. Mogg, Karin Bradley, Brendan P. Pine, Daniel S. TI The time course of attentional bias for emotional faces in anxious children SO COGNITION & EMOTION LA English DT Article DE Attentional bias; Emotional faces; Anxiety; Children ID GENERALIZED ANXIETY DISORDER; SELECTIVE ATTENTION; ANGRY FACES; FACIAL EXPRESSIONS; THREATENING FACES; PREFRONTAL CORTEX; SOCIAL ANXIETY; TRAIT ANXIETY; ADOLESCENTS; AVOIDANCE AB The present study investigated the time course of attentional bias for angry and happy faces in 50 primary school children (9 to 12 years). That is, the study examined the degree to which an anxiety-related attentional bias was moderated by the duration of threat exposure. Using a visual-probe task, children were shown angry and happy faces paired with neutral ones over two exposure durations: 500 and 1250 ms. Results revealed that higher levels of anxiety were associated with an attentional bias towards angry faces across the 500 ms and 1250 ms exposure durations. There were no effects of children's anxiety or stimulus exposure duration on attentional bias for happy faces. Results are discussed in relation to threat-monitoring versus vigilance-avoidance patterns of attentional bias, and developmental considerations, including comparison with findings from studies of anxiety-related attentional biases in adults. C1 [Waters, Allison M.] Griffith Univ, Sch Psychol, Gold Coast, Qld 4222, Australia. [Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Southampton, Hants, England. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RP Waters, AM (reprint author), Griffith Univ, Sch Psychol, Gold Coast, Qld 4222, Australia. EM a.waters@griffith.edu.au RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008; OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271; Waters, Allison/0000-0003-2453-793X NR 39 TC 12 Z9 12 U1 7 U2 19 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PY 2010 VL 24 IS 7 BP 1173 EP 1181 AR PII 927615039 DI 10.1080/02699930903274355 PG 9 WC Psychology, Experimental SC Psychology GA 659QA UT WOS:000282580800006 ER PT J AU Perry, ME AF Perry, Mary Ellen TI The Regulation of the p53-mediated Stress Response by MDM2 and MDM4 SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DNA-DAMAGE; TUMOR-SUPPRESSOR; EMBRYONIC LETHALITY; P53 ACTIVATION; MDM2-DEFICIENT MICE; LIGASE ACTIVITY; MDM4-NULL MICE; GROWTH ARREST; FEEDBACK LOOP; SKIN-CANCER AB Exquisite control of the activity of p53 is necessary for mammalian survival. Too much p53 is lethal, whereas too little permits tumorigenesis. MDM2 and MDM4 are structurally related proteins critical for the control of p53 activity during development, homeostasis, and the response to stress. These two essential proteins regulate both the activation of p53 in response to stress and the recovery of cells following resolution of the damage, yet both are oncogenic when overexpressed. Thus, multiple regulatory circuits ensure that their activities are fine-tuned to promote tumor-free survival. Numerous diverse stressors activate p53, and much research has gone into trying to find commonalities between them that would explain the mechanism by which p53 becomes active. It is now clear that although these diverse stressors activate p53 by different biochemical pathways, one common feature is the effort they direct, through a variety of means, toward disrupting the functions of both MDM2 and MDM4. This article provides an overview of the relationship between MDM2 and MDM4, features the various biochemical mechanisms by which p53 is activated through inhibition of their functions, and proposes some emerging areas for investigation of the p53-mediated stress response. C1 NCI, Lab Prot Dynam & Signaling, NIH, Bethesda, MD 20892 USA. RP Perry, ME (reprint author), NCI, Lab Prot Dynam & Signaling, NIH, Bethesda, MD 20892 USA. EM perryma@mail.nih.gov FU NIH National Cancer Institute, Center for Cancer Research FX The author thanks Drs. Guillermina Lozano of MD Anderson Medical Center and Peter Johnson and Allan Weissman of the National Cancer Institute, National Institutes of Health (NIH), for critical and constructive comments. This work was supported by the intramural research program of the NIH National Cancer Institute, Center for Cancer Research. NR 71 TC 37 Z9 40 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JAN PY 2010 VL 2 IS 1 AR a000968 DI 10.1101/cshperspect.a000968 PG 11 WC Cell Biology SC Cell Biology GA 625FS UT WOS:000279880900004 PM 20182601 ER PT B AU Wolkow, CA Zou, S Mattson, MP AF Wolkow, Catherine A. Zou, Sige Mattson, Mark P. BE Wolf, NS TI Aging of the Nervous System SO COMPARATIVE BIOLOGY OF AGING LA English DT Article; Book Chapter DE Brain; Neuron; Aging; Neurodegenerative; Disease; Oxidative stress; Invertebrate; Canine; Rodent ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID BETA-PEPTIDE; OXIDATIVE DNA-DAMAGE; LIFE-SPAN EXTENSION; MANGANESE SUPEROXIDE-DISMUTASE; MILD COGNITIVE IMPAIRMENT; MEMBRANE REDOX SYSTEM; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION AB The aging nervous system encompasses two related research areas. One is the effect of aging itself on nervous system function. also referred to as "normal" aging. A second area of consideration is that of neurodegenerative diseases with aging-associated onset, which are not representative of normal nervous system aging. This chapter examines both aspects of the aging nervous system, with emphasis on comparative studies that have revealed important insights In these areas. Both normal and pathological nervous system aging involve elevated oxidative stress, perturbed energy metabolism and the accumulation of protein aggregates. Changes in pathways for cell replacement, regeneration and repair are also important factors that are altered in the aging nervous system. The major neurodegenerative diseases associated with aging are Alzheimer's disease, Parkinson's disease, Huntington's disease and ALS. Clinical, Cellular and molecular features of each disease are described. For many of these diseases, underlying genetic and environmental causes have been identified. Environmental factors capable of modifying nervous system aging and neurodegenerative disease susceptibility are also examined. Overall, many factors impact the nervous system during aging in humans as well as other species. Recent studies have shown that some are protective (exercise. dietary energy restriction and cognitive stimulation) while others (diabetes, depression and dietary factors) enhance nervous system decline at the end of life. Comparative approaches have identified those changes that represent evolutionarily conserved aspects of nervous system aging. C1 [Wolkow, Catherine A.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Zou, Sige] NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov NR 247 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-3464-9 PY 2010 BP 319 EP 352 DI 10.1007/978-90-481-3465-6_14 D2 10.1007/978-90-481-3465-6 PG 34 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA BNP40 UT WOS:000275173300014 ER PT B AU Kastrinsky, DB McBride, NS Backus, KM LeBlanc, JJ Barry, CE AF Kastrinsky, David B. McBride, Nicholas S. Backus, Keriann M. LeBlanc, Jason J. Barry, Clifton E., III BE Mander, L Liu, HW TI Mycolic Acid/Cyclopropane Fatty Acid/Fatty Acid Biosynthesis and Health Relations SO COMPREHENSIVE NATURAL PRODUCTS II: CHEMISTRY AND BIOLOGY, VOL 1: NATURAL PRODUCTS STRUCTURAL DIVERSITY-I: SECONDARY METABOLITES: ORGANIZATION AND BIOSYNTHESIS LA English DT Article; Book Chapter ID MYCOBACTERIAL CORD FACTOR; TUMOR-NECROSIS-FACTOR; FACTOR TREHALOSE 6,6'-DIMYCOLATE; BACILLUS-CALMETTE-GUERIN; CELL-WALL PERMEABILITY; DIMYCOCEROSYL PHTHIOCEROL SYNTHESIS; INHIBIT SIDEROPHORE BIOSYNTHESIS; GELATINASE-ASSOCIATED LIPOCALIN; MAJOR EXTRACELLULAR PROTEIN; HUMAN NEUTROPHIL GELATINASE C1 [Kastrinsky, David B.; McBride, Nicholas S.; Backus, Keriann M.; LeBlanc, Jason J.; Barry, Clifton E., III] NIH, Bethesda, MD 20892 USA. RP Kastrinsky, DB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 529 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045382-8; 978-0-08-045381-1 PY 2010 BP 65 EP 145 PG 81 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA4ZP UT WOS:000336457600004 ER PT J AU Cragg, GM Newman, DJ Kingston, DGI AF Cragg, Gordon M. Newman, David J. Kingston, David G. I. BE Mander, L Liu, HW TI Terrestrial Plants as a Source of Novel Pharmaceutical Agents SO COMPREHENSIVE NATURAL PRODUCTS II: CHEMISTRY AND BIOLOGY, VOL 2: NATURAL PRODUCTS STRUCTURAL DIVERSITY-II: SECONDARY METABOLITES: SOURCES, STRUCTURES AND CHEMICAL BIOLOGY LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-KINASE-C; DNA TOPOISOMERASE-II; NF-KAPPA-B; SESQUITERPENE LACTONE PARTHENOLIDE; BOUND PACLITAXEL CONFORMATION; MICROTUBULE ASSEMBLY INVITRO; BETULINIC ACID-DERIVATIVES; VASCULAR DISRUPTING AGENTS; MYELOGENOUS LEUKEMIA STEM C1 [Cragg, Gordon M.] NCI, Frederick, MD 21701 USA. [Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21701 USA. [Kingston, David G. I.