FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sharov, AA Nishiyama, A Piao, YL Correa-Cerro, LS Amano, T Thomas, M Mehta, S Ko, MSH AF Sharov, Alexei A. Nishiyama, Akira Piao, Yulan Correa-Cerro, Lina S. Amano, Tomokazu Thomas, Marshall Mehta, Samir Ko, Minoru S. H. TI Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity SO BMC GENOMICS LA English DT Article ID EMBRYONIC STEM-CELLS; RNA-POLYMERASE-II; CPG ISLANDS; MOUSE; GENOME; METHYLATION; PLURIPOTENT; EXPRESSION; STATE; SET2 AB Background: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. Results: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. Conclusions: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity. C1 [Sharov, Alexei A.; Piao, Yulan; Correa-Cerro, Lina S.; Amano, Tomokazu; Thomas, Marshall; Mehta, Samir; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. [Nishiyama, Akira] Yokohama City Univ, Dept Immunol, Grad Sch Med, Kanagawa 2360004, Japan. [Nishiyama, Akira] Yokohama City Univ, Fac Med, Kanagawa 2360004, Japan. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009; Amano, Tomokazu/F-9720-2013 OI Ko, Minoru/0000-0002-3530-3015; FU NIH, National Institute on Aging FX We thank Bernard Binder for critical reading of the manuscript, Carole Stagg, Yong Qian, and Dawood Dudekula for providing technical help. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 42 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD FEB 9 PY 2011 VL 12 AR 102 DI 10.1186/1471-2164-12-102 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 726AM UT WOS:000287688300001 PM 21306619 ER PT J AU Maier, A Aura, CJ Leopold, DA AF Maier, Alexander Aura, Christopher J. Leopold, David A. TI Infragranular Sources of Sustained Local Field Potential Responses in Macaque Primary Visual Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID RECORDED FLASH-VEP; EVOKED-POTENTIALS; NEURONAL CIRCUITS; SPIKING ACTIVITY; CEREBRAL-CORTEX; STRIATE CORTEX; FEEDBACK AXONS; AWAKE MACAQUE; MONKEY; MECHANISMS AB A local field potential (LFP) response can be measured throughout the visual cortex in response to the abrupt appearance of a visual stimulus. Averaging LFP responses to many stimulus presentations isolates transient, phase-locked components of the response that are consistent from trial to trial. However, stimulus responses are also composed of sustained components, which differ in their phase from trial to trial and therefore must be evaluated using other methods, such as computing the power of the response of each trial before averaging. Here, we investigate the basis of phase-locked and non-phase-locked LFP responses in the primary visual cortex of the macaque monkey using a novel variant of current source density (CSD) analysis. We applied a linear array of electrode contacts spanning the thickness of the cortex to measure the LFP and compute band-limited CSD power to identify the laminar sites of persistent current exchange that may be the basis of sustained visual LFP responses. In agreement with previous studies, we found a short-latency phase-locked current sink, thought to correspond to thalamocortical input to layer 4C. In addition, we found a prominent non-phase-locked component of the CSD that persisted as long as the stimulus was physically present. The latter was relatively broadband, lasted throughout the stimulus presentation, and was centered similar to 500 mu m deeper than the initial current sink. These findings demonstrate a fundamental difference in the neural mechanisms underlying the initial and sustained processing of simple visual stimuli in the V1 microcircuit. C1 [Leopold, David A.] NEI, Neurophysiol Imaging Facil, NIMH, NINDS,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Maier, Alexander; Aura, Christopher J.; Leopold, David A.] NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Leopold, DA (reprint author), NEI, Neurophysiol Imaging Facil, NIMH, NINDS,NIH,Dept Hlth & Human Serv, 49 Convent Dr,1E21,MSC 4400, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov RI Maier, Alexander/B-7489-2009; OI Maier, Alexander/0000-0002-7250-502X; Leopold, David/0000-0002-1345-6360 FU National Institute of Mental Health; National Institute for Neurological Disorders and Stroke; National Eye Institute FX This work was supported by the Intramural Research Programs of the National Institute of Mental Health, National Institute for Neurological Disorders and Stroke, and the National Eye Institute. We thank Katy Smith for technical assistance. NR 47 TC 35 Z9 35 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 9 PY 2011 VL 31 IS 6 BP 1971 EP 1980 DI 10.1523/JNEUROSCI.5300-09.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 721WV UT WOS:000287389400006 PM 21307235 ER PT J AU Sapieha, P Stahl, A Chen, J Seaward, MR Willett, KL Krah, NM Dennison, RJ Connor, KM Aderman, CM Liclican, E Carughi, A Perelman, D Kanaoka, Y SanGiovanni, JP Gronert, K Smith, LEH AF Sapieha, Przemyslaw Stahl, Andreas Chen, Jing Seaward, Molly R. Willett, Keirnan L. Krah, Nathan M. Dennison, Roberta J. Connor, Kip M. Aderman, Christopher M. Liclican, Elvira Carughi, Arianna Perelman, Dalia Kanaoka, Yoshihide SanGiovanni, John Paul Gronert, Karsten Smith, Lois E. H. TI 5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of omega-3 Polyunsaturated Fatty Acids SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID OXYGEN-INDUCED RETINOPATHY; ACTIVATED-RECEPTOR-GAMMA; LIPID MEDIATORS; RETINAL NEOVASCULARIZATION; DOCOSAHEXAENOIC ACID; ANTIINFLAMMATORY ACTIONS; MYOCARDIAL-INFARCTION; ANTI-INFLAMMATION; PROTECTIN D1; PPAR-GAMMA AB Lipid signaling is dysregulated in many diseases with vascular pathology, including cancer, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. We have previously demonstrated that diets enriched in omega-3 polyunsaturated fatty acids (PUFAs) effectively reduce pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy, in part through metabolic products that suppress microglialderived tumor necrosis factor-alpha. To better understand the protective effects of omega-3 PUFAs, we examined the relative importance of major lipid metabolic pathways and their products in contributing to this effect. omega-3 PUFA diets were fed to four lines of mice deficient in each key lipid-processing enzyme (cyclooxygenase 1 or 2, or lipoxygenase 5 or 12/15), retinopathy was induced by oxygen exposure; only loss of 5-lipoxygenase (5-LOX) abrogated the protection against retinopathy of dietary omega-3 PUFAs. This protective effect was due to 5-LOX oxidation of the omega-3 PUFA lipid docosahexaenoic acid to 4-hydroxy-docosahexaenoic acid (4-HDHA). 4-HDHA directly inhibited endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPAR gamma), independent of 4-HDHA's anti-inflammatory effects. Our study suggests that omega-3 PUFAs may be profitably used as an alternative or supplement to current anti-vascular endothelial growth factor (VEGF) treatment for proliferative retinopathy and points to the therapeutic potential of omega-3 PUFAs and metabolites in other diseases of vasoproliferation. It also suggests that cyclooxygenase inhibitors such as aspirin and ibuprofen (but not lipoxygenase inhibitors such as zileuton) might be used without losing the beneficial effect of dietary omega-3 PUFA. C1 [Sapieha, Przemyslaw; Stahl, Andreas; Chen, Jing; Seaward, Molly R.; Willett, Keirnan L.; Krah, Nathan M.; Dennison, Roberta J.; Connor, Kip M.; Aderman, Christopher M.; Smith, Lois E. H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02115 USA. [Sapieha, Przemyslaw] Univ Montreal, Maisonneuve Rosemont Hosp Res Ctr, Dept Ophthalmol, Montreal, PQ H1T 2M4, Canada. [Stahl, Andreas] Univ Eye Hosp Freiburg, D-79106 Freiburg, Germany. [Liclican, Elvira; Gronert, Karsten] Univ Calif Berkeley, Sch Optometry, Vis Sci Program, Berkeley, CA 94720 USA. [Carughi, Arianna; Perelman, Dalia] Hlth Res & Studies Ctr, Los Altos, CA 94022 USA. [Carughi, Arianna; Perelman, Dalia] Palo Alto Med Fdn, Palo Alto, CA 94301 USA. [Kanaoka, Yoshihide] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kanaoka, Yoshihide] Brigham & Womens Hosp, Boston, MA 02115 USA. [SanGiovanni, John Paul] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RP Smith, LEH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM lois.smith@childrens.harvard.edu FU NIH [EY017017, EY017017-04S1, EY016136]; Children's Hospital Boston Mental Retardation and Developmental Disabilities Research Center [P01 HD18655]; Research to Prevent Blindness; Alcon Research Institute; MacTel Foundation; Roche Foundation for Anemia Research; V. Kann Rasmussen Foundation; Canadian Institutes of Health Research; Charles A. King Trust; Canadian National Institute for the Blind; Deutsche Forschungsgemeinschaft; Juvenile Diabetes Research Foundation International; William Randolph Hearst Award [F32 EY017789] FX This work was supported by NIH grants EY017017, EY017017-04S1 (L. E. H. S.), and EY016136 (K. G.); Children's Hospital Boston Mental Retardation and Developmental Disabilities Research Center grant P01 HD18655 (L. E. H. S.); Research to Prevent Blindness Senior Investigator Award (L. E. H. S.); Alcon Research Institute Award (L. E. H. S.); MacTel Foundation (L. E. H. S.); Roche Foundation for Anemia Research (L. E. H. S.); and V. Kann Rasmussen Foundation (L. E. H. S.). P. S. holds a Canada Research Chair in Retinal Cell Biology and is supported by grants from the Canadian Institutes of Health Research, the Charles A. King Trust Award, and the Canadian National Institute for the Blind. A. S. is funded by Deutsche Forschungsgemeinschaft. Additional support was provided by the Juvenile Diabetes Research Foundation International (J.C.), the William Randolph Hearst Award F32 EY017789 (K.M.C.). NR 63 TC 52 Z9 53 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD FEB 9 PY 2011 VL 3 IS 69 AR 69ra12 DI 10.1126/scitranslmed.3001571 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795JS UT WOS:000292971100004 PM 21307302 ER PT J AU Lau-Kilby, AW Kretz, CC Pechhold, S Price, JD Dorta, S Ramos, H Trinchieri, G Tarbell, KV AF Lau-Kilby, Annie W. Kretz, Cosima C. Pechhold, Susanne Price, Jeffrey D. Dorta, Stephanie Ramos, Haydee Trinchieri, Giorgio Tarbell, Kristin V. TI Interleukin-2 inhibits FMS-like tyrosine kinase 3 receptor ligand (flt3L)-dependent development and function of conventional and plasmacytoid dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; NONOBESE DIABETIC MICE; INTERFERON-ALPHA; BONE-MARROW; IN-VIVO; CUTTING EDGE; FLT3 LIGAND; AUTOIMMUNITY; PRECURSORS; TOLERANCE AB Steady-state development of plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) requires the ligand for FMS-like tyrosine kinase 3 receptor (flt3L), but little is known about how other cytokines may also control this process. In this study, we show that IL-2 inhibits the development of both pDCs and cDCs from bone marrow cells under flt3L stimulation, by acting on lineage(-)flt3(+) precursors. This inhibition of DC development by IL-2 requires IL-2R alpha and IL2R beta. IL-2R alpha is specifically expressed in one stage of the DC precursor: the monocyte and DC progenitors (MDPs). Furthermore, more MDPs are found in flt3L-stimulated bone marrow cultures when IL-2 is present, suggesting that IL-2 may be inhibiting DC development at the MDP stage. Consistent with our in vitro findings, we observe that nonobese diabetic (NOD) mice, which express less IL-2 compared with diabetes-resistant NOD.Idd3/5 mice, have more splenic pDCs. Additionally, DCs developed in vitro in the presence of flt3L and IL-2 display reduced ability to stimulate T-cell proliferation compared with DCs developed in the presence of flt3L alone. Although the addition of IL-2 does not increase the apoptosis of DCs during their development, DCs developed in the presence of IL-2 are more prone to apoptosis upon interaction with T cells. Together our data show that IL-2 can inhibit both the development and the function of DCs. This pathway may have implications for the loss of immune tolerance: Reduced IL-2 signaling may lead to increased DC number and T-cell stimulatory capacity. C1 [Lau-Kilby, Annie W.; Kretz, Cosima C.; Price, Jeffrey D.; Dorta, Stephanie; Tarbell, Kristin V.] Natl Inst Diabet Digest & Kidney Dis, Immune Tolerance Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Ramos, Haydee] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Trinchieri, Giorgio] NCI, Expt Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Tarbell, KV (reprint author), Natl Inst Diabet Digest & Kidney Dis, Immune Tolerance Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM tarbellk@niddk.nih.gov OI Lau-Kilby, Annie/0000-0002-2666-1347; Tarbell, Kristin/0000-0003-3738-379X FU National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX We thank Alice Franks, the flow cytometry core facilities at the National Heart, Lung and Blood Institute and the National Institute of Allergic and Infectious Disease, and Helen Su and Qian Zhang for technical support, and Dr. Yasmine Belkaid for critical reading of the manuscript. This work was supported by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, and National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 40 TC 13 Z9 14 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2408 EP 2413 DI 10.1073/pnas.1009738108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500045 PM 21262836 ER PT J AU Shukla, P Nguyen, HT Torian, U Engle, RE Faulk, K Dalton, HR Bendall, RP Keane, FE Purcell, RH Emerson, SU AF Shukla, Priyanka Nguyen, Hanh T. Torian, Udana Engle, Ronald E. Faulk, Kristina Dalton, Harry R. Bendall, Richard P. Keane, Frances E. Purcell, Robert H. Emerson, Suzanne U. TI Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE emerging virus; zoonosis ID PROTEIN; HEPATOMA; RELEASE; GENOMES; PATIENT AB The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene. C1 [Engle, Ronald E.; Faulk, Kristina; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Shukla, Priyanka; Nguyen, Hanh T.; Torian, Udana; Emerson, Suzanne U.] NIAID, Sect Mol Hepatitis, NIH, Bethesda, MD 20892 USA. [Dalton, Harry R.; Bendall, Richard P.; Keane, Frances E.] European Ctr Environm & Human Hlth, Truro TR1 3LJ, Cornwall, England. [Dalton, Harry R.; Bendall, Richard P.; Keane, Frances E.] Univ Plymouth, Truro TR1 3LJ, Cornwall, England. [Dalton, Harry R.; Bendall, Richard P.; Keane, Frances E.] Univ Exeter, Truro TR1 3LJ, Cornwall, England. [Dalton, Harry R.; Bendall, Richard P.; Keane, Frances E.] Royal Cornwall Hosp Trust, Truro TR1 3LJ, Cornwall, England. RP Purcell, RH (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM RPURCELL@niaid.nih.gov; semerson@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Rebecca DerSimonian and Xiao Liu Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, for performing the statistical analyses. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 28 TC 93 Z9 94 U1 3 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2438 EP 2443 DI 10.1073/pnas.1018878108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500050 PM 21262830 ER PT J AU Song, KM Bolton, DL Wei, CJ Wilson, RL Camp, JV Bao, S Mattapallil, JJ Herzenberg, LA Herzenberg, LA Andrews, CA Sadoff, JC Goudsmit, J Pau, MG Seder, RA Kozlowski, PA Nabel, GJ Roederer, M Rao, SS AF Song, Kaimei Bolton, Diane L. Wei, Chih-Jen Wilson, Robert L. Camp, Jeremy V. Bao, Saran Mattapallil, Joseph J. Herzenberg, Leonore A. Herzenberg, Leonard A. Andrews, Charla A. Sadoff, Jerald C. Goudsmit, Jaap Pau, Maria Grazia Seder, Robert A. Kozlowski, Pamela A. Nabel, Gary J. Roederer, Mario Rao, Srinivas S. TI Genetic immunization in the lung induces potent local and systemic immune responses (vol 107, pg 22213, 2010) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Correction C1 [Song, Kaimei; Bolton, Diane L.; Wei, Chih-Jen; Bao, Saran; Andrews, Charla A.; Seder, Robert A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70803 USA. [Wilson, Robert L.; Camp, Jeremy V.; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70803 USA. [Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Herzenberg, Leonore A.; Herzenberg, Leonard A.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Sadoff, Jerald C.] AERAS Global TB Fdn, Rockville, MD 20850 USA. [Goudsmit, Jaap; Pau, Maria Grazia] Crucell Holland BV, Leiden, Netherlands. RP Song, KM (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2629 EP 2629 DI 10.1073/pnas.1100067108 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500083 ER PT J AU Lurie, G Gaudet, MM Spurdle, AB Carney, ME Wilkens, LR Yang, HP Weiss, NS Webb, PM Thompson, PJ Terada, K Setiawan, VW Rebbeck, TR Prescott, J Orlow, I O'Mara, T Olson, SH Narod, SA Matsuno, RK Lissowska, J Liang, XL Levine, DA Le Marchand, L Kolonel, LN Henderson, BE Garcia-Closas, M Doherty, JA De Vivo, I Chen, C Brinton, LA Akbari, MR Goodman, MT AF Lurie, Galina Gaudet, Mia M. Spurdle, Amanda B. Carney, Michael E. Wilkens, Lynne R. Yang, Hannah P. Weiss, Noel S. Webb, Penelope M. Thompson, Pamela J. Terada, Keith Setiawan, Veronica Wendy Rebbeck, Timothy R. Prescott, Jennifer Orlow, Irene O'Mara, Tracy Olson, Sara H. Narod, Steven A. Matsuno, Rayna K. Lissowska, Jolanta Liang, Xiaolin Levine, Douglas A. Le Marchand, Loic Kolonel, Laurence N. Henderson, Brian E. Garcia-Closas, Montserrat Doherty, Jennifer Anne De Vivo, Immaculata Chen, Chu Brinton, Louise A. Akbari, Mohammad R. Goodman, Marc T. CA Epidemiology Endometrial Canc TI The Obesity-Associated Polymorphisms FTO rs9939609 and MC4R rs17782313 and Endometrial Cancer Risk in Non-Hispanic White Women SO PLOS ONE LA English DT Article ID GENE-EXPRESSION; FAT MASS; ENDOGENOUS HORMONES; ENERGY-EXPENDITURE; ADULT OBESITY; FOOD-INTAKE; CHILDREN; VARIANT; CHILDHOOD; INSULIN AB Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [ odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis. C1 [Lurie, Galina; Wilkens, Lynne R.; Thompson, Pamela J.; Matsuno, Rayna K.; Le Marchand, Loic; Kolonel, Laurence N.; Goodman, Marc T.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA. [Gaudet, Mia M.] Amer Canc Soc Inc, Epidemiol Res Program, Atlanta, GA USA. [Spurdle, Amanda B.; Webb, Penelope M.; O'Mara, Tracy] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Spurdle, Amanda B.; Webb, Penelope M.; O'Mara, Tracy] PO Royal Brisbane Hosp, Brisbane, Qld, Australia. [Carney, Michael E.; Terada, Keith] Univ Hawaii, Dept Obstet & Gynecol, John A Burns Sch Med, Honolulu, HI 96813 USA. [Yang, Hannah P.; Garcia-Closas, Montserrat; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Weiss, Noel S.; Chen, Chu] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Weiss, Noel S.; Doherty, Jennifer Anne; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Setiawan, Veronica Wendy; Henderson, Brian E.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Abramson Canc Ctr, Philadelphia, PA USA. [Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Prescott, Jennifer; De Vivo, Immaculata] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Orlow, Irene; Olson, Sara H.; Liang, Xiaolin] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [O'Mara, Tracy] Queensland Univ Technol, Hormone Dependent Canc Grp, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Narod, Steven A.; Akbari, Mohammad R.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Matsuno, Rayna K.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Sch Med, Seattle, WA 98195 USA. RP Lurie, G (reprint author), Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA. EM glurie@crch.hawaii.edu RI Beral, Valerie/B-2979-2013; Bandera, Elisa/M-4169-2014; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Krogh, Vittorio/K-2628-2016; Weiderpass, Elisabete/M-4029-2016; O'Mara, Tracy/M-7508-2016; Spurdle, Amanda/A-4978-2011; OI Bandera, Elisa/0000-0002-8789-2755; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Krogh, Vittorio/0000-0003-0122-8624; Weiderpass, Elisabete/0000-0003-2237-0128; O'Mara, Tracy/0000-0002-5436-3232; Webb, Penelope/0000-0003-0733-5930; Spurdle, Amanda/0000-0003-1337-7897; Lissowska, Jolanta/0000-0003-2695-5799; La Vecchia, Carlo/0000-0003-1441-897X; Sacerdote, Carlotta/0000-0002-8008-5096; Orlow, Irene/0000-0001-6234-6961 FU Australian National Endometrial Cancer Study [339435, 4196615, 403031, 457636]; Estrogen; Diet; Genetics; Endometrial Cancer study, NJ, USA [NIH R01CA38918]; Fred Hutchinson Cancer Research Center Case-Control Study, WA, USA [NIH R35 CA 39779, R01 CA 75977, R03 CA 80636, N01 HD 23166, K05 CA 92002, R01 CA 105212, R01 CA87538]; Fred Hutchinson Cancer Research Center; Hawaii Endometrial Cancer Study, Hawaii, USA [NIH P01CA33619, R01CA58598, N01CN67001, N01 PC35137]; Nurses' Health Study [NIH CAO82838, CA134958]; Polish Endometrial Cancer Study of the NCI; Toronto Case-Control Endometrial Cancer Study (Canadian Institute of Health Research, CIHR), Multiethnic Cohort Study [NIH CA63464, CA54281]; Women's Insights and Shared Experiences, PA, USA [NIH P01-CA77596]; National Cancer Institute FX Australian National Endometrial Cancer Study (NHMRC ID #339435, TCCQ ID #4196615, TCCT IDs #403031 and #457636), Estrogen, Diet, Genetics, and Endometrial Cancer study, NJ, USA (NIH R01CA38918), Fred Hutchinson Cancer Research Center Case-Control Study, WA, USA (NIH R35 CA 39779, R01 CA 75977, R03 CA 80636, N01 HD 23166, K05 CA 92002, R01 CA 105212, R01 CA87538 and funds from the Fred Hutchinson Cancer Research Center), Hawaii Endometrial Cancer Study, Hawaii, USA (NIH P01CA33619, R01CA58598, N01CN67001, N01 PC35137), Nurses' Health Study (NIH CAO82838, CA134958), Polish Endometrial Cancer Study (Intramural Program of the NCI), Toronto Case-Control Endometrial Cancer Study (Canadian Institute of Health Research, CIHR), Multiethnic Cohort Study (NIH CA63464, CA54281), Women's Insights and Shared Experiences, PA, USA (NIH P01-CA77596, Dr. Mia Gaudet (American Cancer Society, Atlanta, GA, USA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; One of the authors, Dr. Mia Gaudet is employed by the American Cancer Society (since October 4th 2010). Dr Gaudet contributed the data for the Polish Endometrial Cancer Study that was funded by the National Cancer Institute. Her current employment by the American Cancer Society does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 33 TC 22 Z9 23 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 8 PY 2011 VL 6 IS 2 AR e16756 DI 10.1371/journal.pone.0016756 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717WH UT WOS:000287077600021 PM 21347432 ER PT J AU McDermott, MM Ferrucci, L Liu, KA Guralnik, JM Tian, L Kibbe, M Liao, YH Tao, HM Criqui, MH AF McDermott, Mary M. Ferrucci, Luigi Liu, Kiang Guralnik, Jack M. Tian, Lu Kibbe, Melina Liao, Yihua Tao, Huimin Criqui, Michael H. TI Women With Peripheral Arterial Disease Experience Faster Functional Decline Than Men With Peripheral Arterial Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE intermittent claudication; peripheral arterial disease; physical functioning; sarcopenia ID SKELETAL-MUSCLE MASS; LOWER-EXTREMITY ISCHEMIA; LEG SYMPTOMS; ASSOCIATIONS; INDEX; CLASSIFICATION; OSTEOARTHRITIS; IMPAIRMENT; PREVALENCE; PREDICTORS AB Objectives We hypothesized that women with lower extremity peripheral arterial disease (PAD) would have greater mobility loss and faster functional decline than men with PAD. Background Whether rates of mobility loss or functional decline differ between men and women with PAD is currently unknown. Methods Three hundred eighty men and women with PAD completed the 6-min walk, were assessed for mobility disability, and underwent measures of 4-m walking velocity at baseline and annually for up to 4 years. Computed tomography-assessed calf muscle characteristics were measured biannually. Outcomes included becoming unable to walk for 6 min continuously among participants who walked continuously for 6 min at baseline. Mobility loss was defined as becoming unable to walk for a quarter mile or to walk up and down 1 flight of stairs without assistance among those without baseline mobility disability. Results were adjusted for age, race, body mass index, physical activity, the ankle brachial index, comorbidities, and other confounders. Results At 4 years of follow-up, women were more likely to become unable to walk for 6 min continuously (hazard ratio: 2.30, 95% confidence interval: 1.30 to 4.06, p = 0.004), more likely to develop mobility disability (hazard ratio: 1.79, 95% confidence interval: 1.30 to 3.03, p = 0.030), and had faster declines in walking velocity (p = 0.022) and the distance achieved in the 6-min walk (p = 0.041) compared with men. Sex differences in functional decline were attenuated after additional adjustment for baseline sex differences in calf muscle area. Conclusions Women with PAD have faster functional decline and greater mobility loss than men with PAD. These sex differences may be attributable to smaller baseline calf muscle area among women with PAD. (J Am Coll Cardiol 2011;57:707-14) (C) 2011 by the American College of Cardiology Foundation C1 [McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. [Guralnik, Jack M.] NIA, NIH, Bethesda, MD 20892 USA. [Tian, Lu] Stanford Univ, Dept Hlth Policy & Res, Palo Alto, CA 94304 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart Lung and Blood Institute [R01-HL58099, R01-HL64739, R01-HL071223, R01-HL076298]; National Center for Research Resources, National Institutes of Health [RR-00048]; National Institute on Aging, National Institutes of Health FX Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, California. Supported by grants R01-HL58099, R01-HL64739, R01-HL071223, and R01-HL076298 from the National Heart Lung and Blood Institute and by grant RR-00048 from the National Center for Research Resources, National Institutes of Health. Supported in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health. The authors have reported that they have no relationships to disclose. Healther L. Gornik, MD, served as Guest Editor for this article. NR 23 TC 25 Z9 25 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 8 PY 2011 VL 57 IS 6 BP 707 EP 714 DI 10.1016/j.jacc.2010.09.042 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 715JH UT WOS:000286880100011 PM 21292130 ER PT J AU Hamid, MMA Remarque, EJ El Hassan, IM Hussain, AA Narum, DL Thomas, AW Kocken, CHM Weiss, WR Faber, BW AF Hamid, Muzamil Mahdi Abdel Remarque, Edmond J. El Hassan, Ibrahim M. Hussain, Ayman A. Narum, David L. Thomas, Alan W. Kocken, Clemens H. M. Weiss, Walter R. Faber, Bart W. TI Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques SO MALARIA JOURNAL LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM SPOROZOITES; MEROZOITE SURFACE-ANTIGENS; IMMUNE-RESPONSES; KNOWLESI MALARIA; IMMUNIZATION; PROTECTION; PRECURSOR; EFFICACY; BERGHEI AB Background: A DNA prime, poxvirus (COPAK) boost vaccination regime with four antigens, i. e. a combination of two Plasmodium knowlesi sporozoite (csp/ ssp2) and two blood stage (ama1/ msp142) genes, leads to self- limited parasitaemia in 60% of rhesus monkeys and survival from an otherwise lethal infection with P. knowlesi. In the present study, the role of the blood stage antigens in protection was studied in depth, focusing on antibody formation against the blood stage antigens and the functionality thereof. Methods: Rhesus macaques were immunized with the four- component vaccine and subsequently challenged i.v. with 100 P. knowlesi sporozoites. During immunization and challenge, antibody titres against the two blood stage antigens were determined, as well as the in vitro growth inhibition capacity of those antibodies. Antigen reversal experiments were performed to determine the relative contribution of antibodies against each of the two blood stage antigens to the inhibition. Results: After vaccination, PkAMA1 and PkMSP119 antibody titres in vaccinated animals were low, which was reflected in low levels of inhibition by these antibodies as determined by in vitro inhibition assays. Interestingly, after sporozoite challenge antibody titres against blood stage antigens were boosted over 30- fold in both protected and not protected animals. The in vitro inhibition levels increased to high levels (median inhibitions of 59% and 56% at 6 mg/ mL total IgG, respectively). As growth inhibition levels were not significantly different between protected and not protected animals, the ability to control infection appeared cannot be explained by GIA levels. Judged by in vitro antigen reversal growth inhibition assays, over 85% of the inhibitory activity of these antibodies was directed against PkAMA1. Conclusions: This is the first report that demonstrates that a DNA prime/ poxvirus boost vaccination regimen induces low levels of malaria parasite growth inhibitory antibodies, which are boosted to high levels upon challenge. No association could, however, be established between the levels of inhibitory capacity in vitro and protection, either after vaccination or after challenge. C1 [Hamid, Muzamil Mahdi Abdel; Remarque, Edmond J.; Thomas, Alan W.; Kocken, Clemens H. M.; Faber, Bart W.] Biomed Primate Res Ctr, Dept Parasitol, Rijswijk, Netherlands. [Hamid, Muzamil Mahdi Abdel; El Hassan, Ibrahim M.; Hussain, Ayman A.] Univ Khartoum, Inst Endem Dis, Khartoum, Sudan. [Weiss, Walter R.] Naval Med Res Ctr, Silver Spring, MD USA. [Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA. [El Hassan, Ibrahim M.] Jazan Univ, Fac Med, Jazan, Saudi Arabia. RP Faber, BW (reprint author), Biomed Primate Res Ctr, Dept Parasitol, Rijswijk, Netherlands. EM faber@bprc.nl OI abdelhamid, muzamil/0000-0002-6157-4388 FU European Malaria Vaccine Initiative (EMVI); Biomedical Primate Research Centre; NIAID, NIH FX This work received financial support from the European Malaria Vaccine Initiative (EMVI) and the Biomedical Primate Research Centre. This research was supported in part by the Intramural Research Program of NIAID, NIH. We thank Vanessa Riasat for excellent technical assistance. NR 37 TC 7 Z9 7 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD FEB 8 PY 2011 VL 10 AR 29 DI 10.1186/1475-2875-10-29 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 740RR UT WOS:000288812600003 PM 21303498 ER PT J AU Wang, MY Spinetti, G Monticone, RE Zhang, J Wu, J Jiang, LQ Khazan, B Telljohann, R Lakatta, EG AF Wang, Mingyi Spinetti, Gaia Monticone, Robert E. Zhang, Jing Wu, James Jiang, Liqun Khazan, Benjamin Telljohann, Richard Lakatta, Edward G. TI A Local Proinflammatory Signalling Loop Facilitates Adverse Age-Associated Arterial Remodeling SO PLOS ONE LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; MATRIX-METALLOPROTEINASE; ANGIOTENSIN-II; TGF-BETA; INVASION; EXPRESSION; DISEASE; MCP-1; ATHEROSCLEROSIS AB Background: The coincidence of vascular smooth muscle cells (VSMC) infiltration and collagen deposition within a diffusely thickened intima is a salient feature of central arterial wall inflammation that accompanies advancing age. However, the molecular mechanisms involved remain undefined. Methodology/Principal Findings: Immunostaining and immunoblotting of rat aortae demonstrate that a triad of proinflammatory molecules, MCP-1, TGF-beta 1, and MMP-2 increases within the aortic wall with aging. Exposure of VSMC isolated from 8-mo-old rats (young) to MCP-1 effects, via CCR-2 signaling, both an increase in TGF-beta 1 activity, up to levels of untreated VSMC from 30-mo-old (old) rats, and a concurrent increase in MMP-2 activation. Furthermore, exposure of young VSMC to TGF-beta 1 increases levels of MCP-1, and MMP-2 activation, to levels of untreated VSMC from old rats. This autocatalytic signaling loop that enhances collagen production and invasiveness of VSMC is effectively suppressed by si-MCP-1, a CCR2 antagonist, or MMP-2 inhibition. Conclusions/Significance: Threshold levels of MCP-1, MMP-2, or TGF-beta 1 activity trigger a feed-forward signaling mechanism that is implicated in the initiation and progression of adverse age-associated arterial wall remodeling. Intervention that suppressed this signaling loop may potentially retard age-associated adverse arterial remodeling. C1 [Wang, Mingyi; Spinetti, Gaia; Monticone, Robert E.; Zhang, Jing; Wu, James; Jiang, Liqun; Khazan, Benjamin; Telljohann, Richard; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Spinetti, Gaia] MultiMed IRCCS, Milan, Italy. RP Wang, MY (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. EM mingyiw@grc.nia.nih.gov OI Spinetti, Gaia/0000-0001-7996-6809 FU National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institute on Aging. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 14 Z9 14 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 8 PY 2011 VL 6 IS 2 AR e16653 DI 10.1371/journal.pone.0016653 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717WH UT WOS:000287077600012 PM 21347430 ER PT J AU Dietze, KK Zelinskyy, G Gibbert, K Schimmer, S Francois, S Myers, L Sparwasser, T Hasenkrug, KJ Dittmer, U AF Dietze, Kirsten K. Zelinskyy, Gennadiy Gibbert, Kathrin Schimmer, Simone Francois, Sandra Myers, Lara Sparwasser, Tim Hasenkrug, Kim J. Dittmer, Ulf TI Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8(+) T cells and reduces chronic retroviral set points SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytotoxic T cells; retrovirus; friend virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTIPLE INHIBITORY RECEPTORS; CHRONIC VIRAL-INFECTION; FRIEND-VIRUS; CUTTING EDGE; DISEASE PROGRESSION; IMMUNE ACTIVATION; HIV-INFECTION; IN-VITRO; CD4(+) AB Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8(+) T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8(+) T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases. C1 [Dietze, Kirsten K.; Zelinskyy, Gennadiy; Gibbert, Kathrin; Schimmer, Simone; Francois, Sandra; Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Univ Clin Essen, D-45122 Essen, Germany. [Myers, Lara; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Sparwasser, Tim] TWINCORE, Inst Infect Immunol, D-30625 Hannover, Germany. RP Dittmer, U (reprint author), Univ Duisburg Essen, Inst Virol, Univ Clin Essen, D-45122 Essen, Germany. EM ulf.dittmer@uni-due.de FU German Research Association (Deutsche Forschungsgemeinschaft) [B4]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the German Research Association (Deutsche Forschungsgemeinschaft), Transregio 60 project B4, and, in part, by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 45 TC 56 Z9 56 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2420 EP 2425 DI 10.1073/pnas.1015148108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500047 PM 21262821 ER PT J AU Wang, Q Chaerkady, R Wu, JA Hwang, HJ Papadopoulos, N Kopelovich, L Maitra, A Matthaei, H Eshleman, JR Hruban, RH Kinzler, KW Pandey, A Vogelstein, B AF Wang, Qing Chaerkady, Raghothama Wu, Jian Hwang, Hee Jung Papadopoulos, Nick Kopelovich, Levy Maitra, Anirban Matthaei, Hanno Eshleman, James R. Hruban, Ralph H. Kinzler, Kenneth W. Pandey, Akhilesh Vogelstein, Bert TI Mutant proteins as cancer-specific biomarkers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; proteomics; pancreatic cancer; genetic diagnosis; companion diagnostics ID MASS-SPECTROMETRY; SHOTGUN PROTEOMICS; PLASMA-PROTEINS; TRANSTHYRETIN; VARIANTS; REPRODUCIBILITY; QUANTIFICATION; CARDIOMYOPATHY; ELECTROSPRAY; QUANTITATION AB Cancer biomarkers are currently the subject of intense research because of their potential utility for diagnosis, prognosis, and targeted therapy. In theory, the gene products resulting from somatic mutations are the ultimate protein biomarkers, being not simply associated with tumors but actually responsible for tumorigenesis. We show here that the altered protein products resulting from somatic mutations can be identified directly and quantified by mass spectrometry. The peptides expressed from normal and mutant alleles were detected by selected reaction monitoring (SRM) of their product ions using a triple-quadrupole mass spectrometer. As a prototypical example of this approach, we demonstrated that it is possible to quantify the number and fraction of mutant Ras protein present in cancer cell lines. There were an average of 1.3 million molecules of Ras protein per cell, and the ratio of mutant to normal Ras proteins ranged from 0.49 to 5.6. Similarly, we found that mutant Ras proteins could be detected and quantified in clinical specimens such as colorectal and pancreatic tumor tissues as well as in premalignant pancreatic cyst fluids. In addition to answering basic questions about the relative levels of genetically abnormal proteins in tumors, this approach could prove useful for diagnostic applications. C1 [Chaerkady, Raghothama; Pandey, Akhilesh] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Maitra, Anirban; Matthaei, Hanno; Eshleman, James R.; Hruban, Ralph H.; Pandey, Akhilesh] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Maitra, Anirban; Matthaei, Hanno; Eshleman, James R.; Hruban, Ralph H.; Pandey, Akhilesh] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Pandey, Akhilesh] Johns Hopkins Med Inst, Dept Biol Chem, Baltimore, MD 21205 USA. [Wang, Qing; Wu, Jian; Hwang, Hee Jung; Papadopoulos, Nick; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. [Wang, Qing; Wu, Jian; Hwang, Hee Jung; Papadopoulos, Nick; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Chaerkady, Raghothama] Inst Bioinformat, Bangalore 560066, Karnataka, India. RP Pandey, A (reprint author), Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM pandey@jhmi.edu; bertvog@gmail.com RI Chaerkady, Raghothama/D-5718-2011; Pandey, Akhilesh/B-4127-2009; Papadopoulos, Nickolas/K-7272-2012 OI Pandey, Akhilesh/0000-0001-9943-6127; FU Lustgarten Foundation for Pancreatic Cancer Research, National Cancer Institute [NO1 CN-43302]; Department of Defense [W81XWH-06-1-0428]; Sol Goldman Center for Pancreatic Cancer Research; Virginia and D. K. Ludwig Fund for Cancer Research; Michael Rolfe Foundation; Joseph L. Rabinowitz Fund for Pancreatic Cancer Research; National Institutes of Health [CA62924, RR020839, CA130938, CA57345] FX This work was supported by the Lustgarten Foundation for Pancreatic Cancer Research, National Cancer Institute Contract NO1 CN-43302, Department of Defense Award W81XWH-06-1-0428, the Sol Goldman Center for Pancreatic Cancer Research, the Virginia and D. K. Ludwig Fund for Cancer Research, the Michael Rolfe Foundation, the Joseph L. Rabinowitz Fund for Pancreatic Cancer Research, and National Institutes of Health Grants CA62924, RR020839, CA130938, and CA57345. NR 37 TC 82 Z9 83 U1 1 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2444 EP 2449 DI 10.1073/pnas.1019203108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500051 PM 21248225 ER PT J AU Kannan, P Brimacombe, KR Kreisl, WC Liow, JS Zoghbi, SS Telu, S Zhang, Y Pike, VW Halldin, C Gottesman, MM Innis, RB Hall, MD AF Kannan, Pavitra Brimacombe, Kyle R. Kreisl, William C. Liow, Jeih-San Zoghbi, Sami S. Telu, Sanjay Zhang, Yi Pike, Victor W. Halldin, Christer Gottesman, Michael M. Innis, Robert B. Hall, Matthew D. TI Lysosomal trapping of a radiolabeled substrate of P-glycoprotein as a mechanism for signal amplification in PET SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ATP-binding cassette; efflux ID BLOOD-BRAIN-BARRIER; DRUG EFFLUX TRANSPORTERS; MULTIDRUG-RESISTANCE; CANCER-CELLS; IN-VIVO; RADIOTRACER; AGENTS; INHIBITOR; HUMANS; SPECT AB The radiotracer [C-11]N-desmethyl-loperamide (dLop) images the in vivo function of P-glycoprotein (P-gp), a transporter that blocks the entry of drugs that are substrates into brain. When P-gp is inhibited, [C-11]dLop, a potent opiate agonist, enters and becomes trapped in the brain. This trapping is beneficial from an imaging perspective, because it amplifies the PET signal, essentially by accumulating radioactivity over time. As we previously demonstrated that this trapping was not caused by binding to opiate receptors, we examined whether [C-11]dLop, a weak base, is ionically trapped in acidic lysosomes. To test this hypothesis, we measured [H-3]dLop accumulation in human cells by using lysosomotropics. Because the in vivo trapping of dLop was seen after P-gp inhibition, we also measured [H-3]dLop uptake in P-gp-expressing cells treated with the P-gp inhibitor tariquidar. All lysosomotropics decreased [H-3]dLop accumulation by at least 50%. In P-gp-expressing cells, tariquidar (and another P-gp inhibitor) surprisingly decreased [H-3]dLop uptake. Consequently, we measured [C-11]dLop uptake before and after tariquidar preadministration in lysosome-rich organs of P-gp KO mice and humans. After tariquidar pretreatment in both species, radioactivity uptake in these organs decreased by 35% to 40%. Our results indicate that dLop is trapped in lysosomes and that tariquidar competes with dLop for lysosomal accumulation in vitro and in vivo. Although tariquidar and dLop compete for lysosomal trapping in the periphery, such competition does not occur in brain because tariquidar has negligible entry into brain. In summary, tariquidar and [C-11]dLop can be used in combination to selectively measure the function of P-gp at the blood-brain barrier. C1 [Kannan, Pavitra; Kreisl, William C.; Liow, Jeih-San; Zoghbi, Sami S.; Telu, Sanjay; Zhang, Yi; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Kannan, Pavitra; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, SE-17176 Stockholm, Sweden. [Brimacombe, Kyle R.; Gottesman, Michael M.; Hall, Matthew D.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM robert.innis@nih.gov OI Kannan, Pavitra/0000-0002-9170-6062 FU National Institute of Mental Health [Z01-MH-002795-07, Z01-MH-002852-07]; National Cancer Institute [Z01-BC-005598] FX We thank Ms. Wenjie Xiao and Dr. Ellen Sidransky for assistance with hippocampal neuron cell culture, Eli Lilly and Co. for providing DCPQ, and Mr. George Leiman for editorial assistance. This research was supported by the Intramural Research Programs of the National Institute of Mental Health Projects Z01-MH-002795-07 and Z01-MH-002852-07 and National Cancer Institute Project Z01-BC-005598. NR 35 TC 25 Z9 26 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 8 PY 2011 VL 108 IS 6 BP 2593 EP 2598 DI 10.1073/pnas.1014641108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717YH UT WOS:000287084500076 PM 21262843 ER PT J AU Mason, CC Hanson, RL Ossowski, V Bian, L Baier, LJ Krakoff, J Bogardus, C AF Mason, Clinton C. Hanson, Robert L. Ossowski, Vicky Bian, Li Baier, Leslie J. Krakoff, Jonathan Bogardus, Clifton TI Bimodal distribution of RNA expression levels in human skeletal muscle tissue SO BMC GENOMICS LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLOBAL GENE-EXPRESSION; INSULIN-RESISTANCE; PIMA-INDIANS; OXIDATIVE-PHOSPHORYLATION; ASSOCIATION; GENOTYPE; DISEASE; OBESE AB Background: Many human diseases and phenotypes are related to RNA expression, levels of which are influenced by a wide spectrum of genetic and exposure-related factors. In a large genome-wide study of muscle tissue expression, we found that some genes exhibited a bimodal distribution of RNA expression, in contrast to what is usually assumed in studies of a single healthy tissue. As bimodality has classically been considered a hallmark of genetic control, we assessed the genome-wide prevalence, cause, and association of this phenomenon with diabetes-related phenotypes in skeletal muscle tissue from 225 healthy Pima Indians using exon array expression chips. Results: Two independent batches of microarrays were used for bimodal assessment and comparison. Of the 17,881 genes analyzed, eight (GSTM1, HLA-DRB1, ERAP2, HLA-DRB5, MAOA, ACTN3, NR4A2, and THNSL2) were found to have bimodal expression replicated in the separate batch groups, while 24 other genes had evidence of bimodality in only one group. Some bimodally expressed genes had modest associations with pre-diabetic phenotypes, of note ACTN3 with insulin resistance. Most of the other bimodal genes have been reported to be involved with various other diseases and characteristics. Association of expression with cis genetic variation in a subset of 149 individuals found all but one of the confirmed bimodal genes and nearly half of all potential ones to be highly significant expression quantitative trait loci (eQTL). The rare prevalence of these bimodally expressed genes found after controlling for batch effects was much lower than the prevalence reported in other studies. Additional validation in data from separate muscle expression studies confirmed the low prevalence of bimodality we observed. Conclusions: We conclude that the prevalence of bimodal gene expression is quite rare in healthy muscle tissue (<0.2%), and is much lower than limited reports from other studies. The major cause of these clearly bimodal expression patterns in homogeneous tissue appears to be cis-polymorphisms, indicating that such bimodal genes are, for the most part, eQTL. The high frequency of disease associations reported with these genes gives hope that this unique feature may identify or actually be an underlying factor responsible for disease development. C1 [Mason, Clinton C.; Hanson, Robert L.; Ossowski, Vicky; Bian, Li; Baier, Leslie J.; Krakoff, Jonathan; Bogardus, Clifton] NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. RP Mason, CC (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM masonclint@niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Kidney Diseases (NIDDK); American Diabetes Association [7-04-DCS-02] FX We gratefully thank the members and participants of the Gila River Indian Community, whose involvement made these findings possible. We acknowledge the additional technical help and data handling of Kristine Friesen and Sayuko Kobes as well as Drs. Paul Franks, Emilio Ortega, and Helen Looker. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Kidney Diseases (NIDDK), and by a DCS award to C.B. from the American Diabetes Association (#7-04-DCS-02). NR 49 TC 19 Z9 19 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD FEB 7 PY 2011 VL 12 AR 98 DI 10.1186/1471-2164-12-98 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 726AL UT WOS:000287688200001 PM 21299892 ER PT J AU Horton, JK Stefanick, DF Zeng, JY Carrozza, MJ Wilson, SH AF Horton, Julie K. Stefanick, Donna F. Zeng, Jennifer Y. Carrozza, Michael J. Wilson, Samuel H. TI Requirement for NBS1 in the S phase checkpoint response to DNA methylation combined with PARP inhibition SO DNA REPAIR LA English DT Article DE PARP inhibitor; Methyl methanesulfonate; NBS1; SMC1; Cell cycle; Chk1; Chk2 ID NIJMEGEN BREAKAGE SYNDROME; BASE EXCISION-REPAIR; POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY; DOUBLE-STRAND BREAKS; CELL-CYCLE; ATAXIA-TELANGIECTASIA; ATM; PROTEIN; DAMAGE; COMPLEX AB Treatment of PARP-1-expressing cells with the combination of a DNA methylating agent (MMS) and the PARP inhibitor 4-amino-1,8-naphthalimide (4-AN) leads to an ATR/Chk1-dependent S phase checkpoint and cell death by apoptosis. Activation of ATM/Chk2 is involved in sustaining the S phase checkpoint, and double strand break (DSB) accumulation was demonstrated. NBS1, part of the MRN complex that responds to DSBs, is known to modulate ATR- and ATM-dependent checkpoint responses to UV and IR, but a role in the response to PARP inhibition has not been addressed. Here we show that the S phase checkpoint observed 4-8h after MMS+ 4-AN treatment was absent in cells deficient in NBS1, but was present in NBS1-complemented (i.e., functionally wild-type) cells, indicating a critical role for NBS1 in this checkpoint response. NBS1 was phosphorylated in response to MMS +4-AN treatment, and this was partially ATR- and ATM-dependent, suggesting involvement of both upstream kinases. NBS1 expression had little effect on AIR-mediated phosphorylation of Chk1 and ATM-mediated phosphorylation of Chk2 in response to MMS + 4-AN. Phosphorylation of SMC1 was also observed in response to MMS+ 4-AN treatment. In the absence of ATM and NBS1, phosphorylation of SMC1 was weak, especially at early times after MMS + 4-AN treatment. In the absence of AIR activation, reduced SMC1 phosphorylation was seen over a 24h time course. These results suggested that both ATR and ATM phosphorylate SMC1 in response to MMS + 4-AN and that this phosphorylation is enhanced by phospho-NBS1. The loss of the MMS + 4-AN-induced S phase checkpoint in NBS1-deficient cells may be due to a reduced cellular level of the critical downstream effector, phospho-SMC1. Published by Elsevier B.V. C1 [Horton, Julie K.; Stefanick, Donna F.; Zeng, Jennifer Y.; Carrozza, Michael J.; 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,POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [ES050159] FX We thank Rebecca Childress for technical assistance, Bonnie Mesmer for editorial assistance, Lois Wyrick and William Beard for help with figure preparation, and Michelle Heacock for discussion and critical reading of the manuscript. We thank Dr. Malgorzata Zdzienicka for allowing us to use the NBS1 and NBS1 comp cells derived in her laboratory, and obtained by us from the laboratory of Dr. Priscilla Cooper. We thank Carl Bortner and the Flow Cytometry Center for assistance. This research was supported by Research Project Number ES050159 in the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 40 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD FEB 7 PY 2011 VL 10 IS 2 BP 225 EP 234 DI 10.1016/j.dnarep.2010.11.003 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 725VI UT WOS:000287673900012 PM 21130714 ER PT J AU Tatem, AJ Campiz, N Gething, PW Snow, RW Linard, C AF Tatem, Andrew J. Campiz, Nicholas Gething, Peter W. Snow, Robert W. Linard, Catherine TI The effects of spatial population dataset choice on estimates of population at risk of disease SO POPULATION HEALTH METRICS LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; GLOBAL DISTRIBUTION; AVIAN INFLUENZA; BOVINE TUBERCULOSIS; INFECTIOUS-DISEASES; POTENTIAL IMPACT; CONTROL PROGRAM; GREAT-BRITAIN; LARGE-SCALE; AFRICA AB Background: The spatial modeling of infectious disease distributions and dynamics is increasingly being undertaken for health services planning and disease control monitoring, implementation, and evaluation. Where risks are heterogeneous in space or dependent on person-to-person transmission, spatial data on human population distributions are required to estimate infectious disease risks, burdens, and dynamics. Several different modeled human population distribution datasets are available and widely used, but the disparities among them and the implications for enumerating disease burdens and populations at risk have not been considered systematically. Here, we quantify some of these effects using global estimates of populations at risk (PAR) of P. falciparum malaria as an example. Methods: The recent construction of a global map of P. falciparum malaria endemicity enabled the testing of different gridded population datasets for providing estimates of PAR by endemicity class. The estimated population numbers within each class were calculated for each country using four different global gridded human population datasets: GRUMP (similar to 1 km spatial resolution), LandScan (similar to 1 km), UNEP Global Population Databases (similar to 5 km), and GPW3 (similar to 5 km). More detailed assessments of PAR variation and accuracy were conducted for three African countries where census data were available at a higher administrative-unit level than used by any of the four gridded population datasets. Results: The estimates of PAR based on the datasets varied by more than 10 million people for some countries, even accounting for the fact that estimates of population totals made by different agencies are used to correct national totals in these datasets and can vary by more than 5% for many low-income countries. In many cases, these variations in PAR estimates comprised more than 10% of the total national population. The detailed country-level assessments suggested that none of the datasets was consistently more accurate than the others in estimating PAR. The sizes of such differences among modeled human populations were related to variations in the methods, input resolution, and date of the census data underlying each dataset. Data quality varied from country to country within the spatial population datasets. Conclusions: Detailed, highly spatially resolved human population data are an essential resource for planning health service delivery for disease control, for the spatial modeling of epidemics, and for decision-making processes related to public health. However, our results highlight that for the low-income regions of the world where disease burden is greatest, existing datasets display substantial variations in estimated population distributions, resulting in uncertainty in disease assessments that utilize them. Increased efforts are required to gather contemporary and spatially detailed demographic data to reduce this uncertainty, particularly in Africa, and to develop population distribution modeling methods that match the rigor, sophistication, and ability to handle uncertainty of contemporary disease mapping and spread modeling. In the meantime, studies that utilize a particular spatial population dataset need to acknowledge the uncertainties inherent within them and consider how the methods and data that comprise each will affect conclusions. C1 [Tatem, Andrew J.; Campiz, Nicholas] Univ Florida, Dept Geog, Gainesville, FL 32611 USA. [Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Gething, Peter W.; Linard, Catherine] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England. [Snow, Robert W.] Univ Oxford, Wellcome Trust Res Programme, KEMRI, Ctr Geog Med,Malaria Publ Hlth & Epidemiol Grp, Nairobi, Kenya. [Snow, Robert W.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, CCVTM, Oxford, England. [Linard, Catherine] Univ Libre Bruxelles, Brussels, Belgium. RP Tatem, AJ (reprint author), Univ Florida, Dept Geog, Gainesville, FL 32611 USA. EM andy.tatem@gmail.com OI Snow, Robert/0000-0003-3725-6088; Gething, Peter/0000-0001-6759-5449 FU Wellcome Trust [079080] NR 91 TC 26 Z9 26 U1 0 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-7954 J9 POPUL HEALTH METR JI Popul. Health Metr. PD FEB 7 PY 2011 VL 9 AR 4 DI 10.1186/1478-7954-9-4 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 891KP UT WOS:000300216000001 PM 21299885 ER PT J AU Scully, CG Karaboue, A Liu, WM Meyer, J Innominato, PF Chon, KH Gorbach, AM Levi, F AF Scully, Christopher G. Karaboue, Abdoulaye Liu, Wei-Min Meyer, Joseph Innominato, Pasquale F. Chon, Ki H. Gorbach, Alexander M. Levi, Francis TI Skin surface temperature rhythms as potential circadian biomarkers for personalized chronotherapeutics in cancer patients SO INTERFACE FOCUS LA English DT Article DE chronotherapeutics; circadian rhythm; biomarker; body temperature; cancer; personalized medicine ID METASTATIC COLORECTAL-CANCER; QUALITY-OF-LIFE; WAVELET ANALYSIS; CLOCKS; SLEEP; OXALIPLATIN; SURVIVAL; DELIVERY; DISEASE; 5-FLUOROURACIL AB Chronotherapeutics involve the administration of treatments according to circadian rhythms. Circadian timing of anti-cancer medications has been shown to improve treatment tolerability up to fivefold and double efficacy in experimental and clinical studies. However, the physiological and the molecular components of the circadian timing system (CTS), as well as gender, critically affect the success of a standardized chronotherapeutic schedule. In addition, a wrongly timed therapy or an excessive drug dose disrupts the CTS. Therefore, a non-invasive approach to accurately detect and monitor circadian rhythms is needed for a dynamic assessment of the CTS in order to personalize chronomodulated drug delivery schedule in cancer patients. Since core body temperature is a robust circadian biomarker, we recorded temperature at multiple locations on the skin of the upper chest and back of controls and cancer patients continuously. Variability in the circadian phase existed among patch locations in individual subjects over the course of 2-6 days, demonstrating the need to monitor multiple skin temperature locations to determine the precise circadian phase. Additionally, we observed that locations identified by infrared imaging as relatively cool had the largest 24 h temperature variations. Disruptions in skin temperature rhythms during treatment were found, pointing to the need to continually assess circadian timing and personalize chronotherapeutic schedules. C1 [Karaboue, Abdoulaye; Innominato, Pasquale F.; Levi, Francis] INSERM, UMRS776, F-94807 Villejuif, France. [Scully, Christopher G.; Liu, Wei-Min; Meyer, Joseph; Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Scully, Christopher G.; Chon, Ki H.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Karaboue, Abdoulaye; Innominato, Pasquale F.; Levi, Francis] Univ Paris 11, UMR S0776, F-91405 Orsay, France. [Innominato, Pasquale F.; Levi, Francis] Hop Paul Brousse, Dept Cancerol, Unite Chronotherapie, AP HP, F-94807 Villejuif, France. RP Levi, F (reprint author), INSERM, UMRS776, F-94807 Villejuif, France. EM francis.levi@inserm.fr FU European Commission through the Network of Excellence BIOSIM [LSHBCT-2004-005137]; Association pour la Recherche sur le Temps Biologique et la Chronotherapie (ARTBC International); Hopital Paul Brousse, Villejuif (France); National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (USA) FX This research was supported, in part, by the European Commission through the Network of Excellence BIOSIM (Biosimulation: a new tool for drug development; contract no. LSHBCT-2004-005137), the Association pour la Recherche sur le Temps Biologique et la Chronotherapie (ARTBC International), Hopital Paul Brousse, Villejuif (France) and the Intramural Research Programme of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (USA). The authors thank the subjects who participated in the study, Dr G. Kato, Dr H. Ackerman and A. Dementyev for insightful discussions and J. Bretes, FLIR Systems ATS France for the loan of infrared equipment and assistance for this study. NR 44 TC 11 Z9 12 U1 1 U2 3 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 2042-8898 J9 INTERFACE FOCUS JI Interface Focus PD FEB 6 PY 2011 VL 1 IS 1 BP 48 EP 60 DI 10.1098/rsfs.2010.0012 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 851LT UT WOS:000297272400007 PM 21544221 ER PT J AU Meltzer, JA Braun, AR AF Meltzer, Jed A. Braun, Allen R. TI An EEG-MEG dissociation between online syntactic comprehension and post hoc reanalysis SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE syntax; Broca's area; semantic; language; complexity; reversibility ID EVENT-RELATED FMRI; VERBAL WORKING-MEMORY; LANGUAGE COMPREHENSION; SENTENCE COMPREHENSION; BROCAS AREA; FREQUENCY; RESPONSES; APHASIA; MAGNETOENCEPHALOGRAPHY; LOCALIZATION AB Successful comprehension of syntactically complex sentences depends on online language comprehension mechanisms as well as reanalysis in working memory. To differentiate the neural substrates of these processes, we recorded electroencephalography and magnetoencephalography (MEG) during sentence-picture-matching in healthy subjects, assessing the effects of two difficulty factors: syntactic complexity (object-embedded vs. subject-embedded relative clauses) and semantic reversibility on neuronal oscillations during sentence presentation, and during a subsequent memory delay prior to picture onset. Synthetic Aperture magnetometry analysis of MEG showed that semantic reversibility induced left lateralized perisylvian power decreases in a broad frequency range, approximately 8-30 Hz. This effect followed the relative clause presentation and persisted throughout the remainder of the sentence and the subsequent memory delay period, shifting to a more frontal distribution during the delay. In contrast, syntactic complexity induced enhanced power decreases only during the delay period, in bilateral frontal and anterior temporal regions. These results indicate that detailed syntactic parsing of auditory language input may be augmented in the absence of alternative cues for thematic role assignment, as reflected by selective perisylvian engagement for reversible sentences, compared with irreversible sentences in which world knowledge constrains possible thematic roles. Furthermore, comprehension of complex syntax appears to depend on post hoc reanalysis in working memory implemented by frontal regions in both hemispheres. C1 [Meltzer, Jed A.; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. RP Meltzer, JA (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bldg 10,Room 5C-410, Bethesda, MD 20892 USA. EM jed.meltzer@aya.yale.edu OI Meltzer, Jed/0000-0002-4301-1901 FU NIH, National Institute on Deafness and Other Communication Disorders FX We gratefully acknowledge technical assistance from Joe McArdle, Suraji Wagage, Elizabeth Rawson, Judy Mitchell-Francis, Tom Holroyd, and Fred Carver. This study was funded through the NIH Intramural Research Program, in the National Institute on Deafness and Other Communication Disorders. NR 56 TC 5 Z9 5 U1 3 U2 12 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD FEB 4 PY 2011 VL 5 AR 10 DI 10.3389/fnhum.2011.00010 PG 15 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 748VK UT WOS:000289420700001 PM 21331355 ER PT J AU Charles, BA Shriner, D Doumatey, A Chen, GJ Zhou, J Huang, HX Herbert, A Gerry, NP Christman, MF Adeyemo, A Rotimi, CN AF Charles, Bashira A. Shriner, Daniel Doumatey, Ayo Chen, Guanjie Zhou, Jie Huang, Hanxia Herbert, Alan Gerry, Norman P. Christman, Michael F. Adeyemo, Adebowale Rotimi, Charles N. TI A genome-wide association study of serum uric acid in African Americans SO BMC MEDICAL GENOMICS LA English DT Article ID PROGRESSIVE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; ESSENTIAL-HYPERTENSION; METABOLIC SYNDROME; RISK-FACTOR; SLC2A9; URATE; HYPERURICEMIA; INCREASES; EVOLUTION AB Background: Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry (EA) have reported associations between serum uric acid levels (SUAL) and specific genomic loci. The purposes of this study were: 1) to replicate major signals reported in EA populations; and 2) to use the weak LD pattern in African ancestry population to better localize (fine-map) reported loci and 3) to explore the identification of novel findings cognizant of the moderate sample size. Methods: African American (AA) participants (n = 1,017) from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix (R) Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs) were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification. Results: Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 x 10(-9) to 1.38 x 10(-9)). Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples. Conclusions: The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA populations GWAS signals in African-ancestry populations with weaker linkage disequilibrium. C1 [Charles, Bashira A.; Shriner, Daniel; Doumatey, Ayo; Chen, Guanjie; Zhou, Jie; Huang, Hanxia; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Herbert, Alan] Boston Univ, Dept Genet & Genom, Boston, MA 02118 USA. [Gerry, Norman P.; Christman, Michael F.] Coriell Inst Med Res, Camden, NJ 08103 USA. RP Rotimi, CN (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. EM rotomic@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU NIGMS/MBRS/SCORE [S06GM008016-320107, S06GM008016-380111]; National Center for Research Resources (NCRR) a component of the National Institutes of Health (NIH) [2M01RR010284]; Coriell Institute for Biomedical Sciences; National Human Genome Research Institute; National Institutes of Health, in the Center for Research in Genomics and Global Health [Z01HG200362] FX The study was supported by grants S06GM008016-320107 to CR and S06GM008016-380111 to AA, both from the NIGMS/MBRS/SCORE Program. Participant enrollment was carried out at the Howard University General Clinical Research Center (GCRC), which is supported by grant number 2M01RR010284 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Additional support was provided by the Coriell Institute for Biomedical Sciences. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, in the Center for Research in Genomics and Global Health (Z01HG200362). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 44 Z9 51 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD FEB 4 PY 2011 VL 4 AR 17 DI 10.1186/1755-8794-4-17 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 726WT UT WOS:000287758200001 PM 21294900 ER PT J AU Hanover, JA AF Hanover, John A. TI A Versatile Sugar Transferase Makes the Cut SO CELL LA English DT Editorial Material ID CELL-PROLIFERATION; HCF-1 AB The nutrient sensor O-GlcNAc transferase modifies proteins with the O-GlcNAc moiety. In this issue, Capotosti et al. (2011) reveal that O-GlcNAc transferase not only glycosylates the cell-cycle regulator host cell factor 1 but activates it through proteolytic cleavage, providing a surprising link between metabolism and epigenetic regulation of the cell cycle. C1 NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM jah@helix.nih.gov NR 10 TC 5 Z9 5 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 4 PY 2011 VL 144 IS 3 BP 321 EP 323 DI 10.1016/j.cell.2011.01.025 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 716MK UT WOS:000286973100003 PM 21295693 ER PT J AU Wong, YF Kopp, JB Roberts, C Scambler, PJ Abe, Y Rankin, AC Dutt, N Hendry, BM Xu, QH AF Wong, Yuen Fei Kopp, Jeffrey B. Roberts, Catherine Scambler, Peter J. Abe, Yoshifusa Rankin, Alexandra C. Dutt, Neelanjana Hendry, Bruce M. Xu, Qihe TI Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System SO PLOS ONE LA English DT Article ID VITAMIN-A-DEFICIENCY; VACUOLAR H+-ATPASE; DEPENDENT ACTIVATION; NEPHRON DEVELOPMENT; MOLECULAR-CLONING; GENE-EXPRESSION; KIDNEY; RECEPTORS; RATS; ORGANOGENESIS AB Background: Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in postnatal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys. Methodology/Principal Findings: RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, beta-galactosidase. Double immunostaining was performed for beta-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules. Conclusions/Significance: Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the collecting duct system. C1 [Wong, Yuen Fei; Rankin, Alexandra C.; Hendry, Bruce M.; Xu, Qihe] Kings Coll London, Dept Renal Med, London WC2R 2LS, England. [Dutt, Neelanjana] Kings Coll Hosp London, Dept Histopathol, London, England. [Kopp, Jeffrey B.; Abe, Yoshifusa] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Roberts, Catherine; Scambler, Peter J.] Inst Child Hlth, Mol Med Unit, London, England. RP Wong, YF (reprint author), Kings Coll London, Dept Renal Med, London WC2R 2LS, England. EM qihe.xu@kcl.ac.uk RI Scambler, Peter/C-4998-2008; OI Scambler, Peter/0000-0002-1487-4628; Kopp, Jeffrey/0000-0001-9052-186X FU Kidney Research United Kingdom project [RP29/2/06]; National Institutes of Health [Z01 DK043308] FX This work was supported by a Kidney Research United Kingdom project grant (RP29/2/06) awarded to QX and BMH and a National Institutes of Health Intramural Program grant (Z01 DK043308) to JBK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 7 Z9 7 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 4 PY 2011 VL 6 IS 2 AR e16770 DI 10.1371/journal.pone.0016770 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717IN UT WOS:000287037000020 PM 21326615 ER PT J AU Oakley, RH Cidlowski, JA AF Oakley, Robert H. Cidlowski, John A. TI Cellular Processing of the Glucocorticoid Receptor Gene and Protein: New Mechanisms for Generating Tissue-specific Actions of Glucocorticoids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PRE-MESSENGER-RNA; BETA-ISOFORM; TRANSCRIPTIONAL ACTIVITY; BINDING DOMAIN; EXPRESSION; CELLS; PHOSPHORYLATION; ALPHA; TRANSACTIVATION; REPRESSION AB Glucocorticoids regulate numerous physiological processes and are mainstays in the treatment of inflammation, autoimmune disease, and cancer. The traditional view that glucocorticoids act through a single glucocorticoid receptor (GR) protein has changed in recent years with the discovery of a large cohort of receptor subtypes arising from alternative processing of the GR gene. These isoforms differ in their expression, gene regulatory, and functional profiles. Post-translational modification of these proteins further expands GR diversity. Here, we discuss the origin and molecular properties of the GR isoforms and their contribution to the sensitivity and specificity of the glucocorticoid response. C1 [Oakley, Robert H.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU NIEHS, National Institutes of Health FX This work was supported, in whole or in part, by the NIEHS Intramural Research Program of the National Institutes of Health. This is the fourth article in the Thematic Minireview Series on Nuclear Receptors in Biology and Diseases. This minireview will be reprinted in the 2011 Minireview Compendium, which will be available in January, 2012. NR 98 TC 129 Z9 135 U1 1 U2 18 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 4 PY 2011 VL 286 IS 5 BP 3177 EP 3184 DI 10.1074/jbc.R110.179325 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712GE UT WOS:000286653200001 PM 21149445 ER PT J AU Van Itallie, CM Mitic, LL Anderson, JM AF Van Itallie, Christina M. Mitic, Laura L. Anderson, James M. TI Claudin-2 Forms Homodimers and Is a Component of a High Molecular Weight Protein Complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLUE NATIVE ELECTROPHORESIS; TIGHT-JUNCTION LOCALIZATION; BIOCHEMICAL-CHARACTERIZATION; PLASMA-MEMBRANE; OCCLUDIN; BARRIER; PALMITOYLATION; SOLUBILIZATION; PERMEABILITY; TRICELLULIN AB Tight junctions are multiprotein complexes that form the fundamental physiologic and anatomic barrier between epithelial and endothelial cells, yet little information is available about their molecular organization. To begin to understand how the transmembrane proteins of the tight junction are organized into multiprotein complexes, we used blue native-PAGE (BN-PAGE) and cross-linking techniques to identify complexes extracted from MDCK II cells and mouse liver. In nonionic detergent extracts from MDCK II cells, the tight junction integral membrane protein claudin-2 was preferentially isolated as a homodimer, whereas claudin-4 was monomeric. Analysis of the interactions between chimeras of claudin-2 and -4 are consistent with the transmembrane domains of claudin-2 being responsible for dimerization, and mutational analysis followed by cross-linking indicated that the second transmembrane domains were arranged in close proximity in homodimers. BN-PAGE of mouse liver membrane identified a relatively discrete high molecular weight complex containing at least claudin-1, claudin-2, and occludin; the difference in the protein complex sizes between cultured cells and tissues may reflect differences in tight junction protein or lipid composition or post-translational modifications. Our results suggest that BN-PAGE may be a useful tool in understanding tight junction structure. C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Mitic, Laura L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. [Anderson, James M.] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. RP Van Itallie, CM (reprint author), NHLBI, NIH, Bldg 50,Rm 4530, Bethesda, MD 20892 USA. EM Christina.VanItallie@nih.gov FU National Institutes of Health [RO1 DK45134] FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 DK45134. NR 44 TC 30 Z9 31 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 4 PY 2011 VL 286 IS 5 BP 3442 EP 3450 DI 10.1074/jbc.M110.195578 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712GE UT WOS:000286653200030 PM 21098027 ER PT J AU Kodama, S Negishi, M AF Kodama, Susumu Negishi, Masahiko TI Pregnane X Receptor PXR Activates the GADD45 beta Gene, Eliciting the p38 MAPK Signal and Cell Migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; NUCLEAR RECEPTORS; CROSS-TALK; TGF-BETA; HEPATOCELLULAR-CARCINOMA; LIVER-REGENERATION; KINASE ACTIVATION; PROTEIN-KINASE; EXPRESSION; CAR AB Pregnane X receptor (PXR) was originally characterized as a transcription factor that induces hepatic drug metabolism by activating cytochrome P450 genes. Here we have now demonstrated a novel function of PXR, that of eliciting p38 mitogen-activated protein kinase (MAPK) phosphorylation for cell migration. Upon xenobiotic activation of ectopic human PXR, human hepatocellular carcinoma HepG2 cells were found to exhibit increased phosphorylation of p38 MAPK and to subsequently change morphology and migrate. p38 MAPK was responsible for the regulation of these morphological changes and cell migration because the p38 MAPK inhibitor SB239063 repressed both. Prior to this phosphorylation, PXR directly activated the early response GADD45 beta gene by binding to a distal direct repeat 4 site of the GADD45 beta promoter. Ectopic expression of GADD45 beta increased p38 MAPK phosphorylation, whereas siRNA knockdown of GADD45 beta decreased the PXR-induced p38 MAPK phosphorylation, confirming that GADD45 beta can regulate PXR-induced p38 MAPK phosphorylation in HepG2 cells. These results indicate that PXR activates the GADD45 beta gene, increasing p38 MAPK phosphorylation, and leading HepG2 cells to change morphology and migrate. The GADD45 beta gene is a direct target for PXR, eliciting cell signals to regulate various cellular functions. C1 [Kodama, Susumu; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU National Institutes of Health through NIEHS [Z01ES1005-01] FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program Grant Z01ES1005-01 through the NIEHS. NR 37 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 4 PY 2011 VL 286 IS 5 BP 3570 EP 3578 DI 10.1074/jbc.M110.179812 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712GE UT WOS:000286653200041 PM 21127053 ER PT J AU Ammosova, T Yedavalli, VRK Niu, XM Jerebtsova, M Van Eynde, A Beullens, M Bollen, M Jeang, KT Nekhai, S AF Ammosova, Tatiana Yedavalli, Venkat R. K. Niu, Xiaomei Jerebtsova, Marina Van Eynde, Aleyde Beullens, Monique Bollen, Mathieu Jeang, Kuan-Teh Nekhai, Sergei TI Expression of a Protein Phosphatase 1 Inhibitor, cdNIPP1, Increases CDK9 Threonine 186 Phosphorylation and Inhibits HIV-1 Transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; LONG-TERMINAL REPEAT; P-TEFB; TAT TRANSACTIVATION; CYCLIN T1; 7SK SNRNA; KINASE; VIRUS; ACETYLATION; ELONGATION AB CDK9/cyclin T1, a key enzyme in HIV-1 transcription, is negatively regulated by 7SK RNA and the HEXIM1 protein. Dephosphorylation of CDK9 on Thr(186) by protein phosphatase 1 (PP1) in stress-induced cells or by protein phosphatase M1A in normally growing cells activates CDK9. Our previous studies showed that HIV-1 Tat protein binds to PP1 through the Tat Q(35)VCF(38) sequence, which is similar to the PP1-binding RVXF motif and that this interaction facilitates HIV-1 transcription. In the present study, we analyzed the effect of expression of the central domain of nuclear inhibitor of PP1 (cdNIPP1) in an engineered cell line and also when cdNIPP1 was expressed as part of HIV-1 pNL4-3 in place of nef. Stable expression of cdNIPP1 increased CDK9 phosphorylation on Thr(186) and the association of CDK9 with 7SK RNA. The stable expression of cdNIPP1 disrupted the interaction of Tat and PP1 and inhibited HIV-1 transcription. Expression of cdNIPP1 as a part of the HIV-1 genome inhibited HIV-1 replication. Our study provides a proof-of-concept for the future development of PP1-targeting compounds as inhibitors of HIV-1 replication. C1 [Ammosova, Tatiana; Niu, Xiaomei; Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20001 USA. [Yedavalli, Venkat R. K.; Jeang, Kuan-Teh] NIAID, Natl Inst Hlth, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20817 USA. [Jerebtsova, Marina] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Van Eynde, Aleyde; Beullens, Monique; Bollen, Mathieu] Catholic Univ Louvain, Dept Mol Cell Biol, B-3000 Louvain, Belgium. RP Nekhai, S (reprint author), Howard Univ, Ctr Sickle Cell Dis, 1840 7th St NW,HURB1,Suite 202, Washington, DC 20001 USA. EM snekhai@howard.edu RI Jeang, Kuan-Teh/A-2424-2008 FU National Institutes of Health Research by NHLBI [2 R25 HL003679-12]; Office of Research on Minority by National Institute for General Medical Sciences [1SC1GM082325-03]; Howard University; Research Centers in Minority Institutions Program, Division of Research Infrastructure, National Center for Research Resources, National Institutes of Health [RCMI-NIH 2G12RR003048-22] FX This work was supported by National Institutes of Health Research Grant 2 R25 HL003679-12 funded by the NHLBI. This work was also supported by the Office of Research on Minority, Grant 1SC1GM082325-03, funded by the National Institute for General Medical Sciences; by a Howard University Seed Grant (to S. N.); and by Grant RCMI-NIH 2G12RR003048-22 from the Research Centers in Minority Institutions Program, Division of Research Infrastructure, National Center for Research Resources, National Institutes of Health. NR 41 TC 22 Z9 22 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 4 PY 2011 VL 286 IS 5 BP 3798 EP 3804 DI 10.1074/jbc.M110.196493 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 712GE UT WOS:000286653200061 PM 21098020 ER PT J AU Beisel, CL Storz, G AF Beisel, Chase L. Storz, Gisela TI The Base-Pairing RNA Spot 42 Participates in a Multioutput Feedforward Loop to Help Enact Catabolite Repression in Escherichia coli SO MOLECULAR CELL LA English DT Article ID REGULATING GENE-EXPRESSION; NETWORK MOTIFS; NONCODING RNA; PROTEIN; CRP; IDENTIFICATION; TRANSCRIPTION; SPOT-42-RNA; METABOLISM; MOLECULE AB Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base-pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multioutput feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base-pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression. C1 [Beisel, Chase L.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Beisel, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM beiselcl@mail.nih.gov; storz@helix.nih.gov RI Beisel, Chase/D-4823-2015; OI Beisel, Chase/0000-0003-0650-9943; Storz, Gisela/0000-0001-6698-1241 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank E. Fozo, R. Fuchs, S. Gottesman, M. Goulian, E. Hobbs, B. Janson, M. Thomason, and L. Waters for their comments on this manuscript and S. Durand for technical assistance. P. Mandin kindly provided the E. coli strain PM1205 and the plasmid pSpot42, and N. Majdalani kindly provided the E. coli strain NM525. Work carried out in the laboratory of G.S. is supported by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. C.L.B. is a Gordon and Betty Moore Foundation Fellow of the Life Sciences Research Foundation. NR 41 TC 89 Z9 90 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD FEB 4 PY 2011 VL 41 IS 3 BP 286 EP 297 DI 10.1016/j.molcel.2010.12.027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 722UM UT WOS:000287460500007 PM 21292161 ER PT J AU Lee, J Romero, R Xu, Y Kim, JS Topping, V Yoo, W Kusanovic, JP Chaiworapongsa, T Hassan, SS Yoon, BH Kim, CJ AF Lee, JoonHo Romero, Roberto Xu, Yi Kim, Jung-Sun Topping, Vanessa Yoo, Wonsuk Pedro Kusanovic, Juan Chaiworapongsa, Tinnakorn Hassan, Sonia S. Yoon, Bo Hyun Kim, Chong Jai TI A Signature of Maternal Anti-Fetal Rejection in Spontaneous Preterm Birth: Chronic Chorioamnionitis, Anti-Human Leukocyte Antigen Antibodies, and C4d SO PLOS ONE LA English DT Article ID NEONATAL ALLOIMMUNE THROMBOCYTOPENIA; SOLID-ORGAN TRANSPLANTATION; RENAL-ALLOGRAFT REJECTION; CLINICAL-SIGNIFICANCE; HLA ANTIBODIES; RECURRENT ABORTION; MEDIATED REJECTION; HUMORAL IMMUNITY; UNKNOWN ETIOLOGY; HUMAN-PREGNANCY AB Background: Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth. Methods and Findings: This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29-28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60-21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42-114.66) were associated with preterm labor and delivery. Conclusions: A major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions. C1 [Lee, JoonHo; Romero, Roberto; Xu, Yi; Topping, Vanessa; Pedro Kusanovic, Juan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Lee, JoonHo; Romero, Roberto; Xu, Yi; Topping, Vanessa; Pedro Kusanovic, Juan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA. [Romero, Roberto; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Yoo, Wonsuk] Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. [Pedro Kusanovic, Juan] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Santiago, Chile. [Pedro Kusanovic, Juan] Pontificia Univ Catolica Chile, Sch Med, Dept Obstet & Gynecol, Santiago, Chile. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. RP Lee, J (reprint author), NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA FX This work was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 40 Z9 41 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 4 PY 2011 VL 6 IS 2 AR e16806 DI 10.1371/journal.pone.0016806 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 717IN UT WOS:000287037000022 PM 21326865 ER PT J AU Collins, FS AF Collins, Francis S. TI Faces of the Genome SO SCIENCE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 14 Z9 15 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 4 PY 2011 VL 331 IS 6017 BP 546 EP 546 DI 10.1126/science.1202894 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 715ZE UT WOS:000286933600037 PM 21292963 ER PT J AU Colbourne, JK Pfrender, ME Gilbert, D Thomas, WK Tucker, A Oakley, TH Tokishita, S Aerts, A Arnold, GJ Basu, MK Bauer, DJ Caceres, CE Carmel, L Casola, C Choi, JH Detter, JC Dong, QF Dusheyko, S Eads, BD Frohlich, T Geiler-Samerotte, KA Gerlach, D Hatcher, P Jogdeo, S Krijgsveld, J Kriventseva, EV Kultz, D Laforsch, C Lindquist, E Lopez, J Manak, JR Muller, J Pangilinan, J Patwardhan, RP Pitluck, S Pritham, EJ Rechtsteiner, A Rho, M Rogozin, IB Sakarya, O Salamov, A Schaack, S Shapiro, H Shiga, Y Skalitzky, C Smith, Z Souvorov, A Sung, W Tang, ZJ Tsuchiya, D Tu, H Vos, H Wang, M Wolf, YI Yamagata, H Yamada, T Ye, YZ Shaw, JR Andrews, J Crease, TJ Tang, HX Lucas, SM Robertson, HM Bork, P Koonin, EV Zdobnov, EM Grigoriev, IV Lynch, M Boore, JL AF Colbourne, John K. Pfrender, Michael E. Gilbert, Donald Thomas, W. Kelley Tucker, Abraham Oakley, Todd H. Tokishita, Shinichi Aerts, Andrea Arnold, Georg J. Basu, Malay Kumar Bauer, Darren J. Caceres, Carla E. Carmel, Liran Casola, Claudio Choi, Jeong-Hyeon Detter, John C. Dong, Qunfeng Dusheyko, Serge Eads, Brian D. Froehlich, Thomas Geiler-Samerotte, Kerry A. Gerlach, Daniel Hatcher, Phil Jogdeo, Sanjuro Krijgsveld, Jeroen Kriventseva, Evgenia V. Kueltz, Dietmar Laforsch, Christian Lindquist, Erika Lopez, Jacqueline Manak, J. Robert Muller, Jean Pangilinan, Jasmyn Patwardhan, Rupali P. Pitluck, Samuel Pritham, Ellen J. Rechtsteiner, Andreas Rho, Mina Rogozin, Igor B. Sakarya, Onur Salamov, Asaf Schaack, Sarah Shapiro, Harris Shiga, Yasuhiro Skalitzky, Courtney Smith, Zachary Souvorov, Alexander Sung, Way Tang, Zuojian Tsuchiya, Dai Tu, Hank Vos, Harmjan Wang, Mei Wolf, Yuri I. Yamagata, Hideo Yamada, Takuji Ye, Yuzhen Shaw, Joseph R. Andrews, Justen Crease, Teresa J. Tang, Haixu Lucas, Susan M. Robertson, Hugh M. Bork, Peer Koonin, Eugene V. Zdobnov, Evgeny M. Grigoriev, Igor V. Lynch, Michael Boore, Jeffrey L. TI The Ecoresponsive Genome of Daphnia pulex SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; DUPLICATE GENES; EXPRESSION; MAGNA; EVOLUTION AB We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges. C1 [Colbourne, John K.; Gilbert, Donald; Choi, Jeong-Hyeon; Dong, Qunfeng; Eads, Brian D.; Lopez, Jacqueline; Patwardhan, Rupali P.; Rechtsteiner, Andreas; Smith, Zachary; Tang, Zuojian; Tsuchiya, Dai; Shaw, Joseph R.; Andrews, Justen; Tang, Haixu] Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA. [Pfrender, Michael E.] Utah State Univ, Dept Biol, Logan, UT 84322 USA. [Gilbert, Donald; Tucker, Abraham; Casola, Claudio; Eads, Brian D.; Schaack, Sarah; Andrews, Justen; Lynch, Michael] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Thomas, W. Kelley; Tucker, Abraham; Bauer, Darren J.; Hatcher, Phil; Jogdeo, Sanjuro; Sung, Way] Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. [Oakley, Todd H.; Geiler-Samerotte, Kerry A.; Sakarya, Onur] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA. [Tokishita, Shinichi; Shiga, Yasuhiro; Yamagata, Hideo] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Div Environm Sci, Lab Environm & Mol Biol, Tokyo 1920392, Japan. [Aerts, Andrea; Detter, John C.; Dusheyko, Serge; Lindquist, Erika; Pangilinan, Jasmyn; Pitluck, Samuel; Salamov, Asaf; Shapiro, Harris; Tu, Hank; Wang, Mei; Lucas, Susan M.; Grigoriev, Igor V.; Boore, Jeffrey L.] JGI, Dept Energy, Walnut Creek, CA 94598 USA. [Arnold, Georg J.; Froehlich, Thomas] Univ Munich, Gene Ctr, Lab Funct Genome Anal LAFUGA, D-82152 Planegg Martinsried, Germany. [Basu, Malay Kumar; Carmel, Liran; Rogozin, Igor B.; Souvorov, Alexander; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Caceres, Carla E.] Univ Illinois, Sch Integrat Biol, Urbana, IL 61801 USA. [Gerlach, Daniel; Kriventseva, Evgenia V.; Zdobnov, Evgeny M.] Univ Geneva, Sch Med, CH-1211 Geneva, Switzerland. [Gerlach, Daniel; Kriventseva, Evgenia V.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Krijgsveld, Jeroen; Vos, Harmjan] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote Grp, NL-3584 CA Utrecht, Netherlands. [Krijgsveld, Jeroen; Vos, Harmjan] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CA Utrecht, Netherlands. [Krijgsveld, Jeroen; Vos, Harmjan] Univ Utrecht, Netherlands Prote Ctr, NL-3584 CA Utrecht, Netherlands. [Kueltz, Dietmar] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. [Laforsch, Christian] Univ Munich, Dept Biol 2, D-82152 Planegg Martinsried, Germany. [Laforsch, Christian] Univ Munich, GeoBio Ctr Munich, D-82152 Planegg Martinsried, Germany. [Manak, J. Robert; Skalitzky, Courtney] Roche NimbleGen Inc, Gene Express, Madison, WI 53719 USA. [Muller, Jean; Yamada, Takuji; Bork, Peer] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany. [Pritham, Ellen J.; Schaack, Sarah] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA. [Rho, Mina; Ye, Yuzhen; Tang, Haixu] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47408 USA. [Shaw, Joseph R.] Indiana Univ, Sch Publ & Environm Affairs, Bloomington, IN 47405 USA. [Crease, Teresa J.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada. [Robertson, Hugh M.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. [Zdobnov, Evgeny M.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Boore, Jeffrey L.] Genome Project Solut, Hercules, CA 94547 USA. [Boore, Jeffrey L.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. RP Colbourne, JK (reprint author), Indiana Univ, Ctr Genom & Bioinformat, 915 E 3rd St, Bloomington, IN 47405 USA. EM jcolbour@indiana.edu RI Choi, Jeong-Hyeon/E-3084-2010; Krijgsveld, Jeroen/F-5974-2011; Zdobnov, Evgeny/K-1133-2012; Bork, Peer/F-1813-2013; Choi, Justin/F-8792-2014; Colbourne, John/L-7748-2014; Crease, Teresa/E-2932-2015; Frohlich, Thomas/C-6735-2011; OI Bork, Peer/0000-0002-2627-833X; Colbourne, John/0000-0002-6966-2972; Crease, Teresa/0000-0001-8074-8024; Oakley, Todd/0000-0002-4478-915X; Gerlach, Daniel/0000-0001-9338-3765; Muller, Jean/0000-0002-7682-559X FU Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]; Daphnia Genomics Consortium (DGC); NSF [0221837, 0328516]; NIH [R24GM07827401]; METACyt Initiative of Indiana University; Lilly Endowment, Inc. FX We thank M. Frazer (JGI), P. Cherbas (CGB), R. Green, and T. Takova (Roche NimbleGen, Inc.). The work conducted by the U.S. Department of Energy Joint Genome Institute (JGI) was supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-05CH11231 and in collaboration with the Daphnia Genomics Consortium (DGC). This project was also supported by NSF grants 0221837 and 0328516 and NIH grant R24GM07827401. Coordination infrastructure for the DGC is provided by the Center for Genomics and Bioinformatics (CGB) at Indiana University, which is supported in part by the METACyt Initiative of Indiana University, funded in part through a major grant from the Lilly Endowment, Inc. Additional contributions and acknowledgments are provided in the SOM. Our work benefits from and contributes to the Daphnia Genomics Consortium. Daphnia pulex genome assembly version 1.1 and annotations are deposited at DNA Data Bank of Japan, European Molecular Biology Laboratory, and GenBank databases under accession ACJG00000000. ESTs (FE274839 to FE425949) are in GenBank. Microarray platforms GPL11200 to GPL11201 and data GSE25823 are deposited at National Center for Biotechnology Information Gene Expression Omnibus database. NR 24 TC 515 Z9 535 U1 31 U2 244 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 4 PY 2011 VL 331 IS 6017 BP 555 EP 561 DI 10.1126/science.1197761 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 715ZE UT WOS:000286933600046 PM 21292972 ER PT J AU Chakrabarty, S Snyder, JT Shen, JJ Azmi, H Hu, PQ Chen, QA Ragheb, JA AF Chakrabarty, Sagarika Snyder, James T. Shen, Jijia Azmi, Hooman Hu, Paul Q. Chen, Qian Ragheb, Jack A. TI Human CD14(hi) monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression SO BLOOD LA English DT Article ID ACTIVATED T-CELLS; GERMINAL CENTER FORMATION; IL-2 MESSENGER-RNA; RESTING B-CELLS; CD40-CD40 LIGAND; ANTIGEN PRESENTATION; HUMORAL IMMUNITY; CD154 EXPRESSION; GAMMA PRODUCTION; IGM SYNDROME AB CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation. (Blood. 2011; 117(5): 1585-1594) C1 [Chakrabarty, Sagarika; Snyder, James T.; Shen, Jijia; Azmi, Hooman; Hu, Paul Q.; Chen, Qian; Ragheb, Jack A.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ragheb, Jack A.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biol Prod,Ctr Drug Evaluat & Res,Dept Hlth &, Bethesda, MD 20014 USA. RP Ragheb, JA (reprint author), 29 Lincoln Dr,Bldg 29B,Rm 4G13,HFD 122, Bethesda, MD 20892 USA. EM jr50b@nih.gov FU Department of Health and Human Services FX This work was supported by the Department of Health and Human Services (intramural funding). NR 68 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 3 PY 2011 VL 117 IS 5 BP 1585 EP 1594 DI 10.1182/blood-2008-01-130252 PG 10 WC Hematology SC Hematology GA 715WV UT WOS:000286925500025 PM 20634374 ER PT J AU Roberts, DD AF Roberts, David D. TI Activate Rac to rescue new vessels SO BLOOD LA English DT Editorial Material ID NITRIC-OXIDE SYNTHASE; ANGIOGENESIS C1 Natl Canc Inst, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 3 PY 2011 VL 117 IS 5 BP 1444 EP 1445 DI 10.1182/blood-2010-11-317198 PG 2 WC Hematology SC Hematology GA 715WV UT WOS:000286925500007 PM 21292786 ER PT J AU Mansoor, A Pittaluga, S Beck, PL Wilson, WH Ferry, JA Jaffe, ES AF Mansoor, Adnan Pittaluga, Stefania Beck, Paul L. Wilson, Wyndham H. Ferry, Judith A. Jaffe, Elaine S. TI NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; DELTA T-CELL; CELIAC-DISEASE; ADAPTIVE IMMUNITY; MUCOSAL; PROLIFERATION; SKIN; LYMPHOCYTES; DISORDER; INNATE AB Intestinal T-cell and natural killer (NK)-cell lymphomas are clinically aggressive and can be challenging to diagnose in small endoscopic biopsies. We describe 8 patients in whom atypical NK-cell lymphoproliferative lesions mimicked NK-or T-cell lymphoma. The patients (2 men; 6 women; ages 27-68 years) presented with vague gastrointestinal symptoms with lesions involving stomach, duodenum, small intestine, and colon. At endoscopy, the lesions exhibited superficial ulceration, edema, and hemorrhage. Biopsies revealed a mucosal infiltrate of atypical cells with an NK-cell phenotype (CD56(+)/TIA-1(+)/Granzyme B(+)/cCD3(+)), which displaced but did not invade the glandular epithelium. Epstein-Barr virus-encoded RNA in situ hybridization was negative, and T-cell receptor-gamma gene rearrangement showed no evidence of a clonal process. Based on an original diagnosis of lymphoma, 3 patients received aggressive chemotherapy followed by autologous bone marrow transplantation in 2. Five patients were followed without treatment. However, no patient developed progressive disease or died of lymphoma (median follow-up, 30 months). Repeat endoscopies in 6 of 8 patients showed persistence or recurrence of superficial gastrointestinal lesions. This unique entity mimics intestinal and NK-/T-cell lymphomas on endoscopic biopsies and can result in erroneous diagnosis, leading to aggressive chemotherapy. We propose the term "NK-cell enteropathy" for this syndrome of as yet unknown etiology. (Blood. 2011; 117(5): 1447-1452) C1 [Mansoor, Adnan] Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada. [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Beck, Paul L.] Univ Calgary, Div Gastroenterol, Calgary, AB, Canada. [Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Jaffe, ES (reprint author), NIH, Hematopathol Sect, Pathol Lab, 10 Ctr Dr,Bldg 10,Rm 2B42, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute FX This work was supported by the intramural research budget of the Center for Cancer Research, National Cancer Institute. NR 39 TC 42 Z9 45 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 3 PY 2011 VL 117 IS 5 BP 1447 EP 1452 DI 10.1182/blood-2010-08-302737 PG 6 WC Hematology SC Hematology GA 715WV UT WOS:000286925500009 PM 20966166 ER PT J AU Larochelle, A Savona, M Wiggins, M Anderson, S Ichwan, B Keyvanfar, K Morrison, SJ Dunbar, CE AF Larochelle, Andre Savona, Michael Wiggins, Michael Anderson, Stephanie Ichwan, Brian Keyvanfar, Keyvan Morrison, Sean J. Dunbar, Cynthia E. TI Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers SO BLOOD LA English DT Article ID CORD BLOOD-CELLS; LONG-TERM; BONE-MARROW; MULTIPOTENT PROGENITORS; CD34(+)CD38(-) CELLS; EXPRESSION; MICE; RECEPTORS; CD34; TRANSPLANTATION AB Various combinations of antibodies directed to cell surface markers have been used to isolate human and rhesus macaque hematopoietic stem cells (HSCs). These protocols result in poor enrichment or require multiple complex steps. Recently, a simple phenotype for HSCs based on cell surface markers from the signaling lymphocyte activation molecule (SLAM) family of receptors has been reported in the mouse. We examined the possibility of using the SLAM markers to facilitate the isolation of highly enriched populations of HSCs in humans and rhesus macaques. We isolated SLAM (CD150(+)CD48(-)) and nonSLAM (not CD150(+)CD48(-)) cells from human umbilical cord blood CD34(+) cells as well as from human and rhesus macaque mobilized peripheral blood CD34(+) cells and compared their ability to form colonies in vitro and reconstitute immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 gamma c receptor(null), NSG) mice. We found that the CD34(+) SLAM population contributed equally or less to colony formation in vitro and to long-term reconstitution in NSG mice compared with the CD34(+) non-SLAM population. Thus, SLAM family markers do not permit the same degree of HSC enrichment in humans and rhesus macaques as in mice. (Blood. 2011; 117(5): 1550-1554) C1 [Larochelle, Andre; Ichwan, Brian; Keyvanfar, Keyvan; Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Savona, Michael; Morrison, Sean J.] Univ Michigan, Howard Hughes Med Inst, Dept Internal Med, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA. [Savona, Michael; Morrison, Sean J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Savona, Michael; Wiggins, Michael; Anderson, Stephanie] San Antonio Mil Med Ctr, Dept Hematol & Oncol, San Antonio, TX USA. RP Dunbar, CE (reprint author), NHLBI, NIH, Bldg 10 CRC,Rm 4-5132,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU University of Michigan Flow Cytometry Core Facility; National Heart, Lung and Blood Institute of the National Institutes of Health; Howard Hughes Medical Institute; Michigan Institute for Clinical and Health Research Pilot FX The authors thank D. Stroncek, J. Procter, M. Sabatino, and S. Leitman for providing human CD34+ cells; Sue Ellen Frodigh and Quyen Chau for processing UCB samples; R. Donahue, M. Metzger, and A. Krouse for mobilization and apheresis of rhesus macaques; D. Adams, M. White, and the University of Michigan Flow Cytometry Core Facility for support; and the animal core facility staff at the National Institutes of Health and the University of Michigan for excellent animal care.; This work was supported in part by the intramural research program of the National Heart, Lung and Blood Institute of the National Institutes of Health and in part by the Howard Hughes Medical Institute and by a Michigan Institute for Clinical and Health Research Pilot Grant. NR 26 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 3 PY 2011 VL 117 IS 5 BP 1550 EP 1554 DI 10.1182/blood-2009-03-212803 PG 5 WC Hematology SC Hematology GA 715WV UT WOS:000286925500021 PM 21163926 ER PT J AU Goldin, LR Landgren, O Kristinsson, SY Bjorkholm, M Paltiel, O AF Goldin, Lynn R. Landgren, Ola Kristinsson, Sigurdur Y. Bjorkholm, Magnus Paltiel, Ora TI Infection in infancy and subsequent risk of developing lymphoma in children and young adults SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; CANCER; AGENTS AB There is evidence that certain infections and autoimmunity predispose to the development of non-Hodgkin lymphomas (NHLs). A previous study reported that hospitalization for infections in infancy led to an increased risk of NHL. By using population-based registries in Sweden, we compared the rate of hospitalization for infections in infancy between lymphoma cases and matched controls for patients born since 1964. A history of infection was associated with a significantly increased risk of aggressive B-cell lymphomas (odds ratio 2.1, 95% confidence interval 1.11-4.04, P = .02). The specific infections involved were respiratory and intestinal. No effects were observed among cases of Hodgkin lymphoma. This association could result from the infection, its treatment, or could be a surrogate marker for underlying immune defects. Further studies are needed to determine whether this association is present among NHL occurring in older adults and if improved survival of patients with immune defects has contributed to the secular increases in incidence of NHLs. (Blood. 2011; 117(5): 1670-1672) C1 [Goldin, Lynn R.] NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Paltiel, Ora] Hadassah Hebrew Univ Hosp, Dept Hematol, Jerusalem, Israel. [Paltiel, Ora] Hadassah Hebrew Univ Hosp, Sch Publ Hlth, Jerusalem, Israel. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU National Cancer Institute, National Institutes of Health; Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health and by grants from the Swedish Cancer Society, Stockholm County Council, and the Karolinska Institutet Foundations. NR 16 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 3 PY 2011 VL 117 IS 5 BP 1670 EP 1672 DI 10.1182/blood-2010-09-306274 PG 3 WC Hematology SC Hematology GA 715WV UT WOS:000286925500034 PM 21127175 ER PT J AU Koh, KK Quon, MJ Han, SH Lee, Y Park, JB Kim, SJ Koh, Y Shin, EK AF Koh, Kwang Kon Quon, Michael J. Han, Seung Hwan Lee, Yonghee Park, Jeong Beom Kim, Soo Jin Koh, Yesl Shin, Eak Kyun TI Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE HMG-CoA reductase inhibitor; Calcium channel blocker; Endothelial function; Adiponectin; Insulin resistance; Hypertension ID ASSESSING INSULIN SENSITIVITY; RANDOMIZED CONTROLLED-TRIAL; ENDOTHELIAL FUNCTION; METABOLIC PARAMETERS; THERAPEUTIC INTERVENTIONS; RECIPROCAL RELATIONSHIPS; CARDIOVASCULAR-DISEASE; GLUCOSE-METABOLISM; ADIPONECTIN LEVELS; OXIDATIVE STRESS AB Background: We hypothesized that atorvastatin combined with amlodipine has additive beneficial vascular and metabolic effects that are superior to monotherapy in patients with hypertension. Methods: Forty-two patients were given atorvastatin 20 mg/day and placebo, atorvastatin 20 mg/day and amlodipine 10 mg/day, or amlodipine 10 mg/day and placebo during each 2-month treatment period of a randomized, single-blind, placebo-controlled cross-over trial with two 2-month washout periods. Results: Atorvastatin combined with amlodipine or amlodipine alone significantly reduced blood pressure to a greater extent than atorvastatin alone (all P<0.001 by ANOVA). Atorvastatin combined with amlodipine significantly reduced plasma malondialdehyde and improved flow-mediated dilation to a greater extent than atorvastatin or amlodipine alone (all P<0.001 by ANOVA). Atorvastatin therapy significantly increased insulin levels (P=0.004) and decreased plasma adiponectin levels (P=0.016) and insulin sensitivity (determined by QUICKI; P=0.026) relative to baseline measurements. Amlodipine therapy significantly decreased insulin levels (P=0.001) and increased adiponectin levels (P<0.001) and insulin sensitivity (P=0.003) relative to baseline measurements. Atorvastatin combined with amlodipine therapy significantly increased adiponectin levels (P<0.001) and insulin sensitivity (P=0.034) relative to baseline measurements. Effects of all three therapeutic arms on adiponectin levels and insulin sensitivity were statistically significant (P<0.001 by ANOVA). Conclusions: Atorvastatin combined with amlodipine therapy improves endothelial function and increases adiponectin levels and insulin sensitivity to a greater extent than monotherapy with either drug in hypertensive patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon; Han, Seung Hwan; Park, Jeong Beom; Kim, Soo Jin; Shin, Eak Kyun] Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit Cardiol, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. [Koh, Yesl] Northwestern Univ, Weinberg Coll Arts & Sci, Evanston, IL USA. [Lee, Yonghee] Univ Seoul, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit Cardiol, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Gachon University Gil Medical Center [2005-1, 2006-1] FX This study was partly supported by grants from established investigator award (2005-1, 2006-1), Gachon University Gil Medical Center and not supported by any pharmaceutical companies. NR 42 TC 18 Z9 18 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD FEB 3 PY 2011 VL 146 IS 3 BP 319 EP 325 DI 10.1016/j.ijcard.2009.07.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709SA UT WOS:000286460500011 PM 19651449 ER PT J AU Koh, KK Quon, MJ Sakuma, I Lee, Y Lim, S Han, SH Shin, EK AF Koh, Kwang Kon Quon, Michael J. Sakuma, Ichiro Lee, Yonghee Lim, Soo Han, Seung Hwan Shin, Eak Kyun TI Effects of simvastatin therapy on circulating adipocytokines in patients with hypercholesterolemia SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Statins; Adipocytokines; Insulin resistance; Metabolic syndrome ID CAUSES INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; METABOLIC PARAMETERS; ADIPONECTIN LEVELS; PRAVASTATIN; INTERVENTIONS; ATORVASTATIN; SENSITIVITY; INHIBITION C1 [Koh, Kwang Kon] Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Sakuma, Ichiro] Hokko Mem Clin, Sapporo, Hokkaido, Japan. [Lee, Yonghee] Univ Seoul, Dept Stat, Seoul, South Korea. [Lim, Soo] Seoul Natl Univ, Coll Med, Seoul Natl Univ Bundang Hosp, Div Endocrinol, Songnam, South Korea. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 19 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD FEB 3 PY 2011 VL 146 IS 3 BP 434 EP 437 DI 10.1016/j.ijcard.2010.10.103 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709SA UT WOS:000286460500039 PM 21095021 ER PT J AU Wang, W Petralia, RS Takamiya, K Xia, J Li, YQ Huganir, RL Tao, YX Yaster, M AF Wang, Wei Petralia, Ronald S. Takamiya, Kogo Xia, Jun Li, Yun-Qing Huganir, Richard L. Tao, Yuan-Xiang Yaster, Myron TI Preserved acute pain and impaired neuropathic pain in mice lacking protein interacting with C Kinase 1 SO MOLECULAR PAIN LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; PERIPHERAL-NERVE INJURY; CORD DORSAL-HORN; SPINAL-CORD; PDZ DOMAIN; PERSISTENT PAIN; EXCITATORY SYNAPSES; INFLAMMATORY PAIN; GANGLION NEURONS; PICK1 INTERACTS AB Protein interacting with C Kinase 1 (PICK1), a PDZ domain-containing scaffolding protein, interacts with multiple different proteins in the mammalian nervous system and is believed to play important roles in diverse physiological and pathological conditions. In this study, we report that PICK1 is expressed in neurons of the dorsal root ganglion (DRG) and spinal cord dorsal horn, two major pain-related regions. PICK1 was present in approximately 29.7% of DRG neurons, most of which were small-less than 750 mu m(2) in cross-sectional area. Some of these PICK1-positive cells co-labeled with isolectin B4 or calcitonin-gene-related peptide. In the dorsal horn, PICK1 immunoreactivity was concentrated in the superficial dorsal horn, where it was prominent in the postsynaptic density, axons, and dendrites. Targeted disruption of PICK1 gene did not affect basal paw withdrawal responses to acute noxious thermal and mechanical stimuli or locomotor reflex activity, but it completely blocked the induction of peripheral nerve injury-induced mechanical and thermal pain hypersensitivities. PICK1 appears to be required for peripheral nerve injury-induced neuropathic pain development and to be a potential biochemical target for treating this disorder. C1 [Wang, Wei; Li, Yun-Qing; Tao, Yuan-Xiang; Yaster, Myron] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Wang, Wei; Li, Yun-Qing] Fourth Mil Med Univ, Dept Anat Histol & Embryol, KK Leung Brain Res Ctr, Xian 710032, Peoples R China. [Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Takamiya, Kogo; Xia, Jun; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Xia, Jun] Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. RP Tao, YX (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. EM ytau@jhmi.edu; myaster1@jhmi.edu RI Xia, Jun/C-7234-2009; OI Xia, Jun/0000-0001-9308-2188 FU National Institutes of Health [NS058886]; Blaustein Pain Research Fund; Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund; Brain Science Institute at the Johns Hopkins University; Department of Anesthesiology; NIDCD FX This work was supported by National Institutes of Health (NS058886), the Blaustein Pain Research Fund, Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund, and Brain Science Institute at the Johns Hopkins University (Y.X.T.), Department of Anesthesiology (M.Y.), and the Intramural Research Program of NIDCD (R.S.P.). We thank Mrs. Ya-Xian Wang for help with the immunogold experiments. The authors thank Claire Levine, MS, for editorial assistance. NR 39 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD FEB 3 PY 2011 VL 7 AR 11 DI 10.1186/1744-8069-7-11 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 720SJ UT WOS:000287300500001 PM 21291534 ER PT J AU Kosti, O Goldman, L Saha, DT Orden, RA Pollock, AJ Madej, HL Hsing, AW Chu, LW Lynch, JH Goldman, R AF Kosti, O. Goldman, L. Saha, D. T. Orden, R. A. Pollock, A. J. Madej, H. L. Hsing, A. W. Chu, L. W. Lynch, J. H. Goldman, R. TI DNA damage phenotype and prostate cancer risk SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Prostate cancer; Benign prostatic hyperplasia; Comet assay; DNA repair; Case-control study ID DOUBLE-STRAND BREAKS; EXCISION-REPAIR CAPACITY; COMET ASSAY; MUTAGEN SENSITIVITY; IONIZING-RADIATION; LUNG-CANCER; BLOOD CELLS; WHOLE-BLOOD; BODY-MASS; INSTABILITY AB The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%) and faster second phase (27% vs. 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles = 3.24, 95% CI = 0.98-10.66, p-trend = 0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals. (C) 2010 Elsevier B.V. All rights reserved. C1 [Goldman, R.] Georgetown Univ, Dept Oncol, LCC, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Hsing, A. W.; Chu, L. W.] NCI, Div Canc Epidembl & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Lynch, J. H.] Georgetown Univ, Dept Urol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Goldman, R (reprint author), Georgetown Univ, Dept Oncol, LCC, Lombardi Comprehens Canc Ctr, S183,3800 Reservoir Rd NW, Washington, DC 20057 USA. EM rg26@georgetown.edu RI Pollock, Allison/E-5367-2016 OI Pollock, Allison/0000-0003-2361-4390 FU National Institutes of Health National Center for Research Resources [M01RR-023942]; Department of Defense [PC081609]; NCI [R01 CA115625]; National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA FX We wish to thank Dr Borges, Department of Urology, Veterans Administration Medical Center, for facilitating recruitment at the VA hospital and Dr Dritschilo, Radiation Medicine, for recruitment at the Georgetown University Hospital. The Clinical Molecular Epidemiology Shared Resources at the Lombardi Comprehensive Cancer Center provided services for questionnaire data entry. This project was conducted through the General Clinical Research Center at Georgetown University and supported by the National Institutes of Health National Center for Research Resources, grant M01RR-023942. This study was supported in part by the Department of Defense Prostate Cancer Research Program grant PC081609 and NCI grant R01 CA115625 awarded to RG and Intramural Research Program of the National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA (AWH and LWC). NR 41 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 3 PY 2011 VL 719 IS 1-2 BP 41 EP 46 DI 10.1016/j.mrgentox.2010.11.005 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 717NY UT WOS:000287055900007 PM 21095241 ER PT J AU Gupta, N Stopfer, M AF Gupta, Nitin Stopfer, Mark TI Negative results need airing too SO NATURE LA English DT Letter C1 [Gupta, Nitin; Stopfer, Mark] NICHD, NIH, Bethesda, MD 20892 USA. RP Gupta, N (reprint author), NICHD, NIH, Bethesda, MD 20892 USA. EM nitin.gupta2@nih.gov NR 0 TC 9 Z9 9 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2011 VL 470 IS 7332 BP 39 EP 39 DI 10.1038/470039a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 715LQ UT WOS:000286886400018 PM 21293361 ER PT J AU Diep, CQ Ma, DD Deo, RC Holm, TM Naylor, RW Arora, N Wingert, RA Bollig, F Djordjevic, G Lichman, B Zhu, H Ikenaga, T Ono, F Englert, C Cowan, CA Hukriede, NA Handin, RI Davidson, AJ AF Diep, Cuong Q. Ma, Dongdong Deo, Rahul C. Holm, Teresa M. Naylor, Richard W. Arora, Natasha Wingert, Rebecca A. Bollig, Frank Djordjevic, Gordana Lichman, Benjamin Zhu, Hao Ikenaga, Takanori Ono, Fumihito Englert, Christoph Cowan, Chad A. Hukriede, Neil A. Handin, Robert I. Davidson, Alan J. TI Identification of adult nephron progenitors capable of kidney regeneration in zebrafish SO NATURE LA English DT Article ID TRANSGENIC ZEBRAFISH; GENES; MORPHOGENESIS; PRONEPHROS; REPORTER AB Loss of kidney function underlies many renal diseases(1). Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones(2,3). By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury(4,5), providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies. C1 [Diep, Cuong Q.; Ma, Dongdong; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ma, Dongdong; Handin, Robert I.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Bollig, Frank; Englert, Christoph] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany. [Zhu, Hao] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ikenaga, Takanori; Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Englert, Christoph] Friedrich Schiller Univ, D-07743 Jena, Germany. [Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hukriede, Neil A.] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA 15260 USA. [Diep, Cuong Q.; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Arora, Natasha; Wingert, Rebecca A.; Djordjevic, Gordana; Lichman, Benjamin; Cowan, Chad A.; Davidson, Alan J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Davidson, AJ (reprint author), Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1142, New Zealand. EM a.davidson@auckland.ac.nz OI Ikenaga, Takanori/0000-0002-7321-9703; Zhu, Hao/0000-0002-8417-9698; Lichman, Benjamin/0000-0002-0033-1120 FU Harvard Stem Cell Institute; American Society of Nephrology; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [P50DK074030] FX We thank E. C. Liao for help with suturing, and R. Ethier and L. Gyr for zebrafish care. A.J.D. was supported by the Harvard Stem Cell Institute, the American Society of Nephrology and the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (P50DK074030). NR 23 TC 105 Z9 108 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2011 VL 470 IS 7332 BP 95 EP U108 DI 10.1038/nature09669 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 715LQ UT WOS:000286886400041 PM 21270795 ER PT J AU Ngo, VN Young, RM Schmitz, R Jhavar, S Xiao, WM Lim, KH Kohlhammer, H Xu, WH Yang, YD Zhao, H Shaffer, AL Romesser, P Wright, G Powell, J Rosenwald, A Muller-Hermelink, HK Ott, G Gascoyne, RD Connors, JM Rimsza, LM Campo, E Jaffe, ES Delabie, J Smeland, EB Fisher, RI Braziel, RM Tubbs, RR Cook, JR Weisenburger, DD Chan, WC Staudt, LM AF Ngo, Vu N. Young, Ryan M. Schmitz, Roland Jhavar, Sameer Xiao, Wenming Lim, Kian-Huat Kohlhammer, Holger Xu, Weihong Yang, Yandan Zhao, Hong Shaffer, Arthur L. Romesser, Paul Wright, George Powell, John Rosenwald, Andreas Muller-Hermelink, Hans Konrad Ott, German Gascoyne, Randy D. Connors, Joseph M. Rimsza, Lisa M. Campo, Elias Jaffe, Elaine S. Delabie, Jan Smeland, Erlend B. Fisher, Richard I. Braziel, Rita M. Tubbs, Raymond R. Cook, J. R. Weisenburger, Denny D. Chan, Wing C. Staudt, Louis M. TI Oncogenically active MYD88 mutations in human lymphoma SO NATURE LA English DT Article ID B-CELL LYMPHOMA; NF-KAPPA-B; TNFAIP3 A20; GENE; INHIBITORS; SIGNATURES; PATHWAYS; SURVIVAL; SUBTYPES; KINASE AB The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy(1). Constitutive nuclear factor (NF)-kappa B and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling(2,3), and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-kappa B signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-beta. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations. C1 [Ngo, Vu N.; Young, Ryan M.; Schmitz, Roland; Jhavar, Sameer; Lim, Kian-Huat; Kohlhammer, Holger; Xu, Weihong; Yang, Yandan; Zhao, Hong; Shaffer, Arthur L.; Romesser, Paul; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Romesser, Paul] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Wright, George] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA. [Rosenwald, Andreas; Muller-Hermelink, Hans Konrad] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, D-70376 Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. [Rimsza, Lisa M.; Fisher, Richard I.; Braziel, Rita M.; Tubbs, Raymond R.; Cook, J. R.] SW Oncol Grp, Ann Arbor, MI 48106 USA. [Campo, Elias] Univ Barcelona, Hosp Clin, E-08036 Barcelona, Spain. [Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Delabie, Jan] Univ Hosp, Rikshosp, Pathol Clin, N-0310 Oslo, Norway. [Smeland, Erlend B.] Univ Hosp, Rikshosp, Inst Canc Res, N-0310 Oslo, Norway. [Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, N-0310 Oslo, Norway. [Fisher, Richard I.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Tubbs, Raymond R.; Cook, J. R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA. [Weisenburger, Denny D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE 68198 USA. [Weisenburger, Denny D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE 68198 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Romesser, Paul/0000-0001-8268-2903; Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301; Lim, Kian-Huat/0000-0002-2766-200X; Campo, elias/0000-0001-9850-9793 FU NIH, National Cancer Institute, Center for Cancer Research; NCI SPECS [UO1-CA 114778]; Foundation for NIH; Lymphoma/Leukemia Molecular Profiling Project (LLMPP); Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe) FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, an NCI SPECS grant (UO1-CA 114778), and by the Foundation for NIH, through a gift from the Richard A. Lauderbaugh Memorial Fund. This study was conducted under the auspices of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP). R.S. is supported by the Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe). P.R. was an HHMI-NIH Research Scholar. This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Maryland (http://biowulf.nih.gov). We thank D. Staudt for discussions, K. Meyer for help with the GEO submission, and X. Li for IRAK1 plasmids. We are grateful to B. Tran and the Center for Cancer Research Sequencing Facility for implementation of next generation RNA sequencing. NR 27 TC 496 Z9 509 U1 10 U2 81 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 3 PY 2011 VL 470 IS 7332 BP 115 EP U133 DI 10.1038/nature09671 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 715LQ UT WOS:000286886400045 PM 21179087 ER PT J AU Christian, KM Miracle, AD Wellman, CL Nakazawa, K AF Christian, K. M. Miracle, A. D. Wellman, C. L. Nakazawa, K. TI CHRONIC STRESS-INDUCED HIPPOCAMPAL DENDRITIC RETRACTION REQUIRES CA3 NMDA RECEPTORS SO NEUROSCIENCE LA English DT Article DE HPA axis; CA3; NMDA receptor; chronic stress; dendritic retraction; Golgi staining ID CHRONIC PSYCHOSOCIAL STRESS; MEDIAL PREFRONTAL CORTEX; PYRAMIDAL NEURONS; APICAL DENDRITES; RAT HIPPOCAMPUS; INDUCED ATROPHY; SPATIAL MEMORY; PLASTICITY; MORPHOLOGY; BRAIN AB Chronic stress induces dendritic retraction in the hippocampal CA3 subregion, but the mechanisms responsible for this retraction and its impact on neural circuitry are not well understood. To determine the role of NMDA (N-methyl-D-aspartic acid) receptor (NMDAR)-mediated signaling in this process, we compared the effects of chronic immobilization stress (CIS) on hippocampal dendritic morphology, hypothalamic-pituitary-adrenal (HPA) axis activation, and anxiety-related and hippocampus-dependent behaviors, in transgenic male mice in which the NMDAR had been selectively deleted in CA3 pyramidal cells and in non-mutant littermates. We found that CIS exposure for 10 consecutive days in non-mutant mice effectively induces HPA axis activation and dendritic retraction of CA3 short-shaft pyramidal neurons, but not CA3 long-shaft pyramidal neurons, suggesting a differential cellular stress response in this region. Dendritic reorganization of short-shaft neurons occurred throughout the longitudinal axis of the hippocampus and, in particular, in the ventral pole of this structure. We also observed a robust retraction of dendrites in dorsal CA1 pyramidal neurons in the non-mutant C57BL/6 mouse strain. Strikingly, chronic stress-induced dendritic retraction was not evident in any of the neurons in either CA3 or CA1 in the mutant mice that had a functional lack of NMDARs restricted to CA3 pyramidal neurons. Interestingly, the prevention of dendritic retraction in the mutant mice had a minimal effect on HPA axis activation and behavioral alterations that were induced by chronic stress. These data support a role for NMDAR-dependent glutamatergic signaling in CA3 in the cell-type specific induction of dendritic retraction in two hippocampal subregions following chronic stress. Published by Elsevier Ltd on behalf of IBRO. C1 [Christian, K. M.; Miracle, A. D.; Nakazawa, K.] NIMH, Unit Genet Cognit & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wellman, C. L.] Indiana Univ, Dept Psychologol & Brain Sci, Bloomington, IN 47405 USA. [Wellman, C. L.] Indiana Univ, Program Neurosci, Bloomington, IN 47405 USA. RP Nakazawa, K (reprint author), NIMH, Unit Genet Cognit & Behav, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM nakazawk@mail.nih.gov RI Nakazawa, Kazutoshi/J-6195-2015 OI Nakazawa, Kazutoshi/0000-0001-5699-9093 FU National Institute of Mental Health FX This work was supported by the Intramural Research Programs of the National Institute of Mental Health. We thank Drs. Cameron HA, Chen G, Young WS, and Holmes A for critical reading of the earlier version of the manuscript. NR 42 TC 46 Z9 49 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB 3 PY 2011 VL 174 BP 26 EP 36 DI 10.1016/j.neuroscience.2010.11.033 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 711AL UT WOS:000286558000003 PM 21108993 ER PT J AU St Hilaire, C Ziegler, SG Markello, TC Brusco, A Groden, C Gill, F Carlson-Donohoe, H Lederman, RJ Chen, MY Yang, D Siegenthaler, MP Arduino, C Mancini, C Freudenthal, B Stanescu, HC Zdebik, AA Chaganti, RK Nussbaum, RL Kleta, R Gahl, WA Boehm, M AF St Hilaire, Cynthia Ziegler, Shira G. Markello, Thomas C. Brusco, Alfredo Groden, Catherine Gill, Fred Carlson-Donohoe, Hannah Lederman, Robert J. Chen, Marcus Y. Yang, Dan Siegenthaler, Michael P. Arduino, Carlo Mancini, Cecilia Freudenthal, Bernard Stanescu, Horia C. Zdebik, Anselm A. Chaganti, R. Krishna Nussbaum, Robert L. Kleta, Robert Gahl, William A. Boehm, Manfred TI NT5E Mutations and Arterial Calcifications SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONSPECIFIC ALKALINE-PHOSPHATASE; VASCULAR CALCIFICATION; MINERALIZATION; ADENOSINE; INFANCY; ENPP1; CELLS AB BACKGROUND Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. METHODS We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. RESULTS We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C -> A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G -> A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C -> A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients' cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification. CONCLUSIONS We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. C1 [Markello, Thomas C.; Groden, Catherine; Gahl, William A.] NHGRI, NIH Undiagnosed Dis Program, NIH, Bethesda, MD 20892 USA. [St Hilaire, Cynthia; Lederman, Robert J.; Chen, Marcus Y.; Yang, Dan; Siegenthaler, Michael P.; Boehm, Manfred] NHLBI, NIH, Bethesda, MD 20892 USA. [Gill, Fred] NIH, Off Rare Dis Res, Ctr Clin, Bethesda, MD 20892 USA. [Brusco, Alfredo; Arduino, Carlo; Mancini, Cecilia] Direz Univ Med Genet, Azienda Osped Univ San Giovanni Battista, Turin, Italy. [Brusco, Alfredo; Arduino, Carlo; Mancini, Cecilia] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Freudenthal, Bernard; Stanescu, Horia C.; Zdebik, Anselm A.; Kleta, Robert] UCL, Dept Med, London WC1E 6BT, England. [Freudenthal, Bernard; Stanescu, Horia C.; Zdebik, Anselm A.; Kleta, Robert] UCL, Dept Physiol, London WC1E 6BT, England. [Chaganti, R. Krishna] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Gahl, WA (reprint author), NHGRI, NIH Undiagnosed Dis Program, NIH, 10 Ctr Dr,Bldg 10,Rm 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov RI St. Hilaire, Cynthia/I-4713-2014; Brusco, Alfredo/A-1811-2013; OI Brusco, Alfredo/0000-0002-8318-7231; St. Hilaire, Cynthia/0000-0003-1871-6915 FU National Human Genome Research Institute (NHGRI); National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health FX Supported by the Intramural Research Programs of the National Human Genome Research Institute (NHGRI) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. NR 29 TC 143 Z9 147 U1 1 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 3 PY 2011 VL 364 IS 5 BP 432 EP 442 DI 10.1056/NEJMoa0912923 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 715LL UT WOS:000286885900008 PM 21288095 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Equipoise and the Dilemma of Randomized Clinical Trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; ESTROGEN PLUS PROGESTIN; THERAPEUTIC MISCONCEPTION; 1ST-LINE CHEMOTHERAPY; RESPONSE RATES; BREAST-CANCER; SURVIVAL; BENEFIT; MELANOMA; ETHICS C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 35 TC 78 Z9 78 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 3 PY 2011 VL 364 IS 5 BP 476 EP 480 DI 10.1056/NEJMsb1011301 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 715LL UT WOS:000286885900016 PM 21288100 ER PT J AU Shad, MU Bidesi, AS Chen, LA Thomas, BP Ernst, M Rao, U AF Shad, Mujeeb U. Bidesi, Anup S. Chen, Li-Ann Thomas, Binu P. Ernst, Monique Rao, Uma TI Neurobiology of decision-making in adolescents SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Neurobiology; Choice; Selection; Adolescents; Decision-making; Rewards ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; FAMILY HISTORY METHOD; ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; NEURAL RESPONSES; CHOICE SELECTION; PUBERTAL CHANGES; MONETARY REWARD; DORSAL STRIATUM AB The study examined the relationship between risk-taking behavior during selection of monetary rewards and activations in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), brain regions that are associated with decision-making. Thirty-three adolescents with no personal or family history of any psychiatric illness were administered the Wheel of Fortune (WOF) task using a functional magnetic resonance imaging protocol. The WOF is a computerized two-choice, probabilistic monetary reward task. Selection of a reward, particularly a low-probability/high-magnitude reward choice, induced greater activations in dorsal ACC, ventrolateral OFC and mPFC than the control condition. Although similar findings have been reported by earlier studies, the results from this study were not impacted by reaction times and expected values and persisted even after controlling for sociodemographic factors. Post hoc analysis revealed greater activation of ACC and mPFC in response to selection of rewards of larger magnitude than those of smaller magnitude when the probability of reward was maintained constant. Adolescents with greater frequency of high-risk behavior (defined as low-probability/high-magnitude reward choice) had lower activation of ACC, OFC and mPFC than those who engaged in this behavior less frequently. These findings suggest individual differences in prefrontal cortical function with regards to decision-making process in adolescents. (C) 2010 Elsevier B.V. All rights reserved. C1 [Shad, Mujeeb U.] Univ Texas Hlth Sci Ctr, Houston, TX 77054 USA. [Bidesi, Anup S.; Chen, Li-Ann; Thomas, Binu P.; Rao, Uma] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Shad, MU (reprint author), Univ Texas Hlth Sci Ctr, 1941 East Rd,BBSB 3118, Houston, TX 77054 USA. EM mujeeb.u.shad@uth.tmc.edu FU Eli Lilly; National Institutes of Health [DA14037, DA15131, DA17804, DA17805, MH62464, MH68391] FX The primary author has received funding from Eli Lilly for other research. The other authors have no conflicts of interest.; This work was supported, in part, by grants from the National Institutes of Health (DA14037, DA15131, DA17804, DA17805, MH62464 and MH68391), and the Sarah M. and Charles. NR 83 TC 10 Z9 11 U1 4 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 2 PY 2011 VL 217 IS 1 BP 67 EP 76 DI 10.1016/j.bbr.2010.09.033 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 710TK UT WOS:000286539700010 PM 20933020 ER PT J AU Barakat, M Doyon, J Debas, K Vandewalle, G Morin, A Poirier, G Martin, N Lafortune, M Karni, A Ungerleider, LG Benali, H Carrier, J AF Barakat, M. Doyon, J. Debas, K. Vandewalle, G. Morin, A. Poirier, G. Martin, N. Lafortune, M. Karni, A. Ungerleider, L. G. Benali, H. Carrier, J. TI Fast and slow spindle involvement in the consolidation of a new motor sequence SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Motor sequence learning; Memory consolidation; Sleep; Fast sleep spindles; Slow sleep spindles ID LEARNING-DEPENDENT CHANGES; EYE-MOVEMENT SLEEP; MEMORY CONSOLIDATION; STAGE-2 SLEEP; REM-SLEEP; TIME-COURSE; PLASTICITY; BRAIN; OSCILLATIONS; PERFORMANCE AB This study aimed to determine the distinct contribution of slow (11-13 Hz) and fast (13-15 Hz) spindles in the consolidation process of a motor sequence learning task (MSL). Young subjects (n = 12) were trained on both a finger MSL task and a control (CTRL) condition, which were administered one week apart in a counterbalanced order. Subjects were asked to practice the MSL or CTRL task in the evening (approximately 9:00 p.m.) and their performance was retested on the same task 12 h later (approximately 9:00 a.m.). Polysomnographic (PSG) recordings were performed during the night following training on either task, and an automatic algorithm was used to detect fast and slow spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Statistical analyses revealed higher fast (but not slow) spindle density after training on the MSL than after practice of the CTRL task. The increase in fast spindle density on the MSL task correlated positively with overnight performance gains on the MSL task and with difference in performance gain between the MSL and CTRL tasks. Together, these results suggest that fast sleep spindles help activate the cerebral network involved in overnight MSL consolidation, while slow spindles do not appear to play a role in this mnemonic process. (C) 2010 Elsevier B.V. All rights reserved. C1 [Barakat, M.; Vandewalle, G.; Morin, A.; Poirier, G.; Martin, N.; Lafortune, M.; Carrier, J.] Hop Sacre Coeur, Ctr Adv Res Sleep Med, Montreal, PQ H4J 1C5, Canada. [Barakat, M.; Doyon, J.; Debas, K.; Vandewalle, G.; Morin, A.; Martin, N.; Lafortune, M.; Carrier, J.] Inst Univ Geriatrie Montreal, Ctr Rech, Unite Neuroimagerie Fonct, Montreal, PQ, Canada. [Karni, A.] Univ Haifa, Brain Behav Ctr, Lab Funct Brain Imaging & Learning Res, IL-31999 Haifa, Israel. [Ungerleider, L. G.] NIMH, NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Benali, H.] Univ Paris 06, Ctr Hosp Univ Pitie Salpetriere, Inst Natl Sante & Rech Med, Unite Mixte Rech S 678, Paris, France. RP Carrier, J (reprint author), Hop Sacre Coeur, Ctr Adv Res Sleep Med, 5400 Gouin Blvd W, Montreal, PQ H4J 1C5, Canada. EM julie.carrier.1@umontreal.ca OI Martin, Nicholas/0000-0003-4069-8020 FU Canadian Institutes of Health Research (CIHR); FRSQ FX Support for this research was provided by a grant from the Canadian Institutes of Health Research (CIHR) to JD, JC, AHT, AK, HB, and LGU, and by an FRSQ scholarship awarded to JC. The authors are grateful to Sonia Frenette and Jean Paquet for their technical assistance. NR 35 TC 72 Z9 74 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 2 PY 2011 VL 217 IS 1 BP 117 EP 121 DI 10.1016/j.bbr.2010.10.019 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 710TK UT WOS:000286539700017 PM 20974183 ER PT J AU Thanos, PK Cho, J Kim, R Michaelides, M Primeaux, S Bray, G Wang, GJ Volkow, ND AF Thanos, Panayotis K. Cho, Jacob Kim, Ronald Michaelides, Michael Primeaux, Stefany Bray, George Wang, Gene-Jack Volkow, Nora D. TI Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Hyperphagia; Addiction; Dopamine; D2; Diet ID DOPAMINE D2 RECEPTOR; ORBITOFRONTAL CORTEX; DEFICIENT MICE; WEIGHT-GAIN; BODY-WEIGHT; IMPULSIVITY; ADDICTION; INHIBITION; BEHAVIOR AB Dopamine (DA) and DA D(2) receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation. Published by Elsevier B.V. C1 [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, NIH, Dept Hlth & Human Serv, Lab Neuroimaging, Bethesda, MD USA. [Thanos, Panayotis K.; Cho, Jacob; Kim, Ronald; Michaelides, Michael; Wang, Gene-Jack; Volkow, Nora D.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Thanos, Panayotis K.; Kim, Ronald; Michaelides, Michael] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Primeaux, Stefany; Bray, George] Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Thanos, PK (reprint author), NIAAA, NIH, Dept Hlth & Human Serv, Lab Neuroimaging, Bethesda, MD USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU NIAAA [AA11034, AA07574, AA07611] FX Support for the study has been contributed by NIAAA Intramural Research Program: (AA11034 and AA07574, AA07611). NR 27 TC 6 Z9 6 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 2 PY 2011 VL 217 IS 1 BP 165 EP 170 DI 10.1016/j.bbr.2010.10.027 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 710TK UT WOS:000286539700024 PM 21034777 ER PT J AU Eddy, MT Hermida, OT Andreas, L Wagner, G Rostovtseva, TK Griffin, RG AF Eddy, Matthew T. Hermida, Oscar T. Andreas, Loren Wagner, Gerhard Rostovtseva, Tatiana K. Griffin, Robert G. TI Investigating VDAC Gating via Magic Angle Spinning NMR and Electrophysiological Measurements Under Extreme pH Conditions: Implications for the Voltage-Gating Mechanism SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Eddy, Matthew T.; Andreas, Loren; Griffin, Robert G.] MIT, Francis Bitter Natl Magnet Lab, Cambridge, MA 02139 USA. [Hermida, Oscar T.; Rostovtseva, Tatiana K.] NICHD, Lab Phys & Struct Biol, PPB, NIH, Bethesda, MD USA. [Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 8 EP 9 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600045 ER PT J AU Forbes, JG Wittebort, RJ Wang, K AF Forbes, Jeffrey G. Wittebort, Richard J. Wang, Kuan TI Transient Alpha and Pi Helical Conversion of BLUE Octads in the Elastic and Disordered Region of C. elegans TTN-1 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Forbes, Jeffrey G.] NIAMS, NIH, DHHS, Bethesda, MD USA. [Wittebort, Richard J.] Univ Louisville, Louisville, KY 40292 USA. [Wang, Kuan] Acad Sinica, Taipei 115, Taiwan. 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 13 EP 14 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600071 ER PT J AU Tjandra, N Ma, JH Edlich, F Youle, R AF Tjandra, Nico Ma, Junhe Edlich, Frank Youle, Richard TI Structural Insights into Cytomegalovirus Resistance to Apoptosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Tjandra, Nico; Ma, Junhe] NHLBI, NIH, Bethesda, MD 20892 USA. [Edlich, Frank; Youle, Richard] 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 17 EP 17 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600088 ER PT J AU Kraft, ML Frisz, JF Lou, K Hanafin, W Weber, PK Carpenter, KJ Zimmerberg, J Hutcheon, ID AF Kraft, Mary L. Frisz, Jessica F. Lou, Kaiyan Hanafin, William Weber, Peter K. Carpenter, Kevin J. Zimmerberg, Joshua Hutcheon, Ian D. TI Chemical Imaging of Lipid Organization in the Plasma Membranes of Intact Cells with High Lateral Resolution SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Kraft, Mary L.; Frisz, Jessica F.; Lou, Kaiyan; Hanafin, William] Univ Illinois, Urbana, IL 61801 USA. [Weber, Peter K.; Carpenter, Kevin J.; Hutcheon, Ian D.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Zimmerberg, Joshua] NIH, Bethesda, MD 20892 USA. RI Lou, Kaiyan/D-4199-2012 OI Lou, Kaiyan/0000-0003-3443-0343 NR 0 TC 0 Z9 0 U1 1 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 19 EP 20 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600102 ER PT J AU Kumar, J Schuck, P Mayer, ML AF Kumar, Janesh Schuck, Peter Mayer, Mark L. TI Structure & Mechanisms Underlying Heteromeric Glutamate Receptor Assembly SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Kumar, Janesh; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD USA. [Schuck, Peter] NIBIB, Lab Bioengn & Phys Sci, NIH, DHHS, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 24 EP 24 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600123 ER PT J AU Kawate, T Robertson, JL Li, MF Silberberg, SD Swartz, KJ AF Kawate, Toshimitsu Robertson, Janice L. Li, Mufeng Silberberg, Shai D. Swartz, Kenton J. TI Ion Access Pathway to the Transmembrane Pore in P2X Receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Kawate, Toshimitsu; Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.] NIH, Bethesda, MD 20892 USA. [Robertson, Janice L.] Brandeis Univ, Waltham, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 25 EP 25 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600127 ER PT J AU Balla, T AF Balla, Tamas TI Mapping the Phosphoinositide Landscape in Mammalian Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 26 EP 26 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600131 ER PT J AU Johnson, ME Hummer, G AF Johnson, Margaret E. Hummer, Gerhard TI Nonspecific Binding Limits the Number of Proteins in a Cell and Shapes their Interaction Networks SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Johnson, Margaret E.; Hummer, Gerhard] NIH, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 32 EP 32 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600164 ER PT J AU Xu, Y Nussionv, R Ma, BY AF Xu, Yu Nussionv, Ruth Ma, Buyong TI Construct and Simulate Virtual Cell with Minimum Genome at the Nanoscale SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Xu, Yu] Minzu Univ China, Inst Chinese Minor Tradit Med, Beijing, Peoples R China. [Nussionv, Ruth; Ma, Buyong] NCI Frederick, SAIC Frederick, NIH, Frederick, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 32 EP 32 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288600162 ER PT J AU Smyth, JT Wu, SL Putney, JW AF Smyth, Jeremy T. Wu, Shilan Putney, James W. TI Definition of STIM1 Phosphorylation Sites that Contribute to Suppression of Store-Operated Calcium Entry During Mitosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Smyth, Jeremy T.; Wu, Shilan; Putney, James W.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 181 EP 181 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288601372 ER PT J AU Rouzina, I Qualley, DF Wu, TY Iwatani, Y Chan, DSB Hertz, A Chaurasiya, K Levin, JG Williams, MC Musier-Forsyth, K AF Rouzina, Ioulia Qualley, Dominic F. Wu, Tiyun Iwatani, Yasumasa Chan, Denise S. B. Hertz, Amber Chaurasiya, Kathy Levin, Judith G. Williams, Mark C. Musier-Forsyth, Karin TI Complex Kinetics of Apobec3g Interaction with Single-Stranded Nucleic Acids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Rouzina, Ioulia] Univ Minnesota, Minneapolis, MN USA. [Qualley, Dominic F.; Musier-Forsyth, Karin] Ohio State Univ, Columbus, OH 43210 USA. [Wu, Tiyun; Hertz, Amber; Levin, Judith G.] NIH, Bethesda, MD 20892 USA. [Iwatani, Yasumasa] Natl Hosp Org, Clin Res Ctr, Nagoya Med Ctr, Nagoya, Aichi, Japan. [Chan, Denise S. B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chaurasiya, Kathy; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 192 EP 192 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288601427 ER PT J AU Jin, AJ Li, EJ Pang, LJ Kotova, S Sackett, DL Smith, PD Lafer, EM Nossal, RJ AF Jin, Albert J. Li, Eileen J. Pang, Lisa J. Kotova, Svetlana Sackett, Dan L. Smith, Paul D. Lafer, Eileen M. Nossal, Ralph J. TI Nanomechanics of Clathrin Protein Shells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Jin, Albert J.; Li, Eileen J.; Pang, Lisa J.; Kotova, Svetlana; Smith, Paul D.] NIBIB, NIH, Bethesda, MD USA. [Sackett, Dan L.; Nossal, Ralph J.] NICHD, NIH, Bethesda, MD USA. [Lafer, Eileen M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. OI Jin, Albert/0000-0003-3826-1081 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 198 EP 199 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288601460 ER PT J AU Hummer, G AF Hummer, Gerhard TI Proton Pumping and Energy Transduction in Cytochrome C Oxidase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Hummer, Gerhard] NIH, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 343 EP 343 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603008 ER PT J AU Chung, HS Gopich, IV McHale, K Louis, JM Eaton, WA AF Chung, Hoi Sung Gopich, Irina V. McHale, Kevin Louis, John M. Eaton, William A. TI Photon-By-Photon Analysis of Single Molecule Fluorescence Trajectories Determines an Upper Bound for the Transition Path Time in Protein Folding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Chung, Hoi Sung; Gopich, Irina V.; McHale, Kevin; Louis, John M.; Eaton, William A.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 7 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 349 EP 349 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603036 ER PT J AU Capone, R Kotler, SA Jang, H Connelly, LS Nussinov, R Lal, R AF Capone, Ricardo Kotler, Samuel A. Jang, Hyunbum Connelly, Laura S. Nussinov, Ruth Lal, Ratnesh TI Probing Structural Features of Alzheimer's beta-Amyloid Ion Channels in Membranes Using A beta Mutants SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura S.; Lal, Ratnesh] Univ Calif San Diego, La Jolla, CA 92093 USA. [Jang, Hyunbum; Nussinov, Ruth] NCI, SAIC Frederick, Ctr Canc Res, Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 350 EP 350 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603041 ER PT J AU Renz, M Lippincott-Schwartz, J AF Renz, Malte Lippincott-Schwartz, Jennifer TI Single-Molecule Counting with Palm SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Renz, Malte; Lippincott-Schwartz, Jennifer] 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 350 EP 350 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603038 ER PT J AU Sengupta, P Talisman, T Veatch, S Lippincott-Schwartz, J AF Sengupta, Prabuddha Talisman, Tijana Veatch, Sarah Lippincott-Schwartz, Jennifer TI Nano-Scale Spatial Organization of Plasma Membrane Revealed by Pair-Correlation Analysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Sengupta, Prabuddha; Talisman, Tijana; Lippincott-Schwartz, Jennifer] NIH, Bethesda, MD 20892 USA. [Veatch, Sarah] Univ Michigan, Ann Arbor, MI 48109 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 350 EP 350 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603040 ER PT J AU Brochet, DXP Yang, DM Cheng, HP Lederer, WJ AF Brochet, Didier X. P. Yang, Dongmei Cheng, Heping Lederer, W. Jonathan TI Small Ca2+ Release Events in Rabbit Ventricular Myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Brochet, Didier X. P.; Lederer, W. Jonathan] BioMET, Baltimore, MD USA. [Yang, Dongmei] NIA, NIH, Baltimore, MD 21224 USA. [Cheng, Heping] Peking Univ, Beijing 100871, Peoples R China. 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 352 EP 353 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603053 ER PT J AU Ma, XF Adelstein, RS AF Ma, Xuefei Adelstein, Robert S. TI The Enzymatic Motor Activity of Nonmuscle Myosin II-B is not Critical for Cardiac Myocyte Cytokinesis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Ma, Xuefei; Adelstein, Robert S.] 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 354 EP 354 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603060 ER PT J AU Castronovo, M Lucesoli, A Choi, D Inverso, V Parisse, P Kurnikova, A Malhotra, A Grassi, M Grassi, G Scaggiante, B Casalis, L Scoles, G AF Castronovo, Matteo Lucesoli, Agnese Choi, Dianne Inverso, Vincent Parisse, Pietro Kurnikova, Anastasia Malhotra, Aseem Grassi, Mario Grassi, Gabriele Scaggiante, Bruna Casalis, Loredana Scoles, Giacinto TI The Effect of Confinement on Enzyme Diffusion and Reactions Inside DNA Nanostructures SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Castronovo, Matteo; Choi, Dianne; Inverso, Vincent; Kurnikova, Anastasia; Malhotra, Aseem; Scoles, Giacinto] Temple Univ, Philadelphia, PA 19122 USA. [Castronovo, Matteo] CBM, Trieste, Italy. [Lucesoli, Agnese] Hosp San Salvatore, Pesaro, Italy. [Lucesoli, Agnese; Scoles, Giacinto] SISSA, I-34014 Trieste, Italy. [Inverso, Vincent] Univ Penn, Philadelphia, PA 19104 USA. [Parisse, Pietro; Casalis, Loredana] Sincrotrone Trieste Scrl, Trieste, Italy. [Kurnikova, Anastasia] NIH, Bethesda, MD 20892 USA. [Grassi, Mario; Grassi, Gabriele; Scaggiante, Bruna] Univ Trieste, Trieste, Italy. [Grassi, Mario] Univ Hosp Cattinara, Trieste, Italy. [Casalis, Loredana] IIT, Trieste, Italy. NR 0 TC 0 Z9 0 U1 1 U2 7 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 357 EP 357 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603075 ER PT J AU Fodeke, AA Minton, AP AF Fodeke, Adedayo A. Minton, Allen P. TI Quantitative Characterization of Protein-Protein and Protein-Polymer Interaction via Nonideal Tracer Sedimentation Equilibrium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Fodeke, Adedayo A.; Minton, Allen P.] NIH, Bethesda, MD 20892 USA. NR 2 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 357 EP 357 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603076 ER PT J AU Zhao, HY Brown, PH Schuck, P AF Zhao, Huaying Brown, Patrick H. Schuck, Peter TI Studying Rapidly Reversible Protein-Protein Interactions by Sedimentation Velocity Analytical Ultracentrifugation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc DE protein interactions; transport; sedimentation; signal transduction C1 [Zhao, Huaying; Brown, Patrick H.; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 387 EP 387 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288603228 ER PT J AU Losert, W Driscoll, M McCann, C Fourkas, J Parent, C AF Losert, Wolfgang Driscoll, Meghan McCann, Colin Fourkas, John Parent, Carole TI Cell Shape Dynamics: from Waves to Motion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Losert, Wolfgang; Driscoll, Meghan; McCann, Colin; Fourkas, John] Univ Maryland, College Pk, MD 20742 USA. [Parent, Carole] NCI, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 513 EP 514 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604310 ER PT J AU Vinogradova, TM Lakatta, EG AF Vinogradova, Tatiana M. Lakatta, Edward G. TI Basal Phospholipase C (PLC) Activation is Obligatory for Cardiac Pacemaker Activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 517 EP 517 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604327 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI The Evolution of the Natively Disordered Region in P53 Family Proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Ma, Buyong; Nussinov, Ruth] NCI Frederick, SAIC Frederick, NIH, Frederick, 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 518 EP 518 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604333 ER PT J AU Soubias, O Teague, WE Hines, KG Gawrisch, K AF Soubias, Olivier Teague, Walter E. Hines, Kirk G. Gawrisch, Klaus TI Rhodopsin - Rhodopsin Oligomerization in Model Lipid Bilayers - Functional Implications SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Soubias, Olivier; Teague, Walter E.; Hines, Kirk G.; Gawrisch, Klaus] NIH, Rockville, MD 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 525 EP 526 PG 2 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604374 ER PT J AU Fawzi, NL Ying, JF Torchia, DA Clore, GM AF Fawzi, Nicolas L. Ying, Jinfa Torchia, Dennis A. Clore, G. Marius TI Kinetics of Amyloid-Beta Monomer to Oligomer Exchange by NMR Relaxation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Fawzi, Nicolas L.; Ying, Jinfa; Torchia, Dennis A.; Clore, G. Marius] NIDDK, NIH, Bethesda, MD USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 531 EP 531 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604403 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Alzheimer A beta Amyloid Annular Fibrils: Insight Into Polymorphism SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 55th Annual Meeting of the Biophysical-Society CY MAR 05-09, 2011 CL Baltimore, MD SP Biophys Soc C1 [Ma, Buyong; Nussinov, Ruth] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 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 FEB 2 PY 2011 VL 100 IS 3 SU 1 BP 531 EP 531 PG 1 WC Biophysics SC Biophysics GA 972PF UT WOS:000306288604401 ER PT J AU Rui, HA Lee, KI Pastor, RW Im, W AF Rui, Huan Lee, Kyu Il Pastor, Richard W. Im, Wonpil TI Molecular Dynamics Studies of Ion Permeation in VDAC SO BIOPHYSICAL JOURNAL LA English DT Article ID DEPENDENT ANION CHANNEL; RAT-LIVER MITOCHONDRIA; PEPTIDE-SPECIFIC ANTIBODIES; OUTER-MEMBRANE; OMPF PORIN; VOLTAGE; SIMULATION; PROTEIN; SELECTIVITY; CHARMM AB The voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria serves an essential role in the transport of metabolites and electrolytes between the cell matrix and mitochondria. To examine its structure, dynamics, and the mechanisms underlying its electrophysiological properties, we performed a total of 1.77 mu s molecular dynamics simulations of human VDAC isoform 1 in DOPE/DOPC mixed bilayers in 1 M KCl solution with transmembrane potentials of 0, +/- 25, +/- 50, +/- 75, and +/- 100 mV. The calculated conductance and ion selectivity are in good agreement with the experimental measurements. In addition, ion density distributions inside the channel reveal possible pathways for different ion species. Based on these observations, a mechanism underlying the anion selectivity is proposed; both ion species are transported across the channel, but the rate for K(+) is smaller than that for Cl(-) because of the attractive interactions between K(+) and residues on the channel wall. This difference leads to the anion selectivity of VDAC. C1 [Rui, Huan; Lee, Kyu Il; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Rui, Huan; Lee, Kyu Il; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. [Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Im, W (reprint author), Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. EM wonpil@ku.edu FU University of Kansas; National Institutes of Health [R01-GM092950]; National Science Foundation [NSF OCI-0503992]; National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported in part by institutional funding from the University of Kansas, including J. R. and Inez Jay funds, the National Institutes of Health (R01-GM092950), the National Science Foundation (NSF OCI-0503992) through TeraGrid resources provided by Purdue University (to W.I.), and the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (to R.W.P.). NR 46 TC 41 Z9 41 U1 1 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 FEB 2 PY 2011 VL 100 IS 3 BP 602 EP 610 DI 10.1016/j.bpj.2010.12.3711 PG 9 WC Biophysics SC Biophysics GA 716GN UT WOS:000286957200010 PM 21281574 ER PT J AU Lee, KI Rui, HA Pastor, RW Im, W AF Lee, Kyu Il Rui, Huan Pastor, Richard W. Im, Wonpil TI Brownian Dynamics Simulations of Ion Transport through the VDAC SO BIOPHYSICAL JOURNAL LA English DT Article ID DEPENDENT ANION CHANNEL; ALPHA-HEMOLYSIN; ELECTRODIFFUSION THEORY; MITOCHONDRIAL CHANNEL; MOLECULAR-DYNAMICS; SELECTIVITY; PERMEATION; PROTEIN; MEMBRANE; MODELS AB It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions. C1 [Lee, Kyu Il; Rui, Huan; Im, Wonpil] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. [Lee, Kyu Il; Rui, Huan; Im, Wonpil] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. [Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Im, W (reprint author), Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. EM wonpil@ku.edu FU University of Kansas; J. R. and Inez Jay Fund; National Institutes of Health [R01-GM092950]; National Science Foundation [NSF OCI-0503992]; National Heart, Lung, and Blood Institute; Korean Government [KRF-2006-352-D00132] FX This work was supported in part by institutional funding from the University of Kansas, the J. R. and Inez Jay Fund, the National Institutes of Health (R01-GM092950), the National Science Foundation (NSF OCI-0503992) through TeraGrid resources provided by Purdue University (to W.I.), and the Intramural Research Program of the National Heart, Lung, and Blood Institute (to R.W.P.). K.I.L. was supported by a Korea Research Foundation Grant funded by the Korean Government (KRF-2006-352-D00132). NR 34 TC 28 Z9 28 U1 2 U2 12 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 FEB 2 PY 2011 VL 100 IS 3 BP 611 EP 619 DI 10.1016/j.bpj.2010.12.3708 PG 9 WC Biophysics SC Biophysics GA 716GN UT WOS:000286957200011 PM 21281575 ER PT J AU Lu, JX Yau, WM Tycko, R AF Lu, Jun-Xia Yau, Wai-Ming Tycko, Robert TI Evidence from Solid-State NMR for Nonhelical Conformations in the Transmembrane Domain of the Amyloid Precursor Protein SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; C-TERMINAL DOMAIN; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; CHEMICAL-SHIFTS; LIPID RAFTS; PHOSPHOLIPID-BILAYERS; SECONDARY-STRUCTURE; C-13 NMR AB The amyloid precursor protein (APP) is subject to proteolytic processing by gamma-secretase within neuronal membranes, leading to Alzheimer's disease-associated beta-amyloid peptide production by cleavage near the midpoint of the single transmembrane (TM) segment of APP. Conformational properties of the TM segment may affect its susceptibility to gamma-secretase cleavage, but these properties have not been established definitively, especially in bilayer membranes with physiologically relevant lipid compositions. In this article, we report an investigation of the APP-TM conformation, using C-13 chemical shifts obtained with two-dimensional solid-state NMR spectroscopy as site-specific conformational probes. We find that the APP-TM conformation is not a simple alpha-helix, particularly at 37 degrees C in multilamellar vesicles with compositions that mimic the composition of neuronal cell membranes. Instead, we observe a mixture of helical and nonhelical conformations at the N- and C-termini and in the vicinity of the gamma-cleavage site. Conformational plasticity of the TM segment of APP may be an important factor in the gamma-secretase cleavage mechanism. C1 [Lu, Jun-Xia; Yau, Wai-Ming; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. NR 54 TC 19 Z9 19 U1 1 U2 19 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 FEB 2 PY 2011 VL 100 IS 3 BP 711 EP 719 DI 10.1016/j.bpj.2010.12.3696 PG 9 WC Biophysics SC Biophysics GA 716GN UT WOS:000286957200022 PM 21281586 ER PT J AU Mishra, SK Tisel, SM Orestes, P Bhangoo, SK Hoon, MA AF Mishra, Santosh K. Tisel, Sarah M. Orestes, Peihan Bhangoo, Sonia K. Hoon, Mark A. TI TRPV1-lineage neurons are required for thermal sensation SO EMBO JOURNAL LA English DT Article DE itch; pain; thermal; TRPM8; TRPV1 ID MAMMALIAN TASTE RECEPTORS; CAPSAICIN-RECEPTOR; MICE LACKING; IN-VIVO; BEHAVIORAL-RESPONSES; NEUROPATHIC PAIN; TRP CHANNEL; COLD; THERMOSENSATION; ACTIVATION AB The ion-channel TRPV1 is believed to be a major sensor of noxious heat, but surprisingly animals lacking TRPV1 still display marked responses to elevated temperature. In this study, we explored the role of TRPV1-expressing neurons in somatosensation by generating mice wherein this lineage of cells was selectively labelled or ablated. Our data show that TRPV1 is an embryonic marker of many nociceptors including all TRPV1- and TRPM8-neurons as well as many Mrg-expressing neurons. Mutant mice lacking these cells are completely insensitive to hot or cold but in marked contrast retain normal touch and mechanical pain sensation. These animals also exhibit defective body temperature control and lose both itch and pain reactions to potent chemical mediators. Together with previous cell ablation studies, our results define and delimit the roles of TRPV1- and TRPM8-neurons in thermosensation, thermoregulation and nociception, thus significantly extending the concept of labelled lines in somatosensory coding. The EMBO Journal (2011) 30, 582-593. doi:10.1038/emboj.2010.325; Published online 7 December 2010 C1 [Mishra, Santosh K.; Tisel, Sarah M.; Orestes, Peihan; Bhangoo, Sonia K.; Hoon, Mark A.] NIDCR, Mol Genet Unit, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. RP Hoon, MA (reprint author), NIDCR, Mol Genet Unit, Lab Sensory Biol, NIH, Bldg 49,Room 1A16,49 Convent Dr, Bethesda, MD 20892 USA. EM mark.hoon@nih.gov FU NIH, NIDCR FX We thank Dr Lars von Buchholtz for the taste data and review of the manuscript. We are also very grateful to Nick Ryba for encouragement and helpful advice and Drs Nguyen, Usdin, Gutkind and Siraganian for valuable suggestions. Transgenic mice were generated by Andrew Cho in the NIDCR-core. This research was supported by the intramural research programme of the NIH, NIDCR (MAH). NR 48 TC 76 Z9 77 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 2 PY 2011 VL 30 IS 3 BP 582 EP 593 DI 10.1038/emboj.2010.325 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 721YN UT WOS:000287394200013 PM 21139565 ER PT J AU Lantos, J Matlock, AM Wendler, D AF Lantos, John Matlock, Ann Marie Wendler, David TI Clinician Integrity and Limits to Patient Autonomy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EMERGENCY CONTRACEPTION; DECISION-MAKING; HEALTH-CARE; CONSCIENCE; VALUES AB A 28-year-old man with chronic granulomatous disease developed worsening respiratory status in the setting of chronic bacterial and fungal infections. The attending physician recommended transfer to the intensive care unit (ICU), but the patient declined. The patient understood that the nurses in the ICU have expertise in caring for patients with poor respiratory function. He also understood that he faced an increased risk of dying if he remained on the medical ward. At the same time, the patient was familiar with the nurses on the medical ward and felt comfortable there. Unsure of whether it was appropriate for clinicians to agree to provide less than optimal care for a critically ill patient, the clinicians on the medical ward requested a bioethics consultation. This article reviews the ethical issues that arise when patients ask clinicians to provide less than optimal care. Although it is well established that clinicians ought to respect patient autonomy, that obligation conflicted, in the present case, with the clinicians' sense of professional integrity. Future research on this vital but underexplored topic is needed to determine the extent to which clinicians' professional integrity places limits on the types of patient requests to which they should agree. JAMA. 2011;305(5):495-499 www.jama.com C1 [Lantos, John] Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, Kansas City, MO 64108 USA. [Matlock, Ann Marie; Wendler, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lantos, J (reprint author), Childrens Mercy Hosp, Childrens Mercy Bioeth Ctr, 2401 Gilham Rd, Kansas City, MO 64108 USA. EM jlantos@cmh.edu FU Department of Bioethics at the National Institutes of Health Clinical Center; National Institutes of Health Clinical Center FX This work was funded by the Department of Bioethics at the National Institutes of Health Clinical Center.; The National Institutes of Health Clinical Center had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 17 TC 23 Z9 23 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 2 PY 2011 VL 305 IS 5 BP 495 EP 499 DI 10.1001/jama.2011.32 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 714LI UT WOS:000286810700023 PM 21285427 ER PT J AU Dobi, A Seabold, GK Christensen, CH Bock, R Alvarez, VA AF Dobi, Alice Seabold, Gail K. Christensen, Christine H. Bock, Roland Alvarez, Veronica A. TI Cocaine-Induced Plasticity in the Nucleus Accumbens Is Cell Specific and Develops without Prolonged Withdrawal SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MEDIUM SPINY NEURONS; VENTRAL TEGMENTAL AREA; LONG-TERM DEPRESSION; DENDRITIC SPINES; BEHAVIORAL SENSITIZATION; DOPAMINE-RECEPTORS; GENE-EXPRESSION; TOPOGRAPHICAL ORGANIZATION; TYROSINE-HYDROXYLASE; SYNAPTIC PLASTICITY AB Cocaine induces plasticity at glutamatergic synapses in the nucleus accumbens (NAc). Withdrawal was suggested to play an important role in the development of this plasticity by studies showing that some changes only appear several weeks after the final cocaine exposure. In this study, the requirement for prolonged withdrawal was evaluated by comparing the changes in glutamatergic transmission induced by two different noncontingent cocaine treatments: a short treatment followed by prolonged withdrawal, and a longer treatment without prolonged withdrawal. Recordings were performed from mouse medium spiny neurons (MSNs) in the NAc at the same time after the first cocaine injection under both treatments. A similar increase in the frequency of glutamate-mediated miniature EPSCs was observed in D(1)-expressing MSNs after both cocaine treatments, demonstrating that prolonged withdrawal was not required. Furthermore, larger AMPA receptor-to-NMDA receptor ratios, higher spine density, and enlarged spine heads were observed in the absence of withdrawal after a long cocaine treatment. These synaptic adaptations expressed in D(1)-containing MSNs of the NAc core were not further enhanced by protracted withdrawal. In conclusion, a few repeated cocaine injections are enough to trigger adaptations at glutamatergic synapses in D(1)-expressing MSNs, which, although they take time to develop, do not require prolonged cocaine withdrawal. C1 [Dobi, Alice; Seabold, Gail K.; Christensen, Christine H.; Bock, Roland; Alvarez, Veronica A.] NIAAA, NIH, Bethesda, MD 20892 USA. RP Alvarez, VA (reprint author), NIAAA, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM alvarezva@mail.nih.gov RI Alvarez, Veronica /E-9745-2015; Bock, Roland/G-2982-2016 OI Alvarez, Veronica /0000-0003-2611-8675; Bock, Roland/0000-0002-8654-1080 FU National Institute on Alcohol Abuse and Alcoholism; National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This work was funded by the intramural programs of National Institute on Alcohol Abuse and Alcoholism and National Institute of Neurological Disorders and Stroke at the National Institutes of Health. We are grateful to Dr. Fumi Ono for sharing his confocal microscope. We thank John T. Williams, Christina Gremel, Christopher Ford, and the members of the Alvarez Laboratory for the helpful comments and discussions of this manuscript. NR 54 TC 42 Z9 42 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 2 PY 2011 VL 31 IS 5 BP 1895 EP 1904 DI 10.1523/JNEUROSCI.5375-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 715WE UT WOS:000286922100038 PM 21289199 ER PT J AU Langhorne, J Buffet, P Galinski, M Good, M Harty, J Leroy, D Mota, MM Pasini, E Renia, L Riley, E Stins, M Duffy, P AF Langhorne, Jean Buffet, Pierre Galinski, Mary Good, Michael Harty, John Leroy, Didier Mota, Maria M. Pasini, Erica Renia, Laurent Riley, Eleanor Stins, Monique Duffy, Patrick TI The relevance of non-human primate and rodent malaria models for humans SO MALARIA JOURNAL LA English DT Editorial Material AB At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. C1 [Langhorne, Jean] MRC Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. [Buffet, Pierre] Grp Hosp Pitie Salpetriere, F-75651 Paris, France. [Galinski, Mary] Emory Univ, Sch Med, Int Ctr Malaria Res Educ & Dev, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Good, Michael] Griffith Univ, Inst Glyc, Griffith, Qld 4222, Australia. [Harty, John] Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA. [Harty, John] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA. [Harty, John] Univ Iowa, Carver Coll Med, Interdisciplinary Program Immunol, Iowa City, IA 52242 USA. [Leroy, Didier] Med Malaria Venture, CH-15 Geneva 15, Switzerland. [Mota, Maria M.] Inst Mol Med, Unidade Malaria, P-1649028 Lisbon, Portugal. [Pasini, Erica] BPRC, NL-2288 GJ Rijswijk, Netherlands. [Renia, Laurent] ASTAR, Singapore Immunol Network, Lab Malaria Immunobiol, Singapore 138648, Singapore. [Riley, Eleanor] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London WC1, England. [Stins, Monique] Johns Hopkins Sch Med, RT Johnson Div NeuroImmunol, Baltimore, MD 21231 USA. [Duffy, Patrick] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. RP Langhorne, J (reprint author), MRC Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. EM jlangho@nimr.mrc.ac.uk RI Renia, Laurent/E-2117-2011; Riley, Eleanor/C-8960-2013; OI Renia, Laurent/0000-0003-0349-1557; Riley, Eleanor/0000-0003-3447-3570; Mota, Maria Manuel/0000-0002-2858-1041 NR 15 TC 55 Z9 57 U1 0 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD FEB 2 PY 2011 VL 10 AR 23 DI 10.1186/1475-2875-10-23 PG 4 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 740RK UT WOS:000288811900004 PM 21288352 ER PT J AU Hancock, DB Haberg, SE Furu, K Whitworth, KW Nafstad, P Nystad, W London, SJ AF Hancock, D. B. Haberg, S. E. Furu, K. Whitworth, K. W. Nafstad, P. Nystad, W. London, S. J. TI Oral Contraceptive Use Before Pregnancy and Respiratory Outcomes in the Offspring: Comparison of Estrogen-Progestin Combined Pills and Progestin-Only Pills SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Hancock, D. B.; Whitworth, K. W.; London, S. J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Haberg, S. E.; Furu, K.; Nafstad, P.; Nystad, W.] Norwegian Inst Publ Hlth, Oslo, Norway. [Nafstad, P.] Univ Oslo, Oslo, Norway. [Furu, K.] Univ Tromso, Tromso, Norway. RI Hancock, Dana/D-8577-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB173 EP AB173 DI 10.1016/j.jaci.2010.12.689 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400671 ER PT J AU Heimall, J Siegel, AM Shaw, PA Hsu, A Holland, SM Freeman, AF Milner, JD AF Heimall, J. Siegel, A. M. Shaw, P. A. Hsu, A. Holland, S. M. Freeman, A. F. Milner, J. D. TI Early onset of Varicella Zoster Virus Reactivation (VZV, Shingles) in Patients with Autosomal Dominant Hyper IgE Syndrome (AD-HIES) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Heimall, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Siegel, A. M.; Shaw, P. A.; Hsu, A.; Holland, S. M.; Freeman, A. F.; Milner, J. D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB88 EP AB88 DI 10.1016/j.jaci.2010.12.356 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400339 ER PT J AU Leiding, JW Heimall, J Song, Y Holland, SM Siegel, RM Freeman, AF AF Leiding, J. W. Heimall, J. Song, Y. Holland, S. M. Siegel, R. M. Freeman, A. F. TI Idiopathic CD4+ Lymphocytopenia: Clinical and Autoimmune Phenotype SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol (AAAAI) C1 [Leiding, J. W.; Holland, S. M.; Freeman, A. F.] Natl Inst Allerg & Infect Dis, Bethesda, MD USA. [Heimall, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Song, Y.; Siegel, R. M.] NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB89 EP AB89 DI 10.1016/j.jaci.2010.12.358 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400341 ER PT J AU Price, CC Rao, VK Danielian, S Meffre, E AF Price, C. C. Rao, V. K. Danielian, S. Meffre, E. TI Defective Peripheral B Cell Tolerance In Alps Patients With Fas Mutations SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Price, C. C.; Meffre, E.] Yale Univ, New Haven, CT USA. [Rao, V. K.] NIH, Bethesda, MD 20892 USA. [Danielian, S.] Hosp Pediat Juan P Garrahan, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB226 EP AB226 DI 10.1016/j.jaci.2010.12.900 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846401015 ER PT J AU Scurlock, AM Leung, DYM Sampson, HA Lindblad, R Liu, AH Wood, RA Jones, SM Plaut, M Burks, W Stablein, D Sicherer, SH AF Scurlock, A. M. Leung, D. Y. M. Sampson, H. A. Lindblad, R. Liu, A. H. Wood, R. A. Jones, S. M. Plaut, M. Burks, W. Stablein, D. Sicherer, S. H. TI Association of Atopic Dermatitis (AD) Severity to Milk and Egg Allergy Outcomes in a Cohort of Atopic, Food-allergic Children (COFAR) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Scurlock, A. M.; Jones, S. M.] UAMS AR Childrens Hosp, Little Rock, AR USA. [Leung, D. Y. M.; Liu, A. H.] Natl Jewish Hlth Ctr, Denver, CO USA. [Sampson, H. A.; Sicherer, S. H.] Mt Sinai Sch Med, New York, NY USA. [Lindblad, R.; Stablein, D.] EMMES Corp, Rockville, MD USA. [Wood, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Plaut, M.] NIAID, NIH, Bethesda, MD 20892 USA. [Burks, W.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB36 EP AB36 DI 10.1016/j.jaci.2010.12.153 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400137 ER PT J AU Sharma, HP Mansoor, DK Sprunger, AC Zalos, K Taylor, H Martin, X Mikhail, IJ AF Sharma, H. P. Mansoor, D. K. Sprunger, A. C. Zalos, K. Taylor, H. Martin, X. Mikhail, I. J. TI Racial Disparities in the Presentation of Pediatric Eosinophilic Esophagitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Sharma, H. P.; Mansoor, D. K.; Sprunger, A. C.; Zalos, K.; Taylor, H.; Martin, X.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Mikhail, I. J.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB110 EP AB110 DI 10.1016/j.jaci.2010.12.440 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400422 ER PT J AU Stellato, C Fang, X Abdelmohsen, K Gorospe, M Ishmael, FT AF Stellato, C. Fang, X. Abdelmohsen, K. Gorospe, M. Ishmael, F. T. TI Glucocorticoid (GC) Modulation of Global miRNA Profile in Human Airway Epithelial Cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Stellato, C.; Fang, X.] Johns Hopkins Univ, Baltimore, MD USA. [Abdelmohsen, K.; Gorospe, M.] NIA, NIH, Baltimore, MD 21224 USA. [Ishmael, F. T.] Penn State Univ, Coll Med, Hershey, PA USA. RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 NR 0 TC 0 Z9 0 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB64 EP AB64 DI 10.1016/j.jaci.2010.12.267 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400250 ER PT J AU Payne, AR Kellman, P Anderson, R Chen, MY McPhaden, AR Watkins, S Schenke, W Wright, V Lederman, RJ Aletras, AH Arai, AE Berry, C AF Payne, A. R. Kellman, P. Anderson, R. Chen, M. Y. McPhaden, A. R. Watkins, S. Schenke, W. Wright, V. Lederman, R. J. Aletras, A. H. Arai, A. E. Berry, C. TI T2-weighted magnetic resonance imaging has high diagnostic accuracy for myocardial haemorrhage in myocardial infarction: a preclinical validation study in swine SO SCOTTISH MEDICAL JOURNAL LA English DT Meeting Abstract C1 [Payne, A. R.; Kellman, P.; Anderson, R.; Chen, M. Y.; Schenke, W.; Wright, V.; Lederman, R. J.; Aletras, A. H.; Arai, A. E.; Berry, C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Payne, A. R.; McPhaden, A. R.; Watkins, S.; Berry, C.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SCOTTISH MEDICAL JOURNAL PI GLASGOW PA MR K BURNSIDE, 12 BUCCLEUCH DRIVE, BEARSDEN, GLASGOW, G61 3LW, SCOTLAND SN 0036-9330 J9 SCOT MED J JI Scott. Med. J. PD FEB PY 2011 VL 56 IS 1 BP 51 EP 51 DI 10.1258/smj.2011.011040 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 824KC UT WOS:000295199800030 ER PT J AU Trimble, EL Fujiwara, K Marth, C Abrams, J AF Trimble, Edward L. Fujiwara, Keiichi Marth, Christian Abrams, Jeffrey TI Use of IP Chemotherapy in Ovarian Cancer: The Critical Questions THE GONZALEZ/GREEN/MUGGIA ARTICLE REVIEWED SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID INTRAPERITONEAL CHEMOTHERAPY; SURVIVAL; SURGERY; METAANALYSIS C1 [Trimble, Edward L.; Abrams, Jeffrey] NCI, Bethesda, MD 20892 USA. [Fujiwara, Keiichi] Saitama Med Univ, Int Med Ctr, Saitama, Japan. [Marth, Christian] Innsbruck Med Univ Hosp, Innsbruck, Austria. RP Trimble, EL (reprint author), NCI, Bethesda, MD 20892 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD FEB PY 2011 VL 25 IS 2 BP 170 EP 174 PG 3 WC Oncology SC Oncology GA 800EM UT WOS:000293342600008 PM 21456388 ER PT J AU Travlos, GS Hard, GC Betz, LJ Kissling, GE AF Travlos, Greg S. Hard, Gordon C. Betz, Laura J. Kissling, Grace E. TI Chronic Progressive Nephropathy in Male F344 Rats in 90-Day Toxicity Studies: Its Occurrence and Association with Renal Tubule Tumors in Subsequent 2-Year Bioassays SO TOXICOLOGIC PATHOLOGY LA English DT Article DE chronic progressive nephropathy; CPN; NIH-07 and NTP-2000 diets; toxicity and carcinogenicity studies; CPN exacerbation; renal tubule neoplasia ID NATIONAL TOXICOLOGY PROGRAM; HUMAN RISK-ASSESSMENT; LABORATORY RAT; KIDNEY TUMORS; CARCINOGENICITY; ALPHA-2U-GLOBULIN; LESIONS; RODENT AB The occurrence and severity of spontaneous chronic progressive nephropathy (CPN) in control male F344 rats as well as the frequency of treatment-related CPN exacerbation were histopathologically reevaluated. A series of 43 National Toxicology Program (NTP) 90-day toxicity studies comparing the influence of NIH-07 or NTP-2000 diets was examined. Relationships between the histopathologic findings at 90 days and renal tubule proliferative lesions recorded in subsequent 2-year bioassays for 24 chemicals were statistically analyzed. CPN lesions were observed in 100% of the control male rats regardless of diet, but CPN was more severe in control rats fed NIH-07. Approximately one-third of the 90-day studies demonstrated a treatment-related exacerbation of CPN severity, which was independent of diet. For chemicals that proceeded to 2-year bioassays, all studies with a statistically significant increase in renal tubule tumors (RTT) at 2 years had treatment-related exacerbation of CPN in the 90-day and 2-year studies. These findings indicate that CPN occurs ubiquitously in young male F344 rats and that treatment-related exacerbation of CPN in 90-day studies is a relatively common occurrence, having the potential to be predictive of an increased incidence of RTT in subsequent 2-year bioassays. C1 [Travlos, Greg S.; Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Betz, Laura J.] SRA Int Inc, Durham, NC USA. RP Travlos, GS (reprint author), NIEHS, NIH, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA. EM travlos@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences; NIH [N01ES55547] FX This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and by NIH contract N01ES55547. The authors wish to thank Drs. Kim Weber and Louise Fitzgerald for their assistance in the preliminary organization of Table 1. NR 37 TC 12 Z9 12 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2011 VL 39 IS 2 BP 381 EP 389 DI 10.1177/0192623310388432 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 800QW UT WOS:000293380000007 PM 21422264 ER PT J AU Reagan, WJ Irizarry-Rovira, A Poitout-Belissent, F Bolliger, AP Ramaiah, SK Travlos, G Walker, D Bounous, D Walter, G AF Reagan, William J. Irizarry-Rovira, Armando Poitout-Belissent, Florence Bolliger, Anne Provencher Ramaiah, Shashi K. Travlos, Greg Walker, Dana Bounous, Denise Walter, Gail CA Bone Marrow Working Grp ASVCP STP TI Best Practices for Evaluation of Bone Marrow in Nonclinical Toxicity Studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE bone marrow; best practice; cytology; histopathology; flow cytometry ID FLOW-CYTOMETRIC EVALUATION; CYNOMOLGUS MONKEYS; CELL COUNTS; WISTAR RATS; ULTRASTRUCTURAL TECHNIQUES; MYELODYSPLASTIC SYNDROMES; PERIPHERAL-BLOOD; FEED RESTRICTION; BIOPSY SPECIMENS; IN-VITRO AB This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant-induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used successfully, and which one is selected will depend on the expertise, preference of the facility, and the nature of the change in the bone marrow. Other specialized techniques such as clonogenic assays or electron microscopy are used rarely to further characterize hematotoxicity. The indications and techniques to successfully employ histological, cytological, or flow cytometric evaluation as well as clonogenic assays and electron microscopy are reviewed. C1 [Reagan, William J.] Pfizer Inc, Groton, CT 06340 USA. [Irizarry-Rovira, Armando] Eli Lilly & Co Inc, Indianapolis, IN USA. [Poitout-Belissent, Florence] Charles River Labs, Senneville, PQ, Canada. [Bolliger, Anne Provencher] Charles River Labs, Sherbrooke, PQ, Canada. [Ramaiah, Shashi K.] Pfizer Inc, Cambridge, MA USA. [Travlos, Greg] NIEHS, Res Triangle Pk, NC 27709 USA. [Walker, Dana] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Bounous, Denise] Bristol Myers Squibb Co, Princeton, NJ USA. [Walter, Gail] DVM PLC, Gail Walter, Kalamazoo, MI USA. RP Reagan, WJ (reprint author), Pfizer Global Res & Dev, Drug Safety Res & Dev, 8274-1203 Eastern Point Rd, Groton, CT 06340 USA. EM william.j.reagan@pfizer.com NR 88 TC 15 Z9 15 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2011 VL 39 IS 2 BP 435 EP 448 DI 10.1177/0192623310396907 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 800QW UT WOS:000293380000015 PM 21300792 ER PT J AU Ratain, MJ Collins, JM Doroshow, JH AF Ratain, M. J. Collins, J. M. Doroshow, J. H. TI Merrill Jon Egorin, MD, 1948-2010 OBITUARY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Biographical-Item AB Merrill Egorin was born in Baltimore, Maryland, where he completed his undergraduate and graduate education. He was a pioneer in understanding the relationship of pharmacokinetic variability to the pharmacodynamics of anticancer agents. He is remembered as a compassionate physician, an outstanding scientist, an entertaining lecturer, a superb mentor, and a friend to many. C1 [Ratain, M. J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Collins, J. M.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Ratain, MJ (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM mratain@medicine.bsd.uchicago.edu NR 1 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 2011 VL 89 IS 2 BP 163 EP 165 DI 10.1038/clpt.2010.294 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 711JA UT WOS:000286585500007 PM 21252931 ER PT J AU Bornstein, MH Mash, C Arterberry, ME AF Bornstein, Marc H. Mash, Clay Arterberry, Martha E. TI Young infants' eye movements over "natural" scenes and "experimental" scenes SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE Infants; Eye movements; Natural scenes; Object perception; Context ID MEMORY RETRIEVAL; STIMULUS CONTEXT; PERCEPTION; RECOGNITION; ATTENTION; OBJECT AB Eye movements of 30 4-month-olds were tracked as infants viewed animals and vehicles in "natural" scenes and, for comparison, in homogeneous "experimental" scenes. Infants showed equivalent looking time preferences for natural and experimental scenes overall, but fixated natural scenes and objects in natural scenes more than experimental scenes and objects in experimental scenes and shifted fixations between objects and contexts more in natural than in experimental scenes. The findings show how infants treat objects and contexts in natural scenes and suggest that they treat more commonly used experimental scenes differently. Published by Elsevier Inc. C1 [Bornstein, Marc H.; Mash, Clay; Arterberry, Martha E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Arterberry, Martha E.] Colby Coll, Waterville, ME 04901 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [Z01 HD001119-20] NR 26 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD FEB PY 2011 VL 34 IS 1 BP 206 EP 210 DI 10.1016/j.infbeh.2010.12.010 PG 5 WC Psychology, Developmental SC Psychology GA 728RI UT WOS:000287891800021 PM 21195480 ER PT J AU Dinse, GE Peddada, SD AF Dinse, Gregg E. Peddada, Shyamal D. TI Comparing Tumor Rates in Current and Historical Control Groups in Rodent Cancer Bioassays SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Bootstrap; Carcinogenicity study; Extra variation; Historical range; National Toxicology Program (NTP); Poly-3 survival adjustment; Quantal response ID TESTS; CARCINOGENICITY; LESIONS AB When evaluating carcinogenicity, tumor rates from the current study are informally assessed within the context of relevant historical control tumor rates. Current rates outside the range of historical rates raise concerns. We propose a statistical procedure that formally compares tumor rates in current and historical control groups. We use a normal approximation for the null distribution of the proposed test when there are at least five historical control groups and the average tumor rate is above 0.5%; otherwise, we apply standard bootstrap techniques. For comparison purposes, we show that formally basing decisions on the range of historical control rates would yield unusually high false positive rates. That is, a range-based decision rule would not maintain the nominal 5% significance level and could produce Type I error rates as high as 67%. In other cases, the power could go to zero. The proposed test, however, controls Type I errors while adjusting for survival and extra variability among the historical studies. We illustrate the methods with data from a study of benzophenone. Compared to a range-based decision rule, the proposed test has several important advantages, including operating at the specified level and being applicable with as few as one historical study. C1 [Dinse, Gregg E.; Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU NIH, National Institute of Environmental Health Sciences [Z01-ES045007, Z01-ES101744] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES045007 and Z01-ES101744). The authors thank Grace Kissling, Joseph Haseman, and the reviewers for their helpful comments. NR 13 TC 5 Z9 5 U1 0 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD FEB PY 2011 VL 3 IS 1 BP 97 EP 105 DI 10.1198/sbr.2010.09044 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791HS UT WOS:000292656400009 PM 21566728 ER PT J AU Powers, JF Fliedner, SM Leav, I Altieri, DC Pacak, K Tischler, AS AF Powers, J. F. Fliedner, S. M. Leav, I. Altieri, D. C. Pacak, K. Tischler, A. S. TI TRAP-1 Is a New Surrogate Marker for SDH Mutation in Pheochromocytoma/Paraganglioma and a Potential Target for Chemotherapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Tufts Med Ctr, Boston, MA USA. NICHD, NIH, Bethesda, MD USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RI Fliedner, Stephanie/D-3406-2012 NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 590 BP 141A EP 141A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000030 ER PT J AU Aung, PP Russell, L Weinstein, D Heller, T Kleiner, D Kammula, U Rudloff, U Avital, I Quezado, M AF Aung, P. P. Russell, L. Weinstein, D. Heller, T. Kleiner, D. Kammula, U. Rudloff, U. Avital, I. Quezado, M. TI Morphologic Findings in a Novel Familial Polyposis Syndrome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 597 BP 143A EP 143A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000037 ER PT J AU Aly, FZ Hanson, JC Yang, W Kreitman, MS Merino, MJ Linehan, MW Pinto, PA Adams, LG Stevenson, HS Edelman, DC Emmert-Buck, MR Rodriguez-Canales, J AF Aly, F. Z. Hanson, J. C. Yang, W. Kreitman, M. S. Merino, M. J. Linehan, M. W. Pinto, P. A. Adams, L. G. Stevenson, H. S. Edelman, D. C. Emmert-Buck, M. R. Rodriguez-Canales, J. TI Regional Variation in Epigenetic Patterns in Prostate Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Aly, F. Z.; Hanson, J. C.; Yang, W.; Kreitman, M. S.; Merino, M. J.; Linehan, M. W.; Pinto, P. A.; Adams, L. G.; Stevenson, H. S.; Edelman, D. C.; Emmert-Buck, M. R.; Rodriguez-Canales, J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 739 BP 176A EP 176A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000179 ER PT J AU Aung, PP Walter, BA Garcia, C Bratslavsky, G Merino, MJ AF Aung, P. P. Walter, B. A. Garcia, C. Bratslavsky, G. Merino, M. J. TI Potential Role of HER2/Neu as a Molecular Target in the Treatment of High Grade Urothelial Cancer. Determination of Gene Amplification by FISH, CISH and IHC SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Univ Salamanca, E-37008 Salamanca, Spain. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 748 BP 179A EP 179A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000189 ER PT J AU Cannata-Ortiz, P Rodriguez, BW Bratslavsky, G Linehan, WM Merino, MJ AF Cannata-Ortiz, P. Rodriguez, B. Walter Bratslavsky, G. Linehan, W. M. Merino, M. J. TI Hybrid Tumors: All You Need To Know and More SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Cannata-Ortiz, P.; Rodriguez, B. Walter; Bratslavsky, G.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 766 BP 182A EP 183A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000206 ER PT J AU Cubilla, AL Chaux, A Rodriguez, IM Barreto, JE Netto, GJ Bosch, FX de Sanjose, S Munoz, N Hildesheim, A AF Cubilla, A. L. Chaux, A. Rodriguez, I. M. Barreto, J. E. Netto, G. J. Bosch, F. X. de Sanjose, S. Munoz, N. Hildesheim, A. TI Phimosis, Lichen Sclerosus, Smoking, Poverty, Sexually Related Epidemiological Factors and Late Diagnosis Are Prevalent among Patients with Penile Cancer in Paraguay SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. Johns Hopkins Univ, Baltimore, MD USA. Inst Catalan Oncol, Barcelona, Spain. CIBER Epidemiol & Salud Publ, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Hildesheim, Allan/B-9760-2015; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI Hildesheim, Allan/0000-0003-0257-2363; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 784 BP 186A EP 187A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000224 ER PT J AU Cubilla, AL Chaux, A Rodriguez, IM Barreto, JE Netto, GJ Bosch, FX de Sanjose, S Munoz, N Hildesheim, A AF Cubilla, A. L. Chaux, A. Rodriguez, I. M. Barreto, J. E. Netto, G. J. Bosch, F. X. de Sanjose, S. Munoz, N. Hildesheim, A. TI Sexual History and Distinctive Pathological Features in HPV-Related Penile Carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. Johns Hopkins Univ, Baltimore, MD USA. Inst Catalan Oncol, Barcelona, Spain. CIBER Epidemiol & Salud Publ, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Hildesheim, Allan/B-9760-2015; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI Hildesheim, Allan/0000-0003-0257-2363; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 785 BP 187A EP 187A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000225 ER PT J AU Sorbellini, M McNeal, B Athauda, G Cohen, B Giubellino, A Simpson, H Coleman, J Getzenberg, RH Netto, GJ Linehan, MW Pinto, PA Bottaro, DP AF Sorbellini, M. McNeal, B. Athauda, G. Cohen, B. Giubellino, A. Simpson, H. Coleman, J. Getzenberg, R. H. Netto, G. J. Linehan, M. W. Pinto, P. A. Bottaro, D. P. TI Urinary Met Level as a Novel Biomarker for Urothelial Carcinoma of the Bladder SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Baltimore, MD USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 951 BP 225A EP 225A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000391 ER PT J AU Romero, VAV Rodriguez, BAW Sobel, M Linehan, WM Merino, MJ AF Romero, V. A. Valera Rodriguez, B. A. Walter Sobel, M. Linehan, W. M. Merino, M. J. TI miR-210 (Hypoxia-Responsive) a Marker of Poor Prognosis in Clear Cell Renal Cell Carcinoma. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Romero, V. A. Valera; Rodriguez, B. A. Walter; Sobel, M.; Linehan, W. M.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 965 BP 228A EP 229A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000405 ER PT J AU Rodriguez, BAW Vargas, MP Romero, VAV Sobel, M Pinto, P Merino, MJ AF Rodriguez, B. A. Walter Vargas, M. P. Romero, V. A. Valera Sobel, M. Pinto, P. Merino, M. J. TI microRNA Expression Profiling in Prostate Cancer: Possible Role as a Biomarkers and/or Molecular Therapy. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. NCI NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 968 BP 229A EP 229A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000408 ER PT J AU Parrilla-Castellar, ER Merino, MJ AF Parrilla-Castellar, E. R. Merino, M. J. TI Cross-Sectional Study of Cervical Cancer among Hispanic Versus Non-Hispanic White Women Living in the United States. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Parrilla-Castellar, E. R.; Merino, M. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1113 BP 262A EP 262A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000553 ER PT J AU Carvajal, A Sua, L Silva, N Pittaluga, S Royo, C Sargent, RL Climent, F Jacobs, SA Delabie, J Naresh, K Bagg, A Harris, NL Swerdlow, SH Jaffe, ES Campo, E AF Carvajal, A. Sua, L. Silva, N. Pittaluga, S. Royo, C. Sargent, R. L. Climent, F. Jacobs, S. A. Delabie, J. Naresh, K. Bagg, A. Harris, N. L. Swerdlow, S. H. Jaffe, E. S. Campo, E. TI "In Situ" Mantle Cell Lymphoma (MCL), an Incidental Finding with an Indolent Clinical Course SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Oslo Univ Hosp, Oslo, Norway. Hammersmith Hosp, London, England. Hosp Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. RI Royo, Cristina/H-3193-2015 OI Royo, Cristina/0000-0002-1214-4656 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1228 BP 289A EP 289A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000668 ER PT J AU Huppmann, AR Leung, AA Jaffe, ES Raffeld, M Pittaluga, S AF Huppmann, A. R. Leung, A. A. Jaffe, E. S. Raffeld, M. Pittaluga, S. TI SOX11 Is a Marker of Follicular Dendritic Cell Neoplasms SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Huppmann, A. R.; Leung, A. A.; Jaffe, E. S.; Raffeld, M.; Pittaluga, S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1284 BP 302A EP 302A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000724 ER PT J AU Liu, Q Jegalian, A Raffeld, M Pittaluga, S Jaffe, ES AF Liu, Q. Jegalian, A. Raffeld, M. Pittaluga, S. Jaffe, E. S. TI Pediatric Follicular Lymphoma: A Comparison with Follicular Lymphoma in Young Adults SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Liu, Q.; Jegalian, A.; Raffeld, M.; Pittaluga, S.; Jaffe, E. S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1308 BP 307A EP 307A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000748 ER PT J AU Maric, I Simakova, O Olivares, N Chew, S Metcalfe, DD Wilson, TM AF Maric, I. Simakova, O. Olivares, N. Chew, S. Metcalfe, D. D. Wilson, T. M. TI Monocytosis in Systemic Mastocytosis: Clinico-Pathological and Prognostic Correlates SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NIH, CC, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1310 BP 308A EP 308A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285000750 ER PT J AU Shao, H Gronborg, M Yuan, CM Kreitman, RJ Stetler-Stevenson, M AF Shao, H. Gronborg, M. Yuan, C. M. Kreitman, R. J. Stetler-Stevenson, M. TI Hairy Cell Leukemia and Variant: Immunophenotypic Comparison and Variations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1362 BP 320A EP 321A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001018 ER PT J AU Song, JY Dunleavy, K Grant, N Davies-Hill, T Raffeld, M Wilson, WH Jaffe, ES Pittaluga, S AF Song, J. Y. Dunleavy, K. Grant, N. Davies-Hill, T. Raffeld, M. Wilson, W. H. Jaffe, E. S. Pittaluga, S. TI Clinicopathologic Features of Lymphomatoid Granulomatosis, a Single Institute Experience SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Song, J. Y.; Dunleavy, K.; Grant, N.; Davies-Hill, T.; Raffeld, M.; Wilson, W. H.; Jaffe, E. S.; Pittaluga, S.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1369 BP 322A EP 323A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001025 ER PT J AU Spencer, DV Foulks, CL Geigerman, CM Akl, PS Lai, AY Wade, PA Jaye, DL Hill, CE AF Spencer, D. V. Foulks, C. L. Geigerman, C. M. Akl, P. S. Lai, A. Y. Wade, P. A. Jaye, D. L. Hill, C. E. TI Gene and Protein Isoform Expression Analysis of the BCL-6 Associated Transcriptional Corepressor MTA3 in B- lineage Cells SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Emory Univ, Atlanta, GA 30322 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1371 BP 323A EP 323A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001027 ER PT J AU Summers, TA Eberle, FC Pittaluga, S Wilson, WH Dunleavy, K Raffeld, M Hewitt, SM Jaffe, ES AF Summers, T. A. Eberle, F. C. Pittaluga, S. Wilson, W. H. Dunleavy, K. Raffeld, M. Hewitt, S. M. Jaffe, E. S. TI Gray Zone Lymphomas: Becoming More Black and White? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Summers, T. A.; Eberle, F. C.; Pittaluga, S.; Wilson, W. H.; Dunleavy, K.; Raffeld, M.; Hewitt, S. M.; Jaffe, E. S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1375 BP 324A EP 324A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001031 ER PT J AU Tembhare, PR Yuan, CM Xi, L Janik, J Morris, J Raffeld, M Stetler-Stevenson, M AF Tembhare, P. R. Yuan, C. M. Xi, L. Janik, J. Morris, J. Raffeld, M. Stetler-Stevenson, M. TI Detection of T Cell Clonality at Diagnosis, in Small Samples and Monitoring of Minimal Residual Disaease (MRD) Using TCR-V Beta Repertoire Analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Ctr Canc Res, Mark O Hatfield Clin Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1381 BP 326A EP 326A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001037 ER PT J AU Venkataraman, G Traverse-Glehen, A Song, JY Eberle, FC Hanson, JC Dirnhofer, S Tzankov, A Heinze, G Raffeld, MA Pittaluga, S Jaffe, ES AF Venkataraman, G. Traverse-Glehen, A. Song, J. Y. Eberle, F. C. Hanson, J. C. Dirnhofer, S. Tzankov, A. Heinze, G. Raffeld, M. A. Pittaluga, S. Jaffe, E. S. TI Aberrant T-Cell Antigen Expression in Classical Hodgkin Lymphoma Is Associated with Decreased Event-Free Survival (EFS) and Overall Survival (OS) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Ctr Hosp Lyon Sud, Hosp Civils Lyon, F-69310 Pierre Benite, France. Univ Basel Hosp, CH-4031 Basel, Switzerland. Med Univ Vienna, Vienna, Austria. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1385 BP 326A EP 327A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001041 ER PT J AU Wang, W Plyler, R Janik, JE Jaffe, ES Calvo, KR AF Wang, W. Plyler, R. Janik, J. E. Jaffe, E. S. Calvo, K. R. TI microRNA Profiling of Follicular Lymphoma and Tumor Infiltrating T-Cells SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1391 BP 328A EP 328A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001047 ER PT J AU Hodgin, JB Nair, V Zhang, H Randolph, A Harris, RC Nelson, RG Brosius, FC Kretzler, M AF Hodgin, J. B. Nair, V. Zhang, H. Randolph, A. Harris, R. C. Nelson, R. G. Brosius, F. C. Kretzler, M. TI Cross-Species Identification of Conserved Glomerular Transcriptional Networks of Progressive Diabetic Nephropathy in Mouse and Man SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Nashville, TN USA. NIDDK, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1466 BP 345A EP 345A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001122 ER PT J AU Yang, HC Wang, SW Pastan, I Matsusaka, T Ichikawa, I Fogo, AB AF Yang, H-C Wang, S-W Pastan, I. Matsusaka, T. Ichikawa, I. Fogo, A. B. TI Angiotensin II Type I Receptor Blocker Is Limited in Protection Against Severe Podocyte Injury-Induced FSGS SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. NCI, NIH, Bethesda, MD 20892 USA. Tokai Univ, Sch Med, Kanagawa 2591100, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1503 BP 354A EP 355A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001159 ER PT J AU Brunt, EM Kleiner, DE Wilson, LA Belt, PH Neuschwander-Tetri, BA AF Brunt, E. M. Kleiner, D. E. Wilson, L. A. Belt, P. H. Neuschwander-Tetri, B. A. TI The Nonalcoholic Fatty Liver Disease Activity Score (NAS) and the Histopathologic Diagnosis in Nonalcoholic Fatty Liver Disease: Distinct Clinicopathologic Meanings SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Washington Univ, Sch Med, St Louis, MO USA. NCI, Washington, DC USA. Johns Hopkins Univ, Baltimore, MD USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1516 BP 357A EP 358A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001172 ER PT J AU Doherty, AR Ferrell, LD Morse, CG Kleiner, DE AF Doherty, A. R. Ferrell, L. D. Morse, C. G. Kleiner, D. E. TI Hepatic Pigment Accumulation in HIV Patients on HAART Therapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1522 BP 359A EP 359A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001178 ER PT J AU Martin, SE Badve, SS Steeg, P Hattab, EM AF Martin, S. E. Badve, S. S. Steeg, P. Hattab, E. M. TI Luminal A Subtype Predicts Improved Survival in Patients with Metastatic Breast Carcinoma to the Brain SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Indiana Univ Sch Med, Indianapolis, IN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1625 BP 383A EP 383A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001281 ER PT J AU Parrilla-Castellar, E Zhou, W Liu, J Tessarollo, L Levens, D AF Parrilla-Castellar, E. Zhou, W. Liu, J. Tessarollo, L. Levens, D. TI FBP Knock-Out Leads to a Hematopoietic Maturation Defect SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. NIH, Frederick, MD USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1686 BP 396A EP 396A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001342 ER PT J AU Liu, C Galli, S Tsokos, M AF Liu, C. Galli, S. Tsokos, M. TI miR-17-5b Inhibition Decreases Rhabdomyosarcoma Cell Growth In Vitro SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Liu, C.; Galli, S.; Tsokos, M.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1712 BP 402A EP 402A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001368 ER PT J AU Vargas, MP Carter, D Merino, MJ AF Vargas, M. P. Carter, D. Merino, M. J. TI Pulmonary Lesions Associated with BHD Syndrome SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Vargas, M. P.; Carter, D.; Merino, M. J.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1813 BP 426A EP 427A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001469 ER PT J AU Killian, K Wang, L Walker, B Glatfelter, A Smith, WI Meltzer, PS AF Killian, K. Wang, L. Walker, B. Glatfelter, A. Smith, W. I. Meltzer, P. S. TI Rapid and Reliable Method To Isolate Nuclei from FFPE Specimens for Genomic-Scale Molecular Profiling. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1887 BP 443A EP 444A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001542 ER PT J AU Hipp, J Cheng, J Hanson, J Yan, W Rodriguez-Canales, J Hipp, J Tangrea, M Emmert-Buck, MR Han, S Hewitt, S Monaco, J Madabhushi, A Balis, U AF Hipp, J. Cheng, J. Hanson, J. Yan, W. Rodriguez-Canales, J. Hipp, J. Tangrea, M. Emmert-Buck, M. R. Han, S. Hewitt, S. Monaco, J. Madabhushi, A. Balis, U. TI SIVQ Image Analysis: A High-Throughput Morphology Discovery Tool for Surgical Pathologists SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Univ Michigan, Ann Arbor, MI 48109 USA. NCI, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Piscataway, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1913 BP 449A EP 449A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 773CQ UT WOS:000291285001568 ER PT J AU Driscoll, JJ Minter, A Driscoll, DA Burris, JK AF Driscoll, James J. Minter, Alex Driscoll, Daniel A. Burris, Jason K. TI The Ubiquitin plus Proteasome Protein Degradation Pathway as a Therapeutic Strategy in the Treatment of Solid Tumor Malignancies SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Ubiquitin; Proteasome; Bortezomib; Solid Tumors ID KINASE INHIBITOR P27; MULTIPLE-MYELOMA CELLS; CANCER-THERAPY; PI3K/AKT/MTOR PATHWAY; MOLECULAR-BASIS; LUNG-CANCER; KAPPA-B; BORTEZOMIB; RESISTANCE; TARGET AB A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e. g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e. g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed. C1 [Driscoll, James J.; Minter, Alex; Burris, Jason K.] NCI, Med Oncol Branch, Magnuson Canc Ctr, NIH, Bethesda, MD 20892 USA. [Minter, Alex; Burris, Jason K.] Walter Reed Army Med Ctr, Dept Med, Hematol Oncol Serv, Washington, DC 20307 USA. [Driscoll, Daniel A.] Harvard Univ, Cambridge, MA 02138 USA. RP Driscoll, JJ (reprint author), NCI, Med Oncol Branch, Magnuson Canc Ctr, NIH, 10 Ctr Dr,12N-226, Bethesda, MD 20892 USA. EM driscollj@mail.nih.gov NR 61 TC 13 Z9 15 U1 0 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 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD FEB PY 2011 VL 11 IS 2 BP 242 EP 246 PG 5 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 764EY UT WOS:000290613000010 PM 21355840 ER PT J AU Weaver, DL Ashikaga, T Krag, DN Skelly, JM Anderson, SJ Harlow, SP Julian, TB Mamounas, EP Wolmark, N AF Weaver, D. L. Ashikaga, T. Krag, D. N. Skelly, J. M. Anderson, S. J. Harlow, S. P. Julian, T. B. Mamounas, E. P. Wolmark, N. TI Survival Impact of Occult Metastases in NSABP B-32: Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Breast Cancer. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Univ Vermont, Coll Med, Burlington, VT 05405 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Aultman Caner Ctr, Canton, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 280 BP 69A EP 69A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282300281 ER PT J AU Powers, JF Fliedner, SM Leav, I Altieri, DC Pacak, K Tischler, AS AF Powers, J. F. Fliedner, S. M. Leav, I. Altieri, D. C. Pacak, K. Tischler, A. S. TI TRAP-1 Is a New Surrogate Marker for SDH Mutation in Pheochromocytoma/Paraganglioma and a Potential Target for Chemotherapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Tufts Med Ctr, Boston, MA USA. NICHD, NIH, Bethesda, MD USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 590 BP 141A EP 141A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282300592 ER PT J AU Aung, PP Walter, BA Garcia, C Bratslavsky, G Merino, MJ AF Aung, P. P. Walter, B. A. Garcia, C. Bratslavsky, G. Merino, M. J. TI Potential Role of HER2/Neu as a Molecular Target in the Treatment of High Grade Urothelial Cancer. Determination of Gene Amplification by FISH, CISH and IHC SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Univ Salamanca, E-37008 Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 749 BP 179A EP 179A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282300751 ER PT J AU Cubilla, AL Chaux, A Rodriguez, IM Barreto, JE Netto, GJ Bosch, FX de Sanjose, S Munoz, N Hildesheim, A AF Cubilla, A. L. Chaux, A. Rodriguez, I. M. Barreto, J. E. Netto, G. J. Bosch, F. X. de Sanjose, S. Munoz, N. Hildesheim, A. TI Phimosis, Lichen Sclerosus, Smoking, Poverty, Sexually Related Epidemiological Factors and Late Diagnosis Are Prevalent among Patients with Penile Cancer in Paraguay. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. Johns Hopkins Univ, Baltimore, MD USA. Inst Catalan Oncol, Barcelona, Spain. CIBER Epidemiol & Salud Publ, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Hildesheim, Allan/B-9760-2015; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI Hildesheim, Allan/0000-0003-0257-2363; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 784 BP 186A EP 187A PG 2 WC Pathology SC Pathology GA 720LN UT WOS:000287282300786 ER PT J AU Cubilla, AL Chaux, A Rodriguez, IM Barreto, JE Netto, GJ Bosch, FX de Sanjose, S Munoz, N Hildesheim, A AF Cubilla, A. L. Chaux, A. Rodriguez, I. M. Barreto, J. E. Netto, G. J. Bosch, F. X. de Sanjose, S. Munoz, N. Hildesheim, A. TI Sexual History and Distinctive Pathological Features in HPV-Related Penile Carcinomas. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Inst Patol & Invest, Asuncion, Paraguay. Johns Hopkins Univ, Baltimore, MD USA. Inst Catalan Oncol, Barcelona, Spain. CIBER Epidemiol & Salud Publ, Barcelona, Spain. NCI, Bethesda, MD 20892 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Hildesheim, Allan/B-9760-2015; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI Hildesheim, Allan/0000-0003-0257-2363; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 785 BP 187A EP 187A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282300787 ER PT J AU Sorbellini, M McNeal, B Athauda, G Cohen, B Giubellino, A Simpson, H Coleman, J Getzenberg, RH Netto, GJ Linehan, MW Pinto, PA Bottaro, DP AF Sorbellini, M. McNeal, B. Athauda, G. Cohen, B. Giubellino, A. Simpson, H. Coleman, J. Getzenberg, R. H. Netto, G. J. Linehan, M. W. Pinto, P. A. Bottaro, D. P. TI Urinary Met Level as a Novel Biomarker for Urothelial Carcinoma of the Bladder SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 951 BP 225A EP 225A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301106 ER PT J AU Carvajal, A Sua, L Silva, N Pittaluga, S Royo, C Sargent, RL Climent, F Jacobs, SA Delabie, J Naresh, K Bagg, A Harris, NL Swerdlow, SH Jaffe, ES Campo, E AF Carvajal, A. Sua, L. Silva, N. Pittaluga, S. Royo, C. Sargent, R. L. Climent, F. Jacobs, S. A. Delabie, J. Naresh, K. Bagg, A. Harris, N. L. Swerdlow, S. H. Jaffe, E. S. Campo, E. TI "In Situ" Mantle Cell Lymphoma (MCL), an Incidental Finding with an Indolent Clinical Course. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Oslo Univ Hosp, Oslo, Norway. Hammersmith Hosp, London, England. Hosp Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. RI Royo, Cristina/H-3193-2015 OI Royo, Cristina/0000-0002-1214-4656 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1228 BP 289A EP 289A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301383 ER PT J AU Shao, H Gronborg, M Yuan, CM Kreitman, RJ Stetler-Stevenson, M AF Shao, H. Gronborg, M. Yuan, C. M. Kreitman, R. J. Stetler-Stevenson, M. TI Hairy Cell Leukemia and Variant: Immunophenotypic Comparison and Variations SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1362 BP 320A EP 321A PG 2 WC Pathology SC Pathology GA 720LN UT WOS:000287282301517 ER PT J AU Shao, H Xi, L Raffeld, M Feldman, AL Ketterling, RP Knudson, R Rodriguez-Canales, J Hanson, J Pittaluga, S Jaffe, ES AF Shao, H. Xi, L. Raffeld, M. Feldman, A. L. Ketterling, R. P. Knudson, R. Rodriguez-Canales, J. Hanson, J. Pittaluga, S. Jaffe, E. S. TI Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with Transformation to Histiocytic/Dendritic Cell Sarcoma: Alterations of 17p as a Potential Risk Factor SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Mayo Clin, Rochester, MN USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1363 BP 321A EP 321A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301518 ER PT J AU Spencer, DV Foulks, CL Geigerman, CM Akl, PS Lai, AY Wade, PA Jaye, DL Hill, CE AF Spencer, D. V. Foulks, C. L. Geigerman, C. M. Akl, P. S. Lai, A. Y. Wade, P. A. Jaye, D. L. Hill, C. E. TI Gene and Protein Isoform Expression Analysis of the BCL-6 Associated Transcriptional Corepressor MTA3 in B- lineage Cells SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Emory Univ, Atlanta, GA 30322 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1371 BP 323A EP 323A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301526 ER PT J AU Venkataraman, G Traverse-Glehen, A Song, JY Eberle, FC Hanson, JC Dirnhofer, S Tzankov, A Heinze, G Raffeld, MA Pittaluga, S Jaffe, ES AF Venkataraman, G. Traverse-Glehen, A. Song, J. Y. Eberle, F. C. Hanson, J. C. Dirnhofer, S. Tzankov, A. Heinze, G. Raffeld, M. A. Pittaluga, S. Jaffe, E. S. TI Aberrant T-Cell Antigen Expression in Classical Hodgkin Lymphoma Is Associated with Decreased Event-Free Survival (EFS) and Overall Survival (OS) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Ctr Hosp Lyon Sud, Hosp Civils Lyon, F-69310 Pierre Benite, France. Univ Basel Hosp, CH-4031 Basel, Switzerland. Med Univ Vienna, Vienna, Austria. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1385 BP 326A EP 327A PG 2 WC Pathology SC Pathology GA 720LN UT WOS:000287282301540 ER PT J AU Hodgin, JB Nair, V Zhang, H Randolph, A Harris, RC Nelson, RG Brosius, FC Kretzler, M AF Hodgin, J. B. Nair, V. Zhang, H. Randolph, A. Harris, R. C. Nelson, R. G. Brosius, F. C. Kretzler, M. TI Cross-Species Identification of Conserved Glomerular Transcriptional Networks of Progressive Diabetic Nephropathy in Mouse and Man. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Nashville, TN USA. NIDDK, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1466 BP 345A EP 345A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301621 ER PT J AU Yang, HC Wang, SW Pastan, I Matsusaka, T Ichikawa, I Fogo, AB AF Yang, H-C Wang, S-W Pastan, I. Matsusaka, T. Ichikawa, I. Fogo, A. B. TI Angiotensin II Type I Receptor Blocker Is Limited in Protection Against Severe Podocyte Injury-Induced FSGS SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. NCI, NIH, Bethesda, MD 20892 USA. Tokai Univ, Sch Med, Kanagawa 2591100, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1503 BP 354A EP 355A PG 2 WC Pathology SC Pathology GA 720LN UT WOS:000287282301658 ER PT J AU Brunt, EM Kleiner, DE Wilson, LA Belt, PH Neuschwander-Tetri, BA AF Brunt, E. M. Kleiner, D. E. Wilson, L. A. Belt, P. H. Neuschwander-Tetri, B. A. TI The Nonalcoholic Fatty Liver Disease Activity Score (NAS) and the Histopathologic Diagnosis in Nonalcoholic Fatty Liver Disease: Distinct Clinicopathologic Meanings SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Washington Univ, Sch Med, St Louis, MO USA. NCI, Washington, DC USA. Johns Hopkins Univ, Baltimore, MD USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1516 BP 357A EP 358A PG 2 WC Pathology SC Pathology GA 720LN UT WOS:000287282301671 ER PT J AU Doherty, AR Ferrell, LD Morse, CG Kleiner, DE AF Doherty, A. R. Ferrell, L. D. Morse, C. G. Kleiner, D. E. TI Hepatic Pigment Accumulation in HIV Patients on HAART Therapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1522 BP 359A EP 359A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282301677 ER PT J AU Martin, SE Badve, SS Steeg, P Hattab, EM AF Martin, S. E. Badve, S. S. Steeg, P. Hattab, E. M. TI Luminal A Subtype Predicts Improved Survival in Patients with Metastatic Breast Carcinoma to the Brain. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Indiana Univ, Sch Med, Indianapolis, IN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1625 BP 383A EP 383A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282302071 ER PT J AU Hipp, J Cheng, J Hanson, J Yan, W Rodriguez-Canales, J Tangrea, M Emmert-Buck, MR Han, S Hewitt, S Monaco, J Madabhushi, A Balis, U AF Hipp, J. Cheng, J. Hanson, J. Yan, W. Rodriguez-Canales, J. Tangrea, M. Emmert-Buck, M. R. Han, S. Hewitt, S. Monaco, J. Madabhushi, A. Balis, U. TI SIVQ Image Analysis: A High-Throughput Morphology Discovery Tool for Surgical Pathologists SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting United States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP United States Canadian Acad Pathol C1 Univ Michigan, Ann Arbor, MI 48109 USA. NCI, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Piscataway, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2011 VL 24 SU 1 MA 1913 BP 449A EP 449A PG 1 WC Pathology SC Pathology GA 720LN UT WOS:000287282302358 ER PT J AU Barkan, D El Touny, LH Michalowski, AM Smith, JA Chu, I Davis, AS Webster, JD Hoover, S Simpson, MR Gauldie, J Green, JE AF Barkan, Dalit El Touny, Lara H. Michalowski, Aleksandra M. Smith, Jane Ann Chu, Isabel Davis, Anne Sally Webster, Joshua D. Hoover, Shelley Simpson, Mark R. Gauldie, Jack Green, Jeffrey E. TI Type I collagen enrichment at the metastatic site: The 'soil' triggering the transition from tumor dormancy to metastatic growth SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Barkan, Dalit] Univ Haifa, IL-31999 Haifa, Israel. [El Touny, Lara H.; Michalowski, Aleksandra M.; Chu, Isabel; Webster, Joshua D.; Hoover, Shelley; Simpson, Mark R.; Green, Jeffrey E.] NCI, Bethesda, MD 20892 USA. [Smith, Jane Ann; Gauldie, Jack] McMaster Univ, Hamilton, ON, Canada. [Davis, Anne Sally] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 174 EP 174 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200057 ER PT J AU Balamurugan, K Sarkar, TR Wang, JM Sharan, S Anver, MM Sterneck, E Leighty, R AF Balamurugan, Kuppusamy Sarkar, Tapasree Roy Wang, Ju M. Sharan, Shikha Anver, Miriam M. Sterneck, Esta Leighty, Robert TI The tumor suppressor C/EBP delta (CEBPD) promotes metastasis of MMTV-Neu mouse mammary tumors and augments mTOR/AKT/HIF-1 activity through inhibition of FBXW7 expression SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Balamurugan, Kuppusamy; Sarkar, Tapasree Roy; Sharan, Shikha; Sterneck, Esta; Leighty, Robert] NCI, Frederick, MD 21701 USA. [Wang, Ju M.] Natl Cheng Kung Univ, Tainan 70101, Taiwan. [Anver, Miriam M.] SAIC, Frederick, MD USA. NR 6 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 185 EP 185 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200093 ER PT J AU Gril, B Palmieri, D Qian, Y Liewehr, DJ Steinberg, SM Ileva, L Steeg, PS AF Gril, Brunilde Palmieri, Diane Qian, Yong Liewehr, David J. Steinberg, Seth M. Ileva, Lilia Steeg, Patricia S. TI Pazopanib reveals a role for B-Raf in tumorigenesis, angiogenesis and prevention of brain metastatic colonization of HER2+breast cancer cells SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Gril, Brunilde; Palmieri, Diane; Qian, Yong; Liewehr, David J.; Steinberg, Seth M.; Steeg, Patricia S.] NCI, Bethesda, MD 20892 USA. [Ileva, Lilia] NCI, Frederick, MD 21701 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 193 EP 194 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200117 ER PT J AU Evans, LM Palmieri, D Steeg, PS AF Evans, Lynda M. Palmieri, Diane Steeg, Patricia S. TI Full-length L1CAM is overexpressed on brain-seeking MDA-MB-231 breast cancer cells and may play a role in binding Tenascin C and colony formation in vitro SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Evans, Lynda M.; Palmieri, Diane; Steeg, Patricia S.] NIH, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 194 EP 194 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200119 ER PT J AU Fitzgerald, DP Palmieri, D Qian, YZ Vega-Valle, E Davis, S Meltzer, P Steeg, PS AF Fitzgerald, Daniel Patrick Palmieri, Diane Qian, Yongzhen Vega-Valle, Eleazar Davis, Sean Meltzer, Paul Steeg, Patricia S. TI Genetic studies in murine/xenograft models of breast cancer brain metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Palmieri, Diane; Davis, Sean; Meltzer, Paul; Steeg, Patricia S.] NCI, Bethesda, MD 20892 USA. [Qian, Yongzhen; Vega-Valle, Eleazar] SAIC, NIH, Frederick, MD USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 194 EP 195 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200120 ER PT J AU Mailer, O Lyons, TR Green, JE Schedin, PJ AF Mailer, Ori Lyons, Traci R. Green, Jeffrey E. Schedin, Pepper J. TI The function of extracellular matrix in breast cancer dormancy SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract ID CELLS C1 [Mailer, Ori; Lyons, Traci R.; Schedin, Pepper J.] Univ Colorado Denver, Aurora, CO USA. [Green, Jeffrey E.] NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 210 EP 210 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200165 ER PT J AU Liu, H Yukinari, K Erzinger, SA Kiriakova, GM Palmieri, D Steeg, PS Price, JE AF Liu, Hui Yukinari, Kato Erzinger, Stephanie A. Kiriakova, Galina M. Palmieri, Diane Steeg, Patricia S. Price, Janet E. TI shRNA mediated inhibition of MMP-1 attenuates breast cancer growth and metastasis to brain SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Liu, Hui; Yukinari, Kato; Erzinger, Stephanie A.; Kiriakova, Galina M.; Price, Janet E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Palmieri, Diane; Steeg, Patricia S.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 220 EP 220 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200192 ER PT J AU Alsarraj, J Walker, RC Webster, JD Simpson, RM Ozato, K Hunter, KW AF Alsarraj, Jude Walker, Renard C. Webster, Joshua D. Simpson, R. Mark Ozato, Keiko Hunter, Kent W. TI A mutant of the metastasis susceptibility gene Brd4 promotes EMT, stem cell-like conversion and metastatic progression in a mouse mammary tumor model SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Alsarraj, Jude; Walker, Renard C.; Webster, Joshua D.; Simpson, R. Mark; Hunter, Kent W.] NCI, NIH, Bethesda, MD 20892 USA. [Ozato, Keiko] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 226 EP 226 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200212 ER PT J AU Clark, RJ Marasa, B Otto, K Gorospe, M Rinker-Schaeffer, C AF Clark, Robert J. Marasa, Bernard Otto, Kristen Gorospe, Myriam Rinker-Schaeffer, Carrie TI The regulation of mitogen-activated kinase kinase 4 by microRNA-24 in prostate cancer cell lines SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Clark, Robert J.; Otto, Kristen; Rinker-Schaeffer, Carrie] Univ Chicago, Chicago, IL 60637 USA. [Marasa, Bernard; Gorospe, Myriam] NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 227 EP 228 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200218 ER PT J AU Mkrtichyan, M Naiiar, YG Raulfs, EC Khleif, SN AF Mkrtichyan, Mikayel Naiiar, Yana G. Raulfs, Estella C. Khleif, Samir N. TI Defining a novel mechanism of a-PD1 synergy with vaccine to induce potent anti-tumor effects SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Mkrtichyan, Mikayel; Naiiar, Yana G.; Raulfs, Estella C.; Khleif, Samir N.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 247 EP 248 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200279 ER PT J AU Murthv, SRK Lee, T Cawley, N Loh, P AF Murthv, Saravana Radha Krishna Lee, Terence Cawley, Niamh Loh, Peng TI A spliced isoform of carboxypeptidase E drives tumor metastasis epigenetically and predicts future malignancy for different cancers SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Murthv, Saravana Radha Krishna; Cawley, Niamh; Loh, Peng] NICHD, NIH, Bethesda, MD USA. [Lee, Terence] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 249 EP 249 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200282 ER PT J AU Flores, NM Sledge, GW Badve, S Palmieri, D Steeg, P AF Flores, Natasha M. Sledge, George W., Jr. Badve, Sunil Palmieri, Diane Steeg, Patricia TI A structural and functional analysis of BARD1 and RAD51 overexpression in the MCF10A cell line SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Flores, Natasha M.; Palmieri, Diane; Steeg, Patricia] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Sledge, George W., Jr.; Badve, Sunil] Indiana Univ Sch Med, Indianapolis, IN USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 259 EP 259 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200309 ER PT J AU Li, M Kapoor, A Mazilu, D Horvath, KA AF Li, Ming Kapoor, Ankur Mazilu, Dumitru Horvath, Keith A. TI Pneumatic Actuated Robotic Assistant System for Aortic Valve Replacement Under MRI Guidance SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE MRI robot; real-time MRI (rtMRI)-guided intervention; transapical aortic valve replacement ID PROSTATE INTERVENTIONS; COMPATIBLE MANIPULATOR; INTERACTIVE MRI; DESIGN; INSTRUMENTS; TRACKING; DEVICES; BREAST AB We present a pneumatic actuated robotic assistant system for transapical aortic valve replacement under MRI guidance in a beating heart. This is a minimally invasive procedure that is currently performed manually inside the MRI bore. A robotic assistance system that integrates an interactive real-time MRI system, a robotic arm with a newly developed robotic valve delivery module, as well as user interfaces for the physician to plan the procedure and manipulate the robot, would be advantageous for the procedure. An Innomotion arm with hands-on cooperative interface was used as a device holder. A compact MRI compatible robotic delivery module was developed for delivering both balloon-expandable and self-expanding prostheses. A compact fiducial that can be placed close to the volume of interest and requires a single image plane was used for image-based robot registration. The system provides different user interfaces at various stages of the procedure. We present the development and evaluation of the components and the system in ex-vivo experiments. C1 [Li, Ming; Kapoor, Ankur; Mazilu, Dumitru; Horvath, Keith A.] NIH, Bethesda, MD 20892 USA. RP Li, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM lim2@mail.nih.gov; kapooran@mail.nih.gov; mazilud@mail.nih.gov; horvathka@mail.nih.gov FU National Heart Lung and Blood Institute and Clinical Center, National Institutes of Health, Department of Health and Human Services, USA FX This work was supported through the Intramural Research Program of the National Heart Lung and Blood Institute and Clinical Center, National Institutes of Health, Department of Health and Human Services, USA. NR 27 TC 15 Z9 16 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2011 VL 58 IS 2 BP 443 EP 451 DI 10.1109/TBME.2010.2089983 PG 9 WC Engineering, Biomedical SC Engineering GA 710LZ UT WOS:000286514500027 PM 21041156 ER PT J AU Kristinsson, SY Landgren, O AF Kristinsson, Sigurdur Y. Landgren, Ola TI What Causes Waldenstrom's Macroglobulinemia: Genetic or Immune-Related Factors, or a Combination? SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article; Proceedings Paper CT 6th International Workshop on Waldenstroms Macroglobulinemia CY OCT 06-10, 2010 CL Venice, ITALY ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; FAMILIAL AGGREGATION; RHEUMATOID-ARTHRITIS; RISK; PATTERNS; SUSCEPTIBILITY; CANCER; TUMORS AB Population-based studies suggest a role for chronic immune stimulation and genetic factors in the causation of lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM). In this review we summarize and discuss our current understanding on etiology and pathogenesis of LPL/WM. We also highlight on gaps in the literature and propose Enure directions for population-based and molecular studies designed to expand our knowledge and uncover biological underpinnings of identified associations. Further, we address clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up. C1 [Kristinsson, Sigurdur Y.] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden. [Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@karolinska.se RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Intramural NIH HHS NR 23 TC 4 Z9 4 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD FEB PY 2011 VL 11 IS 1 BP 85 EP 87 DI 10.3816/CLML.2011.n.015 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 748IF UT WOS:000289383600016 PM 21454199 ER PT J AU Murphy, DL Moya, PR AF Murphy, Dennis L. Moya, Pablo R. TI Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional G x G and G x E differences in health and disease SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; DEPRESSIVE SYMPTOMS; POLYMORPHISMS; ASSOCIATION; METAANALYSIS; GENOTYPE; ANXIETY; MICE; ACTIVATION; MODERATION AB Recent major findings from studies of SLC6A4 and its corresponding protein, the serotonin (5-HT) transporter (SERT) in humans, rodents and non-human primates indicate that combinations of SLC6A4 non-coding 5', 3' UTRs and intronic regions plus coding variants acting together can change 5HT transport as much as 40-fold in vitro. In vivo, SLC6A4 variants in humans and other species lead to marked physiological changes, despite mitigating neurodevelopmental adaptations in 5-HT receptors plus compensatory alterations in 5-HT synthesis and metabolism. Polymorphisms in SLC6A4 are associated with differences in emotional, endocrine, and personality characteristics as well as many diseases. This gene, in combinations with gene x gene (G x G) and gene x environment (G x E) interactions nonetheless remains incompletely understood, with some association findings remaining controversial. Considering its primary importance in the regulation and function of the entire serotonergic system (as evidenced by the consequences of SERT-mediated reuptake inhibition by SRIs like fluoxetine in humans and of genetically engineered changes in mice and rats), it seems likely that SLC6A4 and SERT will remain areas of high interest in our field's attempts to better understand and treat 5-HT-related disorders. C1 [Murphy, Dennis L.; Moya, Pablo R.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA. EM dm30h@nih.gov FU NIMH; NIH FX This research was supported by the Intramural Research Program of the NIMH, NIH. The authors are also grateful to Theresa B. DeGuzman for her editorial and graphical assistance. NR 48 TC 33 Z9 34 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD FEB PY 2011 VL 11 IS 1 BP 3 EP 10 DI 10.1016/j.coph.2011.02.008 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 752NL UT WOS:000289698700002 PM 21439906 ER PT J AU Pinheiro, RO Salles, JD Sarno, EN Sampaio, EP AF Pinheiro, Roberta Olmo Salles, Jorgenilce de Souza Sarno, Euzenir Nunes Sampaio, Elizabeth Pereira TI Mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview SO FUTURE MICROBIOLOGY LA English DT Review DE leprosy; Mycobacterium leprae; Schwann cells; thalidomide; TNF-alpha ID NECROSIS-FACTOR-ALPHA; ERYTHEMA-NODOSUM LEPROSUM; HUMAN SCHWANN-CELLS; TOLL-LIKE RECEPTOR-2; TYPE-1 REVERSAL REACTIONS; PHENOLIC GLYCOLIPID-I; LEPROMATOUS LEPROSY; DC-SIGN; TNF-ALPHA; DENDRITIC CELLS AB Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae-host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. C1 [Pinheiro, Roberta Olmo; Salles, Jorgenilce de Souza; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira] Fiocruz MS, Leprosy Lab, Inst Oswaldo Cruz, BR-21040213 Rio De Janeiro, Brazil. [Sampaio, Elizabeth Pereira] NIH, Immunopathogenesis Sect, Lab Clin Infect Dis, LCID, Bethesda, MD 20892 USA. RP Sampaio, EP (reprint author), Fiocruz MS, Leprosy Lab, Inst Oswaldo Cruz, Av Brasil 4365, BR-21040213 Rio De Janeiro, Brazil. EM esampaio@ioc.fiocruz.br FU IOC/FIOCRUZ; CNPq, Brazil; NIH/NIAID FX This work was supported by IOC/FIOCRUZ, CNPq, Brazil, and in part by the Intramural Research Program of NIH/NIAID. The authors' group at the Rockefeller University, NY, USA, had a patent received for the work on thalidomide action developed in 1990/1991. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 152 TC 14 Z9 14 U1 0 U2 15 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD FEB PY 2011 VL 6 IS 2 BP 217 EP 230 DI 10.2217/FMB.10.173 PG 14 WC Microbiology SC Microbiology GA 737SP UT WOS:000288588800015 PM 21366421 ER PT J AU Hall, RH AF Hall, Robert H. TI A De in the life of cholera SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Review DE Cholera toxin; De; EL Tor; Vibrio cholerae ID VIBRIO-CHOLERAE; VACCINE; DE,S.N.; SCIENCE AB The 50-year commemoration of S.N. De's seminal 1959 publication in Nature provides an opportunity to reflect on scientific discovery, recognition, and public health. De's paper marked the first major conceptual advance in cholera research since 1884, when Robert Koch definitively identified Der Konunabazillus as the aetiological agent of cholera. Unfortunately, Koch reported that systemic toxinosis and multi-organ failure led to severe dehydrating diarrhoea, thereby mistaking cause for effect. As a consequence, while work on other microbial pathogens advanced into the development of vaccines and therapeutics, cholera research languished as scientists injected animals parenterally in decades of futile effort to develop an animal model of diarrhoea. This fundamental misconception in cholera pathogenesis was swept away when S.N. De used ligated loops of rabbit ileum to demonstrate lumenal fluid accumulation in the presence of Vibrio cholerae culture filtrates. After some delay, De's observation of a diarrhoeagenic exotoxin became the founding principle of modern cholera research, vaccination, and treatment; and a burst of discovery saw V. cholerae transformed into the enteric pathogen best understood at the molecular level. The scientific basis for orally administering vaccines to induce mucosal immunity was established, and the success of oral rehydration, what has been described as one of the 20(th) century's most important medical advances, was explained. Nobel laureate Joshua Lederberg wrote of De's iconoclastic creativity, experimental skill, and observational mastery, and many other leaders in the field concurred. De was nominated for the Nobel Prize in Physiology or Medicine more than once. But despite the passage of half a century from De's work, cholera remains a frustrating problem: we are clearly missing something. In reviewing the scientific and programmatic impact of S.N. De on cholera, it is clear that a defining victory against the disease is achievable, but only if basic scientific discoveries are relentlessly driven towards progress in public health. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Hall, RH (reprint author), NIAID, NIH, 6610 Rockledge Dr,Rm 5106, Bethesda, MD 20892 USA. EM rhall@niaid.nih.gov NR 33 TC 0 Z9 0 U1 0 U2 7 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD FEB PY 2011 VL 133 IS 2 BP 146 EP 152 PG 7 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 747LW UT WOS:000289322300005 PM 21415488 ER PT J AU Britton, KA Fox, CS AF Britton, Kathryn A. Fox, Caroline S. TI Perivascular adipose tissue and vascular disease SO CLINICAL LIPIDOLOGY LA English DT Review DE cardiovascular; epidemiology; imaging; mechanisms; perivascular adipose tissue ID NECROSIS-FACTOR-ALPHA; CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY ENDOTHELIAL FUNCTION; MUSCLE RESISTANCE ARTERIES; II-INDUCED HYPERTENSION; VISCERAL ABDOMINAL FAT; NITRIC-OXIDE SYNTHASE; PERICARDIAL FAT; INSULIN-RESISTANCE; EPICARDIAL FAT AB Perivascular adipose tissue is a local deposit of adipose tissue surrounding the vasculature. Perivascular adipose tissue is present throughout the body and has been shown to have a local effect on blood vessels. The influence of perivascular adipose tissue on the vasculature changes with increasing adiposity. This article describes the anatomy and pathophysiology of perivascular adipose tissue and the experimental evidence supporting its local adverse effect on the vasculature. Methods for quantifying perivascular adipose tissue in free-living populations will be described. Finally, the epidemiological literature demonstrating an association between perivascular adipose tissue and cardiometabolic disease will be explored. C1 [Britton, Kathryn A.] NHLBI, Farmingham Heart Study, Framingham, MA USA. [Britton, Kathryn A.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Britton, Kathryn A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. RP Fox, CS (reprint author), 73 mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999, ZIA HL006094-01] NR 85 TC 23 Z9 23 U1 3 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD FEB PY 2011 VL 6 IS 1 BP 79 EP 91 DI 10.2217/CLP.10.89 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 741DX UT WOS:000288844400013 PM 21686058 ER PT J AU Brooks, BP AF Brooks, Brian P. TI Making progress in albinism SO JOURNAL OF AAPOS LA English DT Editorial Material ID EFFICACY C1 NEI, Ophthalm Genet Branch, Bethesda, MD 20892 USA. RP Brooks, BP (reprint author), NEI, Ophthalm Genet Branch, 10 Ctr Dr,MSC 1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD FEB PY 2011 VL 15 IS 1 BP 1 EP 2 DI 10.1016/j.jaapos.2011.01.002 PG 2 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 740VI UT WOS:000288822100001 PM 21397796 ER PT J AU Saporito, RA Norton, RA Andriamaharavo, NR Garraffo, HM Spande, TF AF Saporito, Ralph A. Norton, Roy A. Andriamaharavo, Nirina R. Garraffo, Hugo Martin Spande, Thomas F. TI Alkaloids in the Mite Scheloribates laevigatus: Further Alkaloids Common to Oribatid Mites and Poison Frogs SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE Chemical defense; Dendrobatids; Indolizidines; Oil glands; Opisthonotal glands; Pumiliotoxins; Scheloribatidae; Tricyclic alkaloids; Poison frog ID FEEDING PREFERENCES; ACARI; ANTS; PUMILIOTOXIN; SYMBIONT; PATTERNS; ANATOMY; FOREST; DIET; SKIN AB Poison frogs are chemically defended from predators by diverse alkaloids, almost all of which are sequestered unchanged from alkaloid-containing arthropods in the frog diet. Oribatid mites recently have been proposed as a major dietary source of poison frog alkaloids. Here, we report on alkaloids common to an oribatid mite and poison frogs. Gas chromatographic-mass spectrometric analysis of methanol extracts of adult Scheloribates laevigatus (Oribatida: Scheloribatidae) revealed nine alkaloids. Five of these have been detected previously in the skin glands of poison frogs: two isomers of the pumiliotoxin 291G, two isomers of the 5,6,8-trisubstituted indolizidine 209C, and the 5,6,8-trisubstituted indolizidine 195G. The other four alkaloids, a pumiliotoxin, a tricyclic (coccinelline-like), and two isomers of an izidine, were not previously known, but are similar in structure to alkaloids found in poison frogs. Alkaloids were not detected in immature S. laevigatus, suggesting that they are adult-specific and possibly the result of mite biosynthesis. Although most of the alkaloids detected in S. laevigatus are common to poison frogs, the geographic distributions of these organisms are not sympatric. The findings of this study indicate that oribatid mites, and in particular, members of the genus Scheloribates, represent a relatively unexplored arthropod repository for alkaloids and a significant dietary source of alkaloids in poison frogs. C1 [Saporito, Ralph A.] John Carroll Univ, Dept Biol, University Hts, OH 44118 USA. [Norton, Roy A.] SUNY Syracuse, Coll Environm Sci & Forestry, Syracuse, NY 13210 USA. [Andriamaharavo, Nirina R.; Garraffo, Hugo Martin; Spande, Thomas F.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Saporito, RA (reprint author), John Carroll Univ, Dept Biol, University Hts, OH 44118 USA. EM ralph.saporito@gmail.com FU NIDDK; National Science Foundation; NIH FX J.M. Snyder provided comments that improved the quality of this manuscript. An NIH Courtesy Appointment and a National Science Foundation Postdoctoral Research Fellowship supported R.A.S. The research at NIH was funded by intramural funds of NIDDK. NR 33 TC 17 Z9 17 U1 2 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD FEB PY 2011 VL 37 IS 2 BP 213 EP 218 DI 10.1007/s10886-011-9914-7 PG 6 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 741NI UT WOS:000288870000011 PM 21318398 ER PT J AU Feng, JX Wang, HS Shin, DM Masiuk, M Qi, CF Morse, HC AF Feng, Jianxun Wang, Hongsheng Shin, Dong-Mi Masiuk, Marek Qi, Chen-Feng Morse, Herbert C., III TI IFN Regulatory Factor 8 Restricts the Size of the Marginal Zone and Follicular B Cell Pools SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKEMIA-LIKE SYNDROME; POSITIVE SELECTION; GERMINAL CENTER; IN-VIVO; LYMPHOCYTE DEVELOPMENT; ANTIGEN RECEPTOR; DENDRITIC CELLS; FATE DECISION; LINEAGE; MICE AB Transcriptional control of marginal zone (MZ) and follicular (FO) B cell development remains incompletely understood. The transcription factor, IFN regulatory factor (IRF)8, is known to play important roles in the differentiation of early B cells. In this article, we demonstrate that IRF8 is also required for normal development of MZ and FO B cells. Mice with a conventional knockout of Irf8 (IRF8(-/-)) or a point mutation in the IRF association domain of IRF8 had increased numbers of MZ B cells. To determine the B cell-intrinsic effects of IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with CD19-Cre mice (designated IRF8-conditional knockout [CKO]). These mice had enlarged MZ and increased numbers of MZ and FO B cells compared with controls. The FO B cells of CKO mice exhibited reduced expression of CD23 and moderately increased expression of CD21. Gene-expression profiling showed that increased B cell production in IRF8-CKO mice was associated with changes in expression of genes involved in regulation of transcription, signaling, and inflammation. Functional studies showed that IRF8-CKO mice generated normal Ab responses to T-independent and T-dependent Ags. Thus, IRF8 controls the expansion and maturation of MZ and FO B cells but has little effect on B cell function. The Journal of Immunology, 2011, 186: 1458-1466. C1 [Feng, Jianxun; Wang, Hongsheng; Shin, Dong-Mi; Masiuk, Marek; Qi, Chen-Feng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. [Masiuk, Marek] Pomeranian Med Univ, Dept Pathol, PL-70252 Szczecin, Poland. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM wanghongs@niaid.nih.gov; hmorse@niaid.nih.gov RI Masiuk, Marek/M-8485-2014; OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 48 TC 31 Z9 32 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2011 VL 186 IS 3 BP 1458 EP 1466 DI 10.4049/jimmunol.1001950 PG 9 WC Immunology SC Immunology GA 708RE UT WOS:000286381200024 PM 21178004 ER PT J AU Schenekar, T Winkler, KA Troyer, JL Weiss, S AF Schenekar, Tamara Winkler, Kathrin A. Troyer, Jennifer L. Weiss, Steven TI Isolation and Characterization of the CYP2D6 Gene in Felidae with Comparison to Other Mammals SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE Cytochrome P450; Cats; Selection; dN/dS; Slightly deleterious mutations ID NONSYNONYMOUS NUCLEOTIDE SUBSTITUTIONS; DETECTING POSITIVE SELECTION; HUMAN CYTOCHROME-P450 2D6; ADVERSE DRUG-REACTIONS; AMINO-ACID; MOLECULAR ADAPTATION; MAXIMUM-LIKELIHOOD; EVOLUTION; METABOLISM; POLYMORPHISMS AB The highly polymorphic CYP2D6 protein metabolizes about 25% of commonly used drugs and underlies a broad spectrum of drug responses among individuals. In contrast to extensive knowledge on the human CYP2D6 gene, little is known about the gene in non-human mammals. CYP2D6 mRNA from 23 cats (Felidae) spanning seven species were compared to available CYPD6 sequences in ten additional mammals and multiple allelic variants in humans. A relatively high mean dN/dS ratio (0.565) was observed, especially within Felidae. Pairwise dN/dS ratios were non-monotonically distributed with respect to evolutionary distance suggesting either positive selection or retention of slightly deleterious mutations. Positive selection on specific codons, most notably in regions involved in substrate recognition and membrane anchoring is supported and the possible influence of diet on specific amino acid changes in substrate binding sites is discussed. C1 [Schenekar, Tamara; Winkler, Kathrin A.; Weiss, Steven] Karl Franzens Univ Graz, Inst Zool, A-8010 Graz, Austria. [Troyer, Jennifer L.] NCI, SAIC Frederic Inc, Lab Genom Div, Frederick, MD 21702 USA. RP Weiss, S (reprint author), Karl Franzens Univ Graz, Inst Zool, Univ Pl 2, A-8010 Graz, Austria. EM steven.weiss@uni-graz.at RI Troyer, Jennifer/B-8415-2012; Weiss, Steven/L-6016-2015 OI Weiss, Steven/0000-0002-4734-5984 FU Faculty of Natural Sciences of the Karl-Franzens University Graz; NIH, National Cancer Institute, Center for Cancer Research; National Institutes of Health [HHSN26120080001E]; National Cancer Institute FX We thank Stephen O'Brien for his generous support, provision of tissue samples and access to facilities. We also thank Natalie Baggett for cDNA preparation. The work was partially funded by the Faculty of Natural Sciences of the Karl-Franzens University Graz. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and has also been funded in part with federal funds from the National Cancer Institute and National Institutes of Health, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 57 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD FEB PY 2011 VL 72 IS 2 BP 222 EP 231 DI 10.1007/s00239-010-9424-1 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 740QB UT WOS:000288808400010 PM 21188366 ER PT J AU Prentice, RL Rossouw, JE AF Prentice, Ross L. Rossouw, Jacques E. TI "Preventing breast cancer in postmenopausal women by achievable diet modification: A missed opportunity in public health policy" (Dayal HH and Kalia A, The Breast 2010; 19: 309-311) SO BREAST LA English DT Letter ID MODIFICATION TRIAL; FAT; PATTERN; RISK C1 [Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Rossouw, Jacques E.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM rprentic@fhcrc.org; rossouwj@nhlbi.nih.gov NR 10 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD FEB PY 2011 VL 20 IS 1 BP 99 EP 99 DI 10.1016/j.breast.2010.11.001 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 736GL UT WOS:000288478900019 PM 21112212 ER PT J AU Caron, WP Clewell, H Dedrick, R Ramanathan, R Yu, N Tonda, M Schellens, JH Beijnen, JH Zamboni, WC AF Caron, Whitney P. Clewell, Harvey Dedrick, Robert Ramanathan, Ramesh Yu, Ning Tonda, Margaret Schellens, Jan H. Beijnen, Jos H. Zamboni, William C. TI Symp IXb Preclinical and Translational Pharmacology of Nanoparticle Therapeutics SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE nanoparticles; pharmacology/pharmacokinetics; allometric scaling C1 [Caron, Whitney P.; Zamboni, William C.] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Res Triangle Pk, NC USA. [Clewell, Harvey] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Dedrick, Robert] NIH, Biomed Engn & Instrumentat Branch, Div Res Serv, Publ Hlth Serv,US Dept Hlth Educ & Welf, Bethesda, MD 20892 USA. [Ramanathan, Ramesh] Univ Pittsburgh, Pittsburgh Canc Inst, Mol Therapeut & Drug Discovery Program, Pittsburgh, PA USA. [Yu, Ning; Tonda, Margaret] ALZA Coporat, Mountain View, CA USA. [Schellens, Jan H.; Beijnen, Jos H.] Netherlands Canc Inst, Slotervaart Hosp, Dept Pharm & Pharmacol, Amsterdam, Netherlands. [Zamboni, William C.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Zamboni, William C.] UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC USA. [Zamboni, William C.] Carolina Ctr Canc Nanotechnol Excellence, Chapel Hill, NC USA. [Zamboni, William C.] N Carolina Bioanalyt Innovat Network, Durham, NC USA. NR 0 TC 0 Z9 0 U1 10 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 125 EP 126 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200108 ER PT J AU Miller, FG Brody, H AF Miller, Franklin G. Brody, Howard TI Understanding and Harnessing Placebo Effects: Clearing Away the Underbrush SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE clinical medicine; placebo effect ID CONTEXT AB Despite strong growth in scientific investigation of the placebo effect, understanding of this phenomenon remains deeply confused. We investigate critically seven common conceptual distinctions that impede clear understanding of the placebo effect: (1) verum/placebo, (2) active/inactive, (3) signal/noise, (4) specific/nonspecific, (5) objective/subjective, (6) disease/illness, and (7) intervention/context. We argue that some of these should be eliminated entirely, whereas others must be used with caution to avoid bias. Clearing away the conceptual underbrush is needed to lay down a path to understanding and harnessing placebo effects in clinical medicine. C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Brody, Howard] Univ Texas Med Branch, Galveston, TX USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 18 TC 10 Z9 11 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD FEB PY 2011 VL 36 IS 1 BP 69 EP 78 DI 10.1093/jmp/jhq061 PG 10 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 720BW UT WOS:000287256200005 PM 21220523 ER PT J AU Miller, B Molfese, V Berninger, V AF Miller, Brett Molfese, Victoria Berninger, Virginia TI Introduction to special issue on writing SO READING AND WRITING LA English DT Editorial Material C1 [Miller, Brett] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Molfese, Victoria] Univ Nebraska, Dept Child Youth & Family Studies, Lincoln, NE USA. [Berninger, Virginia] Univ Washington Educ Psychol, Seattle, WA USA. RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. EM millerbre@mail.nih.gov NR 0 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0922-4777 J9 READ WRIT JI Read. Writ. PD FEB PY 2011 VL 24 IS 2 BP 117 EP 119 DI 10.1007/s11145-010-9268-5 PG 3 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA 721MZ UT WOS:000287360300001 ER PT J AU Miller, B McCardle, P AF Miller, Brett McCardle, Peggy TI Reflections on the need for continued research on writing SO READING AND WRITING LA English DT Article DE Writing; Literacy; Research directions; NIH; NICHD ID WRITTEN LANGUAGE; INTERVENTION; METAANALYSIS; STUDENTS AB A focused scientific research effort on writing research and its relationship to language development and reading is needed to address the writing and broader literacy needs of today's and tomorrow's learners and workers. In the United States, as well as in many other nations, research on writing has been neglected in relation to the emphasis on reading and oral language more generally. The authors argue first for why there is a need for this refocused effort, what should be focused on, and how as a field we should consider moving forward and addressing this imperative. In addressing the why, the authors argue that need is not limited to a particular age or developmental range but rather is broad-based, beginning with our youngest learners and continuing through those transitioning into post-secondary and the workplace. The clear message is that the picture is surprisingly similar across age ranges with a demonstrated need beginning with those coming from less advantaged backgrounds into formal education to the majority of students transitioning from twelfth grade into the workplace or post secondary settings. The authors suggest next steps for research addressing both what and how: what areas of science are areas of high need and how the field may consider moving forward to address these needs. Interdisciplinary research on writing is needed that addresses and integrates cognitive, biological, and social-cultural traditions, contributions, and methods. C1 [Miller, Brett; McCardle, Peggy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept Hlth & Human Serv, NIH, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20892 USA. EM millerbre@mail.nih.gov; mccardlp@mail.nih.gov NR 41 TC 14 Z9 14 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0922-4777 J9 READ WRIT JI Read. Writ. PD FEB PY 2011 VL 24 IS 2 BP 121 EP 132 DI 10.1007/s11145-010-9267-6 PG 12 WC Education & Educational Research; Psychology, Educational SC Education & Educational Research; Psychology GA 721MZ UT WOS:000287360300002 ER PT J AU Simoni, JM Safren, SA Manhart, LE Lyda, K Grossman, CI Rao, D Mimiaga, MJ Wong, FY Catz, SL Blank, MB DiClemente, R Wilson, IB AF Simoni, Jane M. Safren, Steven A. Manhart, Lisa E. Lyda, Karen Grossman, Cynthia I. Rao, Deepa Mimiaga, Matthew J. Wong, Frank Y. Catz, Sheryl L. Blank, Michael B. DiClemente, Ralph Wilson, Ira B. TI Challenges in Addressing Depression in HIV Research: Assessment, Cultural Context, and Methods SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Depression; Research methods; Measurement ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; SUBSTANCE USE DISORDERS; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; RANDOMIZED CONTROLLED-TRIAL; POSITIVE PREGNANT-WOMEN; MAJOR DEPRESSION; INFECTED INDIVIDUALS; PRIMARY-CARE; GAY MEN AB Depression is one of the most common co-morbidities of HIV infection. It negatively impacts self-care, quality of life, and biomedical outcomes among people living with HIV (PLWH) and may interfere with their ability to benefit from health promotion interventions. State-of-the-science research among PLWH, therefore, must address depression. To guide researchers, we describe the main diagnostic, screening, and symptom-rating measures of depression, offering suggestions for selecting the most appropriate instrument. We also address cultural considerations in the assessment of depression among PLWH, emphasizing the need to consider measurement equivalence and offering strategies for developing measures that are valid cross-culturally. Finally, acknowledging the high prevalence of depression among PLWH, we provide guidance to researchers on incorporating depression into the theoretical framework of their studies and employing procedures that account for participants with depression. C1 [Simoni, Jane M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Manhart, Lisa E.] UW Ctr AIDS & STD, Dept Epidemiol, Seattle, WA USA. [Lyda, Karen] Univ Colorado Denver, Univ Colorado Hosp, Sch Med, Div Infect Dis, Aurora, CO USA. [Grossman, Cynthia I.] NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. [Rao, Deepa] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Mimiaga, Matthew J.] Fenway Community Hlth, Boston, MA USA. [Wong, Frank Y.; DiClemente, Ralph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Catz, Sheryl L.] Grp Hlth Res Inst, Seattle, WA USA. [Blank, Michael B.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Wilson, Ira B.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. RP Simoni, JM (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA. EM jsimoni@uw.edu RI Wilson, Ira/F-9190-2016; OI Wilson, Ira/0000-0002-0246-738X; Simoni, Jane/0000-0002-8711-1576 FU NIAID NIH HHS [P30 AI027757, P30 AI027757-18]; NIMH NIH HHS [K23 MH084551, K23 MH084551-05, K23 MH084551-06, K24 MH092242] NR 142 TC 31 Z9 31 U1 9 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD FEB PY 2011 VL 15 IS 2 BP 376 EP 388 DI 10.1007/s10461-010-9836-3 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 715YX UT WOS:000286932800014 PM 21046221 ER PT J AU Prosser, LA Stanley, CJ Norman, TL Park, HS Damiano, DL AF Prosser, Laura A. Stanley, Christopher J. Norman, Tracy L. Park, Hyung S. Damiano, Diane L. TI Comparison of elliptical training, stationary cycling, treadmill walking and overground walking. Electromyographic patterns SO GAIT & POSTURE LA English DT Article DE Gait; EMG; Muscle activity; Lower extremity; Elliptical; Cycling ID MUSCLE-ACTIVITY; CEREBRAL-PALSY; KINEMATICS; BIOMECHANICS; ADOLESCENTS; ONSET; SEMG AB The most common functional motor goal of lower extremity rehabilitation is to improve walking ability. For reasons of feasibility, safety or intensity, devices are frequently used to facilitate or augment gait training. The objective of this study was to compare the muscle activity patterns of the rectus femoris and semitendinosus muscles during four conditions: overground walking, treadmill walking, stationary cycling, and elliptical training. Ten healthy adults (six male, four female; mean age 22.7 +/- 2.9 years, range 20-29) participated and surface electromyographic data were recorded. Linear envelope curves were generated and time normalized from 0 to 100% cycle. The mean plus three standard deviations from a static trial was used as the threshold for muscle activity. Repeated measures analysis of variance procedures were used to detect differences between conditions. Elliptical training demonstrated greater rectus femoris activity and greater rectus femoris/semitendinosus coactivation than all other conditions. Consistent with previous work, treadmill walking demonstrated greater rectus femoris activity than overground walking. Minimal differences in semitendinosus activation were observed between conditions, limited to lower peak activity during cycling compared to treadmill walking. These results provide normative values for rectus femoris and semitendinosus activation for different locomotor training methods and may assist in selecting the most appropriate training device for specific patients. Clinicians and researchers should also consider the kinematic and kinetic differences between tasks, which cannot necessarily be inferred from muscle activation patterns. 2010 Published by Elsevier B.V. C1 [Prosser, Laura A.; Stanley, Christopher J.; Norman, Tracy L.; Park, Hyung S.; Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. RP Damiano, DL (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bldg 10,Room 1-1469, Bethesda, MD 20892 USA. EM damianod@cc.nih.gov RI Park, Hyung-Soon/B-3334-2010; Prosser, Laura/C-1242-2009; Van Mulders, Benjamin/P-1241-2014; Damiano, Diane/B-3338-2010 OI Park, Hyung-Soon/0000-0003-4274-7420; Damiano, Diane/0000-0002-2770-5356 FU NIH Clinical Center FX This work was funded by the Intramural Research Program at the NIH Clinical Center. NR 18 TC 15 Z9 15 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD FEB PY 2011 VL 33 IS 2 BP 244 EP 250 DI 10.1016/j.gaitpost.2010.11.013 PG 7 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 737LF UT WOS:000288569600018 PM 21215636 ER PT J AU Boykin, S Diez-Roux, AV Carnethon, M Shrager, S Ni, HY Whitt-Glover, M AF Boykin, Shawn Diez-Roux, Ana V. Carnethon, Mercedes Shrager, Sandi Ni, Hanyu Whitt-Glover, Melicia TI Racial/ethnic Heterogeneity in the Socioeconomic Patterning of CVD Risk Factors: in the United States: The Multi-Ethnic Study of Atherosclerosis SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Cardiovascular disease; risk factors; socioeconomic status; race; ethnicity ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; SERUM-LIPIDS; MORTALITY; EDUCATION; RACE AB Many studies document racial variation, gender differences, and socioeconomic status (SES) patterning in cardiovascular disease (CVD) risk factors but few studies have investigated heterogeneity in SES differences by race/ethnicity or gender. Using data from the Multi-Ethnic Study of Atherosclerosis (N=6,814) and stratified regression models, we investigated race/ethnic differences in the SES patterning of diabetes, hypertension, smoking, and body mass index (BMI). Inverse socioeconomic gradients in hypertension, diabetes, smoking, and BMI were observed in White and Black women but associations were weaker or absent in Hispanic and Chinese women (except in the case of diabetes for Hispanic women). Even greater heterogeneity in social patterning of risk factors was observed in men. In White men all four risk factors were inversely associated with socioeconomic position, although often associations were only present or were stronger for education than for income. The inverse socioeconomic patterning was much less consistent in men of other races/ethnic groups, and higher SES was associated with higher BMI in non-White men. These findings have implications for understanding the causes of social patterning, for the analysis of SES adjusted race/ethnic differences, and for the targeting of interventions. C1 [Boykin, Shawn] Univ Michigan, Sch Publ Hlth, Ctr Integrat Approaches Hlth Dispar, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Diez-Roux, Ana V.] Univ Michigan, Ctr Social Epidemiol Populat Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Carnethon, Mercedes] Northeastern Univ, Feinberg Sch Med, Dept Preventat Med, Boston, MA USA. [Shrager, Sandi] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ni, Hanyu] NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD USA. [Whitt-Glover, Melicia] Gramercy Res Grp, Winston Salem, NC USA. RP Boykin, S (reprint author), Univ Michigan, Sch Publ Hlth, Ctr Integrat Approaches Hlth Dispar, Dept Epidemiol, 1415 Washington Hts,3645 SPH Tower 1, Ann Arbor, MI 48109 USA. EM sdhb@umich.edu FU NHLBI NIH HHS [N01HC95169, N01HC95165, N01-HC-95159, N01-HC-95165, N01-HC-95169, N01HC95159]; NIMHD NIH HHS [P60 MD002249-03, P60 MD002249] NR 41 TC 28 Z9 28 U1 0 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2011 VL 22 IS 1 BP 111 EP 127 PG 17 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 718ZK UT WOS:000287165100010 PM 21317510 ER PT J AU Dunton, GF Atienza, AA Tscherne, J Rodriguez, D AF Dunton, Genevieve Fridlund Atienza, Audie A. Tscherne, James Rodriguez, Daniel TI Identifying Combinations of Risk and Protective Factors Predicting Physical Activity Change in High School Students SO PEDIATRIC EXERCISE SCIENCE LA English DT Article ID DEPRESSIVE SYMPTOMS; ADOLESCENT GIRLS; UNITED-STATES; BEHAVIOR SURVEILLANCE; LOGISTIC-REGRESSION; MIDDLE SCHOOL; SMOKING; YOUTH; QUESTIONNAIRE; VALIDATION AB Research sought to identify combinations of risk and protective factors predicting change in physical activity (PA) over one year in high school students. Adolescents (N = 344; M = 15.7 years) participated in a longitudinal study with assessment of demographics, substance use/smoking exposure, height and weight, psychological factors, and PA in 10th and 11th grade. PA participation in 11th grade was greatest for adolescents who engaged in PA and had high sports competence (78%), and least for adolescents who did not engage in or enjoy PA (13%) in 10th grade. Identifying adolescent subgroups at risk for decreasing PA can inform the development of tailored interventions. C1 [Dunton, Genevieve Fridlund] Univ So Calif, Dept Prevent Med, Alhambra, CA USA. [Atienza, Audie A.] NCI, Hlth Promot Res Branch, Rockville, MD USA. [Tscherne, James; Rodriguez, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Dunton, GF (reprint author), Univ So Calif, Dept Prevent Med, Alhambra, CA USA. FU Prevent Cancer Foundation (Rodriguez, PI) FX This work was supported by the Prevent Cancer Foundation (Rodriguez, PI). NR 42 TC 2 Z9 2 U1 0 U2 0 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 0899-8493 J9 PEDIATR EXERC SCI JI Pediatr. Exerc. Sci. PD FEB PY 2011 VL 23 IS 1 BP 106 EP 121 PG 16 WC Pediatrics; Physiology; Sport Sciences SC Pediatrics; Physiology; Sport Sciences GA 737UC UT WOS:000288592700012 PM 21467595 ER PT J AU Major, EO Ryschkewitsch, CF Jensen, PN Monaco, MC AF Major, Eugene O. Ryschkewitsch, Caroline F. Jensen, Peter N. Monaco, Maria Chiara TI Assay Design and Sample Collection Can Affect Anti-John Cunningham Virus Antibody Detection Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Major, Eugene O.; Ryschkewitsch, Caroline F.; Jensen, Peter N.; Monaco, Maria Chiara] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 NS003049-02] NR 4 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2011 VL 69 IS 2 BP 430 EP 431 DI 10.1002/ana.22364 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 733TD UT WOS:000288284900035 PM 21387394 ER PT J AU Hirankarn, S Hammer, GB Schulman, SR Drover, DR Dombrowsky, E Zajicek, A Cohane, C Barrett, JS AF Hirankarn, S. Hammer, G. B. Schulman, S. R. Drover, D. R. Dombrowsky, E. Zajicek, A. Cohane, C. Barrett, J. S. TI POPULATION K-PD MODEL OF SODIUM NITROPRUSSIDE IN CHILDREN SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Hirankarn, S.; Dombrowsky, E.; Barrett, J. S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hammer, G. B.; Drover, D. R.; Cohane, C.] Stanford Univ, Palo Alto, CA 94304 USA. [Schulman, S. R.] Duke Univ, Durham, NC USA. [Zajicek, A.] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 FEB PY 2011 VL 89 SU 1 BP S55 EP S55 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100176 ER PT J AU Peer, CJ Sissung, TM Jain, L Woo, S Gardner, ER Kirkland, CT English, BC Federspiel, J Figg, WD AF Peer, C. J. Sissung, T. M. Jain, L. Woo, S. Gardner, E. R. Kirkland, C. T. English, B. C. Federspiel, J. Figg, W. D. TI SORAFENIB IS AN INHIBITOR OF UGT1A1 BUT IS METABOLIZED BY UGT1A9: IMPLICATIONS OF UGT1A GENETIC VARIANTS ON SORAFENIB EXPOSURE AND SORAFENIB-INDUCED HYPERBILIRUBINEMIA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Peer, C. J.; Sissung, T. M.; Jain, L.; Woo, S.; Gardner, E. R.; English, B. C.; Figg, W. D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kirkland, C. T.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Federspiel, J.] Georgetown Coll, Dept Chem, Georgetown, KY USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2011 VL 89 SU 1 BP S46 EP S47 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100147 ER PT J AU Sissung, T Fernandez, E Kirkland, CT Gardner, ER Venzon, D Kelly, R Bates, SE Figg, WD AF Sissung, T. Fernandez, E. Kirkland, C. T. Gardner, E. R. Venzon, D. Kelly, R. Bates, S. E. Figg, W. D. TI ABCB1 POLYMORPHISMS ARE ASSOCIATED WITH TARIQUIDAR-INDUCED INCREASES IN DOCETAXEL HALF-LIFE. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Sissung, T.; Fernandez, E.; Kirkland, C. T.; Gardner, E. R.; Venzon, D.; Kelly, R.; Bates, S. E.; Figg, W. D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2011 VL 89 SU 1 BP S75 EP S75 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100242 ER PT J AU Vyas, NS Patel, NH Puri, BK AF Vyas, Nora S. Patel, Neva H. Puri, Basant K. TI Neurobiology and phenotypic expression in early onset schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Review DE adolescence; cognition; imaging; intelligence; prognosis; schizophrenia ID CARDIO-FACIAL SYNDROME; FIRST-EPISODE SCHIZOPHRENIA; 22Q11 DELETION SYNDROME; COPY-NUMBER VARIATION; LONG-TERM COURSE; GRAY-MATTER LOSS; CHILDHOOD-ONSET; ADOLESCENT-ONSET; FOLLOW-UP; PREMORBID ADJUSTMENT AB Aim: Early-onset schizophrenia (onset before adulthood) is a rare and severe form of the disorder that shows phenotypic and neurobiological continuity with adult-onset schizophrenia. Here, we provide a synthesis of keynote findings in this enriched population to understand better the neurobiology and pathophysiology of early-onset schizophrenia. Methods: A synthetic and integrative approach is applied to review studies stemming from epidemiology, phenomenology, cognition, genetics and neuroimaging data. We provide conclusions and future directions of research on early-onset schizophrenia. Results: Childhood and adolescent-onset schizophrenia is associated with severe clinical course, greater rates of premorbid abnormalities, poor psychosocial functioning and increased severity of brain abnormalities. Early-onset cases show similar neurobiological correlates and phenotypic deficits to adult-onset schizophrenia, but show worse long-term psychopathological outcome. Emerging technological advances have provided important insights into the genomic architecture of early-onset schizophrenia, suggesting that some genetic variations may occur more frequently and at a higher rate in young-onset than adult-onset cases. Conclusions: Clinical, cognitive, genetic and imaging data suggest increased severity in early-onset schizophrenia. Studying younger-onset cases can provide useful insights into the neurobiological mechanisms of schizophrenia and the complexity of gene-environment interactions leading to the emergence of this debilitating disorder. C1 [Vyas, Nora S.] Kings Coll London, Inst Psychiat, SGDP Ctr, London SE5 8AF, England. [Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Vyas, Nora S.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Nucl Med, London, England. [Patel, Neva H.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Radiol Sci Unit, London, England. [Puri, Basant K.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Dept Imaging, London, England. [Puri, Basant K.] Univ Limerick, Fac Educ & Hlth Sci, Limerick, Ireland. RP Vyas, NS (reprint author), Kings Coll London, Inst Psychiat, SGDP Ctr, POB 66,Crespigny Pk, London SE5 8AF, England. EM drnoravyas@gmail.com RI Vyas, Nora/C-3570-2011 FU US-UK Fulbright Commission FX Dr Nora S Vyas is supported by the Distinguished Scholar Award by the US-UK Fulbright Commission. The US-UK Fulbright Commission had no further role in writing this review; and in the decision to submit the paper for publication. NR 151 TC 28 Z9 29 U1 9 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD FEB PY 2011 VL 5 IS 1 BP 3 EP 14 DI 10.1111/j.1751-7893.2010.00253.x PG 12 WC Psychiatry SC Psychiatry GA 712LZ UT WOS:000286669600002 PM 21272270 ER PT J AU Madan, RA Gulley, JL AF Madan, Ravi A. Gulley, James L. TI Sipuleucel-T: harbinger of a new age of therapeutics for prostate cancer SO EXPERT REVIEW OF VACCINES LA English DT Article DE cancer treatment; cancer vaccine; immunotherapy; prostate cancer ID ANDROGEN-DEPRIVATION THERAPY; COMBINATION THERAPY; PHASE-II; ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; IMMUNE-RESPONSES; ACID-PHOSPHATASE; DENDRITIC CELLS; PLUS PREDNISONE; END-POINTS AB Sipuleucel-T (Provenge (R)) is the first therapeutic cancer vaccine approved by the US FDA. The approval heralds the long-awaited promise of improved patient survival with minimal toxicity by therapies designed to generate an active, specific anticancer immune response. The development of this first-in-class agent as well as other therapeutic vaccines in clinical evaluation has also led to a better understanding of relevant patient populations and end points for clinical trials. This article discusses the development and approval of sipuleucel-T in the context of other approved therapies for prostate cancer, as well as controversies and novel paradigms brought about by this new agent. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Madan, Ravi A.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z01 BC010666-03] NR 77 TC 9 Z9 12 U1 1 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD FEB PY 2011 VL 10 IS 2 BP 141 EP 150 DI 10.1586/ERV.10.173 PG 10 WC Immunology SC Immunology GA 732NM UT WOS:000288192200006 PM 21332262 ER PT J AU Landgren, O Polliack, A Tadmor, T AF Landgren, Ola Polliack, Aaron Tadmor, Tamar TI Associations between multiple myeloma and other malignancies SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material C1 [Landgren, Ola] NCI, Multiple Myeloma Sect, NIH, Ctr Canc Res,Med Oncol Branch, Bethesda, MD 20892 USA. [Polliack, Aaron] Hebrew Univ Jerusalem, Sch Med, Hadassah Univ Hosp, Dept Hematol, IL-91010 Jerusalem, Israel. [Tadmor, Tamar] Bnai Zion Med Ctr, Hematol Oncol Unit, Haifa, Israel. RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, NIH, Ctr Canc Res,Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD FEB PY 2011 VL 52 IS 2 BP 161 EP 162 DI 10.3109/10428194.2010.538942 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 717ZV UT WOS:000287089100003 PM 21261502 ER PT J AU Maddali, K Kumar, V Marchand, C Pommier, Y Malhotra, SV AF Maddali, Kasthuraiah Kumar, Vineet Marchand, Christophe Pommier, Yves Malhotra, Sanjay V. TI Biological evaluation of imidazolium- and ammonium-based salts as HIV-1 integrase inhibitors SO MEDCHEMCOMM LA English DT Article ID BETA-DIKETO ACIDS; CELL-LINE HELA; IONIC LIQUIDS; ANTI-HIV; STRAND TRANSFER; NUCLEOBASE SCAFFOLDS; CATIONIC SURFACTANTS; VIRAL REPLICATION; CATALYTIC DOMAIN; DNA AB Ammonium- and imidazolium-based ionic salts were studied for their application as inhibitors of HIV-1 integrase (IN). These compounds were active in the inhibition of both the 3'-processing (3'-P) and strand transfer (ST) steps of the integration reaction. A correlation of activity with chain length of the alkyl substituent in both classes of ionic salts was observed. C1 [Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov; malhotrasa@mail.nih.gov FU National Cancer Institute (NCI); NCI, National Institutes of Health [HSN261200800001E]; Center for Cancer Research FX The authors would like to thank the National Cancer Institute (NCI) Developmental Therapeutics Program. This project has been funded in whole or in part with federal funds from the NCI, National Institutes of Health, under Contract No. HSN261200800001E. KM and YP are supported by the Center for Cancer Research, NIH Intramural Program of the National Cancer institute. 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 60 TC 6 Z9 6 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 J9 MEDCHEMCOMM JI MedChemComm PD FEB PY 2011 VL 2 IS 2 BP 143 EP 150 DI 10.1039/c0md00201a PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 733XF UT WOS:000288297100008 ER PT J AU Charizopoulou, N Lelli, A Schraders, M Ray, K Hildebrand, MS Ramesh, A Srisailapathy, CRS Oostrik, J Admiraal, RJC Neely, HR Latoche, JR Smith, RJH Northup, JK Kremer, H Holt, JR Noben-Trauth, K AF Charizopoulou, Nikoletta Lelli, Andrea Schraders, Margit Ray, Kausik Hildebrand, Michael S. Ramesh, Arabandi Srisailapathy, C. R. Srikumari Oostrik, Jaap Admiraal, Ronald J. C. Neely, Harold R. Latoche, Joseph R. Smith, Richard J. H. Northup, John K. Kremer, Hannie Holt, Jeffrey R. Noben-Trauth, Konrad TI Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human SO NATURE COMMUNICATIONS LA English DT Article ID BLACK-SWISS MICE; INNER HAIR CELL; MYOSIN-VI; PDZ DOMAIN; G-PROTEIN; RGS-GAIP; GENE; IMPAIRMENT; RECEPTOR; DEAFNESS AB Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion. A missense mutation in the PDZ domain has an attenuating effect on mechanotransduction and the acquisition of mature inner hair cell potassium currents. Magnitude and temporal progression of wave I amplitude of afferent neurons correlate with susceptibility and resistance to audiogenic seizures. The Gipc3(343A) allele disrupts the structure of the stereocilia bundle and affects long-term function of auditory hair cells and spiral ganglion neurons. Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells. C1 [Charizopoulou, Nikoletta; Neely, Harold R.; Latoche, Joseph R.; Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. [Lelli, Andrea; Holt, Jeffrey R.] Univ Virginia, Dept Neurosci & Otolaryngol, Sch Med, Charlottesville, VA 22908 USA. [Schraders, Margit; Oostrik, Jaap; Admiraal, Ronald J. C.; Kremer, Hannie] Radboud Univ Nijmegen, Dept Otorhinolaryngol, Donders Inst Brain Cognit & Behav, Med Ctr, NL-6525 GA Nijmegen, Netherlands. [Schraders, Margit; Oostrik, Jaap; Kremer, Hannie] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6525 GA Nijmegen, Netherlands. [Ray, Kausik; Northup, John K.] Natl Inst Deafness & Other Commun Disorders, Sect Signal Transduct, Lab Cellular Biol, NIH, Rockville, MD 20850 USA. [Hildebrand, Michael S.; Smith, Richard J. H.] Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. [Ramesh, Arabandi; Srisailapathy, C. R. Srikumari] Univ Madras, Dept Genet, Madras, Tamil Nadu, India. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov RI Kremer, Hannie/F-5126-2010; Admiraal, R.J.C./L-4171-2015; Schraders, Margit/A-1607-2016; Oostrik, Jaap/A-1703-2016; OI Kremer, Hannie/0000-0002-0841-8693; Hildebrand, Michael/0000-0003-2739-0515 FU Division of Intramural Research at NIH/NIDCD; NIH/NIDCD [DC05439, DC002842]; RNID [GR36]; Fonds NutsOhra [SNO-T-0702-102]; EU [LSHG-CT-2004-512063]; Oticon Foundation; University Grants Commission Research Scientist Scheme in New Delhi, India FX We thank Feng Qian, Katerina Vorvolakos and Dennis Drayna for comments on the manuscript. We also thank Charles Askew for assistance with cochlear dissections, M'Hamed Grati and Leonardo De Andrade for SEM imaging, Glen Martin for help with the DPOAEs and Eric Wawrousek of the NEI transgenic core facility. This work was supported by the Division of Intramural Research at NIH/NIDCD (K.N.-T. and J.K.N.), NIH/NIDCD grants DC05439 (J.R.H.) and DC002842 (R.J.H.S.). M.S. was supported by RNID GR36 and H.K. received funds from Fonds NutsOhra (SNO-T-0702-102), the EU (LSHG-CT-2004-512063), and the Oticon Foundation. C.R.S.S. was supported by the University Grants Commission Research Scientist Scheme in New Delhi, India. M.S.H. was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Training Fellowship. NR 46 TC 37 Z9 39 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD FEB PY 2011 VL 2 AR 201 DI 10.1038/ncomms1200 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732YP UT WOS:000288225900030 PM 21326233 ER PT J AU Kim, JH Wu, TH Budde, MD Lee, JM Song, SK AF Kim, Joong Hee Wu, Tzy-Haw Budde, Matthew D. Lee, Jin-Moo Song, Sheng-Kwei TI Noninvasive detection of brainstem and spinal cord axonal degeneration in an amyotrophic lateral sclerosis mouse model SO NMR IN BIOMEDICINE LA English DT Article DE diffusion tensor imaging; mice; cervical spinal cord; axial and radial diffusivity; diffusion anisotropy; G93A-SOD1; amyotrophic lateral sclerosis ID MOTOR-NEURON DEGENERATION; MULTIPLE-SCLEROSIS; TRANSGENIC MICE; DIFFUSION; ALS; INJURY; MRI; DISEASE; NEURODEGENERATION; MARKERS AB Degeneration of motor neurons and their associated axons is a hallmark of amyotrophic lateral sclerosis, but reliable noninvasive lesion detection is lacking. In vivo diffusion tensor imaging was performed to evaluate neurodegeneration in the brainstem and cervical spinal cord of wild-type and G93A-SOD1 transgenic mice, an animal model of amyotrophic lateral sclerosis. A statistically significant reduction in the apparent diffusion coefficient was observed in the motor nuclei VII and XII of G93A-SOD1 transgenic mice relative to wild-type mice. No significant difference in diffusion anisotropy was observed in dorsal white or gray matter in cervical and lumbar segments of the spinal cord. In contrast, statistically significant decreases in axial diffusivity (diffusivity parallel to the axis of the spinal cord) and apparent diffusion coefficient were found in the ventrolateral white matter of G93A-SOD1 mice in both the cervical and lumbar spinal cord. The reduction in axial diffusivity, suggestive of axonal injury, in the white matter of the spinal cord of G93A-SOD1 mice was verified by immunostaining with nonphosphorylated neurofilament. The present study demonstrates that in vivo diffusion tensor imaging-derived axial diffusivity may be used to accurately evaluate axonal degeneration in an animal model of amyotrophic lateral sclerosis. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Kim, Joong Hee] Washington Univ, Sch Med, Biomed MR Lab, Dept Radiol, St Louis, MO 63110 USA. [Wu, Tzy-Haw] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Budde, Matthew D.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Lee, Jin-Moo] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA. [Lee, Jin-Moo] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Kim, JH (reprint author), Washington Univ, Sch Med, Biomed MR Lab, Dept Radiol, Campus Box 8227,Room 2313,4525 Scott Ave, St Louis, MO 63110 USA. EM jhkim@bmr.wustl.edu FU National Multiple Sclerosis Society [RG 3376-A-2/1, CA 1012-A-13]; National Institutes of Health [R01 NS047592, R01 NS048283, P01 NS032636, R01 NS48283, R01 NS67905, P01NS32636]; University of Missouri; Washington University Small Animal Imaging Resource (WUSAIR) [NIH: R24 CA83060]; Animal Models Core of the Hope Center for Neurological Disorders FX This study was supported in part by the National Multiple Sclerosis Society (RG 3376-A-2/1 and CA 1012-A-13), National Institutes of Health (R01 NS047592, R01 NS048283, P01 NS032636, R01 NS48283, R01 NS67905, P01NS32636), University of Missouri Spinal Cord Injuries Program, and the Washington University Small Animal Imaging Resource (WUSAIR) (NIH: R24 CA83060) and the Animal Models Core of the Hope Center for Neurological Disorders. NR 46 TC 11 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD FEB PY 2011 VL 24 IS 2 BP 163 EP 169 DI 10.1002/nbm.1567 PG 7 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 732SG UT WOS:000288209300006 PM 21344532 ER PT J AU Yang, ZW Li, DJ Liu, C Han, P Yang, YL Su, DF Shen, FM AF Yang, Zhong-wei Li, Dong-jie Liu, Chong Han, Ping Yang, Yi-li Su, Ding-feng Shen, Fu-ming TI Role of vascular K-ATP channels in blood pressure variability after sinoaortic denervation in rats SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE ATP-sensitive potassium channels; blood pressure variability; sinoaotic denervation ID SENSITIVE POTASSIUM CHANNELS; LEFT-VENTRICULAR HYPERTROPHY; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; ARTERIAL-PRESSURE; CONSCIOUS RAT; ORGAN DAMAGE; LABILITY; HYPERTENSION; KIR6.1 AB Aim: To investigate the role of ATP-sensitive potassium (K-ATP) channels on blood pressure variability (BPV) in sinoaortic denervated (SAD) rats. Methods: SAD was performed on male Sprague-Dawley rats 4 weeks before the study. mRNA expression of Kir6.1, Kir6.2 and SUR2 in aorta and mesenteric artery was determined using real-time quantitative polymerase chain reaction, and confirmed at the protein level using Western blotting and laser confocal immunofluorescence assays. Concentration-response curves of isolated aortic and mesenteric arterial rings to adenosine and pinacidil were established. Effects of K-ATP channel openers and blocker on BPV were examined in conscious SAD rats. Results: Aortic SUR2 expression was significantly greater, while Kir6.1 was lower, in SAD rats than in sham-operated controls. In contrast, in the mesenteric artery both SUR2 and Kir6.1 expression were markedly lower in SAD rats than controls. For both arteries, Kir6.2 expression was indistinguishable between sham-operated and SAD rats. These findings were confirmed at the protein level. Responses of the aorta to both adenosine and pinacidil were enhanced after SAD, while the mesenteric response to adenosine was attenuated. Pinacidil, diazoxide, nicorandil, and glibenclamide significantly decreased BPV. Conclusion: These findings indicate that expression of vascular K-ATP channels is altered by chronic SAD. These alterations influence vascular reactivity, and may play a role in the increased BPV in chronic SAD rats. C1 [Yang, Zhong-wei; Li, Dong-jie; Liu, Chong; Han, Ping; Su, Ding-feng; Shen, Fu-ming] Second Mil Med Univ, Sch Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China. [Yang, Yi-li] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. RP Shen, FM (reprint author), Second Mil Med Univ, Sch Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China. EM fumingshen@126.com FU National Natural Science Foundation of China [81070118]; Shanghai Municipal Education Commission [10ZZ52]; National Basic Research Program of China [2009CB521900] FX This work was supported in part by the grants from National Natural Science Foundation of China (81070118), Shanghai Municipal Education Commission (10ZZ52), and the National Basic Research Program of China (2009CB521900). NR 36 TC 5 Z9 5 U1 0 U2 6 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 EI 1745-7254 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD FEB PY 2011 VL 32 IS 2 BP 194 EP 200 DI 10.1038/aps.2010.195 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 716KT UT WOS:000286968200009 PM 21293472 ER PT J AU Flatz, L Roychoudhuri, R Honda, M Filali, A Goulet, JP Kettaf, N Roederer, M Haddad, E Sekaly, RP Nabel, GJ AF Flatz, L. Roychoudhuri, R. Honda, M. Filali, A. Goulet, J. P. Kettaf, N. Roederer, M. Haddad, E. Sekaly, R. P. Nabel, G. J. TI Single cell gene expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines SO ALLERGOLOGIE LA English DT Meeting Abstract C1 [Flatz, L.] CHUV, Inst Dermatol, Lausanne, Switzerland. [Roychoudhuri, R.; Honda, M.; Roederer, M.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Filali, A.; Goulet, J. P.; Kettaf, N.; Haddad, E.; Sekaly, R. P.] Vaccine & Gene Therapy Inst, Port St Lucie, FL USA. RI Roychoudhuri, Rahul/A-7442-2010 OI Roychoudhuri, Rahul/0000-0002-5392-1853 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0344-5062 J9 ALLERGOLOGIE JI Allergologie PD FEB PY 2011 VL 34 IS 2 BP 81 EP 81 PG 1 WC Allergy SC Allergy GA 727XM UT WOS:000287836500016 ER PT J AU O'Brien, PMS Backstrom, T Brown, C Dennerstein, L Endicott, J Epperson, CN Eriksson, E Freeman, E Halbreich, U Ismail, KMK Panay, N Pearlstein, T Rapkin, A Reid, R Schmidt, P Steiner, M Studd, J Yonkers, K AF O'Brien, Patrick Michael Shaughn Backstrom, Torbjorn Brown, Candace Dennerstein, Lorraine Endicott, Jean Epperson, C. Neill Eriksson, Elias Freeman, Ellen Halbreich, Uriel Ismail, Khaled M. K. Panay, Nicholas Pearlstein, Teri Rapkin, Andrea Reid, Robert Schmidt, Peter Steiner, Meir Studd, John Yonkers, Kimberley TI Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: the ISPMD Montreal consensus SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Review DE PMS; PMDD; Premenstrual disorder; Diagnostic criteria; Quantification; Trial design; International consensus ID MENSTRUAL-CYCLE; DYSPHORIC DISORDER; HORMONES; WOMEN; MOOD; CYCLICITY AB Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion J Clin Psychiatry 5:30-39, 2003; Halbreich, Gynecol Endocrinol 19:320-334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive, universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD). The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health Organisation's International Classification of Diseases (ICD-11), and the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field. C1 [O'Brien, Patrick Michael Shaughn] Keele Univ, Acad Unit Obstet & Gynaecol, Sch Med, Univ Hosp N Staffordshire, Stoke On Trent, Staffs, England. [Backstrom, Torbjorn] Norrland Univ Hosp, Umea Neurosteroid Res Ctr, Dept Clin Sci, Umea, Sweden. [Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Psychiat, Memphis, TN 38163 USA. [Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Obstet, Memphis, TN 38163 USA. [Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Gynaecol, Memphis, TN 38163 USA. [Dennerstein, Lorraine] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia. [Dennerstein, Lorraine] Natl Ageing Res Inst, Melbourne, Vic, Australia. [Reid, Robert] Queens Univ, Kingston, ON, Canada. [Schmidt, Peter] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA. [Steiner, Meir] McMaster Univ, Dept Psychiat, Hamilton, ON L8P3B6, Canada. [Steiner, Meir] McMaster Univ, Dept Behav Neurosci, Hamilton, ON L8P3B6, Canada. [Steiner, Meir] McMaster Univ, Dept Obstet, Hamilton, ON L8P3B6, Canada. [Steiner, Meir] McMaster Univ, Dept Gynaecol, Hamilton, ON L8P3B6, Canada. [Studd, John] Chelsea & Westminster Hosp, Dept Gynaecol, London, England. [Epperson, C. Neill] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Yonkers, Kimberley] Dept Obstet, New Haven, CT USA. [Yonkers, Kimberley] Dept Gynaecol, New Haven, CT USA. [Halbreich, Uriel] SUNY Buffalo, Buffalo, NY 14260 USA. [Halbreich, Uriel] WPA, New York, NY USA. [Panay, Nicholas] Chelsea & Westminster Hosp, Dept Obstet & Gynaecol, London, England. [Pearlstein, Teri] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Rapkin, Andrea] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Endicott, Jean] Columbia Univ, Dept Psychiat, New York, NY USA. [Epperson, C. Neill] Yale Univ, Sch Med, Dept Obstet & Gynaecol, New Haven, CT USA. [Epperson, C. Neill] Yale Univ, Sch Med, Dept Reprod Sci, New Haven, CT USA. [Eriksson, Elias] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Freeman, Ellen] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freeman, Ellen] Univ Penn, Dept Obstet, Philadelphia, PA 19104 USA. [Freeman, Ellen] Univ Penn, Dept Gynaecol, Philadelphia, PA 19104 USA. RP O'Brien, PMS (reprint author), Keele Univ, Acad Unit Obstet & Gynaecol, Sch Med, Univ Hosp N Staffordshire, Stoke On Trent, Staffs, England. EM pmsob@hotmail.co.uk RI Steiner, Meir /B-2121-2016; OI Steiner, Meir/0000-0001-7838-2246 FU NIDA NIH HHS [K24 DA030301, R01 DA018359]; NIMH NIH HHS [R01 MH064845] NR 34 TC 50 Z9 51 U1 4 U2 10 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD FEB PY 2011 VL 14 IS 1 BP 13 EP 21 DI 10.1007/s00737-010-0201-3 PG 9 WC Psychiatry SC Psychiatry GA 716BM UT WOS:000286939900003 PM 21225438 ER PT J AU Zhang, LP Ten Hagen, KG AF Zhang, Liping Ten Hagen, Kelly G. TI The cellular microenvironment and cell adhesion: a role for O-glycosylation SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE cancer; cell adhesion; double-stranded RNA (dsRNA); Drosophila; extracellular matrix (ECM); O-glycosylation; tumour ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; PS2 INTEGRIN; DROSOPHILA-MELANOGASTER; PROTEIN; TIGGRIN; LIGAND; REQUIREMENTS; MUTATIONS; VIABILITY; BIOLOGY AB Glycosylation is one of the most abundant protein modifications in Nature, having roles in protein stability, secretion and function. Alterations in mucin-type O-glycosylation are responsible for a number of human diseases and developmental defects, as well as associated with certain types of cancer. However, the mechanistic role of this form of glycosylation in many of these instances is unclear. Here we describe how one glycosyltransferase responsible for initiating mucin-type O-glycosylation (PGANT3), specifically modulates integrin-mediated cell adhesion by influencing the secretion and localization of an integrin ligand. The integrin ligand Tiggrin, is normally O-glycosylated and localized to the basal matrix, where adhesion of two opposing cell layers takes place. In pgant3 mutants, Tiggrin is no longer O-glycosylated and fails to be properly secreted to the basal cell layer interface, resulting in disruption of proper cell adhesion. pgant3-mediated effects are dependent on the enzymatic activity of PGANT3 and cannot be rescued by another pgant family member, indicating a unique role for this glycosyltransferase. These results provide in vivo evidence for the role of O-glycosylation in the secretion of specific extracellular matrix proteins, which thereby influences the composition of the cellular 'microenvironment' and modulates cell adhesion events. The studies described in this review provide insight into the long-standing association between aberrant O-glycosylation and tumorigenesis, as changes in tumour environment and cell adhesion are hallmarks of cancer progression. C1 [Zhang, Liping; Ten Hagen, Kelly G.] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. RP Ten Hagen, KG (reprint author), NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. EM Kelly.Tenhagen@nih.gov FU National Institute of Dental and Craniofacial Research of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research of the National Institutes of Health. NR 26 TC 11 Z9 11 U1 0 U2 14 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2011 VL 39 BP 378 EP 382 DI 10.1042/BST0390378 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 722NC UT WOS:000287438000070 PM 21265808 ER PT J AU Archer, TK AF Archer, Trevor K. TI The 26S proteasome: When degradation is just not enough! SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Editorial Material ID UBIQUITIN SYSTEM; DESTRUCTION; PROTEINS C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233,MD D4-01, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov NR 11 TC 0 Z9 0 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 FEB PY 2011 VL 1809 IS 2 SI SI BP 65 EP 66 DI 10.1016/j.bbagrm.2010.11.005 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 722LR UT WOS:000287434200001 PM 21130191 ER PT J AU Amarnath, S Laurence, AD Mariotti, J Foley, JE O'Shea, JJ Fowler, DH AF Amarnath, S. Laurence, A. D. Mariotti, J. Foley, J. E. O'Shea, J. J. Fowler, D. H. TI STAT3 PROMOTES BOTH NATURAL AND INDUCIBLE T REGULATORY CELL PLASTICITY DURING MURINE ACUTE GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Amarnath, S.; Mariotti, J.; Foley, J. E.; Fowler, D. H.] NCI, CCR, Bethesda, MD 20892 USA. [Laurence, A. D.; O'Shea, J. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 372 BP S288 EP S288 DI 10.1016/j.bbmt.2010.12.408 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500372 ER PT J AU Baird, K Steinberg, SM Grkovic, L Pulanic, D Cowen, EW Mitchell, SA Williams, KM Datiles, M Fall-Dickson, JM Carpenter, A Avila, DN Taylor, T Urban, A Joe, G Comis, L Berger, A Stratton, P Shelhamer, J Gea-Banacloche, J Sportes, C Fowler, DH Bishop, MR Gress, RE Pavletic, SZ AF Baird, K. Steinberg, S. M. Grkovic, L. Pulanic, D. Cowen, E. W. Mitchell, S. A. Williams, K. M. Datiles, M. Fall-Dickson, J. M. Carpenter, A. Avila, D. N. Taylor, T. Urban, A. Joe, G. Comis, L. Berger, A. Stratton, P. Shelhamer, J. Gea-Banacloche, J. Sportes, C. Fowler, D. H. Bishop, M. R. Gress, R. E. Pavletic, S. Z. TI VALIDATION OF THE NATIONAL INSTITUTES OF HEALTH (NIH) CONSENSUS CRITERIA FOR CHRONIC GVHD (cGVHD) STAGING CORRELATED WITH ESTABLISHED INDICATORS OF DISEASE SEVERITY AND PROGNOSIS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Baird, K.; Steinberg, S. M.; Grkovic, L.; Pulanic, D.; Cowen, E. W.; Mitchell, S. A.; Williams, K. M.; Datiles, M.; Fall-Dickson, J. M.; Carpenter, A.; Avila, D. N.; Taylor, T.; Urban, A.; Joe, G.; Comis, L.; Berger, A.; Stratton, P.; Shelhamer, J.; Gea-Banacloche, J.; Sportes, C.; Fowler, D. H.; Bishop, M. R.; Gress, R. E.; Pavletic, S. Z.] NIH, Bethesda, MD 20892 USA. [Grkovic, L.; Pulanic, D.] Univ Hosp Ctr Zagreb, Zagreb, Croatia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 27 BP S160 EP S161 DI 10.1016/j.bbmt.2010.12.033 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500028 ER PT J AU Battiwalla, M McIver, Z Draper, D Haggerty, J Koklanaris, E Chawla, K Superata, J Childs, R Kurlander, R Stroncek, D Khuu, H Citrin, D Sabatino, M Leitman, S Barrett, J AF Battiwalla, M. McIver, Z. Draper, D. Haggerty, J. Koklanaris, E. Chawla, K. Superata, J. Childs, R. Kurlander, R. Stroncek, D. Khuu, H. Citrin, D. Sabatino, M. Leitman, S. Barrett, J. TI 4-LOG EX-VIVO T-LYMPHOCYTE DEPLETED MYELOABLATIVE HLA-MATCHED SIBLING TRANSPLANTS; A PLATFORM FOR ADOPTIVE IMMUNOTHERAPY INFLUENCED BY CONDITIONING INTENSITY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Battiwalla, M.; McIver, Z.; Draper, D.; Haggerty, J.; Koklanaris, E.; Chawla, K.; Superata, J.; Childs, R.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Kurlander, R.; Stroncek, D.; Khuu, H.; Sabatino, M.; Leitman, S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Citrin, D.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 368 BP S287 EP S287 DI 10.1016/j.bbmt.2010.12.404 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500368 ER PT J AU Battiwalla, M Le, RQ Melenhorst, J McIver, Z Hill, B Memon, S Hensel, NF Koklanaris, E Keyvanfar, K Hakim, FT Douek, DC Bevans, M Mitchell, S Barrett, J AF Battiwalla, M. Le, R. Q. Melenhorst, J. McIver, Z. Hill, B. Memon, S. Hensel, N. F. Koklanaris, E. Keyvanfar, K. Hakim, F. T. Douek, D. C. Bevans, M. Mitchell, S. Barrett, J. TI SURVIVOR HEALTH AND IMMUNE RECONSTITUTION IN THE SECOND DECADE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Battiwalla, M.; Le, R. Q.; Melenhorst, J.; McIver, Z.; Hensel, N. F.; Koklanaris, E.; Keyvanfar, K.; Barrett, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hill, B.; Douek, D. C.] NIAID, NIH, Bethesda, MD 20892 USA. [Memon, S.; Hakim, F. T.] NCI, NIH, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 228 BP S238 EP S238 DI 10.1016/j.bbmt.2010.12.256 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500228 ER PT J AU Buxbaum, NP Williams, KM Treadwell, S Amarnath, S Eckhans, M Gress, RE AF Buxbaum, N. P. Williams, K. M. Treadwell, S. Amarnath, S. Eckhans, M. Gress, R. E. TI IMPAIRED THYMOPOIESIS WITH NORMAL T REGULATORY CELL NUMBERS IS ASSOCIATED WITH SEVERE CHRONIC GRAFT-VERSUS-HOST DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Buxbaum, N. P.; Williams, K. M.; Treadwell, S.; Amarnath, S.; Eckhans, M.; Gress, R. E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 526 BP S341 EP S342 DI 10.1016/j.bbmt.2010.12.563 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500526 ER PT J AU Foley, JE Amarnath, S Felizardo, TC He, A Fowler, DH AF Foley, J. E. Amarnath, S. Felizardo, T. C. He, A. Fowler, D. H. TI STATI DEFICIENCY FAILS TO PROTECT AGAINST MURINE CHRONIC GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Foley, J. E.; Amarnath, S.; Felizardo, T. C.; He, A.; Fowler, D. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 499 BP S332 EP S333 DI 10.1016/j.bbmt.2010.12.536 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500499 ER PT J AU Fowler, DH Mossoba, ME Hakim, FT Kurlander, R Gea-Banacloche, J Sportes, C Hardy, NM Pavletic, SZ Steinberg, SM Khuu, HM Sabatino, M Stroncek, DF Leitman, SF Rowley, SD Donato, M Goy, A Friedman, TM Korngold, R Pecora, AL Levine, BL June, CH Gress, RE Bishop, MR AF Fowler, D. H. Mossoba, M. E. Hakim, F. T. Kurlander, R. Gea-Banacloche, J. Sportes, C. Hardy, N. M. Pavletic, S. Z. Steinberg, S. M. Khuu, H. M. Sabatino, M. Stroncek, D. F. Leitman, S. F. Rowley, S. D. Donato, M. Goy, A. Friedman, T. M. Korngold, R. Pecora, A. L. Levine, B. L. June, C. H. Gress, R. E. Bishop, M. R. TI T-RAPA CELL DLI SAFELY BALANCES Th1/Th2 CYTOKINE ACTIVATION AFTER LOW-INTENSITY ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Fowler, D. H.; Mossoba, M. E.; Hakim, F. T.; Gea-Banacloche, J.; Sportes, C.; Hardy, N. M.; Pavletic, S. Z.; Steinberg, S. M.; Gress, R. E.; Bishop, M. R.] NCI, Bethesda, MD 20892 USA. [Kurlander, R.; Khuu, H. M.; Sabatino, M.; Stroncek, D. F.; Leitman, S. F.] NIH, Bethesda, MD 20892 USA. [Rowley, S. D.; Donato, M.; Goy, A.; Friedman, T. M.; Korngold, R.; Pecora, A. L.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Levine, B. L.; June, C. H.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 19 BP S157 EP S157 DI 10.1016/j.bbmt.2010.12.023 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500020 ER PT J AU Grkovic, L Baird, K Steinberg, SM Pulanic, D Cowen, EW Mitchell, SA Williams, KM Carpenter, AE Wroblewski, SG Hakim, FT Avila, DN Taylor, TN Rowley, SD Zhang, D Gea-Banachloche, JC Sportes, C Fowler, DH Bishop, MR Gress, RE Pavletic, SZ AF Grkovic, L. Baird, K. Steinberg, S. M. Pulanic, D. Cowen, E. W. Mitchell, S. A. Williams, K. M. Carpenter, A. E. Wroblewski, S. G. Hakim, F. T. Avila, D. N. Taylor, T. N. Rowley, S. D. Zhang, D. Gea-Banachloche, J. C. Sportes, C. Fowler, D. H. Bishop, M. R. Gress, R. E. Pavletic, S. Z. TI ROLE OF CLINICAL LABORATORY MARKERS OF INFLAMMATION IN ASSESSING CHRONIC GRAFT VERSUS HOST DISEASE (CGVHD) ACTIVITY AND SEVERITY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Grkovic, L.; Baird, K.; Steinberg, S. M.; Cowen, E. W.; Mitchell, S. A.; Williams, K. M.; Carpenter, A. E.; Wroblewski, S. G.; Hakim, F. T.; Avila, D. N.; Taylor, T. N.; Zhang, D.; Gea-Banachloche, J. C.; Sportes, C.; Fowler, D. H.; Bishop, M. R.; Gress, R. E.; Pavletic, S. Z.] NCI, NIH, Bethesda, MD 20892 USA. [Pulanic, D.] Univ Hosp Ctr Zagreb, Zagreb, Croatia. [Rowley, S. D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 524 BP S340 EP S341 DI 10.1016/j.bbmt.2010.12.561 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500524 ER PT J AU Hanash, AM Kappel, LW Yim, NL Nejat, RA Goldberg, GL Smith, OM Rao, UK Dykstra, L Na, IK Holland, AM Liu, C Murphy, GF Leonard, WJ Heller, G van den Brink, MRM AF Hanash, A. M. Kappel, L. W. Yim, N. L. Nejat, R. A. Goldberg, G. L. Smith, O. M. Rao, U. K. Dykstra, L. Na, I-K Holland, A. M. Liu, C. Murphy, G. F. Leonard, W. J. Heller, G. van den Brink, M. R. M. TI ABROGATION OF DONOR T CELL IL-21 SIGNALING LEADS TO TISSUE-SPECIFIC MODULATION OF IMMUNITY AND SEPARATION OF GVHD FROM GVL SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Hanash, A. M.; Kappel, L. W.; Yim, N. L.; Nejat, R. A.; Goldberg, G. L.; Smith, O. M.; Rao, U. K.; Dykstra, L.; Holland, A. M.; Heller, G.; van den Brink, M. R. M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Na, I-K] Charite CBF Univ Med Berlin, Berlin, Germany. [Liu, C.] Univ Florida, Coll Med, Gainesville, FL USA. [Murphy, G. F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Leonard, W. J.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 32 BP S163 EP S163 DI 10.1016/j.bbmt.2010.12.038 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500033 ER PT J AU Hardy, NM Hakim, FT Fellowes, VS Rose, JJ Gress, RE Bishop, MR AF Hardy, N. M. Hakim, F. T. Fellowes, V. S. Rose, J. J. Gress, R. E. Bishop, M. R. TI TUMOR-INFILTRATING LYMPHOCYTES ARE PRESENT IN CANCER RELAPSE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLOHSCT), OF DONOR ORIGIN, DISTINCT FROM PERIPHERAL BLOOD DONOR LYMPHOCYTES AND EXHIBIT EFFECTOR FUNCTION WITH CD3/CD28 COSTIMULATION EX-VIVO SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Hardy, N. M.; Hakim, F. T.; Fellowes, V. S.; Rose, J. J.; Gress, R. E.; Bishop, M. R.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 151 BP S209 EP S209 DI 10.1016/j.bbmt.2010.12.174 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500152 ER PT J AU Inamoto, Y Kurland, BF Chai, S Heffernan, MJ Martin, PJ Flowers, MED Carpenter, PA Cutler, C Jacobsohn, D Jagasia, M Johnston, L Vogelsang, GB Pavletic, SZ Lee, SJ AF Inamoto, Y. Kurland, B. F. Chai, S. Heffernan, M. J. Martin, P. J. Flowers, M. E. D. Carpenter, P. A. Cutler, C. Jacobsohn, D. Jagasia, M. Johnston, L. Vogelsang, G. B. Pavletic, S. Z. Lee, S. J. TI EVALUATION OF SCALES CORRELATED WITH CLINICIAN AND PATIENT-PERCEIVED SYMPTOM CHANGE IN OCULAR GRAFT-VERSUS-HOST DISEASE: RESULTS FROM THE CHRONIC GVHD CONSORTIUM SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Inamoto, Y.; Kurland, B. F.; Chai, S.; Heffernan, M. J.; Martin, P. J.; Flowers, M. E. D.; Carpenter, P. A.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cutler, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jacobsohn, D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Jagasia, M.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Johnston, L.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Vogelsang, G. B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Pavletic, S. Z.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 63 BP S175 EP S176 DI 10.1016/j.bbmt.2010.12.073 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500064 ER PT J AU Kang, EM Kelly, C Hilligoss, DM Marquesen, MM DeCastro, R Wilder, J Kwatemaa, AN Khuu, H Stroncek, D Malech, HL AF Kang, E. M. Kelly, C. Hilligoss, D. M. Marquesen, M. M. DeCastro, R. Wilder, J. Kwatemaa, A. N. Khuu, H. Stroncek, D. Malech, H. L. TI A NOVEL NON MYELOABLATIVE REGIMEN FOR RELATED AND UNRELATED ALLOGENEIC TRANSPLANTATION OF HIGH RISK PATIENTS WITH CHRONIC GRANULOMATOUS DISEASE (CGD) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Kang, E. M.; Kelly, C.; Hilligoss, D. M.; Marquesen, M. M.; DeCastro, R.; Wilder, J.; Kwatemaa, A. N.; Khuu, H.; Stroncek, D.; Malech, H. L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 390 BP S295 EP S295 DI 10.1016/j.bbmt.2010.12.426 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500390 ER PT J AU Kang, EM Yau, YY Maxwell, S DeRavin, SS Borge, PD Malech, HL Leitman, SF AF Kang, E. M. Yau, Y. Y. Maxwell, S. DeRavin, S. S. Borge, P. D. Malech, H. L. Leitman, S. F. TI MOBILIZATION OF CD34+CELLS WITH GRANULOCYTE COLONY STIMULATING FACTOR (GCSF) VERSUS GCSF PLUS PLERIXAFOR IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISORDERS (PIDS) UNDERGOING AUTOLOGOUS PERIPHERAL BLOOD STEM CELL (PBSC) COLLECTION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Kang, E. M.; Yau, Y. Y.; Maxwell, S.; DeRavin, S. S.; Borge, P. D.; Malech, H. L.; Leitman, S. F.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 181 BP S220 EP S220 DI 10.1016/j.bbmt.2010.12.205 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500182 ER PT J AU Kochenderfer, JN Dudley, ME Maric, I Feldman, SA Salit, R Hardy, NM Layton, P Blacklock-Schuver, B Wilder, J Devillier, L Gress, RE Morgan, RA Rosenberg, SA Bishop, MR AF Kochenderfer, J. N. Dudley, M. E. Maric, I Feldman, S. A. Salit, R. Hardy, N. M. Layton, P. Blacklock-Schuver, B. Wilder, J. Devillier, L. Gress, R. E. Morgan, R. A. Rosenberg, S. A. Bishop, M. R. TI DRAMATIC REGRESSION OF CHRONIC LYMPHOCYTIC LEUKEMIA IN THE FIRST PATIENT TREATED WITH DONOR-DERIVED GENETICALLY-ENGINEERED ANTI-CD 19-CHIMERIC-ANTIGEN-RECEPTOR-EXPRESSING T CELLS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Kochenderfer, J. N.; Dudley, M. E.; Feldman, S. A.; Salit, R.; Hardy, N. M.; Layton, P.; Blacklock-Schuver, B.; Wilder, J.; Devillier, L.; Gress, R. E.; Morgan, R. A.; Rosenberg, S. A.; Bishop, M. R.] NCI, Bethesda, MD 20892 USA. [Maric, I] NIH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 21 BP S158 EP S158 DI 10.1016/j.bbmt.2010.12.025 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500022 ER PT J AU Lafond, S Pulanic, TK Turner, M Bishop, M Fowler, D Mackall, C Stratton, P AF Lafond, S. Pulanic, Klepac T. Turner, M. Bishop, M. Fowler, D. Mackall, C. Stratton, P. TI GENITAL GRAFT VERSUS HOST DISEASE: ACUTE VERSUS EARLY ONSET CHRONIC DISEASE SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Lafond, S.; Turner, M.; Bishop, M.; Fowler, D.] NCI, NIH, Bethesda, MD 20892 USA. [Lafond, S.] George Washington Univ, Sch Med, Washington, DC USA. [Pulanic, Klepac T.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 532 BP S344 EP S344 DI 10.1016/j.bbmt.2010.12.569 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500532 ER PT J AU Lucas, PJ Sivarapatna, A Wang, J Gress, RE AF Lucas, P. J. Sivarapatna, A. Wang, J. Gress, R. E. TI RAPID PRECLINICAL SCREENING OF CHEMOTHERAPEUTIC AGENTS EFFECTIVE IN COMBINATION WITH IMMUNOTHERAPY SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Lucas, P. J.; Sivarapatna, A.; Wang, J.; Gress, R. E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 512 BP S337 EP S337 DI 10.1016/j.bbmt.2010.12.549 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500512 ER PT J AU McIver, ZA Mielke, S Shenoy, A Fellows, V Stroncek, D Leitman, S Childs, R Batiwalla, M Koklanaris, EK Haggerty, J Savani, BN Rezvani, K Barrett, AJ AF McIver, Z. A. Mielke, S. Shenoy, A. Fellows, V Stroncek, D. Leitman, S. Childs, R. Batiwalla, M. Koklanaris, E. K. Haggerty, J. Savani, B. N. Rezvani, K. Barrett, A. J. TI SELECTIVELY T CELL DEPLETED ALLOGRAFTS FROM HLA-MATCHED SIBLING DONORS FOLLOWED BY LOW-DOSE POST TRANSPLANT IMMUNOSUPPRESSION TO LIMIT DISEASE RELAPSE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [McIver, Z. A.; Fellows, V; Stroncek, D.; Leitman, S.; Childs, R.; Batiwalla, M.; Koklanaris, E. K.; Haggerty, J.; Barrett, A. J.] NIH, Bethesda, MD 20892 USA. [Mielke, S.] Univ Wurzburg, Wurzburg, Germany. [Shenoy, A.] Washington Hosp Ctr, Washington, DC 20010 USA. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Rezvani, K.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 366 BP S286 EP S286 DI 10.1016/j.bbmt.2010.12.402 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500366 ER PT J AU Melenhorst, JJ Leen, AM Bollard, CM Quigley, MF Price, DA Rooney, CM Brenner, MK Barrett, AJ Heslop, HE AF Melenhorst, J. J. Leen, A. M. Bollard, C. M. Quigley, M. F. Price, D. A. Rooney, C. M. Brenner, M. K. Barrett, A. J. Heslop, H. E. TI ALLOGENEIC VIRUS-SPECIFIC T CELLS WITH HLA ALLOREACTIVITY DO NOT PRODUCE GRAFT-VERSUS-HOST DISEASE IN HUMAN SUBJECTS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Melenhorst, J. J.; Barrett, A. J.] NHLBI, Bethesda, MD 20892 USA. [Leen, A. M.; Bollard, C. M.; Rooney, C. M.; Brenner, M. K.; Heslop, H. E.] Baylor Coll Med, Houston, TX 77030 USA. [Quigley, M. F.; Price, D. A.] NIAID, Bethesda, MD 20892 USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 22 BP S158 EP S158 DI 10.1016/j.bbmt.2010.12.026 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500023 ER PT J AU Melver, ZA Battiwalla, M Barrett, AJ AF Melver, Z. A. Battiwalla, M. Barrett, A. J. TI MISMATCHED DONOR LYMPHOCYTE INFUSIONS FOR RELAPSED ACUTE LEUKEMIA FOLLOWING HLA IDENTICAL ALLOGENEIC STEM CELL TRANSPLANT SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Melver, Z. A.; Battiwalla, M.; Barrett, A. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 167 BP S215 EP S215 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500168 ER PT J AU Pantin, JM Robert, HF Chen, MY Timothy, H Randall, CR Childs, RW AF Pantin, J. M. Robert, H. F. Chen, M. Y. Timothy, H. Randall, C. R. Childs, R. W. TI IMPACT OF INJECTION VOLUME AND INFUSION RATE IN A LARGE ANIMAL MODEL DESIGNED TO OPTIMIZE INTRABONE TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Pantin, J. M.; Robert, H. F.; Chen, M. Y.; Timothy, H.; Randall, C. R.; Childs, R. W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 401 BP S299 EP S299 DI 10.1016/j.bbmt.2010.12.437 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500401 ER PT J AU Papanicolau, G Kurtzberg, J Westervelt, P Gea-Banacloche, J Warlick, E Lanier, R Anderson, M Painter, W AF Papanicolau, G. Kurtzberg, J. Westervelt, P. Gea-Banacloche, J. Warlick, E. Lanier, R. Anderson, M. Painter, W. TI EXPERIENCE WITH CMX001, A NOVEL ANTIVIRAL DRUG, FOR CYTOMEGALOVIRUS INFECTIONS IN STEM TRANSPLANT PATIENTS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Papanicolau, G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kurtzberg, J.] Duke Univ, Med Ctr, Durham, NC USA. [Westervelt, P.] Washington Univ, Sch Med, St Louis, MO USA. [Gea-Banacloche, J.] NCI, Bethesda, MD 20892 USA. [Warlick, E.] Univ Minnesota, Minneapolis, MN USA. [Lanier, R.; Anderson, M.; Painter, W.] Chimerix Inc, Durham, NC USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 330 BP S273 EP S274 DI 10.1016/j.bbmt.2010.12.364 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500330 ER PT J AU Pidala, J Kurland, B Chai, X Majhail, N Weisdorf, D Pavletic, S Cutler, C Arai, S Jagasia, M Palmer, J Lee, SJ AF Pidala, J. Kurland, B. Chai, X. Majhail, N. Weisdorf, D. Pavletic, S. Cutler, C. Arai, S. Jagasia, M. Palmer, J. Lee, S. J. TI CHRONIC GVHD SEVERITY AND SENSITIVITY TO CHANGE IN PATIENT-REPORTED QUALITY OF LIFE: RESULTS FROM THE CHRONIC GVHD CONSORTIUM SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Pidala, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kurland, B.; Chai, X.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Majhail, N.; Weisdorf, D.] Univ Minnesota, Minneapolis, MN 55455 USA. [Pavletic, S.] NCI, Bethesda, MD 20892 USA. [Cutler, C.] Dana Farber Canc Inst, Boston, MA USA. [Arai, S.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Jagasia, M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Palmer, J.] Med Coll Wisconsin, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 229 BP S238 EP S238 DI 10.1016/j.bbmt.2010.12.257 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500229 ER PT J AU Ren, J Stroncek, D Jin, P Castiello, L Tran, K Balakumaran, A Robey, P Sabatino, M AF Ren, J. Stroncek, D. Jin, P. Castiello, L. Tran, K. Balakumaran, A. Robey, P. Sabatino, M. TI SENESCENCE OF CULTURED BONE MARROW STROMAL CELLS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Ren, J.; Stroncek, D.; Jin, P.; Castiello, L.; Tran, K.; Balakumaran, A.; Robey, P.; Sabatino, M.] NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 171 BP S216 EP S217 DI 10.1016/j.bbmt.2010.12.194 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500172 ER PT J AU Sullivan, KM Froshaug, DB Furst, DE Nash, RA Mayes, MD Crofford, LJ McSweeney, PA Goldmuntz, EA Keyes-Elstein, L Khanna, D AF Sullivan, K. M. Froshaug, D. B. Furst, D. E. Nash, R. A. Mayes, M. D. Crofford, L. J. McSweeney, P. A. Goldmuntz, E. A. Keyes-Elstein, L. Khanna, D. TI ORGAN FUNCTION AND QUALITY OF LIFE CORRELATES AT RANDOMIZATION ON THE SCOT (SCLERODERMA: CYCLOPHOSPHAMIDE OR TRANSPLANTATION) TRIAL SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Sullivan, K. M.] Duke Univ, Med Ctr, Durham, NC USA. [Froshaug, D. B.; Keyes-Elstein, L.] Rho Fed Syst, Chapel Hill, NC USA. [Furst, D. E.; Khanna, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Nash, R. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mayes, M. D.] Univ Texas Houston, Houston, TX USA. [Crofford, L. J.] Univ Kentucky, Lexington, KY USA. [McSweeney, P. A.] Rocky Mt Canc Ctr, Denver, CO USA. [Goldmuntz, E. A.] NIH, Bethesda, MD 20892 USA. RI Crofford, Leslie/J-8010-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 113 BP S195 EP S195 DI 10.1016/j.bbmt.2010.12.134 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500114 ER PT J AU Watson, TM Fry, TJ Jacobsohn, DA Sande, J Yates, B Stevenson, A AF Watson, T. M. Fry, T. J. Jacobsohn, D. A. Sande, J. Yates, B. Stevenson, A. TI PROCALCITONIN IN PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (AHSCT) RECIPIENTS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Watson, T. M.; Jacobsohn, D. A.; Sande, J.; Yates, B.; Stevenson, A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Fry, T. J.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sande, J.] George Washington Univ, Sch Med, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 314 BP S268 EP S268 DI 10.1016/j.bbmt.2010.12.345 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500314 ER PT J AU Wehrlen, LD Prachenko, O Prince, P Foruraghi, L Shelburne, N Wallen, GR Bevans, MF AF Wehrlen, L. D. Prachenko, O. Prince, P. Foruraghi, L. Shelburne, N. Wallen, G. R. Bevans, M. F. TI THE QUALITY OF THE ADULT CAREGIVER-RECIPIENT RELATIONSHIP MAY BUFFER CAREGIVER BURDEN DURING ALLOGENEIC TRANSPLANTATION SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Wehrlen, L. D.; Prachenko, O.; Prince, P.; Shelburne, N.; Wallen, G. R.; Bevans, M. F.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Foruraghi, L.] NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 109 BP S193 EP S194 DI 10.1016/j.bbmt.2010.12.128 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500110 ER PT J AU Williams, KM Hnatiuk, O Steinberg, SM Mitchell, S Baird, K Gadalla, SM Carpenter, A Avila, D Taylor, T Urban, A Comis, LE Blacklock-Schuver, B Gress, RE Pavletic, SZ AF Williams, K. M. Hnatiuk, O. Steinberg, S. M. Mitchell, S. Baird, K. Gadalla, S. M. Carpenter, A. Avila, D. Taylor, T. Urban, A. Comis, L. E. Blacklock-Schuver, B. Gress, R. E. Pavletic, S. Z. TI NHANES III EQUATIONS FOR PFT INTERPRETATION SIGNIFICANTLY ALTERS BOS DIAGNOSES, SEVERITY, AND PROGNOSIS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Williams, K. M.; Hnatiuk, O.; Steinberg, S. M.; Mitchell, S.; Baird, K.; Gadalla, S. M.; Carpenter, A.; Avila, D.; Taylor, T.; Urban, A.; Comis, L. E.; Blacklock-Schuver, B.; Gress, R. E.; Pavletic, S. Z.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 494 BP S331 EP S331 DI 10.1016/j.bbmt.2010.12.531 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500494 ER PT J AU Williams, KM Moore, AR Gress, RE AF Williams, K. M. Moore, A. R. Gress, R. E. TI FLT-3 LIGAND ENHANCES THYMOPOIESIS IN HEMATOPOIETIC STEM CELL TRANSPLANTS (HSCT) INVOLVING AGED DONOR AND RECIPIENT MICE BY INCREASING SURVIVAL AND TRAFFICKING OF EARLY THYMOCYTE PROGENITORS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood Marrow Transplantat, Ctr Int Blood Marrow Transplant Res C1 [Williams, K. M.; Moore, A. R.; Gress, R. E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 223 BP S236 EP S236 DI 10.1016/j.bbmt.2010.12.250 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500223 ER PT J AU Carter, TC Olney, RS Mitchell, AA Romitti, PA Bell, EM Druschel, CM AF Carter, Tonia C. Olney, Richard S. Mitchell, Allen A. Romitti, Paul A. Bell, Erin M. Druschel, Charlotte M. CA Natl Birth Defects Prevention Stud TI Maternal Self-Reported Genital Tract Infections During Pregnancy and the Risk of Selected Birth Defects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Teratology-Society CY JUN 26-30, 2010 CL Louisville, KY SP Teratol Soc DE Chlamydia; congenital abnormalities; female genital diseases; gonorrhea; herpes genitalis ID HERPES-SIMPLEX-VIRUS; CHLAMYDIA-TRACHOMATIS INFECTION; PELVIC-INFLAMMATORY-DISEASE; NEURAL-TUBE DEFECTS; CONGENITAL-ABNORMALITIES; BACTERIAL VAGINOSIS; PRETERM DELIVERY; HUMAN-PAPILLOMAVIRUS; NO ASSOCIATION; WOMEN AB BACKGROUND: Genital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis-generating study examined whether these infections are associated with selected birth defects. METHODS: We conducted a case-control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997-2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders. RESULTS: Genital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11-7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03-2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04-3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39-5.69). These findings were not statistically significant after adjustment for multiple comparisons. CONCLUSIONS: Caution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed. Birth Defects Research (Part A) 91:108-116, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Carter, Tonia C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. [Olney, Richard S.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Mitchell, Allen A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Bell, Erin M.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA. [Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA. RP Carter, TC (reprint author), 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM carterto@mail.nih.gov RI Publications, NBDPS/B-7692-2013; OI Mitchell, Allen/0000-0003-0950-6799 FU Intramural NIH HHS; NCBDD CDC HHS [U01 DD000492]; PHS HHS [U50/CCU223184] NR 53 TC 7 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD FEB PY 2011 VL 91 IS 2 BP 108 EP 116 DI 10.1002/bdra.20749 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 730LU UT WOS:000288035600006 PM 21319278 ER PT J AU Patel, V Collins, PY Copeland, J Kakuma, R Katontoka, S Lamichhane, J Naik, S Skeen, S AF Patel, Vikram Collins, Pamela Y. Copeland, John Kakuma, Ritsuko Katontoka, Sylvester Lamichhane, Jagannath Naik, Smita Skeen, Sarah TI The Movement for Global Mental Health SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Editorial Material AB The Movement for Global Mental Health is a coalition of individuals and institutions committed to collective actions that aim to close the treatment gap for people living with mental disorders worldwide, based on two fundamental principles: evidence on effective treatments and the human rights of people with mental disorders. C1 [Patel, Vikram; Naik, Smita] Sangath Ctr, Alto Porvorim 403521, Goa, India. [Patel, Vikram] London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London, England. [Collins, Pamela Y.] NIMH, NIH, Bethesda, MD 20892 USA. [Copeland, John] Univ Liverpool, Div Psychiat, Liverpool L69 3BX, Merseyside, England. [Kakuma, Ritsuko] Ctr Addict & Mental Hlth, Hlth Syst Res & Consulting Unit, Toronto, ON, Canada. [Kakuma, Ritsuko] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Kakuma, Ritsuko; Skeen, Sarah] Univ Cape Town, Dept Psychiat & Mental Hlth, Mental Hlth & Poverty Project, ZA-7700 Rondebosch, South Africa. [Katontoka, Sylvester] Mental Hlth Users Network Zambia, Lusaka, Zambia. [Lamichhane, Jagannath] NMHF, Kathmandu, Nepal. RP Patel, V (reprint author), Sangath Ctr, Alto Porvorim 403521, Goa, India. EM vikram.patel@lshtm.ac.uk OI Patel, Vikram/0000-0003-1066-8584 FU Wellcome Trust [091834] NR 8 TC 21 Z9 21 U1 0 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 2011 VL 198 IS 2 BP 88 EP 90 DI 10.1192/bjp.bp.109.074518 PG 3 WC Psychiatry SC Psychiatry GA 719BE UT WOS:000287173400003 PM 21282777 ER PT J AU Selby, P Sitzia, J AF Selby, Peter Sitzia, John TI NHS research governance procedures (December, pg 637, 2010) SO CLINICAL MEDICINE LA English DT Correction C1 [Selby, Peter; Sitzia, John] NIH, Res Clin Res Network, Bethesda, MD 20892 USA. RP Selby, P (reprint author), NIH, Res Clin Res Network, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 4 PU ROY COLL PHYS LONDON EDITORIAL OFFICE PI LONDON PA 11 ST ANDREWS PLACE REGENTS PARK, LONDON NW1 4LE, ENGLAND SN 1470-2118 J9 CLIN MED JI Clin. Med. PD FEB PY 2011 VL 11 IS 1 BP 99 EP 99 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 730SI UT WOS:000288054200037 ER PT J AU Schindler, CW Gilman, JP Panlilio, LV McCann, DJ Goldberg, SR AF Schindler, Charles W. Gilman, Joanne P. Panlilio, Leigh V. McCann, David J. Goldberg, Steven R. TI Comparison of the Effects of Methamphetamine, Bupropion, and Methylphenidate on the Self-Administration of Methamphetamine by Rhesus Monkeys SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE methamphetamine; self-administration; bupropion; methylphenidate; rhesus monkeys ID D-AMPHETAMINE TREATMENT; PROGRESSIVE-RATIO SCHEDULE; PLACEBO-CONTROLLED TRIAL; COCAINE-DEPENDENCE; AGONIST-LIKE; FOOD; ABUSE; PHARMACOTHERAPY; DEXAMPHETAMINE; METHADONE AB The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 30 mu g/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment. C1 [Schindler, Charles W.; Gilman, Joanne P.; Panlilio, Leigh V.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, NIH,Behav Neurosci Branch, Intramural Res Program,US Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [McCann, David J.] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, DHHS, NIH, Baltimore, MD 21224 USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, NIH,Behav Neurosci Branch, Intramural Res Program,US Dept Hlth & Human Serv, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM cschindl@helix.nih.gov FU NIH, NIDA; NIDA Division of Pharmacotherapies and Medical Consequences of Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, NIDA, and by the NIDA Division of Pharmacotherapies and Medical Consequences of Drug Abuse. NR 47 TC 14 Z9 15 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2011 VL 19 IS 1 BP 1 EP 10 DI 10.1037/a0022432 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 722WM UT WOS:000287466000001 PM 21341918 ER PT J AU Gualco, G Weiss, LM Barber, GN Bacchi, CE AF Gualco, Gabriela Weiss, Lawrence M. Barber, Glen N. Bacchi, Carlos E. TI Diffuse Large B-Cell Lymphoma Involving the Central Nervous System SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE primary central nervous system lymphoma; central nervous system lymphoma; diffuse large B-cell lymphoma; WHO classification; human immunodeficiency virus; immunocompromised; immunocompetent; immunohistochemistry; EBV ID PRIMARY CNS LYMPHOMA; EPSTEIN-BARR-VIRUS; GENE-EXPRESSION; IMMUNOCOMPETENT PATIENTS; PATTERN; CXCR4 AB Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell like and nongerminal B-cell like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype. C1 [Gualco, Gabriela; Bacchi, Carlos E.] Consultoria Patol, BR-18602010 Botucatu, SP, Brazil. [Weiss, Lawrence M.] City Hope Natl Med Ctr, Div 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. RP Bacchi, CE (reprint author), Consultoria Patol, Rua Major Leonidas Cardoso 739, BR-18602010 Botucatu, SP, Brazil. EM bacchi@conspat.com.br NR 31 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD FEB PY 2011 VL 19 IS 1 BP 44 EP 50 DI 10.1177/1066896910386476 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 709OY UT WOS:000286451200007 PM 21087986 ER PT J AU Meleth, AD Mettu, P Agron, E Chew, EY Sadda, SR Ferris, FL Wong, WT AF Meleth, Annal D. Mettu, Pradeep Agron, Elvira Chew, Emily Y. Sadda, Srinivas R. Ferris, Frederick L. Wong, Wai T. TI Changes in Retinal Sensitivity in Geographic Atrophy Progression as Measured by Microperimetry SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IDIOPATHIC MACULAR TELANGIECTASIA; AGE-RELATED MACULOPATHY; VISUAL-ACUITY LOSS; FUNDUS AUTOFLUORESCENCE; MP-1 MICROPERIMETER; FIXATION PATTERNS; CENTRAL SCOTOMAS; RISK-FACTORS; DEGENERATION AB PURPOSE. To characterize changes in macular sensitivity during geographic atrophy (GA) progression using microperimetry. METHODS. Retinal sensitivity in the macular area was evaluated by microperimetry in 10 patients with bilateral GA, with adequate data obtained in 9 of 10 patients (n = 18 eyes). Patients had been enrolled in an interventional trial in which one eye had been randomized to treatment and the other eye observed. No treatment effect with regard to GA growth and microperimetric measurements was detected, and all eyes were analyzed. Microperimetric assessments of the central 20 of the macula were performed every 6 months over 24 months. Parameters analyzed included number of scotomatous points, mean retinal sensitivity of responding points, and fixation stability. Autofluorescence imaging and fundus photography were also obtained. RESULTS. Microperimetric parameters demonstrated statistically significant changes as a function of time. Mean number of scotomatous points increased significantly with time (P = 0.004) at a rate of 4.4 points/year. Mean retinal sensitivities of all points, all responding points, and all perilesional points all decreased significantly with time (P < 0.003), as did fixation quality within the 2 and 4 circles (P < 0.002). The growth of GA lesion area was associated with the changes in the number of scotomatous points (P = 0.01) but not with changes in the other microperimetric parameters. CONCLUSIONS. Macular sensitivity and fixation quality undergo progressive change during the GA progression, reflecting alterations in macular function extending beyond the GA lesion proper. Microperimetric measurements may provide useful functional outcome measures for the clinical study of GA. (Invest Ophthalmol Vis Sci. 2011; 52:1119-1126) DOI:10.1167/iovs.10-6075 C1 [Mettu, Pradeep; Wong, Wai T.] NIH, Unit Neuron Glia Interact Retinal Dis, Bethesda, MD 20892 USA. [Meleth, Annal D.; Mettu, Pradeep; Agron, Elvira; Chew, Emily Y.; Ferris, Frederick L.; Wong, Wai T.] NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Sadda, Srinivas R.] Univ So Calif, Keck Sch Med, Doheny Image Reading Ctr, Doheny Eye Inst, Los Angeles, CA 90033 USA. RP Wong, WT (reprint author), NIH, Unit Neuron Glia Interact Retinal Dis, 7 Mem Dr,Bldg 7,Room 217, Bethesda, MD 20892 USA. EM wongw@nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute FX Supported by funding from the National Eye Institute Intramural Research Program. NR 42 TC 31 Z9 32 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2011 VL 52 IS 2 BP 1119 EP 1126 DI 10.1167/iovs.10-6075 PG 8 WC Ophthalmology SC Ophthalmology GA 728AQ UT WOS:000287846300066 PM 20926818 ER PT J AU Arancibia, S Benitez, D Nunez, LE Jewell, CM Langjahr, P Candia, E Zapata-Torres, G Cidlowski, JA Gonzalez, MJ Hermoso, MA AF Arancibia, Sergio Benitez, Dixan Nunez, Lucia E. Jewell, Christine M. Langjahr, Patricia Candia, Enzo Zapata-Torres, Gerald Cidlowski, John A. Gonzalez, Maria-Julieta Hermoso, Marcela A. TI Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE lung mucosa inflammation; TLR2; glucocorticoid receptor; phosphatidylinositol-3-kinase ID NF-KAPPA-B; TOLL-LIKE RECEPTOR-2; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; P65 SUBUNIT; PHOSPHOINOSITIDE 3-KINASE; INNATE IMMUNITY; CELLS; PATHWAY; LIPOPOLYSACCHARIDE AB Airway inflammation is a common condition where glucocorticoids (GC) are a well-established therapy. It has been demonstrated that GC stimulate components of innate immunity. Specifically, GC up-regulate TLR2 expression and activation upon inflammatory stimuli; however, little is known about the signalling involved in this process. To determine the mechanism by which dexamethasone modulates TLR2-induced cytokine production this signalling pathway was monitored in a lung epithelial cell line exposed to the TLR2 synthetic agonist, Pam3-Cys-Ser-Lys4. These experiments demonstrate that phosphatidylinositol 3-kinase (PI3K) is critical for the TLR2 downstream effects of GC. Cells expressing a PI3K mutant (p85-dominant negative, DN; p85 Delta 478-511) and exposed to Pam3-Cys-Ser-Lys4 in the presence or absence of dexamethasone, showed enhanced tumour necrosis factor (TNF)alpha expression while AP-1 and NF-kappa B transcriptional activity were repressed. We provide experimental evidence that PI3K physically interacts with the glucocorticoid receptor (GR) through two putative PI3K recruitment consensus YxxM binding motifs in the GR, suggesting that some functions regulated by this receptor might occur through kinase interaction. Mutations of two tyrosine residues in the GR, 598 and 663, to phenylalanine significantly reduced interaction with PI3K and the GC effects on TLR2-induced TNF-alpha expression. However, these mutations did not alter GR transcriptional activity nor affect cellular localization of the expressed mutant GR in COS-1 cells. Therefore, the PI3K-GR interaction may contribute to the effects of GC on the TLR2 pro-inflammatory signalling cascade, thus defining a novel signalling mechanism with a profound impact on innate immune responses. C1 [Hermoso, Marcela A.] Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Disciplinario Inmunol,Sch Med, Santiago 7, Chile. [Jewell, Christine M.; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Zapata-Torres, Gerald] Univ Chile, Fac Chem & Pharm, Dept Inorgan & Analyt Chem, Santiago 7, Chile. [Gonzalez, Maria-Julieta] Univ Chile, Sch Med, Inst Biomed Sci, Cell & Mol Biol Program, Santiago 7, Chile. RP Hermoso, MA (reprint author), Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Disciplinario Inmunol,Sch Med, Independencia 1027, Santiago 7, Chile. EM mhermoso@med.uchile.cl FU FONDECYT [1080290, 1050451]; NIEHS/NIH FX Funding support from FONDECYT 1080290, 1050451 and NIEHS/NIH, and to P. Silva and C. Beltran for technical support and to Dr. F. Salazar for providing cytokines and cell line supplies. NR 45 TC 7 Z9 8 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD FEB PY 2011 VL 15 IS 2 BP 339 EP 349 DI 10.1111/j.1582-4934.2009.00958.x PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 726TL UT WOS:000287749000015 PM 19874421 ER PT J AU Muller-Hocker, J Horvath, R Schafer, S Hessel, H Muller-Felber, W Kuhr, J Copeland, WC Seibel, P AF Mueller-Hoecker, J. Horvath, R. Schaefer, S. Hessel, H. Mueller-Felber, W. Kuehr, J. Copeland, W. C. Seibel, P. TI Mitochondrial DNA depletion and fatal infantile hepatic failure due to mutations in the mitochondrial polymerase gamma (POLG) gene: a combined morphological/enzyme histochemical and immunocytochemical/biochemical and molecular genetic study SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE depletion of mtDNA; polymerase gamma; mitochondrial single stranded binding protein(mtSSB); mitochondrial transcription factor A (mtTFA); liver failure; in situ hybridization ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DEOXYGUANOSINE KINASE GENE; MTDNA DEPLETION; ALPERS-SYNDROME; RESPIRATORY-CHAIN; TRANSCRIPTION FACTOR; INSITU HYBRIDIZATION; TK2 DEFICIENCY; LIVER-DISEASE; COPY NUMBER AB Combined morphological, immunocytochemical, biochemical and molecular genetic studies were performed on skeletal muscle, heart muscle and liver tissue of a 16-months boy with fatal liver failure. The pathological characterization of the tissues revealed a severe depletion of mtDNA (mitochondrial DNA) that was most pronounced in liver, followed by a less severe, but still significant depletion in skeletal muscle and the heart. The primary cause of the disease was linked to compound heterozygous mutations in the polymerase gamma (POLG) gene (DNA polymerase gamma; A467T, K1191N). We present evidence, that compound heterozygous POLG mutations lead to tissue selective impairment of mtDNA replication and thus to a mosaic defect pattern even in the severely affected liver. A variable defect pattern was found in liver, muscle and heart tissue as revealed by biochemical, cytochemical, immunocytochemical and in situ hybridization analysis. Functionally, a severe deficiency of cytochrome-c-oxidase (cox) activity was seen in the liver. Although mtDNA depletion was detected in heart and skeletal muscle, there was no cox deficiency in these tissues. Depletion of mtDNA and microdissection of cox-positive or negative areas correlated with the histological pattern in the liver. Interestingly, the mosaic pattern detected for cox-activity and mtDNA copy number fully aligned with the immunohistologically revealed defect pattern using Pol gamma, mtSSB-and mtTFA-antibodies, thus substantiating the hypothesis that nuclear encoded proteins located within mitochondria become unstable and are degraded when they are not actively bound to mtDNA. Their disappearance could also aggravate the mtDNA depletion and contribute to the non-homogenous defect pattern. C1 [Mueller-Hoecker, J.; Schaefer, S.; Hessel, H.] Univ Munich, Inst Pathol, D-80337 Munich, Germany. [Horvath, R.] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80337 Munich, Germany. [Horvath, R.] Newcastle Univ, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mueller-Felber, W.] Univ Munich, Neurol Klin & Poliklin, Friedrich Baur Inst, D-80337 Munich, Germany. [Kuehr, J.] Municipal Hosp Karlsruhe, Clin Pediat & Adolescent Med, Karlsruhe, Germany. [Copeland, W. C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Seibel, P.] Univ Leipzig, Biotechnol Biomed Zentrum, Leipzig, Germany. RP Muller-Hocker, J (reprint author), Univ Munich, Inst Pathol, Thalkirchnerstr 36, D-80337 Munich, Germany. EM josef.mueller-hoecker@med.uni-muenchen.de FU National Institutes of Health, NIEHS; Sachsische Ministerium fur Wissenschaft und Kunst; Deutsche Forschungsgemeinschaft [HO 2505/2-1] FX The authors are indebted to Mrs. Diane Raabe and Mrs. Monika Attmanspacher for invaluable help in preparing the manuscript. Funding information: W. C. C. is funded by intramural funds from the National Institutes of Health, NIEHS. This work was in part (P. S.) supported by the Sachsische Ministerium fur Wissenschaft und Kunst. RH is supported by the Deutsche Forschungsgemeinschaft HO 2505/2-1. NR 63 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD FEB PY 2011 VL 15 IS 2 BP 445 EP 456 DI 10.1111/j.1582-4934.2009.00819.x PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 726TL UT WOS:000287749000023 PM 19538466 ER PT J AU Versiani, MA Diyabalanage, T Ratnayake, R Henrich, CJ Bates, SE McMahon, JB Gustafson, KR AF Versiani, Muhammad Ali Diyabalanage, Thushara Ratnayake, Ranjala Henrich, Curtis J. Bates, Susan E. McMahon, James B. Gustafson, Kirk R. TI Flavonoids from Eight Tropical Plant Species That Inhibit the Multidrug Resistance Transporter ABCG2 SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PROTEIN; CANCER; LEAVES; FLAVANONES; AGLYCONES; ASSAY AB Overexpression of ABCG2, a membrane-bound multidrug transporter, can make tumor cells resistant to treatment with conventional chemotherapeutic agents. A high-throughput screening effort with the NCI repository of natural product extracts revealed that eight tropical plant extracts significantly inhibited the function of ABCG2. This activity was tracked throughout the extract fractionation process to a series of ABCG2 inhibitory flavonoids (1-13). Their structures were identified by a combination of NMR, mass spectrometry, and circular dichroism studies, and this resulted in the elucidation of (2S)-5,7,3'-trihydroxy-4'-methoxy-8-(3 ''-methylbut-2 ''-enyl)-flavonone (1), (2S)-5,7,3',5'-tetrahydroxy-8-[3 '',8 ''-dimethylocta-2 ''(E),7 ''-dienyl]flavonone (3), and 5,7,3'-trihydroxy-3,5'-dimethoxy-2'-(3'-methylbut-2-enyl)flavone (12,) as new compounds. C1 [Versiani, Muhammad Ali; Diyabalanage, Thushara; Ratnayake, Ranjala; Henrich, Curtis J.; McMahon, James B.; Gustafson, Kirk R.] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Henrich, Curtis J.] NCI Frederick, SAIC Frederick, Frederick, MD 21702 USA. [Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gustafson, KR (reprint author), NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM gustafki@mail.nih.gov OI Versiani, Muhammad Ali/0000-0002-9587-5891 FU Higher Education Commission (HEC), Government of Pakistan; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank D. Newman (NCI) and T. McCloud (SAIC-Frederick) for the plant extracts and M. Dyba and S. Terasova (Biophysics Resource, SBL, NCI-Frederick) for assistance with the HRLCMS studies, M.A.V. gratefully acknowledges the Higher Education Commission (HEC), Government of Pakistan, for providing a Post Doctoral scholarship. This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. This project was also funded in part with 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 Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 29 TC 10 Z9 11 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 2011 VL 74 IS 2 BP 262 EP 266 DI 10.1021/np100797y PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 725IB UT WOS:000287637300022 PM 21275386 ER PT J AU Le, K Coelho, C Mozeiko, J Grafman, J AF Le, Karen Coelho, Carl Mozeiko, Jennifer Grafman, Jordan TI Measuring Goodness of Story Narratives SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE discourse analysis; content analysis; story grammar; narrative discourse ID TRAUMATIC BRAIN-INJURY; CLOSED-HEAD-INJURY; DISCOURSE PRODUCTION; ADULTS; ADOLESCENTS; KNOWLEDGE; CHILDREN; ABILITY; SKILLS; MILD AB Purpose: The purpose of this article was to evaluate a new measure of story narrative performance: story completeness. It was hypothesized that by combining organizational (story grammar) and completeness measures, story "goodness" could be quantified. Method: Discourse samples from 46 typically developing adults were compared with those from 24 adults with acquired brain injuries. Story retellings were elicited and analyzed for episode structure (story grammar). Each story was also evaluated for the presence of 5 key components, yielding the story completeness score. Story goodness was quantified by combining the story grammar and completeness measures using a 2-coordinate grid system. A multivariate analysis of variance was performed as well as correlational analyses between the story grammar and story completeness scores. Results: There were significant group differences on both story grammar and story completeness. Moderate correlations were noted between the 2 measures, suggesting that the indices were not entirely measuring the same abilities. Plotting the 2 sets of scores into quadrants discriminated the comparison group and the group with brain injury into 4 distinct categories of story "goodness." Conclusion: The combination of measures provided a more accurate depiction of discourse performance than either measure alone. Results suggest the measure is sensitive, is reliable, and has potential utility for investigating discourse deficits in clinical populations. C1 [Le, Karen; Coelho, Carl; Mozeiko, Jennifer] Univ Connecticut, Storrs, CT USA. [Grafman, Jordan] NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, Bldg 10,7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 30 TC 12 Z9 12 U1 0 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD FEB 1 PY 2011 VL 54 IS 1 BP 118 EP 126 DI 10.1044/1092-4388(2010/09-0022) PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 714IY UT WOS:000286804500015 PM 20719868 ER PT J AU Baccarelli, A Benjamin, EJ AF Baccarelli, Andrea Benjamin, Emelia J. TI Triggers of MI for the individual and in the community SO LANCET LA English DT Editorial Material ID AMERICAN-HEART-ASSOCIATION; AIR-POLLUTION; DISEASE; UPDATE C1 [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. RP Baccarelli, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. EM abaccare@hsph.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Benjamin, Emelia/0000-0003-4076-2336 FU NIEHS NIH HHS [P30 ES000002, P30 ES000002-46] NR 10 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB-MAR PY 2011 VL 377 IS 9767 BP 694 EP 696 DI 10.1016/S0140-6736(10)62348-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 729JQ UT WOS:000287946000005 PM 21353302 ER PT J AU Kutlesic, V AF Kutlesic, Vesna TI Empowering schools to serve as safety nets for children with behavior problems in Serbia SO LEARNING AND INDIVIDUAL DIFFERENCES LA English DT Article DE Special education; Behavior problems; Serbia; Eastern Europe AB Children with special needs have been a focus of institutional reforms in Serbia for nearly two decades. Historically, as in other Eastern European countries, children with severe developmental, emotional, and/or behavior disorders in Serbia were often placed in institutions far from their families for much of their lives. Since the fall of communism, extensive government reforms in Serbia, guided by Western development agencies, have focused on deinstitutionalizing youth, but only with modest results. Underdeveloped special education programs within the Serbian public school system, have also contributed to children with special needs being at increased risk for leaving school and having legal problems. However, newly passed legislation is empowering Serbian schools and communities to serve as safety nets for vulnerable youth. Published by Elsevier Inc. C1 [Kutlesic, Vesna] US NIH, UNICEF, Belgrade 11000, Serbia. RP Kutlesic, V (reprint author), US NIH, Off Director, 1 Ctr Dr,Room 114, Bethesda, MD 20892 USA. EM vkutlesic@aol.com NR 25 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1041-6080 J9 LEARN INDIVID DIFFER JI Learn. Individ. Differ. PD FEB PY 2011 VL 21 IS 1 BP 41 EP 48 DI 10.1016/j.lindif.2010.10.007 PG 8 WC Psychology, Educational SC Psychology GA 713EZ UT WOS:000286719100006 ER PT J AU Liu, ZF Jia, B Zhao, HY Chen, XY Wang, F AF Liu, Zhaofei Jia, Bing Zhao, Huiyun Chen, Xiaoyuan Wang, Fan TI Specific Targeting of Human Integrin alpha(v)beta(3) with In-111-Labeled Abegrin (TM) in Nude Mouse Models SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Tumor; Integrin alpha(v)beta(3); In-111; Abegrin (TM); Imaging ID POSITRON-EMISSION-TOMOGRAPHY; RGD-BOMBESIN HETERODIMER; MONOCLONAL-ANTIBODY LA22; IN-VITRO; CANCER-THERAPY; TUMOR; RECEPTOR; ALPHA-V-BETA-3; EXPRESSION; ANGIOGENESIS AB The cell adhesion molecule integrin alpha(v)beta(3) is an important player in the process of tumor angiogenesis and metastasis. Abegrin (TM), a fully humanized anti-integrin alpha(v)beta(3) monoclonal antibody, was currently in clinical trials for cancer therapy. Herein, we labeled Abegrin (TM) with In-111, evaluated the in vitro and in vivo characteristics, and investigated whether the expression of integrin alpha(v)beta(3) in tumors could be imaged with In-111-labeled Abegrin (TM). The binding affinity and specificity of Abegrin (TM) was analyzed using U87MG glioblastoma cells. Abegrin (TM) was coupled with 1,4,7,10-tetraazadodecane-N,N',NaEuro(3),N'aEuro(3)-tetraacetic acid (DOTA) for In-111 radiolabeling. gamma Imaging of In-111-DOTA-Abegrin (TM) was carried out in nude mice bearing both integrin alpha(v)beta(3)-positive U87MG and integrin alpha(v)beta(3)-negative HT-29 tumors. Biodistribution and blocking studies of In-111-DOTA-Abegrin (TM) were investigated in U87MG tumor-bearing nude mice. Abegrin (TM) exhibited high-binding affinity to human integrin alpha(v)beta(3) expressed on U87MG cells (K (d) of 0.35 +/- 0.06 nM). The antibody retained antigen-binding affinity/specificity after DOTA conjugation. gamma Imaging showed that the tumor uptake of In-111-DOTA-Abegrin (TM) in integrin alpha(v)beta(3)-positive U87MG tumors was much higher than that in integrin alpha(v)beta(3)-negative HT-29 tumors. In the HT-29 tumors, Abegrin (TM) was mainly nonspecifically accumulated around the blood vessels, while in the U87MG tumors, besides the nonspecific tumor retention, Abegrin (TM) also specifically bound the human integrin alpha(v)beta(3) expressed on the tumor cells. Biodistribution and blocking studies exhibited that the U87MG tumor uptake of In-111-DOTA-Abegrin (TM) decreased from 14.12 +/- 0.44 to 6.93 +/- 0.94 percentage of injected dose per gram of tissue after coinjection of excess dose of cold Abegrin (TM), which confirmed the in vivo integrin alpha(v)beta(3) binding specificity of In-111-DOTA-Abegrin (TM). Abegrin (TM) showed specific binding to human integrin alpha(v)beta(3) expressed on the tumor cells. In-111-DOTA-Abegrin (TM) can specifically target the human integrin alpha(v)beta(3) expression in the nude mouse model. In-111-DOTA-Abegrin (TM) has a potential for clinical translation as an agent for integrin alpha(v)beta(3)-positive tumor imaging, evaluating tumor angiogenic status and monitoring the therapeutic efficacy of Abegrin (TM)-based cancer therapy. C1 [Liu, Zhaofei; Jia, Bing; Zhao, Huiyun; Wang, Fan] Peking Univ, Sch Basic Med Sci, Med Isotopes Res Ctr, Beijing 100191, Peoples R China. [Liu, Zhaofei; Jia, Bing; Zhao, Huiyun; Wang, Fan] Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China. [Chen, Xiaoyuan] Stanford Univ, Sch Med, MIPS, Dept Radiol,Biophys & Biox Program, Stanford, CA 94305 USA. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Wang, F (reprint author), Peking Univ, Sch Basic Med Sci, Med Isotopes Res Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM wangfan@bjmu.edu.cn RI Jia, Bing/C-3796-2008 FU NSFC [30930030, 30870728, 30900373, 20820102035]; 863 project [2007AA02Z467]; Ministry of Science and Technology of China [2009ZX09103-733, 2009ZX09301-010, 2009ZX09103-746] FX We thank Mr. Zhi Yang and Mr. Cunjing Jin for their excellent technical assistance with gamma-imaging and biodistribution studies. This work is jointly supported by NSFC projects (30930030, 30870728, 30900373, and 20820102035), an 863 project (2007AA02Z467), and grants from the Ministry of Science and Technology of China (2009ZX09103-733, 2009ZX09301-010, and 2009ZX09103-746). NR 39 TC 12 Z9 12 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2011 VL 13 IS 1 BP 112 EP 120 DI 10.1007/s11307-010-0302-4 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 708WS UT WOS:000286395600015 PM 20383594 ER PT J AU Riddle, LR Kumar, R Griffin, SA Grundt, P Newman, AH Luedtke, RR AF Riddle, Lindsay R. Kumar, Rakesh Griffin, Suzy A. Grundt, Peter Newman, Amy Hauck Luedtke, Robert R. TI Evaluation of the D3 dopamine receptor selective agonist/partial agonist PG01042 on L-dopa dependent animal involuntary movements in rats SO NEUROPHARMACOLOGY LA English DT Article DE Parkinson's Disease; Dyskinesia; L-dopa; Dopamine receptors; D3 dopamine receptors ID FUNCTIONALIZED LINKING CHAINS; ABUSE THERAPEUTIC AGENTS; MESSENGER-RNA; IN-VIVO; PREFRONTAL CORTEX; PHOSPHOLIPASE-D; D-3 RECEPTOR; INDUCED DYSKINESIAS; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS AB The substituted 4-phenylpiperazine D3 dopamine receptor selective antagonist PG01037 ((E)-N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-2-enyl)-4-(pyridin-2-yl)benzamide) was reported to attenuate L-dopa-associated abnormal involuntary movements (AIMS) in unilaterally lesioned rats, a model of L-dopa-dependent dyskinesia in patients with Parkinson's Disease (Kumar et al., 2009a). We now report that PG01042 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-3-yl)benzamide), which is a D3 dopamine receptor selective agonist for adenylyl cyclase inhibition and a partial agonist for mitogenesis, is also capable of attenuating AIMs scores. The intrinsic activity of PG01037 and PG01042 were determined using a) a forskolin-dependent adenylyl cyclase inhibition assay and b) an assay for agonist-associated mitogenesis. It was observed that the in vivo efficacy of PG01042 increased when administered by intraperitoneal (i.p.) injection simultaneously with L-dopa/benserazide (8 mg/kg each), as compared to a 60 min or 30 min pretreatment. PG01042 was found to attenuate AIM scores in these animals in a dose dependent manner. While PG01042 did not effectively inhibit SKF 81297-dependent AIMs, it inhibited apomorphine-dependent AIM scores. Rotarod studies indicate that PG01042 at a dose of 10 mg/kg did not adversely affect motor coordination of the unilaterally lesioned rats. Evaluation of lesioned rats using a cylinder test behavioral paradigm indicated that PG01042 did not dramatically attenuate the beneficial effects of L-dopa. These studies and previously published studies suggest that both D3 dopamine receptor selective antagonists, partial agonists and agonists, as defined by an adenylyl cyclase inhibition assay and a mitogenic assay, are pharmacotherapeutic candidates for the treatment of L-dopa-associated dyskinesia in patients with Parkinson's Disease. (C) 2010 Published by Elsevier Ltd. C1 [Riddle, Lindsay R.; Kumar, Rakesh; Griffin, Suzy A.; Luedtke, Robert R.] Univ N Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Grundt, Peter; Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Luedtke, RR (reprint author), Univ N Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie, Ft Worth, TX 76107 USA. EM robert.luedke@unthsc.edu FU Michael J. Fox Foundation for Parkinson's Research; NIDA-IRP; [N01DA-1-8816]; [R-01 DA13584-0351] FX This research was supported by a Community Fast Track 2006 from the Michael J. Fox Foundation for Parkinson's Research and R-01 DA13584-0351 (RRL) and the NIDA-IRP (AHN and PG). The authors would like to thank Drs. Eunson Jung and Nathalie Sumien for their assistance with the statistical analysis and helpful discussions. The authors also thank the NIDA Addiction Treatment Discovery Program for contract resources used to conduct the D2 and D3 receptor based mitogenic assays. These were contract N01DA-1-8816 to SRI International (PI Larry Toll) and interagency agreement IAGY1 DA 5007-05 to the Portland VA Medical Center (PI Aaron Janowsky). NR 79 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD FEB-MAR PY 2011 VL 60 IS 2-3 BP 284 EP 294 DI 10.1016/j.neuropharm.2010.09.011 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 717NL UT WOS:000287054600011 PM 20850462 ER PT J AU Dlamini, JN Hu, ZH Somaroo, H Highbarger, HC Follmann, DA Dewar, RL Pau, AK AF Dlamini, Judith N. Hu, Zonghui Somaroo, Harsha Highbarger, Helene C. Follmann, Dean A. Dewar, Robin L. Pau, Alice K. TI Lack of Effect from a Previous Single Dose of Nevirapine on Virologic and Immunologic Responses After 6 Months of Antiretroviral Regimens Containing Either Efavirenz or Lopinavir-Ritonavir SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 16th Conference on Retroviruses and Opportunistic Infections (CROI) CY FEB 08-11, 2009 CL Montreal, CANADA DE single-dose nevirapine; efavirenz; human immunodeficiency virus; HIV; response; antiretroviral; South Africa; women ID OPEN-LABEL TRIAL; THERAPY; HIV-1; TRANSMISSION; EXPOSURE; WOMEN; RESISTANCE; MOTHERS; AFRICA AB Study Objective. To evaluate the effect of a previous single dose of nevirapine given to prevent mother-to-child transmission of human immunodeficiency virus (HIV) on virologic and immunologic measures after 6 months of an antiretroviral regimen containing either efavirenz or lopinavir-ritonavir. Design. Retrospective subgroup analysis of data from the Phidisa II trial. Setting. Six South African research clinics. Patients. A total of 394 women with HIV who completed 6 months of combination antiretroviral regimen containing either efavirenz or lopinavir-ritonavir as part of the Phidisa II trial. Measurements and Main Results. During the screening process for the Phidisa II study, 478 women were asked about previous nevirapine use: 392 women (82%) were nevirapine naive, and 86 (18%) had received nevirapine. During the study, patients received either an efavirenz-based or lopinavir-ritonavir based antiretroviral regimen. After 6 months of treatment, virologic (HIV RNA levels) and immunologic (CD4(+) cell count) responses were measured. These data were compared between women with or without previous nevirapine exposure, and between women who received efavirenz versus lopinavir-ritonavir. After 6 months of treatment, 394 women (324 nevirapine naive, 70 exposed to nevirapine) had follow-up HIV RNA results. Two hundred twenty-seven (70.1%) of the nevirapine-naive patients and 48 (68.6%) of the nevirapine-exposed patients achieved HIV RNA levels lower than 400 copies/ml (p=0.89), with CD4(+) cell count increases of 115.5 and 120.4 cells/mm(3), respectively (p=0.67). Among the nevirapine-exposed women, 27 (75%) of 36 efavirenz-treated and 21 (61.8%) of 34 lopinavir-ritonavir-treated patients had HIV RNA levels lower than 400 copies/ml at 6 months (p=0.31). Conclusion. In this retrospective analysis of a small cohort, previous exposure to a single dose of nevirapine did not affect virologic outcomes after 6 months of either an efavirenz-based or lopinavir-ritonavir-based antiretroviral regimen. As efavirenz is one of the first-line combination antiretroviral therapies administered in Africa, it remains an option for women who received single-dose nevirapine. C1 [Hu, Zonghui; Follmann, Dean A.; Pau, Alice K.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Dlamini, Judith N.; Somaroo, Harsha] S African Mil Hlth Serv, Project Phidisa, Centurion, South Africa. [Highbarger, Helene C.; Dewar, Robin L.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Pau, AK (reprint author), NIAID, Div Clin Res, NIH, Bldg 10,Room 11C103,MSC 1880, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AI999999] NR 15 TC 0 Z9 0 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD FEB PY 2011 VL 31 IS 2 BP 158 EP 163 DI 10.1592/phco.31.2.158 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 716IX UT WOS:000286963400005 PM 21275494 ER PT J AU Abe, K Puertollano, R AF Abe, Ken Puertollano, Rosa TI Role of TRP Channels in the Regulation of the Endosomal Pathway SO PHYSIOLOGY LA English DT Review ID MUCOLIPIDOSIS TYPE-IV; RECEPTOR POTENTIAL CHANNEL; ADENINE-DINUCLEOTIDE PHOSPHATE; VARITINT-WADDLER PHENOTYPE; CYCLIC ADP-RIBOSE; PLASMA-MEMBRANE; CATION CHANNEL; CA2+-PERMEABLE CHANNEL; ENDOCYTIC PATHWAY; CELL DEGENERATION AB Some members of the transient receptor potential (TRP) channel superfamily have proved to be essential in maintaining adequate ion homeostasis, signaling, and membrane trafficking in the endosomal pathway. The unique properties of the TRP channels confer cells the ability to integrate cytosolic and intraluminal stimuli and allow maintained and regulated release of Ca2+ from endosomes and lysosomes. C1 [Abe, Ken; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Abe, K (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM puertolr@mail.nih.gov FU National Heart, Lung, and Blood Institute FX This project was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 101 TC 26 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD FEB PY 2011 VL 26 IS 1 BP 14 EP 22 DI 10.1152/physiol.00048.2010 PG 9 WC Physiology SC Physiology GA 728GC UT WOS:000287861600003 PM 21357899 ER PT J AU Migueles, SA Rood, JE Berkley, AM Guo, T Mendoza, D Patamawenu, A Hallahan, CW Cogliano, NA Frahm, N Duerr, A McElrath, MJ Connors, M AF Migueles, Stephen A. Rood, Julia E. Berkley, Amy M. Guo, Tiffany Mendoza, Daniel Patamawenu, Andy Hallahan, Claire W. Cogliano, Nancy A. Frahm, Nicole Duerr, Ann McElrath, M. Juliana Connors, Mark TI Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; LONG-TERM NONPROGRESSORS; IMMUNE CONTROL; ELITE SUPPRESSORS; VIRAL LOAD; INFECTION; REPLICATION; PROLIFERATION; IMMUNOGENICITY AB If future HIV vaccine design strategies are to succeed, improved understanding of the mechanisms underlying protection from infection or immune control over HIV replication remains essential. Increased cytotoxic capacity of HIV-specific CD8(+) T-cells associated with efficient elimination of HIV-infected CD4(+) T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease. Here, measurements of granzyme B target cell activity and HIV-1-infected CD4(+) T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP. We observed readily detectable HIV-specific CD8(+) T-cell recall cytotoxic responses in vaccinees at a median of 331 days following the last immunization. The magnitude of these responses was not related to the number of vaccinations, nor did it correlate with the percentages of cytokine-secreting T-cells determined by ICS assays. Although the recall cytotoxic capacity of the CD8(+) T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection. These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8(+) T-cell cytotoxic responses. C1 [Migueles, Stephen A.; Rood, Julia E.; Berkley, Amy M.; Guo, Tiffany; Mendoza, Daniel; Patamawenu, Andy; Cogliano, Nancy A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Frahm, Nicole; Duerr, Ann; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Frahm, Nicole; Duerr, Ann; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA. [Hallahan, Claire W.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Migueles, SA (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov OI Mendoza, Daniel/0000-0002-6362-0771 FU NIH, National Institute of Allergy and Infectious Diseases; HVTN Laboratory (NIH) [U01 AI068618]; Seattle Vaccine Unit (NIH) [U01 AI069481]; HVTN Core Leadership [U01 AI068614] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. The HVTN Laboratory Program (NIH U01 AI068618), the Seattle Vaccine Unit (NIH U01 AI069481) and HVTN Core Leadership (U01 AI068614) provided additional support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 18 Z9 18 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2011 VL 7 IS 2 AR e1002002 DI 10.1371/journal.ppat.1002002 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 726DE UT WOS:000287698200046 PM 21383976 ER PT J AU Whitney, JB Hraber, PT Luedemann, C Giorgi, EE Daniels, MG Bhattacharya, T Rao, SS Mascola, JR Nabel, GJ Korber, BT Letvin, NL AF Whitney, James B. Hraber, Peter T. Luedemann, Corinne Giorgi, Elena E. Daniels, Marcus G. Bhattacharya, Tanmoy Rao, Srinivas S. Mascola, John R. Nabel, Gary J. Korber, Bette T. Letvin, Norman L. TI Genital Tract Sequestration of SIV following Acute Infection SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG-RESISTANCE MUTATIONS; PRIMARY HIV-1 INFECTION; CD4(+) T-CELLS; SEXUAL TRANSMISSION; SEMINAL PLASMA; VIRAL LOAD; HETEROSEXUAL TRANSMISSION; HIV-1-INFECTED MEN; GENETIC ALGORITHM AB We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood-and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection. At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract. However, at the time of virus set point, compartmentalization was apparent in 4 of 7 evaluated monkeys, likely as a consequence of restricted virus gene flow between anatomic compartments after the resolution of primary viremia. These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves. C1 [Whitney, James B.; Luedemann, Corinne; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, Boston, MA 02215 USA. [Whitney, James B.; Letvin, Norman L.] Harvard Univ, Sch Med, Boston, MA USA. [Hraber, Peter T.; Giorgi, Elena E.; Daniels, Marcus G.; Bhattacharya, Tanmoy; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM USA. [Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.; Letvin, Norman L.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Whitney, JB (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, Boston, MA 02215 USA. EM jwhitne2@bidmc.harvard.edu RI Bhattacharya, Tanmoy/J-8956-2013; OI Bhattacharya, Tanmoy/0000-0002-1060-652X; Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU Vaccine Research Center (VRC); National Institute of Allergy and Infectious Diseases (NIAID); Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI067854] FX This work was supported by the Intramural Research Program of the Vaccine Research Center (VRC), and the National Institute of Allergy and Infectious Diseases (NIAID), and the Center for HIV/AIDS Vaccine Immunology (CHAVI) AI067854. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 12 Z9 12 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2011 VL 7 IS 2 AR e1001293 DI 10.1371/journal.ppat.1001293 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 726DE UT WOS:000287698200031 PM 21379569 ER PT J AU Berger, VW AF Berger, Vance W. TI Intent-to-Treat: Further Insight SO RESEARCH IN NURSING & HEALTH LA English DT Letter ID CLINICAL-TRIALS C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD FEB PY 2011 VL 34 IS 1 BP 4 EP 4 DI 10.1002/nur.20405 PG 1 WC Nursing SC Nursing GA 710WH UT WOS:000286547200002 PM 20957665 ER PT J AU Brzezinski, K Dauter, Z Baj, A Walejko, P Witkowski, S AF Brzezinski, Krzysztof Dauter, Zbigniew Baj, Aneta Walejko, Piotr Witkowski, Stanislaw TI rac-6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxamide from synchrotron data SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID (2R,4'R,8'R)-ALPHA-TOCOPHEROL VITAMIN-E; ANTIOXIDANT ACTIVITY; INTERMEDIATE; DERIVATIVES; ENANTIOMERS; PRECURSOR; CHROMANS; ACID AB The crystal structure of the title water-soluble analogue of vitamin E, trolox amide, C14H19NO3, solved and refined against synchrotron diffraction data, contains two molecules in the asymmetric unit. In both molecules, the heterocyclic ring is in a half-chair conformation. The crystal packing features a herring-bone pattern generated by N-H center dot center dot center dot O hydrogen bonds between the hydroxy and amide groups. O-H center dot center dot center dot O hydrogen bonds also occur. C1 [Brzezinski, Krzysztof; Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, MCL, Natl Canc Inst,Biosci Div, Argonne, IL 60439 USA. [Baj, Aneta; Walejko, Piotr; Witkowski, Stanislaw] Univ Bialystok, Inst Chem, PL-15443 Bialystok, Poland. RP Brzezinski, K (reprint author), Argonne Natl Lab, Synchrotron Radiat Res Sect, MCL, Natl Canc Inst,Biosci Div, Bldg 202, Argonne, IL 60439 USA. EM kbrzezinski@anl.gov FU Polish Ministry of Science and Higher Education [N N204 177639]; NIH, National Cancer Institute, Center for Cancer Research; US Department of Energy [W-31-109-Eng-38] FX Financial support from the Polish Ministry of Science and Higher Education (grant No. N N204 177639) is gratefully acknowledged. This work was in part supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. X-ray data were collected at the NECAT 24ID-C beamline of the Advanced Photon Source, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy under contract No. W-31-109-Eng-38. NR 20 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD FEB PY 2011 VL 67 BP O503 EP U1854 DI 10.1107/S1600536811002807 PN 2 PG 14 WC Crystallography SC Crystallography GA 719PF UT WOS:000287216300159 PM 21523156 ER PT J AU Khan, A Nasir, K Khosa, F Saghir, A Sarwar, S Clouse, ME AF Khan, Atif Nasir, Khurram Khosa, Faisal Saghir, Amina Sarwar, Sheryar Clouse, Melvin E. TI Prospective Gating With 320-MDCT Angiography: Effect of Volume Scan Length on Radiation Dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE 320-MDCT; cardiac imaging; coronary artery disease; radiation dose reduction; volume scan length ID MULTISLICE COMPUTED-TOMOGRAPHY; CORONARY CT ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; IMAGE QUALITY; PEDIATRIC-PATIENTS; EXPOSURE; HEART; CHEST; REDUCTION; ARTERIES AB OBJECTIVE. The purpose of this study was to evaluate the relation between radiation dose reduction and volume scan length for prospectively ECG-gated 320-MDCT angiography in the diagnosis of coronary artery disease. MATERIALS AND METHODS. MDCT with prospective ECG gating was performed at one of the three volume scan lengths depending on heart length. Of 175 patients, 95 (55%; body mass index, 29 +/- 5.9; mean heart rate, 59 +/- 7 beats/min) underwent scanning at 160 mm; 46 (26%; body mass index, 30 +/- 4.1; mean heart rate, 56 +/- 5.74 beats/min) at 140 mm; and 34 (19%; body mass index, 30 +/- 3.71; mean heart rate, 58 +/- 3.96 beats/min) at 120 mm. RESULTS. The median radiation doses were 6.5 mSv (95% CI, 6.03-7.2 mSv) for the 95 patients who underwent scanning at a volume scan length of 160 mm, 4.33 mSv (95% CI, 4.06-6.62 mSv) for the 46 patients who underwent scanning at 140 mm, and 3.47 mSv (95% CI, 3.15-3.62 mSv) for the 34 patients who underwent scanning at 120 mm. The reduction in scan length from 160 to 140 mm represented a reduction in scan length of 12.5% and the reduction to 120 mm a reduction of 25%. The median radiation dose was reduced 33% when volume scan length was changed to 140 mm and 47% when the length was changed to 120 mm. CONCLUSION. Dose optimization remains an important concern in cardiac CT, and for 320-MDCT angiography, substantial dose reduction can be achieved by reducing volume scan length so that it is in concert with the patient's heart length. C1 [Khan, Atif; Khosa, Faisal; Saghir, Amina; Sarwar, Sheryar; Clouse, Melvin E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Nasir, Khurram] Boston Univ, Dept Med, Boston Med Ctr, Boston, MA USA. [Khan, Atif] NCI, Bethesda, MD 20892 USA. [Sarwar, Sheryar] NHLBI, Bethesda, MD USA. RP Clouse, ME (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd,WCC 308A, Boston, MA 02215 USA. EM mclouse@bidmc.harvard.edu OI Khosa, Faisal/0000-0001-5681-7683 FU NCI [T32 CA059367-14]; NHLBI [P50-HL083813] FX Supported by grants NCI T32 CA059367-14 and NHLBI P50-HL083813. NR 38 TC 18 Z9 19 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2011 VL 196 IS 2 BP 407 EP 411 DI 10.2214/AJR.10.4903 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 718OZ UT WOS:000287135600026 PM 21257894 ER PT J AU Biagi, JJ Oza, AM ChalChal, HI Grimshaw, R Ellard, SL Lee, U Hirte, H Sederias, J Ivy, SP Eisenhauer, EA AF Biagi, J. J. Oza, A. M. ChalChal, H. I. Grimshaw, R. Ellard, S. L. Lee, U. Hirte, H. Sederias, J. Ivy, S. P. Eisenhauer, E. A. TI A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study SO ANNALS OF ONCOLOGY LA English DT Article DE clinical trial; recurrent ovarian cancer; sunitinib; targeted therapy ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; METASTATIC BREAST-CANCER; CELL LUNG-CANCER; ANTITUMOR-ACTIVITY; FACTOR RECEPTOR; SOLID TUMORS; BEVACIZUMAB; SU11248; VEGF AB Purpose: Sunitinib is a multitargeted receptor tyrosine kinase inhibitor. We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian cancer. Patients and methods: Eligibility required measurable disease and one or two prior chemotherapies, at least one platinum based. Platinum-sensitive or -resistant disease was allowed. Initial dose schedule was sunitinib 50 mg daily, 4 of 6 weeks. Observation of fluid accumulations during off-treatment periods resulted in adoption of continuous 37.5 mg daily dosing in the second stage of accrual. Results: Of 30 eligible patients, most had serous histology (67%), were platinum sensitive (73%) and had two prior chemotherapies (60%). One partial response (3.3%) and three CA125 responses (10%) were observed, all in platinum-sensitive patients using intermittent dosing. Sixteen (53%) had stable disease. Five had >30% decrease in measurable disease. Overall median progression-free survival was 4.1 months. Common adverse events included fatigue, gastrointestinal symptoms, hand-foot syndrome and hypertension. No gastrointestinal perforation occurred. Conclusions: Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer, but only at the 50 mg intermittent dose schedule, suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting. C1 [Biagi, J. J.] Canc Ctr S Eastern Ontario, Dept Oncol, Kingston, ON K7L 5P9, Canada. [Oza, A. M.] Princess Margaret Hosp, Dept Med, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [ChalChal, H. I.] Allan Blair Canc Ctr, Dept Med, Regina, SK, Canada. [Grimshaw, R.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Obstet & Gynecol, Halifax, NS, Canada. [Ellard, S. L.] So Interior Ctr, BC Canc Agcy, Dept Med, Kelowna, BC, Canada. [Lee, U.] Fraser Valley Ctr, Dept Med, Surrey, BC, Canada. [Lee, U.] Fraser Valley Ctr, BC Canc Agcy, Surrey, BC, Canada. [Hirte, H.] Juravinski Canc Ctr, Dept Med, Hamilton, ON, Canada. [Sederias, J.] Queens Univ, Dept Oncol, Kingston, ON, Canada. [Sederias, J.; Eisenhauer, E. A.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. [Ivy, S. P.] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA. RP Biagi, JJ (reprint author), Canc Ctr S Eastern Ontario, Dept Oncol, 25 King St W, Kingston, ON K7L 5P9, Canada. EM jim.biagi@krcc.on.ca FU Canadian Cancer Society FX Canadian Cancer Society to NCIC Clinical Trials Group. NR 28 TC 67 Z9 70 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2011 VL 22 IS 2 BP 335 EP 340 DI 10.1093/annonc/mdq357 PG 6 WC Oncology SC Oncology GA 712NL UT WOS:000286673400014 PM 20705911 ER PT J AU Berger, VW AF Berger, Vance W. TI Assessing the Quality of Surgical Trials Further Insight SO ANNALS OF SURGERY LA English DT Letter C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Ste 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 5 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 2011 VL 253 IS 2 BP 420 EP 421 DI 10.1097/SLA.0b013e318208043a PG 2 WC Surgery SC Surgery GA 708OV UT WOS:000286374400036 PM 21173689 ER PT J AU Piram, M Frenkel, J Gattorno, M Ozen, S Lachmann, HJ Goldbach-Mansky, R Hentgen, V Neven, B Stojanovic, KS Simon, A Kuemmerle-Deschner, J Hoffman, H Stojanov, S Duquesne, A Pillet, P Martini, A Pouchot, J Kone-Paut, I AF Piram, Maryam Frenkel, Joost Gattorno, Marco Ozen, Seza Lachmann, Helen J. Goldbach-Mansky, Raphaela Hentgen, Veronique Neven, Benedicte Stojanovic, Katia Stankovic Simon, Anna Kuemmerle-Deschner, Jasmin Hoffman, Hal Stojanov, Silvia Duquesne, Agnes Pillet, Pascal Martini, Alberto Pouchot, Jacques Kone-Paut, Isabelle CA EUROFEVER Network EUROTRAPS Network TI A preliminary score for the assessment of disease activity in hereditary recurrent fevers: results from the AIDAI (Auto-Inflammatory Diseases Activity Index) Consensus Conference SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID FAMILIAL-MEDITERRANEAN-FEVER; JUVENILE IDIOPATHIC ARTHRITIS; PERIODIC SYNDROME; CRITERIA; CHILDREN; CLASSIFICATION; ADOLESCENTS; DIAGNOSIS; SEVERITY; PATIENT AB Background The systemic autoinflammatory disorders (SAID) share many clinical manifestations, albeit with variable patterns, intensity and frequency. A common definition of disease activity would be rational and useful in the management of these lifelong diseases. Moreover, standardised disease activity scores are required for the assessment of new therapies in constant development. The aim of this study was to develop preliminary activity scores for familial Mediterranean fever, mevalonate kinase deficiency, tumour necrosis factor receptor-1-associated periodic syndrome and cryopyrin-associated periodic syndromes (CAPS). Methods The study was conducted using two well-recognised consensus formation methods: the Delphi technique and the nominal group technique. The results from a two-step survey and data from parent/patient interviews were used as preliminary data to develop the agenda for a consensus conference to build a provisional scoring system. Results 24 of 65 experts in SAID from 20 countries answered the web questionnaire and 16 attended the consensus conference. There was consensus agreement to develop separate activity scores for each disease but with a common format based on patient diaries. Fever and disease-specific clinical variables were scored according to their severity. A final score was generated by summing the score of all the variables divided by the number of days over which the diary was completed. Scores varied from 0 to 16 (0-13 in CAPS). These scores were developed for the purpose of clinical studies but could be used in clinical practice. Conclusion Using widely recognised consensus formation techniques, preliminary scores were obtained to measure disease activity in four main SAID. Further prospective validation study of this instrument will follow. C1 [Piram, Maryam; Kone-Paut, Isabelle] Univ Paris 11, Bicetre Univ Hosp, Natl Reference Ctr Autoinflammatory Disorders, Dept Pediat & Pediat Rheumatol, F-94270 Le Kremlin Bicetre, France. [Frenkel, Joost] Univ Med Ctr, Dept Pediat, Utrtecht, Netherlands. [Gattorno, Marco; Martini, Alberto] Univ Genoa, I-16126 Genoa, Italy. [Gattorno, Marco; Martini, Alberto] G Gaslini Inst Children, UO Pediat 2, Genoa, Italy. [Gattorno, Marco; Martini, Alberto] G Gaslini Inst Children, Dept Pediat, Genoa, Italy. [Ozen, Seza] Hacettepe Univ, Fac Med, Dept Pediat, TR-06100 Ankara, Turkey. [Lachmann, Helen J.] UCL, Sch Med, Natl Amyloidosis Ctr, London W1N 8AA, England. [Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA. [Hentgen, Veronique] A Mignot Hosp, Natl Reference Ctr Autoinflammatory Disorders, Dept Pediat, Versailles, France. [Neven, Benedicte] Necker Enfants Malades Hosp, Dept Pediat Immunohematol & Pediat Rheumatol, Paris, France. [Stojanovic, Katia Stankovic] Univ Paris 06, Tenon Univ Hosp, Natl Reference Ctr Inflammatory Amyloidosis & Fam, Dept Internal Med, Paris, France. [Simon, Anna] Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. [Kuemmerle-Deschner, Jasmin] Univ Tubingen Hosp, Dept Pediat, Div Pediat Rheumatol, Tubingen, Germany. [Hoffman, Hal] Univ Calif San Diego, Rady Childrens Hosp San Diego, Dept Pediat & Med, San Diego, CA 92103 USA. [Stojanov, Silvia] Univ Childrens Hosp, Dept Immunol & Infect Dis, Munich, Germany. [Duquesne, Agnes] Hosp Civils Lyon, Hop Femme Mere Enfant, Dept Nephrol & Pediat Rheumatol, Lyon, France. [Pillet, Pascal] Childrens Hosp Bordeaux, Dept Pediat, Bordeaux, France. [Pouchot, Jacques] Paris Descartes Univ, European Georges Pompidou Hosp, Dept Internal Med, Paris, France. RP Kone-Paut, I (reprint author), Univ Paris 11, Bicetre Univ Hosp, Natl Reference Ctr Autoinflammatory Disorders, Dept Pediat & Pediat Rheumatol, 78 Rue Gen Leclerc, F-94270 Le Kremlin Bicetre, France. EM isabelle.kone-paut@bct.aphp.fr RI Simon, Anna/D-3757-2009; OI Simon, Anna/0000-0002-6141-7921; Lachmann, Helen/0000-0001-8378-2498 FU French Ministry of Health; Assistance Publique-Hopitaux de Paris (APHP) FX This study was supported by grants from the French Ministry of Health (PHRC 2008) and Assistance Publique-Hopitaux de Paris (APHP). NR 25 TC 27 Z9 27 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB PY 2011 VL 70 IS 2 BP 309 EP 314 DI 10.1136/ard.2010.132613 PG 6 WC Rheumatology SC Rheumatology GA 705ZG UT WOS:000286179000014 PM 21081528 ER PT J AU Chen, CZ Kulakova, L Southall, N Marugan, JJ Galkin, A Austin, CP Herzberg, O Zheng, W AF Chen, Catherine Z. Kulakova, Liudmila Southall, Noel Marugan, Juan J. Galkin, Andrey Austin, Christopher P. Herzberg, Osnat Zheng, Wei TI High-Throughput Giardia lamblia Viability Assay Using Bioluminescent ATP Content Measurements SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; DRUG SUSCEPTIBILITY; ANTIGENIC VARIATION; ANAEROBIC PROTOZOA; IDENTIFICATION; INHIBITION; INVITRO; INTESTINALIS; INFECTIONS; DUODENALIS AB The human pathogen Giardia lamblia is an anaerobic protozoan parasite that causes giardiasis, one of the most common diarrheal diseases worldwide. Although several drugs are available for the treatment of giardiasis, drug resistance has been reported and is likely to increase, and recurrent infections are common. The search for new drugs that can overcome the drug-resistant strains of Giardia is an unmet medical need. New drug screen methods can facilitate the drug discovery process and aid with the identification of new drug targets. Using a bioluminescent ATP content assay, we have developed a phenotypic drug screen method to identify compounds that act against the actively growing trophozoite stage of the parasite. This assay is homogeneous, robust, and suitable for high-throughput screening of large compound collections. A screen of 4,096 pharmacologically active small molecules and approved drugs revealed 43 compounds with selective anti-Giardia properties, including 32 previously reported and 11 novel anti-Giardia agents. The most potent novel compound was fumagillin, which showed 50% inhibitory concentrations of 10 nM against the WB isolate and 2 nM against the GS isolate. C1 [Kulakova, Liudmila; Galkin, Andrey; Herzberg, Osnat] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. [Chen, Catherine Z.; Southall, Noel; Marugan, Juan J.; Austin, Christopher P.; Zheng, Wei] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. RP Herzberg, O (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM osnat@umd.edu; wzheng@mail.nih.gov RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU National Institutes of Health [R01 AI059733]; Molecular Libraries Initiative of the NIH Roadmap for Medical Research FX This study was supported by National Institutes of Health grant R01 AI059733 (to O.H.) and the Molecular Libraries Initiative of the NIH Roadmap for Medical Research. NR 53 TC 18 Z9 18 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2011 VL 55 IS 2 BP 667 EP 675 DI 10.1128/AAC.00618-10 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 709FE UT WOS:000286422500028 PM 21078930 ER PT J AU Nybo, K Green, E AF Nybo, Kristie Green, Eric TI Influencing the Field SO BIOTECHNIQUES LA English DT Editorial Material C1 [Green, Eric] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 2011 VL 50 IS 2 BP 83 EP 83 DI 10.2144/000113606 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726KF UT WOS:000287719700002 ER PT J AU Smith, HE AF Smith, Harold E. TI Identifying insertion mutations by whole-genome sequencing SO BIOTECHNIQUES LA English DT Article DE Next-generation sequencing; whole-genome resequencing; mutation identification; insertion mapping ID ESCHERICHIA-COLI AB Insertion mutagenesis via mobile genetic element is a common technique for the analysis of gene function in model organisms. Next-generation sequencing offers an attractive approach for localizing the site of insertion, but alignment-based mapping of mobile genetic elements is challenging. A computational method for identifying insertion sites is reported herein. The technique was validated by mapping transposons in both bacterial and nematode species. The approach should be extensible to other systems that employ mobile genetic elements to generate mutations. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Smith, HE (reprint author), NIDDKD, NIH, 8 Ctr Dr,Room 1A11, Bethesda, MD 20892 USA. EM smith-he2@niddk.nih.gov FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases FX Thanks to Lee Rosner, Bob Martin, and Kevin O'Connell for providing DNA samples, and to Michael Krause for comments on the manuscript and fruitful discussions. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases. This paper is subject to the NIH Public Access Policy. NR 10 TC 10 Z9 10 U1 0 U2 2 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 2011 VL 50 IS 2 BP 96 EP 97 DI 10.2144/000113600 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726KF UT WOS:000287719700006 PM 21486250 ER PT J AU Trabert, B Peters, U De Roos, AJ Scholes, D Holt, VL AF Trabert, Britton Peters, Ulrike De Roos, Anneclaire J. Scholes, Delia Holt, Victoria L. TI Diet and risk of endometriosis in a population-based case-control study SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Case-control studies; Population-based studies; Diet; Endometriosis ID ESTROGEN; CONSUMPTION; FAT; EPIDEMIOLOGY; CARBENDAZIM; DATABASE; DISEASE; WOMEN; SERUM AB Diet plausibly has a role in the aetiology of endometriosis through effects on steroid hormone levels; however, few published studies have examined the diet and endometriosis risk. We evaluated dietary risk factors for endometriosis in a population-based case-control study. Cases were 284 Group Health (GH) enrollees aged 18-49 years with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001. Controls were 660 randomly selected age-matched female GH enrollees without a history of endometriosis. Nutrients and selected food groups were assessed using the Women's Health Initiative FFQ. OR of endometriosis risk associated with dietary exposures were estimated using unconditional logistic regression and adjusted for identified covariates. Increased total fat consumption was associated with decreased endometriosis risk (fourth quartile v. lowest: OR 0.5, 95% CI 0.2, 1.0, P-trend = 0.12). Increased beta-carotene consumption and servings/d of fruit were associated with increased risk (beta-carotene third quartile v. lowest: OR 1.7, 95% CI 1.1, 2.6; fourth quartile v. lowest: OR 1.6, 95% CI 1.0, 2.5, P-trend 0.16; fruit >2 servings/d v. <1: OR 1.5, 95% CI 1.0, 2.3, P-trend = 0.04). We also found a suggestion of decreased endometriosis risk associated with the consumption of dairy products (2 servings/d v. <= 1: OR 0.6, >2 servings/d v. <= 1: OR 0.7), but this association was not statistically significant for the highest tertile. The present study suggests that specific dietary components may be associated with endometriosis risk. C1 [Trabert, Britton; Peters, Ulrike; De Roos, Anneclaire J.; Holt, Victoria L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Trabert, Britton; De Roos, Anneclaire J.; Holt, Victoria L.] Fred Hutchinson Canc Res Ctr, Epidemiol Res Unit, Seattle, WA 98109 USA. [Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Scholes, Delia] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Trabert, B (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. EM trabertbl@mail.nih.gov RI Trabert, Britton/F-8051-2015 FU National Institute of Child Health and Human Services, National Institute of Health [R01 HD33792, T32 HD052462]; Center for Ecogenetics and Environmental Health; University of Washington FX None of the authors has any conflicts of interest. The present research was supported by grants numbered R01 HD33792 and T32 HD052462 from the National Institute of Child Health and Human Services, National Institute of Health. Pilot grant funding from the Center for Ecogenetics and Environmental Health and the Royalty Research Fund at the University of Washington also supported this research. The authors and their contributions are as follows: B. T. was involved with the interpretation and analysis of the data and drafting the manuscript. U. P. was involved with the analysis and interpretation of data and revision of the manuscript. A. J. D. was involved with interpretation of the data and revision of the manuscript. D. S. was involved with study design, data acquisition and revision of the manuscript. V. L. H. was the principal investigator; she was involved with study design, data acquisition, data analysis, interpretation of the data and drafting and revision of the manuscript. NR 29 TC 16 Z9 16 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD FEB PY 2011 VL 105 IS 3 BP 459 EP 467 DI 10.1017/S0007114510003661 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 724VX UT WOS:000287605400015 PM 20875189 ER PT J AU He, JA Zhang, YM Ito, Y Sun, WJ AF He, Jiao Zhang, Yongmin Ito, Yoichiro Sun, Wenji TI Semi-Preparative Isolation and Purification of Three Tauro-Conjugated Cholic Acids from Pulvis Fellis Suis by HSCCC Coupled with ELSD Detection SO CHROMATOGRAPHIA LA English DT Article DE High-speed countercurrent chromatography; Tauro-conjugated cholic acids; Pulvis Fellis Suis; Sus scrofa domestica Brisson ID COUNTER-CURRENT CHROMATOGRAPHY; PREPARATIVE ISOLATION; BILE-ACIDS; SEPARATION AB Coupled with evaporative light scattering detection, a high-speed countercurrent chromatography method was successfully applied to the separation and purification of three tauro-conjugated cholic acids from the traditional Chinese medicine Pulvis Fellis Suis. With a two-phase solvent system composed of chloroform-methanol-water-acetic acid (4:4:2:0.3, v/v), taurochenodeoxycholic acid (10.2 mg), taurohyodeoxycholic acid (11.8 mg) and taurohyocholic acid (5.3 mg), were obtained from 100 mg of the crude extract with purities of 94.6, 96.5 and 95.4%, respectively, in one-step separation. The structures of the three tauro-conjugated cholic acids were identified by ESI-MS, (1)H NMR and (13)C NMR. C1 [He, Jiao; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Zhang, Yongmin] Univ Paris 06, Inst Parisien Chim Mol, CNRS, UMR 7201, F-75005 Paris, France. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Sun, WJ (reprint author), NW Univ Xian, Biomed Key Lab Shaanxi Prov, 229 Taibai N Rd, Xian 710069, Peoples R China. EM cxbml@nwu.edu.cn FU Northwest University of the People's Republic of China [09YZZ61]; Education Department of Shaanxi Provincial Government of the People's Republic of China [2010JS096] FX The authors thank Prof. Zhongfu Wang and Sha Xu of the Key Laboratory of Resource Biology and Biotechnology in western China for assistance in ESI-MS experiments. This work was financially supported in part by the Project of Graduate Innovation and Creativity Funds of Northwest University of the People's Republic of China (09YZZ61) and Project of Scientific Research Plan of Education Department of Shaanxi Provincial Government of the People's Republic of China (2010JS096). NR 29 TC 4 Z9 5 U1 0 U2 14 PU VIEWEG PI WIESBADEN PA ABRAHAM-LINCOLN-STRABE 46, POSTFACH 15 47, D-65005 WIESBADEN, GERMANY SN 0009-5893 J9 CHROMATOGRAPHIA JI Chromatographia PD FEB PY 2011 VL 73 IS 3-4 BP 361 EP 365 DI 10.1007/s10337-010-1893-2 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 719KQ UT WOS:000287204000020 PM 21442029 ER PT J AU Johnson, AD Prakash, S AF Johnson, Andrew D. Prakash, Siddharth TI Top Advances in Functional Genomics and Translational Biology for 2010 SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE function; genomic studies; metabolomics; pharmacogenetics; proteomics ID CORONARY-ARTERY-DISEASE; CHOLESTEROL HOMEOSTASIS; CYP2C19 GENOTYPE; RISK; ASSOCIATION; DELETIONS; OUTCOMES; OBESITY RP Johnson, AD (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM Johnsonad2@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2011 VL 4 IS 1 BP 94 EP 97 DI 10.1161/CIRCGENETICS.111.959502 PG 4 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 721KS UT WOS:000287353200023 PM 21325166 ER PT J AU Rouphael, NG Satola, S Farley, MM Rudolph, K Schmidt, DS Gomez-de-Leon, P Robbins, JB Schneerson, R Carlone, GM Romero-Steiner, S AF Rouphael, Nadine G. Satola, Sarah Farley, Monica M. Rudolph, Karen Schmidt, Daniel S. Gomez-de-Leon, Patricia Robbins, John B. Schneerson, Rachel Carlone, George M. Romero-Steiner, Sandra TI Evaluation of Serum Bactericidal Antibody Assays for Haemophilus influenzae Serotype a SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID CAPSULAR POLYSACCHARIDE; INVASIVE INFECTIONS; A DISEASE; VIRULENCE; EPIDEMIOLOGY; CHILDREN; VACCINE AB Haemophilus influenzae type a (Hia) is an important pathogen for some American Indian, Alaskan native, and Northern Canada aboriginal populations. Assays to measure serum bactericidal activity (SBA) to Hia have not been developed or validated. Here, we describe two methods for the measurement of SBA: SBA with a viability endpoint (CFU counts) and SBA with a fluorometric endpoint using alamarBlue as the metabolic indicator. Both SBA assays measure Hia-specific functional antibody and correlate with anti-Hia IgG enzyme-linked immunosorbent assay (ELISA) concentration of naturally acquired antibodies. C1 [Romero-Steiner, Sandra] Ctr Dis Control & Prevent, Vaccinol Lab, Div Bacterial Dis, Atlanta, GA 30333 USA. [Rouphael, Nadine G.; Satola, Sarah; Farley, Monica M.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30303 USA. [Rudolph, Karen] Ctr Dis Control & Prevent, Arctic Invest Program, Anchorage, AK 99508 USA. [Satola, Sarah; Farley, Monica M.] Atlanta Vet Affairs Med Ctr, Decatur, GA 30033 USA. [Gomez-de-Leon, Patricia] Univ Nacl Autonoma Mexico, Fac Med, Dept Salud Publ, Mexico City 04510, DF, Mexico. [Robbins, John B.; Schneerson, Rachel] NICHHD, NIH, Bethesda, MD 20892 USA. RP Romero-Steiner, S (reprint author), Ctr Dis Control & Prevent, Vaccinol Lab, Div Bacterial Dis, Bldg 18,Room B-105,Mailstop A-36,CDC,1600 Clifton, Atlanta, GA 30333 USA. EM SSteiner@cdc.gov OI Romero-Steiner, Sandra/0000-0003-4128-7768 NR 19 TC 5 Z9 5 U1 0 U2 2 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 FEB PY 2011 VL 18 IS 2 BP 243 EP 247 DI 10.1128/CVI.00219-10 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 712GJ UT WOS:000286653900008 PM 21177919 ER PT J AU Bai, O Rathi, V Lin, P Huang, DD Battapady, H Fei, DY Schneider, L Houdayer, E Chen, XD Hallett, M AF Bai, Ou Rathi, Varun Lin, Peter Huang, Dandan Battapady, Harsha Fei, Ding-Yu Schneider, Logan Houdayer, Elise Chen, Xuedong Hallett, Mark TI Prediction of human voluntary movement before it occurs SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Human intention; Voluntary movement; Prediction; Movement-related cortical potentials (MRCP); Event-related desynchronization (ERD); Electroencephalography (EEG); Brain-computer interface (BCI); Consciousness ID BRAIN-COMPUTER-INTERFACE; EVENT-RELATED DESYNCHRONIZATION; SINGLE-TRIAL EEG; CORTICAL POTENTIALS; FINGER MOVEMENTS; BETA-RHYTHM; CLASSIFICATION; HAND; PROSTHESIS; INITIATION AB Objective: Human voluntary movement is associated with two changes in electroencephalography ( EEG) that can be observed as early as 1.5 s prior to movement: slow DC potentials and frequency power shifts in the alpha and beta bands. Our goal was to determine whether and when we can reliably predict human natural movement BEFORE it occurs from EEG signals ONLINE IN REAL-TIME. Methods: We developed a computational algorithm to support online prediction. Seven healthy volunteers participated in this study and performed wrist extensions at their own pace. Results: The average online prediction time was 0.62 +/- 0.25 s before actual movement monitored by EMG signals. There were also predictions that occurred without subsequent actual movements, where subjects often reported that they were thinking about making a movement. Conclusion: Human voluntary movement can be predicted before movement occurs. Significance: The successful prediction of human movement intention will provide further insight into how the brain prepares for movement, as well as the potential for direct cortical control of a device which may be faster than normal physical control. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Bai, Ou; Rathi, Varun; Huang, Dandan; Battapady, Harsha; Fei, Ding-Yu] Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, Richmond, VA 23284 USA. [Lin, Peter; Schneider, Logan; Houdayer, Elise; Hallett, Mark] Natl Inst Neurol Disorders, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Xuedong] Huazhong Univ Sci & Technol, State Key Lab Digital Mfg Equipment & Technol, Wuhan 430074, Hubei, Peoples R China. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, 401 W Main St,Room 1252,POB 843067, Richmond, VA 23284 USA. EM obai@vcu.edu RI Huang, Dandan/I-3108-2013 FU NIH, National Institute of Neurological Disorders and Stroke; State Key Laboratory of Digital Manufacturing, Equipment & Technology, Huazhong University of Science and Technology FX This research was partly supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. O. Bai received partial support from State Key Laboratory of Digital Manufacturing, Equipment & Technology, Huazhong University of Science and Technology. NR 49 TC 56 Z9 59 U1 0 U2 21 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 FEB PY 2011 VL 122 IS 2 BP 364 EP 372 DI 10.1016/j.clinph.2010.07.010 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 703QP UT WOS:000285995400019 PM 20675187 ER PT J AU White, R Chileshe, M Dawson, L Donnell, D Hillier, S Morar, N Noguchi, L Dixon, D AF White, Rhonda Chileshe, Modesta Dawson, Liza Donnell, Deborah Hillier, Sharon Morar, Neetha Noguchi, Lisa Dixon, Dennis TI Fostering community understanding of sufficient benefit and early stopping for a phase 2B HIV prevention clinical trial in Africa SO CLINICAL TRIALS LA English DT Article AB Background Most trials of interventions are designed to address the traditional null hypothesis of no benefit. VOICE, a phase 2B HIV prevention trial funded by NIH and conducted in Africa, is designed to assess if the intervention will prevent a substantial fraction of infections. Planned interim analysis may provide conclusive evidence against the traditional null hypothesis without establishing substantial benefit. At this interim point, the Data and Safety Monitoring Board would then face the dilemma of knowing the product has some positive effect, but perhaps not as great an effect as the protocol has declared necessary. Purpose In March 2008, NIH program staff recommended that the VOICE protocol team discuss the stopping rules with stakeholders prior to initiating the protocol. The goals of the workshop were to inform community representatives about the potential ethical dilemma associated with stopping rules and engage in dialogue about these issues. We describe the resulting community consultation and summarize the outcomes. Methods A 2-day workshop was convened with the goal of having a clear and transparent consultation with the stakeholders around the question, 'Given emerging evidence that a product could prevent some infections, would the community support a decision to continue accruing to the trial?' Participants included research staff and community stakeholders. Lectures with visual aids, discussions, and exercises using interactive learning tasks were used, with a focus on statistics and interpreting data from trials, particularly interim data. Results Results of oral and written evaluations by participants were reviewed. The feedback was mostly positive, with some residual confusion regarding statistical concepts. However, discussions with attendees later revealed that not all felt prepared to engage fully in the workshop. Limitations This was the presenters' first experience facilitating a formal discussion with an audience that had no advanced science, research, or mathematics training. Community representatives' concern regarding speaking for their communities without consulting them also created a challenge for the workshop. Conclusions Open discussion around trial stopping rules requires that all discussants have an understanding of trial design concepts and feel a sense of empowerment to ask and answer questions. The VOICE CWG workshop was a first step toward the goal of open discussion regarding trial stopping rules and interim results for the study; however, ongoing education and dialogue must occur to ensure that all stakeholders fully participate in the process. Clinical Trials 2011; 8: 103-111. http://ctj.sagepub. C1 [White, Rhonda] FHI, Res Triangle Pk, NC 27709 USA. [Chileshe, Modesta] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Dawson, Liza; Dixon, Dennis] NIAID, NIH, Dept Hlth & Human Serv, Washington, DC USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA. [Hillier, Sharon] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Morar, Neetha] S African MRC, Durban, South Africa. [Noguchi, Lisa] Microbicide Trials Network, Pittsburgh, PA USA. RP White, R (reprint author), FHI, POB 13950, Res Triangle Pk, NC 27709 USA. EM rwhite@fhi.org OI Donnell, Deborah/0000-0002-0587-7480 FU NIAID, US National Institutes of Health [5U01AI068633]; NICHD, US National Institutes of Health; NIMH, US National Institutes of Health FX This effort was supported by the Microbicide Trials Network (MTN), which is funded by NIAID (5U01AI068633), NICHD, and NIMH, all of which are institutes of the US National Institutes of Health. NR 3 TC 5 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD FEB PY 2011 VL 8 IS 1 BP 103 EP 111 DI 10.1177/1740774510387170 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 723LX UT WOS:000287509200011 PM 21335592 ER PT J AU Ingraham, RH Gless, RD Lo, HY AF Ingraham, R. H. Gless, R. D. Lo, H. Y. TI Soluble Epoxide Hydrolase Inhibitors and their Potential for Treatment of Multiple Pathologic Conditions SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE AR9281; BTP2; EPHX2; epoxyeicosatrienoic acid; eicosanoids; sEH; soluble epoxide hydrolase ID ISCHEMIA-REPERFUSION INJURY; EPOXYEICOSATRIENOIC ACIDS; THERAPEUTIC TARGET; BLOOD-PRESSURE; GENE DELETION; CEREBRAL-ISCHEMIA; HYPERTENSIVE-RATS; WATER SOLUBILITY; HIGHLY POTENT; HUMAN BRONCHI AB Epoxyeicosanoids, including the epoxyeicosatrienoic acids, are signaling molecules which appear to help ameliorate the effects of a wide variety of pathological conditions. The enzyme soluble epoxide hydrolase (sEH) metabolizes these molecules by converting them to their corresponding vicinal diols. Inhibition of sEH either by knockout or chemical inhibitors increases epoxyeicosanoid levels in vivo and provides significant organ protection in models of brain, cardiac, and renal injury. sEH also appears to be involved in modulating inflammation, pain pathways, pulmonary function, hypertension, and diabetes. Potent sEH inhibitors have been developed in academic, pharmaceutical, and biotech laboratories and described in the patent and scientific literature. Most of the inhibitor scaffolds employ a urea or amide which functions as an active-site transition state mimic. Arete Therapeutics compound AR9281 successfully completed phase Ia and Ib studies. A phase IIa proof of concept trial for treatment of impaired glucose tolerance has been completed, but the results are not yet reported. C1 [Ingraham, R. H.] NIH, Ctr Sci Review, Bethesda, MD USA. [Lo, H. Y.] Boehringer Ingelheim Pharmaceut Inc, Ingelheim, Germany. RP Ingraham, RH (reprint author), 913 Beacon Sq Court, Gaithersburg, MD USA. EM rhingraham@gmail.com NR 118 TC 16 Z9 16 U1 1 U2 4 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 FEB PY 2011 VL 18 IS 4 BP 587 EP 603 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 720SN UT WOS:000287301000008 PM 21143109 ER PT J AU David, IA Volchan, E Vila, J Keil, A de Oliveira, L Faria, AJP Perakakis, P Dias, EC Mocaiber, I Pereira, MG Machado-Pinheiro, W AF David, Isabel A. Volchan, Eliane Vila, Jaime Keil, Andreas de Oliveira, Leticia Faria-Junior, Aydamari J. P. Perakakis, Pandelis Dias, Elisa C. Mocaiber, Izabela Pereira, Mirtes G. Machado-Pinheiro, Walter TI Stroop matching task: role of feature selection and temporal modulation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Stroop; ERP; Feature attention; Matching task ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED POTENTIALS; FEATURE-BASED ATTENTION; TIME-COURSE; IRRELEVANT INFORMATION; RELEVANT INFORMATION; INTERFERENCE; COLOR; WORD; CONFLICT AB We conducted an event-related potential (ERP) study to investigate the electrocortical dynamics of attentional feature-based processing in the Stroop matching task. Participants in the study (n = 37) compared the ink color of a colored word with the meaning of a color-word in white ink. The two task stimuli were presented simultaneously or with SOAs (Stimulus Onset Asynchrony) of 400 and 1,200 ms. The Stroop matching effect was maximal during SOA-0, was reduced at SOA-400, and was inverted at SOA-1200. We focused the ERP analysis on the N1 component. Paralleling the behavioral results, the N1 amplitude was greater for congruent stimuli than incongruent stimuli during SOA-0. This difference was attenuated at SOA-400, and at SOA-1200, an inverse pattern was observed. The results provide evidence that early selection processing participated in the Stroop matching task phenomenon and also suggest that the temporal modulation of early attention is a function of task characteristics such as SOA. C1 [David, Isabel A.; de Oliveira, Leticia; Pereira, Mirtes G.] Univ Fed Fluminense, Dept Fisiol & Farmacol, Inst Biomed, BR-24210130 Niteroi, RJ, Brazil. [Mocaiber, Izabela; Machado-Pinheiro, Walter] Univ Fed Fluminense, Dept Interdisciplinar, Rio Das Ostras, RJ, Brazil. [Volchan, Eliane] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Programa Neurobiol, BR-21941 Rio De Janeiro, Brazil. [Vila, Jaime; Perakakis, Pandelis] Univ Granada, Fac Psicol, Dept Personalidad Evaluac & Tratamiento Psicol, Granada, Spain. [Keil, Andreas] Univ Florida, Dept Psychol, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. [Faria-Junior, Aydamari J. P.] Univ Fed Amapa, Dept Pesquisa, Macapa, AP, Brazil. [Dias, Elisa C.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP David, IA (reprint author), Univ Fed Fluminense, Dept Fisiol & Farmacol, Inst Biomed, Prof Ernani de Melo 101, BR-24210130 Niteroi, RJ, Brazil. EM isabeldavid@vm.uff.br RI Vila, Jaime/F-9719-2010; Fisiologia, Ciencias Biologicas/C-2407-2012; David, Isabel/I-6090-2012; Keil, Andreas/F-9427-2011; Pereira, Mirtes/J-6222-2016; OI Vila, Jaime/0000-0002-1767-8606; Keil, Andreas/0000-0002-4064-1924; Pereira, Mirtes/0000-0003-4682-223X; Perakakis, Pandelis/0000-0002-9130-3247 FU Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); IBNNet/FINEP; PROPP-UFF; Society for Psychophysiological Research (SPR) FX This research was supported by Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). Partial support was also provided by grants from IBNNet/FINEP and PROPP-UFF. We extend special thanks to the Society for Psychophysiological Research (SPR) for the fellowship training program to the first author (IAD). NR 52 TC 10 Z9 11 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2011 VL 208 IS 4 BP 595 EP 605 DI 10.1007/s00221-010-2507-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 711QV UT WOS:000286607400011 PM 21161193 ER PT J AU Dubrac, S Elentner, A Gonzalez, FJ Schmuth, M AF Dubrac, S. Elentner, A. Gonzalez, F. J. Schmuth, M. TI Pregnane X Receptor (PXR) links xenobiotic metabolism to the cutaneous immune response SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Dubrac, S.; Elentner, A.; Schmuth, M.] Innsbruck Med Univ, Dept Dermatol, A-6020 Innsbruck, Austria. [Gonzalez, F. J.] NIH, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P029 BP 167 EP 167 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200048 ER PT J AU Wolf, R Mascia, F Dharamsi, A Howard, ZO Cattaisson, C Bliskovski, V Winston, J Feigenbaum, L Lichti, U Ruzicka, T Chavakis, T Yuspa, SH AF Wolf, R. Mascia, F. Dharamsi, A. Howard, Z. O. Cattaisson, C. Bliskovski, V. Winston, J. Feigenbaum, L. Lichti, U. Ruzicka, T. Chavakis, T. Yuspa, S. H. TI Small S100 molecules with cutaneous antimicrobial activity prime skin for inflammation: a mouse model for psoriasis susceptibility SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Wolf, R.; Mascia, F.; Dharamsi, A.; Cattaisson, C.; Bliskovski, V.; Winston, J.; Lichti, U.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Wolf, R.; Ruzicka, T.] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Howard, Z. O.] NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA. [Feigenbaum, L.] SAIC, Lab Anim Serv Program, Frederick, MD USA. [Chavakis, T.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Chavakis, T.] Tech Univ Dresden, Dept Med, D-8027 Dresden, Germany. [Chavakis, T.] Tech Univ Dresden, Inst Physiol, D-8027 Dresden, Germany. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P031 BP 167 EP 167 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200050 ER PT J AU Jalili, A Pashenkov, M Kriehuber, E Wagner, C Nakano, H Stingl, G Wagner, SN AF Jalili, A. Pashenkov, M. Kriehuber, E. Wagner, C. Nakano, H. Stingl, G. Wagner, S. N. TI Induction of targeted cell migration by cutaneous administration of a DNA vector encoding a biologically active chemokine CCL21 SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Jalili, A.; Pashenkov, M.; Kriehuber, E.; Wagner, C.; Stingl, G.; Wagner, S. N.] Med Univ Vienna, Div Immunol, Dept Dermatol, Vienna, Austria. [Nakano, H.] NIEHS, NIH, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P086 BP 176 EP 176 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200105 ER PT J AU Ghoreschi, K Laurence, A Yang, X Tato, C McGeachy, M Konkel, J Ramos, H Wei, L Davidson, T Bouladoux, N Grainger, J Chen, Q Kanno, Y Watford, W Sun, H Eberl, G Shevach, E Belkaid, Y Cua, D Chen, W O'Shea, JJ AF Ghoreschi, K. Laurence, A. Yang, X. Tato, C. McGeachy, M. Konkel, J. Ramos, H. Wei, L. Davidson, T. Bouladoux, N. Grainger, J. Chen, Q. Kanno, Y. Watford, W. Sun, H. Eberl, G. Shevach, E. Belkaid, Y. Cua, D. Chen, W. O'Shea, J. J. TI Pathogenic T-bet+Th17 cells develop in the absence of TGF-beta signaling SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Ghoreschi, K.; Laurence, A.; Yang, X.; Konkel, J.; Ramos, H.; Wei, L.; Davidson, T.; Bouladoux, N.; Grainger, J.; Chen, Q.; Kanno, Y.; Watford, W.; Sun, H.; Shevach, E.; Belkaid, Y.; Chen, W.; O'Shea, J. J.] NIH, Bethesda, MD 20892 USA. [Tato, C.; McGeachy, M.; Cua, D.] Merck Res Labs, Palo Alto, CA 94304 USA. [Eberl, G.] Inst Pasteur, F-75724 Paris, France. RI Laurence, Arian/A-8770-2009; Eberl, Gerard/A-1160-2013; Wei, Lai/D-1088-2014 OI Laurence, Arian/0000-0003-0942-8292; NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P150 BP 186 EP 186 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200168 ER PT J AU Wolf, R Voscopolous, C Winston, J Cattaisson, C Darwiche, N Glick, A Weinberg, WC Vogel, JC Goldsmith, P Hennings, H Yuspa, SH AF Wolf, R. Voscopolous, C. Winston, J. Cattaisson, C. Darwiche, N. Glick, A. Weinberg, W. C. Vogel, J. C. Goldsmith, P. Hennings, H. Yuspa, S. H. TI S100A7 (psoriasin) and S100A15 (koebnerisin) marks tumor progression during skin carcinogenesis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Wolf, R.; Voscopolous, C.; Winston, J.; Cattaisson, C.; Darwiche, N.; Glick, A.; Hennings, H.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Wolf, R.] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Weinberg, W. C.] US FDA, Bethesda, MD 20014 USA. [Vogel, J. C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Goldsmith, P.] NCI, Antibody & Prot Purificat Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P222 BP 197 EP 197 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200240 ER PT J AU Eberle, F Rodriguez-Canales, J Wei, L Hanson, J Killian, J Sun, H Adams, L Hewitt, S Wilson, W Pittaluga, S Meltzer, P Staudt, L Emmert-Buck, M Jaffe, E AF Eberle, F. Rodriguez-Canales, J. Wei, L. Hanson, J. Killian, J. Sun, H. Adams, L. Hewitt, S. Wilson, W. Pittaluga, S. Meltzer, P. Staudt, L. Emmert-Buck, M. Jaffe, E. TI Epigenetic profiling of lymphoma reveals a distinctive signature for mediastinalgray zone lymphoma SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Eberle, F.; Rodriguez-Canales, J.; Wei, L.; Hanson, J.; Killian, J.; Sun, H.; Adams, L.; Hewitt, S.; Wilson, W.; Pittaluga, S.; Meltzer, P.; Staudt, L.; Emmert-Buck, M.; Jaffe, E.] NIH, Bethesda, MD 20892 USA. RI Wei, Lai/D-1088-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P255 BP 202 EP 202 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200273 ER PT J AU Conjeevaram, HS Wahed, AS Afdhal, N Howell, CD Everhart, JE Hoofnagle, JH AF Conjeevaram, Hari S. Wahed, Abdus S. Afdhal, Nezam Howell, Charles D. Everhart, James E. Hoofnagle, Jay H. CA Virahep-C Study Grp TI Changes in Insulin Sensitivity and Body Weight During and After Peginterferon and Ribavirin Therapy for Hepatitis C SO GASTROENTEROLOGY LA English DT Article DE Obesity; Metabolic Response; Liver Disease; Clinical Trial ID BETA-CELL FUNCTION; HOMEOSTASIS MODEL ASSESSMENT; VIRUS-INFECTION; DIABETES-MELLITUS; FIBROSIS PROGRESSION; RESISTANCE; STEATOSIS; GLUCOSE AB BACKGROUND & AIMS: Chronic hepatitis C is associated with an increased prevalence of insulin resistance, which might result from liver disease, metabolic factors, or the hepatitis C virus (HCV) itself. The effect of antiviral treatment on insulin sensitivity is not well-known. We evaluated changes in insulin resistance and weight in patients with hepatitis C during and after peginterferon and ribavirin therapy. METHODS: Virahep-C was a prospective, multicenter study of a 48-week course of combination antiviral therapy in patients infected with HCV genotype 1. Insulin resistance (IR) was estimated by the homeostasis model assessment index (HOMA2-IR) based on fasting glucose and insulin levels. RESULTS: Among 341 patients, 40% had insulin resistance (HOMA2-IR > 2.0). The presence of insulin resistance was associated with increasing age, body mass index (BMI), and fibrosis stage. Among patients with insulin resistance at the start of the trial, median decreases in HOMA2-IR values during treatment were 0.74 at 24 weeks and 0.89 at 48 weeks, whereas BMI decreased by 1.2 and 2.2 at the same time points (P < .001 for all). At follow-up, HOMA2-IR and BMI levels returned toward baseline values in patients who did not respond or relapsed, but HOMA2-IR values remained significantly lower in patients with sustained virologic response (SVR) (P < .001), despite increases in BMI. CONCLUSIONS: In patients with HCV genotype 1 infections, therapy with peginterferon and ribavirin is associated with decreases in body weight and insulin resistance. Among patients with insulin resistance before treatment, resolution of HCV infection results in sustained improvements in the HOMA-IR index, suggesting that HCV could have a direct role in the pathogenesis of insulin resistance. C1 [Conjeevaram, Hari S.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Wahed, Abdus S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Afdhal, Nezam] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Howell, Charles D.] Univ Maryland, Baltimore, MD 21201 USA. [Everhart, James E.; Hoofnagle, Jay H.] NIDDK, NIH, Bethesda, MD USA. RP Conjeevaram, HS (reprint author), Univ Michigan, Div Gastroenterol, 3912 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM omsairam@med.umich.edu OI Wahed, Abdus/0000-0001-6911-7221 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center on Minority Health and Health Disparities (NCMHD); National Cancer Institute (NCI); Roche Laboratories, Inc.; National Center for Research Resources (NCRR) [M01 RR00645, M02 RR000079, M01 RR16500, M01 RR000042, M01 RR00046]; [U01 DK60329]; [U01 DK60340]; [U01 DK60324]; [U01 DK60344]; [U01 DK60327]; [U01 DK60335]; [U01 DK60352]; [U01 DK60342]; [U01 DK60345]; [U01 DK60309]; [U01 DK60346]; [U01 DK60349]; [U01 DK60341] FX Supported by a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) with cosupport from the National Center on Minority Health and Health Disparities (NCMHD) and the Intramural Research Program of the National Cancer Institute (NCI) with further support under a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. Clinical trial number: NCT00038974 (URL: http://www.virahepc.org). Grant numbers: U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341. Other support includes the National Center for Research Resources (NCRR) General Clinical Research Centers Program grants: M01 RR00645 (New York Presbyterian), M02 RR000079 (University of California, San Francisco), M01 RR16500 (University of Maryland), M01 RR000042 (University of Michigan), M01 RR00046 (University of North Carolina). NR 26 TC 33 Z9 33 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 469 EP 477 DI 10.1053/j.gastro.2010.11.002 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600026 PM 21070775 ER PT J AU Landry, JW Banerjee, S Taylor, B Aplan, PD Singer, A Wu, C AF Landry, Joseph W. Banerjee, Subhadra Taylor, Barbara Aplan, Peter D. Singer, Alfred Wu, Carl TI Chromatin remodeling complex NURF regulates thymocyte maturation SO GENES & DEVELOPMENT LA English DT Article DE NURF; SRF; AP-1; Bptf; chromatin remodeling; positive selection ID T-CELL DEVELOPMENT; POSITIVE SELECTION; INTERLEUKIN-2 GENE; MOLECULAR-BASIS; LYMPHOCYTE DEVELOPMENT; FUNCTIONAL ELEMENTS; IN-VIVO; NUCLEOSOME; EXPRESSION; TRANSCRIPTION AB The maturation of T cells requires signaling from both cytokine and T-cell receptors to gene targets in chromatin, but how chromatin architecture influences this process is largely unknown. Here we show that thymocyte maturation post-positive selection is dependent on the nucleosome remodeling factor (NURF). Depletion of Bptf (bromodomain PHD finger transcription factor), the largest NURF subunit, in conditional mouse mutants results in developmental arrest beyond the CD4(+) CD8(int) stage without affecting cellular proliferation, cellular apoptosis, or coreceptor gene expression. In the Bptf mutant, specific subsets of genes important for thymocyte development show aberrant expression. We also observed defects in DNase I-hypersensitive chromatin structures at Egr1, a prototypical Bptf-dependent gene that is required for efficient thymocyte development. Moreover, chromatin binding of the sequence-specific factor Srf (serum response factor) to Egr1 regulatory sites is dependent on Bptf function. Physical interactions between NURF and Srf suggest a model in which Srf recruits NURF to facilitate transcription factor binding at Bptf-dependent genes. These findings provide evidence for causal connections between NURF, transcription factor occupancy, and gene regulation during thymocyte development. C1 [Landry, Joseph W.; Wu, Carl] NCI, Lab Biochem & Mol Cell Biol, NIH, Bethesda, MD 20892 USA. [Banerjee, Subhadra; Taylor, Barbara] NCI, FACS Core Lab, NIH, Bethesda, MD 20892 USA. [Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20889 USA. [Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Landry, JW (reprint author), Virginia Commonwealth Univ, Dept Human & Mol Genet, Sch Med, Bldg 37,Room 6068, Richmond, VA 23298 USA. EM jwlandry2@vcu.edu RI Aplan, Peter/K-9064-2016 FU American Cancer Society [PF-05-122-01-DDC]; National Cancer Institute and Mammalian Genome Society; National Institutes of Health FX We thank members of the Wu, Singer, and Aplan laboratories for critically reading the manuscript, discussions, and technical assistance. We thank Ron Schwartz, Remy Bousselut, Paul Love, and John Ashwell for helpful discussions. We thank John Stamatoyannopoulos and his laboratory for help with the quantitative chromatin profiling. We thank Paul Meltzer's laboratory for technical help with microarray experiments. We acknowledge the Frederick Histopathology Laboratory for providing sections of thymus tissue. This research was supported through fellowship #PF-05-122-01-DDC from the American Cancer Society and travel awards from the National Cancer Institute and Mammalian Genome Society to J.L., and National Institutes of Health intramural research grants to A.S., P.A., and C.W. J.L. designed and performed experiments with input from P.A., A.S., and C.W. S.B. and B.T. performed electronic cell sorting. J.L. and C.W. wrote the manuscript and correspondence with contributions from P.A. and A.S. NR 61 TC 29 Z9 29 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 2011 VL 25 IS 3 BP 275 EP 286 DI 10.1101/gad.2007311 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 715JL UT WOS:000286880600009 PM 21289071 ER PT J AU Marenne, G Rodriguez-Santiago, B Closas, MG Perez-Jurado, L Rothman, N Rico, D Pita, G Pisano, DG Kogevinas, M Silverman, DT Valencia, A Real, FX Chanock, SJ Genin, E Malats, N AF Marenne, Gaelle Rodriguez-Santiago, Benjamin Garcia Closas, Montserrat Perez-Jurado, Luis Rothman, Nathaniel Rico, Daniel Pita, Guillermo Pisano, David G. Kogevinas, Manolis Silverman, Debra T. Valencia, Alfonso Real, Francisco X. Chanock, Stephen J. Genin, Emmanuelle Malats, Nuria TI Assessment of Copy Number Variation Using the Illumina Infinium 1M SNP-Array: A Comparison of Methodological Approaches in the Spanish Bladder Cancer/EPICURO Study SO HUMAN MUTATION LA English DT Article DE copy number variation; genome-wide association study; specificity; sensitivity; reliability; accuracy; CNVpartition; PennCNV; QuantiSNP ID GENOME-WIDE ASSOCIATION; HIDDEN-MARKOV MODEL; STRUCTURAL VARIATION; GENOTYPING DATA; HUMAN-DISEASE; SCHIZOPHRENIA; VARIANTS; RISK; GENES; AUTISM AB High-throughput single nucleotide polymorphism (SNP)-array technologies allow to investigate copy number variants (CNVs) in genome-wide scans and specific calling algorithms have been developed to determine CNV location and copy number. We report the results of a reliability analysis comparing data from 96 pairs of samples processed with CNVpartition, PennCNV, and QuantiSNP for Infinium Illumina Human 1Million probe chip data. We also performed a validity assessment with multiplex ligation-dependent probe amplification (MLPA) as a reference standard. The number of CNVs per individual varied according to the calling algorithm. Higher numbers of CNVs were detected in saliva than in blood DNA samples regardless of the algorithm used. All algorithms presented low agreement with mean Kappa Index (KI) < 66. PennCNV was the most reliable algorithm (KI(w)=98.96) when assessing the number of copies. The agreement observed in detecting CNV was higher in blood than in saliva samples. When comparing to MLPA, all algorithms identified poorly known copy aberrations (sensitivity=0.19-0.28). In contrast, specificity was very high (0.97-0.99). Once a CNV was detected, the number of copies was truly assessed (sensitivity > 0.62). Our results indicate that the current calling algorithms should be improved for high performance CNV analysis in genome-wide scans. Further refinement is required to assess CNVs as risk factors in complex diseases. Hum Mutat 32:240-248, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Marenne, Gaelle; Rico, Daniel; Pita, Guillermo; Pisano, David G.; Valencia, Alfonso; Real, Francisco X.; Malats, Nuria] CNIO, Madrid, Spain. [Marenne, Gaelle; Genin, Emmanuelle] Univ Paris Diderot, Inst Univ Hematol, INSERM, UMR S946, Paris, France. [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis] CIBERER, E-08003 Barcelona, Spain. [Garcia Closas, Montserrat; Rothman, Nathaniel; Silverman, Debra T.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. [Perez-Jurado, Luis] Hosp Univ Vall Hebron, Programa Med Mol & Genet, E-08035 Barcelona, Spain. [Perez-Jurado, Luis] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Kogevinas, Manolis] Hosp Mar, IMIM, Barcelona, Spain. [Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. RP Malats, N (reprint author), CNIO, Madrid, Spain. EM nmalats@cnio.es RI Pisano, David/N-5817-2014; Genin, Emmanuelle/C-4974-2013; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Valencia, Alfonso/I-3127-2015; Perez Jurado, Luis Alberto/M-7706-2015; Real Arribas, Francisco/H-5275-2015; Kogevinas, Manolis/C-3918-2017; OI Rico, Daniel/0000-0002-6561-2310; Pisano, David/0000-0002-4895-4124; Genin, Emmanuelle/0000-0003-4117-2813; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Valencia, Alfonso/0000-0002-8937-6789; Real Arribas, Francisco/0000-0001-9501-498X; Rodriguez-Santiago, Benjamin/0000-0003-1167-3852 FU Fondo de Investigacion Sanitaria, Spain [G03/174, PI061614, FI09/00205]; Asociacion Espanola Contra el Cancer (AECC); Fundacio Marato de TV3; Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Spain; Division of Cancer Epidemiology and Genetics, National Cancer Institute; Egide-PHRC Picasso FX Contract grant sponsor: The Fondo de Investigacion Sanitaria, Spain; Contract grant numbers: G03/174; PI061614; FI09/00205; Contract grant sponsors: Asociacion Espanola Contra el Cancer (AECC), Fundacio Marato de TV3, Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Spain; The Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute; Egide-PHRC Picasso Travel Grant. NR 51 TC 25 Z9 26 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD FEB PY 2011 VL 32 IS 2 BP 240 EP 248 DI 10.1002/humu.21398 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 721SU UT WOS:000287376300012 PM 21089066 ER PT J AU Zhou, D Cheung, KF Chen, Y Lau, ST Zhou, QF Shung, KK Luo, HS Dai, JY Chan, HLW AF Zhou, Dan Cheung, Kwok Fung Chen, Yan Lau, Sien Ting Zhou, Qifa Shung, K. Kirk Luo, Hao Su Dai, Jiyan Chan, Helen Lai Wa TI Fabrication and Performance of Endoscopic Ultrasound Radial Arrays Based on PMN-PT Single Crystal/Epoxy 1-3 Composite SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID PIEZOELECTRIC TRANSDUCERS; EUS; DESIGN; PZT; FNA AB In this paper, 0.7Pb(Mg(1/3)Nb(2/3))O(3)-0.3PbTiO(3) (PMN-PT) single crystal/epoxy 1-3 composite was used as the active material of the endoscopic ultrasonic radial array transducer, because this composite exhibited ultrahigh electromechanical coupling coefficient (k(t) = 0.81%), very low mechanical quality factor (Q(m) = 11) and relatively low acoustic impedance (Z(t) = 12 MRayls). A 6.91 MHz PMN-PT/epoxy 1-3 composite radial array transducer with 64 elements was tested in a pulse-echo response measurement. The -6-dB bandwidth of the composite array transducer was 102%, which was similar to 30% larger than that of traditional lead zirconate titanate array transducer. The two-way insertion loss was found to be -32.3 dB. The obtained results show that this broadband array transducer is promising for acquiring high-resolution endoscopic ultrasonic images in many clinical applications. C1 [Zhou, Dan; Cheung, Kwok Fung; Chen, Yan; Shung, K. Kirk; Dai, Jiyan; Chan, Helen Lai Wa] Hong Kong Polytech Univ, Dept Appl Phys, Hong Kong, Hong Kong, Peoples R China. [Zhou, Dan; Cheung, Kwok Fung; Chen, Yan; Shung, K. Kirk; Dai, Jiyan; Chan, Helen Lai Wa] Hong Kong Polytech Univ, Mat Res Ctr, Hong Kong, Hong Kong, Peoples R China. [Lau, Sien Ting; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Lau, Sien Ting; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA USA. [Luo, Hao Su] Chinese Acad Sci, Shanghai Inst Ceram, Informat Mat & Devices Res Ctr, Shanghai 200050, Peoples R China. [Lau, Sien Ting] Univ So Calif, NIH Resource Ctr Med Ultrason Transducer Technol, Los Angeles, CA USA. RP Zhou, D (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 [ZP-1H]; Department of Applied Physics of the Hong Kong Polytechnic University; NIH [P41-EB2182] FX This work was supported by the Hong Kong Innovative Technology Council (Project No. ZP-1H), the Department of Applied Physics of the Hong Kong Polytechnic University and NIH Grant #P41-EB2182. NR 29 TC 20 Z9 21 U1 3 U2 27 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD FEB PY 2011 VL 58 IS 2 BP 477 EP 484 DI 10.1109/TUFFC.2011.1825 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 725TY UT WOS:000287670200022 PM 21342833 ER PT J AU Averdam, A Kuschal, C Otto, N Westphal, N Roos, C Reinhardt, R Walter, L AF Averdam, Anne Kuschal, Christiane Otto, Nicole Westphal, Nico Roos, Christian Reinhardt, Richard Walter, Lutz TI Sequence analysis of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region SO IMMUNOGENETICS LA English DT Article DE MHC class II; Evolution; Polymorphism; Mouse lemur; BAC sequencing ID MAJOR HISTOCOMPATIBILITY COMPLEX; RHESUS MACAQUES; COMPARATIVE GENETICS; CYNOMOLGUS MACAQUES; DRB GENES; POLYMORPHISMS; HAPLOTYPES; MICROSATELLITE; VARIABILITY AB We here report the genomic organisation of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region based on BAC clone analysis. The sequenced Mimu-MHC haplotype spans 343 kb and encompasses the genes TAP2, DOB, DQB, DQA, DRB, DRA, BTNL2 and a further BTNL gene. The DQ and DR genes of this haplotype are not duplicated. Mimu-DOB is not transcribed and represents a pseudogene due to deletions and premature stop codons. Analysis of BAC clone DNA, a cDNA sample and eight genomic DNA samples suggests that Mimu-DRB, Mimu-DQA and Mimu-DQB are highly polymorphic with the majority of peptide-binding residues being affected by polymorphisms. In contrast, Mimu-DRA is moderately polymorphic, and the variable amino acid positions are not part of the peptide-binding region. Phylogenetic analysis of Mimu-DQA and Mimu-DQB and other primate DQA and DQB genes indicates that duplication of DQA and DQB loci occurred in Anthropoidea after the split from Strepsirrhini. C1 [Walter, Lutz] Deutsch Primatenzentrum GmbH, Abt Primatengenet, D-37077 Gottingen, Germany. [Reinhardt, Richard] Max Planck Inst Plant Breeding Res, Genome Ctr Cologne, Cologne, Germany. [Roos, Christian; Walter, Lutz] German Primate Ctr, Gene Bank Primates, Gottingen, Germany. [Kuschal, Christiane] NCI, DNA Repair Sect, DB, CCR,NIH, Bethesda, MD 20892 USA. [Averdam, Anne] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. [Averdam, Anne; Kuschal, Christiane; Otto, Nicole; Westphal, Nico; Roos, Christian; Walter, Lutz] German Primate Ctr, Primate Genet Lab, Gottingen, Germany. RP Walter, L (reprint author), Deutsch Primatenzentrum GmbH, Abt Primatengenet, Kellnerweg 4, D-37077 Gottingen, Germany. EM lwalter@gwdg.de OI Kuschal, Christiane/0000-0001-6113-3585; Walter, Lutz/0000-0001-9408-3131 FU Pakt fur Forschung und Innovation of the Leibniz-Gemeinschaft 'Biodiversitat der Primaten: Erfassung, Ursachen und Erhalt'; Nationales Genomforschungsnetz (NGFN) FX The authors thank Manfred Eberle for providing DNA samples and Fabienne Aujard for the liver sample of M. murinus. This study was supported by the Pakt fur Forschung und Innovation of the Leibniz-Gemeinschaft 'Biodiversitat der Primaten: Erfassung, Ursachen und Erhalt' and by the Nationales Genomforschungsnetz (NGFN). NR 27 TC 7 Z9 7 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 2011 VL 63 IS 2 BP 85 EP 93 DI 10.1007/s00251-010-0487-3 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 718QL UT WOS:000287140500003 PM 20938657 ER PT J AU Nock, CJ Brell, JM Bokar, JA Cooney, MM Cooper, B Gibbons, J Krishnamurthi, S Manda, S Savvides, P Remick, SC Ivy, P Dowlati, A AF Nock, Charles J. Brell, Joanna M. Bokar, Joseph A. Cooney, Matthew M. Cooper, Brenda Gibbons, Joseph Krishnamurthi, Smitha Manda, Sudhir Savvides, Panayiotis Remick, Scot C. Ivy, Percy Dowlati, Afshin TI A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Phase I; Rebeccamycin; Oxaliplatin; Solid tumors; Rebeccamycin analog; Becatecarin ID NSC-655649; TOPOTECAN; CANCER; MALIGNANCIES; DERIVATIVES AB Rebeccamycin analog (RA) is an antitumor antibiotic with both topoisomerase I and II inhibiting activity. Topoisomerase inhibitors have demonstrated synergy with platinum agents. We performed a phase I trial of combination RA with oxaliplatin in patients with refractory solid tumors. RA was administered as a 1-hour infusion daily on days 1-5 with oxaliplatin administered on day 5. Cycles were repeated every 21 days. A total of 17 patients were enrolled. The MTD for RA was 80 mg/m(2)/d for five days along with oxaliplatin 130 mg/m(2) on day 5. Myelosuppression was a common occurrence but was mild except in one instance. Dose limiting toxicities included atrial fibrillation and hypophosphatemia. There was evidence of antitumor activity including 3 partial responses in patients with esophageal, gallbladder and hepato-cellular carcinoma; 5 additional patients had stable disease. Thus, the combination of RA and oxaliplatin is both tolerable and has evidence of clinical activity, but given the lack of significant activity for single agent RA across a variety of disease sites, it is unlikely to proceed to phase II development. C1 [Nock, Charles J.; Brell, Joanna M.; Bokar, Joseph A.; Cooney, Matthew M.; Cooper, Brenda; Gibbons, Joseph; Krishnamurthi, Smitha; Manda, Sudhir; Savvides, Panayiotis; Remick, Scot C.; Ivy, Percy; Dowlati, Afshin] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Nock, Charles J.; Brell, Joanna M.; Bokar, Joseph A.; Cooney, Matthew M.; Cooper, Brenda; Gibbons, Joseph; Krishnamurthi, Smitha; Manda, Sudhir; Savvides, Panayiotis; Remick, Scot C.; Ivy, Percy; Dowlati, Afshin] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ivy, Percy] NCI, Bethesda, MD 20892 USA. RP Dowlati, A (reprint author), Univ Hosp Cleveland, Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM afshin.dowlati@case.edu FU [U01 CA62502]; [MO1 RR00080]; [K23 CA109348] FX Supported in part by grants U01 CA62502, MO1 RR00080 and K23 CA109348. NR 17 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2011 VL 29 IS 1 BP 126 EP 130 DI 10.1007/s10637-009-9322-9 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 702GK UT WOS:000285882400013 PM 19774342 ER PT J AU Burnett, JC Tam, LN AF Burnett, James C. Tam Luong Nguyen TI Is Stoichiometry a New Metric for Evaluating Folded Proteins? SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Editorial Material C1 [Burnett, James C.; Tam Luong Nguyen] NCI Frederick, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Tam, LN (reprint author), NCI Frederick, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. EM nguyent5@mail.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 1 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD FEB PY 2011 VL 28 IS 4 BP 641 EP 642 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 710AI UT WOS:000286482400031 PM 21142245 ER PT J AU Gai, ND Talagala, SL Butman, JA AF Gai, Neville D. Talagala, S. Lalith Butman, John A. TI Whole-Brain Cerebral Blood Flow Mapping Using 3D Echo Planar Imaging and Pulsed Arterial Tagging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE arterial spin labeling; 3D PULSAR; blurring reduction; whole brain perfusion imaging ID LABELING PERFUSION MEASUREMENTS; MRI; SIGNAL; INVERSION AB Purpose: To quantitate cerebral blood flow (CBF) in the entire brain using the 3D echo planar imaging (EPI) PULSAR (pulsed star labeling) technique. Materials and Methods: The PULSAR technique was modified to 1) incorporate a nonselective inversion pulse to suppress background signal; 2) to use 3D EPI acquisition; and 3) to modulate flip angle in such a manner as to minimize the blurring resulting from T1 modulation along the slice encoding direction. Computation of CBF was performed using the general kinetic model (GKM). In a series of healthy volunteers (n = 12), we first investigated the effects of introducing an inversion pulse on the measured value of CBF and on the temporal stability of the perfusion signal. Next we investigated the effect of flip angle modulation on the spatial blurring of the perfusion signal. Finally, we evaluated the repeatability of the CBF measurements, including the influence of the measurement of arterial blood magnetization (a calibration factor for the GKM). Results: The sequence provides sufficient perfusion signal to achieve whole brain coverage in approximate to 5 minutes. Introduction of the inversion pulse for background suppression did not significantly affect computed CBF values, but did reduce the fluctuation in the perfusion signal. Flip angle modulation reduced blurring, resulting in higher estimates of gray matter (GM) CBF and lower estimates of white matter (WM) CBF. The repeatability study showed that measurement of arterial blood signal did not result in significantly higher error in the perfusion measurement. Conclusion: Improvements in acquisition and sequence preparation presented here allow for better quantification and localization of perfusion signal, allowing for accurate whole-brain CBF measurements in 5 minutes. C1 [Gai, Neville D.; Butman, John A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Talagala, S. Lalith] NINDS, NIH MRI Res Facil, NIH, Bethesda, MD 20892 USA. RP Gai, ND (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10,Rm 10502X, Bethesda, MD 20892 USA. EM gaind@cc.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU National Institutes of Health (NIH) FX Contract grant sponsor: Intramural Research Program of the National Institutes of Health (NIH). NR 25 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD FEB PY 2011 VL 33 IS 2 BP 287 EP 295 DI 10.1002/jmri.22437 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 716FA UT WOS:000286953300003 PM 21274969 ER PT J AU Akilov, O Grant, C Geskin, L Piekarz, R Bates, S AF Akilov, Oleg Grant, Cliona Geskin, Larisa Piekarz, Richard Bates, Susan TI Low dose electron beam radiation to localized symptomatic CTCL lesions further improves clinical responses to romidepsin SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the American-Academy-of-Dermatology CY FEB 04-08, 2011 CL New Orleans, LA SP Amer Acad Dermatol C1 [Akilov, Oleg; Geskin, Larisa] Univ Pittsburgh, Pittsburgh, PA USA. [Grant, Cliona; Piekarz, Richard; Bates, Susan] NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2011 VL 64 IS 2 SU 1 BP AB114 EP AB114 PG 1 WC Dermatology SC Dermatology GA 714AY UT WOS:000286780500449 ER PT J AU Baddour, LM Epstein, AE Erickson, CC Knight, BP Levison, ME Lockhart, PB Masoudi, FA Okum, EJ Wilson, WR Beerman, LB Bolger, AF Estes, NAM Gewitz, M Newburger, JW Schron, EB Taubert, KA AF Baddour, Larry M. Epstein, Andrew E. Erickson, Christopher C. Knight, Bradley P. Levison, Matthew E. Lockhart, Peter B. Masoudi, Frederick A. Okum, Eric J. Wilson, Walter R. Beerman, Lee B. Bolger, Ann F. Estes, N. A. Mark, III Gewitz, Michael Newburger, Jane W. Schron, Eleanor B. Taubert, Kathryn A. CA Council Cardiovasc Disease Young Council Cardiovasc Surg & Anesthe Council Cardiovasc Nursing Council Clinical Cardiology Interdisciplinary Council Quality TI A summary of the update on cardiovascular implantable electronic device infections and their management A scientific statement from the American Heart Association SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE American Heart Association scientific statements; infection; device; cardiovascular implantable electronic device; pacemaker; defibrillator; endocarditis; bacteremia; antibiotic prophylaxis ID COAGULASE-NEGATIVE STAPHYLOCOCCI; PERMANENT PACEMAKER IMPLANTATION; ANTIBIOTIC-PROPHYLAXIS; CARDIOVERTER-DEFIBRILLATORS; ANTIMICROBIAL PROPHYLAXIS; ENDOCARDIAL PACEMAKER; SUSTAINED BACTEREMIA; AUREUS BACTEREMIA; DENTAL PROCEDURES; LEAD EXTRACTION AB Background. The purpose of this statement is to update the recommendations by the American Heart Association (AHA) for cardiovascular implantable electronic device (CIED) infections and their management, which were last published in 2003. Methods and Results. The AHA commissioned this scientific statement to educate clinicians about CIED infections, provide explicit recommendations for the care of patients with suspected or established CIED infections and highlight areas of needed research. The recommendations in this statement reflect analyses of relevant literature, to include recent advances in our understanding of the epidemiology, risk factors, microbiology, management and prevention of CIED infections. Conclusion. There are no scientific data to support the use of antimicrobial prophylaxis for dental or other invasive procedures. Clinical Implications. The concerns about life-threatening drug reactions, the development of resistant strains of bacterial pathogens, medicolegal issues and cost to the health care system are, thus, avoided. C1 [Baddour, Larry M.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28232 USA. [Baddour, Larry M.; Wilson, Walter R.] Mayo Clin, Div Infect Dis, Coll Med, Rochester, MN USA. [Epstein, Andrew E.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Epstein, Andrew E.] Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. [Erickson, Christopher C.] Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE USA. [Erickson, Christopher C.] Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. [Erickson, Christopher C.] Creighton Univ, Sch Med, Dept Pediat, Omaha, NE 68178 USA. [Erickson, Christopher C.] Childrens Hosp & Med Ctr, Omaha, NE USA. [Knight, Bradley P.] NW Med Ctr, Div Cardiol, Chicago, IL USA. [Levison, Matthew E.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Levison, Matthew E.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Div Cardiol, Denver, CO USA. [Okum, Eric J.] Cardiac Vasc & Thorac Surg, Cincinnati, OH USA. [Beerman, Lee B.] Univ Pittsburgh, Div Pediat Cardiol, Childrens Hosp Pittsburgh, Ctr Med, Pittsburgh, PA 15260 USA. [Bolger, Ann F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bolger, Ann F.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA USA. [Estes, N. A. Mark, III] Tufts Med Ctr, Cardiac Arrhythmia Serv, Boston, MA USA. [Gewitz, Michael] Maria Fareri Childrens Hosp, Westchester Med Ctr, Valhalla, NY USA. [Gewitz, Michael] New York Med Coll, Valhalla, NY 10595 USA. [Newburger, Jane W.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Schron, Eleanor B.] NEI, Vis Res Program, Natl Inst Hlth, Rockville, MD USA. [Taubert, Kathryn A.] World Heart Federat, Geneva, NY USA. RP Lockhart, PB (reprint author), Carolinas Med Ctr, Dept Oral Med, POB 32861, Charlotte, NC 28232 USA. EM Peter.Lockhart@carolinashealthcare.org FU St. Jude Medical, St. Paul, Minn; Boston Scientific, Natick, Mass FX Dr. Erickson has received a research grant from St. Jude Medical, St. Paul, Minn. Dr. Estes has received research support from Boston Scientific, Natick, Mass.; is a consultant to Boston Scientific; and has received honoraria from Boston Scientific and St. Jude Medical. None of the other authors reported any disclosures. NR 69 TC 15 Z9 16 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 2011 VL 142 IS 2 BP 159 EP 165 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 716UU UT WOS:000286999800017 PM 21282681 ER PT J AU Reedy, J Krebs-Smith, SM AF Reedy, Jill Krebs-Smith, Susan M. TI Labeling Solid Fats and Added Sugars As Empty Calories Response SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter C1 [Reedy, Jill] NCI, Risk Factor Monitoring & Methods Appl Res Program, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. RP Reedy, J (reprint author), NCI, Risk Factor Monitoring & Methods Appl Res Program, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 2011 VL 111 IS 2 BP 223 EP 224 DI 10.1016/j.jada.2010.12.004 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 717UV UT WOS:000287073800008 ER PT J AU Wright, JD Wang, CY AF Wright, Jacqueline D. Wang, Chia-Yih TI Awareness of Federal Dietary Guidance in Persons Aged 16 Years and Older: Results from the National Health and Nutrition Examination Survey 2005-2006 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID USDA FOOD GUIDE; EATING PLAN; TRIAL; RISK; BEHAVIOR AB The National Health and Nutrition Examination Survey 2005-2006 included questions on awareness of the Dietary Guidelines for Americans (DGA), the Food Guide Pyramid, and the 5 A Day for Better Health Program. Prevalence of awareness of federal dietary guidance was estimated and differences were tested across demographic traits, health characteristics, and diet-related attitudes and behavior. The continuous National Health and Nutrition Examination Survey uses a nationally representative cross-sectional sample design. The analytic sample consisted of 5,499 persons aged 16 years and older with complete data. Among persons aged 16 years and older, 83.8% had heard of at least one of the initiatives: 49.2% had heard of the DGA, 80.6% had heard of the Food Guide Pyramid, and 51.2% had heard of the 5 A Day program. There was a linear trend of decreasing awareness of at least one of the guidance efforts with increasing age. Differences by sex, race/ethnicity, education, and income were also observed. Differences by body mass index were not statistically significant; however, significant differences were seen with fatalistic beliefs about body weight. Differences by smoking, self-assessed diet quality, and eating out frequency were not statistically significant after adjustment for sex, age, race/ethnicity, education, and income. These results may be useful in promotion of the upcoming edition of the DGA and to suggest population groups that may benefit from strengthened and more innovative education efforts at the public health program level and at the clinic level. J Am Diet Assoc. 2011;111:295-300. C1 [Wright, Jacqueline D.] NHLBI, Epidemiol Branch, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, Bethesda, MD 20892 USA. [Wright, Jacqueline D.; Wang, Chia-Yih] Ctr Dis Control & Prevent, Div Natl Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Wright, JD (reprint author), NHLBI, Epidemiol Branch, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, Suite 10018,6701 Rockledge Dr MSC 7936, Bethesda, MD 20892 USA. EM jacqueline.wright@nih.gov NR 23 TC 11 Z9 11 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 2011 VL 111 IS 2 BP 295 EP 300 DI 10.1016/j.jada.2010.10.049 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 717UV UT WOS:000287073800019 PM 21272706 ER PT J AU Arnold, MA Shandilya, S Galli, S Killian, JK Raffeld, M Tsokos, M Meltzer, PS Warren, KE Quezado, MM AF Arnold, M. A. Shandilya, S. Galli, S. Killian, J. K. Raffeld, M. Tsokos, M. Meltzer, P. S. Warren, K. E. Quezado, M. M. TI Morphological and Molecular Profiling of Pediatric Brain Stem Gliomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Arnold, M. A.; Shandilya, S.; Galli, S.; Killian, J. K.; Raffeld, M.; Tsokos, M.; Meltzer, P. S.; Warren, K. E.; Quezado, M. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 1 BP 4A EP 4A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400002 ER PT J AU Weaver, DL Ashikaga, T Krag, DN Skelly, JM Anderson, SJ Harlow, SP Julian, TB Mamounas, EP Wolmark, N AF Weaver, D. L. Ashikaga, T. Krag, D. N. Skelly, J. M. Anderson, S. J. Harlow, S. P. Julian, T. B. Mamounas, E. P. Wolmark, N. TI Survival Impact of Occult Metastases in NSABP B-32: Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Breast Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 Univ Vermont, Coll Med, Burlington, VT 05405 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Aultman Caner Ctr, Canton, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 280 BP 69A EP 69A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400281 ER PT J AU Aung, PP Pathak, A Xi, L Filie, AC Raffeld, M AF Aung, P. P. Pathak, A. Xi, L. Filie, A. C. Raffeld, M. TI Identification of a DNA Methylation Marker That Differentiates Malignant Mesothelioma from Reactive Mesothelial Cells on Effusion Samples SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Aung, P. P.; Pathak, A.; Xi, L.; Filie, A. C.; Raffeld, M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 339 BP 83A EP 83A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400341 ER PT J AU Chowdhuri, SR Fetsch, P Hughes, MS Filie, AC AF Chowdhuri, S. Roy Fetsch, P. Hughes, M. S. Filie, A. C. TI KBA.62 and KIT Expression Patterns in Fine-Needle Aspirates of Malignant Melanoma Metastatic to the Liver SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Chowdhuri, S. Roy; Fetsch, P.; Hughes, M. S.; Filie, A. C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 427 BP 103A EP 104A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400429 ER PT J AU Chowdhuri, SR Xi, L Pham, T Hanson, J Giaccone, G Emmerert-Buck, M Raffeld, M Filie, AC AF Chowdhuri, S. Roy Xi, L. Pham, T. Hanson, J. Giaccone, G. Emmerert-Buck, M. Raffeld, M. Filie, A. C. TI High Sensitivity EGFR Mutation Detection in Cytologic Preparations Enabled by Laser Capture Microdissection (LCM) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Chowdhuri, S. Roy; Xi, L.; Pham, T.; Hanson, J.; Giaccone, G.; Emmerert-Buck, M.; Raffeld, M.; Filie, A. C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 428 BP 104A EP 104A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400430 ER PT J AU Liu, YC Rosenberg, SA Lee, CCR AF Liu, Y-C Rosenberg, S. A. Lee, C-C R. TI Target Marker for Immunotherapy in Metastatic Melanomas of Rare Morphology Subtypes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 100th Annual Meeting of the United States and Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2011 CL San Antonio, TX SP Canadian Acad Pathol C1 [Liu, Y-C; Rosenberg, S. A.; Lee, C-C R.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2011 VL 91 SU 1 MA 499 BP 120A EP 120A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 716ZG UT WOS:000287011400501 ER PT J AU Gulley, SP Rasch, EK Chan, L AF Gulley, Stephen P. Rasch, Elizabeth K. Chan, Leighton TI If We Build It, Who Will Come? Working-Age Adults With Chronic Health Care Needs and the Medical Home SO MEDICAL CARE LA English DT Article DE patient-centered care; chronic illness; people with disabilities; health care reform ID CHILDREN; POLICY AB Background: Currently, there is a call to implement and test the patient-centered medical home in adult populations, particularly among those with chronic conditions. However, the size, composition, and service use of the population who might require this coordinated care model need to be assessed, as does the way they are defined and identified. Objectives: Using nationally representative data from the 2002 to 2004 Medical Expenditure Panel Survey, we provide a preliminary profile of the population of working-age adults with chronic health care needs (ACHCN), including those with chronic health conditions and disabilities. Results: ACHCN comprised the majority (52%) of the working-aged population. Relative to persons without chronic health care needs, they had significantly more service use, access problems, and 4 times more health care expenditures. Of the 2 disability groups within the larger population of ACHCN, those reporting need for help or supervision with activities of daily livings (ADLs) or instrumental ADLs (IADLs) had the highest rates/percentages of the following: mean chronic (3.5) and acute (4.4) conditions during the year, service use (all services), and access problems. The ADL/IADL-limited group reported annual medical expenditures totaling 100 billion dollars, more than what was spent on the entire working-age population without chronic health care needs. Conclusions: These data reveal the drawbacks of selecting the potential population targeted for a medical home on the basis of diagnosis alone. New measurement approaches on the basis of shared need for ongoing health and related services are required to bridge the division between disability and chronic health conditions. C1 [Gulley, Stephen P.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Gulley, Stephen P.; Rasch, Elizabeth K.; Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. RP Gulley, SP (reprint author), NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bldg 10-CRC,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM gulley@brandeis.edu FU NIH FX Supported by NIH Intramural Research Program. NR 23 TC 17 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 2011 VL 49 IS 2 BP 149 EP 155 DI 10.1097/MLR.0b013e3182028380 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 706BR UT WOS:000286191000006 PM 21206295 ER PT J AU Melo, VH Pinto, JA Freimanis-Hance, L Gutierrez, C Peixoto, M Santos, B Machado, DM Joao, EC Robergeau, K Read, JS AF Melo, Victor H. Pinto, Jorge A. Freimanis-Hance, Laura Gutierrez, Cesar Peixoto, Mario Santos, Breno Machado, Daisy M. Joao, Esau C. Robergeau, Kathleen Read, Jennifer S. TI Postpartum changes in plasma viral load and CD4 percentage among HIV-infected women from Latin American and Caribbean countries: the NISDI Perinatal Study SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article DE HIV; pregnancy; postpartum period; viral load; CD4 counts ID PREGNANT-WOMEN; ANTIRETROVIRAL TREATMENT; RANDOMIZED-TRIAL; THERAPY; INTERRUPTION; DELIVERY AB The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4(+) percentage (CD4%) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (>= 0.5 log(10)) and decreases in CD4% (>= 20% relative decrease in CD4%) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87% were asymptomatic. The median CD4% values were: HD [34% (PR); 25% (TR)] and PP [29% (PR); 24% (TR)]. The VL increases were 60% (PR) and 19% (TR) (p < 0.0001). The CD4% decreases were 36% (PR) and 18% (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95% CI: 5.5-10.9) and a CD4% decrease (AOR 2.3; 95% CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4% decreases compared to those receiving TR. The clinical implications of these VL and CD4% changes remain to be explored. C1 [Melo, Victor H.; Pinto, Jorge A.] Univ Fed Minas Gerais, Fac Med, BR-30130100 Belo Horizonte, MG, Brazil. [Freimanis-Hance, Laura; Robergeau, Kathleen] Westat Corp, Rockville, MD USA. [Gutierrez, Cesar] Univ Nacl Mayor San Marcos, Lima 14, Peru. [Peixoto, Mario] Hosp Femina, Porto Alegre, RS, Brazil. [Santos, Breno] Hosp Conceicao, Porto Alegre, RS, Brazil. [Machado, Daisy M.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Joao, Esau C.] Hosp Servidores Estado, Rio De Janeiro, Brazil. [Read, Jennifer S.] Natl Inst Child Hlth, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. [Read, Jennifer S.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Melo, VH (reprint author), Univ Fed Minas Gerais, Fac Med, Av Alfredo Balena 190 4 Andar, BR-30130100 Belo Horizonte, MG, Brazil. EM victormelo@terra.com.br FU NICHD [HHSN267200800001C/N01-DK-8-0001] FX Financial support: NICHD (HHSN267200800001C/N01-DK-8-0001) NR 17 TC 6 Z9 6 U1 1 U2 3 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD FEB PY 2011 VL 106 IS 1 BP 97 EP 104 PG 8 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 726HW UT WOS:000287712000016 PM 21340363 ER PT J AU Yang, RQ Gaidamakov, SA Xie, JW Lee, J Martino, L Kozlov, G Crawford, AK Russo, AN Conte, MR Gehring, K Maraia, RJ AF Yang, Ruiqing Gaidamakov, Sergei A. Xie, Jingwei Lee, Joowon Martino, Luigi Kozlov, Guennadi Crawford, Amanda K. Russo, Amy N. Conte, Maria R. Gehring, Kalle Maraia, Richard J. TI La-Related Protein 4 Binds Poly(A), Interacts with the Poly(A)-Binding Protein MLLE Domain via a Variant PAM2w Motif, and Can Promote mRNA Stability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POLYMERASE-III TRANSCRIPTS; C-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; EUKARYOTIC TRANSLATION; STRUCTURAL BASIS; DEPENDENT TRANSLATION; INITIATION-FACTOR; STRESS GRANULES; RECOGNITION; RIBONUCLEOPROTEIN AB The conserved RNA binding protein La recognizes UUU-3`OH on its small nuclear RNA ligands and stabilizes them against 3`-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4 interacts with RACK1, a 40S ribosome-and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all similar to 150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis. C1 [Yang, Ruiqing; Gaidamakov, Sergei A.; Lee, Joowon; Crawford, Amanda K.; Russo, Amy N.; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Martino, Luigi; Conte, Maria R.] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England. [Xie, Jingwei; Kozlov, Guennadi; Gehring, Kalle] McGill Univ, Dept Biochem, Montreal, PQ, Canada. [Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC USA. RP Maraia, RJ (reprint author), 31 Ctr Dr,Bldg 31,Room 2A25, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov RI Conte, Maria/C-4102-2008; Martino, Luigi/B-3491-2009; Gehring, Kalle/I-4403-2013; OI Conte, Maria/0000-0001-8558-2051; Gehring, Kalle/0000-0001-6500-1184; Martino, Luigi/0000-0001-5871-3124 FU NICHD, NIH; Canadian Institutes of Health [MOP-14219] FX This work was supported by Intramural Research Program of the NICHD, NIH, grants to CHESS and Canadian Institutes of Health grant MOP-14219. L.M. is a fellow of the European Molecular Biology Organization (EMBO). M.R.C. acknowledges the Wellcome Trust for the Centre of Biomolecular Spectroscopy. NR 72 TC 18 Z9 18 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2011 VL 31 IS 3 BP 542 EP 556 DI 10.1128/MCB.01162-10 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 706AV UT WOS:000286185900015 PM 21098120 ER PT J AU Bley, A Tifft, C Kahn, S Eichler, F AF Bley, Annette Tifft, Cynthia Kahn, Susan Eichler, Florian TI Natural history of infantile GM2 gangliosidosis - Survey of 97 patients SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 7th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 16-18, 2011 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Bley, Annette; Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tifft, Cynthia] NHGRI, NIH, Bethesda, MD 20892 USA. 