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP Cragg, GM (reprint author), NCI, Frederick, MD 21701 USA. NR 277 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045382-8 PY 2010 BP 5 EP 39 PG 35 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA4ZQ UT WOS:000336458500002 ER PT J AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. BE Mander, L Liu, HW TI Natural Products of Therapeutic Importance SO COMPREHENSIVE NATURAL PRODUCTS II: CHEMISTRY AND BIOLOGY, VOL 2: NATURAL PRODUCTS STRUCTURAL DIVERSITY-II: SECONDARY METABOLITES: SOURCES, STRUCTURES AND CHEMICAL BIOLOGY LA English DT Article; Book Chapter ID ACTINOMYCETE SALINISPORA-TROPICA; MICROTUBULE-STABILIZING AGENTS; CRYPTOPHYCIN ANALOG LY355703; BETA-LACTAM ANTIBIOTICS; SALINOSPORAMIDE-A; ENDOPHYTIC FUNGUS; AMPHOTERICIN-B; LYNGBYA-MAJUSCULA; HYPOCHOLESTEROLEMIC AGENT; CYCLIC DEPSIPEPTIDES C1 [Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21701 USA. [Cragg, Gordon M.] NCI, Frederick, MD 21701 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21701 USA. NR 143 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045382-8 PY 2010 BP 623 EP 650 PG 28 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA4ZQ UT WOS:000336458500019 ER PT J AU Cragg, GM Newman, DJ AF Cragg, Gordon M. Newman, David J. BE Mander, L Liu, HW TI Nature as Source of Medicines; Novel Drugs from Nature; Screening for Antitumor Activity SO COMPREHENSIVE NATURAL PRODUCTS II: CHEMISTRY AND BIOLOGY, VOL 3: DEVELOPMENT & MODIFICATION OF BIOACTIVITY LA English DT Article; Book Chapter ID HISTONE DEACETYLASE INHIBITORS; COMPOUND LIBRARY DEVELOPMENT; NATIONAL-CANCER-INSTITUTE; ARYL-HYDROCARBON RECEPTOR; SOLID-PHASE SYNTHESIS; SPONGE KIRKPATRICKIA-VARIALOSA; THIOREDOXIN REDUCTASE SYSTEM; TYROSINE KINASE INHIBITORS; SCAFFOLD HSP90 INHIBITORS; BIOSYNTHETIC GENE-CLUSTER C1 [Cragg, Gordon M.; Newman, David J.] NCI, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Frederick, MD 21701 USA. NR 292 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045382-8 PY 2010 BP 135 EP 175 PG 41 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA4ZR UT WOS:000336459300006 ER PT J AU Eddy, EM AF Eddy, E. M. BE McQueen, CA TI Evaluation of an Infertile Transgenic Male Animal SO COMPREHENSIVE TOXICOLOGY, VOL 11: REPRODUCTIVE AND ENDOCRINE TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID DEHYDROGENASE-C LDHC; GENE-EXPRESSION; MALE-FERTILITY; IN-VIVO; SPERM MOTILITY; SERTOLI-CELLS; REPORTER GENE; MOUSE MODELS; GERM-CELLS; MALE-MICE C1 NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIH, Res Triangle Pk, NC 27709 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 87 EP 95 PG 9 WC Endocrinology & Metabolism; Reproductive Biology; Toxicology SC Endocrinology & Metabolism; Reproductive Biology; Toxicology GA BA2HG UT WOS:000333406700004 ER PT J AU Tischler, AS Nyska, A Elmore, SA AF Tischler, A. S. Nyska, A. Elmore, S. A. BE McQueen, CA TI Toxic Responses of the Adrenal Medulla SO COMPREHENSIVE TOXICOLOGY, VOL 11: REPRODUCTIVE AND ENDOCRINE TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID NERVE GROWTH-FACTOR; CHROMAFFIN CELL-PROLIFERATION; CATECHOLAMINE-SYNTHESIZING ENZYMES; NEUROFIBROMATOSIS KNOCKOUT MICE; ENDOCRINE NEOPLASIA SYNDROME; GRANULE-CONTAINING CELLS; DENSE CORE VESICLES; LONG-EVANS RATS; MALE F344 RAT; ADULT-RAT C1 [Tischler, A. S.] Tufts Med Ctr, Boston, MA 02111 USA. [Nyska, A.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Elmore, S. A.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Tischler, AS (reprint author), Tufts Med Ctr, Boston, MA 02111 USA. NR 168 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 291 EP 311 PG 21 WC Endocrinology & Metabolism; Reproductive Biology; Toxicology SC Endocrinology & Metabolism; Reproductive Biology; Toxicology GA BA2HG UT WOS:000333406700014 ER PT J AU Keim, SA Kimmel, CA AF Keim, S. A. Kimmel, C. A. BE McQueen, CA TI The National Children's Study: Linking Exposures to Effects in Children's Environmental Health SO COMPREHENSIVE TOXICOLOGY, VOL 12: DEVELOPMENTAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HEART-DISEASE; UNITED-STATES; PREVALENCE; NUTRITION; GROWTH; COHORT; LIFE C1 [Keim, S. A.] NIH, Bethesda, MD 20892 USA. [Kimmel, C. A.] Natl Childrens Study, Southern Shores, NC USA. RP Keim, SA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 45 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 59 EP 68 PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA BA2HH UT WOS:000333408300005 ER PT J AU Bushnell, PJ Tilson, HA AF Bushnell, P. J. Tilson, H. A. BE McQueen, CA TI Cognitive Function SO COMPREHENSIVE TOXICOLOGY, VOL 13: NERVOUS SYSTEM AND BEHAVIORAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID RADIAL-ARM MAZE; MULTIPLE REPEATED ACQUISITION; EXTRADIMENSIONAL SHIFT TASKS; PASSIVE-AVOIDANCE TASK; LEVEL LEAD-EXPOSURE; CRL-CD RATS; SIGNAL-DETECTION; DEVELOPMENTAL NEUROTOXICITY; ACUTE CHLORPYRIFOS; WATER MAZE C1 [Bushnell, P. J.] US EPA, Res Triangle Pk, NC 27711 USA. [Tilson, H. A.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Bushnell, PJ (reprint author), US EPA, Res Triangle Pk, NC 27711 USA. NR 106 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 367 EP 381 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA BA2JT UT WOS:000333465100021 ER PT J AU Crusselle-Davis, VJ Archer, TK AF Crusselle-Davis, V. J. Archer, T. K. BE McQueen, CA TI Chromatin Remodeling SO COMPREHENSIVE TOXICOLOGY, VOL 2: CELLULAR AND MOLECULAR TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID RECEPTOR-MEDIATED TRANSCRIPTION; ENDOCRINE-DISRUPTING CHEMICALS; HISTONE H1 PHOSPHORYLATION; ACTIVATED PROTEIN-KINASE; GENOME-WIDE ANALYSIS; DNA-BINDING DOMAIN; GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; GENE-EXPRESSION; IN-VIVO C1 [Crusselle-Davis, V. J.; Archer, T. K.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Crusselle-Davis, VJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 227 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 359 EP 375 PG 17 WC Toxicology SC Toxicology GA BA2JD UT WOS:000333458300019 ER PT J AU Germolec, DR Luebke, RW Luster, MI AF Germolec, D. R. Luebke, R. W. Luster, M. I. BE McQueen, CA TI Immunotoxicity Studies SO COMPREHENSIVE TOXICOLOGY, VOL 3: TOXICOLOGY TESTING AND EVALUATION, 2ND EDITION LA English DT Article; Book Chapter ID LYMPH-NODE ASSAY; RISK-ASSESSMENT; POLYCHLORINATED-BIPHENYLS; EXTENDED HISTOPATHOLOGY; SKIN SENSITIZATION; ADULT EXPOSURE; IMMUNE STATUS; VALIDATION; CHILDREN; SUSCEPTIBILITY C1 [Germolec, D. R.] NIEHS, Morrisville, NC 27560 USA. [Luebke, R. W.] US EPA, Res Triangle Pk, NC 27711 USA. [Luster, M. I.] Luster Assoc LLC, Morgantown, WV USA. RP Germolec, DR (reprint author), NIEHS, Morrisville, NC 27560 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 211 EP 223 PG 13 WC Toxicology SC Toxicology GA BA2JF UT WOS:000333459000015 ER PT J AU Thornton, AM AF Thornton, A. M. BE McQueen, CA TI Regulatory T Cells SO COMPREHENSIVE TOXICOLOGY, VOL 5: IMMUNE SYSTEM TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID VERSUS-HOST-DISEASE; IMMUNOLOGICAL SELF-TOLERANCE; RENAL-TRANSPLANT RECIPIENTS; TRANSCRIPTION FACTOR FOXP3; ARYL-HYDROCARBON RECEPTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; HUMAN PERIPHERAL-BLOOD; GROWTH-FACTOR-BETA C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Thornton, AM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 228 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 87 EP 107 PG 21 WC Toxicology SC Toxicology GA BA2JI UT WOS:000333459800004 ER PT J AU Hu, TCC Waghorn, B Yanasak, N Silva, AC AF Hu, T. C-C Waghorn, B. Yanasak, N. Silva, A. C. BE McQueen, CA TI Manganese-Enhanced Magnetic Resonance Imaging: Applications to Preclinical Research SO COMPREHENSIVE TOXICOLOGY, VOL 6: CARDIOVASCULAR TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID SODIUM-CALCIUM EXCHANGE; PERFUSED RAT-HEART; SPINAL-CORD-INJURY; MOUSE VENTRICULAR MYOCYTES; TRISODIUM MNDPDP INJECTION; BLOOD-BRAIN-BARRIER; III CLINICAL-TRIALS; EUROPEAN PHASE-III; MR CONTRAST AGENTS; IN-VIVO C1 [Hu, T. C-C; Waghorn, B.; Yanasak, N.] Med Coll Georgia, Small Anim Imaging, Augusta, GA 30912 USA. [Silva, A. C.] NINDS, NIH, Bethesda, MD 20892 USA. RP Hu, TCC (reprint author), Med Coll Georgia, Small Anim Imaging, Augusta, GA 30912 USA. NR 174 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 199 EP 219 PG 21 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA BA2OD UT WOS:000333714400012 ER PT J AU Torres, SM Walker, DM Divi, RL Poirier, MC Walker, VE AF Torres, S. M. Walker, D. M. Divi, R. L. Poirier, M. C. Walker, V. E. BE McQueen, CA TI Transplacental Exposure to Antiretroviral Drugs and Cardiotoxicity in Offspring SO COMPREHENSIVE TOXICOLOGY, VOL 6: CARDIOVASCULAR TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; PERSISTENT MITOCHONDRIAL DYSFUNCTION; UNINFECTED INFANTS; CORD BLOOD; IN-UTERO; PERINATAL EXPOSURE; UMBILICAL-CORD; LONG-TERM; HIV C1 [Torres, S. M.] Univ New Mexico, Albuquerque, NM 87131 USA. [Walker, D. M.; Walker, V. E.] BioMosaics Inc, Burlington, VT USA. [Divi, R. L.; Poirier, M. C.] NCI, NIH, Bethesda, MD 20892 USA. RP Torres, SM (reprint author), Univ New Mexico, Albuquerque, NM 87131 USA. NR 64 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 305 EP 321 PG 17 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA BA2OD UT WOS:000333714400017 ER PT J AU Yee, SB Roth, RA AF Yee, S. B. Roth, R. A. BE McQueen, CA TI Pyrrolizidine Alkaloid-Induced Hepatotoxicity SO COMPREHENSIVE TOXICOLOGY, VOL 9: HEPATIC TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID VENO-OCCLUSIVE DISEASE; HEPATIC VENOOCCLUSIVE DISEASE; PERFUSED-RAT-LIVER; ENDOTHELIAL-CELL INJURY; PYRROLE-TREATED RATS; PROTEIN CROSS-LINKS; RED-BLOOD-CELLS; HERBAL TEA; BACTERIAL LIPOPOLYSACCHARIDE; SENECIO-JACOBAEA C1 [Yee, S. B.] NIH, Bethesda, MD 20892 USA. [Roth, R. A.] Michigan State Univ, E Lansing, MI 48824 USA. RP Yee, SB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 198 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 595 EP 611 PG 17 WC Gastroenterology & Hepatology; Toxicology SC Gastroenterology & Hepatology; Toxicology GA BA2JW UT WOS:000333465800027 ER PT J AU Zang, Y Fung, WK Zheng, G AF Zang, Yong Fung, Wing Kam Zheng, Gang TI Asymptotic powers for matched trend tests and robust matched trend tests in case-control genetic association studies SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article ID GENOME-WIDE ASSOCIATION; SAMPLE-SIZE; CANCER; RISK; STRATIFICATION; STATISTICS; EFFICIENCY; MARKERS; DESIGN AB The matched trend test (MTT), developed using a conditional logistic regression, has been proposed to test for association in matched case-control studies to control the bias of known confounding effects and reduce the potential impact of population stratification. The MTT requires a known genetic model. When the genetic model is unknown, a Monte Carlo robust test, MAX, has been proposed for the analysis of matched case-control studies. The MAX statistic takes the maximum of three MTTs optimal for three common genetic models. We derive the asymptotic power for MTTs and robust tests. In particular, we derive the asymptotic p-value for MAX. Using these analytical results, we conduct simulation studies to compare the performance of MAX and the two-degree-of-freedom Chi-square test for matched case-control studies, where the latter is implemented in most computing software. Our simulation results show that MAX is always asymptotically more powerful than the two-degree-of-freedom Chi-square test under common genetic models. Our results provide guidelines for the analysis of genetic association using matched case-control data. An illustration of our results to a real matched pair case-control etiologic study of sarcoidosis is given. (C) 2009 Elsevier B.V. All rights reserved. C1 [Zang, Yong; Fung, Wing Kam] Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Hong Kong, Peoples R China. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Fung, WK (reprint author), Univ Hong Kong, Dept Stat & Actuarial Sci, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. EM wingfung@hku.hk NR 28 TC 4 Z9 4 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JAN 1 PY 2010 VL 54 IS 1 BP 65 EP 77 DI 10.1016/j.csda.2009.07.011 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 536AW UT WOS:000273015500007 ER PT J AU Le Floc'h, S Cloutier, G Finet, G Tracqui, P Pettigrew, RI Ohayon, J AF Le Floc'h, S. Cloutier, G. Finet, G. Tracqui, P. Pettigrew, R. I. Ohayon, J. TI Vascular imaging modulography: an experimental in vitro study SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Meeting Abstract CT 35th Congress of the Societe-de-Biomecanique CY AUG 25-27, 2010 CL Univ Maine, Le Mans, FRANCE SP Soc Biomech HO Univ Maine DE coronary diseases; inverse problem; linear elasticity; vulnerable plaques ID ELASTOGRAPHY; PLAQUES C1 [Le Floc'h, S.; Tracqui, P.; Ohayon, J.] UJF, CNRS, UMR 5525, Lab TIMC IMAG DynaCell,In3S, Grenoble, France. [Cloutier, G.] CRCHUM, Lab LBUM, Montreal, PQ, Canada. [Finet, G.] Hosp Civils Lyon, INSERM, U886, Lyon, France. [Finet, G.] UCBL, Lyon, France. [Pettigrew, R. I.; Ohayon, J.] NIDDK, NIH, Bethesda, MD USA. [Ohayon, J.] Univ Savoie, Engn Sch Polytech Savoie, Le Bourget Du Lac, France. RP Ohayon, J (reprint author), UJF, CNRS, UMR 5525, Lab TIMC IMAG DynaCell,In3S, Grenoble, France. EM jacques.ohayon@imag.fr RI Ohayon, Jacques/M-6576-2014 NR 7 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-5842 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PY 2010 VL 13 SU 1 BP 89 EP 90 AR PII 926444085 DI 10.1080/10255842.2010.494034 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA 646UE UT WOS:000281567700034 ER PT S AU Cai, L Xu, YR He, L Zhao, YM Yang, X AF Cai, Ling Xu, Yiren He, Lei Zhao, Yuming Yang, Xin BE Zha, H Taniguchi, RI Maybank, S TI An Effective Segmentation for Noise-Based Image Verification Using Gamma Mixture Models SO COMPUTER VISION - ACCV 2009, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 9th Asian Conference on Computer Vision CY SEP 23-27, 2009 CL Xian, PEOPLES R CHINA SP Peking Univ, Key Lab Machine Percept, Chinese Acad Sci, Natl lab Pattern Recognit, Inst Automat, Natl Nat Sci Fdn China, Microsoft Res, Fujitsu, Microview, Luster ID ACTIVE CONTOURS AB Image verification lets been widely used in numerous websites to prevent them front batch registration or automated posting. One category of the image verification is generated by adding noise into character or digit images to make them hard to be recognized by Optical Character Recognition (OCR). In this paper, we propose a novel probability gradient function for active contour models to efficiently segment this type of images for easier recognition. Experiments on a set of images with different intensitics and types of noise show the superiority of the proposed probability gradient to traditional method. The purpose of our paper is to warn sonic websites who are still using such kind of verification: they should improve their defense method to prevent them front the potential risk. C1 [Cai, Ling; Xu, Yiren; Zhao, Yuming; Yang, Xin] Shanghai Jiao Tong Univ, Dept Automat, Shanghai 200340, Peoples R China. [He, Lei] Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Cai, L (reprint author), Shanghai Jiao Tong Univ, Dept Automat, Shanghai 200340, Peoples R China. EM cailing@gmail.com; xuyiren@gmail.com; lei.he@nih.gov; arola_zym@sjtu.edu.cn; yangxin@sjtu.edu.cn NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-12296-5 J9 LECT NOTES COMPUT SC PY 2010 VL 5996 BP 21 EP + PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BPQ60 UT WOS:000279642800003 ER PT J AU Resnik, DB Patrone, D Peddada, S AF Resnik, David B. Patrone, Daniel Peddada, Shyamal TI Evaluating the quality of information about alternatives to research participation in oncology consent forms SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Informed consent; Alternatives; Regulation; Ethics; Oncology ID VIEWS AB A careful consideration of the alternatives to research participation is an essential element of making an informed choice to enroll in a biomedical research study. While there is general agreement on the importance of informing prospective subjects about alternatives to research participation, little is known about how investigators communicate this information. The purpose of this study was to attempt to assess the quality of information about alternatives contained in informed consent documents in oncology randomized controlled trials. Our study indicates that there is room for improvement concerning the discussion of alternatives to research participation in informed consent documents in oncology randomized controlled trials. Though most of the documents in our study met the minimal disclosure standard found in the U.S. federal regulations, less than a third met the reasonable person standard, a widely accepted principle endorsed by the common law and various ethics guidelines and documents. There was a statistically significant difference between the alternative discussions in local and model forms (P<0.0014). The alternatives discussions in local informed consent documents were more likely to receive higher scores than those in model consent documents. with an odds-ratio of 3.5 to 1. Published by Elsevier Inc. C1 [Resnik, David B.; Peddada, Shyamal] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Patrone, Daniel] Union Coll Mt Sinai Sch Med, New York, NY USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) FX This research was sponsored by the intramural program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). It does not represent the views of the NIEHS, NIH, or U.S. government. We are grateful to Stavros Garantziotis, Bill Schrader, and Grace Kissling for helpful comments. NR 12 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2010 VL 31 IS 1 BP 18 EP 21 DI 10.1016/j.cct.2009.11.001 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 556FW UT WOS:000274576400005 PM 19897054 ER PT J AU McCarthy-Keith, D Nurudeen, S Armstrong, A Levens, E Nieman, LK AF McCarthy-Keith, Desiree Nurudeen, Sahadat Armstrong, Alicia Levens, Eric Nieman, Lynnette K. TI Recruitment and retention of women for clinical leiomyoma trials SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Leiomyoma; Clinical trials; Recruitment; Retention ID RANDOMIZED CONTROLLED-TRIAL; PROGESTERONE-RECEPTOR MODULATOR; UTERINE FIBROID EMBOLIZATION; AGE-BASED DISPARITIES; RISK-FACTORS; PARTICIPATION; BARRIERS; HEALTH; HYSTERECTOMY; KNOWLEDGE AB Background: Subject recruitment and retention in clinical leiomyoma trials is challenging. We evaluated strategies to increase patient enrollment and completion in leiomyoma trials. Materials and methods: Randomized trials for treatment of symptomatic leiomyoma published from 2000 through 2008 were evaluated and thirteen trials were selected. Subject enrollment and completion rates. recruitment methods and reasons for patient drop-out were assessed. Results: Recruitment by study personnel or clinic staff during evaluation for symptomatic leiomyoma was the most common strategy for enrollment. Additional methods included local media, internet postings and physician referrals. Seven to 85% of patients enrolled after screening, with a median enrollment of 70%. Sixty-five to 100% of patients completed the study after enrollment with a median completion rate of 89%. Reasons for drop-out at the screening stage included failure to meet inclusion criteria, patient refusal and patient preference for specific treatment. Commonly reported reasons for drop-out after enrollment were refusal of treatment following randomization, adverse reaction to study intervention and noncompliance with study protocol or follow-up visits. Conclusion: Women with symptomatic uterine leiomyomas may be attracted to participate in leiomyoma trials, however desire for specific treatment and persistent symptoms following intervention may hinder their participation. Randomization to placebo treatment and stringent inclusion criteria appear to adversely impact accrual. A wide range of recruiting tactics is needed and media sources or direct mailings may prove particularly effective to improve subject recruitment and retention in clinical leiomyoma trials. Published by Elsevier Inc. C1 [McCarthy-Keith, Desiree; Armstrong, Alicia; Levens, Eric; Nieman, Lynnette K.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Nurudeen, Sahadat] Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 20057 USA. RP McCarthy-Keith, D (reprint author), NICHHD, Program Reprod & Adult Endocrinol, NIH, MSC 1109 Rm 1E3140 CRC 10 Ctr Dr, Bethesda, MD 20892 USA. EM mccartde@mail.nih.gov FU Intramural NIH HHS [NIH0013323419, ZIA HD000637-16] NR 38 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2010 VL 31 IS 1 BP 44 EP 48 DI 10.1016/j.cct.2009.09.007 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 556FW UT WOS:000274576400009 PM 19788933 ER PT J AU Lavine, JE Schwimmer, JB Molleston, JP Scheimann, AO Murray, KF Abrams, SH Rosenthal, P Sanyal, AJ Robuck, PR Brunt, EM Unalp, A Tonascia, J AF Lavine, Joel E. Schwimmer, Jeffrey B. Molleston, Jean P. Scheimann, Ann O. Murray, Karen F. Abrams, Stephanie H. Rosenthal, Philip Sanyal, Arun J. Robuck, Patricia R. Brunt, Elizabeth M. Unalp, Aynur Tonascia, James CA NASH CRN Res Grp TI Treatment of nonalcoholic fatty liver disease in children: TONIC trial design SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Nonalcoholic fatty liver; Nonalcoholic steatohepatitis; Metformin; Vitamin E; RRR-alpha-tocopherol; Randomized controlled trial; Children ID HEPATIC CYTOCHROME-P450 2E1; INSULIN-RESISTANCE; VITAMIN-E; OBESE CHILDREN; NATURAL-HISTORY; STEATOHEPATITIS; ASSOCIATION; ADOLESCENTS; PREVALENCE; NASH AB Background: Nonalcoholic fatty liver disease (NAFLD) in children can lead to steatohepatitis, cirrhosis. and end-stage liver disease. The cause of NAFLD is unknown, but it is commonly associated with obesity. insulin resistance, and dyslipidemia. Objectives: TONIC is conducted to test whether treatment with metformin, an insulin sensitizer, or vitamin E, a naturally available antioxidant, will lead to improvements in biochemical and histological features of nondiabetic children with biopsy-proven NAFLD. Design: TONIC is a randomized, multicenter, double-masked, placebo-controlled trial of 96 weeks of treatment with metformin or vitamin E. The primary outcome measure chosen for the trial is improvement in serum alanine aminotransferase (ALT) levels with treatment as compared to placebo. An improvement in ALT is defined as reduction in serum ALT levels to below 50% of the baseline values or into the normal range (40 U/L or less) during the last 48 weeks of treatment. Histological improvement is defined by changes in liver histology between a baseline and end-of-treatment liver biopsy in regards to (1) steatohepatitis. (2) NAFLD Activity Score, consisting of scores for steatosis, lobular inflammation, and hepatocellular injury (ballooning), and (3) fibrosis score. Methods: Between September 2005 and September 2007, 173 children were enrolled into TONIC at 10 clinical centers in the United States. Participants were randomized to receive either metformin (500 mg b.i.d.), vitamin E (400 IU b.i.d.), or placebo for 96 weeks. This protocol was approved by all participating center Institutional Review Boards (IRBs) and an independent Data and Safety Monitoring Board (DSMB). (ClinicalTrials.gov number, NCT00063635.) (C) 2009 Elsevier Inc. All rights reserved. C1 [Unalp, Aynur; Tonascia, James] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Lavine, Joel E.; Schwimmer, Jeffrey B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Molleston, Jean P.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Scheimann, Ann O.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Abrams, Stephanie H.] Baylor Coll Med, Houston, TX 77030 USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Robuck, Patricia R.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Brunt, Elizabeth M.] Washington Univ, Sch Med, St Louis, MO USA. RP Unalp, A (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Room W5010, Baltimore, MD 21205 USA. EM aunalp@jhsph.edu FU National Institute of Diabetes and Digestive and Kidney Disease; Eunice Kennedy Shriver National Institute of Child Health and Human Developmen; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health General Clinical Research Centers or Clinical and Translational Science [UL1RR024989, UL1RR024128, M01RR000750, UL1RR024131, M01RR000827, UL1RR02501401, M01RR000065, M01RR00188, M01RR020359.] FX TONIC trial is supported by the National Institute of Diabetes and Digestive and Kidney Disease and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The vitamin E capsules and matching placebo are provided by Pharmavite, LLC through a Clinical Trial Agreement with the National Institutes of Health.; The following members of the Nonalcoholic Steatohepatitis Clinical Research Network have been instrumental in the design and conduct of TONIC trial.; Case Western Reserve University, Cleveland, OH: Diane Bringman, RN, BSN (2003-2008); Srinivasan Dasarathy, MD; Ariel Feldstein, MD; Carol Hawkins, RN; Yao-Chang Liu, MD; Arthur McCullough, MD (Principal Investigator); Ruth Sargent, LPN; Margaret Stager, MD.; Duke University Medical Center, Durham, NC: Manal Abdelmalek, MD; Anna Mae Diehl, MD (Principal Investigator); Marcia Gottfried, MD (2004-2008); Cynthia Guy, MD; Paul Killenberg, MD (2004-2008); Samantha Kwan, Yi-Ping Pan, Dawn Piercy, FNP; Melissa Smith, and Johns Hopkins University School of Medicine, Baltimore, MD: Kimberly Pfeifer, RN; Ann O. Scheimann, MD, MBA; Michael Torbenson, MD.; Indiana University School of Medicine, Indianapolis, IN: Prajakta Bhimalli, Elizabeth Byam, Naga Chalasani, MD (Principal Investigator); Oscar W. Cummings, MD; Ann Klipsch, RN; Lydia Lee, Jean P. Molleston, MD; Linda Ragozzino, Girish Subbarao, MD; Raj Vuppalanchi, MD.; Saint Louis University School of Medicine, St Louis, MO: Sarah Barlow, MD (2002-2007); Elizabeth M. Brunt, MD; Jose Derdoy, MD; Joyce Hoffmann, Debra King, RN; Joan Siegner, RN; Susan Stewart, RN; Brent A. Neuschwander-Tetri, MD (Principal Investigator); Judy Thompson, RN; and Baylor College of Medicine, Houston, TX: Stephanie H. Abrams, MD; Diana Arceo, MD, MS; Denise Espinosa, Leanel Angeli Fairly, RN.; University of California San Diego, San Diego, CA: Cynthia Behling, MD, PhD; Lisa Clark, PhD, MPH; Janis Durelle, Tarek Hassanein, MD; Joel E. Lavine, MD, PhD (Principal Investigator); Susana Mendoza, Zana Parman (2003-2007), Heather Patton, MD; Jeffrey B. Schwimmer, MD; Claude Sirlin MD; Tanya Stein, MD; Zobeida Palomares.; University of California San Francisco, San Francisco, CA: Kiran Bambha, MD, Nathan M. Bass, MD, PhD (Principal Investigator); Linda D. Ferrell, MD; Danuta Filipowski, MD; Raphael Merriman, MD (2002-2007); Mark Pabst, Monique Rosenthal, Philip Rosenthal, MD; Tessa Steel (2006-2008).; University of Washington Medical Center (2002-2007), Virginia Mason Medical Center, Seattle, WA: Melissa Coffey, Kris V. Kowdley, MD (Principal Investigator); Jody Mooney, MS; Karen F. Murray, MD; James Nelson, PhD; Cheryl Saunders, MPH; Matthew Yeh, MD, PhD; Melissa Young.; Virginia Commonwealth University, Richmond, VA: Sherry Boyett, RN; Daphne Bryan, MD; Melissa J. Contos, MD; Michael Fuchs, MD; Amy Jones, Velimir AC Luketic, MD; Bimalijit Sandhu, MD; Arun J. Sanyal, MD (Principal Investigator); Carol Sargeant, RN, MPH; Melanie White, RN; and Children's National Medical Center, Washington DC: Parvathi Mohan, MD; Kavita Nair.; National Cancer Institute, Bethesda, MD: David E. Kleiner, MD, PhD.; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD: Edward Doo, MD; Jay Hoofnagle, MD; Patricia R. Robuck, PhD, MPH.; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD: Terry T-K Huang, PhD.; Johns Hopkins University, Bloomberg School of Public Health (Data Coordinating Center), Baltimore, MD: Pat Belt, BS; Fred Brancati, MD, MHS; Jeanne Clark, MD, MPH; Ryan Colvin, MPH; Michele Donithan, MHS; Mika Green, MA; Rosemary Hollick (2004-2005): Milana Isaacson, Wana Kim, Alison Lydecker, MPH (2006-2008); Pamela Mann, MPH; Laura Miriel, Alice Sternberg, ScM; James Tonascia, PhD (Principal Investigator); Aynur Unalp-Arida, MD, PhD; Mark Van Natta, MHS; Laura Wilson, ScM; Kathie Yates, ScM.; The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713. This study is supported in part by the Intramural Research Program of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Other grant support includes the following National Institutes of Health General Clinical Research Centers or Clinical and Translational Science Awards: UL1RR024989, UL1RR024128, M01RR000750, UL1RR024131, M01RR000827, UL1RR02501401, M01RR000065, M01RR00188, M01RR020359. NR 50 TC 39 Z9 43 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2010 VL 31 IS 1 BP 62 EP 70 DI 10.1016/j.cct.2009.09.001 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 556FW UT WOS:000274576400012 PM 19761871 ER PT J AU Alford, R Ogawa, M Hassan, M Gandjbakhche, AH Choyke, PL Kobayashi, H AF Alford, Raphael Ogawa, Mikako Hassan, Moinuddin Gandjbakhche, Amir H. Choyke, Peter L. Kobayashi, Hisataka TI Fluorescence lifetime imaging of activatable target specific molecular probes SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE molecular imaging; fluorescence lifetime; activatable fluorescence probe; cancer; near-infrared ID IN-VIVO; MONOCLONAL-ANTIBODIES; CANCER; CELLS; PROTEINS; CALCIUM; QUIN-2 AB In vivo optical imaging using fluorescently labeled self-quenched monoclonal antibodies, activated through binding and internalization within target cells, results in excellent target-to-background ratios. We hypothesized that these molecular probes could be utilized to accurately report on cellular internalization with fluorescence lifetime imaging (FLI). Two imaging probes were synthesized, consisting of the antibody trastuzumab (targeting HER2/neu) conjugated to Alexa Fluor750 in ratios of either 1:8 or 1:1. Fluorescence intensity and lifetime of each conjugate were initially determined at endosomal pHs. Since the 1:8 conjugate is self-quenched, the fluorescence lifetime of each probe was also determined after exposure to the known dequencher SDS. In vitro imaging experiments were performed using 3T3/HER2(+) and BALB/3T3 (HER2(-)) cell lines. Changes in fluorescence lifetime correlated with temperature- and time-dependent cellular internalization. In vivo imaging studies in mice with dual flank tumors [3T3/HER2(+) and BALB/3T3 (HER2(-))] detected a minimal difference in FLI. In conclusion, fluorescence lifetime imaging monitors the internalization of target-specific activatable antibody-fluorophore conjugates in vitro. Challenges remain in adapting this methodology to in vivo imaging. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Alford, Raphael; Ogawa, Mikako; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hassan, Moinuddin; Gandjbakhche, Amir H.] NICHHD, Program Phys Biol, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Alford, Raphael] Case Western Reserve Sch Med, Cleveland, OH USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Institute of Child Health and Human Development FX Contract/grant sponsors: Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Institute of Child Health and Human Development. NR 29 TC 16 Z9 16 U1 0 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD JAN-FEB PY 2010 VL 5 IS 1 BP 1 EP 8 DI 10.1002/cmmi.360 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 573WH UT WOS:000275945500001 PM 20101762 ER PT J AU Rolli, J Loukili, N Levrand, S Rosenblatt-Velin, N Rignault-Clerc, S Waeber, B Feihl, F Pacher, P Liaudet, L AF Rolli, Joelle Loukili, Noureddine Levrand, Sandra Rosenblatt-Velin, Nathalie Rignault-Clerc, Stephanie Waeber, Bernard Feihl, Francois Pacher, Pal Liaudet, Lucas TI Bacterial flagellin elicits widespread innate immune defense mechanisms, apoptotic signaling, and a sepsis-like systemic inflammatory response in mice SO CRITICAL CARE LA English DT Article ID NF-KAPPA-B; PEROXYNITRITE; SURVIVAL; RECEPTOR; SHOCK; DYSFUNCTION; INHIBITION; ACTIVATION; EXPRESSION; PROTECTION AB Introduction: Systemic inflammation in sepsis is initiated by interactions between pathogen molecular motifs and specific host receptors, especially toll-like receptors (TLRs). Flagellin is the main flagellar protein of motile microorganisms and is the ligand of TLR5. The distribution of TLR5 and the actions of flagellin at the systemic level have not been established. Therefore, we determined TLR5 expression and the ability of flagellin to trigger prototypical innate immune responses and apoptosis in major organs from mice. Methods: Male Balb/C mice (n = 80) were injected intravenously with 1-5 mu g recombinant Salmonella flagellin. Plasma and organ samples were obtained after 0.5 to 6 h, for molecular investigations. The expression of TLR5, the activation state of nuclear factor kappa B (NF kappa B) and mitogen-activated protein kinases (MAPKs) [extracellular related kinase (ERK) and c-jun-NH2 terminal kinase (JNK)], the production of cytokines [tumor necrosis alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), macrophage inhibitory protein-2 (MIP-2) and soluble triggering receptor expressed on myeloid cells (TREM-1)], and the apoptotic cleavage of caspase-3 and its substrate Poly(ADP-ribose) polymerase (PARP) were determined in lung, liver, gut and kidney at different time-points. The time-course of plasma cytokines was evaluated up to 6 h after flagellin. Results: TLR5 mRNA and protein were constitutively expressed in all organs. In these organs, flagellin elicited a robust activation of NF kappa B and MAPKs, and induced significant production of the different cytokines evaluated, with slight interorgan variations. Plasma TNF alpha, IL-6 and MIP-2 disclosed a transient peak, whereas IL-1 beta and soluble TREM-1 steadily increased over 6 h. Flagellin also triggered a marked cleavage of caspase-3 and PARP in the intestine, pointing to its ability to promote significant apoptosis in this organ. Conclusions: Bacterial flagellin elicits prototypical innate immune responses in mice, leading to the release of multiple pro-inflammatory cytokines in the lung, small intestine, liver and kidney, and also activates apoptotic signalling in the gut. Therefore, this bacterial protein may represent a critical mediator of systemic inflammation and intestinal barrier failure in sepsis due to flagellated micro-organisms. C1 [Rolli, Joelle; Loukili, Noureddine; Levrand, Sandra; Liaudet, Lucas] Univ Lausanne Hosp, Med Ctr, Dept Intens Care Med, CH-1010 Lausanne, Switzerland. [Rolli, Joelle; Loukili, Noureddine; Levrand, Sandra; Rosenblatt-Velin, Nathalie; Rignault-Clerc, Stephanie; Waeber, Bernard; Feihl, Francois; Liaudet, Lucas] Fac Biol & Med, CH-1010 Lausanne, Switzerland. [Pacher, Pal] Univ Lausanne Hosp, Med Ctr, Dept Internal Med, Div Pathophysiol, CH-1010 Lausanne, Switzerland. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Liaudet, L (reprint author), Univ Lausanne Hosp, Med Ctr, Dept Intens Care Med, Rue Bugnon 46, CH-1010 Lausanne, Switzerland. EM lucas.liaudet@chuv.ch RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Swiss National Fund for Scientific Research [320000-118174/1]; Lausanne CardioMet Foundation [2007-R07-15] FX This work was supported by a Grant from the Swiss National Fund for Scientific Research (320000-118174/1) and a Grant from The Lausanne CardioMet Foundation (Nr 2007-R07-15) to Lucas Liaudet. NR 36 TC 16 Z9 19 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2010 VL 14 IS 4 AR R160 DI 10.1186/cc9235 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 680JJ UT WOS:000284227900035 PM 20731882 ER PT J AU Barochia, AV Cui, XZ Natanson, C Eichacker, PQ AF Barochia, Amisha V. Cui, Xizhong Natanson, Charles Eichacker, Peter Q. TI Risk of death and the efficacy of eritoran tetrasodium (E5564): Design considerations for clinical trials of anti-inflammatory agents in sepsis SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACTIVATED PROTEIN-C; APACHE-II SCORE; INTENSIVE-CARE; SEVERITY; INHIBITION; MORTALITY; ILLNESS; ADULTS C1 [Barochia, Amisha V.; Cui, Xizhong; Natanson, Charles; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Barochia, AV (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 19 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2010 VL 38 IS 1 BP 306 EP 308 DI 10.1097/CCM.0b013e3181b77fe3 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 539AE UT WOS:000273224800049 PM 20023474 ER PT J AU Navia, JL Byers, T Djordjevic, D Hentges, E King, J Klurfeld, D Llewellyn, C Milner, J Skrypec, D Weed, D AF Navia, Juan L. Byers, Tim Djordjevic, Darinka Hentges, Eric King, Janet Klurfeld, David Llewellyn, Craig Milner, John Skrypec, Daniel Weed, Douglas TI Integrating the Totality of Food and Nutrition Evidence for Public Health Decision Making and Communication SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE epidemiology; weak associations; dietary guidelines; decision making; communication; nutrition; Bayesian; biomarker ID DIETARY MODIFICATION TRIAL; VITAMIN-E SUPPLEMENTATION; RANDOMIZED-TRIALS; METAANALYSIS; MORTALITY; DISEASE; PATTERN; RISK AB The interpretation and integration of epidemiological studies detecting weak associations (RR 2) with data from other study designs (e.g., animal models and human intervention trials) is both challenging and vital for making science-based dietary recommendations in the nutrition and food safety communities. The 2008 ILSI North America oDecision-Making for Recommendations and Communication Based on Totality of Food-Related Researcho workshop provided an overview of epidemiological methods, and case-study examples of how weak associations have been incorporated into decision making for nutritional recommendations. Based on the workshop presentations and dialogue among the participants, three clear strategies were provided for the use of weak associations in informing nutritional recommendations for optimal health. First, enable more effective integration of data from all sources through the use of genetic and nutritional biomarkers; second, minimize the risk of bias and confounding through the adoption of rigorous quality-control standards, greater emphasis on the replication of study results, and better integration of results from independent studies, perhaps using adaptive study designs and Bayesian meta-analysis methods; and third, emphasize more effective and truthful communication to the public about the evolving understanding of the often complex relationship between nutrition, lifestyle, and optimal health. C1 [Navia, Juan L.] McNeil Nutr LLC, Ft Washington, PA 19034 USA. [Byers, Tim] Univ Colorado, Aurora, CO USA. [Djordjevic, Darinka; Hentges, Eric] ILSI N Amer, Washington, DC USA. [King, Janet] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Klurfeld, David] USDA ARS, Beltsville, MD USA. [Llewellyn, Craig; Skrypec, Daniel] Kraft Gen Foods Inc, Glenview, IL 60025 USA. [Milner, John] NIH, Rockville, MD USA. [Weed, Douglas] DLW Consulting Serv LLC, Kensington, MD USA. RP Navia, JL (reprint author), McNeil Nutr LLC, 601 Off Ctr Dr, Ft Washington, PA 19034 USA. EM jnavia@its.jnj.com FU Technical Committees on Food and Chemical Safety, Carbohydrates and Dietary Lipids of the North American Branch of the International Life Sciences Institute (ILSI); American Meat Institute Foundation FX This work was supported by the Technical Committees on Food and Chemical