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2011 VL 102 IS 2 BP S9 EP S9 DI 10.1016/j.ymgme.2010.11.028 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 715CW UT WOS:000286859000047 ER PT J AU Choi, J Motabar, O Zheng, W Marugan, J Sidransky, E Goldin, E AF Choi, Jae Motabar, Omid Zheng, Wei Marugan, Juan Sidransky, Ellen Goldin, Ehud TI The use of saposin C and phosphatidylserine in functional studies of glucocerebrosidase SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 7th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 16-18, 2011 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Choi, Jae; Sidransky, Ellen; Goldin, Ehud] NHGRI, NIH, Bethesda, MD 20892 USA. [Motabar, Omid; Zheng, Wei; Marugan, Juan] NIH Chem Genom Ctr, Rockville, 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2011 VL 102 IS 2 BP S11 EP S11 DI 10.1016/j.ymgme.2010.11.037 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 715CW UT WOS:000286859000055 ER PT J AU Gustafson, AM Velayati, A Blech-Hermoni, Y Choi, J Westbroek, W Landazabal, C Goldin, E Stubblefield, B Sidransky, E Tayebi, N AF Gustafson, Ann Marie Velayati, Arash Blech-Hermoni, Yotam Choi, Jae Westbroek, Wendy Landazabal, Claudia Goldin, Ehud Stubblefield, Barbara Sidransky, Ellen Tayebi, Nahid TI The evaluation of a loss-of-function GBA variant found in Gaucher patients with Parkinson disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 7th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 16-18, 2011 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Gustafson, Ann Marie; Velayati, Arash; Blech-Hermoni, Yotam; Choi, Jae; Westbroek, Wendy; Landazabal, Claudia; Goldin, Ehud; Stubblefield, Barbara; Sidransky, Ellen; Tayebi, Nahid] NHGRI, 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2011 VL 102 IS 2 BP S19 EP S20 DI 10.1016/j.ymgme.2010.11.066 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 715CW UT WOS:000286859000084 ER PT J AU Sidransky, E Ozlem, GA Masdeu, J Kohn, P Lopez, G Eisenberg, D Groden, C Chaflin, M Ianni, A Berman, K Sidransky, E AF Sidransky, Ellen Ozlem, Goker-Alpan Masdeu, Joseph Kohn, Phillip Lopez, Grisel Eisenberg, Daniel Groden, Catherine Chaflin, M. Ianni, Angela Berman, Karen Sidransky, Ellen TI The neurobiology of glucocerebrosidase associated PD: studies of dopamine synthesis and rCBF in GBA mutation carriers with and without parkinsonism SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 7th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 16-18, 2011 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Sidransky, Ellen; Ozlem, Goker-Alpan; Masdeu, Joseph; Kohn, Phillip; Lopez, Grisel; Eisenberg, Daniel; Groden, Catherine; Chaflin, M.; Ianni, Angela; Berman, Karen; Sidransky, Ellen] NHGRI, NIH, Bethesda, MD 20892 USA. RI Eisenberg, Daniel/C-7432-2014; Eisenberg, Daniel/S-4342-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2011 VL 102 IS 2 BP S41 EP S42 DI 10.1016/j.ymgme.2010.11.139 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 715CW UT WOS:000286859000156 ER PT J AU Velayati, A Moaven, N Saranjam, H Westbroek, W Goldin, E Tayebi, N Stubblefield, B Sidransky, E AF Velayati, Arash Moaven, Nima Saranjam, Hamid Westbroek, Wendy Goldin, Ehud Tayebi, Nahid Stubblefield, Barbara Sidransky, Ellen TI Exploring the interaction between glucocerebrosidase and alpha-synuclein SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 7th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 16-18, 2011 CL Las Vegas, NV SP Lysosomal Dis Network C1 [Velayati, Arash; Moaven, Nima; Saranjam, Hamid; Westbroek, Wendy; Goldin, Ehud; Tayebi, Nahid; Stubblefield, Barbara; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2011 VL 102 IS 2 BP S43 EP S43 DI 10.1016/j.ymgme.2010.11.145 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 715CW UT WOS:000286859000162 ER PT J AU Renaud, S Loukinov, D Alberti, L Vostrov, A Kwon, YW Bosman, FT Lobanenkov, V Benhattar, J AF Renaud, Stephanie Loukinov, Dmitri Alberti, Loredana Vostrov, Alexander Kwon, Yoo-Wook Bosman, Fred T. Lobanenkov, Victor Benhattar, Jean TI BORIS/CTCFL-mediated transcriptional regulation of the hTERT telomerase gene in testicular and ovarian tumor cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CATALYTIC SUBUNIT HTERT; REVERSE-TRANSCRIPTASE; DNA METHYLATION; CANCER-CELLS; CPG ISLAND; PROMOTER REGION; RNA COMPONENT; CTCF-BINDING; FACTOR BORIS; EXPRESSION AB Telomerase activity, not detectable in somatic cells but frequently activated during carcinogenesis, confers immortality to tumors. Mechanisms governing expression of the catalytic subunit hTERT, the limiting factor for telomerase activity, still remain unclear. We previously proposed a model in which the binding of the transcription factor CTCF to the two first exons of hTERT results in transcriptional inhibition in normal cells. This inhibition is abrogated, however, by methylation of CTCF binding sites in 85% of tumors. Here, we showed that hTERT was unmethylated in testicular and ovarian tumors and in derivative cell lines. We demonstrated that CTCF and its paralogue, BORIS/CTCFL, were both present in the nucleus of the same cancer cells and bound to the first exon of hTERT in vivo. Moreover, exogenous BORIS expression in normal BORIS-negative cells was sufficient to activate hTERT transcription with an increasing number of cell passages. Thus, expression of BORIS was sufficient to allow hTERT transcription in normal cells and to counteract the inhibitory effect of CTCF in testicular and ovarian tumor cells. These results define an important contribution of BORIS to immortalization during tumorigenesis. C1 [Renaud, Stephanie; Alberti, Loredana; Bosman, Fred T.; Benhattar, Jean] CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. [Renaud, Stephanie; Loukinov, Dmitri; Vostrov, Alexander; Kwon, Yoo-Wook; Lobanenkov, Victor] NIAID, Immunopathol Lab, NIH, Rockville, MD 20892 USA. RP Benhattar, J (reprint author), CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. EM jean.benhattar@chuv.ch OI Lobanenkov, Victor/0000-0001-6665-3635 FU Swiss National Science Foundation [3100AO-101732, 3100A0-113505]; National Institutes of Health, National Institute of Allergy and Infectious Diseases FX Swiss National Science Foundation (3100AO-101732 and 3100A0-113505, in part); Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. Funding for open access charge: Swiss National Science Foundation. NR 54 TC 25 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2011 VL 39 IS 3 BP 862 EP 873 DI 10.1093/nar/gkq827 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 720CJ UT WOS:000287257500014 PM 20876690 ER PT J AU Bebenek, K Pedersen, LC Kunkel, TA AF Bebenek, Katarzyna Pedersen, Lars C. Kunkel, Thomas A. TI Replication infidelity via a mismatch with Watson-Crick geometry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mutagenesis; replication fidelity; nascent base pair; mispair ID DNA-POLYMERASE-LAMBDA; ACTIVE-SITE; DEOXYRIBONUCLEIC-ACID; STRAND MISALIGNMENT; POL LAMBDA; FIDELITY; INTERMEDIATE; ERRORS; METAL; BETA AB In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase lambda variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G.T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA. C1 [Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065070] FX We thank Lee Pedersen and William Beard for helpful discussions and critical reading of the manuscript. Data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID (or 22-BM) beamline at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. This work was supported by the Division of Intramural Research of the National Institutes of Health, National Institute of Environmental Health Sciences (Project Z01 ES065070 to T.A.K.). NR 34 TC 65 Z9 66 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2011 VL 108 IS 5 BP 1862 EP 1867 DI 10.1073/pnas.1012825108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714JA UT WOS:000286804700024 PM 21233421 ER PT J AU Gapud, EJ Dorsett, Y Yin, B Callen, E Bredemeyer, A Mahowald, GK Omi, KQ Walker, LM Bednarski, JJ McKinnon, PJ Bassing, CH Nussenzweig, A Sleckman, BP AF Gapud, Eric J. Dorsett, Yair Yin, Bu Callen, Elsa Bredemeyer, Andrea Mahowald, Grace K. Omi, Kazuo Q. Walker, Laura M. Bednarski, Jeffrey J. McKinnon, Peter J. Bassing, Craig H. Nussenzweig, Andre Sleckman, Barry P. TI Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA repair; lymphoid tumors; lymphocyte development ID DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND-BREAK; T-CELL DEVELOPMENT; V(D)J RECOMBINATION; PHOSPHORYLATION SITES; CATALYTIC SUBUNIT; DEFICIENT LYMPHOCYTES; RAG PROTEINS; RSS ENDS; IN-VIVO AB Lymphocyte antigen receptor gene assembly occurs through the process of V(D)J recombination, which is initiated when the RAG endonuclease introduces DNA DSBs at two recombining gene segments to form broken DNA coding end pairs and signal end pairs. These paired DNA ends are joined by proteins of the nonhomologous end-joining (NHEJ) pathway of DSB repair to form a coding joint and signal joint, respectively. RAG DSBs are generated in G1-phase developing lymphocytes, where they activate the ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases to orchestrate diverse cellular DNA damage responses including DSB repair. Paradoxically, although Atm and DNA-PKcs both function during coding joint formation, Atm appears to be dispensible for signal joint formation; and although some studies have revealed an activity for DNA-PKcs during signal joint formation, others have not. Here we show that Atm and DNA-PKcs have overlapping catalytic activities that are required for chromosomal signal joint formation and for preventing the aberrant resolution of signal ends as potentially oncogenic chromosomal translocations. C1 [Gapud, Eric J.; Dorsett, Yair; Bredemeyer, Andrea; Mahowald, Grace K.; Omi, Kazuo Q.; Walker, Laura M.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Bednarski, Jeffrey J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Callen, Elsa; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Yin, Bu; Bassing, Craig H.] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Abramson Family Canc Res Inst,Sch Med,Ctr Childho, Philadelphia, PA 19104 USA. [McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. RP Sleckman, BP (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM sleckman@wustl.edu OI Bredemeyer, Andrea/0000-0003-2970-5998 FU National Institutes of Health [AI074953, AI47829, CA136470, CA125195, CA096832]; Cancer Research Institute; Washington University; National Institutes of Health Ruth L. Kirschstein National Research Service Award [T32 HD007499]; Children's Discovery Institute FX We thank Dr. Eugene Oltz for critical review of the manuscript and Drs. Greg Longmore and Yunfeng Feng for pFLRU, pHR'Delta 8.2R, and pCMV-VSVg. This work is supported by National Institutes of Health Grants AI074953 (to B. P. S.), AI47829 (to B. P. S.), CA136470 (to B. P. S and C. H. B), CA125195 (to C. H. B.), and CA096832 (to P.J.M.). B.Y. and E.J.G. are supported by the Cancer Research Institute Pre-doctoral Emphasis Pathway in Tumor Immunology Training grant awarded to the University of Pennsylvania (to B.Y.) and Washington University (to E.J.G.). J.J.B. is supported by a National Institutes of Health Ruth L. Kirschstein National Research Service Award (T32 HD007499) and a Children's Discovery Institute Fellows Award. C. H. B. is a Pew Scholar in the Biomedical Sciences program. NR 46 TC 29 Z9 29 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2011 VL 108 IS 5 BP 2022 EP 2027 DI 10.1073/pnas.1013295108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714JA UT WOS:000286804700052 PM 21245316 ER PT J AU Chew, EY Glassman, AR Beck, RW Bressler, NM Fish, GE Ferris, FL Kinyoun, JL AF Chew, Emily Y. Glassman, Adam R. Beck, Roy W. Bressler, Neil M. Fish, Gary E. Ferris, Fredrick L. Kinyoun, James L. CA Diabet Retinopathy Clinical Res TI OCULAR SIDE EFFECTS ASSOCIATED WITH PERIBULBAR INJECTIONS OF TRIAMCINOLONE ACETONIDE FOR DIABETIC MACULAR EDEMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE triamcinolone acetonide; diabetic macular edema; peribulbar injections ID INTRAVITREAL; PHOTOCOAGULATION; INFUSION; TRIAL AB Purpose: To evaluate long-term effects of anterior and posterior peribulbar injections of triamcinolone acetonide on intraocular pressure (IOP) elevation and cataract development. Methods: This study reports on IOP and cataract progression through 2 years in 96 eyes with diabetic macular edema randomized to focal/grid photocoagulation, 20 mg triamcinolone acetonide anterior injection, anterior injection followed by laser, 40 mg triamcinolone acetonide posterior injection, or posterior injection followed by laser. Results: Intraocular pressure increased from baseline by >= 10 mmHg at >= 1 visit through 2 years in 2 eyes (8%) in the laser group, 11 eyes (31%) in the anterior groups, and 6 eyes (17%) in the posterior groups. Among phakic eyes at baseline, 0, 5 (17%), and 1 (3%) in the 3 groups, respectively, underwent cataract surgery before the 2-year visit. Conclusion: Based on this small randomized trial, it appears that over 2 years, anterior peribulbar triamcinolone acetonide injections are associated with an increased incidence of IOP elevation and an increased risk of cataract development compared with laser or posterior peribulbar injections. The association of posterior injections with IOP elevation is less certain. Although the study involved eyes with diabetic macular edema, the results should be relevant to other conditions treated with peribulbar corticosteroids. RETINA 31: 284-289, 2011 C1 [Glassman, Adam R.; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Chew, Emily Y.; Ferris, Fredrick L.] NIH, NEI, Bethesda, MD 20892 USA. [Bressler, Neil M.] Wilmer Eye Inst, Baltimore, MD 21287 USA. [Fish, Gary E.] Texas Retina Associates, Dallas, TX USA. [Kinyoun, James L.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat2@jaeb.org FU NEI NIH HHS [EY14231, EY14229, EY018817, U10 EY014229, U10 EY014231, U10 EY018817, U10 EY023207] NR 17 TC 10 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD FEB PY 2011 VL 31 IS 2 BP 284 EP 289 DI 10.1097/IAE.0b013e3181f049a8 PG 6 WC Ophthalmology SC Ophthalmology GA 711JG UT WOS:000286586500011 PM 20948459 ER PT J AU Misteli, T AF Misteli, Tom TI The Inner Life of the Genome SO SCIENTIFIC AMERICAN LA English DT Article C1 NCI, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 8 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD FEB PY 2011 VL 304 IS 2 BP 66 EP 73 DI 10.1038/scientificamerican0211-66 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 707VR UT WOS:000286318300033 PM 21319544 ER PT J AU Harrison, A Lemey, P Hurles, M Moyes, C Horn, S Pryor, J Malani, J Supuri, M Masta, A Teriboriki, B Toatu, T Penny, D Rambaut, A Shapiro, B AF Harrison, Abby Lemey, Philippe Hurles, Matthew Moyes, Chris Horn, Susanne Pryor, Jan Malani, Joji Supuri, Mathias Masta, Andrew Teriboriki, Burentau Toatu, Tebuka Penny, David Rambaut, Andrew Shapiro, Beth TI Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation SO VIRUSES-BASEL LA English DT Article DE hepatitis B virus; molecular clock; Bayesian phylogenetics ID CORE PROMOTER; VERTICAL TRANSMISSION; MOLECULAR EVOLUTION; SEQUENCE VARIATION; C VIRUS; INFECTION; HISTORY; POPULATIONS; MUTATIONS; HBV AB Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements. C1 [Harrison, Abby] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Harrison, Abby; Pryor, Jan; Malani, Joji] Fiji Sch Med, Suva, Fiji. [Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, B-3000 Louvain, Belgium. [Hurles, Matthew] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Moyes, Chris] Hepatitis Fdn New Zealand, Ohope 3121, Whakatane, New Zealand. [Horn, Susanne] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany. [Supuri, Mathias; Masta, Andrew] Univ Papua New Guinea, Sch Med & Hlth Sci, Port Moresby, Ncd, Papua N Guinea. [Teriboriki, Burentau; Toatu, Tebuka] Nawerwere Hosp, Kiribati Minist Hlth, Tawara, Kiribati. [Penny, David] Massey Univ, Allan Wilson Ctr Mol Ecol & Evolut, Palmerston North 4442, New Zealand. [Rambaut, Andrew] Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH8 3JT, Midlothian, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Shapiro, Beth] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Harrison, A (reprint author), Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM a.g.l.harrison@gmail.com; philippe.lemey@rega.kuleuven.be; meh@sanger.ac.uk; chris.moyes@bopdhb.govt.nz; horn@eva.mpg.de; pryor.jan@gmail.com; joji.malani@fnu.ac.fj; sapuri@daltron.com.pg; masta@daltron.com.pg; dhsmhms@yahoo.com; tebtoatu@yahoo.com; d.penny@massey.ac.nz; a.rambaut@ed.ac.uk; beth.shapiro@psu.edu RI Penny, David/E-9410-2011; OI Rambaut, Andrew/0000-0003-4337-3707; Shapiro, Beth/0000-0002-2733-7776 FU NIH [R01 GM083983-01]; Wellcome Trust; New Zealand Health Research Council FX Thanks to the following for provision of or assistance with the collection of HBV samples: Nakapi Teferani, John Vince, and Mark Paul from the University of Papua New Guinea School of Medicine and Health Sciences Papua New Guinea (UPNG-SMHS); Peta Siba from the Papua New Guinea Institute of Medical Research (PNG-IMR); Gilbert Hiawaly from the Papua New Guinea Ministry of Health (PNG-MOH); Elenoa Areito, Bale Maleli Naiguilevu from the Fiji School of Medicine (FSM) Fiji; Kabwea Tiban, Airam Metai, Tekaibeti Tarataake, Artin Ruatu and Rosemary Tekoaua from the Kiribati Ministry of Health (KMOH) Kiribati; J. Clegg From the Oxford University England (retired); A. Berlioz-Arthaud from the Institut Pasteur de Nouvelle Caledonie; W. Schienfenhovel of the Max Planck-Institute of Behavioural Physiology, Andechs, Germany. This work was partially supported by NIH R01 GM083983-01, the Wellcome Trust and the New Zealand Health Research Council. NR 54 TC 14 Z9 14 U1 0 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD FEB PY 2011 VL 3 IS 2 BP 83 EP 101 DI 10.3390/v3020083 PG 19 WC Virology SC Virology GA 726NC UT WOS:000287728600002 PM 21765983 ER PT J AU Higgins, RD AF Higgins, Rosemary D. TI Untitled SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Editorial Material ID PATENT DUCTUS-ARTERIOSUS; PREMATURE-INFANTS; ORAL IBUPROFEN; CLOSURE C1 NICHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Higgins, RD (reprint author), NICHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD FEB PY 2011 VL 28 IS 2 BP 89 EP 90 DI 10.1055/s-0031-1272553 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 716KJ UT WOS:000286967200001 ER PT J AU Jiang, FX Lin, DC Horkay, F Langrana, NA AF Jiang, Frank Xue Lin, David C. Horkay, Ferenc Langrana, Noshir A. TI Probing Mechanical Adaptation of Neurite Outgrowth on a Hydrogel Material Using Atomic Force Microscopy SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Spinal cord neuron; Stiffness; Topography; Mechanical stiffness; Elasticity map ID EXTRACELLULAR-MATRIX; ROBUST STRATEGIES; CURVE ANALYSIS; NEURONS; CELLS; SOFT; NANOMECHANICS; INDENTATION; ADHESION; GROWTH AB In this study, we describe the design and initial results of probing mechanical adaptation of neurite growth of lightly fixed neurons on a hydrogel substrate by using atomic force microscopy (AFM). It has been shown previously that cells are responsive to the physical conditions of their micro-environment, and that certain cells can adjust their own stiffness as part of the adaptation to the substrate. AFM, a powerful tool to probe micro- and nano-scale structures, has been utilized in assessing topography, morphology, and structural change of neuronal cells. We used AFM with a robust force analysis approach in this study to probe the mechanical properties of both neurites and the substrate at close proximity. We first confirmed the robustness and consistency of the approach specific to soft materials by comparing measurements made on the same reference material using different methods. Subsequently, it was found that the primary spinal cord neurons that were lightly fixed exhibited different stiffnesses between the cell body and neurites. Furthermore, in comparison to the rigidity of the substrate, the stiffness of the neurites was lower, whereas that of the neuronal cell body was higher. C1 [Jiang, Frank Xue; Langrana, Noshir A.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Langrana, Noshir A.] Rutgers State Univ, Dept Mech & Aerosp Engn, Piscataway, NJ 08854 USA. [Lin, David C.; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. RP Langrana, NA (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM langrana@rutgers.edu FU NIH; New Jersey Commission on Spinal Cord Research; NIH, NICHD FX F.X.J. and N.A.L. acknowledge the support from NIH and New Jersey Commission on Spinal Cord Research, and D. C. L. and F. H. acknowledge the support of the Intramural Research Program of the NIH, NICHD. We would like to thank Dr. Emillios K. Dimitriadis (NIBIB, NIH) for his assistance with the AFM measurements and data analysis, Dr. Bonnie Firestein's laboratory for assistance with neuronal culture, and Dr. Michelle L. Previtera for constructive comments. NR 26 TC 9 Z9 9 U1 2 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD FEB PY 2011 VL 39 IS 2 BP 706 EP 713 DI 10.1007/s10439-010-0194-0 PG 8 WC Engineering, Biomedical SC Engineering GA 719OD UT WOS:000287213300009 PM 21063777 ER PT J AU Shukla, S Fujita, KI Xiao, Q Liao, ZY Garfield, S Srinivasula, SM AF Shukla, Sudhanshu Fujita, Ken-ichi Xiao, Qi Liao, Zhiyong Garfield, Susan Srinivasula, Srinivasa M. TI A shear stress responsive gene product PP1201 protects against Fas-mediated apoptosis by reducing Fas expression on the cell surface SO APOPTOSIS LA English DT Article DE Apoptosis; Fas; PP1201; Golgi; Trafficking; Cystic medial degeneration ID HUMAN ENDOTHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; FAS/FAS-L PATHWAY; LIFEGUARD/NEURONAL MEMBRANE-PROTEIN-35; DEATH; TRAFFICKING; MECHANISM; RECEPTOR; SIGNALS AB Cells that form vascular system employ different mechanisms to offset deleterious consequences of exposure to cytokines and cells present in blood. Vascular homeostasis is sustained in part by genes, whose expression increases in response to hemodynamic forces in these cells. PP1201 (also known as RECS1) is one such gene whose expression level increases in response to laminar shear stress. Aged mice deficient in PP1201 are prone to develop cystic medial degeneration (CMD), a form of aortic aneurism manifested with loss of smooth muscle cells and accumulation of basophilic substances. Here we found that higher levels of PP1201 can protect against Fas ligand (FasL)-induced apoptosis. PP1201 interacted with the Fas receptor (CD95/Apo1) and colocalized with it in the Golgi compartment. Unlike its homolog lifeguard (LFG), PP1201 overexpression in several types of cells including primary human aortic smooth muscle cells (AoSMC) decreased the expression of Fas on the plasma membrane without changing the total Fas levels. Only high but not constitutive level of PP1201 controls Fas signaling. Our data suggest that PP1201 functions as an anti-apoptotic protein and its increased expression in vascular cells can contribute to homeostasis by reducing Fas trafficking to the cell membrane. C1 [Shukla, Sudhanshu; Fujita, Ken-ichi; Xiao, Qi; Liao, Zhiyong; Srinivasula, Srinivasa M.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Garfield, Susan] NCI, Confocal Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. RP Srinivasula, SM (reprint author), 9000 Rockville Pike,Bldg 37,Room 3016A, Bethesda, MD 20892 USA. EM srinivsr@mail.nih.gov OI Shukla, Sudhanshu/0000-0002-7091-7215 FU National Institutes of Health, Center for Cancer research, National Cancer Institute FX This work was supported by the intramural Research Program of the National Institutes of Health, Center for Cancer research, National Cancer Institute. We thank Richard Siegel for CFP-Fas plasmid, Stanley Lipkowitz for GST-TRAIL and Hiroshi Nojima for human PP1201 cDNA containing plasmids. NR 38 TC 8 Z9 9 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD FEB PY 2011 VL 16 IS 2 BP 162 EP 173 DI 10.1007/s10495-010-0556-y PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 718RE UT WOS:000287142800006 PM 21107705 ER PT J AU Kuntsche, E Kuntsche, S Knibbe, R Simons-Morton, B Farhat, T Hublet, A Bendtsen, P Godeau, E Demetrovics, Z AF Kuntsche, Emmanuel Kuntsche, Sandra Knibbe, Ronald Simons-Morton, Bruce Farhat, Tilda Hublet, Anne Bendtsen, Pernille Godeau, Emmanuelle Demetrovics, Zsolt TI Cultural and Gender Convergence in Adolescent Drunkenness Evidence From 23 European and North American Countries SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DRINKING; BEHAVIOR; TRENDS AB Objective: To investigate time-trend changes in the frequency of drunkenness among European and North American adolescents. Design: Cross-sectional surveys in the 1997/1998 and 2005/2006 Health Behaviour in School-Aged Children Study (HBSC). Setting: High schools in 23 countries. Participants: A sample of 77 586 adolescents aged 15 years was analyzed by means of hierarchical linear modeling. Main Outcome Measure: The frequency of drunkenness. Results: We observed a significant increase of about 40% in the mean frequency of drunkenness in all 7 participating Eastern European countries. This increase was evident among both genders, but most consistently among girls. Meanwhile, it declined in 13 of 16 Western countries, about 25% on average. Declines in Western countries were particularly notable among boys and in North America, Scandinavia, the United Kingdom, and Ireland. Despite this gender convergence, with few exceptions (Greenland, Norway, United Kingdom) boys continued to have a higher frequency of drunkenness in 2005/2006 than girls. Conclusions: The confirmed cultural convergence implies that adoption and implementation of evidence-based measures to mitigate the frequency of adolescent drunkenness such as tax increases and restricting alcohol access and advertisement should get the same priority in Eastern European countries as in Western countries. Policy measures that might facilitate decreases in drunkenness such as server training and the promotion of alcohol-free leisure-time activities should be reinforced in Western countries. The gender convergence implies that prevention policy should be less exclusively focused on male adolescents. C1 [Kuntsche, Emmanuel; Kuntsche, Sandra] Addict Info Switzerland, Res Inst, CH-1001 Lausanne, Switzerland. [Kuntsche, Emmanuel] Univ Lausanne, Inst Social & Prevent Med, Res Grp Adolescent Hlth, Lausanne, Switzerland. [Kuntsche, Emmanuel] Radboud Univ Nijmegen, Inst Behav Sci, NL-6525 ED Nijmegen, Netherlands. [Knibbe, Ronald] Univ Maastricht, Dept Hlth Promot, Maastricht, Netherlands. [Simons-Morton, Bruce; Farhat, Tilda] NICHHD, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. [Hublet, Anne] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium. [Bendtsen, Pernille] Univ So Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark. [Godeau, Emmanuelle] Univ Toulouse 3, Unite Mixte Rech, Inst Natl Sante, F-31062 Toulouse, France. [Godeau, Emmanuelle] Univ Toulouse 3, Rech Med Unit 558, F-31062 Toulouse, France. [Godeau, Emmanuelle] Serv Med Rectorat, Toulouse, France. [Demetrovics, Zsolt] Eotvos Lorand Univ, Inst Grp Addict Res, Budapest, Hungary. [Demetrovics, Zsolt] Natl Inst Drug Prevent, Budapest, Hungary. RP Kuntsche, E (reprint author), Addict Info Switzerland, Res Inst, POB 870, CH-1001 Lausanne, Switzerland. EM ekuntsche@addiction-info.ch OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Swiss Federal Office of Public Health [09.000925/204.0001/-573]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [N01-HD-53401] FX Data collection was funded by each of the participating countries and regions separately. Elaboration of the manuscript was mainly funded by grant 09.000925/204.0001/-573 from the Swiss Federal Office of Public Health and in part by grant N01-HD-53401 from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Additional Information: Data from the following countries were included in the present study (principal investigators are listed in parentheses): Austria (Wolfgang Dur), Belgium (Flemish-speaking: Lea Maes [1997/ 1998] and Carine Vereecken [2005/2006]; French-speaking: Danielle Piette), Canada (William Boyce), Czech Republic (Ladislav Csemy), Denmark (Bjorn Hostein [1997/1998] and Pernille Due [2005/2006]), Estonia (Mai Maser [1997/1998] and Katrin Aasvee [2005/2006]), Finland (Jorma Tynj l), France (Emmanuelle Godeau), Germany (Klaus Hurrelmann [1997/1998] and Ulrike Ravens-Sieberer [2005/2006]), Greece (Anna Kokkevi), Hungary (Anna Aszmann [1997/1998] and Agnes Nemeth [2005/2006]), Ireland (Saoirse Nic Gabhainn), Latvia (Ieva Ranka [1997/1998] and Iveta Pudule [2005/2006]), Lithuania (Apolinaras Zaborskis), Norway (Oddrun Samdal), Poland (Barbara Woynarowska [1997/1998] and Joanna Mazur [2005/2006]), Portugal (Margarida Gaspar De Matos), Russian Federation (Alexander Komkov), Sweden (Ulla Marklund [1997/1998] and Lilly Eriksson [2005/2006]), Switzerland (Beatrice Janin Jacquat [1997/1998] and Emmanuel Kuntsche [2005/2006]), Ukraine (Olga Balakireva), United Kingdom (England: Antony Morgan; Scotland: Candace Currie; Wales: Chris Roberts), and United States (Mary Overpeck [1997/1998] and Ronald Iannotti [2005/2006]). NR 29 TC 54 Z9 54 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD FEB PY 2011 VL 165 IS 2 BP 152 EP 158 DI 10.1001/archpediatrics.2010.191 PG 7 WC Pediatrics SC Pediatrics GA 717KH UT WOS:000287042100009 PM 20921343 ER PT J AU Greinix, HT Loddenkemper, C Pavletic, SZ Holler, E Socie, G Lawitschka, A Halter, J Wolff, D AF Greinix, Hildegard T. Loddenkemper, Christoph Pavletic, Steven Z. Holler, Ernst Socie, Gerard Lawitschka, Anita Halter, Joerg Wolff, Daniel TI Diagnosis and Staging of Chronic Graft-versus-Host Disease in the Clinical Practice SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic GVHD; Staging; Severity scoring ID CONSENSUS DEVELOPMENT PROJECT; STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; BONE-MARROW-TRANSPLANTATION; CHRONIC GVHD; BRONCHIOLITIS OBLITERANS; CRITERIA; TRIALS; MULTICENTER; SURVIVAL AB Based on expert opinion and retrospective data the National Institutes of Health (NIH) Consensus Development Project proposed criteria for diagnosis and staging of both overall severity as well as organ severity of chronic graft-versus-host disease (cGVHD) for use in clinical trials. In 2008, representatives of German and Austrian allogeneic hematopoietic stem cell transplant (HSCT) centers established a study group on cGVHD during the annual meeting of the German Working Group on Bone Marrow and Blood Stem Cell Transplantation (DAG-KBT) to intensify a dialog among HSCT physicians, pathologists, and medical consultants focusing on the usefulness of the NIH consensus criteria for patient care in clinical practice and to promote collaborations between HSCT centers as well as different medical specialities involved in HSCT. We first conducted a survey of current practices of diagnosis, staging, and overall grading of cGVHD in daily clinical routine by sending an electronic questionnaire to the heads of the HSCT centers. During 3 meetings in 2009, more representatives of allogeneic HSCT centers were included into the discussion process, resulting in 81% participation representing 88% of all allogeneic HSCT activities in Germany, Austria, and Switzerland. During the third consensus meeting held in Regensburg, Germany, from November 6 to November 7, 2009, important agreements were achieved among participant having a strong impact on care of patients with cGVHD. Areas of disagreement such as distinction between classical NIH cGVHD and overlap syndrome or assignment of liver GVHD after day 100 to acute or chronic category will be further assessed in prospective observational studies among participants in the near future. Bioi Blood Marrow Transplant 17: 167-175 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Greinix, Hildegard T.] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria. [Loddenkemper, Christoph] Charite, Inst Pathol, Res Ctr ImmunoSci RCIS, D-13353 Berlin, Germany. [Loddenkemper, Christoph] Tech Univ Muenchen, Inst Pathol, Munich, Germany. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Holler, Ernst; Wolff, Daniel] Univ Regensburg, Dept Hematol & Oncol, D-8400 Regensburg, Germany. [Socie, Gerard] Hop St Louis, Serv Hematol Greffe, Paris, France. [Socie, Gerard] Hop St Louis, INSERM, Paris, France. [Lawitschka, Anita] St Anna Childrens Hosp, Dept Stem Cell Transplantat, A-1090 Vienna, Austria. [Halter, Joerg] Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. RP Greinix, HT (reprint author), Med Univ Wien, Innere Med Klin 1, Knochenmarktransplanta Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM hildegard.greinix@meduniwien.ac.at RI Halter, Joerg/C-9487-2012 FU Jose Carreras Foundation; European Commission [037703] FX The authors are grateful to Stephanie Lee, Mohamad Mohty, and Sharon Elad for their contributions and would like to thank all participants of the consensus meetings for their valuable input. The conference in Regensburg was supported by the Jose Carreras Foundation project "Competence centre Regensburg." The authors are grateful to the German Registry of Stem Cell Transplantation (DRST), the Austrian Registry of Stem Cell Transplantation (ASCT), and die Swiss National Stem Cell Transplant Registry for providing the information on annual HSCT numbers in these countries.; H.T. was supported by European Commission Grant 037703 STEMDIAGNOSTICS. NR 35 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 BP 167 EP 175 DI 10.1016/j.bbmt.2010.07.017 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JW UT WOS:000287350400002 PM 20691801 ER PT J AU Garantziotis, S AF Garantziotis, S. TI Modulation of plasma complement by the initial dose of epirubicin/docetaxel therapy in breast cancer and its predictive value SO BRITISH JOURNAL OF CANCER LA English DT Letter ID ALPHA-TRYPSIN INHIBITOR; PROTEINS C1 [Garantziotis, S.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Garantziotis, S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Garantziotis, S (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, POB 12233,MD-CU01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM garantziotis@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 8 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 1 PY 2011 VL 104 IS 3 BP 542 EP 542 DI 10.1038/sj.bjc.6606068 PG 1 WC Oncology SC Oncology GA 722IY UT WOS:000287427100025 PM 21224852 ER PT J AU Schiffman, M AF Schiffman, Mark TI The Need for Forward-Looking Decision Analyses to Guide Cervical Cancer Prevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID HUMAN-PAPILLOMAVIRUS; WOMEN; COLPOSCOPY; RISK C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7012, Rockville, MD 20852 USA. EM schiffmm@mail.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 2 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 FEB PY 2011 VL 20 IS 2 BP 219 EP 220 DI 10.1158/1055-9965.EPI-10-1130 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 717CU UT WOS:000287021400001 PM 21300615 ER PT J AU Zhou, J Enewold, L Zahm, SH Devesa, SS Anderson, WF Potter, JF McGlynn, KA Zhu, KM AF Zhou, Jing Enewold, Lindsey Zahm, Shelia H. Devesa, Susan S. Anderson, William F. Potter, John F. McGlynn, Katherine A. Zhu, Kangmin TI Melanoma Incidence Rates among Whites in the U.S. Military SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONMELANOMA SKIN-CANCER; VITAMIN-D; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; SUN PROTECTION; UNITED-STATES; TANNING BEDS; RISK-FACTORS; EPIDEMIOLOGY; PREVENTION AB Background: The U. S. Military and general populations may differ in the exposure to sunlight and other risk factors for melanoma and therefore the incidence rates of melanoma may be different in these two populations. However, few studies have compared melanoma incidence rates and trends over time between the military and the general population. Methods: Melanoma incidence rates from 1990 to 2004 among white active-duty military personnel and the general U. S. population were compared using data from the Department of Defense Automated Central Tumor Registry and the National Cancer Institute Surveillance, Epidemiology, and End Results program. Results: Age-adjusted melanoma rates overall were significantly lower in the military than in the general population; the incidence rate ratio was 0.75 for men and 0.56 for women. Age-specific rates, however, were significantly lower among individuals younger than 45 years, but significantly higher among those 45 years or older (P < 0.05). Melanoma incidence increased from 1990-1994 to 2000-2004 in both populations, with the most rapid increase (40%) among younger men in the military. Melanoma incidence rates also varied by branch of military service; rates were highest in the air force. Conclusion: These results suggest that melanoma incidence rate patterns differ between the military and the general population. Impact: Further studies of risk factors for melanoma in the military are needed to explain these findings. Cancer Epidemiol Biomarkers Prev; 20(2); 318-23. (C)2010 AACR. C1 [Zhou, Jing; Enewold, Lindsey; Potter, John F.; Zhu, Kangmin] Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. [Zahm, Shelia H.; Devesa, Susan S.; Anderson, William F.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Potter, John F.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Zhu, KM (reprint author), Walter Reed Army Med Ctr, US Mil Canc Inst, Bldg 1,Suite A-109,6900 Georgia Ave NW, Washington, DC 20307 USA. EM Kangmin.zhu@amedd.army.mil RI Zahm, Shelia/B-5025-2015 FU United States Military Cancer Institute via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine; Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute FX This research was supported by the United States Military Cancer Institute via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine and by the Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute. NR 44 TC 4 Z9 5 U1 0 U2 8 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 FEB PY 2011 VL 20 IS 2 BP 318 EP 323 DI 10.1158/1055-9965.EPI-10-0869 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 717CU UT WOS:000287021400014 PM 21148122 ER PT J AU Douglas, JB Silverman, DT Weinstein, SJ Graubard, BI Pollak, MN Tao, YZ Virtamo, J Albanes, D Stolzenberg-Solomon, RZ AF Douglas, Jason B. Silverman, Debra T. Weinstein, Stephanie J. Graubard, Barry I. Pollak, Michael N. Tao, Yuzhen Virtamo, Jarmo Albanes, Demetrius Stolzenberg-Solomon, Rachael Z. TI Serum C-Reactive Protein and Risk of Pancreatic Cancer in Two Nested, Case-Control Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DUCTAL ADENOCARCINOMA; COLORECTAL-CANCER; INFLAMMATORY RESPONSE; SCREENING TRIAL; MALE SMOKERS; VITAMIN-D; REPRODUCIBILITY; QUESTIONNAIRE; PROSTATE; PLASMA AB Background: Many epidemiologic studies have examined the association between C-reactive protein (CRP) and risk of cancer with inconsistent results. Methods: We conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to test whether prediagnostic circulating CRP concentrations were associated with pancreatic adenocarcinoma. Between 1985 and 2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in PLCO. Controls (n = 510 in ATBC, n = 374 in PLCO) were alive at the time the case was diagnosed and were matched by age, date of blood draw, sex, and race. We used conditional logistic regression adjusted for smoking to calculate OR and 95% CI for pancreatic cancer. Results: CRP concentrations (ng/mL) tended to be inversely or not associated with pancreatic cancer risk in ATBC, PLCO, and combined analyses [per standardized quintile increase in CRP, continuous OR = 0.94 (95% CI, 0.89-0.99), OR = 0.99 (95% CI, 0.95-1.04), OR = 0.98 (95% CI, 0.95-1.01), respectively]. In combined analyses, we observed a significant interaction (P(interaction) = 0.02) such that inverse associations were suggestive in younger (OR = 0.95; 95% CI, 0.90-1.01), but not older, participants. Conclusion: Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer. Impact: Our results highlight the importance of investigating more specific biomarkers for inflammation that may reflect the biological mechanisms underlying pancreatic cancer in prospective cohort studies. Cancer Epidemiol Biomarkers Prev; 20(2); 359-69. (C)2010 AACR. C1 [Douglas, Jason B.; Weinstein, Stephanie J.; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Dept Hlth & Human Serv, Rockville, MD USA. [Silverman, Debra T.] NCI, Occupat Epidemiol Branch, Dept Hlth & Human Serv, Rockville, MD USA. [Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. [Pollak, Michael N.; Tao, Yuzhen] McGill Univ, Jewish Gen Hosp, Cancer Prevent Program, Montreal, PQ H3T 1E2, Canada. [Virtamo, Jarmo] Natl Inst Hlth & Welfare, Dept Chron Dis Prevent, Helsinki, Finland. RP Stolzenberg-Solomon, RZ (reprint author), 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015 OI Pollak, Michael/0000-0003-3047-0604; FU National Institutes of Health, Division of Cancer Epidemiology and Genetics; National Cancer Institute, Department of Health and Human Services FX This study was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services. NR 31 TC 10 Z9 11 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 FEB PY 2011 VL 20 IS 2 BP 359 EP 369 DI 10.1158/1055-9965.EPI-10-1024 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 717CU UT WOS:000287021400018 PM 21173171 ER PT J AU Liu, AM Yang, JL Gonzalez, FJ Cheng, GQ Dai, RK AF Liu, Aiming Yang, Julin Gonzalez, Frank J. Cheng, Gary Q. Dai, Renke TI Biphasic Regulation of Intracellular Calcium by Gemfibrozil Contributes to Inhibiting L6 Myoblast Differentiation: Implications for Clinical Myotoxicity SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIPID-LOWERING DRUGS; SKELETAL-MUSCLE; MITOCHONDRIAL-FUNCTION; GLUCURONIDE INHIBIT; HEPATIC-UPTAKE; STATINS; RAT; RHABDOMYOLYSIS; CERIVASTATIN; APOPTOSIS AB Gemfibrozil is the most myotoxic fibrate drug commonly used for dyslipidemia, but the mechanism is poorly understood. The current study revealed that gemfibrozil inhibits myoblast differentiation through the regulation of intracellular calcium ([Ca(2+)]i) as revealed in L6 myoblasts by use of laser scan confocal microscopy and flow cytometry using Fluo-4 AM as a probe. Gemfibrozil at 20-400 mu M, could regulate [Ca(2+)]i in L6 cells in a biphasic manner, and sustained reduction was observed when the concentration reached 200 mu M. Inhibition of L6 differentiation by gemfibrozil was concentration-dependent with maximal effect noted between 200 and 400 mu M, as indicated by creatine kinase activities and the differentiation index, respectively. In differentiating L6 myoblasts, gemfibrozil at concentrations below 400 mu M led to no significant signs of apoptosis or cytotoxicity, whereas differentiation, inhibited by 200 mu M gemfibrozil, was only partially recovered. A good correlation was noted between gemfibrozil concentrations that regulate [Ca(2+)]i and inhibit L6 myoblasts differentiation, and both are within the range of total serum concentrations found in the clinic. These data suggest a potential pharmacodynamic effect of gemfibrozil on myogenesis as a warning sign, in addition to the complex pharmacokinetic interactions. It is also noteworthy that mobilization of [Ca(2+)]i by gemfibrozil may trigger complex biological responses besides myocyte differentiation. Information revealed in this study explores the mechanism of gemfibrozil-induced myotoxicity through the regulation of intracellular calcium. C1 [Dai, Renke] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510641, Guangdong, Peoples R China. [Liu, Aiming] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China. [Yang, Julin] Ningbo Coll Hlth Sci, Ningbo 315100, Zhejiang, Peoples R China. [Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. [Cheng, Gary Q.] S China Ctr Innovat Pharmaceut, Guangzhou 510006, Guangdong, Peoples R China. RP Dai, RK (reprint author), S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510641, Guangdong, Peoples R China. EM renke_dai@yahoo.com FU Zhejiang Provincial Education Department [Y200906207]; Ningbo Natural Science Foundation [2010A610069]; Chinese government [2008AA02Z314, 2009DFA31530, 2009ZX09301-015] FX This study was supported by Scientific Research Fund of Zhejiang Provincial Education Department [grant Y200906207], Ningbo Natural Science Foundation [grant 2010A610069], and Chinese government grants [2008AA02Z314, 2009DFA31530 and 2009ZX09301-015]. NR 39 TC 4 Z9 6 U1 2 U2 7 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 FEB PY 2011 VL 24 IS 2 BP 229 EP 237 DI 10.1021/tx100312h PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 721XP UT WOS:000287391400011 PM 21175127 ER PT J AU Huang, MC Greig, NH Luo, WN Tweedie, D Schwartz, JB Longo, DL Ferrucci, L Ershler, WB Goetzl, EJ AF Huang, Mei-Chuan Greig, Nigel H. Luo, Weinning Tweedie, David Schwartz, Janice B. Longo, Dan L. Ferrucci, Luigi Ershler, William B. Goetzl, Edward J. TI Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide SO CLINICAL IMMUNOLOGY LA English DT Article DE Human; T lymphocytes; Cytokines; Proliferation; Apoptosis; Chemotaxis ID ALPHA INHIBITORY-ACTIVITY; IMMUNOMODULATORY DRUGS; TNF-ALPHA; DENDRITIC CELLS; AGED HUMANS; THALIDOMIDE; CD4(+); NAIVE; MEMORY; INTERLEUKIN-2 AB Lenalidomide, an analog of thalidomide, modified responses of stimulated T cells from healthy young (ages 21-40 years) and (>= old age 65 years) subjects. At 0.03 mu M to 1 mu M, lenalidomide enhanced generation of IL-2 and IFN-gamma by T cell receptor-stimulated T cells of young subjects up to respective maximum increases of 17-fold and three-fold, but at 0.3 mu M and 1 mu M suppressed IL-17 generation. The same concentrations of lenalidomide enhanced IL-2 and IFN-gamma generation by stimulated T cells of old subjects more, with greater respective maximal increases of up to 120-fold and six-fold, without suppressing IL-17 generation. Lenalidomide enhanced proliferation and suppressed apoptosis of stimulated T cells from old subjects, by IL-2-dependent mechanisms, and restored diminished T cell chemotactic responses to CCL21 and sphingosine 1-phosphate. The reversal of T cell abnormalities of immunosenescence by low concentrations of lenalidomide suggest a potential for improvement of immunity in the elderly. (C) 2010 Elsevier Inc. All rights reserved. C1 [Goetzl, Edward J.] Univ Calif San Francisco, Med Ctr, Dept Med, San Francisco, CA 94143 USA. [Greig, Nigel H.; Luo, Weinning; Tweedie, David; Longo, Dan L.; Ferrucci, Luigi; Ershler, William B.] NIA, NIH, Baltimore, MD 21224 USA. [Goetzl, Edward J.] Univ Calif San Francisco, Dept Microbiol Immunol, San Francisco, CA 94143 USA. RP Goetzl, EJ (reprint author), Univ Calif San Francisco, Med Ctr, Dept Med, Room UB8B UC,Box 0711,533 Parnassus & 4th Ave, San Francisco, CA 94143 USA. EM edward.goetzl@ucsf.edu FU Kenneth Rainin Foundation; National Institute on Aging FX This research was supported by a grant from the Kenneth Rainin Foundation and by the Intramural Research Program of the National Institute on Aging. The authors are grateful to Judith H. Goetzl for preparation of graphics and for textual editing. The authors declare no conflicts of interest. Authors' contributions: N.H.G., D.L.L., J.B.S. and E.J.G. designed research; L.F., W.B.E.,. J.B.S. and E.J.G. identified and evaluated subjects; D.T., W.L. and N.H.G. synthesized and analyzed compounds: M.-C. H. and E.J.G. performed research and analyzed data; E.J.G., L.F. and J.B.S. wrote the paper. NR 49 TC 8 Z9 9 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. PD FEB PY 2011 VL 138 IS 2 BP 201 EP 211 DI 10.1016/j.clim.2010.11.002 PG 11 WC Immunology SC Immunology GA 719QP UT WOS:000287223800009 PM 21130040 ER PT J AU Schecter, A Smith, S Colacino, J Malik, N Opel, M Paepke, O Birnbaum, L AF Schecter, Arnold Smith, Sarah Colacino, Justin Malik, Noor Opel, Matthias Paepke, Olaf Birnbaum, Linda TI Contamination of U.S. Butter with Polybrominated Diphenyl Ethers from Wrapping Paper SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE butter; dietary intake; food; PBDEs; United States ID DIETARY-INTAKE; HUMAN EXPOSURE; UNITED-STATES; MARKET BASKET; HOUSE-DUST; POLYCHLORINATED DIOXINS; AGENT-ORANGE; INDOOR DUST; PBDE LEVELS; FOOD AB OBJECTIVES: Our aim was to report the first known incidence of U.S. butter contamination with extremely high levels of polybrominated diphenyl ethers (PBDEs). METHODS: Ten butter samples were individually analyzed for PBDEs. One of the samples and its paper wrapper contained very high levels of higher-brominated PBDEs. Dietary estimates were calculated using the 2007 U.S. Department of Agriculture Loss-Adjusted Food Availability data, excluding the elevated sample. RESULTS: The highly contaminated butter sample had a total upper bound PBDE level of 42,252 pg/g wet weight (ww). Levels of brominated diphenyl ether (BDE)-206, -207, and -209 were 2,000, 2,290, and 37,600 pg/g ww, respectively. Its wrapping paper contained a total upper-bound PBDE concentration of 804,751 pg/g ww, with levels of BDE-206, -207, and -209 of 51,000, 11,700, and 614,000 pg/g, respectively. Total PBDE levels in the remaining nine butter samples ranged from 180 to 1,212 pg/g, with geometric mean of 483 and median of 284 pg/g. Excluding the outlier, total PBDE daily intake from all food was 22,764 pg/day, lower than some previous U.S. dietary intake estimates. CONCLUSION: Higher-brominated PBDE congeners were likely transferred from contaminated wrapping paper to butter. A larger representative survey may help determine how frequently PBDE contamination occurs. Sampling at various stages in food production may identify contamination sources and reduce risk. C1 [Schecter, Arnold; Smith, Sarah; Malik, Noor] Univ Texas Sch Publ Hlth Dallas, Dallas, TX 75390 USA. [Colacino, Justin] Univ Michigan Sch Publ Hlth, Ann Arbor, MI USA. [Opel, Matthias; Paepke, Olaf] Eurofins GfA GmbH, Hamburg, Germany. [Birnbaum, Linda] NCI, Natl Inst Environm Sci, NIH, Dept Hlth & Human Resources, Res Triangle Pk, NC USA. RP Schecter, A (reprint author), Univ Texas Sch Publ Hlth Dallas, 5323 Harry Hines,V8-112, Dallas, TX 75390 USA. EM arnold.schecter@utsouthwestern.edu FU Gustavus and Louise Pfeiffer Research Foundation FX The authors acknowledge the Gustavus and Louise Pfeiffer Research Foundation for their generous grant, which funded this research. NR 38 TC 14 Z9 14 U1 1 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2011 VL 119 IS 2 BP 151 EP 154 DI 10.1289/ehp.1002604 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 714IP UT WOS:000286803400014 PM 21138809 ER PT J AU Purdue, MP Bakke, B Stewart, P De Roos, AJ Schenk, M Lynch, CF Bernstein, L Morton, LM Cerhan, JR Severson, RK Cozen, W Davis, S Rothman, N Hartge, P Colt, JS AF Purdue, Mark P. Bakke, Berit Stewart, Patricia De Roos, Anneclaire J. Schenk, Maryjean Lynch, Charles F. Bernstein, Leslie Morton, Lindsay M. Cerhan, James R. Severson, Richard K. Cozen, Wendy Davis, Scott Rothman, Nathaniel Hartge, Patricia Colt, Joanne S. TI A Case-Control Study of Occupational Exposure to Trichloroethylene and Non-Hodgkin Lymphoma SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer; non-Hodgkin lymphoma; occupational; solvents; trichloroethylene ID CANCER INCIDENCE; ORGANIC-SOLVENTS; NONDIFFERENTIAL MISCLASSIFICATION; AEROSPACE WORKERS; RISK; MORTALITY; COHORT; CHLOROPHENOLS; EPIDEMIOLOGY; CHEMICALS AB BACKGROUND: Previous epidemiologic findings suggest an association between exposure to trichloro-ethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL). OBJECTIVES: We investigated the association between occupational TCE exposure and NHL within a population-based case-control study using detailed exposure assessment methods. METHODS: Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group. RESULTS: We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1-6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0-5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose-response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0-4.7). CONCLUSIONS: Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated. C1 [Purdue, Mark P.; Bakke, Berit; Stewart, Patricia; Morton, Lindsay M.; Rothman, Nathaniel; Hartge, Patricia; Colt, Joanne S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Bakke, Berit] Natl Inst Occupat Hlth, Oslo, Norway. [Stewart, Patricia] Stewart Exposure Assessments LLC, Arlington, VA USA. [De Roos, Anneclaire J.; Davis, Scott] Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. [De Roos, Anneclaire J.; Davis, Scott] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Schenk, Maryjean; Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Cerhan, James R.] Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Cozen, Wendy] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8114,6120 Execut Blvd, Rockville, MD 20892 USA. EM purduem@mail.nih.gov RI Morton, Lindsay/B-5234-2015; Purdue, Mark/C-9228-2016; OI Morton, Lindsay/0000-0001-9767-2310; Purdue, Mark/0000-0003-1177-3108; Cerhan, James/0000-0002-7482-178X FU NIH, National Cancer Institute; Public Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, with Public Health Service contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, and N02-PC-71105. NR 44 TC 22 Z9 24 U1 2 U2 14 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2011 VL 119 IS 2 BP 232 EP 238 DI 10.1289/ehp.1002106 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 714IP UT WOS:000286803400026 PM 21370516 ER PT J AU Jung, P AF Jung, Paul TI Product Biomonitoring and Responsible Reporting SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID ETHICS C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Jung, P (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM jungp@niehs.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2011 VL 119 IS 2 BP A58 EP A59 DI 10.1289/ehp.1003355 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 714IP UT WOS:000286803400004 PM 21288807 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI The virus world, horizontal gene transfer vehicles and the perennial arms race SO ENVIRONMENTAL MICROBIOLOGY REPORTS LA English DT Editorial Material ID TRANSFER AGENT; CRISPR; PROKARYOTES; BACTERIA; DEFENSE; ARCHAEA C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 16 TC 0 Z9 0 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1758-2229 J9 ENV MICROBIOL REP JI Environ. Microbiol. Rep. PD FEB PY 2011 VL 3 IS 1 BP 10 EP 12 PG 3 WC Environmental Sciences; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 718RS UT WOS:000287144400006 ER PT J AU Manalo, KB Choong, PFM Becerra, SP Dass, CR AF Manalo, Katrina B. Choong, Peter F. M. Becerra, S. Patricia Dass, Crispin R. TI Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: a patent perspective SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Article DE angiogenesis; cancer; drug; patent; PEDF; PEDF receptor; therapy ID FACTOR PEDF; RETINOBLASTOMA CELLS; OSTEOSARCOMA; GROWTH; BINDING; ANGIOGENESIS; SERPIN; PHOTORECEPTORS; FIBROBLASTS; EXPRESSION AB Traditional forms of cancer therapy, which include chemotherapy, have largely been overhauled due to the significant degree of toxicity they pose to normal, otherwise healthy tissue. It is hoped that the use of biological agents, most of which are endogenously present in the body, will lead to safer treatment outcomes, without sacrificing efficacy. The finding that pigment epithelium-derived factor (PEDF), a naturally-occurring protein, is a potent angiogenesis inhibitor has become the basis for studying the role of PEDF in tumours that are highly resistant to chemotherapy. The determination of the direct role of PEDF against cancer paves the way for understanding and developing PEDF as a novel drug. This review focuses on the patent applications behind testing the anticancer therapeutic effect of PEDF via its receptors as an antiangiogenic agent and as a direct anticancer agent. The majority of the PEDF patents describe the antiangiogenic ability and usage of recombinant vectors as the mode of treatment delivery. PEDF's therapeutic potential against different diseases and the discovery of its receptors open possibilities for improving PEDF-based peptide design and drug delivery modes. C1 [Dass, Crispin R.] Victoria Univ, Sch Biomed & Hlth Sci, St Albans, Vic, Australia. [Manalo, Katrina B.] St Vincents Hosp, Dept Orthopaed, Sydney, NSW, Australia. [Manalo, Katrina B.] Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic 3010, Australia. [Choong, Peter F. M.] Univ Melbourne, Dept Surg, Melbourne, Vic 3010, Australia. [Choong, Peter F. M.] Peter MacCallum Canc Inst, Sarcoma Serv, Melbourne, Vic, Australia. [Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Dass, CR (reprint author), Victoria Univ, Sch Biomed & Hlth Sci, St Albans, Vic, Australia. EM crispin.dass@vu.edu.au FU Intramural NIH HHS [ZIA EY000306-16, ZIA EY000306-18] NR 49 TC 18 Z9 18 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD FEB PY 2011 VL 21 IS 2 BP 121 EP 130 DI 10.1517/13543776.2011.545347 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 720PB UT WOS:000287291500001 PM 21204726 ER PT J AU Park, JK AF Park, John K. TI Recurrent Glioblastoma: Not Only Surgery Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20889 USA. RP Park, JK (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20889 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2011 VL 29 IS 4 BP R103 EP R103 DI 10.1200/JCO.2010.32.7676 PG 1 WC Oncology SC Oncology GA 717XR UT WOS:000287081800015 ER PT J AU Sugaya, M Reed, S Rose, PP de la Motte, S Raggo, CM Kurtz, SE Moses, AV Fruh, K Blauvelt, A AF Sugaya, Makoto Reed, Stacy Rose, Patrick P. de la Motte, Stacy Raggo, Camilo M. Kurtz, Stephen E. Moses, Ashlee V. Frueh, Klaus Blauvelt, Andrew TI Kaposi's sarcoma and human dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus express CCL21 SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Letter ID CHEMOKINE RECEPTOR CCR7; ONCOSTATIN-M C1 [Sugaya, Makoto] Univ Tokyo, Dept Dermatol, Fac Med, Bunkyo Ku, Tokyo 1138655, Japan. [Sugaya, Makoto; Blauvelt, Andrew] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Reed, Stacy; de la Motte, Stacy; Kurtz, Stephen E.; Blauvelt, Andrew] VA Med Ctr, Dermatol Serv, Portland, OR USA. [Rose, Patrick P.; Raggo, Camilo M.; Moses, Ashlee V.; Frueh, Klaus] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. [Rose, Patrick P.; Raggo, Camilo M.; Moses, Ashlee V.; Frueh, Klaus; Blauvelt, Andrew] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Blauvelt, Andrew] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. RP Sugaya, M (reprint author), Univ Tokyo, Dept Dermatol, Fac Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM sugayam-der@h.u-tokyo.ac.jp FU NCI NIH HHS [R01 CA099906, R01CA99906]; NIAID NIH HHS [R01CA/AI94011]; NIAMS NIH HHS [R21 AR054495] NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD FEB PY 2011 VL 61 IS 2 BP 139 EP 142 DI 10.1016/j.jdermsci.2010.11.017 PG 4 WC Dermatology SC Dermatology GA 724BG UT WOS:000287550500011 PM 21176872 ER PT J AU Edwards, DRV Romero, R Kusanovic, JP Hassan, SS Mazaki-Tovi, S Vaisbuch, E Kim, CJ Erez, O Chaiworapongsa, T Pearce, BD Bartlett, J Friel, LA Salisbury, BA Anant, MK Vovis, GF Lee, MS Gomez, R Behnke, E Oyarzun, E Tromp, G Menon, R Williams, SM AF Edwards, Digna R. Velez Romero, Roberto Kusanovic, Juan Pedro Hassan, Sonia S. Mazaki-Tovi, Shali Vaisbuch, Edi Kim, Chong Jai Erez, Offer Chaiworapongsa, Tinnakorn Pearce, Brad D. Bartlett, Jacquelaine Friel, Lara A. Salisbury, Benjamin A. Anant, Madan Kumar Vovis, Gerald F. Lee, Min Seob Gomez, Ricardo Behnke, Ernesto Oyarzun, Enrique Tromp, Gerard Menon, Ramkumar Williams, Scott M. TI Polymorphisms in maternal and fetal genes encoding for proteins involved in extracellular matrix metabolism alter the risk for small-for-gestational-age SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE DNA variants; extracellular matrix; genetic association study; genomics; genotype; haplotype; high dimensional biology; SNP; intrauterine growth restriction; genetic epidemiology; complex disease ID INTRAUTERINE GROWTH RESTRICTION; UTERINE ARTERY DOPPLER; LOW-BIRTH-WEIGHT; MULTIFACTOR-DIMENSIONALITY REDUCTION; HARDY-WEINBERG EQUILIBRIUM; FALSE DISCOVERY RATE; SIB-PAIR LINKAGE; PLACENTAL GROWTH; FACTOR RECEPTOR-1; ANGIOGENIC FACTORS AB Objective. To examine the association between maternal and fetal genetic variants and small-for-gestational-age (SGA). Methods. A case-control study was conducted in patients with SGA neonates (530 maternal and 436 fetal) and controls (599 maternal and 628 fetal); 190 candidate genes and 775 SNPs were studied. Single-locus, multi-locus and haplotype association analyses were performed on maternal and fetal data with logistic regression, multifactor dimensionality reduction (MDR) analysis, and haplotype-based association with 2 and 3 marker sliding windows, respectively. Ingenuity pathway analysis (IPA) software was used to assess pathways that associate with SGA. Results. The most significant single-locus association in maternal data was with a SNP in tissue inhibitor of metalloproteinase 2 (TIMP2) (rs2277698 OR = 1.71, 95% CI [1.26-2.32], p = 0.0006) while in the fetus it was with a SNP in fibronectin 1 isoform 3 preproprotein (FN1) (rs3796123, OR = 1.46, 95% CI [1.20-1.78], p = 0.0001). Both SNPs were adjusted for potential confounders (maternal body mass index and fetal sex). Haplotypc analyses resulted in associations in alpha 1 type I collagen preproprotein (COL1A1, rs1007086-rs2141279-rs17639446, global p = 0.006) in mothers and FN1 (rs2304573-rs1250204-rs1250215, global p = 0.045) in fetuses. Multi-locus analyses with MDR identified a two SNP model with maternal variants collagen type V alpha 2 (COL5A2) and plasminogen activator urokinase (PLAU) predicting SGA outcome correctly 59% of the time (p = 0.035). Conclusions. Genetic variants in extracellular matrix-related genes showed significant single-locus association with SGA. These data are consistent with other studies that have observed elevated circulating fibronectin concentrations in association with increased risk of SGA. The present study supports the hypothesis that DNA variants can partially explain the risk of SGA in a cohort of Hispanic women. C1 [Edwards, Digna R. Velez] Vanderbilt Univ, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Romero, Roberto; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn; Friel, Lara A.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn; Friel, Lara A.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto; Tromp, Gerard] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Pearce, Brad D.; Menon, Ramkumar] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Bartlett, Jacquelaine; Williams, Scott M.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Salisbury, Benjamin A.; Anant, Madan Kumar] PGxHealth LLC, New Haven, CT USA. [Vovis, Gerald F.] Helix Therapeut LLC, New Haven, CT USA. [Lee, Min Seob] GenomeCare Inc, San Diego, CA USA. [Gomez, Ricardo; Behnke, Ernesto] Hosp Dr Sotero del Rio, CEDIP Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Santiago, Chile. [Gomez, Ricardo; Oyarzun, Enrique] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. [Williams, Scott M.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu; smwilliams@chgr.mc.vanderbilt.edu RI Williams, Scott/B-9491-2012; Velez Edwards, Digna/C-1090-2012; Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Vaisbuch, Edi/0000-0002-8400-9031; Salisbury, Benjamin/0000-0003-0796-6492 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 162 TC 6 Z9 9 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD FEB PY 2011 VL 24 IS 2 BP 362 EP 380 DI 10.3109/14767058.2010.497572 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 716XZ UT WOS:000287008100031 PM 20617897 ER PT J AU Liu, XD Sun, J Sun, LG Liu, WQ Wang, YH AF Liu, Xiaodong Sun, Jing Sun, Liguang Liu, Wenqi Wang, Yuhong TI Reflectance spectroscopy: a new approach for reconstructing penguin population size from Antarctic ornithogenic sediments SO JOURNAL OF PALEOLIMNOLOGY LA English DT Article DE Reflectance spectroscopy; Ornithogenic sediments; Historical penguin populations; Antarctica ID NEAR-INFRARED SPECTROSCOPY; LAKE-SEDIMENTS; ORGANIC-MATTER; SOIL PROPERTIES; ARDLEY ISLAND; WATER; CONTAMINATION; FEASIBILITY; MARITIME; SPECTRA AB Reflectance spectroscopy has several advantages compared to traditional chemical methods in paleolimnology. It requires little cost, involves minimal or no sample preparation and is rapid. There has, however, been limited use of reflectance spectroscopy in polar paleolimnological studies. This paper explores the application of reflectance spectroscopy to reconstruct historical changes in penguin population size in the maritime Antarctic. Two ornithogenic sediment cores on Ardley Island, Antarctica were analyzed. Penguin droppings and weathered soils were analyzed as reference materials. Principal component analysis and linear mixing modeling were performed on the spectral data to estimate the proportion of penguin guano in the sediments and these values were used to infer historical penguin population numbers. Historical penguin population size versus time, reconstructed from reflectance spectra, and population numbers inferred from previous geochemical analysis of bio-elements, were quite similar. Our results illustrate the feasibility of rapidly inferring historical changes in penguin population size using reflectance spectroscopy on Antarctic ornithogenic sediments. Our findings suggest that this technique has potential for reconstructing past population numbers of other seabirds and mammals using lake sediments influenced by animal excrement. C1 [Liu, Xiaodong; Sun, Liguang] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Sun, Jing] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA. [Liu, Wenqi] Univ Sci & Technol China, Instruments Ctr Phys Sci, Hefei 230026, Anhui, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. RP Liu, XD (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM ycx@ustc.edu.cn RI Sun, Jing /B-9248-2017 OI Sun, Jing /0000-0002-0129-5184 FU National Natural Science Foundation [40876096, 41076123, 40730107, 40606003]; SOA Key Laboratory for Polar Science [KP2007002]; CAAA [20070202]; CAS FX We thank the Chinese Antarctic and Arctic Administration of National Oceanic Bureau for logistical support. This study was supported by the National Natural Science Foundation (Grant Nos. 40876096, 41076123, 40730107 and 40606003), open research fund from SOA Key Laboratory for Polar Science (KP2007002), the young fund for strategic research of the Chinese Polar Sciences from CAAA (No. 20070202), and the special fund for excellent PhD theses of CAS. We especially appreciate three anonymous reviewers for their critical reviews and careful corrections of this manuscript. NR 50 TC 9 Z9 10 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-2728 J9 J PALEOLIMNOL JI J. Paleolimn. PD FEB PY 2011 VL 45 IS 2 BP 213 EP 222 DI 10.1007/s10933-010-9493-6 PG 10 WC Environmental Sciences; Geosciences, Multidisciplinary; Limnology SC Environmental Sciences & Ecology; Geology; Marine & Freshwater Biology GA 712OV UT WOS:000286677000007 ER PT J AU Huang, T Sun, LG Wang, YH Kong, DM AF Huang, Tao Sun, Liguang Wang, Yuhong Kong, Deming TI Late Holocene Ad,lie penguin population dynamics at Zolotov Island, Vestfold Hills, Antarctica SO JOURNAL OF PALEOLIMNOLOGY LA English DT Article DE Adelie penguin; Antarctic climates; Ice core; Ornithogenic sediments; Western Antarctic Peninsula; Little Ice Age ID SEA-ICE EXTENT; CLIMATE-CHANGE; EASTERN ANTARCTICA; PALEONTOLOGICAL EVIDENCE; DIATOM ASSEMBLAGES; PENINSULA REGION; ADELIE PENGUINS; LAKE-SEDIMENTS; TRACE-ELEMENTS; ARDLEY ISLAND AB We inferred late Holocene Ad,lie penguin occupation history and population dynamics on Zolotov Island, Vestfold Hills, Antarctica, using geochemical data from a dated ornithogenic sediment core (ZOL4). Radiocarbon dates on fossil penguin bones in the core indicate that Ad,lie penguins occupied the island as early as 1,800 years before present (yr BP), following the retreat of the Sorsdal glacier. This occupation began similar to 1,200 years later than that observed at Ardley Island and King George Island, in the South Shetland Islands. Phosphorus was identified as the most indicative bio-element for penguin guano in core ZOL4, and was used to infer past penguin population dynamics. Around 1,800 years ago, the Ad,lie penguin populations at both Zolotov Island and Ardley Island increased rapidly and reached their highest levels similar to 1,000 yr BP. For the past similar to 900 years, the penguin populations at Zolotov Island have shown a general rising trend, with fluctuations, while those at Ardley Island have shown a moderate decreasing trend. The Ad,lie penguin populations at both Ardley Island and Zolotov Island showed a clear decline similar to 300 years ago, which we interpret as a response to the Little Ice Age, or a neoglacial cooling event. C1 [Huang, Tao; Sun, Liguang; Wang, Yuhong; Kong, Deming] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China. EM slg@ustc.edu.cn RI Huang, Tao/B-5915-2009 FU National Natural Science Foundation of China [40730107]; National Science and Technology Supporting Program [2006BAB18B07]; Major State Basic Research and Development Program of China (973 program) [2010CB428902]; Australian Antarctic Division Science Project [AAD2873] FX This study was funded by the National Natural Science Foundation of China (No. 40730107), the National Science and Technology Supporting Program (2006BAB18B07), the Major State Basic Research and Development Program of China (973 program, No. 2010CB428902) and the Australian Antarctic Division Science Project (AAD2873). We thank the Chinese Arctic and Antarctic Administration, Polar Research Institute of China, Australian Antarctic Division for logistical support in field, Dr. Renbin Zhu for collection of samples and Dr. William Cooper for assistance with radiocarbon dating. We especially thank the reviewers for their critical comments and Dr. Dominic Hodgson and Dr. Mark Brenner for their help in improving this manuscript. NR 65 TC 9 Z9 10 U1 3 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-2728 J9 J PALEOLIMNOL JI J. Paleolimn. PD FEB PY 2011 VL 45 IS 2 BP 273 EP 285 DI 10.1007/s10933-011-9497-x PG 13 WC Environmental Sciences; Geosciences, Multidisciplinary; Limnology SC Environmental Sciences & Ecology; Geology; Marine & Freshwater Biology GA 712OV UT WOS:000286677000011 ER PT J AU Simitsopoulou, M Roilides, E Georgiadou, E Paliogianni, F Walsh, TJ AF Simitsopoulou, Maria Roilides, Emmanuel Georgiadou, Elpiniki Paliogianni, Fotini Walsh, Thomas J. TI Differential transcriptional profiles induced by amphotericin B formulations on human monocytes during response to hyphae of Aspergillus fumigatus SO MEDICAL MYCOLOGY LA English DT Article DE monocytes; cytokines; chemokines; immunoregulation; gene arrays; ELISA ID INVASIVE PULMONARY ASPERGILLOSIS; HUMAN MONONUCLEAR-CELLS; TOLL-LIKE RECEPTORS; LIPID FORMULATIONS; HOST-DEFENSE; FUNGAL-INFECTIONS; CANDIDA-ALBICANS; GENE-EXPRESSION; MICROARRAY ANALYSIS; CYTOKINE BALANCE AB Amphotericin B formulations possess diverse immunomodulatory properties that may contribute to the activity of phagocytes against invasive aspergillosis. In this work we provide a novel set of data on different gene transcriptional profiles of monocytes exposed to the combination of Aspergillus fumigatus and amphotericin B formulations. We used pathway-specific microarray analysis, RT-PCR analysis and enzyme-linked immunosorbent assays to compare the effects of amphotericin B deoxycholate (DAMB) at 1 mu g/ml and amphotericin B lipid complex (ABLC) at 5 mu g/ml to assess gene expression of immune molecules of THP-1 cells exposed to A. fumigatus hyphae (AF) for 4 h. A. fumigatus hyphae at effector/target ratio 10/1 induced mostly chemotactic factors for monocyte recruitment. DAMB at 1 mu g/ml in the presence or absence of AF induced the most pronounced changes in pro-inflammatory and chemokine gene expression, while ABLC under the same conditions caused less dramatic effect. There was a reciprocal response of increased expression of the genes encoding IL-1 beta and IL-20 and decreased expression of IL-10, IL-2 and IL-3 in response of monocytes to both the hyphae and antifungal agents. These results demonstrate that amphotericin B formulations exert differential effects on genes encoding pro-inflammatory molecules, immunoregulatory molecules and chemokines by human monocytes during response to A. fumigatus and that these molecules may affect antifungal activity. C1 [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Coll, Transplantat Oncol Infect Dis Program, Div Infect Dis, New York, NY 10065 USA. [Walsh, Thomas J.] New York Presbyterian Hosp, New York, NY 10065 USA. [Simitsopoulou, Maria; Roilides, Emmanuel; Georgiadou, Elpiniki] Aristotle Univ Thessaloniki, Hippokrat Hosp, Sch Med, Infect Dis Lab,Dept Pediat 3, GR-54006 Thessaloniki, Greece. [Paliogianni, Fotini] Univ Patras, Sch Med, Dept Microbiol, GR-26110 Patras, Greece. [Roilides, Emmanuel; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), Cornell Univ, Weill Cornell Med Coll, Transplantat Oncol Infect Dis Program, Div Infect Dis, 1300 York Ave,Room A-421, New York, NY 10065 USA. EM thw2003@med.cornell.edu FU Enzon Pharmaceuticals Inc.; National Cancer Institute FX This research was supported in part by a research grant from Enzon Pharmaceuticals Inc. to the Aristotle University of Thessaloniki and by the intramural research program of the National Cancer Institute. NR 51 TC 6 Z9 6 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD FEB PY 2011 VL 49 IS 2 BP 176 EP 185 DI 10.3109/13693786.2010.510539 PG 10 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 722RH UT WOS:000287451500010 PM 20807031 ER PT J AU Chen, H You, MJ Jiang, Y Wang, W Li, L AF Chen, H. You, M. J. Jiang, Y. Wang, W. Li, L. TI RMI1 Attenuates Tumor Development and is Essential for Early Embryonic Survival SO MOLECULAR CARCINOGENESIS LA English DT Article DE tumor development; radiation; RMI1; bloom syndrome; genomic instability ID BLOOMS-SYNDROME GENE; HOMOLOGOUS RECOMBINATION; ESSENTIAL COMPONENT; P53-DEFICIENT MICE; HOLLIDAY JUNCTIONS; TOPOISOMERASE III; SYNDROME HELICASE; GENOME STABILITY; SYNDROME PROTEIN; BLM AB RMI1/BLAP75 (RecQ-mediated genome instability 1/Bloom-associated protein 75) is an OB-fold protein highly conserved from yeast to human. Previous studies showed that RMI1 is required for the stability of the BLM/RMI1/Top3 alpha complex and for the suppression of elevated sister chromatids exchange (SCE). The presence of RMI1 strongly stimulates Holliday dissolution activity of the Bloom helicase in vitro. The in vivo function of RMI1, however, remains largely undefined. To address this question, we generated RMI1 knockout mice through homologous replacement targeting. We found that, while RMI1(+/-) mice showed no obvious developmental phenotype, deletion of both mRMI1 alleles resulted in early embryonic lethality before implantation. To determine whether RMI1 plays a role in tumorigenesis, we generated RMI1/p53 double heterozygous mice and analyzed their onset of ionizing radiation-induced tumor development. RMI1(+/-)/p53(+/-) mice succumbed to tumor with a higher frequency and exhibited a substantially shortened survival when compared to the wild type, RMI1(+/-) and p53(+/-) cohorts. These results demonstrated a dual-role of RMI1 in embryonic development and tumor suppression. (C) 2010 Wiley-Liss, Inc. C1 [Li, L.] Univ Texas MD Anderson Canc Ctr, Unit 66, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [You, M. J.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Wang, W.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Li, L.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. RP Li, L (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 66, Dept Expt Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Jiang, Yingjun/I-8919-2014 FU National Cancer Institute [CA127945, CA097175]; UT MDACC; American Cancer Society IRG; UT MDACC IRG; Ladies Leukemia League; National Institute on Aging, National Institute of Health [Z01 AG000657-08] FX The authors wish to thank Dr. Gigi Lozano (Department of Genetics, UT MDACC) for critical suggestions to this work. The GEF Core facility provided ES cell selection and blastocyst injection services for the generation of the knockout mice. This work was supported, in whole or in part, by grants from the National Cancer Institute CA127945 and CA097175 (to L.L.) and UT MDACC Physician Scientist Award, American Cancer Society IRG, UT MDACC IRG and Ladies Leukemia League (to MJ.Y.). This work was also supported in part by the Intramural Research Program of the National Institute on Aging (Z01 AG000657-08), National Institute of Health (to W.W.). NR 37 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2011 VL 50 IS 2 BP 80 EP 88 DI 10.1002/mc.20694 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 715CG UT WOS:000286857400003 PM 21229605 ER PT J AU Moore, NM Kuhn, NZ Hanlon, SE Lee, JSH Nagahara, LA AF Moore, N. M. Kuhn, N. Z. Hanlon, S. E. Lee, J. S. H. Nagahara, L. A. TI De-convoluting cancer's complexity: using a 'physical sciences lens' to provide a different (clearer) perspective of cancer PREFACE SO PHYSICAL BIOLOGY LA English DT Editorial Material ID BIOLOGY C1 [Moore, N. M.; Kuhn, N. Z.; Hanlon, S. E.; Lee, J. S. H.; Nagahara, L. A.] NCI, Off Phys Sci Oncol, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. RP Moore, NM (reprint author), NCI, Off Phys Sci Oncol, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. RI Lee, Jerry/A-3189-2008; Lee, Jerry/K-4553-2014 OI Lee, Jerry/0000-0003-1515-0952; NR 5 TC 8 Z9 8 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD FEB PY 2011 VL 8 IS 1 AR 010302 DI 10.1088/1478-3975/8/1/010302 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 717LE UT WOS:000287044600003 PM 21368346 ER PT J AU Guenterberg, KD Grignol, VP Relekar, KV Varker, KA Chen, HX Kendra, KL Olencki, TE Carson, WE AF Guenterberg, Kristan D. Grignol, Valerie P. Relekar, Kiran V. Varker, Kimberly A. Chen, Helen X. Kendra, Kari L. Olencki, Thomas E. Carson, William E., III TI A Pilot Study of Bevacizumab and Interferon-alpha 2b in Ocular Melanoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE bevacizumab; vascular endothelial growth factor; angiogenic factor; interferon-alpha2b; uveal neoplasm ID ENDOTHELIAL-GROWTH-FACTOR; METASTATIC UVEAL MELANOMA; CUTANEOUS MELANOMA; COLORECTAL-CANCER; SYSTEMIC THERAPY; DACARBAZINE BOLD; BREAST-CANCER; CELL LINES; ANGIOGENESIS; EXPRESSION AB Objectives: We hypothesized that administration of bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, in combination with high-dose interferon-alpha2b (IFN-alpha 2b), an inhibitor of basic fibroblast growth factor, would have clinical activity in patients with metastatic ocular melanoma. Methods: Patients with metastatic ocular melanoma received bevacizumab (15 mg/kg intravenously every 2 weeks) plus IFN-alpha 2b (5 MU/m(2) subcutaneously 3 times weekly for 2 weeks followed by a dose of 10 MU/m(2) subcutaneously thereafter). Patients exhibiting a clinical response or stabilization of disease were treated until disease progression. Results: In this pilot study, 5 patients were treated (3 men, 2 women) with a mean age of 63.8 years (range, 53-71 years). Overall, the regimen was well-tolerated. The following adverse events were noted: grade 3 dyspnea (2 patients), grade 3 and 4 fatigue (2), grade 3 muscle weakness (1), grade 3 anorexia (1), grade 1 and 2 proteinuria (2), and grade 3 diarrhea (1). All adverse events resolved with a treatment holiday or dose reduction. One patient had reduction in tumor burden of 23% by Response Evaluation Criteria in Solid Tumors criteria and 2 patients had stabilization of disease lasting 28 and 36 weeks, respectively. Two patients failed to respond and progressed after 6 and 7 weeks of therapy. Conclusion: Bevacizumab and IFN-alpha 2b were well tolerated in this patient population, and clinical activity was observed. Further study of high-dose IFN-alpha 2b in combination with bevacizumab in this setting is warranted. C1 [Guenterberg, Kristan D.; Grignol, Valerie P.; Relekar, Kiran V.; Varker, Kimberly A.; Carson, William E., III] Ohio State Univ, Div Surg Oncol, Columbus, OH 43210 USA. [Chen, Helen X.] NCI, CTEP, Bethesda, MD 20892 USA. [Kendra, Kari L.; Olencki, Thomas E.] Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. RP Carson, WE (reprint author), Ohio State Univ, Div Surg Oncol, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM william.carson@osumc.edu RI Carson, William/E-2846-2011 FU National Institutes of Health [U01 CA76576, N01 CM62207, K24 CA093670, T32 CA009338, CA093071] FX Supported by National Institutes of Health Grants U01 CA76576, N01 CM62207, K24 CA093670, T32 CA009338, and CA093071. NR 42 TC 6 Z9 6 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2011 VL 34 IS 1 BP 87 EP 91 DI 10.1097/COC.0b013e3181d2ed67 PG 5 WC Oncology SC Oncology GA 711XF UT WOS:000286624100018 PM 20458209 ER PT J AU Corbin, M McLean, D 't Mannetje, A Dryson, E Walls, C McKenzie, F Maule, M Cheng, S Cunningham, C Kromhout, H Blair, A Pearce, N AF Corbin, Marine McLean, David 't Mannetje, Andrea Dryson, Evan Walls, Chris McKenzie, Fiona Maule, Milena Cheng, Soo Cunningham, Chris Kromhout, Hans Blair, Aaron Pearce, Neil TI Lung Cancer and Occupation: A New Zealand Cancer Registry-Based Case-Control Study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE lung cancer; occupation; case-control study; wood workers; metal workers; welding; machine operators; food process workers ID DRY-CLEANING WORKERS; ASBESTOS TEXTILE WORKERS; MULTICENTER CASE-CONTROL; HIGH-RISK OCCUPATIONS; INDUSTRY WORKERS; COHORT MORTALITY; BRITISH-COLUMBIA; EMPIRICAL-BAYES; MEAT INDUSTRY; EXPOSURES AB Background There are many proven and suspected occupational causes of lung calico; which will become relatively more important over time, as smoking prevalence decreases. Methods We interviewed 457 cases aged 20-75 years notified to the New Zealand Cancer Registry during 2007-2008, and 792 population controls. We collected information on demographic details, potential confounders, and employment history. Associations were estimated using logistic regression adjusted for gender; age, ethnicity, smoking, and socio-economic status. Results Among occupations of a priori interest, elevated odds ratios (ORs) were observed for sawmill, wood panel and related wood-processing plant operators (OR 4.63; 95% CI 1.05-20.29), butchers (OR 8.77, 95% CI 1.06-72.55), rubber and plastics products machine operators (4.27; 1.16-15.66), heavy truck drivers (2.24; 1.19-4.21) and workers in petroleum, coal, chemical and associated product manufacturing (1.80; 1.11-2.90); non-significantly elevated risks were also observed for loggers (4.67; 0.81-27.03), welders and flame-cutters (2.50; 0.86-7.25), pressers (5.74; 0.96-34.42), and electric and electronic equipment assemblers (3.61; 0.96-13.57). Several occupations and industries not of a priori interest also showed increased risks, including nursing associate professionals (5.45; 2.29-12.99), enrolled nurses (7.95; 3.10-20.42), care givers (3.47; 1.40-8.59), plant and machine operators and assemblers (1.61; 1.20-2.16), stationary machine operators and assemblers (1.67; 1.22-2.28), food and related products processing machine operators (1.98; 1.23-3.19), laborers and related elementary service workers (1.45; 1.05-2.00), manufacturing (1.34; 1.02-1.77), car retailing (3.08; 1.36-6.94), and road freight transport (3.02; 1.45-6.27). Conclusions Certain occupations and industries have increased lung cancer risks in New Zealand, including wood workers, metal workers, meat workers, textile workers and drivers. Am. J. Ind. Med. 54:89-101, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Corbin, Marine; McLean, David; 't Mannetje, Andrea; Dryson, Evan; Walls, Chris; McKenzie, Fiona; Cheng, Soo; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Corbin, Marine; Maule, Milena] Univ Turin, Canc Epidemiol Unit, CeRMS & CPO Piemonte, Turin, Italy. [Cunningham, Chris] Massey Univ, Res Ctr Maori Hlth & Dev, Wellington, New Zealand. [Kromhout, Hans] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Blair, Aaron] Occupat Canc Res Ctr, Toronto, ON, Canada. [Pearce, Neil] London Sch Hyg & Trop Med, Dept Epidemiol & Publ Hlth, London WC1, England. RP Pearce, N (reprint author), Massey Univ, Ctr Publ Hlth Res, Wellington Campus,Private Box 756, Wellington, New Zealand. EM n.e.pearce@massey.ac.nz OI Pearce, Neil/0000-0002-9938-7852 FU Health Research Council of New Zealand; New Zealand Department of Labour; Lottery Health Research; Cancer Society of New Zealand; Accident Compensation Corporation (ACC); Health Research Council FX Contract grant sponsor: Health Research Council of New Zealand; Contract grant sponsor: New Zealand Department of Labour; Contract grant sponsor: Lottery Health Research; Contract grant sponsor: Cancer Society of New Zealand; Contract grant sponsor: Accident Compensation Corporation (ACC).; This project was funded by the Health Research Council of New Zealand, by the New Zealand Department of Labour, by Lottery Health Research, by the Cancer Society of New Zealand, and by the Accident Compensation Corporation (ACC). Views and/or conclusions in this article are those of Massey University and may not reflect the position of ACC. The Centre for Public Health Research is supported by a Programme Grant from the Health Research Council. We thank Pam Miley-Terry, Joy Stubbs, Nicky Curran, and Heather Duckett. We also thank the staff of the New Zealand Cancer Registry at the New Zealand Health Information Service for collecting and making available information on cancer registrations. We also thank Miria Hudson for her assistance. NR 64 TC 18 Z9 18 U1 4 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 2011 VL 54 IS 2 BP 89 EP 101 DI 10.1002/ajim.20906 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 712XH UT WOS:000286699100001 PM 20957667 ER PT J AU Meehan, B Appu, S St Croix, B Rak-Poznanska, K Klotz, L Rak, J AF Meehan, Brian Appu, Sree St Croix, Brad Rak-Poznanska, Krystyna Klotz, Laurence Rak, Janusz TI Age-related properties of the tumour vasculature in renal cell carcinoma SO BJU INTERNATIONAL LA English DT Article DE RCC; angiogenesis; arteriogenesis; ageing; endothelial nitric oxide synthase ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; MICROVESSEL DENSITY; PROGNOSTIC-SIGNIFICANCE; CLINICAL-SIGNIFICANCE; BLOOD-VESSELS; ANGIOGENESIS; EXPRESSION; CANCER; ARTERIOGENESIS AB What's known on the subject? and What does the study add? Little is known about the impact of vascular ageing on the angiogenic features of clear cell renal cell carcinoma, a disease in which antiangiogenic therapy currently has a well established role. It is also rather surprising that this question has not been raised in a disease context where patients' age may differ by several decades. We provide the first glimpse in to the related vasclar changes, including morphology and some of the molecular features. OBJECTIVE To assess whether ageing processes influence angiogenesis in renal cell carcinoma (RCC) we carried out a pilot study of vascular properties in a series of archival primary kidney tumours in patients of different ages. PATIENTS AND METHODS A cohort of patients with RCC was identified restrospectively, with an age range of 35-84 years. Paraffin-embedded, formalin-fixed sections of surgical tumour specimens were stained for endothelial (CD31, von Willebrand factor [vWF]), pericyte (alpha smooth muscle actin [SMA]) and leucocytic (CD45) markers, as well as for proliferative (Ki67) and angiogenic activity (tumour endothelial markers [TEMs], delta-like 4 [Dll4], Dll1, endothelial nitric oxide synthase [eNOS]). Vascular properties were compared between patients above and below 65 years of age. RESULTS Microvascular density (MVD) within capillary hot spots was generally higher in patients with non-metastatic clear-cell RCC (ccRCC; n = 21) than in those with metastatic RCC (mRCC; n = 9). Patients with ccRCC who were more than 65 years old showed significantly higher MVD than their younger (< 65 years) counterparts. There were dividing (Ki67-positive) endothelial and mural cells in both small (< 20 mu m) capillary and large (> 20 mu m), pre-capillary vessels, suggesting the involvement of both angiogenic and remodelling/arteriogenic processes. Tumour endothelial markers (TEM1, TEM7, TEM8), Notch ligands (Dll1, Dll4), and other molecular characteristics (eNOS) were analysed. Age-related differences were observed in the frequency of pre-capillary vessels expressing Dll1, which was significantly higher in tumours of younger patients (< 65 years), while eNOS was more prevalent among capillaries associated with ccRCC in older patients (> 65 years). CONCLUSIONS The results of the present study suggest that age influences the structural and molecular properties of the tumour vasculature in ccRCC. We postulate that vascular ageing could also be relevant in the context of anti-angiogenic therapy. C1 [Meehan, Brian; Rak, Janusz] McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3Z 2Z3, Canada. [Appu, Sree; Klotz, Laurence] Univ Toronto, Sunnybrook Res Inst, Toronto, ON, Canada. [St Croix, Brad] NCI, Frederick, MD 21701 USA. [Rak-Poznanska, Krystyna] Prov Specialist Hosp, Res & Dev Ctr Wroclaw, Wroclaw, Poland. RP Rak, J (reprint author), McGill Univ, Montreal Childrens Hosp, Res Inst, 4060 Ste Catherine W, Montreal, PQ H3Z 2Z3, Canada. EM janusz.rak@mcgill.ca FU Cancer Research Society; Canadian Cancer Society; Jack Cole Chair in Pediatric Oncology FX None declared. Source of Funding: this work was supported by grants from the Cancer Research Society and partially by funds from the Canadian Cancer Society, both to J.R., who is also a recipient of the Jack Cole Chair in Pediatric Oncology. Infrastructure support was provided by Fonds de la Recherche en Sante Quebec. NR 55 TC 9 Z9 10 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2011 VL 107 IS 3 BP 416 EP 424 DI 10.1111/j.1464-410X.2010.09569.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 711MW UT WOS:000286596700013 PM 20804487 ER PT J AU Pedone, C Napoli, N Pozzilli, P Lauretani, F Bandinelli, S Ferrucci, L Antonelli-Incalzi, R AF Pedone, Claudio Napoli, Nicola Pozzilli, Paolo Lauretani, Fulvio Bandinelli, Stefania Ferrucci, Luigi Antonelli-Incalzi, Raffaele TI Quality of diet and potential renal acid load as risk factors for reduced bone density in elderly women Reply SO BONE LA English DT Letter C1 [Pedone, Claudio; Antonelli-Incalzi, Raffaele] Univ Campus Biomed, Area Geriatria, I-00128 Rome, Italy. [Pedone, Claudio; Napoli, Nicola; Pozzilli, Paolo] Fdn Alberto Sordi Onlus, Rome, Italy. [Napoli, Nicola; Pozzilli, Paolo] Univ Campus Biomed, Area Endocrinol & Malattie Metab, I-00128 Rome, Italy. [Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Antonelli-Incalzi, Raffaele] Fdn San Raffaele Cittadella della Carita, Taranto, Italy. RP Pedone, C (reprint author), Univ Campus Biomed, Area Geriatria, Via Alvaro del Portillo 21, I-00128 Rome, Italy. EM c.pedone@unicampus.it RI Antonelli Incalzi, Raffaele/G-3978-2012; OI Pedone, Claudio/0000-0003-1847-9032 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD FEB 1 PY 2011 VL 48 IS 2 BP 416 EP 416 DI 10.1016/j.bone.2010.09.004 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710UY UT WOS:000286543700032 ER PT J AU Kolesar, J Brundage, RC Pomplun, M Alberti, D Holen, K Traynor, A Ivy, P Wilding, G AF Kolesar, Jill Brundage, Richard C. Pomplun, Marcia Alberti, Dona Holen, Kyle Traynor, Anne Ivy, Percy Wilding, George TI Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine (R)) in cancer patients SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Triapine (R); 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone; Population pharmacokinetics; Phase 1 ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; BLOOD MONONUCLEAR-CELLS; ADVANCED SOLID TUMORS; PHASE-I; 3-AP; TRIAL; GEMCITABINE; COMBINATION; CONSORTIUM; CARCINOMA AB The purpose of this study was to develop a population pharmacokinetic (PK) model for 3-AP, to evaluate the effect of ABCB1 polymorphisms on the pharmacokinetic profile of 3-AP, and to assess the relationship between 3AP disposition and patient covariates. A total of 40 patients with advanced cancer from two phase 1 studies were included in the population PK model building. Patients received 3-AP 25-105 mg/m(2) IV on day 1. 3-AP plasma and erythrocyte levels were sampled at 10 timepoints over a 24-h period and measured by a validated HPLC method. Data were analyzed by a nonlinear mixed-effects modeling approach using the NONMEM system. 3-AP pharmacokinetics were described as a 3-compartment model with first-order elimination, with one compartment representing the plasma and another representing erythrocyte concentrations. Gender was associated with volume of distribution, in which women had a lower V2. The number of cycles administered was associated with clearance; those with decreased clearance were more likely to receive less than 2 cycles before going off study. This study suggests that monitoring 3-AP plasma concentrations in the first cycle and dose adjustment in those with decreased clearance may be helpful in decreasing toxicity associated with the 3-AP. C1 [Kolesar, Jill; Pomplun, Marcia; Alberti, Dona; Holen, Kyle; Traynor, Anne; Wilding, George] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA. [Kolesar, Jill] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA. [Brundage, Richard C.] Univ Minnesota, Ctr Forecasting Drug Response, Minneapolis, MN USA. [Alberti, Dona; Holen, Kyle; Traynor, Anne; Wilding, George] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Ivy, Percy] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA. RP Kolesar, J (reprint author), Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, 600 Highland Ave,K4-554, Madison, WI 53792 USA. EM jmkolesar@pharmacy.wisc.edu FU NCI [U01CA062491]; CTEP Translational Research Initiative [24XS090]; National Center for Research Resources, NIH [1ULRR0 25011]; American College of Clinical Pharmacy FX Supported by: U01CA062491 "Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis" NCI; CTEP Translational Research Initiative Funding 24XS090, and 1ULRR0 25011 Clinical and Translational Science Award of the National Center for Research Resources, NIH and the American College of Clinical Pharmacy. NR 21 TC 17 Z9 17 U1 0 U2 7 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 FEB PY 2011 VL 67 IS 2 BP 393 EP 400 DI 10.1007/s00280-010-1331-z PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 711YE UT WOS:000286627400016 PM 20440618 ER PT J AU Beumer, JH Eiseman, JL Gilbert, JA Holleran, JL Yellow-Duke, AE Clausen, DM D'Argenio, DZ Ames, MM Hershberger, PA Parise, RA Bai, L Covey, JM Egorin, MJ AF Beumer, Jan H. Eiseman, Julie L. Gilbert, Judith A. Holleran, Julianne L. Yellow-Duke, Archibong E. Clausen, Dana M. D'Argenio, David Z. Ames, Matthew M. Hershberger, Pamela A. Parise, Robert A. Bai, Lihua Covey, Joseph M. Egorin, Merrill J. TI Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Tetrahydrouridine; THU; Bioavailability; Metabolism; Mouse; Cytidine deaminase ID METHYLTRANSFERASE INHIBITOR 5-FLUORO-2'-DEOXYCYTIDINE; CYTIDINE DEAMINASE INHIBITOR; CYTOSINE-ARABINOSIDE; DEOXYCYTIDYLATE DEAMINASE; TETRAHYDROURIDINE THU; CLINICAL-PHARMACOLOGY; PHASE-I; METABOLISM; URIDINE; PN401 AB Cytidine drugs, such as gemcitabine, undergo rapid catabolism and inactivation by cytidine deaminase (CD). 3,4,5,6-tetrahydrouridine (THU), a potent CD inhibitor, has been applied preclinically and clinically as a modulator of cytidine analogue metabolism. However, THU is only 20% orally bioavailable, which limits its preclinical evaluation and clinical use. Therefore, we characterized THU pharmacokinetics after the administration to mice of the more lipophilic pro-drug triacetyl-THU (taTHU). Mice were dosed with 150 mg/kg taTHU i.v. or p.o. Plasma and urine THU concentrations were quantitated with a validated LC-MS/MS assay. Plasma and urine pharmacokinetic parameters were calculated non-compartmentally and compartmentally. taTHU did not inhibit CD. THU, after 150 mg/kg taTHU i.v., had a 235-min terminal half-life and produced plasma THU concentrations > 1 mu g/mL, the concentration shown to inhibit CD, for 10 h. Renal excretion accounted for 40-55% of the i.v. taTHU dose, 6-12% of the p.o. taTHU dose. A two-compartment model of taTHU generating THU fitted the i.v. taTHU data best. taTHU, at 150 mg/kg p.o., produced a concentration versus time profile with a plateau of approximately 10 mu g/mL from 0.5-2 h, followed by a decline with a 122-min half-life. Approximately 68% of i.v. taTHU is converted to THU. Approximately 30% of p.o. taTHU reaches the systemic circulation as THU. The availability of THU after p.o. taTHU is 30%, when compared to the 20% achieved with p.o. THU. These data will support the clinical studies of taTHU. C1 [Beumer, Jan H.; Eiseman, Julie L.; Holleran, Julianne L.; Yellow-Duke, Archibong E.; Clausen, Dana M.; Hershberger, Pamela A.; Parise, Robert A.; Bai, Lihua; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Drug Discovery Program, Pittsburgh, PA 15213 USA. [Beumer, Jan H.; Parise, Robert A.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Eiseman, Julie L.; Hershberger, Pamela A.; Bai, Lihua; Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Gilbert, Judith A.; Ames, Matthew M.] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. [D'Argenio, David Z.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Covey, Joseph M.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Drug Discovery Program, Hillman Res Pavil,Room G27D,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU National Cancer Institute [NO1-CM-52202, P30-CA47904, P41-EB001978]; Hillman Fellows for Innovative Cancer Research Award; American Society of Clinical Oncology Cancer Foundation FX We thank Dr. B. Rao Vishnuvajjala for his advice, Dr. Richard M. Weinshilboum of Mayo Clinic for recombinant human CD preparation, Diane Mazzei and her colleagues at the University of Pittsburgh Animal Facility for their expert assistance, and the University of Pittsburgh Cancer Institute Hematology/Oncology Writing Group for constructive suggestions regarding the manuscript. This work was supported by contract NO1-CM-52202 and grants P30-CA47904 and P41-EB001978 from the National Cancer Institute. JHB is the recipient of a Hillman Fellows for Innovative Cancer Research Award. MJE is the recipient of an American Society of Clinical Oncology Cancer Foundation Translational Research Professorship. NR 37 TC 5 Z9 6 U1 0 U2 3 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 FEB PY 2011 VL 67 IS 2 BP 421 EP 430 DI 10.1007/s00280-010-1337-6 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 711YE UT WOS:000286627400019 PM 20443002 ER PT J AU Sonoda, S Li, HCA Tajima, K AF Sonoda, Shunro Li, Hong Chuan Tajima, Kazuo TI Ethnoepidemiology of HTLV-1 related diseases: Ethnic determinants of HTLV-1 susceptibility and its worldwide dispersal SO CANCER SCIENCE LA English DT Review ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; PERIPHERAL-BLOOD LYMPHOCYTES; INFECTIVE DERMATITIS; CHILD TRANSMISSION; MYELOPATHY; LYMPHOMA; RISK; CARRIERS AB Human T-cell lymphotropic virus type 1 is vertically transmitted in neonatal life and is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in adults. Persistence of HTLV-1 in host T cells, clonal expansion of the HTLV-1 carrying T cells, and emergence of malignantly transformed T cells are in accord with the multistep model of human cancer and roles for continuous interaction between host genes and environmental factors. This article reviews two lines of HTLV-1 investigation, one regarding worldwide surveillance of HTLV-1 infection foci by serological testing and molecular analysis of HTLV-1 isolates, and the other focusing on genetics of the human leukocyte antigen (HLA) that determines the ethnic background of HTLV-1 permissiveness and susceptibility to ATL or HAM/TSP. The serological surveillance revealed transcontinental dispersal of HTLV-1 in the prehistoric era that started out of Africa, spread to Austro-Melanesia and the Asian continent, then moved to North America and through to the southern edge of South America. This was highlighted by an Andean mummy study that proved ancient migration of paleo-mongoloid HTLV-1 from Asia to South America. Phylogenetic analysis of HLA alleles provided a basis for ethnic susceptibility to HTLV-1 infection and associated diseases, both ATL and HAM/TSP. Ethnicity-based sampling of peripheral blood lymphocytes has great potential for genome-wide association studies to illuminate ethnically defined host factors for viral oncogenesis with reference to HTLV-1 and other pathogenic elements causatively associated with chronic disease and malignancies. (Cancer Sci 2011; 102: 295-301) C1 [Sonoda, Shunro; Li, Hong Chuan] Kagoshima Univ, Dept Virol, Kagoshima 890, Japan. [Sonoda, Shunro] Kagoshima Univ, Fac Med, Kagoshima 890, Japan. [Sonoda, Shunro] So Reg Hosp, Makurazaki, Japan. [Li, Hong Chuan] NCI, Div Canc Epidemiol & Genet, Frederick, MD 21701 USA. [Tajima, Kazuo] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 464, Japan. RP Sonoda, S (reprint author), Kagoshima Univ, Dept Virol, Kagoshima 890, Japan. EM sumikoshunro@ybb.ne.jp; ktajima@aichi-cc.jp FU Ministry of Science, Education, Sports and Technology of Japan FX We greatly thank Drs. V. Zaninovic, A. Blank, M. Blank (Colombia), L. Cartier, L. Ramirez, L Nunez (Chile), L. Hurtado, L. V. Hurtado, R. Andrade (Bolivia), B. Hanchard, O. Morgan, B. Cranston (Jamaica), A. Manns, W. Blattner, P. Levine, N. Mueller, M. Hisada, R. Biggar, J. Goedert, V. Franchini, S. Jacobson, W. Harrington Jr., J. Byrnes, M. Hojo (USA), G. de The, A. Gessain (France), B. Kitze (Germany), W. Hall (Ireland), K. Takahashi, Y.Nagata, K. Kawakami, T. Takezaki, N. Arima, K. Usuku, S. Yashiki, T. Fujiyoshi, L. Hong, M. Osame, A. Utsunomiya, S. Kashiwagi, T. Miura, M. Hayami, S. Horai, and M. Moore (Japan) for their kind collaboration in our field studies and laboratory work, as well as in preparation of this article. We highly appreciate Drs. I. Danjoh, Y. Nakamura, and Y. Obata, the Rikken Bio-Resource Center of Japan for their expertise in preserving peripheral blood lymphocytes collected in our field studies and in establishing B cell lines for future studies on human genome diversity and genome-wide scans of disease-susceptible genes. The present investigation was supported by the Monbusho International Collaborative Study of Cancer Research and by Grants-in-Aid from the Ministry of Science, Education, Sports and Technology of Japan. NR 79 TC 31 Z9 34 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD FEB PY 2011 VL 102 IS 2 BP 295 EP 301 DI 10.1111/j.1349-7006.2010.01820.x PG 7 WC Oncology SC Oncology GA 711PQ UT WOS:000286604300001 PM 21205073 ER PT J AU Holleley, CE Nichols, RA Whitehead, MR Gunn, MR Gupta, J Sherwin, WB AF Holleley, Clare E. Nichols, Richard A. Whitehead, Michael R. Gunn, Melissa R. Gupta, Jyoutsna Sherwin, William B. TI Induced dispersal in wildlife management: experimental evaluation of the risk of hybrid breakdown and the benefit of hybrid vigor in the F1 generation SO CONSERVATION GENETICS LA English DT Article DE Hybrid vigor; Hybrid breakdown; Inbreeding depression; Drosophila melanogaster; Conservation; Management; Genetic drift ID CAPTIVE DROSOPHILA POPULATIONS; OUTBREEDING DEPRESSION; INBRED POPULATIONS; MODELING PROBLEMS; COLLARED LIZARDS; MISSOURI OZARKS; MELANOGASTER; HETEROSIS; CONSERVATION; DYSGENESIS AB Management practices often aim to increase the level of gene flow by either: introducing animals from captive breeding programs, translocating animals from abundant areas, or increasing the chance of animals dispersing between populations by creating habitat corridors. These practices provide opportunity for the hybrid offspring of introduced and resident animals to experience either increased fitness (hybrid vigor) or decreased fitness (hybrid breakdown). There is very little quantitative data available to adequately assess whether hybridization is likely to be beneficial or detrimental to populations managed in these ways. Using Drosophila melanogaster populations, we conducted two experiments that simulate the common management practices of translocation and wildlife habitat corridors. We monitored the frequency and magnitude of hybrid vigor and hybrid breakdown in F1 hybrids to assess the relative risks and benefits to populations and also monitored net productivity (number of adults produced from controlled crosses) to assess whether the populations were stable or in decline. In the translocation experiment, we observed instances of both significant hybrid vigor and hybrid breakdown, both occurring at a frequency of 9%. In the habitat corridor experiments, populations with moderate to high dispersal (1-4% per generation) did not develop significant hybrid vigor or hybrid breakdown. However, of the populations experiencing low dispersal (0.25% per generation) for 34 generations, 6% displayed significant hybrid vigor and 6% displayed significant hybrid breakdown. These results suggest that in first generation hybrids there may be limited opportunity to utilize hybrid vigor as a tool to increase the short-term viability of populations because there is an equal likelihood of encountering hybrid breakdown that may drive the population into further decline. However, our results apply only to populations of moderate size (N = 50; N (e) = 14.3) in the absence of deliberate consanguineous mating. Lastly, we observed that net productivity was positively correlated with dispersal rate, suggesting that initial F1 declines in fitness may be temporary and that it is preferable to maintain high levels of selectable variation via induced dispersal to assist the long-term survival of vulnerable populations. C1 [Holleley, Clare E.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Holleley, Clare E.; Whitehead, Michael R.; Gunn, Melissa R.; Gupta, Jyoutsna; Sherwin, William B.] Univ New S Wales, Evolut & Ecol Res Ctr, Sydney, NSW 2052, Australia. [Holleley, Clare E.; Whitehead, Michael R.; Gunn, Melissa R.; Gupta, Jyoutsna; Sherwin, William B.] Univ New S Wales, Sch Biol Earth & Environm Sci, Sydney, NSW 2052, Australia. [Nichols, Richard A.] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England. [Whitehead, Michael R.] Australian Natl Univ, Sch Biol Sci, Canberra, ACT 0200, Australia. [Gunn, Melissa R.] Food & Environm Res Agcy, York Y041 1LZ, N Yorkshire, England. RP Holleley, CE (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM holleleyce@mail.nih.gov RI Holleley, Clare/C-4629-2011; Sherwin, William B/C-3432-2008; OI Holleley, Clare/0000-0002-5257-0019; Sherwin, William B/0000-0002-1578-8473; Whitehead, Michael/0000-0002-9038-5746; Nichols, Richard Alan/0000-0002-4801-9312 FU Australian Research Council [DP0559363] FX We acknowledge L. Tsai, E. Ho and J. Chao for fly culture assistance; O. E. Gaggiotti, A. R. Templeton, J. L. Wang and M. Mariette for comments on the manuscript and the Ramaciotti Centre for Gene Function Analysis for DNA fragment size analysis. This research was supported by Australian Research Council Grant DP0559363 to WBS and RAN. NR 57 TC 4 Z9 4 U1 1 U2 24 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1566-0621 EI 1572-9737 J9 CONSERV GENET JI Conserv. Genet. PD FEB PY 2011 VL 12 IS 1 BP 31 EP 40 DI 10.1007/s10592-009-9984-z PG 10 WC Biodiversity Conservation; Genetics & Heredity SC Biodiversity & Conservation; Genetics & Heredity GA 703IP UT WOS:000285971900003 ER PT J AU Okuno, T Hooper, LC Ursea, R Smith, J Nussenblatt, R Hooks, JJ Hayashi, K AF Okuno, Toshiomi Hooper, Laura C. Ursea, Roxana Smith, Janine Nussenblatt, Robert Hooks, John J. Hayashi, Kozaburo TI Role of Human Herpes Virus 6 in Corneal Inflammation Alone or With Human Herpesviruses SO CORNEA LA English DT Article DE human herpesvirus 6; herpes simplex virus; varicella zoster virus; cornea; inflammation; polymerase chain reaction ID HUMAN-HERPESVIRUS-6 INFECTION; EXANTHEM-SUBITUM; HHV-6; SUPPRESSION; HIV-1 AB Purpose: The purpose of this study was to determine the association of human herpes virus 6 (HHV-6) and/or other human herpesviruses in corneal inflammation using polymerase chain reaction (PCR). Methods: We collected tear films, conjunctival smears, and a corneal button of inflamed cornea, and the presence of HHV-6 and other herpesviruses in these samples were assessed by a nested PCR. Results: In tear films collected from 3 of 9 patients with dendritic keratitis, HHV-6 DNA was positive twice, together with herpes simplex virus (HSV) or varicella zoster virus DNA most often, during the acute phase of the disease. Two other patients in this group were either positive for HSV-1 and varicella zoster virus or for HSV-1 and Epstein-Barr virus DNA but negative for HHV-6. When another 12 patients' smear samples from corneal ulcer or keratouveitis were examined, 9 were positive for HHV-6 DNA. Of these, 4 were positive for HSV-1 simultaneously, whereas the remaining 5 patients were negative for HSV-1. One patient's smear was positive for HSV-1 but not for HHV-6. In the corneal button, both HSV and HHV-6 DNAs were positive by nested PCR. HHV-6 was also positive by nested PCR in the conjunctival swab obtained from the contralateral inflamed eye of the patient. Conclusions: In 22 patients with corneal inflammation, HHV-6 was positive in 14 of 22 patients and HSV-1 was found in 9 of those patients. These data indicated that the association of HHV-6 with disease was more frequent than with other herpesviruses and that HHV-6 may be another sole causative agent for corneal inflammation. C1 [Okuno, Toshiomi] Hyogo Coll Med, Dept Microbiol, Nishinomiya, Hyogo 6638501, Japan. [Hooper, Laura C.; Nussenblatt, Robert; Hooks, John J.; Hayashi, Kozaburo] Res Inst, Immunol Lab, Lucknow 226001, Uttar Pradesh, India. [Ursea, Roxana; Smith, Janine; Nussenblatt, Robert] NEI, Ophthalmol Clin, NIH, Bethesda, MD 20892 USA. RP Okuno, T (reprint author), Hyogo Coll Med, Dept Microbiol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. EM tmokuno@hyo-med.ac.jp FU National Eye Institute, National Institutes of Health FX Supported (in part) by the Intramural Research Program of the National Eye Institute, National Institutes of Health. NR 19 TC 7 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD FEB PY 2011 VL 30 IS 2 BP 204 EP 207 DI 10.1097/ICO.0b013e3181e2e9be PG 4 WC Ophthalmology SC Ophthalmology GA 702SD UT WOS:000285914700019 PM 20847652 ER PT J AU Simon, SL Bouville, A Beck, HL Ibrahim, S AF Simon, Steven L. Bouville, Andre Beck, Harold L. Ibrahim, Shawki TI 1997 THYROID ABSORBED DOSE ESTIMATES FOR THE NORTHERN MARSHALL ISLANDS RESPONSE SO HEALTH PHYSICS LA English DT Letter ID NUCLEAR-WEAPONS TESTS; FALLOUT; BIKINI C1 [Simon, Steven L.; Bouville, Andre] NCI, Bethesda, MD 20892 USA. [Ibrahim, Shawki] Colorado State Univ, Ft Collins, CO 80523 USA. RP Simon, SL (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 2011 VL 100 IS 2 BP 229 EP 230 DI 10.1097/HP.0b013e3181f8c6a5 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 700BR UT WOS:000285707600014 ER PT J AU Devaney, JM Gordish-Dressman, H Harmon, BT Bradbury, MK Devaney, SA Harris, TB Thompson, PD Clarkson, PM Price, TB Angelopoulos, TJ Gordon, PM Moyna, NM Pescatello, LS Visich, PS Zoeller, RF Seip, RL Seo, J Kim, BH Tosi, LL Garcia, M Li, RL Zmuda, JM Delmonico, MJ Lindsay, RS Howard, BV Kraus, WE Hoffman, EP AF Devaney, Joseph M. Gordish-Dressman, Heather Harmon, Brennan T. Bradbury, Margaret K. Devaney, Stephanie A. Harris, Tamara B. Thompson, Paul D. Clarkson, Priscilla M. Price, Thomas B. Angelopoulos, Theodore J. Gordon, Paul M. Moyna, Niall M. Pescatello, Linda S. Visich, Paul S. Zoeller, Robert F. Seip, Richard L. Seo, Jinwook Kim, Bo Hyoung Tosi, Laura L. Garcia, Melissa Li, Rongling Zmuda, Joseph M. Delmonico, Matthew J. Lindsay, Robert S. Howard, Barbara V. Kraus, William E. Hoffman, Eric P. TI AKT1 polymorphisms are associated with risk for metabolic syndrome SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; INSULIN-SECRETION; AMERICAN-INDIANS; DENATURING HPLC; GLUCOSE-LEVELS; EMERGING ROLE; MUSCLE MASS; PROTEIN; LOCI; SUSCEPTIBILITY AB Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 +/- A 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 +/- A 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 +/- A 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40-65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations. C1 [Devaney, Joseph M.; Gordish-Dressman, Heather; Harmon, Brennan T.; Bradbury, Margaret K.; Devaney, Stephanie A.; Seo, Jinwook; Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Dept Integrat Syst Biol, Washington, DC 20010 USA. [Harris, Tamara B.; Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Thompson, Paul D.; Price, Thomas B.; Seip, Richard L.] Hartford Hosp, Henry Low Heart Ctr, Div Cardiol, Hartford, CT 06102 USA. [Clarkson, Priscilla M.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA. [Price, Thomas B.