Safety, Carbohydrates and Dietary Lipids of the North American Branch of the International Life Sciences Institute (ILSI). ILSI North America is a public, non-profit foundation that provides a forum to advance understanding of scientific issues related to the nutritional quality and safety of the food supply by sponsoring research programs, educational seminars and workshops, and publications. ILSI North America receives support primarily from its industry membership. Partial financial contribution was provided by the American Meat Institute Foundation. We acknowledge Dr. Sanjiv Agarwal for his contributions to early drafts of this manuscript, and we thank Ms. Cheryl Toner for all of her help in finalizing this manuscript. We also acknowledge scientific input from all of the Committees' members and workshop speakers for their helpful suggestions during development of the 2008 workshop and review of the manuscript. NR 36 TC 3 Z9 4 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2010 VL 50 SU 1 BP 1 EP 8 AR PII 930670477 DI 10.1080/10408398.2010.526825 PG 8 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 689UL UT WOS:000284955300001 PM 21132578 ER PT J AU Picciano, MF AF Picciano, Mary Frances TI Vitamin D Status and Health SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review ID FUNCTIONAL OUTCOMES; SUPPLEMENTATION AB Vitamin D is a unique nutrient in that it is actually a prohormone obtained by endogenous synthesis from sun exposure on 7-dehydrocholesterol in skin and from certain foods and dietary supplements. Endogenous synthesis produces cholecalciferol (vitamin D3) and is transported to the liver bound to the vitamin D-binding protein (DBP). In foods and dietary supplements, vitamin D exists either as cholecalciferol or plant-derived ergocalciferol (vitamin D2). Both forms of the ingested vitamin are absorbed via the lymphatic system and transported to the liver. Vitamin D occurs naturally in a limited number of foods, and fish are found to have the highest amounts of the vitamin. Fortified foods provide the major dietary food sources of vitamin D (e.g., milk and milk products, margarines, and breakfast cereals) in the United States (Whiting and Calvo, 2006). In the liver, vitamin D is converted to 25(OH)D by the enzyme 25-hydroxylase. Conversion to the active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], is achieved in renal tissue by the enzyme 1-hydroxylase (1-OHase). The 1,25(OH)2D form of vitamin D can depress the activity of 1-OHase, and the parathyroid hormone (PTH) can stimulate its activity. As such, 1,25(OH)2D exerts its effects by binding to a specific nuclear receptor (vitamin D receptor [VDR]), a ligand-dependent transcription factor that recognizes specific DNA sequences known as vitamin D response elements (DeLuca, 2004). The main circulating vitamin D metabolite is 25(OH)D, which is used as an indicator of vitamin D nutrition status. The appearance in the circulation of native vitamin D is brief because it is rapidly metabolized in the liver or stored in adipose tissue (Holick, 2007). DBP binds approximately 99% of circulating vitamin D and its metabolites and has a higher affinity for 25(OH)D than 1,25(OH)2D or native vitamin D. Vitamin D deficiency results in diseases such as rickets in infants and children, and osteomalacia in adults (Prentice et al., 2008). Investigations into possible non-bone-related functions of vitamin D are increasing because of the recognition that (1) expression of 1-OHase occurs in many extrarenal tissues and (2) the VDR appears not only in the target cells of enterocytes, osteoblasts, and distal renal tubule cells, but also in parathyroid gland cells, skin keratinocytes, promyelocytes, lymphocytes, colon cells, pituitary gland cells, and ovarian cells (Jones et al., 1998). Areas of promising research include osteoporosis, type-1 diabetes, some cancers, autoimmune diseases, and infectious diseases such as tuberculosis (Brannon et al., 2008). The most commonly used method for assessing Vitamin D status is the measurement of circulating 25(OH)D. There are major limitations of using 25(OH)D as a status biomarker, including the unknown extent of storage of vitamin D, potential dangers of its accumulation in adipose tissue, regulation of its mobilization from these stores, and the consequences of the saturation of this storage. Different methods are used to measure serum or plasma 25(OH)D concentration and comparisons have been complicated by a lack of a standardized reference material. Different laboratories and different methods yield different results using the same sample. The international Vitamin D Quality Assessment Scheme (DEQAS), established in 1989, monitors the performance of 25(OH)D assays and currently has over 100 registered participants from 18 countries (Carter et al., 2004). The DEQAS has shown that samples analyzed by most commercially available methods are capable of providig results close to the target value for 25(OH)D3, but that results are highly dependent on the laboratory of analysis and the skill of the operator. The DEQAS has also shown that not all assay methods are capable of detecting 25(OH)D2 with the same efficiency as 25(OH)D3. The National Institute of Standards and Technology released standard reference materials (SRMS) for 25(OH)D2 and D3 in July 2009 (NIST, 2009). The availability of these SRMs should permit greater accuracy and precision for measuring 25(OH) D2 and D3 and enable meaningful comparison across laboratories. Vitamin D insufficiency or hypovitaminosis D is likely to be evident in individuals with 25(OH)D values less than 11 ng/mL or 27.5 nmol/L. However, there is no agreement for levels corresponding to sufficiency or ooptimalo vitamin D status. From associations between 25(OH) D concentrations with PTH concentrations and fractional calcium absorption rates, researchers have proposed that plasma 25(OH)D values greater than 50 and 75 nmol/L should define vitamin D sufficiency and ooptimalo concentrations (Dawson-Hughes, 2008; Heaney, 2008). Assessment of Vitamin D status in nationally representative samples from the National Health and Nutrition Examination Surveys (NHANES) 2000-2004 were compared with NHANES III 1988-1994 data (Looker et al., 2008). Mean serum 25(OH)D concentrations were significantly lower in 2000 to 2004 than in 1988 to 1994 in all of the groups examined. Adjustment for assay changes noticeably reduced the difference between surveys. This remaining difference likely represents a real decline in vitamin D status. Changes in body mass index, milk intake, and sun protection seemed to contribute to this decline. Ingested vitamin D is potentially toxic if taken in high amounts over long periods of time. Unfortunately, the available evidence on the quantitative aspects of the safety of vitamin D is very limited. Most of the available information is from studies of short duration. In the Women's Health Initiative, postmenopausal women supplemented with 10 g (400 IU) of vitamin D per day in combination with 1000 mg Ca/d exhibited a 17% increase in kidney stones (Jackson et al., 2006). Despite the considerable progress made in recent years, the available evidence on the relationship between vitamin D and health is far from complete. Investigations are needed that focus on understudied key population subgroups, such as dark-skinned individuals; reproductive-age, pregnant, and lactating women; infants; and adolescents. This article is not subject to US copyright law. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Picciano, MF (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 10 U2 68 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2010 VL 50 SU 1 BP 24 EP 25 AR PII 930669875 DI 10.1080/10408398.2010.526858 PG 2 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 689UL UT WOS:000284955300009 ER PT J AU Pacheco-Rodriguez, G Moss, J AF Pacheco-Rodriguez, Gustavo Moss, Joel TI The Role of Chemokines in Migration of Metastatic-like Lymphangioleiomyomatosis Cells SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE cell motility; chemokines; chemokine receptors; cystic lung disease; lymphangioleiomyomatosis; metastasis; mammalian target of rapamycin; smooth muscle cells; tuberous sclerosis complex ID TUBEROUS SCLEROSIS COMPLEX; SINGLE-LUNG TRANSPLANTATION; TUMOR-SUPPRESSOR TSC2; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; SIGNALING PATHWAY; CANCER METASTASIS; DIRECT TARGET; EXPRESSION; RECEPTORS; PATHOGENESIS AB Lymphangioleiomyomatosis (LAM), a rare cystic lung disease with multi-organ involvement, occurs primarily in women of childbearing age. LAM can present sporadically or in association with tuberous sclerosis complex (TSC). Loss of lung function in patients with LAM can be attributed to the dysregulated growth of LAM cells, with dysfunctional TSC1 or TSC2 genes, which encode hamartin and tuberin, respectively, leading to hyperactivation of the mammalian target of rapamycin (mTOR). LAM cells are smooth muscle-like cells that express melanoma antigens such as gp100, a splice variant of the Pmel17 gene. Tuberin and hamartin form heterodimers that act as negative regulators of mTOR. Lack of TSC2 function, as occurs in LAM cells, leads to the production of the chemokine CCL2/monocyte chemotactic protein 1 (MCP-1), which increases LAM cell mobility. Although many chemokines and their receptors could influence LAM cell mobilization, we propose that a positive-feedback loop is generated when dysfunctional TSC2 is present in LAM cells. We identified a group of chemokine receptors that is expressed in LAM cells and differs from those on smooth muscle and melanoma cells (Malme-3M). Chemokines have been implicated in tumor metastasis, and our data suggest a role for chemokines in LAM cell mobilization and thereby in the pathogenesis of LAM. C1 [Pacheco-Rodriguez, Gustavo; Moss, Joel] NHLBI, NIH, Translat Med Branch, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, NIH, Translat Med Branch, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL002541-12, ZIA HL002541-14, Z01 HL002541-13] NR 54 TC 9 Z9 10 U1 0 U2 2 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 EI 2162-6472 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2010 VL 30 IS 4 BP 387 EP 394 PG 8 WC Immunology SC Immunology GA 667QL UT WOS:000283208600004 PM 20666708 ER PT J AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI IL-21 Is an Immune Activator That also Mediates Suppression via IL-10 SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE IL-21; IL-10; autoimmunity; Tr1 cell; EAE; SLE ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC VIRAL-INFECTION; NATURAL-KILLER-CELLS; REGULATORY T-CELL; TGF-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; CYTOKINE PRODUCTION; IL10 GENE; IN-VIVO; B-CELLS AB Interleukin-21 (IL-21) is a pleiotropic type I cytokine that is produced predominantly by CD4(+) T cells and natural killer T (NKT) cells Although IL-21 production is relatively restricted to these two populations of immune cells, its targets are numerous, including multiple lympho-hematopoietic as well as non-hematopoietic lineages The effects of IL-21 are specific not only to the target cell type, but also depend on the developmental stage of the target cell as well as the available co-stimulatory signals Accordingly, IL-21 functions not only as a strong inducer of differentiation and proliferation but also as a pro-apoptotic factor Although most of the effects of IL-21 are immunostimulatory, it has become clear that one of the cytokines that is potently induced by IL-21 in a number of lymphoid lineages is interleukin-10 (IL-10), one of the most immunosuppressive cytokines The seemingly contradictory actions of IL-21 and IL-10 and the consequences of their co-expression are currently being explored in numerous infectious models, autoimmune diseases, and tumor responses This review seeks to critically evaluate the evidence concerning the regulation of IL-10 by IL-21 in a number of lineage subsets as well as to discuss the potential positive versus deleterious roles that this co-expression may play in a range of disease models C1 [Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. FU National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health R S and W J L are inventors on patents and patent applications related to IL-21 We thank Dr Mohit Kashyap for critical comments We thank Ms Anne Nichols for help in designing and preparing Fig 1 NR 72 TC 12 Z9 12 U1 0 U2 2 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2010 VL 30 IS 6 BP 559 EP 570 PG 12 WC Immunology SC Immunology GA 698AA UT WOS:000285561700005 PM 21175418 ER PT J AU Marques, AR AF Marques, Adriana R. TI Lyme Disease: A Review SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review DE Lyme disease; Borrelia burgdorferi; Infection; Tick-borne illness ID BURGDORFERI SENSU-STRICTO; POLYMERASE-CHAIN-REACTION; OUTER SURFACE PROTEIN; HUMAN GRANULOCYTIC ANAPLASMOSIS; CONFIRMED ERYTHEMA MIGRANS; LINKED-IMMUNOSORBENT-ASSAY; T-CELL EPITOPES; BORRELIA-BURGDORFERI; ARTHRITIS DEVELOPMENT; CEREBROSPINAL-FLUID AB Lyme disease is the most common vector-borne illness in the United States and is also endemic in Europe and Asia. It is caused by the spirochete Borrelia burgdorferi and transmitted by the bite of the Ixodes (deer) tick. It occurs most frequently during spring and summer and may involve the skin, nervous system, heart, and joints. This article reviews the pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,Room 11 N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 66 TC 30 Z9 33 U1 3 U2 31 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JAN PY 2010 VL 10 IS 1 BP 13 EP 20 DI 10.1007/s11882-009-0077-3 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 586KR UT WOS:000276907600003 PM 20425509 ER PT J AU Giovannetti, E Honeywell, R Hanauske, AR Tekle, C Kuenen, B Sigmond, J Giaccone, G Peters, GJ AF Giovannetti, Elisa Honeywell, Richard Hanauske, Axel R. Tekle, Christina Kuenen, Bart Sigmond, Jennifer Giaccone, Giuseppe Peters, Godefridus J. TI Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC) SO CURRENT DRUG TARGETS LA English DT Review DE New anticancer targeted agents; drug combination; protein kinase C; thymidylate synthase; angiogenesis; apoptosis ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; REDUCED FOLATE CARRIER; BETA-INHIBITOR ENZASTAURIN; HUMAN-BREAST-CANCER; HUMAN COLON-CANCER; PHASE-III TRIAL; THYMIDYLATE SYNTHASE EXPRESSION; ADVANCED COLORECTAL-CANCER; MESSENGER-RNA LEVELS AB Conventional regimens have limited impact against NSCLC. Current research is focusing on multiple pathways as potential targets, and this review describes pharmacological aspects underlying the combination of the PKC beta-inhibitor enzastaurin with the multitargeted antifolate pemetrexed. Pemetrexed is commonly used, alone or combined with platinum compounds, in NSCLC treatment, and ongoing studies are evaluating its target, thymidylate synthase (TS), as predictor of drug activity. Enzastaurin is a biological targeted agent actively being investigated against different tumors as single agent or in combination. All the downstream events following PKC beta inhibition by enzastaurin are not completely known, and assays to evaluate possible biomarkers, such as expression of PKC, VEGF and GSK3 beta, in tissues and/or in blood samples, are being developed. Enzastaurin-pemetrexed combination was synergistic in preclinical models, including NSCLC cells, where enzastaurin reduced phosphoCdc25C, resulting in G2/M-checkpoint abrogation, and Akt and GSK3 beta phosphorylation, favoring apoptosis induction in pemetrexed-damaged cells. Enzastaurin also significantly reduced VEGF secretion and pemetrexed-induced upregulation of TS expression, possibly via E2F-1 reduction, while the combination decreased TS activity. Similarly, the accumulation of deoxyuridine (a marker of TS inhibition) and the reduction of GSK3 beta phosphorylation were detectable in clinical samples from a phase-Ib trial of pemetrexed-enzastaurin combination. In conclusion, the favorable toxicity profile and the multiple effects of enzastaurin on signaling pathways involved in cell cycle control, apoptosis and angiogenesis, as well as on proteins involved in pemetrexed activity, provide experimental basis for future studies on enzastaurin-pemetrexed combination and their possible pharmacodynamic markers in NSCLC patients. C1 [Peters, Godefridus J.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. [Hanauske, Axel R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Tekle, Christina] Univ Oslo, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Kuenen, Bart] Martini Hosp, Groningen, Netherlands. RP Peters, GJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM gj.peters@vumc.nl RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Giovannetti, Elisa/0000-0002-7565-7504 NR 176 TC 11 Z9 12 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD JAN PY 2010 VL 11 IS 1 BP 12 EP 28 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 532KO UT WOS:000272747000003 PM 19839931 ER PT J AU Wei, LY Malhotra, SV AF Wei, Linyi Malhotra, Sanjay V. TI Recent Development of Cyclic Amide (Pyridone/Lactam) Moiety Containing Heterocycles as Protein Kinase Inhibitors SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Protein Kinase Inhibitor; Cyclic Amide (Pyridone/lactam); Staurosporine; Hydroxyfasudil; Pyridone 6; Kinase-biased Library; High-throughput Screenings; Cancer ID REBECCAMYCIN ANALOG NSC-655649; ACUTE MYELOID-LEUKEMIA; ANEURYSMAL SUBARACHNOID HEMORRHAGE; INDOLOCARBAZOLES TOTAL-SYNTHESIS; N-PROTECTED STAUROSPORINONES; EFFICIENT SYNTHETIC APPROACH; ANAPLASTIC LYMPHOMA KINASE; ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA AB Staurosporine, pyridone 6 and hydroxyfasudil are cyclic amide (pyridone/lactam) moiety containing heterocycles that are discovered/developed as potent protein kinase inhibitors targeting on the ATP (Adenosine-5'-triphosphate) binding pocket. Despite different molecular shapes ( pentacycle, tetracycle and bicycle, respectively), they all bind to the residues of the hinge region at ATP binding pocket of protein kinases in a very similar manner: the cyclic amide moiety occupies the adenine region of ATP binding pocket and forms at least two hydrogen bonding interaction with the hinge region via its hydrogen bond acceptor/donor pair. Using a few examples of cyclic amide (pyridone/lactam) moiety containing heterocyclic protein kinase inhibitors, this review discusses their therapeutic application, structural basis of kinase inhibition, as well as their associated syntheses. It is anticipated that the design, synthesis and profiling of the kinase-biased library based upon the cyclic amide (pyridone/lactam) moiety containing core scaffolds may significantly enhance the efficiency of high-throughput screenings (HTS), accelerate hit-to-lead process and improve the success rate in the development of protein kinase inhibitors for the treatment of various diseases especially cancer. C1 [Wei, Linyi; Malhotra, Sanjay V.] Natl Canc Inst Frederick, Lab Synthet Chem, Dev Therapeut Program Support, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Malhotra, SV (reprint author), Natl Canc Inst Frederick, Lab Synthet Chem, Dev Therapeut Program Support, SAIC Frederick Inc, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov NR 171 TC 11 Z9 14 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JAN