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Angelopoulos, Theodore J.] Univ Cent Florida, Dept Hlth Profess, Ctr Lifestyle Med, Orlando, FL 32816 USA. [Gordon, Paul M.] Univ Michigan, Lab Phys Act & Exercise Intervent Res, Ann Arbor, MI 48108 USA. [Moyna, Niall M.] Dublin City Univ, Dept Sport Sci & Hlth, Dublin 9, Ireland. [Pescatello, Linda S.] Univ Connecticut, Sch Allied Hlth, Storrs, CT 06269 USA. [Visich, Paul S.] Cent Michigan Univ, Human Performance Lab, Mt Pleasant, MI 48859 USA. [Zoeller, Robert F.] Florida Atlantic Univ, Dept Exercise Sci & Hlth Promot, Davie, FL 33314 USA. [Kim, Bo Hyoung] INFINITT Technol, Seoul, South Korea. [Tosi, Laura L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Li, Rongling] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol & Human Genet, Pittsburgh, PA 15261 USA. [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Lindsay, Robert S.] Univ Glasgow, Fac Med, Glasgow, Lanark, Scotland. [Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD 20783 USA. [Kraus, William E.] Duke Univ, Med Ctr, Duke Ctr Living, Durham, NC 27710 USA. RP Hoffman, EP (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, Dept Integrat Syst Biol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM ehoffman@cnmcresearch.org RI gordon, paul/E-3862-2015 OI Kraus, William E/0000-0003-1930-9684; gordon, paul/0000-0003-4403-0888 FU NHLBI NIH HHS [U01 HL066614-04, U01 HL066614]; NIAMS NIH HHS [R01 AR055100, R01 AR055100-08]; NICHD NIH HHS [R24 HD050846, R24 HD050846-06] NR 40 TC 12 Z9 13 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2011 VL 129 IS 2 BP 129 EP 139 DI 10.1007/s00439-010-0910-8 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 706CJ UT WOS:000286194000002 PM 21061022 ER PT J AU Yahiro, K Satoh, M Morinaga, N Tsutsuki, H Ogura, K Nagasawa, S Nomura, F Moss, J Noda, M AF Yahiro, Kinnosuke Satoh, Mamoru Morinaga, Naoko Tsutsuki, Hiroyasu Ogura, Kohei Nagasawa, Sayaka Nomura, Fumio Moss, Joel Noda, Masatoshi TI Identification of Subtilase Cytotoxin (SubAB) Receptors Whose Signaling, in Association with SubAB-Induced BiP Cleavage, Is Responsible for Apoptosis in HeLa Cells SO INFECTION AND IMMUNITY LA English DT Article ID FOCAL ADHESION KINASE; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; TOXIGENIC ESCHERICHIA-COLI; ANCHORAGE-DEPENDENT APOPTOSIS; INTESTINAL EPITHELIAL-CELLS; BREAST-CARCINOMA CELLS; NG2 PROTEOGLYCAN; DOWN-REGULATION; CHAPERONE BIP AB Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic Escherichia coli (STEC), causes the 78-kDa glucose-regulated protein (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress, leading to caspase-dependent apoptosis via mitochondrial membrane damage by Bax/Bak activation. The purpose of the present study was to identify SubAB receptors responsible for HeLa cell death. Four proteins, NG2, alpha 2 beta 1 integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor receptor (Met), were identified to be SubAB-binding proteins by immunoprecipitation and purification, followed by liquid chromatography-tandem mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak complex formation, caspase activation, and cell death were decreased in beta 1 ITG, NG2, and L1CAM small interfering RNA-transfected cells, but unexpectedly, BiP cleavage was still observed. Pretreatment of cells with a function-blocking beta 1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced caspase activation; MAb P5D2 alone had no effect on caspase activation. Furthermore, we found that SubAB induced focal adhesion kinase fragmentation, which was mediated by a proteasome-dependent pathway, and caspase activation was suppressed in the presence of proteasome inhibitor. Thus, beta 1 ITG serves as a SubAB-binding protein and may interact with SubAB-signaling pathways, leading to cell death. Our results raise the possibility that although BiP cleavage is necessary for SubAB-induced apoptotic cell death, signaling pathways associated with functional SubAB receptors may be required for activation of SubAB-dependent apoptotic pathways. C1 [Yahiro, Kinnosuke] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan. [Satoh, Mamoru; Nomura, Fumio] Chiba Univ, Grad Sch Med, Dept Mol Diag, Chiba 2608670, Japan. [Nagasawa, Sayaka] Chiba Univ, Grad Sch Med, Dept Legal Med, Chiba 2608670, Japan. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM yahirok@faculty.chiba-u.jp FU Ministry of Education, Science, and Culture of Japan; Japan Science and Technology Agency; National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by grants in aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan and Improvement of Research Environment for Young Researchers from the Japan Science and Technology Agency. Joel Moss was supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 79 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2011 VL 79 IS 2 BP 617 EP 627 DI 10.1128/IAI.01020-10 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 709SP UT WOS:000286462000007 PM 21098100 ER PT J AU Brett, PJ Burtnick, MN Heiss, C Azadi, P DeShazer, D Woods, DE Gherardini, FC AF Brett, Paul J. Burtnick, Mary N. Heiss, Christian Azadi, Parastoo DeShazer, David Woods, Donald E. Gherardini, Frank C. TI Burkholderia thailandensis oacA Mutants Facilitate the Expression of Burkholderia mallei-Like O Polysaccharides SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE DETERMINANT; MURINE MACROPHAGES; PSEUDOMALLEI; LIPOPOLYSACCHARIDE; ACETYLATION; GLANDERS; ANTIGEN; IDENTIFICATION; MELIOIDOSIS; STRATEGIES AB Previous studies have shown that the O polysaccharides (OPS) expressed by Burkholderia mallei are similar to those produced by Burkholderia thailandensis except that they lack the 4-O-acetyl modifications on their 6-deoxy-alpha-L-talopyranosyl residues. In the present study, we describe the identification and characterization of an open reading frame, designated oacA, expressed by B. thailandensis that accounts for this phenomenon. Utilizing the B. thailandensis and B. mallei lipopolysaccharide (LPS)-specific monoclonal antibodies Pp-PS-W and 3D11, Western immunoblot analyses demonstrated that the LPS antigens expressed by the oacA mutant, B. thailandensis ZT0715, were antigenically similar to those produced by B. mallei ATCC 23344. In addition, immunoblot analyses demonstrated that when B. mallei ATCC 23344 was complemented in trans with oacA, it synthesized B. thailandensis-like LPS antigens. To elucidate the structure of the OPS moieties expressed by ZT0715, purified samples were analyzed via nuclear magnetic resonance spectroscopy. As predicted, these studies demonstrated that the loss of OacA activity influenced the O acetylation phenotype of the OPS moieties. Unexpectedly, however, the results indicated that the O methylation status of the OPS antigens was also affected by the loss of OacA activity. Nonetheless, it was revealed that the LPS moieties expressed by the oacA mutant reacted strongly with the B. mallei LPS-specific protective monoclonal antibody 9C1-2. Based on these findings, it appears that OacA is required for the 4-O acetylation and 2-O methylation of B. thailandensis OPS antigens and that ZT0715 may provide a safe and cost-effective source of B. mallei-like OPS to facilitate the synthesis of glanders subunit vaccine candidates. C1 [Brett, Paul J.; Burtnick, Mary N.] Univ S Alabama, Dept Microbiol & Immunol, Mobile, AL 36688 USA. [Heiss, Christian; Azadi, Parastoo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [DeShazer, David] USA, Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD 21702 USA. [Woods, Donald E.] Univ Calgary, Hlth Sci Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. [Gherardini, Frank C.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Brett, PJ (reprint author), Univ S Alabama, Dept Microbiol & Immunol, 5851 USA Dr N, Mobile, AL 36688 USA. EM pbrett@jaguar1.usouthal.edu FU NIH, National Institute of Allergy and Infectious Diseases; Department of Energy [DE-FG09-93ER-20097]; University of South Alabama FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, the Department of Energy-funded (DE-FG09-93ER-20097) Center for Plant and Microbial Complex Carbohydrates, and lab start-up funds from the University of South Alabama. NR 43 TC 12 Z9 12 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2011 VL 79 IS 2 BP 961 EP 969 DI 10.1128/IAI.01023-10 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 709SP UT WOS:000286462000043 PM 21115721 ER PT J AU Beachler, DC Gellert, LL Jacobson, LP Ambinder, RF Breen, EC Martinez-Maza, O Rabkin, CC Kaslow, RA D'Souza, G AF Beachler, Daniel C. Gellert, Lan L. Jacobson, Lisa P. Ambinder, Richard F. Breen, Elizabeth C. Martinez-Maza, Otoniel Rabkin, Charles C. Kaslow, Richard A. D'Souza, Gypsyamber TI Kaposi Sarcoma-Associated Herpesvirus Serum DNA and Antibodies Not Associated With Subsequent Non-Hodgkin Lymphoma Risk SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE Kaposi sarcoma-associated herpesvirus; non-Hodgkin lymphoma; MACS; human herpesvirus 8; DNA; AIDS cancer ID MULTICENTER AIDS COHORT; HUMAN-HERPESVIRUS-8 INFECTION; HIV; VIRUS; PARTICIPANTS; CANCER; ADULTS AB Kaposi sarcoma-associated herpes virus (KSHV) infects B-cells and is found in non-Hodgkin lymphoma (NHL) B-cell tumors and could therefore contribute to the occurrence of NHL. We performed a nested case-control study including 155 incident NHL cases and matched noncancer controls. Pre-NHL serum was tested for KSHV DNA and antibodies. Serum KSHV DNA was more common in cases than controls (14% versus 6%, P = 0.03), but after adjustment, the difference was not significant. Epstein-Barr virus serum DNA was similarly unassociated with NHL as were KSHV antibodies. KSHV is not a primary cause of NHL in HIV-infected men who have sex with men. C1 [Beachler, Daniel C.; Gellert, Lan L.; Jacobson, Lisa P.; D'Souza, Gypsyamber] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Gellert, Lan L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Ambinder, Richard F.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD USA. [Breen, Elizabeth C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynaecol, Los Angeles, CA 90095 USA. [Rabkin, Charles C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Kaslow, Richard A.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. RP D'Souza, G (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6132, Baltimore, MD 21205 USA. EM gdsouza@jhsph.edu RI Martinez-Maza, Otoniel/B-2667-2009; OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Beachler, Daniel /0000-0003-2788-3061 FU National Institute of Allergy and Infectious Diseases [U01-AI-35043, 1P50 CA96888]; National Cancer Institute [P50 CA96888, UO1-AI-35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041] FX This study was supported by funding from the National Institute of Allergy and Infectious Diseases (U01-AI-35043, Principal Investigator L. Jacobson) and (1P50 CA96888, Principal Investigator R. Amibinder).; Data in this article were collected by the Multicenter AIDS Cohort Study (MACS) with centers (Principal Investigators) at The Johns Hopkins Bloomberg School of Public Health (Joseph B. Margolick, Lisa P. Jacobson), Howard Brown Health Center, Feinberg School of Medicine, Northwestern University and Cook County Bureau of Health Services (John P. Phair, Steven M. Wolinsky), University of California, Los Angeles (Roger Detels, Otoniel Martinez-Maza), and University of Pittsburgh (Charles R. Rinaldo). The MACS is funded by the National Institute of Allergy and Infectious Diseases with additional supplemental funding from the National Cancer Institute P50 CA96888, UO1-AI-35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041. Web site located at http://www.statepi.jhsph.edu/macs/macs.html. NR 24 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2011 VL 56 IS 2 BP 188 EP 192 DI 10.1097/QAI.0b013e3181ff976b PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 714KE UT WOS:000286807700020 PM 21116187 ER PT J AU Combs, CA Smirnov, A Chess, D McGavern, DB Schroeder, JL Riley, J Kang, SS Lugar-Hammer, M Gandjbakhche, A Knutson, JR Balaban, RS AF Combs, C. A. Smirnov, A. Chess, D. McGavern, D. B. Schroeder, J. L. Riley, J. Kang, S. S. Lugar-Hammer, M. Gandjbakhche, A. Knutson, J. R. Balaban, R. S. TI Optimizing multiphoton fluorescence microscopy light collection from living tissue by noncontact total emission detection (epiTED) SO JOURNAL OF MICROSCOPY LA English DT Article DE Brain; epi-detection; imaging; kidney; light collection improvement; muscle; photon diffusion simulations; scattering; two-photon microscopy ID 2-PHOTON EXCITATION MICROSCOPY; NONLINEAR MICROSCOPY; IN-VIVO; INJURY AB P>A benefit of multiphoton fluorescence microscopy is the inherent optical sectioning that occurs during excitation at the diffraction-limited spot. The scanned collection of fluorescence emission is incoherent; that is, no real image needs to be formed on the detector plane. The nearly isotropic emission of fluorescence excited at the focal spot allows for new detection schemes that efficiently funnel all attainable photons to detector(s). We previously showed [Combs, C.A., et al. (2007) Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector. J. Microsc. 228, 330-337] that parabolic mirrors and condensers could be combined to collect the totality of solid angle around the excitation spot for tissue blocks, leading to similar to 8-fold signal gain. Using a similar approach, we have developed an in vivo total emission detection (epiTED) instrument modified to make noncontact images from outside of living tissue. Simulations suggest that a similar to 4-fold enhancement may be possible (much larger with lower NA objectives than the 0.95 NA used here) with this approach, depending on objective characteristics, imaging depth and the characteristics of the sample being imaged. In our initial prototype, 2-fold improvements were demonstrated in the mouse brain and skeletal muscle as well as the rat kidney, using a variety of fluorophores and no compromise of spatial resolution. These results show this epiTED prototype effectively doubles emission signal in vivo; thus, it will maintain the image signal-to-noise ratio at two times the scan rate or enable full scan rate at approximately 30% reduced laser power (to minimize photo-damage). C1 [Combs, C. A.] NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA. [Smirnov, A.; Knutson, J. R.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Chess, D.; Schroeder, J. L.; Lugar-Hammer, M.; Balaban, R. S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. [McGavern, D. B.; Kang, S. S.] NINDS, Viral Immunol & Intravital Imaging Unit, NIH, Bethesda, MD 20892 USA. [Riley, J.; Gandjbakhche, A.] NICHD, Program Pediat Imaging & Tissue Sci PPITS, Sect Analyt & Funct Biophoton SAFB, NIH, Bethesda, MD USA. RP Combs, CA (reprint author), 9000 Rockville Pike,10-6N-309, Bethesda, MD 20892 USA. EM combsc@nih.gov OI McGavern, Dorian/0000-0001-9568-545X FU Intramural NIH HHS [ZIC HL006019-01] NR 22 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 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.. PD FEB PY 2011 VL 241 IS 2 BP 153 EP 161 DI 10.1111/j.1365-2818.2010.03411.x PG 9 WC Microscopy SC Microscopy GA 705EA UT WOS:000286110500006 PM 21118209 ER PT J AU Heiss, BL Maximova, OA Pletnev, AG AF Heiss, Brian L. Maximova, Olga A. Pletnev, Alexander G. TI Insertion of MicroRNA Targets into the Flavivirus Genome Alters Its Highly Neurovirulent Phenotype SO JOURNAL OF VIROLOGY LA English DT Article ID TICK-BORNE ENCEPHALITIS; ATTENUATED VIRUS-VACCINES; DENGUE TYPE-4 VIRUSES; NEURONAL DIFFERENTIATION; EXPRESSION; BRAIN; RNA; DETERMINANTS; MUTATIONS; MONKEYS AB Flaviviruses such as West Nile, Japanese encephalitis, and tick-borne encephalitis (TBEV) viruses are important neurotropic human pathogens, causing a devastating and often fatal neuroinfection. Here, we demonstrate that incorporation into the viral genome of a target sequence for cellular microRNAs expressed in the central nervous system (CNS) enables alteration of the neurovirulence of the virus and control of the neuropathogenesis of flavivirus infection. As a model virus for this type of modification, we used a neurovirulent chimeric tick-borne encephalitis/dengue virus (TBEV/DEN4) that contained the structural protein genes of a highly pathogenic TBEV. The inclusion of just a single target copy for a brain tissue-expressed mir-9, mir-124a, mir-128a, mir-218, or let-7c microRNA into the TBEV/DEN4 genome was sufficient to prevent the development of otherwise lethal encephalitis in mice infected intracerebrally with a large dose of virus. Viruses bearing a complementary target for mir-9 or mir-124a were highly restricted in replication in primary neuronal cells, had limited access into the CNS of immunodeficient mice, and retained the ability to induce a strong humoral immune response in monkeys. This work suggests that microRNA targeting to control flavivirus tissue tropism and pathogenesis might represent a rational approach for virus attenuation and vaccine development. C1 [Heiss, Brian L.; Maximova, Olga A.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3W10A,33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 41 TC 26 Z9 29 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2011 VL 85 IS 4 BP 1464 EP 1472 DI 10.1128/JVI.02091-10 PG 9 WC Virology SC Virology GA 709EP UT WOS:000286420900005 PM 21123372 ER PT J AU Jones, CP Datta, SAK Rein, A Rouzina, I Musier-Forsyth, K AF Jones, Christopher P. Datta, Siddhartha A. K. Rein, Alan Rouzina, Ioulia Musier-Forsyth, Karin TI Matrix Domain Modulates HIV-1 Gag's Nucleic Acid Chaperone Activity via Inositol Phosphate Binding SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL NUCLEOCAPSID PROTEINS; TRANSFER-RNA SYNTHETASE; IN-VITRO; GENOMIC RNA; REVERSE TRANSCRIPTION; PLASMA-MEMBRANE; CONFORMATIONAL-CHANGES; STRAND TRANSFER; LEUKEMIA-VIRUS AB Retroviruses replicate by reverse transcribing their single-stranded RNA genomes into double-stranded DNA using specific cellular tRNAs to prime cDNA synthesis. In HIV-1, human tRNA3 Lys serves as the primer and is packaged into virions during assembly. The viral Gag protein is believed to chaperone tRNA3 Lys placement onto the genomic RNA primer binding site; however, the timing and possible regulation of this event are currently unknown. Composed of the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains, the multifunctional HIV-1 Gag polyprotein orchestrates the highly coordinated process of virion assembly, but the contribution of these domains to tRNA3 Lys annealing is unclear. Here, we show that NC is absolutely essential for annealing and that the MA domain inhibits Gag's tRNA annealing capability. During assembly, MA specifically interacts with inositol phosphate (IP)-containing lipids in the plasma membrane (PM). Surprisingly, we find that IPs stimulate Gag-facilitated tRNA annealing but do not stimulate annealing in Gag variants lacking the MA domain or containing point mutations involved in PM binding. Moreover, we find that IPs prevent MA from binding to nucleic acids but have little effect on NC or Gag. We propose that Gag binds to RNA either with both NC and MA domains or with NC alone and that MA-IP interactions alter Gag's binding mode. We propose that MA's interactions with the PM trigger the switch between these two binding modes and stimulate Gag's chaperone function, which may be important for the regulation of events such as tRNA primer annealing. C1 [Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Dept Chem, Ctr Retroviral Res, Columbus, OH 43210 USA. [Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Dept Biochem, Ctr Retroviral Res, Columbus, OH 43210 USA. [Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA. [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. RP Musier-Forsyth, K (reprint author), Ohio State Univ, Dept Chem, Ctr Retroviral Res, 100 W 18th Ave, Columbus, OH 43210 USA. EM musier@chemistry.ohio-state.edu OI Datta, Siddhartha/0000-0002-4098-7490 FU NIH, National Cancer Institute, Center for Cancer Research; NIH [GM065056, T32 GM008512] FX This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by NIH grant GM065056 (to K.M.-F.). C.P.J. was supported by NIH Training Grant T32 GM008512. NR 77 TC 37 Z9 38 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2011 VL 85 IS 4 BP 1594 EP 1603 DI 10.1128/JVI.01809-10 PG 10 WC Virology SC Virology GA 709EP UT WOS:000286420900017 PM 21123373 ER PT J AU Lee, EG Roy, J Jackson, D Clark, P Boyer, PL Hughes, SH Linial, ML AF Lee, Eun-Gyung Roy, Jacqueline Jackson, Dana Clark, Patrick Boyer, Paul L. Hughes, Stephen H. Linial, Maxine L. TI Foamy Retrovirus Integrase Contains a Pol Dimerization Domain Required for Protease Activation SO JOURNAL OF VIROLOGY LA English DT Article ID BIMOLECULAR FLUORESCENCE COMPLEMENTATION; VIRUS REVERSE-TRANSCRIPTASE; LIVING CELLS; CRYSTAL-STRUCTURE; HIV-1 PROTEASE; C-TERMINUS; GAG; VISUALIZATION; POLYPROTEIN; PRECURSOR AB Unlike orthoretroviruses, foamy retroviruses (FV) synthesize Pol independently of Gag. The FV Pol precursor is cleaved only once between reverse transcriptase (RT) and integrase (IN) by the protease (PR), resulting in a PR-RT and an IN protein. Only the Pol precursor, not the cleaved subunits, is packaged into virions. Like orthoretroviral PRs, FV PR needs to dimerize to be active. Previously, we showed that a Pol mutant lacking IN has defects in PR activity and Pol packaging into virions. We now show that introduction of a leucine zipper (zip) dimerization motif in an IN truncation mutant can restore PR activity, leading to Pol processing in cells. However, these zip mutants neither cleave Gag nor incorporate Pol into virions. We propose that IN is required for Pol dimerization, which is necessary for the creation of a functional PR active site. C1 [Lee, Eun-Gyung; Roy, Jacqueline; Jackson, Dana; Linial, Maxine L.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. [Clark, Patrick] SAIC Frederick, Basic Sci Program, Frederick, MD 21702 USA. [Boyer, Paul L.; Hughes, Stephen H.] Natl Canc Res Inst Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, POB B, Frederick, MD 21783 USA. EM hughesst@mail.nih.gov FU NIH [R01 CA 18282]; NIH (National Cancer Institute) FX This research was supported by NIH grant R01 CA 18282 to M. L. L. and by the Intramural Research Program of the NIH (National Cancer Institute). NR 38 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2011 VL 85 IS 4 BP 1655 EP 1661 DI 10.1128/JVI.01873-09 PG 7 WC Virology SC Virology GA 709EP UT WOS:000286420900023 PM 21123385 ER PT J AU Goldner, J Peters, TL Richards, MH Pearce, S AF Goldner, Jonathan Peters, Tracy L. Richards, Maryse H. Pearce, Steven TI Exposure to Community Violence and Protective and Risky Contexts Among Low Income Urban African American Adolescents: A Prospective Study SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE Time sampling technique; Exposure to community violence; African American; Urban low income ID INNER-CITY; ROUTINE ACTIVITIES; YOUNG ADOLESCENTS; CHILDREN; YOUTH; RESILIENCE; VICTIMIZATION; NEIGHBORHOODS; INTERVENTION; DELINQUENCY AB This study examined protective and risky companionship and locations for exposure to community violence among African American young adolescents living in high crime, urban areas. The Experience Sampling Method (ESM), an in vivo data collection method, was employed to gather information from 233 students (62% female) over 3 years, beginning in the 6th grade. Questionnaire variables of exposure to community violence were regressed onto ESM companionship and location variables, cross-sectionally and longitudinally, separately for boys and girls. At different points, time spent with parents, in school, and outside in private space was associated with less exposure to violence for boys and girls, while time spent with girls was protective for boys. In addition, time spent outside in public and with older peers was associated with increased risk for boys and girls. These findings are discussed in relation to previous and potential future research, and to strategies to prevent exposure to community violence. C1 [Goldner, Jonathan; Peters, Tracy L.; Richards, Maryse H.; Pearce, Steven] Loyola Univ, Dept Psychol, Chicago, IL 60626 USA. [Peters, Tracy L.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Richards, MH (reprint author), Loyola Univ, Dept Psychol, 6525 N Sheridan Rd, Chicago, IL 60626 USA. EM mrichar@luc.edu NR 55 TC 5 Z9 5 U1 4 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD FEB PY 2011 VL 40 IS 2 BP 174 EP 186 DI 10.1007/s10964-010-9527-4 PG 13 WC Psychology, Developmental SC Psychology GA 705FO UT WOS:000286114500004 PM 20352310 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. [Gipson, Chester] USDA, APHIS, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD FEB PY 2011 VL 40 IS 2 BP 36 EP 36 DI 10.1038/laban0211-36a PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 712DX UT WOS:000286646000008 PM 21252974 ER PT J AU Shi, ZM Yuan, BJ Zhang, CL Zhou, MH Holmboe-Ottesen, G AF Shi, Zumin Yuan, Baojun Zhang, Cuilin Zhou, Minghao Holmboe-Ottesen, Gerd TI Egg consumption and the risk of diabetes in adults, Jiangsu, China SO NUTRITION LA English DT Article DE Egg consumption; Diabetes; China ID HEART-DISEASE RISK; PHYSICIANS HEALTH; CHOLESTEROL; METAANALYSIS; POPULATION; RESPONSES; PLASMA; TYPE-2 AB Background: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. Method: Data from a household survey in the year 2002 among 2849 adults aged >= 20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. Results: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and >= 1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed >= 2 eggs/wk than those who consumed eggs less often. Conclusion: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. (C) 2011 Elsevier Inc. All rights reserved. C1 [Shi, Zumin; Yuan, Baojun; Zhou, Minghao] Jiangsu Prov Ctr Dis Control & Prevention, Nanjing, Peoples R China. [Shi, Zumin; Holmboe-Ottesen, Gerd] Univ Oslo, Dept Gen Practice & Community Med, Inst Hlth & Soc, Oslo, Norway. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Shi, ZM (reprint author), Jiangsu Prov Ctr Dis Control & Prevention, Nanjing, Peoples R China. EM zumins@vip.sina.com RI Shi, Zumin/A-1093-2009 OI Shi, Zumin/0000-0002-3099-3299 FU Jiangsu Provincial Natural Science Foundation [BK2008464]; Jiangsu Provincial Health Bureau; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX The authors thank the participating Regional Centers for Disease Control and Prevention in Jiangsu Province, including the Nanjing, Xuzhou, Jiangyin, Taicang, Suining, Jurong, Sihong, and Haimen Centres for their support for the data collection. This study was financed by Jiangsu Provincial Natural Science Foundation (BK2008464) and Jiangsu Provincial Health Bureau. Dr. Cuilin Zhang is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 21 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD FEB PY 2011 VL 27 IS 2 BP 194 EP 198 DI 10.1016/j.nut.2010.01.012 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 710UL UT WOS:000286542400013 PM 20471806 ER PT J AU Boyce, JA Assa'a, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SE Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'a, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan E. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the diagnosis and management of food allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO NUTRITION LA English DT Article C1 [Plaut, Marshall; Cooper, Susan E.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Brigham & Womens Hosp, Dept Emergency Med,Div Rheumatol Allergy & Immuno, Massachusetts Gen Hosp,Dept Med, Boston, MA 02115 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Pulm & Crit Med Div, Boston, MA 02115 USA. [Assa'a, Amal] Univ Cincinnati, Div Allergy & Immunol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45221 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27706 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27706 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Div Allergy & Immunol, Dept Pediat, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Southampton SO9 5NH, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport PO30 5TG, Isle Of Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton SO16 6YD, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Allergy & Immunol Sect, Dept Pediat, Baton Rouge, LA 70803 USA. [Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, Rochester, NY 14642 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Sect Pediat Gastroenterol Hepatol & Nutr, Digest Hlth Inst, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. Univ Colorado, Denver Sch Med, Dept Pediat, Aurora, CO USA. Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. Univ Tennessee, Coll Med, Dept Med, Div Allergy & Immunol, Knoxville, TN 37996 USA. US FDA, Off Food Addit Safety, College Pk, MD USA. Childrens Hosp Orange Cty, Orange, CA USA. Childrens Hosp Boston, Div Immunol, Boston, MA USA. Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB R3T 2N2, Canada. Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. Olmsted Med Ctr, Dept Res, Rochester, MN USA. Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 6503, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU NIAID; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; National Institutes of Health; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; Dey; Novartis; Astellas; Astellas, Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc.; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; AllerGen; Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health, Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious, Diseases: National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX NIAID-sponsored Expert Panel; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoSmithKline and as a speaker for the American College of Allergy, Asthma, and, Immunology, the North East Allergy Society, the Virginia Allergy Society, the New, England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has, received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Dannon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received, funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the, National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G. T. Furuta has served as a consultant and/or speaker to Caption Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J. M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc. Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; F. E. R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health, Research.; S.J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious, Diseases: National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 0 TC 18 Z9 18 U1 1 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD FEB PY 2011 VL 27 IS 2 BP 253 EP 267 DI 10.1016/j.nut.2010.12.001 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 710UL UT WOS:000286542400022 PM 21215925 ER PT J AU Landon, MB Mele, L Spong, CY Carpenter, MW Ramin, SM Casey, B Wapner, RJ Varner, MW Rouse, DJ Thorp, JM Sciscione, A Catalano, P Harper, M Saade, G Caritis, SN Sorokin, Y Peaceman, AM Tolosa, JE Anderson, GD AF Landon, Mark B. Mele, Lisa Spong, Catherine Y. Carpenter, Marshall W. Ramin, Susan M. Casey, Brian Wapner, Ronald J. Varner, Michael W. Rouse, Dwight J. Thorp, John M., Jr. Sciscione, Anthony Catalano, Patrick Harper, Margaret Saade, George Caritis, Steve N. Sorokin, Yoram Peaceman, Alan M. Tolosa, Jorge E. Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst TI The Relationship Between Maternal Glycemia and Perinatal Outcome SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; GLUCOSE-TOLERANCE TEST; PREGNANCY OUTCOMES; SCREENING-TESTS; CRITERIA; INTOLERANCE; TRIAL AB OBJECTIVE: To examine the relationship between varying degrees of maternal hyperglycemia and pregnancy outcomes. METHODS: This was a secondary analysis of a treatment trial for mild gestational diabetes including four cohorts: 1) 473 women with untreated mild gestational diabetes; 2) 256 women with a positive 50-g screen and one abnormal oral glucose tolerance test (OGTT) value; 3) 675 women with a positive screen and no abnormal OGTT values; and 4) 437 women with a normal 50-g screen. Groups were compared by test of trend for a composite perinatal outcome (neonatal hypoglycemia, hyperbilirubinemia, elevated cord C-peptide level, and perinatal trauma or death), frequency of large for gestational age neonates, shoulder dystocia, and pregnancy-related hypertension. Three-hour OGTT levels (fasting, 1-, 2-, and 3-hour) levels were divided into categories and analyzed for their relationship to perinatal and maternal outcomes. RESULTS: There were significant trends by glycemic status among the four cohorts for the composite and all other outcomes (P<.001). Analysis for trend according to OGTT categories showed an increasing relationship between fasting and all postload levels and the various outcomes (P<.05). Fasting glucose 90 mg/dL or greater and 1 hour 165 mg/dL or greater were associated with an increased risk for the composite outcome (odds ratios and 95% confidence intervals of 2.0 [1.03-4.15] and 1.46 [1.02-2.11] to 1.52 [1.08-2.15] for the fasting and 1 hour, respectively). A 1 hour glucose 150 mg/dL or greater was associated with an increased risk for large for gestational age (odds ratios, 1.8 [1.02-3.18] to 2.35 [1.35-4.14]); however, 2- and 3-hour glucose levels did not increase the risk for the composite or large for gestational age until well beyond current gestational diabetes diagnostic thresholds. CONCLUSION: A monotonic relationship exists between increasing maternal glycemia and perinatal morbidity. Current OGTT criteria require reevaluation in determining thresholds for the diagnosis and treatment of gestational diabetes. (Obstet Gynecol 2011;117:218-24) DOI: 10.1097/AOG.0b013e318203ebe0 C1 [Landon, Mark B.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. Brown Univ, Dept Obstet, Providence, RI 02912 USA. Brown Univ, Dept Gynecol, Providence, RI 02912 USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Columbia Univ, New York, NY USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Drexel Univ, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Univ Texas Med Branch, Galveston, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Wayne State Univ, Detroit, MI USA. Northwestern Univ, Chicago, IL 60611 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Landon, MB (reprint author), Ohio State Univ, Coll Med, Dept Obstet & Gynecol, 395 12th Ave,Suite 572, Columbus, OH 43210 USA. EM Mark.Landon@osumc.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers [M01-RR00034]; National Center for Research Resources [UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801), General Clinical Research Centers Grant (M01-RR00034), and the National Center for Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234) and does not necessarily represent the official views of the National Institute of Child Health and Human Development or the National Institutes of Health. NR 16 TC 52 Z9 55 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2011 VL 117 IS 2 BP 218 EP 224 DI 10.1097/AOG.0b013e318203ebe0 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 709SB UT WOS:000286460600004 PM 21309194 ER PT J AU Rouse, DJ Weiner, SJ Bloom, SL Varner, MW Spong, CY Ramin, SM Caritis, SN Grobman, WA Sorokin, Y Sciscione, A Carpenter, MW Mercer, BM Thorp, JM Malone, FD Harper, M Iams, JD Anderson, GD AF Rouse, Dwight J. Weiner, Steven J. Bloom, Steven L. Varner, Michael W. Spong, Catherine Y. Ramin, Susan M. Caritis, Steve N. Grobman, William A. Sorokin, Yoram Sciscione, Anthony Carpenter, Marshall W. Mercer, Brian M. Thorp, John M., Jr. Malone, Fergal D. Harper, Margaret Iams, Jay D. Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst TI Failed Labor Induction Toward an Objective Diagnosis SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NULLIPAROUS WOMEN; CESAREAN DELIVERY; TERM AB METHODS: This was a secondary analysis of a randomized multicenter trial in which all cervical examinations from admission were recorded. Inclusion criteria: nulliparas at or beyond 36 weeks of gestation undergoing induction with a cervix of 2 cm or less dilated and less than completely effaced. The latent phase of labor was defined as ending at a cervical dilation of 4 cm and effacement of at least 90%, or at a cervical dilation of 5 cm regardless of effacement. RESULTS: A total of 1,347 women were analyzed. The overall vaginal delivery rate was 63.2%. Most women had exited the latent phase after 6 hours of oxytocin and membrane rupture (n = 939; 69.7%); only 5% remained in the latent phase after 12 hours. The longer the latent phase, the lower the vaginal delivery rate. Even so, 39.4% of the 71 women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Chorioamnionitis, endometritis, or both, and uterine atony were the only maternal adverse outcomes related to latent-phase duration: adjusted odds ratios (95% confidence intervals) of 1.12 (1.07, 1.17) and 1.13 (1.06, 1.19), respectively, for each additional hour. Neonatal outcomes were not related to latent-phase duration. CONCLUSION: Almost 40% of the women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Therefore, it is reasonable to avoid deeming labor induction a failure in the latent phase until oxytocin has been administered for at least 12 hours after membrane rupture. (Obstet Gynecol 2011;117:267-72) DOI: 10.1097/AOG.0b013e318207887a C1 [Rouse, Dwight J.] Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02905 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Utah, Salt Lake City, UT USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. Wayne State Univ, Detroit, MI USA. Drexel Univ, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Univ N Carolina, Chapel Hill, NC USA. Columbia Univ, New York, NY USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Texas Med Branch, Galveston, TX USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Rouse, DJ (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, 101 Dudley St,3rd Floor, Providence, RI 02905 USA. EM drouse@wihri.org RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, and HD36801] and does not necessarily represent the official views of the NICHD or the NIH. NR 9 TC 29 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2011 VL 117 IS 2 BP 267 EP 272 DI 10.1097/AOG.0b013e318207887a PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 709SB UT WOS:000286460600010 PM 21252738 ER PT J AU Wakamatsu, K Hearing, V AF Wakamatsu, Kazumasa Hearing, Vincent TI Shosuke Ito PROFILE SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Biographical-Item C1 [Wakamatsu, Kazumasa] Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi, Japan. [Hearing, Vincent] NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Wakamatsu, K (reprint author), Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi, Japan. EM kwaka@fujita-hu.ac.jp; hearingv@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD FEB PY 2011 VL 24 IS 1 BP 247 EP 247 DI 10.1111/j.1755-148X.2010.00739.x PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 706IA UT WOS:000286210400032 PM 21232028 ER PT J AU Fitzgerald, PJ AF Fitzgerald, Paul J. TI A neurochemical yin and yang: does serotonin activate and norepinephrine deactivate the prefrontal cortex? SO PSYCHOPHARMACOLOGY LA English DT Review DE Executive function; Impulsivity; Cognitive flexibility; Reversal learning; Working memory; Fluoxetine; Clonidine; Propranolol; Guanfacine ID SPATIAL WORKING-MEMORY; ACUTE TRYPTOPHAN DEPLETION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; RECEPTOR KNOCKOUT MICE; AGED RHESUS-MONKEYS; REACTION-TIME-TASK; COGNITIVE FLEXIBILITY; LOCUS-COERULEUS; IMPULSIVE BEHAVIOR AB The prefrontal cortex (PFC) receives serotonergic input from the dorsal raphe nucleus of the brainstem, as well as noradrenergic input from another brainstem nucleus, the locus coeruleus. A large number of studies have shown that these two neurotransmitter systems, and drugs that affect them, modulate the functional properties of the PFC in both humans and animal models. Here I examine the hypothesis that serotonin (5-HT) plays a general role in activating the PFC, whereas norepinephrine (NE) plays a general role in deactivating this brain region. In this manner, the two neurotransmitter systems may have opposing effects on PFC-influenced behavior. To assess this hypothesis, three primary lines of evidence are examined comprising the effects of 5-HT and NE on impulsivity, cognitive flexibility, and working memory. While all of the existing data do not unequivocally support the activation/deactivation hypothesis, there is a large body of support for it. C1 [Fitzgerald, Paul J.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA. RP Fitzgerald, PJ (reprint author), NIAAA, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM pfitz@mbi.mb.jhu.edu NR 129 TC 15 Z9 15 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2011 VL 213 IS 2-3 BP 171 EP 182 DI 10.1007/s00213-010-1856-1 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 716AT UT WOS:000286938000002 PM 20386882 ER PT J AU Li, JX Crocker, C Koek, W Rice, KC France, CP AF Li, Jun-Xu Crocker, Caroline Koek, Wouter Rice, Kenner C. France, Charles P. TI Effects of serotonin (5-HT)(1A) and 5-HT2A receptor agonists on schedule-controlled responding in rats: drug combination studies SO PSYCHOPHARMACOLOGY LA English DT Article DE Serotonin; Receptor; Drug interaction; Additivity; Rat; Schedule-controlling responding; Agonist; Antagonist ID ANTAGONIST; EFFICACY; DOI AB Indirect-acting serotonin (5-HT) receptor agonists (e.g., selective 5-HT reuptake inhibitors [SSRI]) stimulate multiple 5-HT receptors, although the role of particular receptors as well as interaction(s) among different receptors in the therapeutic effects of SSRIs is not fully understood. Relatively few studies have systematically examined direct-acting agonists in combination. This study examined the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (8-OH-DPAT; 0.01-10.0 mg/kg) and 3-chloro-4-fluorophenyl-4-fluoro-4-([(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl)-piperidin-1-yl-methanone (F13714; 0.01-1.0 mg/kg) and the 5-HT2A receptor agonists 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 0.32-10.0 mg/kg) and dipropyltryptamine (DPT; 1.0-32.0 mg/kg), alone and in combination, in rats responding under a fixed ratio schedule of food presentation. When administered alone, each drug decreased the rate of responding in a dose-related manner with the potency order being F13714 > 8-OH-DPAT > DOM > DPT. WAY100635 (5-HT1A receptor antagonist; 0.01-0.1 mg/kg) attenuated the rate-decreasing effects of 8-OH-DPAT and F13714 while MDL100907 (5-HT2A receptor antagonist; 0.01-0.1 mg/kg) attenuated the rate-decreasing effects of DOM and DPT. Dose addition analysis showed that the interaction between 8-OH-DPAT and F13714, as well as the interaction between DOM and DPT, was additive. In contrast, the interaction between 8-OH-DPAT and DOM, as well as the interaction between F13714 and DOM, was infra-additive. This study shows that for some dose combinations, agonist actions at one 5-HT receptor subtype attenuate agonist actions at another 5-HT receptor subtype; thus, the combined neuropharmacological actions and therapeutic effects of indirect-acting agonists are not likely to be adequately characterized by examining in isolation activity at particular 5-HT receptor subtypes. C1 [Li, Jun-Xu; Crocker, Caroline; Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Lab, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU National Institute on Drug Abuse, National Institutes of Health [K05 DA17918] FX CPF is supported by a Senior Scientist Award from the National Institute on Drug Abuse, National Institutes of Health (K05 DA17918). This research was supported, in part, by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the views of the National Institute on Drug Abuse or the National Institutes of Health. NR 21 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2011 VL 213 IS 2-3 BP 489 EP 497 DI 10.1007/s00213-010-2136-9 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 716AT UT WOS:000286938000022 PM 21174080 ER PT J AU Liu, HJ Fergusson, MM Wu, JJ Rovira, II Liu, J Gavrilova, O Lu, T Bao, JJ Han, DH Sack, MN Finkel, T AF Liu, Hongjun Fergusson, Maria M. Wu, J. Julie Rovira, Ilsa I. Liu, Jie Gavrilova, Oksana Lu, Teng Bao, Jianjun Han, Donghe Sack, Michael N. Finkel, Toren TI Wnt Signaling Regulates Hepatic Metabolism SO SCIENCE SIGNALING LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; BETA-CATENIN; GLUCOSE-PRODUCTION; TCF7L2 GENE; LIVER; GLUCONEOGENESIS; RISK; EXPRESSION; MICE; MECHANISMS AB The contribution of the Wnt pathway has been extensively characterized in embryogenesis, differentiation, and stem cell biology but not in mammalian metabolism. Here, using in vivo gain-and loss-of-function models, we demonstrate an important role for Wnt signaling in hepatic metabolism. In particular, beta-catenin, the downstream mediator of canonical Wnt signaling, altered serum glucose concentrations and regulated hepatic glucose production. beta-Catenin also modulated hepatic insulin signaling. Furthermore, beta-catenin interacted with the transcription factor FoxO1 in livers from mice under starved conditions. The interaction of FoxO1 with beta-catenin regulated the transcriptional activation of the genes encoding glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), the two rate-limiting enzymes in hepatic gluconeogenesis. Moreover, starvation induced the hepatic expression of mRNAs encoding different Wnt isoforms. In addition, nutrient deprivation appeared to favor the association of beta-catenin with FoxO family members, rather than with members of the T cell factor of transcriptional activators. Notably, in a model of diet-induced obesity, hepatic deletion of beta-catenin improved overall metabolic homeostasis. These observations implicate Wnt signaling in the modulation of hepatic metabolism and raise the possibility that Wnt signaling may play a similar role in the metabolic regulation of other tissues. C1 [Liu, Hongjun; Fergusson, Maria M.; Wu, J. Julie; Rovira, Ilsa I.; Liu, Jie; Lu, Teng; Bao, Jianjun; Sack, Michael N.; Finkel, Toren] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, Bethesda, MD 20892 USA. [Lu, Teng] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Han, Donghe] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU NIA NIH HHS [R00 AG032356, R00 AG032356-03] NR 48 TC 65 Z9 66 U1 0 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD FEB 1 PY 2011 VL 4 IS 158 AR ra6 DI 10.1126/scisignal.2001249 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 714HY UT WOS:000286801000001 PM 21285411 ER PT J AU Collins, BJ Stout, MD Levine, KE Kissling, GE Melnick, RL Fennell, TR Pritchard, JB Walden, R Abdo, K Fernando, RA Burka, LT Hooth, MJ AF Collins, Bradley J. Stout, Matthew D. Levine, Keith E. Kissling, Grace E. Melnick, Ronald L. Fennell, Timothy R. Pritchard, John B. Walden, Ramsey Abdo, Kamal Fernando, Reshan A. Burka, Leo T. Hooth, Michelle J. TI Hexavalent Chromium in Drinking Water, Reply SO TOXICOLOGICAL SCIENCES LA English DT Letter C1 [Collins, Bradley J.; Stout, Matthew D.; Kissling, Grace E.; Melnick, Ronald L.; Abdo, Kamal; Burka, Leo T.; Hooth, Michelle J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Levine, Keith E.; Fennell, Timothy R.; Fernando, Reshan A.] RTI Int, Discovery & Analyt Sci, Res Triangle Pk, NC 27709 USA. [Pritchard, John B.; Walden, Ramsey] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Collins, BJ (reprint author), NIEHS, Natl Toxicol Program, 111 Alexander Dr,MD K2-13, Res Triangle Pk, NC 27709 USA. EM collin10@niehs.nih.gov RI Fennell, Tim/D-9936-2013 NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2011 VL 119 IS 2 BP 425 EP 425 DI 10.1093/toxsci/kfq348 PG 1 WC Toxicology SC Toxicology GA 710XH UT WOS:000286549800019 ER PT J AU Hunn, JP Feng, CG Sher, A Howard, JC AF Hunn, Julia P. Feng, Carl G. Sher, Alan Howard, Jonathan C. TI The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens SO MAMMALIAN GENOME LA English DT Article ID INDUCIBLY EXPRESSED GTPASE; TOXOPLASMA-GONDII; IFN-GAMMA; P47 GTPASES; INTERFERON-GAMMA; HOST-DEFENSE; TRYPANOSOMA-CRUZI; POPULATION BIOLOGY; NUCLEOTIDE-BINDING; CROHNS-DISEASE AB The immunity-related GTPases (IRGs) belong to the family of large, interferon-inducible GTPases and constitute a cell-autonomous resistance system essential for the control of vacuolar pathogens like Toxoplasma gondii in mice. Recent results demonstrated that numerous IRG members accumulate collaboratively at the parasitophorous vacuole of invading T. gondii leading to the destruction of the vacuole and the parasite and subsequent necrotic host cell death. Complex regulatory interactions between different IRG proteins are necessary for these processes. Disturbance of this finely balanced system, e.g., by single genetic deficiency for the important negative regulator Irgm1 or the autophagic regulator Atg5, leads to spontaneous activation of the effector IRG proteins when induced by IFN gamma. This activation has cytotoxic consequences resulting in a severe lymphopenia, macrophage defects, and failure of the adaptive immune system in Irgm1-deficient mice. However, alternative functions in phagosome maturation and induction of autophagy have been proposed for Irgm1. The IRG system has been studied primarily in mice, but IRG genes are present throughout the mammalian lineage. Interestingly, the number, type, and diversity of genes present differ greatly even between closely related species, probably reflecting intimate host-pathogen coevolution driven by an armed race between the IRG resistance proteins and pathogen virulence factors. IRG proteins are targets for polymorphic T. gondii virulence factors, and genetic variation in the IRG system between different mouse strains correlates with resistance and susceptibility to virulent T. gondii strains. C1 [Hunn, Julia P.; Howard, Jonathan C.] Univ Cologne, Inst Genet, D-50674 Cologne, Germany. [Feng, Carl G.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Howard, JC (reprint author), Univ Cologne, Inst Genet, Zuelpicher Str 47A, D-50674 Cologne, Germany. EM j.howard@uni-koeln.de OI Howard, Jonathan/0000-0003-2756-5143 FU Deutsche Forschungsgemeinschaft [SFB635, SFB670, SFB680, SPP1399]; NIAID, NIH FX JCH and JPH were supported by SFB635, SFB670, SFB680 and SPP1399 from the Deutsche Forschungsgemeinschaft; and CGF and AS were supported by the Intramural Research Program of the NIAID, NIH. We are grateful to our colleague Gregory Taylor for his pioneering work on the IRG system. NR 85 TC 44 Z9 44 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 2011 VL 22 IS 1-2 BP 43 EP 54 DI 10.1007/s00335-010-9293-3 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 711UG UT WOS:000286616300005 PM 21052678 ER PT J AU Gotts, SJ Milleville, SC Bellgowan, PSF Martin, A AF Gotts, Stephen J. Milleville, Shawn C. Bellgowan, Patrick S. F. Martin, Alex TI Broad and Narrow Conceptual Tuning in the Human Frontal Lobes SO CEREBRAL CORTEX LA English DT Article DE animals; category; fMRI adaptation; semantic memory; visual objects ID HUMAN VISUAL-CORTEX; POSTERIOR INFEROTEMPORAL CORTEX; RESONANCE-IMAGING EVIDENCE; PRIMATE PREFRONTAL CORTEX; INFERIOR TEMPORAL CORTEX; NEURAL MECHANISMS; OBJECT RECOGNITION; SEMANTIC MEMORY; OCCIPITAL CORTEX; FUNCTIONAL ARCHITECTURE AB Previous work has implicated prefrontal cortices in selecting among and retrieving conceptual information stored elsewhere. However, recent neurophysiological work in monkeys suggests that prefrontal cortex may play a more direct role in representing conceptual information in a flexible context-specific manner. Here, we investigate the nature of visual object representations from perceptual to conceptual levels in an unbiased data-driven manner using a functional magnetic resonance imaging adaptation paradigm with pictures of animals. Throughout much of occipital cortex, activity was highly sensitive to changes in 2D stimulus form, consistent with tuning to form and position within retinotopic coordinates and matching an automated measure of shape similarity. Broad superordinate conceptual information was represented as early as extrastriate and posterior ventral temporal cortex. These regions were not completely invariant to form, suggesting that form similarity remains an important organizational constraint into the temporal cortex. Separate sites within prefrontal cortex represented broad and narrow conceptual tuning, with more anterior sites tuned narrowly to close conceptual associates in a manner that was invariant to stimulus form/position and that matched independent similarity ratings of the stimuli. The combination of broad and narrow conceptual tuning within prefrontal cortex may support flexible selection, retrieval, and classification of objects at different levels of categorical abstraction. C1 [Gotts, Stephen J.; Milleville, Shawn C.; Bellgowan, Patrick S. F.; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Gotts, SJ (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C-217, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov RI martin, alex/B-6176-2009; Gotts, Stephen/J-4842-2012 FU National Institute of Mental Health, Division of Intramural Research FX National Institute of Mental Health, Division of Intramural Research. NR 89 TC 12 Z9 12 U1 2 U2 4 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 FEB PY 2011 VL 21 IS 2 BP 477 EP 491 DI 10.1093/cercor/bhq113 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 706KK UT WOS:000286217100025 PM 20562319 ER PT J AU Dickstein, LP Zoghbi, SS Fujimura, Y Imaizumi, M Zhang, Y Pike, VW Innis, RB Fujita, M AF Dickstein, Leah P. Zoghbi, Sami S. Fujimura, Yota Imaizumi, Masao Zhang, Yi Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Comparison of F-18- and C-11-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Compartment model; Kinetic analysis; Inflammation; Translocator protein (18 kDa); PET ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; IN-VIVO; 18 KDA; NONHUMAN-PRIMATES; PET RADIOLIGAND; NEUROINFLAMMATION; QUANTIFICATION; NOMENCLATURE; INFLAMMATION; LIGANDS AB Translocator protein (TSPO) is a promising biomarker for neuroinflammation. We developed two new PET ligands, F-18-PBR06 and C-11-PBR28, to image TSPOs. Although our prior studies suggest that either of the two ligands could be used to quantify TSPOs in human brain, the studies were done in different sets of subjects. In this study, we directly compared F-18-PBR06 and C-11-PBR28 in eight human subjects to determine (1) whether either ligand provides more precise measurements of TSPOs and (2) whether the higher in vitro affinity of PBR06 compared to PBR28 led to higher in vivo binding of F-18-PBR06 compared to C-11-PBR28. In vivo binding was calculated as total distribution volume (V (T)), using an unconstrained two-tissue compartment model. V (T) was corrected for plasma free fraction (f (P)) to measure ligand binding based on free ligand concentration in brain. Both ligands measured V (T) with similar precision, as evidenced by similarly good identifiability. However, V (T) for both radioligands increased with increasing lengths of data acquisition, consistent with the accumulation of radiometabolites in brain. Despite its higher lipophilicity and higher in vitro affinity, V (T)/f (P) of F-18-PBR06 was similar to that of C-11-PBR28. Both F-18-PBR06 and C-11-PBR28 are similar in terms of precision, sensitivity to accumulation of radiometabolites, and magnitude of in vivo binding. Thus, selection between the two radioligands will be primarily determined by the logistical impact of the different half-lives of the two radionuclides (110 vs 20 min). C1 [Dickstein, Leah P.; Zoghbi, Sami S.; Fujimura, Yota; Imaizumi, Masao; Zhang, Yi; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B1D43,10 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA. EM FujitaM@intra.nimh.nih.gov OI Dickstein, Leah/0000-0002-4779-4122 FU NIMH [Z01-MH-002795-07, Z01-MH-002793-07] FX This research was supported by the Intramural Program of NIMH (project #Z01-MH-002795-07 and #Z01-MH-002793-07). We thank Kacey Anderson, M. Desiree Ferraris Araneta, Robert L. Gladding, Kimberly Jenko, William C. Kreisl, Barbara Scepura, Cheryl Wallisch, and the staff of the PET Department for successful completion of the studies, PMOD Technologies (Zurich, Switzerland) for providing its image analysis and modeling software, and Jussi Hirvonen for assisting statistical analyses. NR 14 TC 13 Z9 13 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD FEB PY 2011 VL 38 IS 2 BP 352 EP 357 DI 10.1007/s00259-010-1622-y PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 706GC UT WOS:000286205000017 PM 21085954 ER PT J AU Yu, B Ruman, J Christman, G AF Yu, Bo Ruman, Jane Christman, Gregory TI The role of peripheral gonadotropin-releasing hormone receptors in female reproduction SO FERTILITY AND STERILITY LA English DT Article DE GnRH; peripheral GnRH receptor; central GnRH receptor; GnRH agonist; chemotherapy; apoptosis; ovarian damage; implantation; placenta ID INDUCED OVARIAN DAMAGE; PLACENTAL GNRH RECEPTOR; BREAST-CANCER PATIENTS; HUMAN ENDOMETRIAL; CHORIONIC-GONADOTROPIN; YOUNG-WOMEN; GENE-EXPRESSION; FERTILITY PRESERVATION; INDUCED GONADOTOXICITY; EMBRYONIC-DEVELOPMENT AB Objective: To review the physiologic functions and clinical significance of peripheral GnRH receptors. Design: Literature review. All peer-reviewed journal articles published before 2010 on peripheral GnRH receptors were searched for in the Pubmed database, and relevant findings were summarized. Result(s): Peripheral GnRH/GnRH receptor systems may serve as regulators of hCG synthesis and implantation, and play crucial roles in antiproliferation and apoptosis. Currently, GnRH agonists have been used in cancer treatment and ovary protection during chemotherapy, taking advantage of the local direct effect mediated by peripheral GnRH receptors. Conclusion(s): The ubiquitous GnRH/GnRH receptor system in human tissues has been shown to have some important physiologic functions. Further research to clarify functions of these peripheral GnRH receptors may lead to discovery of new therapeutic options. (Fertil Steril (R) 2011;95:465-73. (C)2011 by American Society for Reproductive Medicine.) C1 [Yu, Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA. [Ruman, Jane] Mt Sinai Med Ctr, Dept Obstet & Gynecol, New York, NY 10029 USA. [Christman, Gregory] Univ Michigan, Med Ctr, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. RP Yu, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, 10 Ctr Dr,1E-3140, Bethesda, MD 20892 USA. EM yub4@mail.nih.gov NR 83 TC 16 Z9 20 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2011 VL 95 IS 2 BP 465 EP 473 DI 10.1016/j.fertnstert.2010.08.045 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 709EA UT WOS:000286419000007 PM 20888559 ER PT J AU Kuehn, D Carter, TC Aros, S Conley, MR Troendle, J Cassorla, F Mills, JL AF Kuehn, D. Carter, T. C. Aros, S. Conley, M. R. Troendle, J. Cassorla, F. Mills, J. L. TI HEAVY PRENATAL EXPOSURE TO ALCOHOL AND THE RISK FOR GROWTH, FACIAL AND NEUROLOGIC ABNORMALITIES IN CHILDREN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting CY FEB 17-19, 2011 CL New Orleans, LA C1 [Kuehn, D.; Carter, T. C.; Conley, M. R.; Troendle, J.; Mills, J. L.] NICHD, Eunice Kennedy Shriver, NIH, DHHS, Bethesda, MD USA. [Kuehn, D.] USUHS, Bethesda, MD USA. [Aros, S.; Cassorla, F.] Univ Chile, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2011 VL 59 IS 2 MA 128 BP 408 EP 408 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 709SK UT WOS:000286461500139 ER PT J AU Li, LQ Jothi, R Cui, KR Lee, JY Cohen, T Gorivodsky, M Tzchori, I Zhao, YG Hayes, SM Bresnick, EH Zhao, KJ Westphal, H Love, PE AF Li, LiQi Jothi, Raja Cui, Kairong Lee, Jan Y. Cohen, Tsadok Gorivodsky, Marat Tzchori, Itai Zhao, Yangu Hayes, Sandra M. Bresnick, Emery H. Zhao, Keji Westphal, Heiner Love, Paul E. TI Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells SO NATURE IMMUNOLOGY LA English DT Article ID SELF-RENEWAL; IN-VIVO; PROGENITOR CELLS; PROTEIN LMO2; GATA FACTORS; MICE; LEUKEMIA; DIFFERENTIATION; IDENTIFICATION; EXPRESSION AB The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs. C1 [Li, LiQi; Lee, Jan Y.; Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Cohen, Tsadok; Gorivodsky, Marat; Tzchori, Itai; Zhao, Yangu; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mammalian Mol Genet, NIH, Bethesda, MD USA. [Hayes, Sandra M.] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA. [Bresnick, Emery H.] Univ Wisconsin, Sch Med & Publ Hlth, Paul Carbone Canc Ctr, Wisconsin Inst Med Res, Madison, WI USA. RP Love, PE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM lovep@mail.nih.gov RI Jothi, Raja/G-3780-2015 FU National Institutes of Health [DK068634] FX We thank D. El-Khoury and A. Grinberg for technical support, and M. Mukhopadhyay for advice about mouse experiments. Supported by the Intramural Research Program of the National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health and Human Development, L. L., J.Y.L., T. C., M. G., I. T., Y.Z., H. W. and P. E. L.; National Institute of Environmental Health Sciences, R.J.; National Heart, Lung, and Blood Institute, K. C. and K.Z.) and the National Institutes of Health (DK068634 to E.H.B.). NR 45 TC 56 Z9 59 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2011 VL 12 IS 2 BP 129 EP U38 DI 10.1038/ni.1978 PG 9 WC Immunology SC Immunology GA 708QF UT WOS:000286378400006 PM 21186366 ER PT J AU Kannan, P Telu, S Shukla, S Ambudkar, SV Pike, VW Halldin, C Gottesman, MM Innis, RB Hall, MD AF Kannan, Pavitra Telu, Sanjay Shukla, Suneet Ambudkar, Suresh V. Pike, Victor W. Halldin, Christer Gottesman, Michael M. Innis, Robert B. Hall, Matthew D. TI The "Specific" P-Glycoprotein Inhibitor Tariquidar Is Also a Substrate and an Inhibitor for Breast Cancer Resistance Protein (BCRP/ABCG2) SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Positron emission tomography; drug transporters; P-glycoprotein; breast cancer resistance protein; blood-brain barrier; transport inhibitors; tariquidar ID BLOOD-BRAIN-BARRIER; DRUG EFFLUX TRANSPORTERS; MULTIDRUG-RESISTANCE; XR9576; ABCG2; RADIOTRACERS; LYMPHOCYTES; REVERSAL AB Tariquidar was developed as a specific inhibitor of the efflux transporter ABCB1. Recent positron emission tomographic brain imaging studies using [(11)C]-tariquidar to measure ABCB1 (P-gp, P-glycoprotein) density in mice indicate that the inhibitor may not be as specific as previously thought. We examined its selectivity as an inhibitor and a substrate for the human transporters P-gp, breast cancer resistance protein (BCRP, ABCG2), and multidrug resistance protein 1 (MRP1, ABCC1). Our results show that at low concentrations, tariquidar acts selectively as an inhibitor of P-gp and also as a substrate of BCRP. At much higher concentrations (>= 100 nM), tariquidar acts as an inhibitor of both P-gp and BCRP. Thus, the in vivo specificity of tariquidar depends on concentration and the relative density and capacity of P-gp vs BCRP. C1 [Kannan, Pavitra; Telu, Sanjay; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Kannan, Pavitra; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Shukla, Suneet; Ambudkar, Suresh V.; Gottesman, Michael M.; Hall, Matthew D.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr,Rm B1D43, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI shukla, suneet/B-4626-2012; OI Kannan, Pavitra/0000-0002-9170-6062 FU National Institutes of Mental Health [Z01-MH-002852-04, MH002793-09]; National Cancer Institute at the National Institutes of Health [Z01-BC-005598, Z01-BC-010030-12] FX This research was supported by the Intramural Research Programs of the National Institutes of Mental Health (Project Nos. Z01-MH-002852-04 and MH002793-09) and the National Cancer Institute (Project No. Z01-BC-005598 and No. Z01-BC-010030-12) at the National Institutes of Health. NR 33 TC 60 Z9 62 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD FEB PY 2011 VL 2 IS 2 BP 82 EP 89 DI 10.1021/cn100078a PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 724GU UT WOS:000287564900004 PM 22778859 ER PT J AU Wang, YY Park, KD Salome, C Wilson, SM Stables, JP Liu, RH Khanna, R Kohn, H AF Wang, Yuying Park, Ki Duk Salome, Christophe Wilson, Sarah M. Stables, James P. Liu, Rihe Khanna, Rajesh Kohn, Harold TI Development and Characterization of Novel Derivatives of the Antiepileptic Drug Lacosamide That Exhibit Far Greater Enhancement in Slow Inactivation of Voltage-Gated Sodium Channels SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Lacosamide; sodium channel; slow inactivation; affinity bait ID ANTICONVULSANT ACTIVITIES; OPIOID RECEPTORS; STEM-CELLS; EPILEPSY; DIFFERENTIATION; NEURONS; BINDING; SITE; CARBAMAZEPINE; MECHANISMS AB The novel antiepileptic drug (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide, Vimpat ((R)-1)) was recently approved in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. (R)-1 preferentially enhances slow inactivation of voltage-gated Na(+) currents, a pharmacological process relevant in the hyperexcitable neuron. We have advanced a strategy to identify lacosamide binding partners by attaching affinity bait (AB) and chemical reporter (CR) groups to (R)-1 to aid receptor detection and isolation. We showed that select lacosamide AB and AB&CR derivatives exhibited excellent activities similar to (R)-1 in the maximal electroshock seizure model in rodents. Here, we examined the effect of these lacosamide AB and AB&CR derivatives and compared them with (R)-1 on Na(+) channel function in central nervous system (CNS) catecholaminergic (CAD) cells. Using whole-cell patch clamp electrophysiology, we demonstrated that the test compounds do not affect the Na+ channel fast inactivation process, that they were far better modulators of slow inactivation than (R)-1, and that modulation of the slow inactivation process was stereospecific. The lacosamide AB agents that contained either an electrophilic isothiocyanate ((R)-5) or a photolabile azide ((R)-8) unit upon AB activation gave modest levels of permanent N(+) channel slow inactivation, providing initial evidence that these compounds may have covalently reacted with their cognate receptor(s). Our findings support the further use of these agents to delineate the (R)-1-mediated Na(+) channel slow inactivation process. C1 [Wang, Yuying; Khanna, Rajesh] Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USA. [Wang, Yuying; Khanna, Rajesh] Indiana Univ, Sch Med, Dept Toxicol, Indianapolis, IN 46202 USA. [Wilson, Sarah M.; Khanna, Rajesh] Indiana Univ, Sch Med, Paul & Carole Stark Neurosci Res Inst, Program Med Neurosci, Indianapolis, IN 46202 USA. [Kohn, Harold] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Liu, Rihe] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Park, Ki Duk; Salome, Christophe; Liu, Rihe; Kohn, Harold] Univ N Carolina, UNC Eshelman Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Stables, James P.] NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Khanna, R (reprint author), Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USA. EM khanna5@iupui.edu; harold_kohn@email.unc.edu OI Khanna, Rajesh/0000-0002-9066-2969 FU National Institutes of Health (NIH) [R01NS054112]; Indiana State Department of Health Spinal Cord and Brain Injury Fund [A70-9-079138]; Indiana University [2286501] FX This work is supported by grants from the National Institutes of Health (NIH) (R01NS054112 to H.K., R.L.), the Indiana State Department of Health Spinal Cord and Brain Injury Fund (A70-9-079138 to R.K.), and the Indiana University Biomedical Committee Research Support Funds (2286501 to R.K). S.M.W. is a Stark Scholar. NR 58 TC 25 Z9 27 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD FEB PY 2011 VL 2 IS 2 BP 90 EP 106 DI 10.1021/cn100089b PG 17 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 724GU UT WOS:000287564900005 PM 21532923 ER PT J AU Song, EQ Hu, J Wen, CY Tian, ZQ Yu, X Zhang, ZL Shi, YB Pang, DW AF Song, Er-Qun Hu, Jun Wen, Cong-Ying Tian, Zhi-Quan Yu, Xu Zhang, Zhi-Ling Shi, Yun-Bo Pang, Dai-Wen TI Fluorescent-Magnetic-Biotargeting Multifunctional Nanobioprobes for Detecting and Isolating Multiple Types of Tumor Cells SO ACS NANO LA English DT Article DE tumor; cancer; quantum dot; magnetic; multifunctional nanoparticle; multifunctional nanosphere; multifunctional nanobioprobe ID APTAMER-CONJUGATED NANOPARTICLES; SEMICONDUCTOR QUANTUM DOTS; ONE-POT SYNTHESIS; CANCER-CELLS; BIOMEDICAL APPLICATIONS; PHOTOTHERMAL THERAPY; GOLD NANOSHELLS; SEPARATION; DIAGNOSIS; NANOSPHERES AB Fluorescent-magnetic-biotargeting multifunctional nanobioprobes (FMBMNs) have attracted great attention in recent years due to their increasing, important applications in biomedical research, clinical diagnosis, and biomedicine. We have previously developed such nanobioprobes for the detection and isolation of a single kind of tumor cells. Detection and isolation of multiple tumor markers or tumor cells from complex samples sensitively and with high efficiency Is critical for the early diagnosis of tumors, especially malignant tumors or cancers, which will Improve clinical diagnosis outcomes and help to select effective treatment approaches. Here, we expanded the application of the monoclonal antibody (mAb)-coupled FMBMNs for multiplexed assays. Multiple types of cancer cells, such as leukemia cells and prostate cancer cells, were detected and collected from mixed samples within 25 min by using a magnet and an ordinary fluorescence microscope. The capture efficiencies of mAb-coupled FMBMNs for the above-mentioned two types of cells were 96% and 97%, respectively. Furthermore, by using the mAb-coupled FMBMNs, specific and sensitive detection and rapid separation of a small number of spiked leukemia cells and prostate cancer cells in a large population of cultured normal cells (about 0.01% were tumor cells) were achieved simply and inexpensively without any sample pretreatment before cell analysis. Therefore, mAb-coupled multicolor FMBMNs may be used for very sensitive detection and rapid isolation of multiple cancer cells in biomedical research and medical diagnostics. C1 [Song, Er-Qun; Hu, Jun; Wen, Cong-Ying; Tian, Zhi-Quan; Yu, Xu; Zhang, Zhi-Ling; Pang, Dai-Wen] Wuhan Univ, Key Lab Analyt Chem Biol & Med, Coll Chem & Mol Sci,MOE Innovat Platform 985, Res Ctr Nanobiol & Nanomed,Minist Educ, Wuhan 430072, Peoples R China. [Song, Er-Qun] Southwest Univ, Coll Pharmaceut Sci, Minist Educ, Key Lab Luminescence & Real Time Anal, Chongqing, Peoples R China. [Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Pang, DW (reprint author), Wuhan Univ, Key Lab Analyt Chem Biol & Med, Coll Chem & Mol Sci,MOE Innovat Platform 985, Res Ctr Nanobiol & Nanomed,Minist Educ, Wuhan 430072, Peoples R China. EM dwpang@whu.edu.cn RI 林, 毅/E-5033-2011; Zhang, Zhi-Ling/B-3135-2010; Yu, Xu /C-9578-2015; Tian, Zhi-Quan/K-5304-2012 OI Zhang, Zhi-Ling/0000-0001-7807-2264; Yu, Xu /0000-0002-3587-7019; FU National Key Scientific Program (973)-Nanoscience and Nanotechnology [2006CB933100, 2011CB933600]; Science Fund for Creative Research Groups of NSFC [20621502, 20921062]; National Natural Science Foundation of China [20833006, 20875071, 21005056, 210050641]; Ministry of Public Health [2009ZX10004-107, 2008ZX10004-004]; NICHD, NIH, USA FX This work was supported by the National Key Scientific Program (973)-Nanoscience and Nanotechnology (2006CB933100; 2011CB933600), the Science Fund for Creative Research Groups of NSFC (20621502; 20921062), the National Natural Science Foundation of China (20833006; 20875071; 21005056; 210050641, the Ministry of Public Health (2009ZX10004-107; 2008ZX10004-004), and the Intramural Research Program of NICHD, NIH, USA. NR 62 TC 123 Z9 130 U1 24 U2 200 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD FEB PY 2011 VL 5 IS 2 BP 761 EP 770 DI 10.1021/nn1011336 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 724CN UT WOS:000287553800009 PM 21250650 ER PT J AU Brion, M Sanchez-Salorio, M Corton, M de la Fuente, M Pazos, B Othman, M Swaroop, A Abecasis, G Sobrino, B Carracedo, A AF Brion, Maria Sanchez-Salorio, Manuel Corton, Marta de la Fuente, Maria Pazos, Belen Othman, Mohammad Swaroop, Anand Abecasis, Goncalo Sobrino, Beatriz Carracedo, Angel CA Spanish Multi-Ctr Grp AMD TI Genetic association study of age-related macular degeneration in the Spanish population SO ACTA OPHTHALMOLOGICA LA English DT Article DE ABCA4; age-related macular degeneration; ARMS2; case-control study; CFH; FGF2; genetic association ID COMPLEMENT-FACTOR-H; STARGARDT DISEASE GENE; GENOME SCAN; CHOROIDAL NEOVASCULARIZATION; JAPANESE POPULATION; SUSCEPTIBILITY LOCI; HEMICENTIN-1 GENES; EXTENDED FAMILIES; GROWTH-FACTORS; MESSENGER-RNA AB Purpose: To investigate new genetic risk factors and replicate reported associations with advanced age-related macular degeneration (AMD) in a prospective case-control study developed with a Spanish cohort. Methods: Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex (TM) genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results: In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3' UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion: We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. C1 [Brion, Maria] Hospital Univ Complex Santiago CHUS, Santiago De Compostela, Spain. [Brion, Maria; Corton, Marta; Sobrino, Beatriz; Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Santiago De Compostela, Spain. [Sanchez-Salorio, Manuel; de la Fuente, Maria; Pazos, Belen] Inst Gallego Oftalmol INGO, Santiago De Compostela, Spain. [Othman, Mohammad; Swaroop, Anand] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. [Othman, Mohammad; Swaroop, Anand] Univ Michigan, Dept Visual Sci & Human Genet, Ann Arbor, MI USA. [Swaroop, Anand] NEI, Natl Inst Hlth, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD USA. [Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sobrino, Beatriz; Carracedo, Angel] Univ Santiago de Compostela, Natl Genotyping Ctr CEGEN, Santiago De Compostela, Spain. RP Brion, M (reprint author), Univ Santiago de Compostela, Fac Med, San Francisco S-N, Santiago De Compostela 5782, Spain. EM maria.brion@usc.es RI Coco-Martin, Rosa/H-4511-2015; OI Coco-Martin, Rosa/0000-0002-1811-1417; Brion, Maria/0000-0001-7463-2148; Abecasis, Goncalo/0000-0003-1509-1825; Swaroop, Anand/0000-0002-1975-1141; Carracedo, Angel/0000-0003-1085-8986 FU Xunta de Galicia [PGI-DIT06PXIB208204PR]; Instituto de Salud Carlos III [EMER07/018]; National Institutes of Health, USA FX This study was supported by grants from the Xunta de Galicia (PGI-DIT06PXIB208204PR), the Instituto de Salud Carlos III (EMER07/018), and National Institutes of Health, USA. The sponsor or funding organization had no role in the design or conduct of this research. NR 74 TC 19 Z9 22 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD FEB PY 2011 VL 89 IS 1 BP E12 EP E22 DI 10.1111/j.1755-3768.2010.02040.x PG 11 WC Ophthalmology SC Ophthalmology GA 711YL UT WOS:000286628100002 PM 21106043 ER PT J AU Redon, CE Nakamura, AJ Martin, OA Parekh, PR Weyemi, US Bonner, WM AF Redon, Christophe E. Nakamura, Asako J. Martin, Olga A. Parekh, Palak R. Weyemi, Urbain S. Bonner, William M. TI Recent developments in the use of gamma-H2AX as a quantitative DNA double-strand break biomarker SO AGING-US LA English DT Article DE DNA damage; DNA repair; gamma-H2AX; double-strand break; biomarker; cancer; senescent cells ID BLOOD-LYMPHOCYTES; DAMAGE RESPONSE; ADIPOSE-TISSUE; RADIATION-EXPOSURE; TUMOR-CELLS; IN-VIVO; REPAIR; ASSAY; H2AX; POLY(ADP-RIBOSE) AB The past year has seen considerable developments in the use of the DNA double-strand breaks (DSBs) to evaluate genome alterations in cells undergoing a variety of genotoxic stresses in vitro and in vivo. When the gamma-H2AX foci which mark the DSBs are stained, individual breaks are detectible, making the assay suitable for situations requiring great sensitivity. While the methods for the detection of gamma-H2AX foci are still evolving, particularly for in vivo detection, the basic assay has proven to be useful in several diverse areas of research. We will highlight recent developments of the assay in four areas: radiation biodosimetry, the evaluation or validation of new cancer drugs in clinical studies, chronic inflammation, and environmental genotoxicity. C1 [Redon, Christophe E.; Nakamura, Asako J.; Martin, Olga A.; Parekh, Palak R.; Weyemi, Urbain S.; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM bonnerw@mail.nih.gov RI Parekh, Palak/B-7042-2015; Weyemi, Urbain/E-2083-2016 OI Parekh, Palak/0000-0001-9201-5194; FU National Cancer Institute, NIH FX This work was supported by the Intramural Research Program of the National Cancer Institute, NIH. NR 42 TC 76 Z9 78 U1 1 U2 8 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD FEB PY 2011 VL 3 IS 2 BP 168 EP 174 PG 7 WC Cell Biology SC Cell Biology GA 732FM UT WOS:000288170400013 PM 21325706 ER PT J AU Leggio, L Addolorato, G Cippitelli, A Jerlhag, E Kampov-Polevoy, AB Swift, RM AF Leggio, Lorenzo Addolorato, Giovanni Cippitelli, Andrea Jerlhag, Elisabet Kampov-Polevoy, Alexei B. Swift, Robert M. TI Role of Feeding-Related Pathways in Alcohol Dependence: A Focus on Sweet Preference, NPY, and Ghrelin SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcohol Dependence; Alcohol Craving; Appetite; Feeding-Related Pathways; Sweet Preference; Feeding-Related Peptides; Neuropeptide Y; Ghrelin ID NEUROPEPTIDE-Y NPY; CORTICOTROPIN-RELEASING-FACTOR; STIMULATES LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; FAMILY-HISTORY; PARAVENTRICULAR NUCLEUS; HYPOTHALAMIC NUCLEI; DOPAMINE-OVERFLOW; TASTE INTENSITY; ETHANOL INTAKE AB Converging research evidence suggests that alcohol and food-seeking behaviors share common neural pathways. There is preclinical and clinical evidence linking the consumption of sweets to alcohol intake in both animals and humans. In addition, a growing body of animal and human literature suggests the involvement of "feeding-related" peptides in alcohol-seeking behavior. In particular, both central and peripheral appetitive peptides have shown a possible role in alcohol dependence. The present mini-review will summarize the literature on the link between sweet preference and alcohol dependence, and on the role of feeding-related peptides in alcohol dependence. Specifically, in an attempt to narrow the field, the present mini-review will focus on 2 specific pathways, the central neuropeptide Y and the peripheral gut peptide ghrelin. Although more research is needed, data available suggest that studying feeding-related pathways in alcohol dependence may have theoretic, biologic, diagnostic, and therapeutic implications. C1 [Leggio, Lorenzo; Swift, Robert M.] Brown Univ, Ctr Alcohol & Addict Studies, Sch Med, Providence, RI 02912 USA. [Leggio, Lorenzo; Addolorato, Giovanni] Univ Cattolica Sacro Cuore, Rome, Italy. [Cippitelli, Andrea] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Jerlhag, Elisabet] Univ Gothenburg, Pharmacol Sect, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden. [Kampov-Polevoy, Alexei B.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Leggio, L (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Sch Med, Box GS 121-4, Providence, RI 02912 USA. EM lorenzo_leggio@brown.edu RI Leggio, Lorenzo/M-2972-2016; OI Addolorato, Giovanni/0000-0002-1522-9946 NR 83 TC 29 Z9 29 U1 0 U2 18 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2011 VL 35 IS 2 BP 194 EP 202 DI 10.1111/j.1530-0277.2010.01334.x PG 9 WC Substance Abuse SC Substance Abuse GA 710KH UT WOS:000286510000002 PM 21058960 ER PT J AU Liu, JX Zhou, ZF Hodgkinson, CA Yuan, QP Shen, PH Mulligan, CJ Wang, A Gray, RR Roy, A Virkkunen, M Goldman, D Enoch, MA AF Liu, Jixia Zhou, Zhifeng Hodgkinson, Colin A. Yuan, Qiaoping Shen, Pei-Hong Mulligan, Connie J. Wang, Alex Gray, Rebecca R. Roy, Alec Virkkunen, Matti Goldman, David Enoch, Mary-Anne TI Haplotype-Based Study of the Association of Alcohol-Metabolizing Genes With Alcohol Dependence in Four Independent Populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Alcohol Dehydrogenases; Aldehyde Dehydrogenases; Haplotype Association; ALDH1A1 ID ALDEHYDE DEHYDROGENASE-DEFICIENCY; WHITE COLLEGE-STUDENTS; PROMOTER POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; EUROPEAN AMERICANS; MISSION INDIANS; BINGE DRINKING; ALDH GENES; RISK; JAPANESE AB Background: Ethanol is metabolized by 2 rate-limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses to maximize the chances of capturing functional variation. Methods: Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case control sample sizes were the following: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72. Results: In all four populations, as well as HapMap populations, 5 haplotype blocks were identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B; (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks and ALDH2 by 1 block. No haplotype or SNP association results were significant after correction for multiple comparisons; however, several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. Conclusions: The systematic evaluation of alcohol-metabolizing genes in four non-East Asian populations has shown only modest associations with AD, largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin yang haplotypes in several populations warrants further study. C1 [Liu, Jixia; Zhou, Zhifeng; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Wang, Alex; Goldman, David; Enoch, Mary-Anne] NIAAA, NIH, LNG, Bethesda, MD 20892 USA. [Mulligan, Connie J.; Wang, Alex; Gray, Rebecca R.] Univ Florida, Dept Anthropol, Gainesville, FL 32611 USA. [Roy, Alec] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. [Virkkunen, Matti] Univ Helsinki, Dept Psychiat, Inst Clin Med, FIN-00014 Helsinki, Finland. [Virkkunen, Matti] Kellokoski Hosp, Kellokoski, Finland. RP Liu, JX (reprint author), NIAAA, NIH, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM liujixia@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU National Institute on Alcohol Abuse and Alcoholism, NIH [RO1 DA 10336-02]; National Institute of Drug Abuse, NIH; NIH [R03 AA12906] FX This research was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH and in part by grant RO1 DA 10336-02 to AR from the National Institute of Drug Abuse, NIH and by NIH grant R03 AA12906 to C.J.M. We gratefully acknowledge the work performed by Robert Robin and Bernard Albaugh in recruiting and interviewing the SW Indians and Plains Indians, respectively. Longina Akhtar and Elisa Moore provided technical support. Danielle Muchnik, Angelica Gonzalez-Oliver, David Mayorga, Ben Burkley, and Jena Chojnowski assisted in genotyping samples. NR 63 TC 25 Z9 25 U1 3 U2 23 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2011 VL 35 IS 2 BP 304 EP 316 DI 10.1111/j.1530-0277.2010.01346.x PG 13 WC Substance Abuse SC Substance Abuse GA 710KH UT WOS:000286510000014 PM 21083667 ER PT J AU Li, JS Colan, SD Sleeper, LA Newburger, JW Pemberton, VL Atz, AM Cohen, MS Golding, F Klein, GL Lacro, RV Radojewski, E Richmond, ME Minich, LL AF Li, Jennifer S. Colan, Steven D. Sleeper, Lynn A. Newburger, Jane W. Pemberton, Victoria L. Atz, Andrew M. Cohen, Meryl S. Golding, Fraser Klein, Gloria L. Lacro, Ronald V. Radojewski, Elizabeth Richmond, Marc E. Minich, L. LuAnn CA Pediat Heart Network Investigators TI Lessons learned from a pediatric clinical trial: The Pediatric Heart Network Angiotensin-Converting Enzyme Inhibition in Mitral Regurgitation Study SO AMERICAN HEART JOURNAL LA English DT Article ID ATRIOVENTRICULAR-CANAL DEFECTS; SURGICAL REPAIR; OFF-LABEL; SEPTAL-DEFECT; CHILDREN; ECHOCARDIOGRAPHY; REPRESENTATION; MULTICENTER; ENALAPRIL; DISEASE AB Background Mitral regurgitation is the most common indication for reoperation in children following repair of atrioventricular septal defect (AVSD). We hypothesized that angiotensin-converting enzyme inhibitor therapy would decrease the severity of mitral regurgitation and limit left ventricular volume overload in children following AVSD repair. Methods The Pediatric Heart Network designed a placebo-controlled randomized trial of enalapril in this population. The primary aim was to test the effect of enalapril on the change in left ventricular end-diastolic dimension body surface area-adjusted z score. Before the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. Trial experience Seventeen months after the start of the study, 349 patients were screened, 8 were trial eligible, and only 5 were enrolled. The study was subsequently terminated because of low patient accrual. Several factors led to the problems with patient accrual, including (1) the use of criteria to assess disease severity in the feasibility study that were not identical to those used in the trial, (2) failure to achieve equipoise for the study among clinicians and referring physicians, (3) reliance on methodology developed in adult populations with different disease mechanisms, and (4) absence of adequate data to define the natural history of the disease process under study. Progress in the treatment of children with cardiovascular disease will depend on the future of multicenter collaborative clinical trials. The lessons learned from this study may contribute to improvements in this research. (Am Heart J 2011;161:233-40.) C1 [Li, Jennifer S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol,Dept Pediat, Durham, NC 27715 USA. [Colan, Steven D.; Sleeper, Lynn A.; Klein, Gloria L.] New England Res Inst, Watertown, MA 02172 USA. [Newburger, Jane W.; Lacro, Ronald V.] Childrens Hosp, Boston, MA 02115 USA. [Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cohen, Meryl S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Golding, Fraser; Radojewski, Elizabeth] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Richmond, Marc E.] Columbia Univ, New York, NY USA. [Minich, L. LuAnn] Univ Utah, Salt Lake City, UT USA. RP Li, JS (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol,Dept Pediat, POB 17969, Durham, NC 27715 USA. EM jennifer.li@duke.edu FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057] FX Supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057). NR 32 TC 9 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2011 VL 161 IS 2 BP 233 EP 240 DI 10.1016/j.ahj.2010.10.030 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 719FX UT WOS:000287188000005 PM 21315203 ER PT J AU Shen, JA Johnson, VM Sullivan, LM Jacques, PF Magnani, JW Lubitz, SA Pandey, S Levy, D Vasan, RS Quatromoni, PA Junyent, M Ordovas, JM Benjamin, EJ AF Shen, Jian Johnson, Victor M. Sullivan, Lisa M. Jacques, Paul F. Magnani, Jared W. Lubitz, Steven A. Pandey, Shivda Levy, Daniel Vasan, Ramachandran S. Quatromoni, Paula A. Junyent, Mireia Ordovas, Jose M. Benjamin, Emelia J. TI Dietary factors and incident atrial fibrillation: the Framingham Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID POLYUNSATURATED-FATTY-ACIDS; ALCOHOL-CONSUMPTION; FISH-OIL; BLOOD INSTITUTE; NATIONAL HEART; RISK-FACTORS; DANISH DIET; WHOLE-GRAIN; DISEASE; HEALTH AB Background: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). Objective: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. Design: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. Results: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n-3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of,1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). Conclusions: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population. Am J Clin Nutr 2011;93:261-6. C1 [Magnani, Jared W.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Farmingham Heart Study, Framingham, MA 01702 USA. [Shen, Jian; Jacques, Paul F.; Junyent, Mireia; Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Quatromoni, Paula A.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Magnani, Jared W.; Pandey, Shivda; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Evans Mem Dept Med, Cardiol Sect, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Evans Mem Dept Med, Sect Prevent Med, Boston, MA 02215 USA. [Quatromoni, Paula A.] Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Hlth Sci, Boston, MA 02215 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), NHLBI, Farmingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU Heart, Lung, and Blood Institute [HL-54776]; National Institute of Diabetes and Digestive and Kidney Diseases [DK075030]; US Department of Agriculture Research [53-K06-5-10, 58-1950-9-001]; American Heart Association [09FTF2190028]; National Institutes of Health [N01-HC 25195, 6R01-NS 17950, RC1HL101056, HL092577, 1R01HL102214] FX Supported by the National Heart, Lung, and Blood Institute (grants HL-54776; to JS and JMO), the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK075030; to JMO), the US Department of Agriculture Research (contracts 53-K06-5-10 and 58-1950-9-001; to JS and JMO), the American Heart Association (award 09FTF2190028; to JWM), and the National Institutes of Health (grants N01-HC 25195, 6R01-NS 17950, RC1HL101056, HL092577, and 1R01HL102214; to EJB). NR 47 TC 44 Z9 44 U1 0 U2 14 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2011 VL 93 IS 2 BP 261 EP 266 DI 10.3945/ajcn.110.001305 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 709DQ UT WOS:000286417900006 PM 21106919 ER PT J AU Persson, C Canedo, P Machado, JC El-Omar, EM Forman, D AF Persson, Christina Canedo, Paulo Machado, Jose C. El-Omar, Emad M. Forman, David TI Polymorphisms in Inflammatory Response Genes and Their Association With Gastric Cancer: A HuGE Systematic Review and Meta-Analyses SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE epidemiology; genetics; Helicobacter pylori; interleukins; meta-analysis; polymorphism; genetic; stomach neoplasms ID HELICOBACTER-PYLORI INFECTION; NECROSIS-FACTOR-ALPHA; RECEPTOR ANTAGONIST GENE; SQUAMOUS-CELL CARCINOMA; EPSTEIN-BARR-VIRUS; TNF-A GENES; INCREASED RISK; CHINESE POPULATION; INTERLEUKIN-1 POLYMORPHISMS; PROMOTER POLYMORPHISM AB To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date. C1 [Persson, Christina] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Persson, Christina] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Canedo, Paulo; Machado, Jose C.] Univ Porto, Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal. [El-Omar, Emad M.] Univ Aberdeen, Dept Med, Aberdeen, Scotland. [Forman, David] Int Agcy Res Canc, Sect Canc Informat, F-69372 Lyon, France. RP Persson, C (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM christina.persson@nih.gov RI Machado, Jose Carlos/C-5907-2009; Kim, Seongman/N-6910-2014; Canedo, Paulo/C-4947-2008 OI Machado, Jose Carlos/0000-0003-4741-8415; Canedo, Paulo/0000-0001-6838-5726 FU Marie Curie Training in Molecular Epidemiology fellowship FX This review was supported by a Marie Curie Training in Molecular Epidemiology fellowship award. NR 73 TC 91 Z9 96 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2011 VL 173 IS 3 BP 259 EP 270 DI 10.1093/aje/kwq370 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 709TC UT WOS:000286463300002 PM 21178102 ER PT J AU Hsu, WL Yu, KJ Chien, YC Chiang, CJ Cheng, YJ Chen, JY Liu, MY Chou, SP You, SL Hsu, MM Lou, PJ Wang, CP Hong, JH Leu, YS Tsai, MH Su, MC Tsai, ST Chao, WY Ger, LP Chen, PR Yang, CS Hildesheim, A Diehl, SR Chen, CJ AF Hsu, Wan-Lun Yu, Kelly J. Chien, Yin-Chu Chiang, Chun-Ju Cheng, Yu-Juen Chen, Jen-Yang Liu, Mei-Ying Chou, Sheng-Ping You, San-Lin Hsu, Mow-Ming Lou, Pei-Jen Wang, Cheng-Ping Hong, Ji- Hong Leu, Yi-Shing Tsai, Ming-Hsui Su, Mao-Chang Tsai, Sen-Tien Chao, Wen-Yuan Ger, Luo-Ping Chen, Peir-Rong Yang, Czau-Siung Hildesheim, Allan Diehl, Scott R. Chen, Chien-Jen TI Familial Tendency and Risk of Nasopharyngeal Carcinoma in Taiwan: Effects of Covariates on Risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carcinoma; cohort studies; herpesvirus 4; human ID EPSTEIN-BARR-VIRUS; CIGARETTE-SMOKING; CHINA; CANCER; COHORT; INFECTION; GUANGZHOU; AREA AB In the present study, the authors compared the long-term risk of nasopharyngeal carcinoma (NPC) of male participants in an NPC multiplex family cohort with that of controls in a community cohort in Taiwan after adjustment for anti-Epstein-Barr virus (EBV) seromarkers and cigarette smoking. A total of 43 incident NPC cases were identified from the 1,019 males in the NPC multiplex family cohort and the 9,622 males in the community cohort, for a total of 8,061 person-years and 185,587 person-years, respectively. The adjusted hazard ratio was 6.8 (95% confidence interval (CI): 2.3, 20.1) for the multiplex family cohort compared with the community cohort. In the evaluation of anti-EBV viral capsid antigen immunoglobulin A and anti-EBV deoxyribonuclease, the adjusted hazard ratios were 2.8 (95% CI: 1.3, 6.0) and 15.1 (95% CI: 4.2, 54.1) for those positive for 1 EBV seromarker and positive for both seromarkers, respectively, compared with those negative for both EBV seromarkers. The adjusted hazard ratio was 31.0 (95% CI: 9.7, 98.7) for participants who reported a family history of NPC and who were anti-EBV-seropositive compared with individuals without such a history who were anti-EBV-seronegative. The findings suggest that both family history of NPC and anti-EBV seropositivity are important determinants of subsequent NPC risk and that the effect of family history on NPC risk cannot be fully explained by mediation through EBV serologic responses. C1 [Hsu, Wan-Lun; Chien, Yin-Chu; You, San-Lin; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Hsu, Wan-Lun; Chiang, Chun-Ju; Cheng, Yu-Juen; Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Yu, Kelly J.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chen, Jen-Yang; Chou, Sheng-Ping] Natl Hlth Res Inst, Natl Inst Canc Res, Chunan, Taiwan. [Chen, Jen-Yang; Yang, Czau-Siung] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 10764, Taiwan. [Liu, Mei-Ying] Natl Taipei Coll Nursing, Ctr Gen Educ, Taipei, Taiwan. [Hsu, Mow-Ming; Lou, Pei-Jen; Wang, Cheng-Ping] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. [Wang, Cheng-Ping] Natl Taiwan Univ, Coll Med, Inst Biomed Engn, Taipei 10764, Taiwan. [Wang, Cheng-Ping] Natl Taiwan Univ, Coll Engn, Taipei 10764, Taiwan. [Hong, Ji- Hong] Chang Gung Mem Hosp, Dept Radiat Oncol, Tao Yuan, Taiwan. [Leu, Yi-Shing] MacKay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. [Tsai, Ming-Hsui] China Med Univ Hosp, Dept Otolaryngol, Taichung, Taiwan. [Su, Mao-Chang] Chung Shan Med Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Taichung, Taiwan. [Su, Mao-Chang] Chung Shan Med Univ Hosp, Dept Speech Language Pathol & Audiol, Taichung, Taiwan. [Su, Mao-Chang] Chung Shan Med Univ Hosp, Sch Med, Taichung, Taiwan. [Tsai, Sen-Tien; Chao, Wen-Yuan] Natl Cheng Kung Univ Hosp, Dept Otolaryngol, Tainan 70428, Taiwan. [Ger, Luo-Ping] Kaohsiung Vet Gen Hosp, Dept Educ & Res, Kaohsiung, Taiwan. [Chen, Peir-Rong] Buddhist Tzu Chi Gen Hosp, Dept Otolaryngol, Hualien, Taiwan. [Diehl, Scott R.] New Jersey Dent, Ctr Pharmacogenom & Complex Dis Res, Newark, NJ USA. RP Chen, CJ (reprint author), Acad Sinica, Genom Res Ctr, 128 Acad Rd,Sect 2, Taipei 115, Taiwan. EM cjchen@ntu.edu.tw RI Chen, Chien-Jen/C-6976-2008; Chen, Jen-Yang/D-2085-2010; Hildesheim, Allan/B-9760-2015; OI Hildesheim, Allan/0000-0003-0257-2363; WANG, CHENG-PING/0000-0001-7872-1463; LOU, PEI-JEN/0000-0002-3383-8593 FU Intramural NIH HHS NR 35 TC 11 Z9 12 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2011 VL 173 IS 3 BP 292 EP 299 DI 10.1093/aje/kwq358 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 709TC UT WOS:000286463300005 PM 21148719 ER PT J AU Quinlan, SC Pfeiffer, RM Morton, LM Engels, EA AF Quinlan, Scott C. Pfeiffer, Ruth M. Morton, Lindsay M. Engels, Eric A. TI Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID NON-HODGKIN-LYMPHOMA; EPSTEIN-BARR-VIRUS; SOLID-ORGAN TRANSPLANTATION; RENAL-TRANSPLANTATION; DISTINCT ENTITY; IMMUNOSUPPRESSION; EPIDEMIOLOGY; DISEASE; MALIGNANCY; INFECTION AB Solid-organ transplant recipients have an elevated risk for some malignancies because of the requirement for immunosuppression [1]. In particular, non-Hodgkin's lymphoma (NHL) is common and comprises one end of a spectrum of post-transplant lymphoproliferative disorder (PTLD) ranging from benign hyperplasia to lymphoid malignancy [2]. PTLD risk is influenced by the type of organ transplanted, the age and Epstein-Barr virus (EBV) serostatus of the transplant recipient, and the intensity of immunosuppression [3-9]. PTLD incidence is high immediately after transplantation, decreases subsequently, and then rises again 4-5 years from transplantation [10,11]. This incidence pattern suggests the presence of separate early-onset and late-onset PTLD subtypes. Early-onset PTLDs tend to be EBV-positive and, when extranodal, are more likely than late-onset PTLDs to be localized to the transplanted organ [12,13]. Late-onset PTLD is less likely to be associated with EBV and, overall, is more likely than early-onset PTLD to be extranodal [13,14]. The Scientific Registry of Transplant Recipients (SRTR) includes data on a large number of solid-organ transplant recipients in the United States and information on malignancies diagnosed post-transplantation. We used these data to conduct a retrospective cohort study among kidney transplant recipients to examine differences in risk factors between early-onset PTLD and late-onset PTLD. C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Rockville, MD 20892 USA. RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA. EM engelse@exchange.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU The National Cancer Institute; HRSA is part of the U.S. Department of Health and Human Services [231-00-0116] FX Grant sponsor: Intramural Research Program of The National Cancer Institute. Grant sponsor: HRSA is part of the U.S. Department of Health and Human Services; Grant number: 231-00-0116 [to The Scientific Registry of Transplant Recipients (SRTR)] NR 29 TC 56 Z9 57 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2011 VL 86 IS 2 BP 206 EP 209 DI 10.1002/ajh.21911 PG 4 WC Hematology SC Hematology GA 718UL UT WOS:000287151700015 PM 21264909 ER PT J AU Huson, SM Acosta, MT Belzberg, AJ Bernards, A Chernoff, J Cichowski, K Evans, DG Ferner, RE Giovannini, M Korf, BR Listernick, R North, KN Packer, RJ Parada, LF Peltonen, J Ramesh, V Reilly, KM Risner, JW Schorry, EK Upadhyaya, M Viskochil, DH Zhu, YA Hunter-Schaedle, K Giancotti, FG AF Huson, Susan M. Acosta, Maria T. Belzberg, Allan J. Bernards, Andre Chernoff, Jonathan Cichowski, Karen Evans, D. Gareth Ferner, Rosalie E. Giovannini, Marco Korf, Bruce R. Listernick, Robert North, Kathryn N. Packer, Roger J. Parada, Luis F. Peltonen, Juha Ramesh, Vijaya Reilly, Karlyne M. Risner, John W. Schorry, Elizabeth K. Upadhyaya, Meena Viskochil, David H. Zhu, Yuan Hunter-Schaedle, Kim Giancotti, Filippo G. TI Back to the Future: Proceedings From the 2010 NF Conference SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurofibromatosis; schwannomatosis; NF1; NF2; neurofibroma; learning disabilities; bone dysplasia; MPNST ID GROWTH-FACTOR RECEPTOR; PERIPHERAL-NERVE; NEUROFIBROMATOSIS TYPE-2; PHENOTYPE; TUMORIGENESIS; EXPRESSION; PLEXIFORM; MUTATIONS; SPRED1; TUMORS AB The neurofibromatoses (NF) encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect 100,000 Americans; over 2 million persons worldwide; and are caused by mutation of tumor suppressor genes. Individuals with NF1 in particular may develop tumors anywhere in the nervous system; additional manifestations can include learning disabilities, bone dysplasia, cardiovascular defects, unmanageable pain, and physical disfigurement. Ultimately, the NFs can cause blindness, deafness, severe morbidity, and increased mortality and NF1 includes a risk of malignant cancer. Today there is no treatment for the NFs (other than symptomatic); however, research efforts to understand these genetic conditions have made tremendous strides in the past few years. Progress is being made on all fronts, from discovery studies-understanding the molecular signaling deficits that cause the manifestations of NF-to the growth of preclinical drug screening initiatives and the emergence of a number of clinical trials. An important element in fuelling this progress is the sharing of knowledge, and to this end, for over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share ideas and build collaborations. The 2010 NF Conference held in Baltimore, MD June 5-8, 2010 hosted over 300 NF researchers and clinicians. This paper provides a synthesis of the highlights presented at the Conference and as such, is a "state-of-the-field" for NF research in 2010. (C) 2010 Wiley-Liss, Inc. C1 [Risner, John W.; Hunter-Schaedle, Kim] Childrens Tumor Fdn, New York, NY 10005 USA. [Huson, Susan M.; Evans, D. Gareth] Univ Manchester, St Marys Hosp, Manchester M13 0JH, Lancs, England. [Acosta, Maria T.; Packer, Roger J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Belzberg, Allan J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Bernards, Andre; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chernoff, Jonathan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cichowski, Karen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ferner, Rosalie E.] Guys & St Thomas NHS Hosp Trust, London, England. [Giovannini, Marco] House Ear Res Inst, Los Angeles, CA USA. [Korf, Bruce R.] Univ Alabama, Birmingham, AL USA. [Listernick, Robert] Childrens Mem Hosp, Chicago, IL 60614 USA. [North, Kathryn N.] Univ Sydney, Sydney, NSW 2006, Australia. [Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Peltonen, Juha] Inst Biomed, Helsinki, Finland. [Reilly, Karlyne M.] NCI, NIH, Frederick, MD 21701 USA. [Schorry, Elizabeth K.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Upadhyaya, Meena] Cardiff Univ, Cardiff, S Glam, Wales. [Viskochil, David H.] Univ Utah, Salt Lake City, UT USA. [Zhu, Yuan] Univ Michigan, Ann Arbor, MI 48109 USA. [Giancotti, Filippo G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Hunter-Schaedle, K (reprint author), Childrens Tumor Fdn, 95 Pine St, New York, NY 10005 USA. EM khs@ctf.org RI Peltonen, Juha/C-2817-2008; Parada, luis/B-9400-2014; Chernoff, Jonathan/I-7631-2014; North, Kathryn/K-6476-2012; OI Peltonen, Juha/0000-0002-5732-4167; Chernoff, Jonathan/0000-0002-4803-7836; North, Kathryn/0000-0003-0841-8009; Evans, Gareth/0000-0002-8482-5784 FU National Institutes of Health [1R13NS070505-01] FX Grant sponsor: National Institutes of Health; Grant number: 1R13NS070505-01. NR 31 TC 11 Z9 11 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB PY 2011 VL 155A IS 2 BP 307 EP 321 DI 10.1002/ajmg.a.33804 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 718VE UT WOS:000287153700009 PM 21271647 ER PT J AU Conde-Agudelo, A Romero, R Kusanovic, JP AF Conde-Agudelo, Agustin Romero, Roberto Kusanovic, Juan Pedro TI Nifedipine in the management of preterm labor: a systematic review and metaanalysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE calcium channel blocker; neonatal morbidity; pregnancy; premature birth; preterm birth; tocolysis; uterine contractility ID RANDOMIZED CONTROLLED-TRIAL; CALCIUM-CHANNEL BLOCKERS; MAGNESIUM-SULFATE; ORAL NIFEDIPINE; INFLAMMATORY RESPONSE; MYOCARDIAL-INFARCTION; CLINICAL-SIGNIFICANCE; ANTAGONIST ATOSIBAN; ACUTE TOCOLYSIS; RITODRINE AB OBJECTIVE: To determine the efficacy and safety of nifedipine as a tocolytic agent in women with preterm labor. STUDY DESIGN: A systematic review and metaanalysis of randomized controlled trials. RESULTS: Twenty-six trials (2179 women) were included. Nifedipine was associated with a significant reduction in the risk of delivery within 7 days of initiation of treatment and before 34 weeks' gestation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, and admission to the neonatal intensive care unit when compared with beta(2)-adrenergic-receptor agonists. There was no difference between nifedipine and magnesium sulfate in tocolytic efficacy. Nifedipine was associated with significantly fewer maternal adverse events than beta(2)-adrenergic-receptor agonists and magnesium sulfate. Maintenance nifedipine tocolysis was ineffective in prolonging gestation or improving neonatal outcomes when compared with placebo or no treatment. CONCLUSION: Nifedipine is superior to beta(2)-adrenergic-receptor agonists and magnesium sulfate for tocolysis in women with preterm labor. C1 [Conde-Agudelo, Agustin; Romero, Roberto; Kusanovic, Juan Pedro] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Conde-Agudelo, Agustin; Romero, Roberto; Kusanovic, Juan Pedro] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This study was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 79 TC 7 Z9 9 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2011 VL 204 IS 2 AR 134.e1 DI 10.1016/j.ajog.2010.11.038 PG 20 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 715HV UT WOS:000286874900017 PM 21284967 ER PT J AU Mittal, P Romero, R Tarca, AL Draghici, S Nhan-Chang, CL Chaiworapongsa, T Hotra, J Gomez, R Kusanovic, JP Lee, DC Kim, CJ Hassan, SS AF Mittal, Pooja Romero, Roberto Tarca, Adi L. Draghici, Sorin Nhan-Chang, Chia-Ling Chaiworapongsa, Tinnakorn Hotra, John Gomez, Ricardo Kusanovic, Juan Pedro Lee, Deug-Chan Kim, Chong Jai Hassan, Sonia S. TI A molecular signature of an arrest of descent in human parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE adenosine triphosphatase; Na plus /K plus transporting; alpha 1 polypeptide; ATP1A1; COX2; HIF1A; hypoxia inducible factor-1; inflammation; interleukin-6; myometrium; parturition; pregnancy; prostaglandin-endoperoxide synthase 2; PTGS2; spontaneous term labor; systems biology; transcriptomics ID TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE-CELLS; HUMAN-FETAL MEMBRANES; HUMAN MYOMETRIAL CELLS; CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA EXPRESSION; AMNIOTIC-FLUID INTERLEUKIN-6; SPONTANEOUS PRETERM LABOR; PROSTAGLANDIN-E SYNTHASE; HUMAN UTERINE MYOCYTES AB OBJECTIVE: This study was undertaken to identify the molecular basis of an arrest of descent. STUDY DESIGN: Human myometrium was obtained from women in term labor (TL; n = 29) and arrest of descent (AODes; n = 21). Gene expression was characterized using Illumina HumanHT-12 microarrays. A moderated Student t test and false discovery rate adjustment were applied for analysis. Confirmatory quantitative reverse transcription-polymerase chain reaction and immunoblot were performed in an independent sample set. RESULTS: Four hundred genes were differentially expressed between women with an AODes compared with those with TL. Gene Ontology analysis indicated enrichment of biological processes and molecular functions related to inflammation and muscle function. Impacted pathways included inflammation and the actin cytoskeleton. Overexpression of hypoxia inducible factor-1a, interleukin -6, and prostaglandin-endoperoxide synthase 2 in AODes was confirmed. CONCLUSION: We have identified a stereotypic pattern of gene expression in the myometrium of women with an arrest of descent. This represents the first study examining the molecular basis of an arrest of descent using a genome-wide approach. C1 [Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Draghici, Sorin; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Hotra, John; Kusanovic, Juan Pedro; Lee, Deug-Chan; Kim, Chong Jai; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mittal, Pooja; Romero, Roberto; Tarca, Adi L.; Draghici, Sorin; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Hotra, John; Kusanovic, Juan Pedro; Lee, Deug-Chan; Kim, Chong Jai; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Mittal, Pooja; Nhan-Chang, Chia-Ling; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Tarca, Adi L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Univ Catolica Chile, Sotero Rio Hosp, Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Puente Alto, Chile. RP Mittal, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, 3990 John R,Box 4, Detroit, MI 48201 USA. EM pmittal@med.wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This study was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 308 TC 3 Z9 3 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2011 VL 204 IS 2 AR 177.e15 DI 10.1016/j.ajog.2010.09.025 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 715HV UT WOS:000286874900040 PM 21284969 ER PT J AU Vaisbuch, E Whitty, JE Hassan, SS Romero, R Kusanovic, JP Cotton, DB Sorokin, Y Karumanchi, SA AF Vaisbuch, Edi Whitty, Janice E. Hassan, Sonia S. Romero, Roberto Kusanovic, Juan Pedro Cotton, David B. Sorokin, Yoram Karumanchi, S. Ananth TI Circulating angiogenic and antiangiogenic factors in women with eclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE placental growth factor; preeclampsia; pregnancy; soluble endoglin; soluble fms-like tyrosine kinase 1; soluble vascular endothelial growth factor receptor-1 ID ENDOTHELIAL GROWTH-FACTOR; UTERINE ARTERY DOPPLER; FOR-GESTATIONAL-AGE; LATE-ONSET PREECLAMPSIA; TYROSINE KINASE-1; FACTOR RECEPTOR-1; MATERNAL SERUM; EARLY-PREGNANCY; DEVELOP PREECLAMPSIA; SOLUBLE ENDOGLIN AB OBJECTIVE: The objective of the study was to determine whether eclampsia has a different circulating profile of angiogenic (placental growth factor [PlGF]) and antiangiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) from severe preeclampsia. STUDY DESIGN: This cross-sectional study included pregnant women in the following groups: (1) normal pregnancy (n = 40); (2) severe preeclampsia (n = 40); and (3) eclampsia (n = 20). Maternal serum PlGF, sVEGFR-1, and sEng concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: The study results included the following: (1) the median concentration of sVEGFR-1 and sEng was higher and of PlGF was lower in severe preeclampsia or eclampsia than in normal pregnancy (P<.001 for all); and (2) the median concentrations of these 3 analytes did not differ significantly between patients with severe preeclampsia and those with eclampsia. CONCLUSION: Eclampsia is associated with higher maternal circulating concentrations of sVEGFR-1 and sEng and lower concentrations of PlGF than normal pregnancy but with similar concentrations to severe preeclampsia. These findings suggest that eclampsia shares a common pathogenic pathway as severe preeclampsia. C1 [Vaisbuch, Edi; Hassan, Sonia S.; Romero, Roberto; Kusanovic, Juan Pedro] Wayne State Univ, Perinatol Res Branch, Intramural Div,Dept Hlth & Human Serv,NIH, Hutzel Womens Hosp,Eunice Kennedy Shriver Natl In, Detroit, MI 48201 USA. [Vaisbuch, Edi; Hassan, Sonia S.; Kusanovic, Juan Pedro; Cotton, David B.; Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Whitty, Janice E.] Hubbard Hosp, Meharry Med Coll, Dept Obstet & Gynecol, Nashville, TN USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, Intramural Div,Dept Hlth & Human Serv,NIH, Hutzel Womens Hosp,Eunice Kennedy Shriver Natl In, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services; Burroughs Welcome Fund FX This study was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. S.A.K. is an investigator of the Howard Hughes Medical Institute and is supported by the Burroughs Welcome Fund Clinical Scientist Award. S.A.K. is a coinventor on multiple patents held by the Beth Israel Deaconess Medical Center for the diagnosis/therapy of preeclampsia that has been outlicensed to multiple companies. In addition, S.A.K. is a consultant to Beckman Coulter, Abbott Diagnostics, Roche Diagnostics, and Johnson & Johnson. NR 100 TC 8 Z9 8 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2011 VL 204 IS 2 AR 152.e1 DI 10.1016/j.ajog.2010.08.049 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 715HV UT WOS:000286874900025 PM 21062661 ER PT J AU Sei, Y Lu, XP Liou, A Zhao, XL Wank, SA AF Sei, Yoshitatsu Lu, Xinping Liou, Alice Zhao, Xilin Wank, Stephen A. TI A stem cell marker-expressing subset of enteroendocrine cells resides at the crypt base in the small intestine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE green fluorescent protein; leucine-rich repeat-containing G protein-coupled receptor 5; organoid ID PROGENITOR CELLS; ENDOCRINE-CELLS; CHROMOGRANIN-A; ADULT-MOUSE; DIFFERENTIATION; EPITHELIUM; FATE; SPECIFICATION; NEUROGENIN-3; SIGNALS AB Sei Y, Lu X, Liou A, Zhao X, Wank SA. A stem cell marker-expressing subset of enteroendocrine cells resides at the crypt base in the small intestine. Am J Physiol Gastrointest Liver Physiol 300: G345-G356, 2011. First published November 18, 2010; doi:10.1152/ajpgi.00278.2010.-The spatial orientation of the enteroendocrine cells along the crypt-villus axis is closely associated with their differentiation in the intestine. Here we studied this relationship using primary duodenal crypts and an ex vivo organoid system established from cholecystokinin-green fluorescent protein (CCK-GFP) transgenic mice. In the primary duodenal crypts, GFP+ cells were found not only in the upper crypt but also at the crypt base, where the stem cells reside. Many GFP+ cells below +4 position were positive for the putative intestinal stem cell markers, leucine-rich repeat-containing G protein-coupled receptor 5, CD133, and doublecortin and CaM kinase-like-1, and also for the neuroendocrine transcription factor neurogenin 3. However, these cells were neither stem nor transient amplifying precursor cells because they were negative for both Ki-67 and phospho-Histone H3 and positive for the mature endocrine marker chromogranin A. Furthermore, these cells expressed multiple endocrine hormones. Tracking of GFP+ cells in the organoids from CCK-GFP mice indicated that GFP+ cells were first observed around the +4 position, some of which localized to the crypt base later in the culture period. These results suggest that a subset of enteroendocrine cells migrates down to the crypt base or stays localized at the crypt base, where they express stem and postmitotic endocrine markers. Further investigation of the function of this subset may provide novel insights into the genesis and development of enteroendocrine cells as well as enteroendocrine tumorigenesis. C1 [Sei, Yoshitatsu; Lu, Xinping; Liou, Alice; Zhao, Xilin; Wank, Stephen A.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Sei, Y (reprint author), Natl Inst Diabet Digest & Kidney Dis, Gastroenterol Sect, 10 Ctr Dr,Bldg 10,Rm 9C-112,MSC1804, Bethesda, MD 20892 USA. EM seiy@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 34 TC 26 Z9 26 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD FEB PY 2011 VL 300 IS 2 BP G345 EP G356 DI 10.1152/ajpgi.00278.2010 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 713GX UT WOS:000286724600017 PM 21088235 ER PT J AU Miller, RL AF Miller, R. Lance TI Transgenic mice: beyond the knockout SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE Cre; enhanced green fluorescent protein; high-throughput; renal-specific; transgenics ID TRANSLATIONAL PROFILING APPROACH; DESIGNED G(I)-COUPLED RECEPTOR; GREEN FLUORESCENT PROTEIN; CNS CELL-TYPES; CONDITIONAL EXPRESSION; CRE RECOMBINASE; IN-VIVO; COUPLED RECEPTORS; STEM-CELLS; MOUSE AB Miller RL. Transgenic mice: beyond the knockout. Am J Physiol Renal Physiol 300: F291-F300, 2011. First published November 10, 2010; doi: 10.1152/ajprenal.00082.2010.-Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interactions using multiple fluorescent proteins in the same mouse, and the cell cycle in real time and in the whole animal, and they can be used to perform deep tissue imaging in the whole animal, follow cell lineage during development and disease, and isolate large quantities of a pure cell type directly from organs. These novel transgenic mice and their applications provide the means for studying of molecular and biochemical events in the whole animal that was previously limited to cell cultures. In conclusion, transgenic mice are not just for generating knockouts. C1 NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Miller, RL (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N312, Bethesda, MD 20892 USA. EM lance.miller@nih.gov NR 62 TC 9 Z9 11 U1 0 U2 18 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2011 VL 300 IS 2 BP F291 EP F300 DI 10.1152/ajprenal.00082.2010 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 715XQ UT WOS:000286929200001 PM 21068085 ER PT J AU Schnermann, J AF Schnermann, Jurgen TI Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE PPADS; suramin; stop-flow pressure; proximal reabsorption; micropuncture ID DEFICIENT MICE; GLOMERULAR HEMODYNAMICS; ADENOSINE; FLOW; PRESSURE; ATP; ACTIVATION; BLOCKADE; RELEASE; RENIN AB Schnermann J. Maintained tubuloglomerular feedback responses during acute inhibition of P2 purinergic receptors in mice. Am J Physiol Renal Physiol 300: F339-F344, 2011. First published December 8, 2010; doi:10.1152/ajprenal.00637.2010.-Tubuloglomerular feedback (TGF), the change of afferent arteriolar resistance initiated by changes of luminal NaCl concentration, is thought to be related to NaCl-dependent release of ATP by macula densa cells. In the present study, we have explored the possibility that the released ATP may directly interact with vasoconstrictor P2 purinergic receptors in the vicinity of the glomerular vascular pole. In two different strains of wild-type mice (SWR/J and FVB), TGF responses were determined in vivo by measuring the stop flow pressure (P-SF) change caused by a saturating increase in loop of Henle flow rate before and during the administration of the P2 receptor inhibitors PPADS (12 mg/kg + 35 mg.kg(-1).h(-1) iv) or suramin (50 mg/kg + 150 mg.kg(-1).h(-1)). Both agents significantly reduced the blood pressure response to the P2X agonist alpha,beta-methylene ATP. In SWR/J and FVB mice, elevating flow to 30 nl/min reduced P-SF by 16.4 +/- 2.2 and 17.1 +/- 1.8%. During infusion of PPADS, P-SF fell by 18.8 +/- 2 (P = 0.4) and 16.5 +/- 1.5% (P = 0.82) in the two strains of mice. During suramin infusion, P-SF decreased by 14.7 +/- 2.4 (P = 0.62) and 15 +/- 1.3% (P = 0.4) in SWR/J and FVB mice, respectively. Including PPADS (10(-4) M) in the loop perfusate did not significantly alter the P-SF response (18.9 +/- 1.8%; P = 0.54). Arterial blood pressure was not systematically affected by the P2 inhibitors. As measured by free-flow micropuncture, PPADS significantly reduced proximal tubular fluid reabsorption in both fractional and absolute terms. These results indicate that the direct activation of P2 purinergic receptors by ATP is not a major cause of TGF-induced vasoconstriction in vivo. C1 NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDK, Kidney Dis Branch, NIH, Bldg 10,Rm 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. NR 34 TC 14 Z9 14 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2011 VL 300 IS 2 BP F339 EP F344 DI 10.1152/ajprenal.00637.2010 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 715XQ UT WOS:000286929200006 PM 21147842 ER PT J AU Leibenluft, E AF Leibenluft, Ellen TI Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; HOSPITALIZED AGGRESSIVE-CHILDREN; ADOLESCENT PSYCHIATRIC-DISORDERS; VENTROMEDIAL PREFRONTAL CORTEX; DISRUPTIVE BEHAVIOR DISORDERS; DOUBLE-BLIND; CONDUCT DISORDER AB In recent years, increasing numbers of children have been diagnosed with bipolar disorder. In some cases, children with unstable mood clearly meet current diagnostic criteria for bipolar disorder, and in others, the diagnosis is unclear. Severe mood dysregulation is a syndrome defined to capture the symptomatology of children whose diagnostic status with respect to bipolar disorder is uncertain, that is, those who have severe, nonepisodic irritability and the hyperarousal symptoms characteristic of mania but who lack the well-demarcated periods of elevated or irritable mood characteristic of bipolar disorder. Levels of impairment are comparable between youths with bipolar disorder and those with severe mood dysregulation. An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood. Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups. No specific treatment for severe mood dysregulation currently exists, but verification of its identity as a syndrome distinct from bipolar disorder by further research should include treatment trials. C1 NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bldg 15K,MSC-2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov FU NIMH FX Supported by the NIMH Intramural Research Program. NR 105 TC 181 Z9 183 U1 17 U2 50 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2011 VL 168 IS 2 BP 129 EP 142 DI 10.1176/appi.ajp.2010.10050766 PG 14 WC Psychiatry SC Psychiatry GA 716MI UT WOS:000286972800007 PM 21123313 ER PT J AU Shaw, P Gilliam, M Liverpool, M Weddle, C Malek, M Sharp, W Greenstein, D Evans, A Rapoport, J Giedd, J AF Shaw, Philip Gilliam, Mary Liverpool, Maria Weddle, Catherine Malek, Meaghan Sharp, Wendy Greenstein, Deanna Evans, Alan Rapoport, Judith Giedd, Jay TI Cortical Development in Typically Developing Children With Symptoms of Hyperactivity and Impulsivity: Support for a Dimensional View of Attention Deficit Hyperactivity Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AUTOMATED 3-D EXTRACTION; REVISED CONNERS PARENT; DEFICIT/HYPERACTIVITY DISORDER; LATENT CLASS; BRAIN ABNORMALITIES; CEREBRAL-CORTEX; MATTER VOLUME; RATING-SCALE; GREY-MATTER; ADOLESCENTS AB Objective: There is considerable epidemiological and neuropsychological evidence that attention deficit hyperactivity disorder (ADHD) is best considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive impairments. The authors investigated whether cortical brain development in typically developing children with symptoms of hyperactivity and impulsivity resembles that found in the syndrome of ADHD. Specifically, they examined whether a slower rate of cortical thinning during late childhood and adolescence, which they previously found in ADHD, is also linked to the severity of symptoms of hyperactivity and impulsivity in typically developing children. Method: In a longitudinal analysis, a total of 193 typically developing children with 389 neuroanatomic magnetic resonance images and varying levels of symptoms of hyperactivity and impulsivity (measured with the Conners' Parent Rating Scale) were contrasted with 197 children with ADHD with 337 imaging scans. The relationship between the rates of regional cortical thinning and severity of symptoms of hyperactivity/impulsivity was determined. Results: Youth with higher levels of hyperactivity/impulsivity had a slower rate of cortical thinning, predominantly in prefrontal cortical regions, bilaterally in the middle frontal/premotor gyri, extending down the medial prefrontal wall to the anterior cingulate; the orbitofrontal cortex; and the right inferior frontal gyrus. For each increase of one point in the hyperactivity/impulsivity score, there was a decrease in the rate of regional cortical thinning of 0.0054 mm/year (SE=0.0019 mm/year). Children with ADHD had the slowest rate of cortical thinning. Conclusions: Slower cortical thinning during adolescence characterizes the presence of both the symptoms and syndrome of ADHD, providing neurobiological evidence for dimensionality of the disorder. C1 [Shaw, Philip] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Rm 3N202,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Giedd, Jay/A-3080-2008 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; FU National Institute of Mental Health FX Supported by the Intramural Research Program of the National Institute of Mental Health. NR 53 TC 106 Z9 108 U1 2 U2 28 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2011 VL 168 IS 2 BP 143 EP 151 DI 10.1176/appi.ajp.2010.10030385 PG 9 WC Psychiatry SC Psychiatry GA 716MI UT WOS:000286972800008 PM 21159727 ER PT J AU Finger, EC Marsh, AA Blair, KS Reid, ME Sims, C Ng, P Pine, DS Blair, RJR AF Finger, Elizabeth C. Marsh, Abigail A. Blair, Karina S. Reid, Marguerite E. Sims, Courtney Ng, Pamela Pine, Daniel S. Blair, R. James R. TI Disrupted Reinforcement Signaling in the Orbitofrontal Cortex and Caudate in Youths With Conduct Disorder or Oppositional Defiant Disorder and a High Level of Psychopathic Traits SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; PROBABILISTIC RESPONSE REVERSAL; DORSAL ANTERIOR CINGULATE; COMMON STEREOTACTIC SPACE; PASSIVE-AVOIDANCE; BASOLATERAL AMYGDALA; DISSOCIABLE ROLES; HUMAN BRAIN; CHILDREN AB Objective: Dysfunction in the amygdala and orbitofrontal cortex has been reported in youths and adults with psychopathic traits. The specific nature of the functional irregularities within these structures remains poorly understood. The authors used a passive avoidance task to examine the responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. Method: While performing the passive avoidance learning task, 15 youths with conduct disorder or oppositional defiant disorder plus a high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI scan. Results: Relative to the comparison youths, the youths with a disruptive behavior disorder plus psychopathic traits showed less orbitofrontal responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as less caudate response to early stimulus-reinforcement exposure. There were no group differences in amygdala responsiveness to these two task measures, but amygdala responsiveness throughout the task was lower in the youths with psychopathic traits. Conclusions: Compromised sensitivity to early reinforcement information in the orbitofrontal cortex and caudate and to reward outcome information in the orbitofrontal cortex of youths with conduct disorder or oppositional defiant disorder plus psychopathic traits suggests that the integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be disrupted. This provides a functional neural basis for why such youths are more likely to repeat disadvantageous decisions. New treatment possibilities are raised, as pharmacologic modulations of serotonin and dopamine can affect this form of learning. C1 [Finger, Elizabeth C.] Univ Western Ontario, Dept Clin Neurol Sci, Schulich Sch Med, London, ON N6A 5A5, Canada. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. RP Finger, EC (reprint author), Univ Western Ontario, Dept Clin Neurol Sci, Schulich Sch Med, B10-004,339 Windermere Rd, London, ON N6A 5A5, Canada. EM elizabeth.finger@lhsc.on.ca RI Finger, Elizabeth/B-6453-2015 FU NIMH; School of Psychiatry, University of New South Wales, Sydney, Australia FX Supported by the NIMH Intramural Research Program and by sponsorship of Ms. Ng by the School of Psychiatry, University of New South Wales, Sydney, Australia. NR 63 TC 76 Z9 78 U1 6 U2 29 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2011 VL 168 IS 2 BP 152 EP 162 DI 10.1176/appi.ajp.2010.10010129 PG 11 WC Psychiatry SC Psychiatry GA 716MI UT WOS:000286972800009 PM 21078707 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI Milton Terris (1915-2002): Outspoken Advocate for Progressive Public Health Policy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 2 TC 0 Z9 0 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2011 VL 101 IS 2 BP 253 EP 253 DI 10.2105/AJPH.2010.196667 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 707QH UT WOS:000286300600015 PM 21228289 ER PT J AU Parry, M AF Parry, Manon TI Ralph Nader: Public Health Advocate and Political Agitator SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Parry, Manon] Univ Maryland, College Pk, MD 20742 USA. RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2011 VL 101 IS 2 BP 257 EP 257 DI 10.2105/AJPH.2009.191163 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 707QH UT WOS:000286300600017 PM 21228291 ER PT J AU Gulley, SP Rasch, EK Chan, L AF Gulley, Stephen P. Rasch, Elizabeth K. Chan, Leighton TI Ongoing Coverage for Ongoing Care: Access, Utilization, and Out-of-Pocket Spending Among Uninsured Working-Aged Adults with Chronic Health Care Needs SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DISABILITIES; INSURANCE; SERVICES; MEDICARE; POPULATION; PHYSICIAN; AMERICANS; QUALITY; PEOPLE; SYSTEM AB Objectives. We sought to determine how part-year and full-year gaps in health insurance coverage affected working-aged persons with chronic health care needs. Methods. We conducted multivariate analyses of the 2002-2004 Medical Expenditure Panel Survey to compare access, utilization, and out-of-pocket spending burden among key groups of persons with chronic conditions and disabilities. The results are generalizable to the US community-dwelling population aged 18 to 64 years. Results. Among 92 million adults with chronic conditions, 21% experienced at least 1 month uninsured during the average year (2002-2004). Among the 25 million persons reporting both chronic conditions and disabilities, 23% were uninsured during the average year. These gaps in coverage were associated with significantly higher levels of access problems, lower rates of ambulatory visits and prescription drug use, and higher levels of out-of-pocket spending. Conclusions. Implementation of health care reform must focus not only on the prevention of chronic conditions and the expansion of insurance coverage but also on the long-term stability of the coverage to be offered. (Am J Public Health. 2011;101:368-375. doi:10.2105/AJPH.2010.191569) C1 [Gulley, Stephen P.; Rasch, Elizabeth K.; Chan, Leighton] NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. [Gulley, Stephen P.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. RP Gulley, SP (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bldg 10 CRC,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM gulley@brandeis.edu FU National Institutes of Health Clinical Research Center, Rehabilitation Medicine Department FX This research was supported by the Intramural Research Program of the National Institutes of Health Clinical Research Center, Rehabilitation Medicine Department. NR 43 TC 13 Z9 13 U1 1 U2 8 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2011 VL 101 IS 2 BP 368 EP 375 DI 10.2105/AJPH.2010.191569 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 707QH UT WOS:000286300600035 PM 21164090 ER PT J AU Cardenas, I Mor, G Aldo, P Lang, SM Stabach, P Sharp, A Romero, R Mazaki-Tovi, S Gervasi, M Means, RE AF Cardenas, Ingrid Mor, Gil Aldo, Paulomi Lang, Sabine M. Stabach, Paul Sharp, Andrew Romero, Roberto Mazaki-Tovi, Shali Gervasi, MariaTeresa Means, Robert E. TI Placental Viral Infection Sensitizes to Endotoxin-Induced Pre-Term Labor: A Double Hit Hypothesis SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Double hit hypothesis; lipopolysaccharide; placenta; toll-like receptors; trophoblast; viral infection ID BARR-VIRUS INFECTIONS; HERPES-SIMPLEX-VIRUS; TOLL-LIKE RECEPTORS; INTRAUTERINE INFECTION; PREGNANCY; TROPHOBLAST; INFLAMMATION; DELIVERY; LIPOPOLYSACCHARIDE AB Problem Among pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. We evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (LPS). Our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral sensitization to LPS. Method C57B/6 wild-type mice were injected with murine gammaherpesvirus 68 (MHV68) at E8.5. Either PBS or LPS was injected i.p. at E15.5. Pregnancy outcome and cytokine/chemokine profile from implantation sites were analyzed by multiplex. Results LPS treatment of MHV-68-infected animals induced pre-term delivery and fetal death in 100% of the mice. Pre-term labor was characterized by a upregulation of pro-inflammatory cytokines and chemokines in both placenta and decidua. Similar profiles were observed from MHV-68-infected human primary trophoblast and trophoblast cell lines in response to LPS. Conclusion We describe for the first time that a sub-clinical viral infection in pregnant mice might sensitize to a bacterial infection leading to pre-term delivery. We propose the 'Double Hit Hypothesis' where the presence of a viral infection enhances the effect of bacterial products during pregnancy leading not only to pre-term labor but likely larger adverse outcomes. C1 [Cardenas, Ingrid; Mor, Gil; Aldo, Paulomi; Sharp, Andrew] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. [Lang, Sabine M.; Stabach, Paul; Means, Robert E.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Romero, Roberto; Mazaki-Tovi, Shali] Wayne State Univ, Perinatol Res Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH,DHHS, Detroit, MI USA. [Gervasi, MariaTeresa] Azienda Osped Padova, Dept Obstet & Gynecol, Padua, Italy. 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 National Institutes of Health, NICDH [P01HD054713, 3N01 HD23342]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This study is in part funded by grants from the National Institutes of Health, NICDH P01HD054713 and 3N01 HD23342 and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 31 TC 48 Z9 49 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD FEB PY 2011 VL 65 IS 2 BP 110 EP 117 DI 10.1111/j.1600-0897.2010.00908.x PG 8 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 703TA UT WOS:000286003000004 PM 20712808 ER PT J AU Aaron, CP Tandri, H Barr, RG Johnson, WC Bagiella, E Chahal, H Jain, A Kizer, JR Bertoni, AG Lima, JAC Bluemke, DA Kawut, SM AF Aaron, Carrie P. Tandri, Harikrishna Barr, R. Graham Johnson, W. Craig Bagiella, Emilia Chahal, Harjit Jain, Aditya Kizer, Jorge R. Bertoni, Alain G. Lima, Joao A. C. Bluemke, David A. Kawut, Steven M. TI Physical Activity and Right Ventricular Structure and Function The MESA-Right Ventricle Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging ID ATHLETES HEART; PULMONARY-HYPERTENSION; STRENUOUS EXERCISE; CARDIAC STRUCTURE; ATHEROSCLEROSIS; MASS; HYPERTROPHY; LUNG; RAT; PERFORMANCE AB Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown. Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent-minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity. Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 +/- 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes. Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications. C1 [Kawut, Steven M.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Dept Med, Philadelphia, PA 19104 USA. [Kawut, Steven M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Aaron, Carrie P.; Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Bagiella, Emilia] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA. [Tandri, Harikrishna; Chahal, Harjit; Jain, Aditya; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Johnson, W. Craig] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kizer, Jorge R.] Weill Cornell Med Ctr, Dept Med, New York, NY USA. [Kizer, Jorge R.] Weill Cornell Med Ctr, Dept Publ Hlth, New York, NY USA. [Bertoni, Alain G.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Kawut, SM (reprint author), Univ Penn, Sch Med, Penn Cardiovasc Inst, Dept Med, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kawut@mail.med.upenn.edu OI Bluemke, David/0000-0002-8323-8086 FU National Institute of Health [R01-HL086719, R01-HL077612, N01-HC95159, HC95165, N01-HC95169]; Tethys Bioscience; Gilead; Novartis; Pfizer; Actelion; Gileac; United Therapeutics; Lung Rx; Merck FX Supported by National Institute of Health grants R01-HL086719 (S.M.K.), R01-HL077612 (R.G.B.), N01-HC95159 through HC95165; and N01-HC95169.; C.P.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.G.B. received a sponsored grant from National Institutes of Health (NIH) for more than $100,001. W.C.J. received a sponsored grant from NIH for $50,001-$100,000. E.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.K. received a sponsored grant from NIH for more than $100,001. A.B. received consultancy fees from Tethys Bioscience for $1,001-$5,000 and a sponsored grant for $50,001-8100,000, both for diabetic research. A.B. also received a sponsored research grant from NIH for more than $100,001. J.A.C.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.A.B. is a full-time employee of NIH Clinical Center. S.M.K. received consultancy fees from Gilead and Novartis for $1,001-$5,000 each and served on the advisory board of Bayer for $1,001-$5,000, Gilead for $1,001-$5,000 and (twice) for $10,001-$50,000, and Pfizer for $5001-$10,000. S.M.K. also received lecture fees from Gilead for $1,001-$5,000 and Actelion for $1,001-$5,000. S.M.K. received sponsored grants from Actelion, Gileac, United Therapeutics, Lung Rx, Merck, and Pfizer, all for $10,001-$50,000 each, and from Bayer for $5,001-$10,000 and Pfizer for 850,001-$100,000. S.M.K. served on the advisory board of NIH for less than $1,000, and the American Lung Association for $1,001-$5,000. S.M.K. received a sponsored grant from NIH for more than $100,001. NR 34 TC 24 Z9 24 U1 1 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2011 VL 183 IS 3 BP 396 EP 404 DI 10.1164/rccm.201003-0469OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 720QD UT WOS:000287294300017 PM 20813888 ER PT J AU Valderrama-Aguirre, A Zuniga-Soto, E Marino-Ramirez, L Moreno, LA Escalante, AA Arevalo-Herrera, M Herrera, S AF Valderrama-Aguirre, Augusto Zuniga-Soto, Evelin Marino-Ramirez, Leonardo Angela Moreno, Luz Escalante, Ananias A. Arevalo-Herrera, Myriam Herrera, Socrates TI Polymorphism of the Pv200L Fragment of Merozoite Surface Protein-1 of Plasmodium vivax in Clinical Isolates from the Pacific Coast of Colombia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID SEQUENCE ALIGNMENT; DNA POLYMORPHISM; MALARIA; VACCINE; MSP1; IMMUNOGENICITY; RECOMBINATION; SAFETY AB Merozoite surface protein 1 (MSP-1) is a polymorphic malaria protein with functional domains involved in parasite erythrocyte interaction. Plasmodium vivax MSP-1 has a fragment (Pv200L) that has been identified as a potential subunit vaccine because it is highly immunogenic and induces partial protection against infectious parasite challenge in vaccinated monkeys. To determine the extent of genetic polymorphism and its effect on the translated protein, we sequenced the Pv200L coding region from isolates of 26 P vivax-infected patients in a malaria-endemic area of Colombia. The extent of nucleotide diversity (pi) in these isolates (0.061 +/- 0.004) was significantly lower (P <= 0.001) than that observed in Thai and Brazilian isolates; 0.083 +/- 0.006 and 0.090 +/- 0.006, respectively. We found two new alleles and several previously unidentified dimorphic substitutions and significant size polymorphism. The presence of highly conserved blocks in this fragment has important implications for the development of Pv200L as a subunit vaccine candidate. C1 [Valderrama-Aguirre, Augusto; Zuniga-Soto, Evelin; Angela Moreno, Luz; Arevalo-Herrera, Myriam; Herrera, Socrates] Malaria Vaccine & Drug Dev Ctr, Cali, Colombia. [Valderrama-Aguirre, Augusto; Zuniga-Soto, Evelin; Angela Moreno, Luz; Arevalo-Herrera, Myriam; Herrera, Socrates] Univ Valle, Fac Salud, Inst Inmunol, Cali, Colombia. [Marino-Ramirez, Leonardo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Computat Biol Branch, Bethesda, MD 20892 USA. [Escalante, Ananias A.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. RP Herrera, S (reprint author), Malaria Vaccine & Drug Dev Ctr, Carrera 37,2Bis 5E-08, Cali, Colombia. EM avalderrama@inmuno.org; ezuniga@inmuno.org; marino@ncbi.nlm.nih.gov; luzangelmo@hotmail.com; Ananias.Escalante@asu.edu; marevalo@inmuno.org; sherrera@inmuno.org RI Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Valderrama-Aguirre, Augusto/0000-0002-5255-1440 FU National Institute of Allergy and Infectious Diseases (NIAID) [A1-49486/ TMRC]; National Bureau of Sciences; University of Valle State [245-2004]; COLCIENCIAS [1106-04-16489]; Colombian Ministry of Social Protection [2304-04-19524, 253-2005]; National Institutes of Health, USA [R01GM080586]; International Center of Excellence for Malaria Research NIAID/ICEMR [U 19AI089702] FX This study was supported through a P. vivax vaccine research program granted by the National Institute of Allergy and Infectious Diseases (NIAID grant no. A1-49486/ TMRC), National Bureau of Sciences, University of Valle State (contract no. 245-2004), COLCIENCIAS (grant 1106-04-16489), and the Colombian Ministry of Social Protection (grant 2304-04-19524) (contract no. 253-2005). Ananias A. Escalante is supported by the grant R01GM080586 from the National Institutes of Health, USA and through an International Center of Excellence for Malaria Research NIAID/ICEMR grant no U 19AI089702. NR 25 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 2011 VL 84 IS 2 SU 2 BP 64 EP 70 DI 10.4269/ajtmh.2011.09-0517 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 716WL UT WOS:000287004100010 PM 21292880 ER PT J AU Gu, DY Ma, Y Niu, G Yan, YJ Lang, LX Aisaand, HA Gao, HK Kiesewetter, DO Chen, XY AF Gu, Dongyu Ma, Ying Niu, Gang Yan, Yongjun Lang, Lixin Aisaand, Haji Akber Gao, Haokao Kiesewetter, Dale O. Chen, Xiaoyuan TI LC/MS evaluation of metabolism and membrane transport of bombesin peptides SO AMINO ACIDS LA English DT Article DE LC/MS/MS; Gastrin-releasing peptide receptor (GRPR); Bombesin (BBN); Agonist; Antagonist ID HUMAN PROSTATE ADENOCARCINOMA; IN-VITRO; RECEPTOR EXPRESSION; CANCER; HETERODIMER; ANTAGONISTS; ANALOGS; TUMORS; PET AB Two bombsin peptides, GRPR agonist [Aca-QWAVGHLM-NH(2)] and antagonist [fQWAVGHL-NHEthyl] were evaluated. We employed the highly sensitive Waters Q-Tof Premier MS coupled with a UPLC system to identify the metabolites produced by rat hepatocytes or PC-3 human prostate cancer cells; and we utilized the AB/MDS 4000 Q-Trap LC/MS/MS system with highly sensitive quantitative and qualitative performance, to quantitatively analyze the internalization of GRPR agonist and antagonist in PC-3 cells. The major metabolites of both GRPR agonist and antagonist were the result of peptide bond hydrolysis between W and A which was demonstrated by observation of the N-terminal fragment m/z 446 (Aca-QW-OH) for agonist and m/z 480 (fQW-OH) for antagonist. Both peptides were also hydrolyzed between A and V which formed peaks m/z 517 [Aca-QWA-OH] and m/z 555 (VGHLM-NH2) for the agonist and m/z 551 [fQWA-OH] and m/z 452 (VGHL-NHEthyl) for the antagonist. The peptide agonist also formed a unique metabolite that resulted from hydrolysis of the C-terminal amide. The antagonist showed significantly slower metabolism as compared to the agonist in both rat hepatocytes and PC-3 cells. The antagonist also showed significantly lower PC-3 cell internalization rate than that of the agonist. In conclusion, the metabolism profiles of both GRPR agonist and antagonist peptides were identified by LC/MS. The antagonist peptide was more stable than the agonist peptide in rat hepatocyte incubation. One major factor could be the hydrolysis-resistant C-terminal L-NHEthyl group compared with the unsubstituted amide of the agonist. Another factor could be different amino acid sequences of the agonist and antagonist that may also influence the enzymatic hydrolysis. The antagonist ligand is potentially more useful for receptor-targeted imaging due primarily to its higher metabolic stability. C1 [Gu, Dongyu; Ma, Ying; Niu, Gang; Yan, Yongjun; Lang, Lixin; Gao, Haokao; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Gu, Dongyu; Aisaand, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Urumqi, Peoples R China. [Gu, Dongyu] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM dk7k@nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX The research was supported by Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 21 TC 8 Z9 8 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2011 VL 40 IS 2 BP 669 EP 675 DI 10.1007/s00726-010-0696-y PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706BK UT WOS:000286189600035 PM 20676905 ER PT J AU Park, SS Maudsley, S AF Park, Sung-Soo Maudsley, Stuart TI Discontinuous pH gradient-mediated separation of TiO2-enriched phosphopeptides SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Titanium dioxide; Phosphoproteomics; Mass spectrometry; pH-dependent elution ID MASS-SPECTROMETRY; TITANIUM-DIOXIDE; PHOSPHORYLATED PEPTIDES; SIGNALING PATHWAYS; FEMTOMOLE LEVEL; RECEPTOR; ENRICHMENT; CELLS; IDENTIFICATION; STRATEGY AB Global profiling of phosphoproteomes has proven to be a great challenge due to the relatively low stoichiometry of protein phosphorylation and poor ionization efficiency in mass spectrometers. Effective, physiologically relevant, phosphoproteome research relies on the efficient phosphopeptide enrichment from complex samples. Immobilized metal affinity chromatography and titanium dioxide chromatography can greatly assist selective phosphopeptide enrichment. However, the complexity of resultant enriched samples is often still high, suggesting that further separation of enriched phosphopeptides is required. We have developed a pH gradient elution technique for enhanced phosphopeptide identification in conjunction with titanium dioxide chromatography. Using this process, we demonstrated its superiority to the traditional "one-pot" strategies for differential protein identification. Our technique generated a highly specific separation of phosphopeptides by an applied pH gradient between 9.2 and 11.3. The most efficient elution range for high-resolution phosphopeptide separation was between pHs 9.2 and 9.4. High-resolution separation of multiply phosphorylated peptides was primarily achieved using elution ranges greater than pH 9.4. Investigation of phosphopeptide sequences identified in each pH fraction indicated that phosphopeptides with phosphorylated residues proximal to acidic residues, including glutamic acid, aspartic acid, and other phosphorylated residues, were preferentially eluted at higher pH values. Published by Elsevier Inc. C1 [Park, Sung-Soo; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU National Institutes of Health FX This work was carried out entirely with the support of the Intramural Research Program of the National Institutes of Health. NR 36 TC 19 Z9 19 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 2011 VL 409 IS 1 BP 81 EP 88 DI 10.1016/j.ab.2010.10.003 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 705KE UT WOS:000286126500012 PM 20946866 ER PT J AU Ferrer, RA Huedo-Medina, TB Johnson, BT Ryan, S Pescatello, LS AF Ferrer, Rebecca A. Huedo-Medina, Tania B. Johnson, Blair T. Ryan, Stacey Pescatello, Linda S. TI Exercise Interventions for Cancer Survivors: A Meta-Analysis of Quality of Life Outcomes SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Cancer; Oncology; Exercise; Behavioral interventions; Quality of life; Meta-analysis; Exercise interventions; Cancer survivors ID RANDOMIZED CONTROLLED-TRIAL; RECEIVING ADJUVANT CHEMOTHERAPY; PHYSICAL-ACTIVITY INTERVENTION; ANDROGEN DEPRIVATION THERAPY; STEM-CELL TRANSPLANTATION; BREAST-CANCER; PROSTATE-CANCER; FUNCTIONAL ASSESSMENT; AEROBIC EXERCISE; RESISTANCE EXERCISE AB Exercise improves quality of life (QOL) in cancer survivors, although characteristics of efficacious exercise interventions for this population have not been identified. The present meta-analysis examines the efficacy of exercise interventions in improving QOL in cancer survivors, as well as features that may moderate such effects. Studies were identified and coded, and QOL effect sizes were calculated and analyzed for trends. Overall, exercise interventions increased QOL, but this tendency depended to some extent on exercise and patient features. Although several features were associated with effect sizes, models revealed that interventions were particularly successful if they targeted more intense aerobic exercise and addressed women. These tendencies emerged over longer periods of time and were more prominent in studies with higher methodological quality. Appropriately designed exercise interventions enhance QOL for cancer survivors and this pattern is especially evident for women. Limitations are discussed. C1 [Ferrer, Rebecca A.] NCI, Div Canc Control & Populat, Behav Res Program, Rockville, MD 20852 USA. [Huedo-Medina, Tania B.; Johnson, Blair T.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Huedo-Medina, Tania B.; Johnson, Blair T.; Ryan, Stacey; Pescatello, Linda S.] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA. [Ryan, Stacey; Pescatello, Linda S.] Univ Connecticut, Dept Kinesiol, Storrs, CT USA. RP Ferrer, RA (reprint author), NCI, Div Canc Control & Populat, Behav Res Program, 6130 Executive Blvd,MSC 7326,Room 4089A, Rockville, MD 20852 USA. EM ferrerra@mail.nih.gov FU NIMH NIH HHS [R01 MH058563-13, F31 MH080626, F31MH080626, R01 MH058563, R01-MH58563] NR 142 TC 92 Z9 93 U1 4 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FEB PY 2011 VL 41 IS 1 BP 32 EP 47 DI 10.1007/s12160-010-9225-1 PG 16 WC Psychology, Multidisciplinary SC Psychology GA 717KB UT WOS:000287041400004 PM 20931309 ER PT J AU Cohen, SS Gammon, MD Signorello, LB North, KE Lange, EM Fowke, JH Hargreaves, MK Cai, QY Zheng, W Blot, WJ Matthews, CE AF Cohen, Sarah S. Gammon, Marilie D. Signorello, Lisa B. North, Kari E. Lange, Ethan M. Fowke, Jay H. Hargreaves, Margaret K. Cai, Qiuyin Zheng, Wei Blot, William J. Matthews, Charles E. TI Serum Adiponectin in Relation to Body Mass Index and Other Correlates in Black and White Women SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Adiponectin; African Americans; Obesity ID FOOD FREQUENCY QUESTIONNAIRE; SOUTHERN COMMUNITY COHORT; INSULIN SENSITIVITY; AFRICAN-AMERICANS; FAT DISTRIBUTION; GLYCEMIC LOAD; UNITED-STATES; PLASMA; RISK; HYPERTENSION AB PURPOSE: Adiponectin is a promising biomarker linking obesity and disease risk; however, limited data are available regarding adiponectin in black women among whom obesity is highly prevalent. METHODS: A cross-sectional analysis was conducted to assess racial differences and correlates of serum adiponectin measured in 996 black and 996 white women enrolled in the Southern Community Cohort Study through Community Health Centers in 12 southeastern states from 2002 to 2006. RESULTS: Black subjects had significantly lower adiponectin levels than white subjects (median 10.9 vs 14.9 mu g/mL, Wilcoxonp < .0001). Among black subjects, adiponectin was lower among overweight and obese women compared with healthy weight women but showed no clear decreasing trend with increasing severity of obesity; adjusted geometric means (95% confidence interval) were 15.0 [13.8-16.4], 11.5 [10.6-12.5], 9.7 [9.0-10.6], 11.4 [10.3-12.6], and 10.9 [9.5-12.6] mu g/mL for body mass index [BMI] categories of 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40-45, p for trend < .0001). In contrast, among whites there was a monotonic reduction in adiponectin over increasing BMI (adjusted geometric means = 19.9 [18.3-21.7], 15.1 [13.9-16.4], 14.3 [13.2-15.5], 12.5 [11.2-13.9], and 11.0 [9.7-12.5] mu g/mL, p for trend < .0001). BMI, age, high-density lipoprotein cholesterol, and hypertension were important correlates of adiponectin in both groups. CONCLUSIONS: Among women, racial differences exist in both the magnitude and form of the adiponectin-BMI association. Ann Epidemiol 2011;21:86-94. (C) 2011 Elsevier Inc. All rights reserved. C1 [Cohen, Sarah S.; Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA. [Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Signorello, Lisa B.; Fowke, Jay H.; Cai, Qiuyin; Zheng, Wei; Blot, William J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Signorello, Lisa B.; Fowke, Jay H.; Cai, Qiuyin; Zheng, Wei; Blot, William J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Hargreaves, Margaret K.] Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Rockville, MD USA. RP Cohen, SS (reprint author), Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA. EM sarah@ieixmail.com RI matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU Susan G. Komen for the Cure [OP05-0927-DR1]; National Cancer Institute (NCI) [R01 CA92447, T32 GA09330-26, 5-R25-CA057726]; National Institute of Environmental Health Sciences [P30ES10126]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This project was funded in part by grant OP05-0927-DR1 from Susan G. Komen for the Cure. The Southern Community Cohort Study is funded by grant R01 CA92447 from the National Cancer Institute (NCI). Dr. Cohen also received support from NCI Training Grants T32 GA09330-26 and 5-R25-CA057726. Dr. Gammon is supported in part from P30ES10126 from the National Institute of Environmental Health Sciences.; Serum sample preparation was conducted at the Survey and Biospecimen Shared Resource that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 38 TC 21 Z9 22 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2011 VL 21 IS 2 BP 86 EP 94 DI 10.1016/j.annepidem.2010.10.011 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 708FR UT WOS:000286348200003 PM 21109453 ER PT J AU Kiesewetter, DO Jacobson, O Lang, LX Chen, XY AF Kiesewetter, Dale O. Jacobson, Orit Lang, Lixin Chen, Xiaoyuan TI Automated radiochemical synthesis of [F-18]FBEM: A thiol reactive synthon for radiofluorination of peptides and proteins SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE PET; Fluorine-18; Thiol reactive synthon; [F-18]FBEM ID F-18-LABELING AGENT; RGD PEPTIDE; F-18; PACLITAXEL AB The automated radiochemical synthesis of N-[2-(4-[F-18]fluorobenzamido)ethyl]maleimide ([F-18]FBEM, IUPAC name: N-maleoylethyl-4-[F-18]fluorobenzamide), a prosthetic group for radiolabeling the free sulfhydryl groups of peptides and proteins, is herein described. 4-[F-18]fluorobenzoic acid was first prepared by nucleophilic displacement of a trimethylammonium moiety on a pentamethylbenzyl benzoate ester with [F-18]fluoride. In the second step the ester was cleaved under acidic conditions. Finally, 4-[F-18]fluorobenzoic acid was coupled to N-(2-aminoethyl)maleimide using diethylcyanophosphate and diisopropylethyl amine. Following high-performance liquid chromatography (HPLC) purification, [F-18]FBEM was obtained in 17.3 +/- 7.1% yield (not decay corrected) in approximately 95 min. Isolation from the HPLC eluate and preparation for subsequent use, which was conducted manually, required an additional 10-15 min. The measured specific activity for three batches was 181.3, 251.6, and 351.5 GBq/ mu mol at the end of bombardment (EOB). Published by Elsevier Ltd. C1 [Kiesewetter, Dale O.; Jacobson, Orit; Lang, Lixin; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bldg 10,Room 1C401,MSC 1180, Bethesda, MD 20892 USA. EM dk7k@nih.gov FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. Technical assistance was provided by Eckert & Ziegler Eurotope GmbH for programming suggestions. NR 14 TC 26 Z9 26 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD FEB PY 2011 VL 69 IS 2 BP 410 EP 414 DI 10.1016/j.apradiso.2010.09.023 PG 5 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 717QY UT WOS:000287063700021 PM 20965741 ER PT J AU Mickey, BJ Zhou, ZF Heitzeg, MM Heinz, E Hodgkinson, CA Hsu, DT Langenecker, SA Love, TM Pecina, M Shafir, T Stohler, CS Goldman, D Zubieta, JK AF Mickey, Brian J. Zhou, Zhifeng Heitzeg, Mary M. Heinz, Elizabeth Hodgkinson, Colin A. Hsu, David T. Langenecker, Scott A. Love, Tiffany M. Pecina, Marta Shafir, Tal Stohler, Christian S. Goldman, David Zubieta, Jon-Kar TI Emotion Processing, Major Depression, and Functional Genetic Variation of Neuropeptide Y SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PREFRONTAL CORTEX; TRAUMA EXPOSURE; NEURAL BASIS; PEPTIDE-YY; NPY; STRESS; BRAIN; DISORDER; PAIN; NEUROCIRCUITRY AB Context: Despite recent progress in describing the common neural circuitry of emotion and stress processing, the bases of individual variation are less well understood. Genetic variants that underlie psychiatric disease have proven particularly difficult to elucidate. Functional genetic variation of neuropeptide Y (NPY) was recently identified as a source of individual differences in emotion. Low NPY levels have been reported in major depressive disorder (MDD). Objective: To determine whether low-expression NPY genotypes are associated with negative emotional processing at 3 levels of analysis. Design: Cross-sectional, case-control study. Setting: Academic medical center. Participants: Among 44 individuals with MDD and 137 healthy controls, 152 (84%) had an NPY genotype classified as low, intermediate, or high expression according to previously established haplotype-based expression data. Main Outcome Measures: Healthy subjects participated in functional magnetic resonance imaging while viewing negative (vs neutral) words (n=58) and rated positive and negative affect during a pain-stress challenge (n=78). Genotype distribution was compared between 113 control subjects and 39 subjects with MDD. Results: Among healthy individuals, negatively valenced words activated the medial prefrontal cortex. Activation within this region was inversely related to genotype predicted NPY expression (P=. 03). Whole-brain regression of responses to negative words showed that the rostral anterior cingulate cortex activated in the low-expression group and deactivated in the high-expression group (P<.05). During the stress challenge, individuals with low-expression NPY genotypes reported more negative affective experience before and after pain (P=. 002). Low-expression NPY genotypes were overrepresented in subjects with MDD after controlling for age and sex (P=.004). Population stratification did not account for the results. Conclusions: These findings support a model in which NPY genetic variation predisposes certain individuals to low NPY expression, thereby increasing neural responsivity to negative stimuli within key affective circuit elements, including the medial prefrontal and anterior cingulate cortices. These genetically influenced neural response patterns appear to mediate risk for some forms of MDD. C1 [Mickey, Brian J.; Heitzeg, Mary M.; Hsu, David T.; Langenecker, Scott A.; Love, Tiffany M.; Pecina, Marta; Shafir, Tal; Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Mickey, Brian J.; Heitzeg, Mary M.; Hsu, David T.; Langenecker, Scott A.; Shafir, Tal; Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Zhou, Zhifeng; Heinz, Elizabeth; Hodgkinson, Colin A.; Goldman, David] Natl Inst Alcohol Abuse & Alcoholism, Neurogenet Lab, Rockville, MD USA. [Stohler, Christian S.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. RP Mickey, BJ (reprint author), Univ Michigan, Mol & Behav Neurosci Inst, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM bmickey@umich.edu RI Langenecker, Scott/F-3548-2012; Mickey, Brian/J-1756-2014; Hsu, David/J-5814-2014; Goldman, David/F-9772-2010; OI Langenecker, Scott/0000-0002-7932-5494; Mickey, Brian/0000-0002-7847-7680; Goldman, David/0000-0002-1724-5405; Love, Tiffany/0000-0001-9299-3190 FU National Institute of Mental Health [P01 MH42251, R25 MH6374, K23 MH074459]; National Institute on Drug Abuse [R01 DA016423, R01 DA 022520]; National Institute on Alcohol Abuse and Alcoholism; Phil F. Jenkins Research Fund FX This work was supported by grants P01 MH42251, R25 MH6374, and K23 MH074459 from the National Institute of Mental Health, grants R01 DA016423 and R01 DA 022520 from the National Institute on Drug Abuse, the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, and the Phil F. Jenkins Research Fund. NR 50 TC 49 Z9 51 U1 0 U2 9 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 FEB PY 2011 VL 68 IS 2 BP 158 EP 166 DI 10.1001/archgenpsychiatry.2010.197 PG 9 WC Psychiatry SC Psychiatry GA 717KC UT WOS:000287041500007 PM 21300944 ER PT J AU Wang, H O'Reilly, EJ Weisskopf, MG Logroscino, G McCullough, ML Thun, MJ Schatzkin, A Kolonel, LN Ascherio, A AF Wang, Hao O'Reilly, Eilis J. Weisskopf, Marc G. Logroscino, Giancarlo McCullough, Marji L. Thun, Michael J. Schatzkin, Arthur Kolonel, Laurence N. Ascherio, Alberto TI Smoking and Risk of Amyotrophic Lateral Sclerosis A Pooled Analysis of 5 Prospective Cohorts SO ARCHIVES OF NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; RECREATIONAL PHYSICAL-ACTIVITY; POSTMENOPAUSAL BREAST-CANCER; BASE-LINE CHARACTERISTICS; WESTERN WASHINGTON-STATE; II NUTRITION COHORT; CIGARETTE-SMOKING; ALCOHOL-CONSUMPTION; MULTIETHNIC COHORT; ANTECEDENT EVENTS AB Background: Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but epidemiological studies supporting this hypothesis have been small and mostly retrospective. Objective: To prospectively examine the relation between smoking and ALS in 5 well-established large cohorts. Design: Five prospective cohorts with study-specific follow-up ranging from 7 to 28 years. Setting: Academic research. Patients: Participants in the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, and the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study. Main Outcome Measures: Amyotrophic lateral sclerosis deaths identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal incident ALS was also included. Results: A total of 832 participants with ALS were documented among 562 804 men and 556 276 women. Smokers had a higher risk of ALS than never smokers, with age- and sex-adjusted relative risks of 1.44 (95% confidence interval, 1.23-1.68; P <.001) for former smokers and 1.42(95% confidence interval, 1.07-1.88; P=.02) for current smokers. Although the risk of ALS was positively associated with pack-years smoked(P <.001), duration of smoking(9% increase for each 10 years of smoking, P=.006), and the number of cigarettes smoked per day (10% increase for each increment of 10 cigarettes smoked per day, P <.001), these associations did not persist when never smokers were excluded. However, among ever smokers, the risk of ALS increased as age at smoking initiation decreased (P=.03). Conclusions: Results of this large longitudinal study support the hypothesis that cigarette smoking increases the risk of ALS. The potential importance of age at smoking initiation and the lack of a dose response deserve further investigation. Arch Neurol. 2011; 68(2):207-213 C1 [Wang, Hao; O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA. [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Weisskopf, Marc G.] Harvard Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Logroscino, Giancarlo] Univ Bari, Dept Neurol & Psychiat, Sch Med, Bari, Italy. [McCullough, Marji L.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Schatzkin, Arthur] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA. RP O'Reilly, EJ (reprint author), Harvard Univ, Dept Nutr, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM eoreilly@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU National Institute of Neurological Diseases and Stroke [R01 NS045893] FX This work was supported by grant R01 NS045893 from the National Institute of Neurological Diseases and Stroke (Dr Ascherio). NR 50 TC 44 Z9 45 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2011 VL 68 IS 2 BP 207 EP 213 DI 10.1001/archneurol.2010.367 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 721CY UT WOS:000287330300008 PM 21320987 ER PT J AU Lin, FR Metter, EJ O'Brien, RJ Resnick, SM Zonderman, AB Ferrucci, L AF Lin, Frank R. Metter, E. Jeffrey O'Brien, Richard J. Resnick, Susan M. Zonderman, Alan B. Ferrucci, Luigi TI Hearing Loss and Incident Dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; OLDER-ADULTS; COGNITIVE DECLINE; IMPAIRMENT; PREVALENCE; AGE; HEALTH; DYSFUNCTION; POPULATION AB Objective: To determine whether hearing loss is associated with incident all-cause dementia and Alzheimer disease (AD). Design: Prospective study of 639 individuals who underwent audiometric testing and were dementia free in 1990 to 1994. Hearing loss was defined by a pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear (normal, < 25 dB [n=455]; mild loss, 25-40 dB [n=125]; moderate loss, 41-70 dB [n=53]; and severe loss, > 70 dB [n=6]). Diagnosis of incident dementia was made by consensus diagnostic conference. Cox proportional hazards models were used to model time to incident dementia according to severity of hearing loss and were adjusted for age, sex, race, education, diabetes mellitus, smoking, and hypertension. Setting: Baltimore Longitudinal Study of Aging. Participants: Six hundred thirty-nine individuals aged 36 to 90 years. Main Outcome Measure: Incident caces of all-cause dementia and AD until May 31, 2008. Results: During a median follow-up of 11.9 years, 58 cases of incident all-cause dementia were diagnosed, of which 37 cases were AD. The risk of incident all-cause dementia increased log linearly with the severity of baseline hearing loss (1.27 per 10-dB loss; 95% confidence interval, 1.06-1.50). Compared with normal hearing, the hazard ratio (95% confidence interval) for incident all-cause dementia was 1.89 (1.00-3.58) for mild hearing loss, 3.00 (1.43-6.30) for moderate hearing loss, and 4.94 (1.09-22.40) for severe hearing loss. The risk of incident AD also increased with baseline hearing loss (1.20 per 10 dB of hearing loss) but with a wider confidence interval (0.94-1.53). Conclusions: Hearing loss is independently associated with incident all-cause dementia. Whether hearing loss is a marker for early-stage dementia or is actually a modifiable risk factor for dementia deserves further study. Arch Neurol. 2011; 68(2):214-220 C1 [Lin, Frank R.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Lin, Frank R.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. [O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD USA. [Resnick, Susan M.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Lin, FR (reprint author), Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, JHOC 6120,601 N Caroline St, Baltimore, MD 21287 USA. EM flin1@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging; National Institute on Deafness and Other Communication Disorders [1K23DC011279-01] FX This work was supported by the Intramural Research Program of the National Institute on Aging and grant 1K23DC011279-01 from the National Institute on Deafness and Other Communication Disorders (Dr Lin). NR 44 TC 191 Z9 211 U1 12 U2 57 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2011 VL 68 IS 2 BP 214 EP 220 DI 10.1001/archneurol.2010.362 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 721CY UT WOS:000287330300009 PM 21320988 ER PT J AU Sojkova, J Driscoll, I Iacono, D Zhou, Y Codispoti, KE Kraut, MA Ferrucci, L Pletnikova, O Mathis, CA Klunk, WE O'Brien, RJ Wong, DF Troncoso, JC Resnick, SM AF Sojkova, Jitka Driscoll, Ira Iacono, Diego Zhou, Yun Codispoti, Kari-Elise Kraut, Michael A. Ferrucci, Luigi Pletnikova, Olga Mathis, Chester A. Klunk, William E. O'Brien, Richard J. Wong, Dean F. Troncoso, Juan C. Resnick, Susan M. TI In Vivo Fibrillar beta-Amyloid Detected Using [C-11]PiB Positron Emission Tomography and Neuropathologic Assessment in Older Adults SO ARCHIVES OF NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; REFERENCE TISSUE MODEL; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; SPATIAL CONSTRAINT; DIAGNOSIS; PET; MARKER; PIB AB Background: In demented older adults, in vivo amyloid imaging shows agreement with diagnostic neuropathologic assessment of beta-amyloid (A beta). However, the extent of agreement in nondemented older adults remains unclear. Objective: To compare A beta quantified using in vivo carbon 11-labeled Pittsburgh Compound B positron emission tomography and postmortem neuropathologic assessment of A beta in older adults. Design: Case series. Setting: Community-dwelling older adults who came to autopsy. Participants: Five nondemented and 1 demented participant from the Baltimore Longitudinal Study of Aging. Main Outcome Measure: Agreement between the mean cortical distribution volume ratio and the Consortium to Establish a Registry for AD (CERAD) neuritic plaque (NP) score used for pathologic diagnosis of Alzheimer disease. Results: Of the 6 participants, 4 had moderate NPs, 2 had sparse or no detectable NPs, and 3 had microscopic findings of cerebral amyloid angiopathy at autopsy. On in vivo imaging, the mean cortical distribution volume ratio ranged from 0.96 to 1.59. Although there was agreement between in vivo amyloid imaging and CERAD NP scores in participants with either high or negligible A beta levels in vivo, only limited agreement was observed among those with intermediate levels of A beta. The best overall agreement was achieved at a distribution volume ratio of 1.2. Conclusions: In older adults, variable agreement between in vivo imaging and CERAD NP score was observed. The limited agreement may, in part, reflect differences in typical measurements of A beta using imaging compared with the CERAD neuropathologic protocol. Direct quantification of regional A beta in relation to in vivo imaging is necessary to further enhance our understanding of the imaging-pathologic assessment correlation. Arch Neurol. 2011; 68(2):232-240 C1 [Resnick, Susan M.] NIA, Lab Behav Neurosci, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Sojkova, Jitka; Zhou, Yun; Codispoti, Kari-Elise; Kraut, Michael A.; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Iacono, Diego; Codispoti, Kari-Elise; Pletnikova, Olga; Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Wong, Dean F.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. [Wong, Dean F.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, Biomed Res Ctr, NIH, 251 Bayview Blvd,Room 4B317, Baltimore, MD 21224 USA. EM resnicks@grc.nia.nih.gov OI Klunk, William/0000-0001-5512-0251 FU National Institute on Aging, National Institutes of Health; Johns Hopkins University Alzheimer's Disease Research Center [N01-AG-3-2124, K24 DA00412, P50 AG005133, R37 AG025516, P01 AG025204, P50 AG05146] FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, and N01-AG-3-2124 and extramural grants K24 DA00412 (Dr Wong), P50 AG005133, R37 AG025516 (Dr Klunk), and P01 AG025204 (Dr Klunk) and by grant P50 AG05146 from The Johns Hopkins University Alzheimer's Disease Research Center. NR 22 TC 50 Z9 50 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2011 VL 68 IS 2 BP 232 EP 240 DI 10.1001/archneurol.2010.357 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 721CY UT WOS:000287330300011 PM 21320990 ER PT J AU Gavrielides, MA Gallas, BD Lenz, P Badano, A Hewitt, SM AF Gavrielides, Marios A. Gallas, Brandon D. Lenz, Petra Badano, Aldo Hewitt, Stephen M. TI Observer Variability in the Interpretation of HER2/neu Immunohistochemical Expression With Unaided and Computer-Aided Digital Microscopy SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CELLULAR IMAGING-SYSTEM; IN-SITU HYBRIDIZATION; BREAST-CANCER; TISSUE MICROARRAYS; VIRTUAL MICROSCOPY; INTEROBSERVER REPRODUCIBILITY; QUANTITATIVE-ANALYSIS; PROTEIN EXPRESSION; HER-2/NEU STATUS; RECEPTOR STATUS AB Context.-Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice. Objectives.-To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy. Design.-A set of 335 digital microscopy images extracted from 64 breast cancer tissue slides stained with a HER2 antibody, were read by 14 observers in 2 reading modes: the unaided mode and the computer-aided mode. In the unaided mode, HER2 images were displayed on a calibrated color monitor with no other information, whereas in the computer-aided mode, observers were shown a HER2 image along with a corresponding feature plot showing computer-extracted values of membrane staining intensity and membrane completeness for the particular image under examination and, at the same time, mean feature values of the different HER2 categories. In both modes, observers were asked to provide a continuous score of HER2 expression. Results.-Agreement analysis performed on the output of the study showed significant improvement in both interobserver and intraobserver agreement when the computer-aided reading mode was used to evaluate preselected image fields. Conclusion.-The role of computer-aided digital microscopy in reducing observer variability in immunohistochemistry is promising. (Arch Pathol Lab Med. 2011;135:233-242) C1 [Gavrielides, Marios A.; Gallas, Brandon D.; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Lenz, Petra; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4114, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; Hewitt, Stephen/0000-0001-8283-1788; badano, aldo/0000-0003-3712-6670 NR 43 TC 30 Z9 31 U1 1 U2 7 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2011 VL 135 IS 2 BP 233 EP 242 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 722KG UT WOS:000287430500017 PM 21284444 ER PT J AU Rossouw, J Bray, P Liu, JM Kooperberg, C Hsia, J Lewis, C Cushman, M Bonds, D Hendrix, S Papanicolaou, G Howard, T Herrington, D AF Rossouw, Jacques Bray, Paul Liu, Jingmin Kooperberg, Charles Hsia, Judith Lewis, Cora Cushman, Mary Bonds, Denise Hendrix, Susan Papanicolaou, George Howard, Timothy Herrington, David TI Estrogen Receptor Polymorphisms and the Vascular Effects of Hormone Therapy SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE blood coagulation; clinical trials; coronary artery disease; epidemiology; pulmonary embolism; receptors; stroke; estrogen ID ALPHA GENE POLYMORPHISMS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGEN; POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; REPLACEMENT THERAPY AB Objective-To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thromboembolism. Methods and Results-The design was a nested case-control study in the Women's Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: 359 cases of coronary heart disease, 248 of stroke, and 217 of venous thromboembolism. Six estrogen receptor-alpha polymorphisms and 1 estrogen receptor-beta polymorphism were genotyped; 8 biomarkers known to be affected by hormone therapy were measured at baseline and 1 year after randomization. The polymorphisms were not associated with risk of vascular events and did not modify the increased risks of coronary heart disease, stroke, or venous thromboembolism due to hormone therapy. However, a reduced response of plasmin-antiplasmin to hormone therapy was noted for estrogen receptor-1 IVS1 (intron number 1)-354 (interaction P<0.0001, corrected for multiple comparisons P=0.014) and estrogen receptor-1 IVS1-1415 (interaction P<0.0001, corrected P=0.014). Conclusion-Estrogen receptor polymorphisms reduce the effect of postmenopausal hormone therapy on plasmin-antiplasmin, a marker of coagulation and fibrinolysis. However, screening for estrogen receptor polymorphisms to identify women at less risk of adverse cardiovascular outcomes is not likely to be useful in making decisions about hormone therapy treatment. (Arterioscler Thromb Vasc Biol. 2011;31:464-469.) C1 [Rossouw, Jacques; Bonds, Denise; Papanicolaou, George] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Bray, Paul] Thomas Jefferson Univ, Dept Hematol, Philadelphia, PA 19107 USA. [Liu, Jingmin] Canc Res Ctr, Fred Hutchinson Publ Hlth Sci Div, Seattle, WA USA. [Hsia, Judith] George Washington Univ, Dept Cardiol, Washington, DC USA. [Lewis, Cora] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Hendrix, Susan] Detroit Med Ctr, Dept Obstet & Gynecol, Detroit, MI USA. [Howard, Timothy] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom & Pesonalized Med Res, Winston Salem, NC USA. [Herrington, David] Wake Forest Univ, Bowman Gray Sch Med, Dept Cardiol, Winston Salem, NC USA. RP Rossouw, J (reprint author), NHLBI, Div Cardiovasc Sci, Rockledge 2,Rm 9192,6701 Rockledge Ave, Bethesda, MD 20892 USA. EM rossouwj@nih.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health [N01WH 2211, 2452, 32100, 32101, 32102, 32105, 32106, 32107, 32108, 32109, 32111, 32112, 32113, 32115, 32118, 32119, 32122, 42107, 42108, 42109, 42110, 42112, 42113, 42115, 42116, 42117, 42118, 42119, 42120, 42121, 42122, 42123, 42124, 42125, 42126, 42129, 42130, 42131, 42132, 44221] FX The Women's Health Initiative is funded by contracts N01WH 2211, 2452, 32100 to 32102, 32105 to 32106, 32108 to 32109, 32111 to 32113, 32115, 32118 to 32119, 32122, 42107 to 42126, 42129 to 42132, and 44221 from the National Heart, Lung, and Blood Institute, National Institutes of Health. Study drugs were donated by Wyeth Research, St. Davids, Pa. NR 35 TC 16 Z9 16 U1 0 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 FEB PY 2011 VL 31 IS 2 BP 464 EP U433 DI 10.1161/ATVBAHA.110.215087 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708PS UT WOS:000286376800034 PM 21106950 ER PT J AU Alevizos, I Alexander, S Turner, RJ Illei, GG AF Alevizos, Ilias Alexander, Stefanie Turner, R. James Illei, Gabor G. TI MicroRNA Expression Profiles as Biomarkers of Minor Salivary Gland Inflammation and Dysfunction in Sjogren's Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FIBROBLAST-LIKE SYNOVIOCYTES; RHEUMATOID-ARTHRITIS; IMMUNE-SYSTEM; LUNG-CANCER; DISEASE; PROGNOSIS; DIAGNOSIS; BIOPSIES; PLAYERS AB Objective. MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjogren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. Methods. MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. Results. MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. Conclusion. Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers. C1 [Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Clin, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr,1N110, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU National Institute of Dental and Craniofacial Research, NIH FX Supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH. NR 27 TC 49 Z9 53 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD FEB PY 2011 VL 63 IS 2 BP 535 EP 544 DI 10.1002/art.30131 PG 10 WC Rheumatology SC Rheumatology GA 719KC UT WOS:000287202600031 PM 21280008 ER PT J AU Parks, CG Walitt, BT Pettinger, M Chen, JC de Roos, AJ Hunt, J Sarto, G Howard, BV AF Parks, Christine G. Walitt, Brian T. Pettinger, Mary Chen, Jiu-Chiuan de Roos, Anneclaire J. Hunt, Julie Sarto, Gloria Howard, Barbara V. TI Insecticide Use and Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus in the Women's Health Initiative Observational Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID UNITED-STATES; OCCUPATIONAL EXPOSURES; ORGANOCHLORINE PESTICIDES; SOCIOECONOMIC-STATUS; DISEASE; MORTALITY; FARMERS; DETERMINANTS; AUTOIMMUNITY; ASSOCIATIONS AB Objective. Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown. Methods. We analyzed data from the Women's Health Initiative Observational Study (n = 76,861 postmenopausal women, ages 50-79 years). Incident cases (n = 213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self-report and use of disease-modifying antirheumatic drugs at year 3 of followup. We examined self-reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities. Results. Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17-3.56 for >= 6 times/year) and duration (HR 1.97, 95% CI 1.20-3.23 for >= 20 years). Risk was also associated with long-term insecticide application by others (HR 1.85, 95% CI 1.07-3.20 for >= 20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10-6.78 for >= 6 times/year). Conclusion. These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases. C1 [Parks, Christine G.] NIEHS, Durham, NC USA. [Walitt, Brian T.] Washington Hosp Ctr, Washington, DC 20010 USA. [Pettinger, Mary; de Roos, Anneclaire J.; Hunt, Julie] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chen, Jiu-Chiuan] Univ Calif Los Angeles, Keck Sch Med, Los Angeles, CA USA. [Sarto, Gloria] Univ Wisconsin, Med Ctr, Madison, WI 53706 USA. [Howard, Barbara V.] MedStar Hlth Res Inst, Washington, DC USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA. EM parks1@mail.nih.gov RI Chen, JC/I-2261-2016; OI Parks, Christine/0000-0002-5734-3456 FU NIH, National Institute of Environmental Health Sciences; National Heart, Lung, and Blood Institute; NIH; US Department of Health and Human Services [N01-WH-22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Merck/Schering-Plough FX Supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute, the NIH, and the US Department of Health and Human Services (contracts N01-WH-22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221).; Dr. Howard has received consultant fees and speaking fees (less than $10,000) and research support in the form of drug donation from Merck/Schering-Plough. NR 42 TC 30 Z9 30 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2011 VL 63 IS 2 BP 184 EP 194 DI 10.1002/acr.20335 PG 11 WC Rheumatology SC Rheumatology GA 719ML UT WOS:000287208800003 PM 20740609 ER PT J AU Louie, GH Tektonidou, MG Caban-Martinez, AJ Ward, MM AF Louie, Grant H. Tektonidou, Maria G. Caban-Martinez, Alberto J. Ward, Michael M. TI Sleep Disturbances in Adults With Arthritis: Prevalence, Mediators, and Subgroups at Greatest Risk. Data From the 2007 National Health Interview Survey SO ARTHRITIS CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; CHRONIC PAIN; DAYTIME SLEEPINESS; UNITED-STATES; OLDER-ADULTS; INSOMNIA; DISORDERS; POPULATION; DEPRESSION AB Objective. To examine the prevalence of sleep disturbances in adults with arthritis in a nationally representative sample, mediators of sleep difficulties, and subgroups of individuals with arthritis at greatest risk. Methods. Using data on US adults ages >= 18 years participating in the 2007 National Health Interview Survey, we computed the prevalence of 3 measures of sleep disturbance (insomnia, excessive daytime sleepiness, and sleep duration <6 hours) among persons with arthritis. We used logistic regression analysis to examine if the association of arthritis and sleep disturbances was independent of sociodemographic characteristics and comorbidities, and to identify potential mediators. We used classification trees to identify subgroups at higher risk. Results. The adjusted prevalence of insomnia was higher among adults with arthritis than those without arthritis (23.1% versus 16.4%; P < 0.0001), but was similar to those with other chronic diseases. Adults with arthritis were more likely than those without arthritis to report insomnia (unadjusted odds ratio 2.92, 95% confidence interval 2.68-3.17), but adjustment for sociodemographic characteristics and comorbidities attenuated this association. Joint pain and limitation due to pain mediated the association between arthritis and insomnia. Among adults with arthritis, those with depression and anxiety were at highest risk for sleep disturbance. Results for excessive daytime sleepiness and sleep duration < 6 hours were similar. Conclusion. Sleep disturbance affects up to 10.2 million US adults with arthritis, and is mediated by joint pain and limitation due to pain. Among individuals with arthritis, those with depression and anxiety are at greatest risk. C1 [Louie, Grant H.; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Tektonidou, Maria G.] Natl Univ Athens, Athens, Greece. [Caban-Martinez, Alberto J.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. RP Louie, GH (reprint author), Johns Hopkins Univ, Sch Med, 5200 Eastern Ave,Mason F Lord Bldg,Ctr Tower,Suit, Baltimore, MD 21224 USA. EM glouie2@jhmi.edu OI Caban-Martinez, Alberto/0000-0002-5960-1308 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH FX Supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the NIH. NR 50 TC 21 Z9 21 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2011 VL 63 IS 2 BP 247 EP 260 DI 10.1002/acr.20362 PG 14 WC Rheumatology SC Rheumatology GA 719ML UT WOS:000287208800011 PM 20890980 ER PT J AU Yang, M Perry, K Weber, MD Katz, AM Crawley, JN AF Yang, Mu Perry, Kayla Weber, Michael D. Katz, Adam M. Crawley, Jacqueline N. TI Social Peers Rescue Autism-Relevant Sociability Deficits in Adolescent Mice SO AUTISM RESEARCH LA English DT Article DE autism; BTBR inbred strain; mouse model; peer enrichment; social enrichment; behavioral intervention ID FRAGILE-X-SYNDROME; INTENSIVE BEHAVIORAL TREATMENT; INTEGRATED PLAY GROUPS; BTBR-T+TF/J MICE; SPECTRUM DISORDERS; REPETITIVE BEHAVIOR; INBRED STRAINS; EARLY-CHILDHOOD; TASKS RELEVANT; MOUSE MODELS AB Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming in BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions. C1 [Yang, Mu] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Yang, M (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bldg 35,Room 1C-909,Mail Code 3730, Bethesda, MD 20892 USA. EM yangmu@mail.nih.gov OI Perry, Kayla/0000-0002-2629-1083 FU National Institute of Mental Health FX Grant sponsor: National Institute of Mental Health Intramural Research Program. NR 80 TC 44 Z9 44 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD FEB PY 2011 VL 4 IS 1 SI SI BP 17 EP 27 DI 10.1002/aur.163 PG 11 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 729JP UT WOS:000287945900003 PM 20928844 ER PT J AU Carter, MD Shah, CR Muller, CL Crawley, JN Carneiro, AMD Veenstra-VanderWeele, J AF Carter, Michelle D. Shah, Charisma R. Muller, Christopher L. Crawley, Jacqueline N. Carneiro, Ana M. D. Veenstra-VanderWeele, Jeremy TI Absence of Preference for Social Novelty and Increased Grooming in Integrin beta 3 Knockout Mice: Initial Studies and Future Directions SO AUTISM RESEARCH LA English DT Article DE autism; genetic; integrin; cell adhesion; serotonin; social memory; grooming; obsessive-compulsive disorder ID WHOLE-BLOOD SEROTONIN; AUTISM SPECTRUM DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; RECEPTOR GENE OXTR; COPY NUMBER VARIATION; MOUSE MODEL; 1ST-DEGREE RELATIVES; MENTAL-RETARDATION; ULTRASONIC VOCALIZATIONS; BEHAVIORAL PHENOTYPES AB Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin beta 3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin beta 3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene gene interaction between the integrin beta 3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin beta 3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin beta 3 receptor subunit (Itgb3+/- and -/-) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin beta 3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin beta 3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin beta 3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin beta 3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms. C1 [Carter, Michelle D.; Shah, Charisma R.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Muller, Christopher L.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN USA. [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Carneiro, Ana M. D.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Carneiro, Ana M. D.; Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN USA. [Veenstra-VanderWeele, Jeremy] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. RP Veenstra-VanderWeele, J (reprint author), 465 21st Ave S,7158 MRB 3, Nashville, TN 37232 USA. EM j.vvw@vanderbilt.edu RI Veenstra-VanderWeele, Jeremy/K-1935-2015 OI Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076 FU Seaside Therapeutics; Roche Pharmaceuticals; Novartis; NIH [K08-MH081066, T32-MH065215, HD15052]; NIH (Vanderbilt Kennedy Center) [T32-MH065215, HD15052, MH081066] FX Dr. Veenstra-VanderWeele receives research support from Seaside Therapeutics, Roche Pharmaceuticals, and Novartis, for clinical trials unrelated to the current research.; Grant sponsor: NIH; Grant numbers: K08-MH081066; T32-MH065215; HD15052.; We are especially grateful to the families who participated in the original genetic studies. We also thank Randy Blakely for helpful advice and generous mentorship. This work was supported, in part, by NIH grants MH081066 (JV), T32-MH065215 (JV), and HD15052 (Vanderbilt Kennedy Center). NR 97 TC 42 Z9 42 U1 3 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD FEB PY 2011 VL 4 IS 1 SI SI BP 57 EP 67 DI 10.1002/aur.180 PG 11 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 729JP UT WOS:000287945900006 PM 21254450 ER PT J AU Kidd, LR Hein, DW Woodson, K Taylor, PR Albanes, D Virtamo, J Tangrea, JA AF Kidd, LaCreis R. Hein, David W. Woodson, Karen Taylor, Philip R. Albanes, Demetrius Virtamo, Jarmo Tangrea, Joseph A. TI Lack of Association of the N-acetyltransferase NAT1*10 Allele with Prostate Cancer Incidence, Grade, or Stage Among Smokers in Finland SO BIOCHEMICAL GENETICS LA English DT Article DE N-acetyltransferase 1; Prostate cancer; Disease progression; Arylamine carcinogens ID NON-HODGKIN-LYMPHOMA; NAT2 GENETIC POLYMORPHISMS; DNA ADDUCT FORMATION; HAIR DYE USE; N-ACETYLTRANSFERASE-1 NAT1; CIGARETTE-SMOKING; MEAT INTAKE; COLORECTAL-CANCER; PANCREATIC-CANCER; EPITHELIAL-CELLS AB Genetic variations in xenobiotic metabolizing genes can influence susceptibility to many environmentally induced cancers. Inheritance of the N-acetyltransferase 1 allele (NAT1*10), linked with increased metabolic activation of pro-carcinogens, is associated with an increased susceptibility to many cancers in which cigarette- or meat-derived carcinogens have been implicated in their etiology. The role of NAT1*10 in prostate cancer is under studied. Although cigarette smoking is not considered a risk factor for prostate cancer, a recent review suggests it may play a role in disease progression. Consequently, we examined the association of NAT1*10 with prostate cancer risk, grade, and stage among 400 Finnish male smokers using a case-control study design. Following genotyping of 206 patients and 196 healthy controls, our results do not support the role of NAT1*10 in relation to prostate cancer risk (OR = 1.28; 95% CI, 0.66-2.47), aggressive disease (OR = 0.58; 95% CI, 0.13-2.67), or advanced disease (OR = 1.19; 95% CI, 0.49-2.91). C1 [Kidd, LaCreis R.; Hein, David W.] Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, Hlth Sci Ctr, Louisville, KY 40292 USA. [Kidd, LaCreis R.; Woodson, Karen; Taylor, Philip R.; Tangrea, Joseph A.] NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Kidd, LR (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, Hlth Sci Ctr, 306 Clin & Translat Res Bldg,505 S Hancock St, Louisville, KY 40292 USA. EM lrkidd01@louisville.edu RI Hein, David/A-9707-2008; Albanes, Demetrius/B-9749-2015 FU National Cancer Institute, United States Department of Health and Human Services [NO1 CN45165, 45035] FX We thank Rama Modali and Kirsten Taylor for technical support and Mike Barrett, Kirk Snyder, and Tan Carly for data management. This study was supported in part by Public Health Service contracts NO1 CN45165 and 45035 from the National Cancer Institute, United States Department of Health and Human Services. NR 58 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0006-2928 J9 BIOCHEM GENET JI Biochem. Genet. PD FEB PY 2011 VL 49 IS 1-2 BP 73 EP 82 DI 10.1007/s10528-010-9386-4 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 732ES UT WOS:000288168400008 PM 20931357 ER PT J AU Kendrick, AA Choudhury, M Rahman, SM McCurdy, CE Friederich, M Van Hove, JLK Watson, PA Birdsey, N Bao, JJ Gius, D Sack, MN Jing, EX Kahn, CR Friedman, JE Jonscher, KR AF Kendrick, Agnieszka A. Choudhury, Mahua Rahman, Shaikh M. McCurdy, Carrie E. Friederich, Marisa Van Hove, Johan L. K. Watson, Peter A. Birdsey, Nicholas Bao, Jianjun Gius, David Sack, Michael N. Jing, Enxuan Kahn, C. Ronald Friedman, Jacob E. Jonscher, Karen R. TI Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation SO BIOCHEMICAL JOURNAL LA English DT Article DE cellular metabolism; mitochondrial metabolism; NAD; non-alcoholic fatty liver disease; obesity; proteomics; sirtuin ID LYSINE ACETYLATION; INSULIN-RESISTANCE; OXIDATIVE STRESS; PYRUVATE-CARBOXYLASE; DEACETYLASE ACTIVITY; HISTONE DEACETYLASE; GENE-EXPRESSION; ACID OXIDATION; OBESITY; METABOLISM AB Acetylation has recently emerged as an important mechanism for controlling a broad array of proteins mediating cellular adaptation to metabolic fuels. Acetylation is governed, in part, by SIRTs (sirtuins), class III NAD(+)-dependent deacetylases that regulate lipid and glucose metabolism in liver during fasting and aging. However, the role of acetylation or SIRTs in pathogenic hepatic fuel metabolism under nutrient excess is unknown. In the present study, we isolated acetylated proteins from total liver proteome and observed 193 preferentially acetylated proteins in mice fed on an HFD (high-fat diet) compared with controls, including 11 proteins not previously identified in acetylation studies. Exposure to the HFD led to hyperacetylation of proteins involved in gluconeogenesis, mitochondrial oxidative metabolism, methionine metabolism, liver injury and the ER (endoplasmic reticulum) stress response. Livers of mice fed on the HFD had reduced SIRT3 activity, a 3-fold decrease in hepatic NAD(+) levels and increased mitochondrial protein oxidation. In contrast, neither SIRT1 nor histone acetyltransferase activities were altered, implicating SIRT3 as a dominant factor contributing to the observed phenotype. In Sirt3(-/-) mice, exposure to the HFD further increased the acetylation status of liver proteins and reduced the activity of respiratory complexes III and IV. This is the first study to identify acetylation patterns in liver proteins of HFD-fed mice. Our results suggest that SIRT3 is an integral regulator of mitochondrial function and its depletion results in hyperacetylation of critical mitochondrial proteins that protect against hepatic lipotoxicity under conditions of nutrient excess. C1 [Kendrick, Agnieszka A.; Friedman, Jacob E.; Jonscher, Karen R.] Univ Colorado, Sch Med, Dept Anesthesiol, NORC,Mass Spectrometry Core Facil, Aurora, CO 80045 USA. [Choudhury, Mahua; Rahman, Shaikh M.; McCurdy, Carrie E.; Friederich, Marisa; Van Hove, Johan L. K.; Friedman, Jacob E.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Watson, Peter A.; Birdsey, Nicholas] Denver VA Med Ctr, Denver, CO 80220 USA. [Bao, Jianjun; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Gius, David] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jing, Enxuan; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Friedman, JE (reprint author), Univ Colorado, Sch Med, Dept Anesthesiol, NORC,Mass Spectrometry Core Facil, Aurora, CO 80045 USA. EM jed.friedman@ucdenver.edu OI Jonscher, Karen/0000-0002-7929-4886 FU National Institutes of Health [DK59767, P30-DK48520, K12 HD057022]; University of Colorado, Center for Human Nutrition [P30-DK048520-09]; American Heart Association [09BGIA2060705]; American Diabetes Mentor-based Post-Doctoral Fellowship [7-08-MN-17]; Veterans Administration; National Heart, Lung, and Blood Institute; Center for Cancer Research, National Cancer Institute FX This work was supported by the National Institutes of Health [grant numbers DK59767, P30-DK48520 (to J.E.F.)]; a Pilot & Feasibility Award from the University of Colorado, Center for Human Nutrition [grant number P30-DK048520-09 to K.R.J.)]; the National Institutes of Health Office of Research in Women's Health BIRCWH Program [grant number K12 HD057022 (to C.E.M.)]; a Beginning Grant in Aid from the American Heart Association [grant number 09BGIA2060705 (to S.M.R.)]; and an American Diabetes Mentor-based Post-Doctoral Fellowship [grant number 7-08-MN-17 (to MC.)]. P.W. was supported by Veterans Administration Merit Awards. J.B. and M.N.S. were funded by the National Heart, Lung, and Blood Institute. D.G. was supported by the Center for Cancer Research, National Cancer Institute. NR 53 TC 122 Z9 129 U1 4 U2 28 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 2011 VL 433 BP 505 EP 514 DI 10.1042/BJ20100791 PN 3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757AJ UT WOS:000290055900012 PM 21044047 ER PT J AU Keppler, BR Archer, TK Kinyamu, HK AF Keppler, Brian R. Archer, Trevor K. Kinyamu, H. Karimi TI Emerging roles of the 26S proteasome in nuclear hormone receptor-regulated transcription SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE Proteasome; Nuclear hormone receptor; Transcription; Chromatin ID RNA-POLYMERASE-II; CHROMATIN-REMODELING COMPLEX; BREAST-CANCER CELLS; GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; DEPENDENT TRANSCRIPTION; ANDROGEN RECEPTOR; TARGET GENES; IN-VIVO; MOLECULAR CHAPERONES AB The mechanisms by which nuclear hormone receptors (NHRs) regulate transcription are highly dynamic and require interplay between a myriad of regulatory protein complexes including the 26S proteasome. Protein degradation is the most well-established role of the proteasome; however, an increasing body of evidence suggests that the 26S proteasome may regulate transcription in proteolytic and nonproteolytic mechanisms. Here we review how these mechanisms may apply to NHR-mediated transcriptional regulation. This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough! Published by Elsevier B.V. C1 [Keppler, Brian R.; Archer, Trevor K.; Kinyamu, H. Karimi] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kinyamu, HK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Kinyamu@niehs.nih.gov OI Keppler, Bernhard/0000-0003-0877-1822 FU National Institute of Environmental Health Sciences, NIH [Z01 ES071006-10] FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH (project no. Z01 ES071006-10, to T.A.). We thank Drs. Heather King, Paul Wade, and Sergei Nechaev for critically reviewing the manuscript. NR 106 TC 8 Z9 8 U1 0 U2 4 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 FEB PY 2011 VL 1809 IS 2 SI SI BP 109 EP 118 DI 10.1016/j.bbagrm.2010.08.005 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 722LR UT WOS:000287434200006 PM 20728592 ER PT J AU Kim, HW Rao, JS Rapoport, SI Igarashi, M AF Kim, Hyung-Wook Rao, Jagadeesh S. Rapoport, Stanley I. Igarashi, Miki TI Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE Arachidonic; Brain; PUFA; Phospholipase; Lipoxygenase; SREBP ID POLYUNSATURATED FATTY-ACIDS; INDEPENDENT PHOSPHOLIPASE A(2); DESATURASE MESSENGER-RNA; AIN-93 PURIFIED DIETS; GROUP-SPECIFIC ASSAYS; ALPHA-LINOLENIC ACID; GENE-EXPRESSION; FRONTAL-CORTEX; CANCER CELLS; INHIBITORS AB Background: Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase A(2) (cPLA(2)) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent iPLA(2) VIA. Assuming that these enzyme changes represent brain homeostatic responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would produce changes in the opposite directions. Methods: Brain expression of PUFA-metabolizing enzymes and their transcription factors was quantified in male rats fed an n-6 PUFA adequate or deficient diet for 15 weeks post-weaning. Results: The deficient compared with adequate diet increased brain mRNA, protein and activity of iPLA(2) VIA and 15-lipoxygenase (LOX), but decreased cPLA(2) IVA and COX-2 expression. The brain protein level of the iPLA(2) transcription factor SREBP-1 was elevated, while protein levels were decreased for AP-2 alpha and NF-kappa B p65, cPLA(2) and COX-2 transcription factors, respectively. Conclusions: With dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of their transcription factors change in a way that would homeostatically dampen reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA metabolizing enzyme expression is increased. The changes correspond to reported in vitro enzyme selectivities for AA compared with DHA. Published by Elsevier B.V. C1 [Kim, Hyung-Wook; Rao, Jagadeesh S.; Rapoport, Stanley I.; Igarashi, Miki] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Kim, HW (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM kimhyung@mail.nih.gov FU National Institute on Aging, NIH FX This research was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. The authors thank the NIH Fellows' Editorial Board and Dr. Eugene Streicher for editorial assistance. NR 54 TC 20 Z9 21 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD FEB PY 2011 VL 1811 IS 2 BP 111 EP 117 DI 10.1016/j.bbalip.2010.10.005 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 716UH UT WOS:000286998500007 PM 21070866 ER PT J AU Lee, S Choi, KY Chung, H Ryu, JH Lee, A Koo, H Youn, IC Park, JH Kim, IS Kim, SY Chen, X Jeong, SY Kwon, IC Kim, K Choi, K AF Lee, Seulki Choi, Ki Young Chung, Hyunjin Ryu, Ju Hee Lee, Aeju Koo, Heebeom Youn, In-Chan Park, Jae Hyung Kim, In-San Kim, Sang Yoon Chen, Xiaoyuan Jeong, Seo Young Kwon, Ick Chan Kim, Kwangmeyung Choi, Kuiwon TI Real Time, High Resolution Video Imaging of Apoptosis in Single Cells with a Polymeric Nanoprobe SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PROBES AB We report a new apoptosis nanoprobe (Apo-NP) designed on the basis of a polymer nanoparticle platform. This simple one-step technique is capable of boosting fluorescence signals upon apoptosis in living cells, enabling real-time imaging of apoptosis in single cells and in vivo. The Apo-NP efficiently delivers chemically labeled, dual-quenched caspase-3-sensitive fluorogenic peptides into cells, allowing caspase-3-dependent strong fluorescence amplification to be imaged in apoptotic cells in real-time and at high resolution. The design platform of the Apo-NP is flexible and can be fine-tuned for a wide array of applications such as identification of caspase-related apoptosis in pathologies and for monitoring therapeutic efficacy of apoptotic drugs in cancer treatment. C1 [Lee, Seulki; Choi, Ki Young; Chung, Hyunjin; Ryu, Ju Hee; Lee, Aeju; Koo, Heebeom; Youn, In-Chan; Kwon, Ick Chan; Kim, Kwangmeyung; Choi, Kuiwon] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul 136791, South Korea. [Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Choi, Ki Young; Park, Jae Hyung] Kyung Hee Univ, Coll Engn, Dept Chem Engn, Gyeonggi Do 449701, South Korea. [Choi, Ki Young; Lee, Aeju; Park, Jae Hyung; Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea. [Kim, In-San] Kyungpook Natl Univ, Daeggu 700422, South Korea. [Kim, Sang Yoon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol, Seoul 138736, South Korea. RP Kim, K (reprint author), Korea Inst Sci & Technol, Biomed Res Ctr, 39-1 Haweolgog Dong, Seoul 136791, South Korea. EM kim@kist.re.kr; choi@kist.re.kr RI byun, jaehyun/G-5584-2014; 김, 인산/I-8988-2014; CHOI, KI YOUNG/Q-7177-2016; Kim, In-San/D-3956-2017 FU MEST; KIST, Theragnosis; Korea Health 21 RD Project [A062254]; NIH/NIST NRC FX This work was financially supported by the Real-Time Molecular Imaging Project and Global Research Laboratory Project of MEST and by a grant to the Intramural Research Program of the KIST, Theragnosis, and by a grant (A062254) of the Korea Health 21 R&D Project. S.L. was partially funded by the NIH/NIST NRC fellowship. NR 18 TC 26 Z9 27 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD FEB PY 2011 VL 22 IS 2 BP 125 EP 131 DI 10.1021/bc1004119 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 720RE UT WOS:000287297000003 PM 21218786 ER PT J AU Doughty, E Kertesz-Farkas, A Bodenreider, O Thompson, G Adadey, A Peterson, T Kann, MG AF Doughty, Emily Kertesz-Farkas, Attila Bodenreider, Olivier Thompson, Gary Adadey, Asa Peterson, Thomas Kann, Maricel G. TI Toward an automatic method for extracting cancer- and other disease-related point mutations from the biomedical literature SO BIOINFORMATICS LA English DT Article ID PROSTATE-CANCER; GROWTH-FACTOR; GENE; SYSTEM; VALIDATION; DATABASE; TEXT AB Motivation: A major goal of biomedical research in personalized medicine is to find relationships between mutations and their corresponding disease phenotypes. However, most of the disease-related mutational data are currently buried in the biomedical literature in textual form and lack the necessary structure to allow easy retrieval and visualization. We introduce a high-throughput computational method for the identification of relevant disease mutations in PubMed abstracts applied to prostate (PCa) and breast cancer (BCa) mutations. Results: We developed the extractor of mutations (EMU) tool to identify mutations and their associated genes. We benchmarked EMU against MutationFinder-a tool to extract point mutations from text. Our results show that both methods achieve comparable performance on two manually curated datasets. We also benchmarked EMU's performance for extracting the complete mutational information and phenotype. Remarkably, we show that one of the steps in our approach, a filter based on sequence analysis, increases the precision for that task from 0.34 to 0.59 (PCa) and from 0.39 to 0.61 (BCa). We also show that this high-throughput approach can be extended to other diseases. Discussion: Our method improves the current status of disease-mutation databases by significantly increasing the number of annotated mutations. We found 51 and 128 mutations manually verified to be related to PCa and Bca, respectively, that are not currently annotated for these cancer types in the OMIM or Swiss-Prot databases. EMU's retrieval performance represents a 2-fold improvement in the number of annotated mutations for PCa and BCa. We further show that our method can benefit from full-text analysis once there is an increase in Open Access availability of full-text articles. C1 [Doughty, Emily; Kertesz-Farkas, Attila; Thompson, Gary; Adadey, Asa; Peterson, Thomas; Kann, Maricel G.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Kertesz-Farkas, Attila] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Bodenreider, Olivier] Natl Lib Med, Bethesda, MD 20894 USA. RP Kann, MG (reprint author), Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. EM mkann@umbc.edu RI Kann, Maricel/E-5701-2012 FU National Institutes of Health (NIH) [1K22CA143148, R01LM009722]; Centre for Devices and Radiological Health; US Food and Drug Administration; NIH, National Library of Medicine FX This work was supported by the National Institutes of Health (NIH) [1K22CA143148, MGK (PI) and R01LM009722, MGK (collaborator)]. A. K. F. acknowledges funding from the Research Fellowship Program of the Centre for Devices and Radiological Health, administrated by the Oak Ridge Associated Universities through a contact with the US Food and Drug Administration. Additional funding (OB) was provided by the Intramural Research Program of the NIH, National Library of Medicine. NR 32 TC 26 Z9 26 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD FEB 1 PY 2011 VL 27 IS 3 BP 408 EP 415 DI 10.1093/bioinformatics/btq667 PG 8 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 716RN UT WOS:000286991300016 PM 21138947 ER PT J AU Garces-Ramirez, L Green, JL Hiranita, T Kopajtic, TA Mereu, M Thomas, AM Mesangeau, C Narayanan, S McCurdy, CR Katz, JL Tanda, G AF Garces-Ramirez, Linda Green, Jennifer L. Hiranita, Takato Kopajtic, Theresa A. Mereu, Maddalena Thomas, Alexandra M. Mesangeau, Christophe Narayanan, Sanju McCurdy, Christopher R. Katz, Jonathan L. Tanda, Gianluigi TI Sigma Receptor Agonists: Receptor Binding and Effects on Mesolimbic Dopamine Neurotransmission Assessed by Microdialysis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Abuse liability; addiction; cocaine; dopamine microdialysis; nucleus accumbens; reinforcing effects; sigma receptors ID CENTRAL-NERVOUS-SYSTEM; NUCLEUS-ACCUMBENS; IN-VIVO; EXTRACELLULAR CONCENTRATION; COCAINE BINDING; GUINEA-PIG; LIGANDS; RAT; DRUGS; TRANSMISSION AB Background: Subtypes of sigma (sigma) receptors, sigma(1) and sigma(2), can be pharmacologically distinguished, and each may be involved in substance-abuse disorders. sigma-Receptor antagonists block cocaine place conditioning and sigma-receptor agonists are self-administered in rats that previously self-administered cocaine. Self-administration of abused drugs has been related to increased dopamine (DA) neurotransmission, however, sigma-receptor agonist effects on mesolimbic DA are not fully characterized. Methods: Receptor-binding studies assessed affinities of sigma-receptor ligands for sigma-receptor subtypes and the DA transporter; effects on DA transmission in the rat nucleus accumbens shell were assessed using in vivo microdialysis. Results: Cocaine (.1-1.0 mg/kg intravenous [IV]), the nonselective sigma(1/2)-receptor agonist DTG (1.0-5.6 mg/kg IV), and the selective sigma(1)-receptor agonist PRE-084 (.32-10 mg/kg IV) dose-dependently increased DA to similar to 275%, similar to 150%, and similar to 160% maxima, respectively. DTG-induced stimulation of DA was antagonized by the nonselective sigma(1/2)-receptor antagonist BD 1008 (10 mg/kg intraperitoneal [IP]) and the preferential sigma(2)-receptor antagonist SN 79 (1-3 mg/kg IP), but not by the preferential sigma(1)-receptor antagonist, BD 1063 (10-30 mg/kg IP). Neither PRE-084 nor cocaine was antagonized by BD 1063 or BD 1008. Conclusions: sigma-Receptor agonists stimulated DA in a brain area critical for reinforcing effects of cocaine. DTG effects on DA appear to be mediated by sigma(2)-receptors rather than sigma(1)-receptors. However, DA stimulation by cocaine or PRE-084 does not likely involve sigma-receptors. The relatively low potency on DA transmission of the selective sigma(1)-receptor agonist, PRE-084, and its previously reported potent reinforcing effects, suggest a dopamine-independent reinforcing pathway that may contribute to substance-abuse disorders. C1 [Garces-Ramirez, Linda; Green, Jennifer L.; Hiranita, Takato; Kopajtic, Theresa A.; Mereu, Maddalena; Thomas, Alexandra M.; Katz, Jonathan L.; Tanda, Gianluigi] NIDA, NIH, Dept Hlth & Human Serv, Intramural Res Program,Psychobiol Sect,Medicat Di, Baltimore, MD 21224 USA. [Hiranita, Takato] NIH, Japan Soc Promot Sci, Baltimore, MD USA. [Garces-Ramirez, Linda] Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico. [Mesangeau, Christophe; Narayanan, Sanju; McCurdy, Christopher R.] Univ Mississippi, Dept Med Chem, Oxford, MS USA. RP Tanda, G (reprint author), NIDA, NIH, Dept Hlth & Human Serv, Intramural Res Program,Psychobiol Sect,Medicat Di, Bldg C,Room 321,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Hiranita, Takato/G-6567-2011; OI Tanda, Gianluigi/0000-0001-9526-9878; Katz, Jonathan/0000-0002-1068-1159 FU National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services; NIDA [DA023205 [CRM]]; Consejo Nacional de Ciencia y Tecnologia, Mexico FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health, Department of Health and Human Services, and in part by NIDA Grant (DA023205 [CRM]). LG-R was recipient of a scholarship from Consejo Nacional de Ciencia y Tecnologia, Mexico. NR 51 TC 27 Z9 28 U1 1 U2 5 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 FEB 1 PY 2011 VL 69 IS 3 BP 208 EP 217 DI 10.1016/j.biopsych.2010.07.026 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 708PZ UT WOS:000286377600004 PM 20950794 ER PT J AU Pantin, JM Tian, X Keyvanfar, K Zerfas, P Eckhaus, M Childs, RW AF Pantin, J. M. Tian, X. Keyvanfar, K. Zerfas, P. Eckhaus, M. Childs, R. W. TI SUPERIOR ENGRAFTMENT AND SURVIVAL AND LESS GVHD IN NOD-SCID IL2RG(NULL) (NSG) MICE RECEIVING INTRABONE COMPARED WITH IV TRANSPLANTS OF HUMAN T-CELL REPLETE G-CSF MOBILIZED PERIPHERAL BLOOD STEM CELLS SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem CY FEB 17-21, 2011 CL Honolulu, HI SP Amer Soc Blood & Marrow Transplant, Ctr Int Blood & Marrow Transplant Res Tandem C1 [Pantin, J. M.; Tian, X.; Keyvanfar, K.; Childs, R. W.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2011 VL 17 IS 2 SU 2 MA 41 BP S166 EP S167 DI 10.1016/j.bbmt.2010.12.047 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 721JX UT WOS:000287350500042 ER PT J AU Chatterjee, K Sun, LM Chow, LC Young, MF Simon, CG AF Chatterjee, Kaushik Sun, Limin Chow, Laurence C. Young, Marian F. Simon, Carl G., Jr. TI Combinatorial screening of osteoblast response to 3D calcium phosphate/poly(is an element of-caprolactone) scaffolds using gradients and arrays SO BIOMATERIALS LA English DT Article DE 3D scaffolds; Calcium phosphate; Combinatorial screening; Nanoparticles; Osteoblast; Tissue engineering ID STEM-CELLS; BONE REGENERATION; PHOSPHATE; DIFFERENTIATION; BIOMATERIALS; BIOCERAMICS; INTERFACES; COMPOSITE; CULTURE; MODEL AB There is a need for combinatorial and high-throughput methods for screening cell-biomaterial interactions to maximize tissue generation in scaffolds. Current methods employ a flat two-dimensional (2D) format even though three-dimensional (3D) scaffolds are more representative of the tissue environment in vivo and cells are responsive to topographical differences of 2D substrates and 3D scaffolds. Thus, combinatorial libraries of 3D porous scaffolds were developed and used to screen the effect of nano-amorphous calcium phosphate (nACP) particles on osteoblast response. Increasing nACP content in poly (is an element of-caprolactone) (PCL) scaffolds promoted osteoblast adhesion and proliferation. The nACP-containing scaffolds released calcium and phosphate ions which are known to activate osteoblast function. Scaffold libraries were fabricated in two formats, gradients and arrays, and the magnitude of the effect of nACP on osteoblast proliferation was greater for arrays than gradients. The enhanced response in arrays can be explained by differences in cell culture designs, diffusional effects and differences in the ratio of "scaffold mass to culture medium". These results introduce a gradient library approach for screening large pore 3D scaffolds and demonstrate that inclusion of the nACP particles enhances osteoblast proliferation in 3D scaffolds. Further, comparison of gradients and arrays suggests that gradients were more sensitive for detecting effects of scaffold composition on cell adhesion (short time points, 1 day) whereas arrays were more sensitive at detecting effects on cell proliferation (longer time points, 14 day). Published by Elsevier Ltd. C1 [Chatterjee, Kaushik; Simon, Carl G., Jr.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. [Chatterjee, Kaushik; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Sun, Limin; Chow, Laurence C.] Natl Inst Stand & Technol, Amer Dent Assoc Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. RP Simon, CG (reprint author), Natl Inst Stand & Technol, Div Polymers, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM carl.simon@nist.gov RI Sanders, Susan/G-1957-2011 FU National Research Council of the National Academy of Sciences in the Joint NIH-NIBIB/NIST; NIST; NIH-NIDCR (National Institute of Dental and Craniofacial Research) [NIH-NIBIB R21 EB006497-01, NIH-NIDCR R01DE16416] FX K.C. acknowledges support from a Research Associateship Award from the National Research Council of the National Academy of Sciences in the Joint NIH-NIBIB/NIST Postdoctoral Program (National Institutes of Health-National Institute of Biomedical Imaging and Bioengineering/National Institute of Standards and Technology). This work was supported by NIST, the Intramural Program of the NIH-NIDCR (National Institute of Dental and Craniofacial Research), NIH-NIBIB R21 EB006497-01 and NIH-NIDCR R01DE16416. The standard deviation (S.D.) is the same as the "combined standard uncertainty of the mean" for the purposes of this work. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH, NIBIB, NIDCR, NIST or ADA (American Dental Association). This article, a contribution of NIST and NIH, is not subject to US copyright. Certain equipment and instruments or materials are identified in the paper to adequately specify the experimental details. Such identification does not imply recommendation by NIST, nor does it imply the materials are necessarily the best available for the purpose. NR 40 TC 25 Z9 25 U1 1 U2 33 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2011 VL 32 IS 5 BP 1361 EP 1369 DI 10.1016/j.biomaterials.2010.10.043 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 717UN UT WOS:000287073000012 PM 21074846 ER PT J AU Sawyer, RT Maier, LA AF Sawyer, Richard T. Maier, Lisa A. TI Chronic beryllium disease: an updated model interaction between innate and acquired immunity SO BIOMETALS LA English DT Article DE Beryllium; Chronic beryllium disease; Granuloma; Innate immunity; Acquired immunity ID CD4(+) T-CELLS; MHC-CLASS-II; PERIPHERAL-BLOOD MONONUCLEAR; ANTIGEN-PRESENTING CELLS; HUMAN-LEUKOCYTE ANTIGEN; NECROSIS-FACTOR-ALPHA; HLA-DP; TNF-ALPHA; DENDRITIC CELLS; LYMPHOCYTE-PROLIFERATION AB During the last decade, there have been concerted efforts to reduce beryllium (Be) exposure in the workplace and thereby reduce potential cases of this occupational lung disorder. Despite these efforts, it is estimated that there are at least one million Be-exposed individuals in the U.S. who are potentially at risk for developing chronic beryllium disease (CBD). Previously, we reviewed the current CBD literature and proposed that CBD represents a model interaction between innate and acquired immunity (Sawyer et al., Int Immunopharmacol 2:249-261, 2002). We closed this review with a section on "future directions" that identified key gaps in our understanding of the pathogenesis of CBD. In the intervening period, progress has been made to fill in some of these gaps, and the current review will provide an update on that progress. Based on recent findings, we provide a new hypothesis to explain how Be drives sustained chronic inflammation and granuloma formation in CBD leading to progressive compromised lung function in CBD patients. This paradigm has direct implications for our understanding of the development of an immune response to Be, but is also likely applicable to other immune-mediated lung diseases of known and unknown etiology. C1 [Maier, Lisa A.] Natl Jewish Hlth, Robert H Hollis Lab Environm & Occupat Hlth Sci, Div Environm & Occupat Hlth Sci, Dept Med, Denver, CO USA. [Sawyer, Richard T.] NIAID, Asthma Allergy & Inflammat Branch, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Maier, Lisa A.] Univ Colorado, Sch Med, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Maier, Lisa A.] Univ Colorado, Dept Environm & Occupat Hlth, Colorado Sch Publ Hlth, Denver, CO USA. RP Maier, LA (reprint author), Natl Jewish Hlth, Robert H Hollis Lab Environm & Occupat Hlth Sci, Div Environm & Occupat Hlth Sci, Dept Med, Denver, CO USA. EM maierl@njc.org FU NIEHS NIH HHS [P01 ES011810-06A1, P01 ES011810] NR 120 TC 9 Z9 10 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD FEB PY 2011 VL 24 IS 1 BP 1 EP 17 DI 10.1007/s10534-010-9376-3 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 707WW UT WOS:000286322800001 PM 20981472 ER PT J AU Jugessur, A Shi, M Gjessing, HK Lie, RT Wilcox, AJ Weinberg, CR Christensen, K Boyles, AL Daack-Hirsch, S Nguyen, TT Christiansen, L Lidral, AC Murray, JC AF Jugessur, Astanand Shi, Min Gjessing, Hakon Kristian Lie, Rolv Terje Wilcox, Allen James Weinberg, Clarice Ring Christensen, Kaare Boyles, Abee Lowman Daack-Hirsch, Sandra Nguyen, Truc Trung Christiansen, Lene Lidral, Andrew Carl Murray, Jeffrey Clark TI Fetal Genetic Risk of Isolated Cleft Lip Only versus Isolated Cleft Lip and Palate: A Subphenotype Analysis using Two Population-Based Studies of Orofacial Clefts in Scandinavia SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE birth defects; orofacial cleft; cleft lip; cleft palate; genetic epidemiology ID CASE-PARENT TRIADS; ORAL CLEFTS; CRANIOFACIAL DEVELOPMENT; CANDIDATE GENES; FACIAL CLEFTS; AND/OR PALATE; FLIP-FLOP; PHENOTYPE; ASSOCIATION; MUTATIONS AB BACKGROUND: Cleft lip only (CLO) and cleft lip and palate (CLP) are commonly regarded as variants of the same defect and are traditionally combined to form the single group of cleft lip with or without cleft palate (CL/P) prior to analysis. However, recent data have suggested that at least a subgroup of isolated CLO may be etiologically distinct from isolated CLP. METHODS: To explore fetal genetic risk of isolated CLO separately from isolated CLP, we performed a subphenotype analysis using two population-based studies of clefts in Scandinavia. One hundred twenty-one isolated CLO, 190 isolated CLP, and 592 control triads were available from Norway (1996-2001), and a further 76 isolated CLO and 107 isolated CLP triads were available from Denmark (19912001). Genotypes for 1315 SNPs in 334 autosomal cleft candidate genes were analyzed using two complementary statistical methods, Triad Multi-Marker (TRIMM; Shi et al., 2007)) and HAPLIN (Gjessing and Lie, 2006), to look for genetic associations across the two national samples. RESULTS: Both TRIMM and HAPLIN identified strong associations between FGF12 and isolated CLO in both populations. In addition, only TRIMM identified associations with IRF6 and VCL, and only HAPLIN found an association with CX43. When analyses were repeated on the larger sample of isolated CLP, no significant associations were found with FGF12, IRF6, VCL, or CX43. CONCLUSIONS: Despite some inconsistency in the pattern of associations across the two populations, the associations themselves were phenotype-specific. While both IRF6 and FGF12 have previously shown strong associations with isolated CL/P, the associations with VCL and CX43 are novel and warrant further investigation in other isolated CLO samples. Birth Defects Research (Part A) 91:85-92, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Jugessur, Astanand; Gjessing, Hakon Kristian] Norwegian Inst Publ Hlth, Div Epidemiol, N-0403 Oslo, Norway. [Jugessur, Astanand] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Shi, Min; Weinberg, Clarice Ring] NIEHS, Biostat Branch, Durham, NC USA. [Gjessing, Hakon Kristian; Lie, Rolv Terje] Univ Bergen, Fac Med & Dent, Dept Publ Hlth & Primary Hlth Care, N-5018 Bergen, Norway. [Lie, Rolv Terje; Nguyen, Truc Trung] Norwegian Inst Publ Hlth, Med Birth Registry Norway, N-5018 Bergen, Norway. [Wilcox, Allen James; Boyles, Abee Lowman] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Christensen, Kaare; Christiansen, Lene; Murray, Jeffrey Clark] Univ So Denmark, Dept Epidemiol, DK-5000 Odense, Denmark. [Christensen, Kaare] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, DK-5000 Odense, Denmark. [Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Daack-Hirsch, Sandra] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Lidral, Andrew Carl; Murray, Jeffrey Clark] Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. RP Jugessur, A (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway. EM astanand.jugessur@fhi.no RI Christensen, Kaare/C-2360-2009; Gjessing, Hakon/A-5871-2012; OI Christensen, Kaare/0000-0002-5429-5292; Boyles, Abee/0000-0002-8711-2077; Wilcox, Allen/0000-0002-3376-1311 FU U.S. National Institute of Environmental Health Sciences (NIEHS); U.S. National Institutes of Health (NIH) [P60 DE13076, DE08559, DE11948, P30 ES05605, RO1 DE-11948-04]; Norwegian Research Council [NFR 177522]; National Institutes of Health (NIH) [N01-HG-65403] FX Supported by a grant from: This research was supported in part by the Intramural Research Program of the U.S. National Institute of Environmental Health Sciences (NIEHS); by U.S. National Institutes of Health (NIH) grants DE08559, P60 DE13076, DE08559, DE11948, P30 ES05605, and RO1 DE-11948-04; and by the Norwegian Research Council (NFR 177522).; We thank all participating families who made this study possible. Special thanks go to the following individuals for their input in candidate gene selection and sample preparation: Kathy Frees, Ecaterina Dragan, Adela Mansilla, Bridget Riley, Dorthe Grosen, Brian Schutte, Edward Lammer, Temis Felix, Michael Lovett, Satoshi Suzuki, Andrew Olshan, Rulang Jiang, Diana Caprau, Richard Finnell, Christine Jewell, John Cidlowski, Fedik Rahimov, Jack Taylor, and Alexandre Vieira. We are particularly grateful to Susie McConnell and Jacqueline Leung-Heras for outstanding secretarial support. Genotyping services were provided by the Center for Inherited Disease Research (CIDR), which is funded through a federal contract from the National Institutes of Health (NIH) to the Johns Hopkins University (grant N01-HG-65403). We thank Ivy McMullen, Corinne Boehm, Kim Doheny, and other CIDR staff involved in this project. We also thank the U.S. National Institute of Dental and Craniofacial Research (NIDCR) for underwriting a significant proportion of the genotyping costs by CIDR. NR 59 TC 15 Z9 17 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD FEB PY 2011 VL 91 IS 2 BP 85 EP 92 DI 10.1002/bdra.20747 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 730LU UT WOS:000288035600003 PM 21319277 ER PT J AU Sanford, TH Storey, BB Linehan, WM Rogers, CA Pinto, PA Bratslavsky, G AF Sanford, Thomas H. Storey, Benjamin Barckley Linehan, William Marston Rogers, Craig A. Pinto, Peter A. Bratslavsky, Gennady TI Outcomes and timing for intervention of partial adrenalectomy in patients with a solitary adrenal remnant and history of bilateral phaeochromocytomas SO BJU INTERNATIONAL LA English DT Article DE adrenal-sparing surgery; complications; partial adrenalectomy; treatment outcome ID ENDOCRINE NEOPLASIA TYPE-2; HEREDITARY PHEOCHROMOCYTOMA; SURGICAL-MANAGEMENT; SPARING SURGERY; EXPERIENCE; TUMORS AB What's known on the subject? and What does the study add? At the present time, outcomes of the patients treated with partial adrenalectomy on a solitary adrenal are described in less than 100 patients in the world literature. In patients with bilateral pheochromocytomas, the timing for intervention as well as size threshold to allow for steroid independence is not known. This manuscript provides evidence that staged adrenal surgery as well as operating on the solitary adrenal before the largest tumour reaches 4 cm may allow for best functional outcomes and steroid independence. OBJECTIVE To evaluate the outcomes and timing of intervention for adrenal-sparing surgery in patients left with a solitary adrenal remnant after bilateral adrenal surgeries. PATIENTS AND METHODS Patients were included in the study if they had undergone bilateral adrenal surgery as a treatment for phaeochromocytoma and were left with a solitary adrenal remnant. Perioperative, functional and oncological outcomes were evaluated in 21 patients who met the inclusion criteria. RESULTS There was minimal perioperative morbidity and no perioperative mortality. After a median (range) follow-up of 21 (3-143) months, there were two cases of persistent disease. Ten patients (48%) required steroid supplementation upon discharge, with four subsequently discontinuing this treatment. Patients were more likely to require steroid supplementation after surgery if they underwent simultaneous adrenalectomy and contralateral partial adrenalectomy, rather than staged procedures (86 vs 40%, P = 0.02). Patients who underwent surgery for tumours > 4 cm were more likely to require long-term steroids than patients who underwent surgery for lesions < 4 cm (75 vs 18%, P = 0.05). CONCLUSIONS Patients left with a solitary adrenal remnant after bilateral adrenal surgery have low surgical morbidity, reasonable functional outcomes and low rates of recurrence at an intermediate follow-up period. A staged approach could decrease the immediate postoperative need for steroids, and intervention before the largest tumour reaches 4 cm could decrease the rate of long-term steroid dependence. C1 [Sanford, Thomas H.; Storey, Benjamin Barckley; Linehan, William Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Rogers, Craig A.] Henry Ford Hosp, Dept Urol, Detroit, MI 48202 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX None declared. Source of Funding: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 8 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2011 VL 107 IS 4 BP 571 EP 575 DI 10.1111/j.1464-410X.2010.09568.