PY 2010 VL 17 IS 3 BP 234 EP 253 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 545NQ UT WOS:000273740400005 PM 20214566 ER PT J AU Chou, JY Jun, HS Mansfield, BC AF Chou, Janice Y. Jun, Hyun S. Mansfield, Brian C. TI Neutropenia in type Ib glycogen storage disease SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE apoptosis; endoplasmic reticulum; glucose-6-phosphatase; glucose-6-phosphate transporter; glycogen storage disease type I; neutropenia ID COLONY-STIMULATING FACTOR; HUMAN GLUCOSE-6-PHOSPHATE TRANSPORTER; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; ACUTE MYELOGENOUS LEUKEMIA; UNFOLDED PROTEIN RESPONSE; LIVER-TRANSPLANTATION; CONGENITAL NEUTROPENIA; TRANSMEMBRANE TOPOLOGY; ENDOPLASMIC-RETICULUM; ANTIPORTER DEFICIENT AB Purpose of review Glycogen storage disease type lb, characterized by disturbed glucose homeostasis, neutropenia, and neutrophil dysfunction, is caused by a deficiency in a ubiquitously expressed glucose-6-phosphate transporter (G6PT). G6PT translocates glucose-6-phosphate (G6P) from the cytoplasm into the lumen of the endoplasmic reticulum, in which it is hydrolyzed to glucose either by a liver/kidney/intestine-restricted glucose-6-phosphatase-alpha (G6Pase-alpha) or by a ubiquitously expressed G6Pase-beta. The role of the G6PT/G6Pase-alpha complex is well established and readily explains why G6PT disruptions disturb interprandial blood glucose homeostasis. However, the basis for neutropenia and neutrophil dysfunction in glycogen storage disease type lb is poorly understood. Recent studies that are now starting to unveil the mechanisms are presented in this review. Recent findings Characterization of G6Pase-beta and generation of mice lacking either G6PT or G6Pase-beta have shown that neutrophils express the G6PT/G6Pase-beta complex capable of producing endogenous glucose. Loss of G6PT activity leads to enhanced endoplasmic reticulum stress, oxidative stress, and apoptosis that underlie neutropenia and neutrophil dysfunction in glycogen storage disease type lb. Summary Neutrophil function is intimately linked to the regulation of glucose and G6P metabolism by the G6PT/G6Pase-beta complex. Understanding the molecular mechanisms that govern energy homeostasis in neutrophils has revealed a previously unrecognized pathway of intracellular G6P metabolism in neutrophils. C1 [Chou, Janice Y.; Jun, Hyun S.; Mansfield, Brian C.] NICHHD, Program Dev Endocrinol & Genet, Sect Cellular Differentiat, NIH, Bethesda, MD 20892 USA. [Mansfield, Brian C.] Correlog Syst Inc, Germantown, MD USA. RP Chou, JY (reprint author), NICHHD, Program Dev Endocrinol & Genet, Sect Cellular Differentiat, NIH, Room 9D42,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov RI Jun, Hyun Sik/C-6799-2013; OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural Research Program of the NICHD, NIH FX This research was supported by the Intramural Research Program of the NICHD, NIH. NR 77 TC 17 Z9 21 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2010 VL 17 IS 1 BP 36 EP 42 DI 10.1097/MOH.0b013e328331df85 PG 7 WC Hematology SC Hematology GA 537LO UT WOS:000273114600007 PM 19741523 ER PT J AU Hsieh, TC Jarrett, TW Pinto, PA AF Hsieh, Tung-Chin Jarrett, Thomas W. Pinto, Peter A. TI Current status of nephron-sparing robotic partial nephrectomy SO CURRENT OPINION IN UROLOGY LA English DT Review DE laparoscopic surgery; partial nephrectomy; robotic ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; CHRONIC KIDNEY-DISEASE; RENAL TUMORS; EXPERIENCE; SURGERY AB Purpose of review Partial nephrectomy has become the standard of treatment for renal tumors less than 4 cm in size. Recent reports have even applied this technique for T1b lesions as well. With advancement in minimally invasive techniques, laparoscopic and robotic surgeries are performed with the advantage of decreased morbidity while maintaining the same oncologic principles as those of open surgery. Recent findings Feasibility studies confirmed that robot-assisted partial nephrectomy can be performed safely. Short-term outcomes are similar to those of laparoscopic and open partial nephrectomy. Complex renal tumors, such as hilar and endophytic lesions, have also been performed robotically. Summary Robot-assisted partial nephrectomy is feasible with short-term results comparable to those of open and laparoscopic surgery. With challenges of pure laparoscopic surgery, robotic assistance may provide more opportunities for minimally invasive nephron-sparing surgery. C1 [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Hsieh, Tung-Chin; Jarrett, Thomas W.] George Washington Univ, Dept Urol, Washington, DC USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210 Bldg,10 CRC,Room 2W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 23 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD JAN PY 2010 VL 20 IS 1 BP 65 EP 69 DI 10.1097/MOU.0b013e3283337b76 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 534JH UT WOS:000272891900012 PM 19898240 ER PT J AU Franke, RM Gardner, ER Sparreboom, A AF Franke, R. M. Gardner, E. R. Sparreboom, A. TI Pharmacogenetics of Drug Transporters SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID SINGLE NUCLEOTIDE POLYMORPHISMS; CANCER-RESISTANCE-PROTEIN; ORGANIC CATION TRANSPORTER; ATP-BINDING CASSETTE; CELL LUNG-CANCER; INTESTINAL P-GLYCOPROTEIN; MEDIATED HEPATIC-UPTAKE; MDR1 GENE AFFECTS; OATP1B1 OATP-C; MULTIDRUG TRANSPORTER AB During the last decade, a greater focus has been given to impact of genetic variation in membrane transporters on the pharmacokinetics and toxicity of numerous therapeutic drugs. While the majority of transporter-related pharmacogenetic research has been in regards to classic genes encoding the outward-directed ATP-binding cassette (ABC) transporters, such as ABCB1 (P-glycoprotein), ABCC2 (MRP2), and ABCG2 (BCRP), more studies have been conducted in recent years evaluating genes encoding solute carriers (SLC) that mediate the cellular uptake of drugs, such as SLCO1B1 (OATP1B1) and SLC22A1 (OCT1). The distribution of ABC and SLC transporters in tissues key to pharmacokinetics, such as intestine (absorption), blood-brain-barrier (distribution), liver (metabolism), and kidneys (excretion), strongly suggests that genetic variation associated with changes in protein expression or function of these transporters may have a substantial impact on systemic drug exposure and toxicity. In this current article, we will review recent advances in understanding the contribution of critical ABC and SLC transporters to interindividual pharmacokinetic and dynamic variability of substrate drugs. C1 [Franke, R. M.; Sparreboom, A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gardner, E. R.] NCI, Clin Pharmacol Program, SAIC Frederick, Ft Detrick, MD 21702 USA. RP Sparreboom, A (reprint author), St Jude Childrens Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. EM alex.sparreboom@stjude.org FU NIH [HHSN-261200800001E]; National Cancer Institute; Center for Cancer Research; American Lebanese Syrian Associated Charities (ALSAC) FX This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, the American Lebanese Syrian Associated Charities (ALSAC), and federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN-261200800001E (ERG). 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. NR 150 TC 45 Z9 47 U1 1 U2 24 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2010 VL 16 IS 2 BP 220 EP 230 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 532TU UT WOS:000272773600009 PM 19835554 ER PT J AU Mondoux, MA Krause, MW Hanover, JA AF Mondoux, Michelle A. Krause, Michael W. Hanover, John A. TI C-elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways SO CURRENT SIGNAL TRANSDUCTION THERAPY LA English DT Review ID LINKED N-ACETYLGLUCOSAMINE; NEMATODE CAENORHABDITIS-ELEGANS; ACTIVATED PROTEIN-KINASE; FORKHEAD TRANSCRIPTION FACTOR; PANCREATIC BETA-CELLS; REGULATES LIFE-SPAN; INSULIN-RESISTANCE; SKELETAL-MUSCLE; INNATE IMMUNITY; FUNCTIONAL INTERACTION AB Caenorhabditis elegans is perhaps the best-understood metazoan in terms of cell fate, neural connectivity, nutrient sensing, and longevity. The study of this genetically amenable model has greatly accelerated progress in understanding human aging-associated diseases, such as diabetes and neurodegeneration. The nutrient-responsive cycling of O-GlcNAc on key intracellular targets may play a key, yet unappreciated, role in human disease. Unlike their mammalian counterparts, loss-of-function mutants of ogt-1 (O-GlcNAc Transferase) and oga-1 (O-GlcNAcase) are viable in C. elegans, allowing the impact of the loss of O-GlcNAc cycling to be monitored in a living organism. C. elegans forward and reverse genetics, coupled with proteomics and chemical genomics, reveal networks of interactions and signaling pathways in which O-GlcNAc cycling may participate. The results point to a key regulatory role for O-GlcNAc cycling in cellular functions as diverse as nutrient uptake and salvage, cellular signaling, and transcription. The impact of altered O-GlcNAc cycling on the organism includes many of the hallmarks of aging-associated diseases: altered metabolism, lifespan, stress resistance, and immunity. C1 [Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Mondoux, Michelle A.; Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bldg 8,Rm B127,8 Ctr Dr MSC 0850, Bethesda, MD 20892 USA. EM jah@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 NR 138 TC 2 Z9 4 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-3624 J9 CURR SIGNAL TRANSD T JI Curr. Signal Transduct. Ther. PD JAN PY 2010 VL 5 IS 1 BP 60 EP 73 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 532VR UT WOS:000272778700008 ER EF