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 713WE UT WOS:000286767300009 PM 20726977 ER PT J AU Tanno, T Rabel, A Alleyne, M Lee, YT Dahut, WL Gulley, JL Miller, JL AF Tanno, Toshihiko Rabel, Antoinette Alleyne, Michael Lee, Y. Terry Dahut, William L. Gulley, James L. Miller, Jeffery L. TI HEPCIDIN, ANAEMIA, AND PROSTATE CANCER SO BJU INTERNATIONAL LA English DT Letter ID GENE-EXPRESSION C1 [Tanno, Toshihiko; Rabel, Antoinette; Alleyne, Michael; Lee, Y. Terry; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Alleyne, Michael; Dahut, William L.; Gulley, James L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Gulley, James L.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tanno, T (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [ZIA DK025100-04] NR 7 TC 11 Z9 12 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2011 VL 107 IS 4 BP 678 EP 679 DI 10.1111/j.1464-410X.2011.10108.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 713WE UT WOS:000286767300024 PM 21276178 ER PT J AU Valenti, RM Amodio, E Nam, JM Preiss, L Graubard, BI Romano, N Goedert, JJ AF Valenti, R. M. Amodio, E. Nam, J-M Preiss, L. Graubard, B. I. Romano, N. Goedert, J. J. TI Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls SO BRITISH JOURNAL OF CANCER LA English DT Article DE delayed-type hypersensitivity; Kaposi sarcoma; herpesviruses; human immunodeficiency virus (HIV); transplantation; Italy ID RISK-FACTORS; HERPESVIRUS; PROGRESSION; RESPONSES AB BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (-2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy. British Journal of Cancer (2011) 104, 433-436. doi:10.1038/sj.bjc.6606088 www.bjcancer.com Published online 18 January 2011 (C) 2011 Cancer Research UK C1 [Nam, J-M; Graubard, B. I.; Goedert, J. J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Valenti, R. M.; Amodio, E.; Romano, N.] Univ Palermo, Sect Hyg, Dept Sci Hlth Promot G DAlessandro, I-90127 Palermo, Italy. [Preiss, L.] RTI Int, Rockville, MD 20852 USA. RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU National Cancer Institute, NIH FX This work was supported in part by the Intramural Research Program of the National Cancer Institute, NIH. We thank Enza Viviano, MD, for performing the DTH; Charles Rabkin, MD, and Eric Engels, MD, for comments on the paper; James M Schmitt, MD, Division of Occupational Safety and Health, National Institutes of Health, for the ball-point pen measurement method and for helping with pilot assessment of DTH in the leg; and the study participants. NR 20 TC 3 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 1 PY 2011 VL 104 IS 3 BP 433 EP 436 DI 10.1038/sj.bjc.6606088 PG 4 WC Oncology SC Oncology GA 722IY UT WOS:000287427100009 PM 21245864 ER PT J AU Lew, JQ Chow, WH Hollenbeck, AR Schatzkin, A Park, Y AF Lew, J. Q. Chow, W-H Hollenbeck, A. R. Schatzkin, A. Park, Y. TI Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study SO BRITISH JOURNAL OF CANCER LA English DT Article DE alcohol; renal cell cancer; cohort ID KIDNEY CANCER; CARCINOMA; WOMEN; DRINKING; COHORT; BEVERAGES; GENDER AB BACKGROUND: The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear. METHOD The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n = 49 2187, 1814 cases). RESULTS: Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <3C and >= 30g per day was, 0.75 (0.63-0.90) and 0.71 (0.59-0.85), respectively, in men and 0.67 (0.42-1.07) and 0.43 (0.22-0.84), respectively, in women. CONCLUSION: Alcohol consumption was inversely associated with RCC in a dose-response manner. The inverse association may be extended to >= 30 g per day of alcohol intake. British Journal of Cancer (2011) 104, 537-541. doi:10.1038/sj.bjc.6606089 www.bjcancer.com Published online 18 January 2011 (C) 2011 Cancer Research UK C1 [Lew, J. Q.; Chow, W-H; Schatzkin, A.; Park, Y.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lew, J. Q.] Washington Univ, St Louis Childrens Hosp, Med Ctr, St Louis, MO 63110 USA. [Hollenbeck, A. R.] AARP, Washington, DC USA. RP Park, Y (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM parkyik@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X FU Florida Department of Health (FDOH) FX Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis. NR 21 TC 13 Z9 13 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB 1 PY 2011 VL 104 IS 3 BP 537 EP 541 DI 10.1038/sj.bjc.6606089 PG 5 WC Oncology SC Oncology GA 722IY UT WOS:000287427100024 PM 21245859 ER PT J AU Hartge, P AF Hartge, Patricia TI Reducing Ovarian Cancer Death Rates Through Screening SO CANCER LA English DT Editorial Material C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8090, Rockville, MD 20852 USA. EM hartgep@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2011 VL 117 IS 3 BP 449 EP 450 DI 10.1002/cncr.25622 PG 2 WC Oncology SC Oncology GA 709JC UT WOS:000286433300007 PM 21254048 ER PT J AU Li, DH Tang, HW Hassan, MM Holly, EA Bracci, PM Silverman, DT AF Li, Donghui Tang, Hongwei Hassan, Manal M. Holly, Elizabeth A. Bracci, Paige M. Silverman, Debra T. TI Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies SO CANCER CAUSES & CONTROL LA English DT Article DE Diabetes; Pancreatic cancer; Case-control study; Epidemiology ID FRANCISCO-BAY AREA; DIRECT INTERVIEWS; CIGARETTE-SMOKING; MELLITUS; ASSOCIATION; MORTALITY; GLUCOSE; METAANALYSIS; HISTORY; WOMEN AB Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case-control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5-2.1]. Risk estimates decreased with increasing years with diabetes (a parts per thousand currency sign2 years OR = 2.9, 95% CI = 2.1-3.9; 3-5 years OR = 1.9, 95% CI = 1.3-2.6; 6-10 years OR = 1.6, 95% CI = 1.2-2.3; 11-15 years OR = 1.3, 95% CI = 0.9-2.0; > 15 years OR = 1.4, 95% CI = 1.0-2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6-3.7) and was restricted to insulin use of a parts per thousand currency sign3 years (OR = 2.4). Insulin use of > 10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3-0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking. C1 [Li, Donghui; Tang, Hongwei; Hassan, Manal M.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Holly, Elizabeth A.; Bracci, Paige M.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Li, DH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Unit 426, Houston, TX 77030 USA. EM dLi@mdanderson.org FU National Institute of Health, NCI [CA59706, CA89726, CA108370, CA109767, CA98380]; Rombauer Pancreatic Cancer Research Fund (UCSF); Lockton Pancreatic Cancer Research Fund (MDACC); Division of Cancer Epidemiology and Genetics of the National Cancer institute FX Grant support is given by National Institute of Health, NCI grants CA59706, CA89726, CA108370, CA109767 (Holly E.A.: PI), CA98380 (Li D.: PI), The Rombauer Pancreatic Cancer Research Fund (UCSF) and The Lockton Pancreatic Cancer Research Fund (MDACC). The NCI study was supported by the intramural program of the Division of Cancer Epidemiology and Genetics of the National Cancer institute (Silverman D.T.: PI). NR 42 TC 59 Z9 66 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2011 VL 22 IS 2 BP 189 EP 197 DI 10.1007/s10552-010-9686-3 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 709TT UT WOS:000286465000004 PM 21104117 ER PT J AU Byun, W Sui, XM Hebert, JR Church, TS Lee, IM Matthews, CE Blair, SN AF Byun, Wonwoo Sui, Xuemei Hebert, James R. Church, Timothy S. Lee, I-Min Matthews, Charles E. Blair, Steven N. TI Cardiorespiratory fitness and risk of prostate cancer: Findings from the Aerobics Center Longitudinal Study SO CANCER EPIDEMIOLOGY LA English DT Article DE Cardiorespiratory fitness; Prostate cancer; Cohort studies; Attitude to health; Screening/detection bias ID RECREATIONAL PHYSICAL-ACTIVITY; ALL-CAUSE MORTALITY; UNITED-STATES; HYPERTENSION INCIDENCE; ASYMPTOMATIC WOMEN; BODY-MASS; FOLLOW-UP; MEN; EPIDEMIOLOGY; PREDICTOR AB Objective: To examine the association between cardiorespiratory fitness (CRF) and risk of incident prostate cancer (PrCA). Methods: Participants were 19,042 male subjects in the Aerobics Center Longitudinal Study (ACLS), ages 20-82 years, who received a baseline medical examination including a maximal treadmill exercise test between 1976 and 2003. CRF levels were defined as low (lowest 20%), moderate (middle 40%), and high (upper 40%) according to age-specific distribution of treadmill duration from the overall ACLS population. PrCA was assessed from responses to mail-back health surveys during 1982-2004. Cox proportional hazards regression models, adjusted for potential confounders, were used to compute hazard ratios (HRs), 95% confidence intervals (95% CIs), and incidence rates (per 10,000 person-years of follow-up). Results: A total of 634 men reported a diagnosis of incident PrCA during an average of 9.3 +/- 7.1 years of follow-up. Adjusted HRs (95% CIs) in men with moderate and high CRF relative to low CRF were, 1.68 (1.13-2.48) and 1.74 (1.15-2.62), respectively. The positive association between CRF and PrCA was observed only in the strata of men who were not obese, had >= 1 follow-up examination, or who were diagnosed <= 1995. Conclusions: Rather than revealing a causal relationship, the unexpected positive association observed between CRF and incident PrCA is most likely due to a screening/detection bias in more fit men who also are more health-conscious. Results have important implications for understanding the health-related factors that predispose men to receive PrCA screening that may lead to over-detection of indolent disease. Published by Elsevier Ltd. C1 [Byun, Wonwoo] Univ S Carolina, Publ Hlth Res Ctr, Arnold Sch Publ Hlth, Dept Exercise Sci, Columbia, SC 29208 USA. [Hebert, James R.; Blair, Steven N.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Hebert, James R.; Blair, Steven N.] Univ S Carolina, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Church, Timothy S.] Pennington Biomed Res Ctr, Prevent Med Lab, Baton Rouge, LA USA. [Lee, I-Min] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA. [Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA. RP Byun, W (reprint author), Univ S Carolina, Publ Hlth Res Ctr, Arnold Sch Publ Hlth, Dept Exercise Sci, 921 Assembly St, Columbia, SC 29208 USA. EM byun@email.sc.edu RI matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU National Institutes of Health [AG06945, HL62508, K05 CA136975, R21 DK088195]; Coca-Cola Company FX This study was supported by National Institutes of Health grants AG06945, HL62508, K05 CA136975 (to JR Hebert from the Cancer Training Branch of the National Cancer Institute), R21 DK088195 (to X Sui from the National Institute of Diabetes and Digestive and Kidney Diseases) and an unrestricted research fund from The Coca-Cola Company. We thank all the Cooper Clinic physicians and technicians for collecting the baseline data, and staff at the Cooper Institute for data entry and data management. NR 58 TC 9 Z9 10 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD FEB PY 2011 VL 35 IS 1 BP 59 EP 65 DI 10.1016/j.canep.2010.07.013 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736CL UT WOS:000288467500010 PM 20708996 ER PT J AU Weaver, KE Rowland, JH Augustson, E Atienza, AA AF Weaver, Kathryn E. Rowland, Julia H. Augustson, Erik Atienza, Audie A. TI Smoking Concordance in Lung and Colorectal Cancer Patient-Caregiver Dyads and Quality of Life SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEALTH BEHAVIORS; TOBACCO USE; SHORT-FORM; SURVIVORS; WOMEN; DEPENDENCE; CESSATION; RELATIVES; ADULTS AB Background: Distress may be heightened among members of cancer patient-caregiver dyads that are mismatched on smoking status (either the patient or caregiver smokes, but the other does not), negatively affecting quality of life (QoL). The purpose of this study was to examine associations between patient-caregiver smoking concordance, caregiver psychological adjustment, and caregiver and patient mental and physical QoL. Methods: Lung and colorectal patient-caregiver dyads (N = 742) were identified from the Cancer Care Outcomes Research and Surveillance (CanCORS) and CanCORS Caregiver studies. The majority of the cancer patients were male (67.0%) with local (45.6%) or regional (12.9%) disease. The majority of the informal caregivers were females (78.6%), under 65 years of age (69.6%), and often spouses (57.8%) of the patients. Results: Lung and colorectal cancer caregivers, who were members of dyads where one or both members continued to smoke, reported worse mental health QoL than nonsmoking dyads. For colorectal cancer patients, continuing to smoke when the caregiver did not was associated with worse mental health QoL compared with nonsmoking dyads. Dyad smoking was less strongly associated with physical QoL for both caregivers and patients. Conclusion: Results highlight the importance of assessing smoking in both cancer patients and their caregivers and referring families to appropriate psychosocial and smoking cessation services. Impact: This is the first study to show associations between cancer patient-caregiver smoking status and QoL for both dyad members. Future studies will need to confirm these associations longitudinally and investigate potential mechanisms linking dyad smoking and QoL. Cancer Epidemiol Biomarkers Prev; 20(2); 239 48. (C) 2010 AACR. C1 [Weaver, Kathryn E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Weaver, Kathryn E.; Rowland, Julia H.; Augustson, Erik; Atienza, Audie A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Weaver, Kathryn E.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Weaver, KE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM keweaver@wfubmc.edu FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093326]; Department of Veteran's Affairs [U01 CDA093344, HARQ 03-438MO-03] FX This work from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana Farber Cancer Institute/Cancer Research NetworkU01 CA093332, Harvard Medical School/Northern California Cancer CenterU01 CA093324, RAND/UCLA U01 CA093348, University of Alabama at BirminghamU01 CA093329, University of IowaU01 CA01013, University of North CarolinaU01 CA093326), and by a Department of Veteran's Affairs grant to the Durham VA Medical CenterU01 CDA093344 (MOU) and HARQ 03-438MO-03). NR 38 TC 15 Z9 15 U1 1 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 FEB PY 2011 VL 20 IS 2 BP 239 EP 248 DI 10.1158/1055-9965.EPI-10-0666 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 717CU UT WOS:000287021400005 PM 21177426 ER PT J AU Vergati, M Cereda, V Madan, RA Gulley, JL Huen, NY Rogers, CJ Hance, KW Arlen, PM Schlom, J Tsang, KY AF Vergati, Matteo Cereda, Vittore Madan, Ravi A. Gulley, James L. Huen, Ngar-Yee Rogers, Connie J. Hance, Kenneth W. Arlen, Philip M. Schlom, Jeffrey Tsang, Kwong Y. TI Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Cancer vaccine; Prostate cancer; Immunotherapy; Regulatory T cells; Vaccination ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANSCRIPTION FACTOR FOXP3; PERIPHERAL-BLOOD; TRYPTOPHAN CATABOLISM; SUPPRESSIVE FUNCTION; CARCINOMA PATIENTS; OVARIAN-CANCER; BREAST-CANCER; EXPRESSION; MELANOMA AB We have previously shown that the suppressive function of regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) is enhanced in patients with prostate cancer when compared with healthy individuals. Two phase II studies using the PSA-TRICOM vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC) showed evidence of patient benefit in terms of enhanced survival. The Halabi nomogram has been used to predict survival (HPS) of patients with mCRPC treated with conventional chemotherapy or second-line hormonal therapy. Tregs from PBMCs of patients (n = 23) with mCRPC were obtained pre- and post-three monthly vaccinations, and analyzed for number, phenotype, and suppressive function. Changes post- versus pre-vaccination in these parameters were compared with 3-year survival and HPS. No differences in Treg numbers were observed post- versus pre-vaccination. Trends (P = 0.029) were observed between overall survival (OS) and a decrease in Treg suppressive function post- versus pre-vaccination. Trends were also observed in analyzing effector:Treg (CD4(+)CD25(+)CD127(-)FoxP3(+)CTLA4(+)) ratio post- versus pre-vaccination with OS versus HPS. These data provide preliminary evidence for a possible association between improved OS and a decrease in Treg function when PBMCs are analyzed after three monthly vaccinations. Patients with an OS > HPS were more likely to have decreased Treg function following vaccine. Larger studies to confirm and extend these findings are warranted. C1 [Vergati, Matteo; Cereda, Vittore; Madan, Ravi A.; Gulley, James L.; Huen, Ngar-Yee; Rogers, Connie J.; Hance, Kenneth W.; Arlen, Philip M.; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Madan, Ravi A.; Gulley, James L.; Arlen, Philip M.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, 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 Intramural NIH HHS [Z01 BC010666-04, ZIA BC010973-03, Z01 BC010973-01] NR 58 TC 31 Z9 32 U1 0 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 FEB PY 2011 VL 60 IS 2 BP 197 EP 206 DI 10.1007/s00262-010-0927-9 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 709TD UT WOS:000286463400005 PM 20976449 ER PT J AU Limburg, PJ Mahoney, MR Ziegler, KLA Sontag, SJ Schoen, RE Benya, R Lawson, MJ Weinberg, DS Stoffel, E Chiorean, M Heigh, R Levine, J Della'Zanna, G Rodriguez, L Richmond, E Gostout, C Mandrekar, SJ Smyrk, TC AF Limburg, Paul J. Mahoney, Michelle R. Ziegler, Katie L. Allen Sontag, Stephen J. Schoen, Robert E. Benya, Richard Lawson, Michael J. Weinberg, David S. Stoffel, Elena Chiorean, Michael Heigh, Russell Levine, Joel Della'Zanna, Gary Rodriguez, Luz Richmond, Ellen Gostout, Christopher Mandrekar, Sumithra J. Smyrk, Thomas C. CA Canc Prevention Network TI Randomized Phase II Trial of Sulindac, Atorvastatin, and Prebiotic Dietary Fiber for Colorectal Cancer Chemoprevention SO CANCER PREVENTION RESEARCH LA English DT Article ID ABERRANT CRYPT FOCI; FAMILIAL ADENOMATOUS POLYPOSIS; COLON-CANCER; RISK-FACTORS; STATINS; HUMANS; CARCINOGENESIS; METAANALYSIS; PREVENTION; HISTORY AB Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) was performed to identify and characterize rectal aberrant crypt foci (ACF); eligibility criteria required five or more rectal ACFs at baseline. Intervention assignments were as follows: (a) atorvastatin 20 mg qd; (b) sulindac 150 mg bid; (c) oligofructose-enriched inulin (as ORAFTI (R) Synergy1) 6 gm bid; or (d) control (maltodextrin) 6 gm bid, for 6 months. Percent change in rectal ACF number (%Delta ACF) within arm was the primary endpoint. Secondary endpoints included changes in proliferation (Ki67) and apoptosis (caspase-3), as measured from normal mucosa biopsy samples. Among 85 eligible randomized subjects, 76 (86%) completed the trial per protocol. The median (range) of rectal ACF was 9 (5-34) and 8 (0-37) at baseline and postintervention, respectively. The median (SD) for %Delta ACF was 5.6 (-69% to 143%), -18.6 (-83% to 160%), -3.6 (-88% to 83%), and -10.0 (-100% to 117%) in the atorvastatin, sulindac, ORAFTI (R) Synergy1 and control arms, respectively. Neither within-arm (P = 0.12-0.59) nor between-arm (P = 0.30-0.92) comparisons of %Delta ACF were statistically significant. The active and control interventions also seemed to have similar effects on mucosal proliferation and apoptosis (P > 0.05 for each comparison). Data from this multicenter, phase II trial do not provide convincing evidence of CRC risk reduction from 6-month interventions with atorvastatin, sulindac, or ORAFTI (R) Synergy1, although statistical power was limited by the relatively small sample size. Cancer Prev Res; 4(2); 259-69. (C)2011 AACR. C1 [Limburg, Paul J.; Mahoney, Michelle R.; Ziegler, Katie L. Allen; Gostout, Christopher; Mandrekar, Sumithra J.; Smyrk, Thomas C.] Mayo Clin, Rochester, MN USA. [Sontag, Stephen J.] Hines Vet Adm, Hines, IL USA. [Schoen, Robert E.] Univ Pittsburgh, Pittsburgh, PA USA. [Benya, Richard] Univ Illinois, Chicago, IL USA. [Lawson, Michael J.] Kaiser Permanente Med Grp, Sacramento, CA USA. [Weinberg, David S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoffel, Elena] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chiorean, Michael] Indiana Univ, Indianapolis, IN 46204 USA. [Heigh, Russell] Mayo Clin Arizona, Scottsdale, AZ USA. [Levine, Joel] Univ Connecticut, Farmington, CT USA. [Della'Zanna, Gary; Rodriguez, Luz; Richmond, Ellen] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Limburg, PJ (reprint author), 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu FU National Cancer Institute, Division of Cancer Prevention [N01-CN-35000]; Beneo Group; Olympus America; [M01-RR00585] FX This work was sponsored by the National Cancer Institute, Division of Cancer Prevention (contract no. N01-CN-35000). Mayo Clinic Clinical Research Unit is supported by grant M01-RR00585. Research support (study supplies, equipment and/or meeting support) was also provided by the Beneo Group and Olympus America. NR 37 TC 28 Z9 29 U1 1 U2 13 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 FEB PY 2011 VL 4 IS 2 BP 259 EP 269 DI 10.1158/1940-6207.CAPR-10-0215 PG 11 WC Oncology SC Oncology GA 715KH UT WOS:000286882900010 PM 21209397 ER PT J AU Zhang, Q Pan, J Zhang, JJ Liu, PY Chen, R Chen, DR Lubet, R Wang, YA You, M AF Zhang, Qi Pan, Jing Zhang, Jingjie Liu, Pengyuan Chen, Ruth Chen, Da-ren Lubet, Ronald Wang, Yian You, Ming TI Aerosolized Bexarotene Inhibits Lung Tumorigenesis without Increasing Plasma Triglyceride and Cholesterol Levels in Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID A/J MICE; CANCER CHEMOPREVENTION; MAMMARY CANCERS; CLINICAL-TRIAL; PREVENTION; TARGRETIN; LGD1069; CARCINOGENESIS; PROGRESSION; BUDESONIDE AB Prior studies have shown the retinoid X receptor (RXR) agonist bexarotene has preventive efficacy in rodent models of mammary and lung tumorigenesis albeit causing hypertriglyceridemia and hypercholesterolemia. We reasoned that bexarotene delivered by inhalation may provide sufficient dose directly to the respiratory tract to achieve efficacy while avoiding these side effects. In this study, the chemopreventive activity of aerosolized bexarotene was investigated in the benzo(a) pyrene [B(a)P]-induced mouse lung tumor model as assessed by tumor multiplicity and tumor load. Aerosolized bexarotene significantly decreased tumor multiplicity and tumor load by 43% and 74%, respectively. Our data showed that bexarotene can both inhibit proliferation and promote apoptosis in vivo. Our data also show that aerosolized bexarotene did not increase plasma total cholesterol and triglyceride level compared with diet group. These results indicate that aerosolization may be a safe and effective route of administering bexarotene for chemoprevention of lung cancer. Cancer Prev Res; 4(2); 270-6. (C)2010 AACR. C1 [Zhang, Qi; Pan, Jing; Liu, Pengyuan; Wang, Yian; You, Ming] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA. [Zhang, Jingjie; Chen, Ruth; Chen, Da-ren] Washington Univ, Dept Energy Environm & Chem Engn, St Louis, MO 63110 USA. [Lubet, Ronald] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Dept Surg, Sch Med, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@wustl.edu NR 28 TC 10 Z9 10 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 FEB PY 2011 VL 4 IS 2 BP 270 EP 276 DI 10.1158/1940-6207.CAPR-10-0246 PG 7 WC Oncology SC Oncology GA 715KH UT WOS:000286882900011 PM 21163938 ER PT J AU Saydam, O Senol, O Wurdinger, T Mizrak, A Ozdener, GB Stemmer-Rachamimov, AO Yi, M Stephens, RM Krichevsky, AM Saydam, N Brenner, GJ Breakefield, XO AF Saydam, Okay Senol, Ozlem Wuerdinger, Thomas Mizrak, Arda Ozdener, Gokhan Baris Stemmer-Rachamimov, Anat O. Yi, Ming Stephens, Robert M. Krichevsky, Anna M. Saydam, Nurten Brenner, Gary J. Breakefield, Xandra O. TI miRNA-7 Attenuation in Schwannoma Tumors Stimulates Growth by Upregulating Three Oncogenic Signaling Pathways SO CANCER RESEARCH LA English DT Article ID P21-ACTIVATED KINASES; CANCER-CELLS; PROSTATE-CANCER; SUPPRESSOR GENE; FACTOR RECEPTOR; NEUROFIBROMATOSIS; MICRORNAS; EXPRESSION; MERLIN; INHIBITOR AB Micro RNAs (miRNA) negatively regulate protein-coding genes at the posttranscriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap nerve fibers to help support and insulate nerves. In this study, we carried out high-throughput miRNA expression profiling of human vestibular schwannomas by using an array representing 407 known miRNAs to explore the role of miRNAs in tumor growth. Twelve miRNAs were found to be significantly deregulated in tumor samples as compared with control nerve tissue, defining a schwannoma-typical signature. Among these miRNAs, we focused on miR-7, which was one of the most downregulated in these tumors and has several known oncogene targets, including mRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1 (Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growth both in culture and in xenograft tumor models in vivo, which correlated with downregulation of these signaling pathways. Furthermore, we identified a novel direct target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with the expression levels of miR-7 and Ack1 being inversely correlated in human schwannoma samples. These results represent the first miRNA profiling of schwannomas and the first report of a tumor suppressor function for miR-7 in these tumors that is mediated by targeting the EGFR, Pak1, and Ack1 oncogenes. Our findings suggest miR-7 as a potential therapeutic molecule for schwannoma treatment, and they prompt clinical evaluation of drugs that can inhibit the EGFR, Pak1, and Ack1 signaling pathways to treat this tumor type. Cancer Res; 71(3); 852-61. (C) 2010 AACR. C1 [Saydam, Okay; Saydam, Nurten] Med Univ Vienna, Dept Pediat, A-1090 Vienna, Austria. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Dept Pathol, Mol Neurooncol Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brenner, Gary J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. [Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Bethesda, MD 20892 USA. [Saydam, Okay; Senol, Ozlem; Wuerdinger, Thomas; Mizrak, Arda; Ozdener, Gokhan Baris; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Saydam, Okay; Senol, Ozlem; Wuerdinger, Thomas; Mizrak, Arda; Ozdener, Gokhan Baris; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Saydam, O (reprint author), Med Univ Vienna, Dept Pediat, A-1090 Vienna, Austria. EM okay.saydam@meduniwien.ac.at FU NIH/NINDS [P01 NS24279]; DOD [W81XWH-091-0476]; Children's Tumor Foundation [2007-01-043] FX NIH/NINDS P01 NS24279 (X.O. Breakefield/O. Saydam), DOD W81XWH-091-0476 (X.O. Breakefield/O. Saydam), and Children's Tumor Foundation 2007-01-043 (O. Saydam). NR 38 TC 80 Z9 91 U1 0 U2 11 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 FEB 1 PY 2011 VL 71 IS 3 BP 852 EP 861 DI 10.1158/0008-5472.CAN-10-1219 PG 10 WC Oncology SC Oncology GA 714SW UT WOS:000286830300025 PM 21156648 ER PT J AU Solier, S Pommier, Y AF Solier, Stephanie Pommier, Yves TI MDC1 Cleavage by Caspase-3: A Novel Mechanism for Inactivating the DNA Damage Response during Apoptosis SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2AX; S-PHASE; ACTIVATION; CANCER; GAMMA-H2AX; RECOGNITION; CHECKPOINT; MEDIATORS; REPAIR AB Recently, we identified the "apoptotic ring," containing phosphorylated histone H2AX (gamma-H2AX), as an early chromatin modification during apoptosis. Because gamma-H2AX initiates the DNA damage response (DDR), we tested whether the apoptotic H2AX response leads to the full recruitment of the DDR factors that normally coordinate DNA repair and cell-cycle checkpoints. We show that the apoptotic H2AX response does not recruit the DDR factors because MDC1 (mediator of DNA damage checkpoint protein 1), which normally binds to gamma-H2AX in response to DNA damage and amplifies the DDR, is cleaved by caspase-3. This cleavage separates the BRCT and FHA domains of MDC1 and constitutes a novel mechanism for the inactivation of DNA repair in apoptotic cells. Also, we show that downregulation of MDC1 increases the apoptotic response to TRAIL. Together, these results implicate MDC1 in the cellular apoptotic response. Cancer Res; 71(3); 906-13. (C)2010 AACR. C1 [Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS [Z01 BC006150-26] NR 33 TC 12 Z9 15 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2011 VL 71 IS 3 BP 906 EP 913 DI 10.1158/0008-5472.CAN-10-3297 PG 8 WC Oncology SC Oncology GA 714SW UT WOS:000286830300030 PM 21148072 ER PT J AU Moore, LE Baris, DR Figueroa, JD Garcia-Closas, M Karagas, MR Schwenn, MR Johnson, AT Lubin, JH Hein, DW Dagnall, CL Colt, JS Kida, M Jones, MA Schned, AR Cherala, SS Chanock, SJ Cantor, KP Silverman, DT Rothman, N AF Moore, L. E. Baris, D. R. Figueroa, J. D. Garcia-Closas, M. Karagas, M. R. Schwenn, M. R. Johnson, A. T. Lubin, J. H. Hein, D. W. Dagnall, C. L. Colt, J. S. Kida, M. Jones, M. A. Schned, A. R. Cherala, S. S. Chanock, S. J. Cantor, K. P. Silverman, D. T. Rothman, N. TI GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis SO CARCINOGENESIS LA English DT Article ID GENETIC POLYMORPHISMS; SUSCEPTIBILITY; ASSOCIATION; POPULATION; EXPOSURE; TOBACCO; GSTT1 AB Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity. C1 [Moore, L. E.; Baris, D. R.; Figueroa, J. D.; Garcia-Closas, M.; Lubin, J. H.; Dagnall, C. L.; Colt, J. S.; Chanock, S. J.; Cantor, K. P.; Silverman, D. T.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20852 USA. [Karagas, M. R.; Schned, A. R.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA. [Schwenn, M. R.] ME Ctr Dis Control, Maine Canc Registry, Augusta, ME 04333 USA. [Johnson, A. T.] Vermont Canc Registry, Burlington, VT 05401 USA. [Hein, D. W.] Univ Louisville, Dept Pharmacol & Toxicol, Sch Med, Louisville, KY 40202 USA. [Kida, M.] Vermont Coll Med Pathol, Dept Anat & Phys Pathol, Burlington, VT 05401 USA. [Jones, M. A.] So Maine Med Ctr, Dept Clin Pathol, Portland, ME 04102 USA. [Cherala, S. S.] New Hampshire Canc Registry, Div Publ Hlth Serv, Concord, NH 03301 USA. [Dagnall, C. L.] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Bethesda, MD 20892 USA. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Room 8102, Bethesda, MD 20852 USA. EM moorele@mail.nih.gov RI Hein, David/A-9707-2008; Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Dagnall, Casey/0000-0001-7334-4718 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch. NR 27 TC 60 Z9 64 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2011 VL 32 IS 2 BP 182 EP 189 DI 10.1093/carcin/bgq223 PG 8 WC Oncology SC Oncology GA 712OP UT WOS:000286676400008 PM 21037224 ER PT J AU Wang, HS Yamamoto, JF Caberto, C Saltzman, B Decker, R Vogt, TM Yokochi, L Chanock, S Wilkens, LR Le Marchand, L AF Wang, Hansong Yamamoto, Jennifer F. Caberto, Christian Saltzman, Barbara Decker, Robert Vogt, Thomas M. Yokochi, Lance Chanock, Stephen Wilkens, Lynne R. Le Marchand, Loic TI Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia SO CARCINOGENESIS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; DONE RED MEAT; METABOLIZING-ENZYMES; DIET HISTORY; AH RECEPTOR; CANCER RISK; PHASE-I; CYP1A1; HAWAII; N-ACETYLTRANSFERASE-2 AB Animal work implicates chemical carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to the development of colorectal cancer (CRC). The epidemiologic evidence, however, remains inconsistent possibly due to intra-individual variation in bioactivation of these compounds. We conducted a case-control study of colorectal adenoma (914 cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans, European Americans and Native Hawaiians to investigate the association of genetic variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR and ARNT) identified through sequencing with risk of colorectal neoplasia, as well as their interactions with smoking and intakes of red meat and HAAs. The A allele for ARNT rs12410394 was significantly inversely associated with CRC [odds ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes: 1.00, 0.66 (0.48-0.89), 0.54 (0.37-0.78), P-trend = 0.0008] after multiple comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated with CRC, where each copy of the T allele was associated with reduced risk (OR: 0.72, 95% CI: 0.58-0.88, P-trend = 0.0017). No heterogeneity of genetic effects across racial/ethnic groups was detected. In addition, no significant interaction was observed after adjusting for multiple testing between genetic variants and pack-years of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC. C1 [Wang, Hansong; Yamamoto, Jennifer F.; Caberto, Christian; Saltzman, Barbara; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Decker, Robert; Vogt, Thomas M.] Kaiser Permanente Hawaii, Honolulu, HI 96819 USA. [Yokochi, Lance] Pacific Hlth Res Inst, Honolulu, HI 96813 USA. [Chanock, Stephen] NCI, Bethesda, MD 20892 USA. RP Le Marchand, L (reprint author), Univ Hawaii, Program Epidemiol, Canc Res Ctr Hawaii, 1236 Lauhala St,Suite 407, Honolulu, HI 96813 USA. EM loic@crch.hawaii.edu FU National Cancer Institute [R01 CA60987, CA72520]; Hawaii Tumor Registry (National Cancer Institute) [N01-PC-35137] FX National Cancer Institute (R01 CA60987, CA72520).; The authors thank Jean Sato for coordinating the data collection, Maj Earle and Anne Tome for data management and Annette Lum-Jones and Ann Seifried for performing the laboratory assays. We also thank the Hawaii Tumor Registry (National Cancer Institute contract N01-PC-35137) for assistance in CRC case identification. NR 40 TC 34 Z9 34 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2011 VL 32 IS 2 BP 203 EP 209 DI 10.1093/carcin/bgq237 PG 7 WC Oncology SC Oncology GA 712OP UT WOS:000286676400011 PM 21081473 ER PT J AU Loukili, N Rosenblatt-Velin, N Li, JH Clerc, S Pacher, P Feihl, F Waeber, B Liaudet, L AF Loukili, Noureddine Rosenblatt-Velin, Nathalie Li, Jianhui Clerc, Stephanie Pacher, Pal Feihl, Francois Waeber, Bernard Liaudet, Lucas TI Peroxynitrite induces HMGB1 release by cardiac cells in vitro and HMGB1 upregulation in the infarcted myocardium in vivo SO CARDIOVASCULAR RESEARCH LA English DT Article DE Myocardial infarction; Peroxynitrite; High-mobility group box 1; Inflammation; Cardiomyocytes ID ISCHEMIA-REPERFUSION INJURY; MOBILITY GROUP BOX-1; FACTOR-KAPPA-B; ISCHEMIA/REPERFUSION INJURY; NITRIC-OXIDE; DECOMPOSITION CATALYSTS; HYDROGEN-PEROXIDE; HEART-FAILURE; POSTINFARCTION; INFLAMMATION AB Aims High-mobility group box 1 (HMGB1) is a nuclear protein actively secreted by immune cells and passively released by necrotic cells that initiates pro-inflammatory signalling through binding to the receptor for advance glycation end-products. HMGB1 has been established as a key inflammatory mediator during myocardial infarction, but the proximal mechanisms responsible for myocardial HMGB1 expression and release in this setting remain unclear. Here, we investigated the possible involvement of peroxynitrite, a potent cytotoxic oxidant formed during myocardial infarction, on these processes. Methods and results The ability of peroxynitrite to induce necrosis and HMGB1 release in vitro was evaluated in H9c2 cardiomyoblasts and in primary murine cardiac cells (myocytes and non-myocytes). In vivo, myocardial HMGB1 expression and nitrotyrosine content (a marker of peroxynitrite generation) were determined following myocardial ischaemia and reperfusion in rats, whereas peroxynitrite formation was inhibited by two different peroxynitrite decomposition catalysts: 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (III) (FeTPPS) or Mn(III)-tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP). In all types of cells studied, peroxynitrite (100 mu M) elicited significant necrosis, the loss of intracellular HMGB1, and its passive release into the medium. In vivo, myocardial ischaemia-reperfusion induced significant myocardial necrosis, cardiac nitrotyrosine formation, and marked overexpression of myocardial HMGB1. FeTPPS reduced nitrotyrosine, decreased infarct size, and suppressed HMGB1 overexpression, an effect that was similarly obtained with MnTBAP. Conclusion These findings indicate that peroxynitrite represents a key mediator of HMGB1 overexpression and release by cardiac cells and provide a novel mechanism linking myocardial oxidative/nitrosative stress with post-infarction myocardial inflammation. C1 [Loukili, Noureddine; Li, Jianhui; Liaudet, Lucas] Univ Hosp Ctr, Dept Intens Care Med, CH-1011 Lausanne, Switzerland. [Loukili, Noureddine; Rosenblatt-Velin, Nathalie; Li, Jianhui; Clerc, Stephanie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Fac Biol & Med, CH-1011 Lausanne, Switzerland. [Rosenblatt-Velin, Nathalie; Clerc, Stephanie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Univ Hosp Ctr, Div Clin Pathophysiol, CH-1011 Lausanne, Switzerland. [Li, Jianhui] Zhejiang Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China. [Pacher, Pal] NIAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Liaudet, L (reprint author), Univ Hosp Ctr, Dept Intens Care Med, CH-1011 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]; NIAAA, National Institutes of Health FX This work was supported by a Grant from the Swiss National Fund for Scientific Research (No. 320000-118174/1) and a Grant from The Lausanne CardioMet Foundation (No. 2007-R07-15) to L.L. This work was also supported by the Intramural Research Program of the NIAAA, National Institutes of Health to P.P. NR 49 TC 31 Z9 32 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 2011 VL 89 IS 3 BP 586 EP 594 DI 10.1093/cvr/cvq373 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 712OT UT WOS:000286676800016 PM 21113057 ER PT J AU Cleland, MM Norris, KL Karbowski, M Wang, C Suen, DF Jiao, S George, NM Luo, X Li, Z Youle, RJ AF Cleland, M. M. Norris, K. L. Karbowski, M. Wang, C. Suen, D-F Jiao, S. George, N. M. Luo, X. Li, Z. Youle, R. J. TI Bcl-2 family interaction with the mitochondrial morphogenesis machinery SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Bax; mitochondria fusion; Bak; apoptosis; Mfn2 ID MAMMALIAN-CELLS; BAX ACTIVATION; APOPTOSIS; FUSION; FISSION; PROTEIN; DOMAIN; MORPHOLOGY; DYNAMICS; NEURONS AB The regulation of both mitochondrial dynamics and apoptosis is key for maintaining the health of a cell. Bcl-2 family proteins, central in apoptosis regulation, also have roles in the maintenance of the mitochondrial network. Here we report that Bax and Bak participate in the regulation of mitochondrial fusion in mouse embryonic fibroblasts, primary mouse neurons and human colon carcinoma cells. To assess how Bcl-2 family members may regulate mitochondrial morphogenesis, we determined the binding of a series of chimeras between Bcl-xL and Bax to the mitofusins, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2). One chimera (containing helix 5 (H5) of Bax replacing H5 of Bcl-xL (Bcl-xL/Bax H5)) co-immunoprecipitated with Mfn1 and Mfn2 significantly better than either wild-type Bax or Bcl-xL. Expression of Bcl-xL/Bax H5 in cells reduced the mobility of Mfn1 and Mfn2 and colocalized with ectopic Mfn1 and Mfn2, as well as endogenous Mfn2 to a greater extent than wild-type Bax. Ultimately, Bcl-xL/Bax H5 induced substantial mitochondrial fragmentation in healthy cells. Therefore, we propose that Bcl-xL/Bax H5 disturbs mitochondrial morphology by binding and inhibiting Mfn1 and Mfn2 activity, supporting the hypothesis that Bcl-2 family members have the capacity to regulate mitochondrial morphology through binding to the mitofusins in healthy cells. Cell Death and Differentiation (2011) 18, 235-247; doi: 10.1038/cdd.2010.89; published online 30 July 2010 C1 [Cleland, M. M.; Norris, K. L.; Wang, C.; Suen, D-F; Youle, R. J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Karbowski, M.] Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Bethesda, MD USA. [Jiao, S.; Li, Z.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [George, N. M.; Luo, X.] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA. RP Youle, RJ (reprint author), 35 Convent Dr,Room 2C917, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov RI Li, Zheng/I-8016-2014; Wang, Chunxin/B-9312-2016; Jiao, Song/L-2803-2015; OI Li, Zheng/0000-0002-2978-2531; Wang, Chunxin/0000-0001-6015-6806; Jiao, Song/0000-0003-0496-6454; Harwig, Megan/0000-0003-2140-5739 FU National Institute of General Medical Science [RO1-GM083131, RO1-GM76237]; NINDS, NIH FX We would like to thank Drs. David Huang and Kym Lowes for the C57BL/6 WT and Bax-/-Bak-/- cells and their comments on the manuscript; Dr. Kuan Hong Wang for his thoughtful reading of the manuscript; Susan Smith for her tissue culture assistance; and the NINDS DNA sequencing facility, the NINDS imaging facility and Sungyoung Auh for her assistance with statistical analysis. We would also like to thank Dr. Fred Bunz for the pSEPT vector and advice on gene targeting strategy; Dr. Seung-Wook Ryu for cloning FLAG-Mfn2; Dr. Liqiang Zhang for cloning GFP-Bax/Bcl-xL H5; and Dr. Benoit Pierrat for the gift of anti-endophilin B2. MK and XL thankfully acknowledge financial support from National Institute of General Medical Science (RO1-GM083131 to MK and RO1-GM76237 to XL). This work was supported in part by the Intramural Research Program, NINDS, NIH. NR 39 TC 51 Z9 52 U1 4 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2011 VL 18 IS 2 BP 235 EP 247 DI 10.1038/cdd.2010.89 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 704IW UT WOS:000286045800005 PM 20671748 ER PT J AU Goldberg, ME Torjman, MC Schwartzman, RJ Mager, DE Wainer, IW AF Goldberg, Michael E. Torjman, Marc C. Schwartzman, Robert J. Mager, Donald E. Wainer, Irving W. TI Enantioselective Pharmacokinetics of (R)- and (S)-Ketamine After a 5-Day Infusion in Patients with Complex Regional Pain Syndrome SO CHIRALITY LA English DT Article DE ketamine; norketamine; CRPS; pharmacokinetics; pharmacodynamics; enantioselective; liquid chromatography; mass spectrometry ID HUMAN LIVER-MICROSOMES; REFLEX SYMPATHETIC DYSTROPHY; COMPARATIVE PHARMACOLOGY; MASS-SPECTROMETRY; N-DEMETHYLATION; KETAMINE; NORKETAMINE; ENANTIOMERS; METABOLITES; VOLUNTEERS AB Introduction: This study determined the pharmacokinetics and pharmacodynamics of (R)- and (S)-ketamine and (R)- and (S)-norketamine following a 5-day moderate dose, as a continuous (R, S)-ketamine infusion in complex regional pain syndrome (CRPS) patients. Materials and methods: Ketamine was titrated to 10-40 mg/h and maintained for 5 days. (R)and (S)-Ketamine and (R)- and (S)-norketamine pharmacokinetic and pharmacodynamic studies were performed. Blood samples were obtained on Day 1 preinfusion, and at 60-90, 120-150, 180-210, and 240-300 min after the start of the infusion, on Days 2, 3, 4, 5, and on Day 5 at 60 min after the end of infusion. The plasma concentrations of (R)- and (S)-ketamine and (R)- and (S)-norketamine were determined using enantioselective liquid chromatography-mass spectrometry. Results: Ketamine and norketamine levels stabilized 5 h after the start of the infusion. (R)-Ketamine clearance was significantly lower resulting in higher steady-state plasma concentrations than (S)-ketamine. The first-order elimination for (S)-norketamine was significantly greater than that of (R)-enantiomer. When comparing the pharmacokinetic parameters of the patients who responded to ketamine treatment with those who did not, no differences were observed in ketamine clearance and the first-order elimination of norketamine. Conclusion: The results indicate that (R)- and (S)-ketamine and (R)- and (S)-norketamine plasma concentrations do not explain the antinociceptive activity of the drug in patients suffering from CRPS. Chirality 23:138-143, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Goldberg, Michael E.; Torjman, Marc C.] UMDNJ Robert Wood Johnson Med Sch, Dept Anesthesiol, Cooper Univ Hosp, Camden, NJ 08103 USA. [Schwartzman, Robert J.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. [Mager, Donald E.] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. [Wainer, Irving W.] NIA, Bioanalyt Chem & Drug Discovery Sect, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Goldberg, ME (reprint author), UMDNJ Robert Wood Johnson Med Sch, Dept Anesthesiol, Cooper Univ Hosp, 1 Cooper Plaza, Camden, NJ 08103 USA. EM Goldberg-Mike@Cooperhealth.edu FU National Institute on Aging/NIH FX Contract grant sponsor: National Institute on Aging/NIH (Intramural Research Program) NR 30 TC 8 Z9 8 U1 1 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-0042 J9 CHIRALITY JI Chirality PD FEB PY 2011 VL 23 IS 2 BP 138 EP 143 DI 10.1002/chir.20890 PG 6 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 703KM UT WOS:000285976800008 PM 20803495 ER PT J AU Wirka, RC Gore, S Van Wagoner, DR Arking, DE Lubitz, SA Lunetta, KL Benjamin, EJ Alonso, A Ellinor, PT Barnard, J Chung, MK Smith, JD AF Wirka, Robert C. Gore, Shamone Van Wagoner, David R. Arking, Dan E. Lubitz, Steven A. Lunetta, Kathryn L. Benjamin, Emelia J. Alonso, Alvaro Ellinor, Patrick T. Barnard, John Chung, Mina K. Smith, Jonathan D. TI A Common Connexin-40 Gene Promoter Variant Affects Connexin-40 Expression in Human Atria and Is Associated With Atrial Fibrillation SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ion channels; genetics; allelic expression imbalance ID HAPLOTYPE RECONSTRUCTION; HEART-DISEASE; GENOTYPE; RISK; MICE AB Background-A common single-nucleotide polymorphism (SNP) in the promoter of the Connexin-40 (Cx40) gene GJA5 was suggested to affect Cx40 promoter activity and the risk of atrial fibrillation (AF), but the role of other common Cx40 polymorphisms is unknown. Methods and Results-Eight SNPs within the Cx40 gene region were tested for association with Cx40 levels measured in atrial tissue from 61 individuals. The previously described Cx40 promoter SNP (rs35594137, -44G -> A) was not associated with Cx40 mRNA levels. However, a common SNP (rs10465885) located in the TATA box of an alternative Cx40 promoter was strongly associated with Cx40 mRNA expression (P < 0.0001) and displayed strong and consistent allelic expression imbalance in human atrial tissue. A promoter-luciferase assay in cultured murine cardiomyocytes demonstrated reduced activity of the promoter containing the minor allele of this SNP (P < 0.0001). Both rs35594137 and rs10465885 were tested for association with early-onset lone AF (<= 60 years of age) in 384 cases and 3010 population control subjects. rs10465885 was associated with the AF phenotype (odds ratio, 1.18; P=0.046). This result was confirmed in a meta-analysis including 2 additional early-onset lone AF case-control cohorts (odds ratio, 1.16, P=0.022). rs35594137 was not associated with the lone AF phenotype in any of the cohorts studied or in a combined analysis. Conclusions-A previously described Cx40 promoter SNP was not found to influence Cx40 expression or risk of AF. We describe an alternate promoter polymorphism that directly affects levels of Cx40 mRNA in vivo and is associated with early-onset lone AF. (Circ Arrhythm Electrophysiol. 2011;4:87-93.) C1 [Wirka, Robert C.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Smith, Jonathan D.] Cleveland Clin, Dept Cell Biol & Cardiovasc Med, Cleveland, OH 44195 USA. [Gore, Shamone] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44195 USA. [Van Wagoner, David R.] Cleveland Clin, Dept Mol Cardiol & Cardiovasc Med, Cleveland, OH 44195 USA. [Barnard, John] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Chung, Mina K.] Cleveland Clin, Dept Cardiovasc Med & Mol Cardiol, Cleveland, OH 44195 USA. [Arking, Dan E.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Smith, JD (reprint author), Cleveland Clin, Dept Cell Biol & Cardiovasc Med, 9500 Euclid Ave,NC-10, Cleveland, OH 44195 USA. EM barnarj@ccf.org; chungm@ccf.org; smithj4@ccf.org RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Lunetta, Kathryn/0000-0002-9268-810X; Benjamin, Emelia/0000-0003-4076-2336 FU CCR NIH HHS [RC1 HL099452-02]; Howard Hughes Medical Institute; NCRR NIH HHS [1UL-RR024989, UL1 RR024989, UL1 RR024989-05, UL1 RR025005, UL1 RR025005-05, UL1RR025005]; NHGRI NIH HHS [U01 HG004402, U01 HG004402-01, U01HG004402]; NHLBI NIH HHS [RC1 HL101056, 1RC1HL099452, HL090620, HL092577, N01 HC055015, N01 HC055016, N01 HC055018, N01 HC055019, N01 HC055020, N01 HC055021, N01 HC055022, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, R01 HL059367, R01 HL059367-10, R01 HL086694, R01 HL086694-03, R01 HL087641, R01 HL087641-03, R01 HL090620, R01 HL090620-04, R01 HL092577, R01 HL092577-03, R01 HL104156, R01HL086694, R01HL087641, R01HL59367, RC1 HL099452, RC1 HL099452-02, RC1 HL101056-02, T32 HL007575, T32 HL007575-26A1, T32HL007575]; NIDA NIH HHS [DA027021, R21 DA027021, R21 DA027021-02]; PHS HHS [HHSN268200625226C] NR 26 TC 41 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2011 VL 4 IS 1 BP 87 EP + DI 10.1161/CIRCEP.110.959726 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721LL UT WOS:000287356000015 PM 21076161 ER PT J AU Kelly, RJ Draper, D Chen, CC Robey, RW Figg, WD Piekarz, RL Chen, XH Gardner, ER Balis, FM Venkatesan, AM Steinberg, SM Fojo, T Bates, SE AF Kelly, Ronan J. Draper, Deborah Chen, Clara C. Robey, Robert W. Figg, William D. Piekarz, Richard L. Chen, Xiaohong Gardner, Erin R. Balis, Frank M. Venkatesan, Aradhana M. Steinberg, Seth M. Fojo, Tito Bates, Susan E. TI A Pharmacodynamic Study of Docetaxel in Combination with the P-glycoprotein Antagonist Tariquidar (XR9576) in Patients with Lung, Ovarian, and Cervical Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; MEDIATED MULTIDRUG-RESISTANCE; IN-VIVO REVERSAL; PHASE-I; CHEMOTHERAPY RESPONSE; TC-99M TETROFOSMIN; VALSPODAR PSC-833; CELL CARCINOMA; SOLID TUMORS; PSC 833 AB Purpose: P-glycoprotein (Pgp) antagonists have been difficult to develop because of complex pharmacokinetic interactions and a failure to show meaningful results. Here we report the results of a pharmacokinetic and pharmacodynamic trial using a third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576), in combination with docetaxel. Experimental Design: In the first treatment cycle, the pharmacokinetics of docetaxel (40 mg/m(2)) were evaluated after day 1 and day 8 doses, which were administered with or without tariquidar (150 mg). 99m Tc-sestamibi scanning and CD56(+) mononuclear cell rhodamine efflux assays were conducted to assess Pgp inhibition. In subsequent cycles, 75 mg/m2 docetaxel was administered with 150 mg tariquidar every 3 weeks. Results: Forty-eight patients were enrolled onto the trial. Nonhematologic grade 3/4 toxicities in 235 cycles were minimal. Tariquidar inhibited Pgp-mediated rhodamine efflux from CD56(+) cells and reduced 99m Tc-sestamibi clearance from the liver. There was striking variability in basal sestamibi uptake; a 12% to 24% increase in visible lesions was noted in 8 of 10 patients with lung cancer. No significant difference in docetaxel disposition was observed in pairwise comparison with and without tariquidar. Four partial responses (PR) were seen (4/48); 3 in the non-small cell lung cancer (NSCLC) cohort, measuring 40%, 57%, and 67% by RECIST, and 1 PR in a patient with ovarian cancer. Conclusions: Tariquidar is well tolerated, with less observed systemic pharmacokinetic interaction than previous Pgp antagonists. Variable effects of tariquidar on retention of sestamibi in imageable lung cancers suggest that follow-up studies assessing tumor drug uptake in this patient population would be worthwhile. Clin Cancer Res; 17(3); 569-80. (C) 2010 AACR. C1 [Kelly, Ronan J.; Draper, Deborah; Robey, Robert W.; Figg, William D.; Piekarz, Richard L.; Chen, Xiaohong; Fojo, Tito; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Clara C.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD USA. [Chen, Clara C.] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, SAIC Frederick, Clin Pharmacol Program, Frederick, MD 21701 USA. [Balis, Frank M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Venkatesan, Aradhana M.] NCI, Dept Radiol & Imaging Sci, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute, NIH [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E (E.R.G.). This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 67 Z9 70 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 FEB 1 PY 2011 VL 17 IS 3 BP 569 EP 580 DI 10.1158/1078-0432.CCR-10-1725 PG 12 WC Oncology SC Oncology GA 715HI UT WOS:000286873400019 PM 21081657 ER PT J AU Bagatell, R Herzog, CE Trippett, M Grippo, JF Cirrincione-Dall, G Fox, E Macy, M Bish, J Whitcomb, P Aikin, A Wright, G Yurasov, S Balis, FM Gore, L AF Bagatell, R. Herzog, C. E. Trippett, M. Grippo, J. F. Cirrincione-Dall, G. Fox, E. Macy, M. Bish, J. Whitcomb, P. Aikin, A. Wright, G. Yurasov, S. Balis, F. M. Gore, L. TI Pharmacokinetically Guided Phase 1 Trial of the IGF-1 Receptor Antagonist RG1507 in Children with Recurrent or Refractory Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID EWINGS-SARCOMA CELLS; I RECEPTOR; RHABDOMYOSARCOMA CELLS; ANTITUMOR-ACTIVITY; GROWTH; EXPRESSION; ANTIBODY; INHIBITION; INCREASES; MICE AB Purpose: This pediatric phase I study was designed to identify the doses of RG1507, a monoclonal antibody against the Type 1 Insulin-like Growth Factor Receptor (IGF1R), that achieves exposures equivalent to those achieved in adults at recommended doses. Experimental Design: Children with relapsed or refractory solid tumors were treated using the same doses and administration schedules of RG1507 (3 and 9 mg/kg/wk, and 16 mg/kg every 3 weeks [q3W]) as those studied in adults. Detailed pharmacokinetic (PK) sampling was performed after the first dose; selected peak and trough levels were subsequently obtained. Target exposures were >= 85% of mean areas under concentration x time curves (AUCs) in adults at doses of 9 mg/kg/wk and 16 mg/kg q3W. A maximum tolerated dose could be identified if dose-limiting toxicities (DLT) occurred. Results: Thirty-one evaluable patients aged 3-17 years were enrolled at 3 mg/kg/wk (n = 3), 9 mg/kg/wk (n 18), or 16 mg/kg q3W (n 10). There were no DLTs. At 9 mg/kg/wk the mean AUC(0-7d) (21,000 mu g h/mL) exceeded the target (16,000 mg h/mL). At 16 mg/kg q3W, the mean AUC(021d) (70,000 mg h/mL) exceeded the target (59,400 mg h/mL). Clearance normalized to body weight was age dependent. There were no objective responses. Seven patients had stable disease for > 12 weeks, including two patients with osteosarcoma with stable disease for 52+ and 78+ weeks. Conclusions: The recommended doses of RG1507 in children with solid tumors are 9 mg/kg/wk and 16 mg/kg q3W. This flexible design is well suited for trials of agents associated with limited toxicity. Clin Cancer Res; 17(3); 611-9. (C) 2010 AACR. C1 [Bagatell, R.; Fox, E.; Bish, J.; Balis, F. M.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19066 USA. [Herzog, C. E.] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA. [Trippett, M.; Wright, G.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Grippo, J. F.; Cirrincione-Dall, G.; Yurasov, S.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Macy, M.; Gore, L.] Childrens Hosp, Dept Pediat, Aurora, CO USA. [Macy, M.; Gore, L.] Univ Colorado Denver, Aurora, CO USA. [Whitcomb, P.; Aikin, A.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Bagatell, R (reprint author), Childrens Hosp Philadelphia, Dept Pediat, CTRB 4022,3501 Civ Ctr Blvd, Philadelphia, PA 19066 USA. EM bagatellr@email.chop.edu FU Hoffmann-La Roche Inc; NIH (National Cancer Institute, Center for Cancer Research); Alex's Lemonade Stand Foundation; Caitlin Robb Foundation; Morgan Adams Foundation FX The research support was provided by Hoffmann-La Roche Inc. This research was also supported in part by the Intramural Research Program of the NIH (National Cancer Institute, Center for Cancer Research), Alex's Lemonade Stand Foundation, the Caitlin Robb Foundation, and the Morgan Adams Foundation. NR 19 TC 21 Z9 21 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 FEB 1 PY 2011 VL 17 IS 3 BP 611 EP 619 DI 10.1158/1078-0432.CCR-10-1731 PG 9 WC Oncology SC Oncology GA 715HI UT WOS:000286873400023 PM 21127194 ER PT J AU Alsarraj, J Walker, RC Webster, JD Simpson, RM Ozato, K Hunter, KW AF Alsarraj, Jude Walker, Renard C. Webster, Joshua D. Simpson, R. Mark Ozato, Keiko Hunter, Kent W. TI A mutant of the metastasis susceptibility gene Brd4 promotes EMT, stem cell-like conversion, and metastatic progression in a mouse mammary tumor model SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Alsarraj, Jude; Walker, Renard C.; Webster, Joshua D.; Simpson, R. Mark; Hunter, Kent W.] NCI, NIH, Bethesda, MD 20892 USA. [Ozato, Keiko] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 159 EP 160 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200013 ER PT J AU Winter, SF Hunter, KW AF Winter, Scott F. Hunter, Kent W. TI Arid4b: a candidate breast cancer progression modifier gene SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Winter, Scott F.; Hunter, Kent W.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 166 EP 166 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200030 ER PT J AU Guedez, L Kwityn, CJ Stetler-Stevenson, WG AF Guedez, Liliana Kwityn, Clifford J. Stetler-Stevenson, William G. TI Inflammation linked to the deficiency of tissue inhibitor of metalloproteinase-2 accelerates tumorogenesis of Lewis-lung carcinoma SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Guedez, Liliana; Kwityn, Clifford J.; Stetler-Stevenson, William G.] NCI, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 171 EP 171 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200048 ER PT J AU Tsai, YC Weissman, AM Maditz, R AF Tsai, Yien Che Weissman, Allan M. Maditz, Rhyan TI Regulation of ER-associated degradation and ER stress in metastasis: insights from studies on an ER ubiquitin ligase SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Tsai, Yien Che; Weissman, Allan M.; Maditz, Rhyan] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 190 EP 190 PG 1 WC Oncology SC Oncology GA 753RB UT WOS:000289796200106 ER PT J AU Goldberger, NE Tran, B Hunter, K AF Goldberger, Natalie E. Bao Tran Hunter, Kent TI Identification of candidate microRNAs regulating breast cancer metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Goldberger, Natalie E.; Hunter, Kent] NCI, Bethesda, MD 20892 USA. [Bao Tran] SAIC, Frederick, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 212 EP 213 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200171 ER PT J AU Marino, N Marshall, JCA Collins, J Veenstra, T Zhou, M Steeg, PS AF Marino, Natascia Marshall, Jean-Claude A. Collins, Joshua Veenstra, Timothy Zhou, Ming Steeg, Patricia S. TI The actin-binding protein Gelsolin as a potential binding partner of Nm23 SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Marino, Natascia; Marshall, Jean-Claude A.; Collins, Joshua; Steeg, Patricia S.] NIH, Bethesda, MD 20892 USA. [Veenstra, Timothy; Zhou, Ming] NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 228 EP 229 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200221 ER PT J AU Sourbier, C Kim, YS Lee, S Trepel, J Neckers, L Linehan, M AF Sourbier, Carole Kim, Yeono-Sang Lee, Sunmin Trepel, Jane Neckers, Len Linehan, Marston TI Invasion of HLRCC tumors: assessing the contribution of HIF, ROS, and lipids SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Sourbier, Carole; Kim, Yeono-Sang; Lee, Sunmin; Trepel, Jane; Neckers, Len; Linehan, Marston] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD FEB PY 2011 VL 28 IS 2 BP 257 EP 258 PG 2 WC Oncology SC Oncology GA 753RB UT WOS:000289796200305 ER PT J AU Desai, V Donsante, A Swoboda, KJ Martensen, M Thompson, J Kaler, SG AF Desai, V. Donsante, A. Swoboda, K. J. Martensen, M. Thompson, J. Kaler, S. G. TI Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease SO CLINICAL GENETICS LA English DT Article DE ATP7A; junction fragment; Menkes disease; skewing; X-inactivation ID OCCIPITAL-HORN-SYNDROME; CHROMOSOME INACTIVATION; CANDIDATE GENE; NEONATAL DIAGNOSIS; LINKED DISEASE; PROTEIN; PLASMA; MICE; TRANSLOCATION; ACTIVATION AB Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in ATP7A, which is located at Xq13.1-q21. ATP7A encodes a copper-transporting P-type ATPase and plays a critical role in development of the central nervous system. With rare exceptions involving sex chromosome aneuploidy or X-autosome translocations, female carriers of ATP7A mutations are asymptomatic except for subtle hair and skin abnormalities, although the mechanism for this neurological sparing has not been reported. We studied a three-generation family in which a severe ATP7A mutation, a 5.5-kb genomic deletion spanning exons 13 and 14, segregated. The deletion junction fragment was amplified from the proband by long-range polymerase chain reaction and sequenced to characterize the breakpoints. We screened at-risk females in the family for this junction fragment and analyzed their X-inactivation patterns using the human androgen-receptor (HUMARA) gene methylation assay. We detected the junction fragment in the proband, two obligate heterozygotes, and four of six at-risk females. Skewed inactivation of the X chromosome harboring the deletion was noted in all female carriers of the deletion (n = 6), whereas random X-inactivation was observed in all non-carriers (n = 2). Our results formally document one mechanism for neurological sparing in female carriers of ATP7A mutations. Based on review of X-inactivation patterns in female carriers of other X-linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A-related distal motor neuropathy. C1 [Desai, V.; Donsante, A.; Kaler, S. G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Swoboda, K. J.; Martensen, M.; Thompson, J.] Univ Utah, Sch Med, Dept Neurol, Pediat Motor Disorders Res Program, Salt Lake City, UT USA. [Swoboda, K. J.; Martensen, M.; Thompson, J.] Univ Utah, Sch Med, Dept Pediat, Pediat Motor Disorders Res Program, Salt Lake City, UT USA. RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10,Room 5-2571,10 Ctr Dr,MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU NIH FX We are grateful to the family for their participation and to Sarah Godwin for mutation identification in the proband. This work was supported by the NIH Intramural Research Program. NR 40 TC 15 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD FEB PY 2011 VL 79 IS 2 BP 176 EP 182 DI 10.1111/j.1399-0004.2010.01451.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 703HE UT WOS:000285968200011 PM 20497190 ER PT J AU Vinh, DC Schwartz, B Hsu, AP Miranda, DJ Valdez, PA Fink, D Lau, KP Long-Priel, D Kuhns, DB Uzel, G Pittaluga, S Hoover, S Galgiani, JN Holland, SM AF Vinh, Donald C. Schwartz, Brian Hsu, Amy P. Miranda, David J. Valdez, Patricia A. Fink, Danielle Lau, Karen P. Long-Priel, Debra Kuhns, Douglas B. Uzel, Gulbu Pittaluga, Stefania Hoover, Susan Galgiani, John N. Holland, Steven M. TI Interleukin-12 Receptor beta 1 Deficiency Predisposing to Disseminated Coccidioidomycosis SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; INTERFERON; IMMITIS C1 [Vinh, Donald C.; Hsu, Amy P.; Miranda, David J.; Uzel, Gulbu; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Schwartz, Brian] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. [Valdez, Patricia A.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Fink, Danielle; Lau, Karen P.; Long-Priel, Debra; Kuhns, Douglas B.] SAIC Frederick, Neutrophil Monitoring Lab, Clin Serv Program, Frederick, MD USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Frederick, MD 21701 USA. [Hoover, Susan; Galgiani, John N.] Univ Arizona, Valley Fever Ctr Excellence, Tucson, AZ USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bldg 10CRC,Rm B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov RI Hoover, Susan/F-8580-2015; OI VINH, DONALD/0000-0003-1347-7767 FU Canadian Institutes of Health Research; Intramural NIH HHS NR 14 TC 31 Z9 31 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 2011 VL 52 IS 4 BP E99 EP E102 DI 10.1093/cid/ciq215 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 712PD UT WOS:000286677800003 PM 21258095 ER PT J AU Tamura, MK Xie, DW Yaffe, K Cohen, DL Teal, V Kasner, SE Messe, SR Sehgal, AR Kusek, J DeSalvo, KB Cornish-Zirker, D Cohan, J Seliger, SL Chertow, GM Go, AS AF Tamura, Manjula Kurella Xie, Dawei Yaffe, Kristine Cohen, Debbie L. Teal, Valerie Kasner, Scott E. Messe, Steven R. Sehgal, Ashwini R. Kusek, John DeSalvo, Karen B. Cornish-Zirker, Denise Cohan, Janet Seliger, Stephen L. Chertow, Glenn M. Go, Alan S. TI Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CARDIOVASCULAR HEALTH COGNITION; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; DEMENTIA; BRAIN; ANEMIA; ADULTS; PERFORMANCE; COMMUNITY; OUTCOMES AB Background and objectives Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear. Design, setting, participants, & measurements We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score >1 SD below the mean score. Results Among 3591 participants, the mean age was 58.2 +/- 11.0 years, and the mean estimated GFR (eGFR) was 43.4 +/- 13.5 ml/min per 1.73 m(2). Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR <30 ml /min per 1.73 m(2) was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m(2). This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders. Conclusions The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia. Clin J Am Soc Nephrol 6: 248-256, 2011. doi: 10.2215/CJN.02660310 C1 [Tamura, Manjula Kurella; Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Tamura, Manjula Kurella] Vet Affairs Palo Alto Geriatr Res & Educ Clin Ctr, Palo Alto, CA USA. [Xie, Dawei; Teal, Valerie; Kasner, Scott E.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Epidemiol, San Francisco, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Cohen, Debbie L.] Univ Penn, Renal Electrolyte Div, Philadelphia, PA 19104 USA. [Kasner, Scott E.; Messe, Steven R.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Sehgal, Ashwini R.] Case Western Reserve Univ, Div Nephrol, Cleveland, OH 44106 USA. [Kusek, John] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. [DeSalvo, Karen B.] Tulane Univ, Sect Gen Internal Med & Geriatr, New Orleans, LA 70118 USA. [Cornish-Zirker, Denise] Univ Michigan, Div Cardiovasc Med & Hypertens, Ann Arbor, MI 48109 USA. [Cohan, Janet] Univ Illinois, Dept Med, Chicago, IL USA. [Seliger, Stephen L.] Univ Maryland, Div Nephrol, Baltimore, MD 21201 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Biostat, San Francisco, CA USA. RP Tamura, MK (reprint author), Stanford Univ, Sch Med, Div Nephrol, 780 Welch Rd,Suite 106, Palo Alto, CA 94304 USA. EM mktamura@stanford.edu RI Kasner, Scott/C-6109-2011; Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902, R01DK069406]; National Institutes of Health [UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, UL1RR024131]; National Institute of Aging [K23AG028952]; Amgen FX The CRIC Study is supported by cooperative agreement project grants 5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902 from the National Institute of Diabetes and Digestive and Kidney Diseases and by grants UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, and UL1RR024131 from the National Institutes of Health. Dr. Kurella Tamura received support from the National Institute of Aging (grant K23AG028952). Dr. Yaffe was supported by R01DK069406, also from the National Institute of Diabetes and Digestive and Kidney Diseases. These results were presented in abstract form at the American Society of Nephrology Meeting.; Dr. Kurella Tamura has previously received grant support from Amgen. NR 36 TC 41 Z9 47 U1 1 U2 9 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 FEB PY 2011 VL 6 IS 2 BP 248 EP 256 DI 10.2215/CJN.02660310 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 722KJ UT WOS:000287430800004 ER PT J AU Onumah, C Kimmel, PL Rosenberg, ME AF Onumah, Chavon Kimmel, Paul L. Rosenberg, Mark E. TI Race Disparities in US Nephrology Fellowship Training SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GRADUATE MEDICAL-EDUCATION; STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; HEALTH-CARE-SYSTEM; RACIAL-DIFFERENCES; UNITED-STATES; TRUST; PATIENT; DISCRIMINATION; RECRUITMENT AB Background and objectives Renal disease disproportionately affects African-American patients. Trust has been implicated as an important factor in patient outcomes. Higher levels of trust and better interpersonal care have been reported when race of patient and physician are concordant. The purpose of this analysis was to examine trends in the racial background of U.S. medical school graduates, internal medicine residents, nephrology fellows, and patients with ESRD. Design, setting, participants, & measurements Data for medical school graduates were obtained from the Association of American Medical Colleges and data for internal medicine and nephrology trainees from GME Track. ESRD data were obtained from U.S. Renal Data System (USRDS) annual reports. Results A significant disparity continues to exist between the proportional race makeup of African-American nephrology fellows (3.8%) and ESRD patients (32%). The low numbers of African-American nephrology fellows, and consequently new nephrologists, in light of the increase in ESRD patients has important implications for patient-centered nephrology care. Conclusions Efforts are needed to increase minority recruitment into nephrology training programs, to more closely balance the racial background of trainees and patients in hopes of fostering improved trust between ESRD caregivers and patients, increasing access to care, alleviating ESRD health care disparities, and improving patient care. Clin J Am Soc Nephrol 6: 390-394, 2011. doi: 10.2215/CJN.04450510 C1 [Onumah, Chavon; Rosenberg, Mark E.] Univ Minnesota, Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN 55417 USA. [Kimmel, Paul L.] NIDDK, Bethesda, MD USA. RP Rosenberg, ME (reprint author), Univ Minnesota, Minneapolis VA Med Ctr, Dept Med, 1 Vet Dr, Minneapolis, MN 55417 USA. EM rosen001@umn.edu NR 42 TC 3 Z9 3 U1 0 U2 2 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 FEB PY 2011 VL 6 IS 2 BP 390 EP 394 DI 10.2215/CJN.04450510 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 722KJ UT WOS:000287430800022 PM 21273375 ER PT J AU Visvader, JE Smith, GH AF Visvader, Jane E. Smith, Gilbert H. TI Murine Mammary Epithelial Stem Cells: Discovery, Function, and Current Status SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; PROGENITOR CELLS; GLAND DEVELOPMENT; BREAST-CANCER; IN-VIVO; CHEMICAL CARCINOGENESIS; TGF-BETA-1 EXPRESSION; SELF-RENEWAL; MOUSE; DIFFERENTIATION AB An entire mammary epithelial outgrowth, capable of full secretory differentiation, may comprise the progeny of a single cellular antecedent, i.e., may be generated from a single mammary epithelial stem cell. Early studies showed that any portion of an intact murine mammary gland containing epithelium could recapitulate an entire mammary epithelial tree on transplantation into an epithelium-free mammary fat pad. More recent studies have shown that a hierarchy of mammary stem/progenitor cells exists among the mammary epithelium and that their behavior and maintenance is dependent on signals generated both locally and systemically. In this review, we have attempted to develop the scientific saga surrounding the discovery and characterization of the murine mammary stem/progenitor cell hierarchy and to suggest further approaches that will enhance our knowledge and understanding of these cells and their role in both normal development and neoplasia. C1 [Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Visvader, Jane E.] Walter & Eliza Hall Inst Med Res, Stem Cells & Canc Div, Parkville, Vic 3050, Australia. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 85 TC 33 Z9 35 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD FEB PY 2011 VL 3 IS 2 AR a004879 DI 10.1101/cshperspect.a004879 PG 14 WC Cell Biology SC Cell Biology GA 714LD UT WOS:000286810200009 ER PT J AU Yang, YN Remmers, EF Ogunwole, CB Kastner, DL Gregersen, PK Li, WT AF Yang, Yaning Remmers, Elaine F. Ogunwole, Chukwuma B. Kastner, Daniel L. Gregersen, Peter K. Li, Wentian TI Effective sample size: Quick estimation of the effect of related samples in genetic case-control association analyses SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE Genetic association; Correlation; Variance inflation; Effective sample size ID GENOME-WIDE ASSOCIATION; COMPLEX HUMAN-DISEASES; CASE-CONTROL DESIGNS; LINKAGE DISEQUILIBRIUM; RHEUMATOID-ARTHRITIS; POPULATION STRATIFICATION; ESTIMATING EQUATIONS; ALLELE FREQUENCIES; CORRELATED DATA; INDIVIDUALS AB Affected relatives are essential for pedigree linkage analysis, however, they cause a violation of the independent sample assumption in case-control association studies. To avoid the correlation between samples, a common practice is to take only one affected sample per pedigree in association analysis. Although several methods exist in handling correlated samples, they are still not widely used in part because these are not easily implemented, or because they are not widely known. We advocate the effective sample size method as a simple and accessible approach for case-control association analysis with correlated samples. This method modifies the chi-square test statistic, p-value, and 95% confidence interval of the odds-ratio by replacing the apparent number of allele or genotype counts with the effective ones in the standard formula, without the need for specialized computer programs. We present a simple formula for calculating effective sample size for many types of relative pairs and relative sets. For allele frequency estimation, the effective sample size method captures the variance inflation exactly. For genotype frequency, simulations showed that effective sample size provides a satisfactory approximation. A gene which is previously identified as a type 1 diabetes susceptibility locus, the interferon-induced helicase gene (IFIH1), is shown to be significantly associated with rheumatoid arthritis when the effective sample size method is applied. This significant association is not established if only one affected sib per pedigree were used in the association analysis. Relationship between the effective sample size method and other methods - the generalized estimation equation, variance of eigenvalues for correlation matrices, and genomic controls - are discussed. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Gregersen, Peter K.; Li, Wentian] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY 11030 USA. [Yang, Yaning] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. [Remmers, Elaine F.; Ogunwole, Chukwuma B.; Kastner, Daniel L.] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. RP Li, WT (reprint author), N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, 350 Community Dr, Manhasset, NY 11030 USA. EM wli@nslij-genetics.org OI Li, Wentian/0000-0003-1155-110X FU National Institute of Health [R01-AR44422, NO1-AR22263]; National Natural Science Foundation of China [10671189]; Chinese Academy of Science [KJCX3-SYW-S02]; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX WL and PKG are supported by the National Institute of Health grant R01-AR44422, NO1-AR22263. YY is supported by the National Natural Science Foundation of China Grant 10671189 and the Chinese Academy of Science Grant No. KJCX3-SYW-S02. EFR, CBO and DLK was supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. We would like to thank Chris Amos, Yongchao Ge, Jianxin Shi, Jan Freudenberg for helpful discussion. NR 76 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1476-9271 J9 COMPUT BIOL CHEM JI Comput. Biol. Chem. PD FEB PY 2011 VL 35 IS 1 BP 40 EP 49 DI 10.1016/j.compbiolchem.2010.12.006 PG 10 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 741EI UT WOS:000288845500006 PM 21333602 ER PT J AU Moody, TW Ito, T Osefo, N Jensen, RT AF Moody, Terry W. Ito, Tetsuhide Osefo, Nuramy Jensen, Robert T. TI VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studies SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE circadian rhythm; depression; diabetes; motility; neuroprotection; neurotransmitter; obesity; PACAP; schizophrenia; VIP ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; ADENYLATE-CYCLASE; DEFICIENT MICE; SUPRACHIASMATIC NUCLEI; RECEPTOR AGONIST; NEUROPROTECTIVE PEPTIDE; SUSTAINED RELAXATION; EXTRACELLULAR DOMAIN; VPAC(1) RECEPTORS AB Purpose of review Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as the three classes of G-protein-coupled receptors mediating their effects, are widely distributed in the central nervous system (CNS) and peripheral tissues. These peptides are reported to have many effects in different tissues, which are physiological or pharmacological, and which receptor mediates which effect, has been difficult to determine, primarily due to lack of potent, stable, selective agonists/antagonists. Recently the use of animals with targeted knockout of the peptide or a specific receptor has provided important insights into their role in normal physiology and disease states. Recent findings During the review period, considerable progress and insights has occurred in the understanding of the role of VIP/PACAP as well as their receptors in a number of different disorders/areas. Particularly, insights into their roles in energy metabolism, glucose regulation, various gastrointestinal processes including gastrointestinal inflammatory conditions and motility and their role in the CNS as well as CNS diseases has greatly expanded. Summary PACAP/VIP as well as their three classes of receptors are important in many physiological/pathophysiological processes, some of which are identified in these studies using knockout animals. These studies may lead to new novel treatment approaches. Particularly important are their roles in glucose metabolism and on islets leading to possible novel approaches in diabetes; their novel anti-inflammatory, cytoprotective effects, their CNS neuroprotective effects, and their possible roles in diseases such as schizophrenia and chronic depression. C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Moody, Terry W.; Osefo, Nuramy] NCI, Dept Hlth & Human Serv, Natl Canc Inst Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Ito, Tetsuhide] Kyushu Univ, Dept Med & Bioregulatory Sci, Grad Sch Med Sci, Fukuoka 812, Japan. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK; NCI FX The work was partially supported by intramural funds of NIDDK and NCI. NR 92 TC 30 Z9 38 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2011 VL 18 IS 1 BP 61 EP 67 DI 10.1097/MED.0b013e328342568a PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 697TW UT WOS:000285542100012 PM 21157320 ER PT J AU Athar, M Elmets, CA Kopelovich, L AF Athar, Mohammad Elmets, Craig A. Kopelovich, Levy TI Pharmacological Activation of p53 in Cancer Cells SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE p53; cancer therapeutics; mutant p53 refolding; restoration of tumor suppressor functions; mdm2 ID WILD-TYPE P53; SMALL-MOLECULE ANTAGONISTS; PRIMA-1 INDUCES APOPTOSIS; MYELOID-LEUKEMIA CELLS; REGRESSION IN-VIVO; MUTANT P53; DEPENDENT APOPTOSIS; TUMOR-SUPPRESSOR; GENE-THERAPY; COLORECTAL-CANCER AB Tumor suppressor p53 is a transcription factor that regulates a large number of genes and guards against genomic instability. Under multiple cellular stress conditions, p53 functions to block cell cycle progression transiently unless proper DNA repair occurs. Failure of DNA repair mechanisms leads to p53-mediated induction of cell death programs. p53 also induces permanent cell cycle arrest known as cellular senescence. During neoplastic progression, p53 is often mutated and fails to efficiently perform these functions. It has been observed that cancers carrying a wild-type p53 may also have interrupted downstream p53 regulatory signaling leading to disruption in p53 functions. Therefore, strategies to reactivate p53 provide an attractive approach for blocking tumor pathogenesis and its progression. p53 activation may also lead to regression of existing early neoplastic lesions and therefore may be important in developing cancer chemoprevention protocols. A large number of small molecules capable of reactivating p53 have been developed and some are progressing through clinical trials for prospective human applications. However, several questions remain to be answered at this stage. For example, it is not certain if pharmacological activation of p53 will restore all of its multifaceted biological responses, assuming that the targeted cell is not killed following p53 activation. It remains to be demonstrated whether the distinct biological effects regulated by specific post-translationally modified p53 can effectively be restored by refolding mutant p53. Mutant p53 can be classified as a loss-of-function or gain-of-function protein depending on the type of mutation. It is also unclear whether reactivation of mutant p53 has similar consequences in cells carrying gain-of-function and loss-of-function p53 mutants. This review provides a description of various pharmacological approaches tested to activate p53 (both wild-type and mutant) and to assess the effects of activated p53 on neoplastic progression. C1 [Athar, Mohammad; Elmets, Craig A.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Athar, Mohammad; Elmets, Craig A.] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Athar, M (reprint author), Univ Alabama Birmingham, Dept Dermatol, Volker Hall,Room 509,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mathar@uab.edu FU [R01 ES015323]; [R21ES017494]; [NCI NO1-CN-43300 261200433001C-521958]; [P30AR050948] FX Grant Support from the following awards, R01 ES015323, R21ES017494, NCI NO1-CN-43300 261200433001C-521958, P30AR050948. NR 118 TC 20 Z9 20 U1 1 U2 18 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 FEB PY 2011 VL 17 IS 6 BP 631 EP 639 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768PI UT WOS:000290947000010 PM 21391904 ER PT J AU Schelonka, RL Maheshwari, A Carlo, WA Taylor, S Hansen, NI Schendel, DE Thorsen, P Skogstrand, K Hougaard, DM Higgins, RD AF Schelonka, Robert L. Maheshwari, Akhil Carlo, Waldemar A. Taylor, Sarah Hansen, Nellie I. Schendel, Diana E. Thorsen, Poul Skogstrand, Kristin Hougaard, David M. Higgins, Rosemary D. CA NICHD Neonatal Res Network TI T cell cytokines and the risk of blood stream infection in extremely low birth weight infants SO CYTOKINE LA English DT Article DE Cytokine; Infection; Sepsis; Neonate ID ONSET NEONATAL SEPSIS; DIAGNOSTIC MARKERS; INTERLEUKIN-6; DIVERSITY; IMMUNITY; RECEPTOR; NETWORK; INNATE; HELPER AB Cytokines mediate the host immune response to infectious micro-organisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6, and IL-10) and inflammatory cytokines (Interferon-gamma [INF-gamma], tumor necrosis factor-beta [TNF-beta], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the five sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (p = 0.01), and higher levels of the regulatory cytokines, IL-6 (p = 0.01) and IL-10 (p < 0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Schelonka, Robert L.; Maheshwari, Akhil; Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Taylor, Sarah; Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Schendel, Diana E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Thorsen, Poul] Lillebaelt Hosp, Dept Obstet & Gynecol, Kolding, Denmark. [Skogstrand, Kristin; Hougaard, David M.] Statens Serum Inst, Dept Clin Biochem & Immunol, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Schelonka, RL (reprint author), Oregon Hlth & Sci Univ, Mail Code CDRCP,707 SW Gaines St, Portland, OR 97239 USA. EM schelonk@ohsu.edu OI Skogstrand, Kristin/0000-0002-0026-3711 FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Centers for Disease Control and Prevention [Y1-HD-5000-01] FX The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention (via an Interagency Agreement Y1-HD-5000-01) provided grant support for recruitment during 1999-2001 and data analysis for the Neonatal Research Network's Cytokines Study. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. NR 30 TC 21 Z9 22 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD FEB PY 2011 VL 53 IS 2 BP 249 EP 255 DI 10.1016/j.cyto.2010.11.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 720HX UT WOS:000287272700020 PM 21145756 ER PT J AU Roederer, M AF Roederer, Mario TI Interpretation of Cellular Proliferation Data: Avoid the Panglossian SO CYTOMETRY PART A LA English DT Editorial Material DE CFSE; mathematical modeling; precursor frequency; cell division ID LYMPHOCYTE-PROLIFERATION; DIVISION AB There are several statistics that may be calculated to characterize a cellular proliferation experiment. By far, the most commonly-reported statistic is the percent of cells in the final culture that have divided; however, this statistic has significant limitations. Other statistics provided by software modeling provide a much richer characterization of the biological response; however, their use also comes with caveats. Here, I discuss the practical application of these statistics, including their limitations and interdependencies, using hypothetical data. The goal of this perspective is to prevent the blind reliance or overly optimistic ("panglossian") interpretation of the statistics generated by software, so that researchers and reviewers have a more-informed basis for drawing conclusions from the data. Published 2011 Wiley-Liss, Inc.(dagger) C1 NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov NR 10 TC 40 Z9 40 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2011 VL 79A IS 2 BP 95 EP 101 DI 10.1002/cyto.a.21010 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 715SW UT WOS:000286908900003 PM 21265003 ER PT J AU Roederer, M Nozzi, JL Nason, MC AF Roederer, Mario Nozzi, Joshua L. Nason, Martha C. TI SPICE: Exploration and Analysis of Post-Cytometric Complex Multivariate Datasets SO CYTOMETRY PART A LA English DT Article DE immunophenotyping; data analysis; subsets; multivariate; polyfunctional ID T-CELL RESPONSES; FLOW-CYTOMETRY; HIV-1 INFECTION; REPLICATION; PROTECTION; CORRELATE; AVIDITY; DISEASE; QUALITY; FUTURE AB Polychromatic flow cytometry results in complex, multivariate datasets. To date, tools for the aggregate analysis of these datasets across multiple specimens grouped by different categorical variables, such as demographic information, have not been optimized. Often, the exploration of such datasets is accomplished by visualization of patterns with pie charts or bar charts, without easy access to statistical comparisons of measurements that comprise multiple components. Here we report on algorithms and a graphical interface we developed for these purposes. In particular, we discuss thresholding necessary for accurate representation of data in pie charts, the implications for display and comparison of normalized versus unnormalized data, and the effects of averaging when samples with significant background noise are present. Finally, we define a statistic for the nonparametric comparison of complex distributions to test for difference between groups of samples based on multi-component measurements. While originally developed to support the analysis of T cell functional profiles, these techniques are amenable to a broad range of datatypes. Published 2011 Wiley-Liss, Inc.(dagger) C1 [Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nozzi, Joshua L.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. [Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov FU NIAID; NIH FX Grant sponsors: NIAID, NIH NR 25 TC 297 Z9 297 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2011 VL 79A IS 2 BP 167 EP 174 DI 10.1002/cyto.a.21015 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 715SW UT WOS:000286908900011 PM 21265010 ER PT J AU Kim, L Brzostowski, J Majithia, A Lee, NS McMains, V Kimmel, AR AF Kim, Leung Brzostowski, Joseph Majithia, Amit Lee, Nam-Sihk McMains, Vanessa Kimmel, Alan R. TI Combinatorial cell-specific regulation of GSK3 directs cell differentiation and polarity in Dictyostelium SO DEVELOPMENT LA English DT Article DE cAMP; Cell polarity; Receptors; Protein phosphorylation; Chemotaxis; Dictyostelium ID GLYCOGEN-SYNTHASE KINASE-3; WNT SIGNAL-TRANSDUCTION; NEURONAL POLARITY; TERMINAL DIFFERENTIATION; FATE SPECIFICATION; MITOTIC SPINDLE; BETA-CATENIN; C. ELEGANS; DISCOIDEUM; PATHWAY AB In Dictyostelium, the interaction of secreted cAMP with specific cell surface receptors regulates the activation/de-activation of GSK3, which mediates developmental cell patterning. In addition, Dictyostelium cells polarize in response to extracellular cAMP, although a potential role for GSK3 in this pathway has not been investigated. Previously, we had shown that ZAK1 was an activating tyrosine kinase for GSK3 function in Dictyostelium and we now identify ZAK2 as the other tyrosine kinase in the cAMP-activation pathway for GSK3; no additional family members exist. We also now show that tyrosine phosphorylation/activation of GSK3 by ZAK2 and ZAK1 separately regulate GSK3 in distinct differentiated cell populations, and that ZAK2 acts in both autonomous and non-autonomous pathways to regulate these cell-type differentiations. Finally, we demonstrate that efficient polarization of Dictyostelium towards cAMP depends on ZAK1-mediated tyrosine phosphorylation of GSK3. Combinatorial regulation of GSK3 by ZAK kinases in Dictyostelium guides cell polarity, directional cell migration and cell differentiation, pathways that extend the complexity of GSK3 signaling throughout the development of Dictyostelium. C1 [Kim, Leung; Brzostowski, Joseph; Majithia, Amit; McMains, Vanessa; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Kim, Leung; Lee, Nam-Sihk] Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Ms J. Liu deserves appreciation for superb technical support. We thank Dr A. Kuspa for advice on prespore purification and Dr B. Raaka for use of the FACS. We are indebted to Drs Shaulsky, Kuspa and Zupan, and their co-workers for their generosity in providing RNA-seq data prior to publication (Parikh et al., 2010) and access to dictyExpress (Rot et al., 2009) (http://www.ailab.si/dictyexpress/). Finally, we are grateful for discussions with Drs T. Khruana and D. Rosel. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. A. M. is a Howard Hughes Medical Institute-National Institutes of Health Research Scholar. Deposited in PMC for release after 6 months. NR 57 TC 8 Z9 12 U1 3 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB 1 PY 2011 VL 138 IS 3 BP 421 EP 430 DI 10.1242/dev.055335 PG 10 WC Developmental Biology SC Developmental Biology GA 702CS UT WOS:000285872800004 PM 21205787 ER PT J AU Song, JK Giniger, E AF Song, Jeong K. Giniger, Edward TI Noncanonical Notch Function in Motor Axon Guidance Is Mediated by Rac GTPase and the GEF1 Domain of Trio SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Notch; Trio; Rac; Abl; axon guidance; Drosophila ID ABL TYROSINE KINASE; NUCLEOTIDE-EXCHANGE FACTORS; ACTIN STRESS FIBERS; RHO FAMILY GTPASES; GENETIC INTERACTIONS; C. ELEGANS; DROSOPHILA; RECEPTOR; PROTEIN; MIDLINE AB The receptor Notch interacts with the Abl tyrosine kinase signaling pathway to control axon growth and guidance in Drosophila motor neurons. In part, this is mediated by binding to Trio, a guanine nucleotide exchange factor (GEF) for Rho GTPases. We show here that one of the two GEF domains of Trio, the Rac-specific GEF1, is essential for Trio-dependent motor axon guidance and for the genetic suppression of Notch function in motor axon patterning, but the Rho-specific GEF2 domain is not. Consistent with this, we show that Rac, and not Rho1 or Cdc42, interacts genetically with Notch in a manner indistinguishable from that of bona fide Abl signaling components. We infer, therefore, that Rac is a key component of Abl signaling in Drosophila motor axons, and specifically that it is the crucial Rho GTPase in "noncanonical" Notch/Abl signaling. Developmental Dynamics 240:324-332, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Song, Jeong K.; Giniger, Edward] NINDS, Axon Guidance & Neural Connect Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Giniger, E (reprint author), Room 1016,37 Convent Dr, Bethesda, MD 20892 USA. EM ginigere@ninds.nih.gov RI Giniger, Edward/C-1764-2015 OI Giniger, Edward/0000-0002-8340-6158 FU NIH [NINDS: Z01NS003013] FX We thank K. Zinn, L. Belluscio and the members of the Giniger Lab for comments on the manuscript, D. Crowner and Z. Liu for technical assistance, the Bloomington Drosophila Stock Center for fly lines, and Developmental Studies Hybridoma Bank for antibody reagents. E.G. was funded in part by the Intramural Research Program of the NIH (NINDS: Z01NS003013). NR 51 TC 20 Z9 20 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2011 VL 240 IS 2 BP 324 EP 332 DI 10.1002/dvdy.22525 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 717VQ UT WOS:000287075900003 PM 21246649 ER PT J AU Kang, L Ayala, JE Lee-Young, RS Zhang, ZH James, FD Neufer, PD Pozzi, A Zutter, MM Wasserman, DH AF Kang, Li Ayala, Julio E. Lee-Young, Robert S. Zhang, Zhonghua James, Freyja D. Neufer, P. Darrell Pozzi, Ambra Zutter, Mary M. Wasserman, David H. TI Diet-Induced Muscle Insulin Resistance Is Associated With Extracellular Matrix Remodeling and Interaction With Integrin alpha(2)beta(1) in Mice SO DIABETES LA English DT Article ID TUMOR-NECROSIS-FACTOR; SKELETAL-MUSCLE; GENE-EXPRESSION; INDIVIDUAL TISSUES; COLLAGEN GENE; ACTIVATION; ALPHA-2-BETA-1; ALPHA-1-BETA-1; MECHANISM; RECEPTOR AB OBJECTIVE-The hypothesis that high-fat (HF) feeding causes skeletal muscle extracellular matrix (ECM) remodeling in C57BL/6J mice and that this remodeling contributes to diet-induced muscle insulin resistance (IR) through the collagen receptor integrin alpha(2)beta(1) was tested. RESEARCH DESIGN AND METHODS-The association between IR and ECM remodeling was studied in mice fed chow or HF diet. Specific genetic and pharmacological murine models were used to study effects of HF feeding on ECM in the absence of IR. The role of ECM-integrin interaction in IR was studied using hyperinsulinemic-euglycemic clamps on integrin alpha(2)beta(1)-null (itga2(-/-)), integrin alpha(1)beta(1)-null (itga1(-/-)), and wild-type littermate mice fed chow or HF. Integrin alpha(2)beta(1) and integrin alpha(1)beta(1) signaling pathways have opposing actions. RESULTS-HF-fed mice had IR and increased muscle collagen (Col) III and ColIV protein; the former was associated with increased transcript, whereas the latter was associated with reduced matrix metalloproteinase 9 activity. Rescue of muscle IR by genetic muscle-specific mitochondria-targeted catalase overexpression or by the phosphodiesterase 5a inhibitor, sildenafil, reversed HF feeding effects on ECM remodeling and increased muscle vascularity. Collagen remained elevated in HF-fed itga2(-/-) mice. Nevertheless, muscle insulin action and vascularity were increased. Muscle IR in HF-fed itga1(-/-) mice was unchanged. Insulin sensitivity in chow-fed itga1(-/-) and itga2(-/-) mice was not different from wild-type littermates. CONCLUSIONS-ECM collagen expansion is tightly associated with muscle IR. Studies with itga2(-/-) mice provide mechanistic insight for this association by showing that the link between muscle IR and increased collagen can be uncoupled by the absence of collagen-integrin alpha(2)beta(1) interaction. Diabetes 60:416-426, 2011 C1 [Kang, Li; Ayala, Julio E.; Lee-Young, Robert S.; James, Freyja D.; Wasserman, David H.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Ayala, Julio E.; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. [Zhang, Zhonghua; Zutter, Mary M.] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA. [Neufer, P. Darrell] E Carolina Univ, Dept Exercise & Sport Sci & Physiol, Greenville, NC USA. [Pozzi, Ambra] Vanderbilt Univ, Div Nephrol, Nashville, TN 37232 USA. RP Kang, L (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. EM li.kang@vanderbilt.edu FU National Institutes of Health [DK-54902, DK-59637] FX This work was supported by National Institutes of Health Grants DK-54902 and DK-59637 (Mouse Metabolic Phenotyping Center). NR 41 TC 40 Z9 40 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2011 VL 60 IS 2 BP 416 EP 426 DI 10.2337/db10-1116 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 719AR UT WOS:000287172100009 PM 21270253 ER PT J AU Yanovski, JA Krakoff, J Salaita, CG McDuffie, JR Kozlosky, M Sebring, NG Reynolds, JC Brady, SM Calis, KA AF Yanovski, Jack A. Krakoff, Jonathan Salaita, Christine G. McDuffie, Jennifer R. Kozlosky, Merel Sebring, Nancy G. Reynolds, James C. Brady, Sheila M. Calis, Karim A. TI Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children A Randomized Clinical Trial SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; POLYCYSTIC-OVARY-SYNDROME; LIFE-STYLE INTERVENTION; FAMILY-BASED TREATMENT; METABOLIC SYNDROME; CHILDHOOD OBESITY; PEDIATRIC OBESITY; GLUCOSE-TOLERANCE; RISK-FACTORS; MASS INDEX AB OBJECTIVE-Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant. RESEARCH DESIGN AND METHODS-This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 +/- 6.6 kg/m(2)) insulin-resistant children aged 6-12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program. RESULTS-Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference -1.09 kg/m(2), CI -1.87 to -0.31, P = 0.006), body weight (difference -3.38 kg, CI -5.2 to -1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups -0.07, CI -0.12 to -0.01, P = 0.02), and fat mass (difference -1.40 kg, CI -2.74 to -0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score furl her. CONCLUSIONS-Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program. Diabetes 60:477-485, 2011 C1 [Yanovski, Jack A.; McDuffie, Jennifer R.; Brady, Sheila M.; Calis, Karim A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Krakoff, Jonathan] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Phoenix Epidemiol & Clin Res Branch, Bethesda, MD USA. [Salaita, Christine G.; Kozlosky, Merel; Sebring, Nancy G.] NIH, Dept Nutr, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Diagnost Radiol & Imaging Sci, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Calis, Karim A.] NIH, Dept Pharm, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Eunice Kennedy Shriver NICHD, NIH [Z01-HD-000641]; NCMHD, NIH; NIDDK; Obecure FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver NICHD, NIH (Grant Z01-HD-000641), and NCMHD, NIH (both to J.A.Y.), and in part by NIDDK (J.K.).; J.A.Y. received a grant from Obecure and has a material transfer agreement with Roche for support of other obesity-medication treatment studies. No other potential conflicts of interest relevant to this article were reported. NR 51 TC 57 Z9 58 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2011 VL 60 IS 2 BP 477 EP 485 DI 10.2337/db10-1185 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 719AR UT WOS:000287172100016 PM 21228310 ER PT J AU Palmer, ND Hester, JM An, SS Adeyemo, A Rotimi, C Langefeld, CD Freedman, BI Ng, MCY Bowden, DW AF Palmer, Nicholette D. Hester, Jessica M. An, S. Sandy Adeyemo, Adebowale Rotimi, Charles Langefeld, Carl D. Freedman, Barry I. Ng, Maggie C. Y. Bowden, Donald W. TI Resequencing and Analysis of Variation in the TCF7L2 Gene in African Americans Suggests That SNP rs7903146 Is the Causal Diabetes Susceptibility Variant SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; STAGE RENAL-DISEASE; COMMON VARIANTS; RISK LOCI; TYPE-2; POPULATION; POLYMORPHISMS; REPLICATION; NEPHROPATHY; FAMILY AB OBJECTIVE-Variation in the transcription factor 7-like 2 (TCF7L2) locus is associated with type 2 diabetes across multiple ethnicities. The aim of this study was to elucidate which variant in TCF7L2 confers diabetes susceptibility in African Americans. RESEARCH DESIGN AND METHODS-Through the evaluation of tagging single nucleotide polymorphisms (SNPs), type 2 diabetes susceptibility was limited to a 4.3-kb interval, which contains the YRI (African) linkage disequilibrium (LD) block containing rs7903146. To better define the relationship between type 2 diabetes risk and genetic variation we resequenced this 4.3-kb region in 96 African American DNAs. Thirty-three novel and 13 known SNPs were identified: 20 with minor allele frequencies (MAF) >0.05 and 12 with MAF >0.10. These polymorphisms and the previously identified DG10S478 microsatellite were evaluated in African American type 2 diabetic cases (n = 1,033) and controls (n = 1,106). RESULTS-Variants identified from direct sequencing and databases were genotyped or imputed. Fifteen SNPs showed association with type 2 diabetes (P < 0.05) with rs7903146 being the most significant (P = 6.32 x 10(-6)). Results of imputation, haplotype, and conditional analysis of SNPs were consistent with rs7903146 being the trait-defining SNP. Analysis of the DG10S478 microsatellite, which is outside the 4.3-kb LD block, revealed consistent association of risk allele 8 with type 2 diabetes (odds ratio [OR] = 1.33; P = 0.022) as reported in European populations; however, allele 16 (MAF = 0.016 cases and 0.032 controls) was strongly associated with reduced risk (OR = 0.39; P = 5.02 x 10(-6)) in contrast with previous studies. CONCLUSIONS-In African Americans, these observations suggest that rs7903146 is the trait-defining polymorphism associated with type 2 diabetes risk. Collectively, these results support ethnic differences in type 2 diabetes associations. Diabetes 60:662-668, 2011 C1 [Palmer, Nicholette D.; An, S. Sandy; Bowden, Donald W.] Wake Forest Univ, Dept Biochem, Winston Salem, NC 27109 USA. [Palmer, Nicholette D.; Hester, Jessica M.; An, S. Sandy; Ng, Maggie C. Y.; Bowden, Donald W.] Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA. [Palmer, Nicholette D.; Hester, Jessica M.; An, S. Sandy; Ng, Maggie C. Y.; Bowden, Donald W.] Wake Forest Univ, Ctr Diabet Res, Winston Salem, NC 27109 USA. [Hester, Jessica M.] Wake Forest Univ, Program Mol Genet & Genom, Winston Salem, NC 27109 USA. [Adeyemo, Adebowale; Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Freedman, Barry I.] Wake Forest Univ, Dept Internal Med, Nephrol Sect, Winston Salem, NC 27109 USA. [Ng, Maggie C. Y.] Wake Forest Univ, Dept Pediat, Winston Salem, NC 27109 USA. RP Bowden, DW (reprint author), Wake Forest Univ, Dept Biochem, Winston Salem, NC 27109 USA. EM dbowden@wfubmc.edu OI Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [K99-DK081350, R01-DK066358, R01-DK053591, R01-HL56266, R01-DK070941]; General Clinical Research Center of the Wake Forest University School of Medicine [M01-RR07122] FX This work was supported by National Institutes of Health grants K99-DK081350 (to N.D.P.), R01-DK066358 (to D.W.B.), R01-DK053591 (to D.W.B.), R01-HL56266 (to B.I.F.), and R01-DK070941 (to B.I.F.), and in part by the General Clinical Research Center of the Wake Forest University School of Medicine Grant M01-RR07122. NR 34 TC 38 Z9 39 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2011 VL 60 IS 2 BP 662 EP 668 DI 10.2337/db10-0134 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 719AR UT WOS:000287172100037 PM 20980453 ER PT J AU Liu, JK Fox, CS Hickson, DA May, WL Ding, JZ Carr, JJ Taylor, HA AF Liu, Jiankang Fox, Caroline S. Hickson, DeMarc A. May, Warren L. Ding, Jingzhong Carr, J. Jeffery Taylor, Herman A. TI Pericardial Fat and Echocardiographic Measures of Cardiac Abnormalities The Jackson Heart Study SO DIABETES CARE LA English DT Article ID EPICARDIAL ADIPOSE-TISSUE; LEFT-VENTRICULAR HYPERTROPHY; DISEASE RISK-FACTORS; OBESITY; ATHEROSCLEROSIS; DYSFUNCTION; POPULATION; ASSOCIATION; GUIDELINES; COMMUNITY AB OBJECTIVE-Pericardial adipose tissue (PAT), a regional fat depot adjacent to the myocardium, may mediate the complex relation between obesity and cardiac left ventricular (LV) abnormalities. We sought to evaluate the association of PAT with echocardiographic measures of LV abnormalities in the Jackson Heart Study (JHS). RESEARCH DESIGN AND METHODS-A total of 1,414 African Americans (35% men; mean age 58 years) from the JHS underwent computed tomographic assessment of PAT and abdominal visceral adipose tissue (VAT) from 2007 to 2009 and echocardiography examination between 2000 and 2004. Echocardiographic measures of left atrial (LA) internal diameter, LV mass, LV ejection fraction (LVEF), and E-wave velocity-to-A-wave velocity ratio (E/A ratio) were examined in relation to PAT, VAT, BMI, and waist circumference (WC). RESULTS-All adiposity measures were positively correlated with LA diameter and LV mass and negatively correlated with E/A ratio (P = 0.02 to 0.0001) and were not with LVEF (P = 0.36-0.61). In women, per 1-SD increment of PAT, we observed association with higher LV mass (9.0 +/- 1.7 gm, P = 0.0001) and LA diameter (1.0 +/- 0.1 mm, P = 0.0001). However, the magnitude of the association between PAT and cardiac measures was similar compared with VAT (P = 0.65 [LV mass]; P = 0.26 [LA diameter]) and was smallercompared with BM I (P = 0.002 [LV mass]; P = 0.01 [LA diameter]) and WC (P = 0.009 [LA diameter]). CONCLUSIONS-PAT is correlated with echocardiographic measures of cardiac LV abnormalities, but the association is not stronger than other adiposity measures. C1 [Liu, Jiankang; Hickson, DeMarc A.; May, Warren L.; Taylor, Herman A.] Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, NHLBI,Framingham Heart Study, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Ding, Jingzhong] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Carr, J. Jeffery] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA. RP Liu, JK (reprint author), Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA. EM jliu@umc.edu RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95170, N01-HC-95171, N01-C-95172]; National Center on Minority Health and Health Disparities (NCMHD) FX The JHS is supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Center on Minority Health and Health Disparities (NCMHD). Funding for H.A.T. was provided under contracts N01-HC-95170, N01-HC-95171, and N01-C-95172 from the NHLBI and the NCMHD. NR 25 TC 15 Z9 15 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2011 VL 34 IS 2 BP 341 EP 346 DI 10.2337/dc10-1312 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 722LO UT WOS:000287433900018 PM 21228247 ER PT J AU Wang, WY Lee, ET Howard, BV Fabsitz, RR Devereux, RB Welty, TK AF Wang, Wenyu Lee, Elisa T. Howard, Barbara V. Fabsitz, Richard R. Devereux, Richard B. Welty, Thomas K. TI Fasting Plasma Glucose and Hemoglobin A(1c) in Identifying and Predicting Diabetes The Strong Heart Study SO DIABETES CARE LA English DT Article ID OPERATING CHARACTERISTIC CURVES; CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS; HIGH-RISK; METABOLIC SYNDROME; PREVALENCE; MELLITUS; AREAS; POPULATION; TOLERANCE AB OBJECTIVE-To compare fasting plasma glucose (FPG) and HbA(1c) in identifying and predicting type 2 diabetes in a population with high rates of diabetes. RESEARCH DESIGN AND METHODS-Diabetes was defined as an FPG level >= 126 mg/dL or an HbA(1c) level >= 6.5%. Data collected from the baseline and second exams (1989-1995) of the Strong Heart Study were used. RESULTS-For cases of diabetes identified by FPG >= 126 mg/dL, using HbA(1c) >= 6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA(1c) >= 6.5%, using FPG >= 126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA(1c) levels were common significant risk factors for incident diabetes defined by either FPG or HbA(1c); triglyceride levels were significant for diabetes defined by HbA(1c) alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA(1c) in diabetes prediction identified more people at risk than using either measure alone. CONCLUSIONS-Among undiagnosed participants, using HbA(1c) alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA(1c) alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion. C1 [Wang, Wenyu; Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. [Howard, Barbara V.] MedStar Hlth Res Inst, Washington, DC USA. [Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA. [Welty, Thomas K.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. RP Wang, WY (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. EM wenyu-wang@ouhsc.edu FU National Heart, Lung, and Blood Institute [UO1 HL-41642, UO1 HL-41652, UO1 HL-41654, U01-HL65521]; American Indian tribes/communities; Indian Health Service FX This study was supported by grants UO1 HL-41642, UO1 HL-41652, UO1 HL-41654, and U01-HL65521 from the National Heart, Lung, and Blood Institute.; The authors express their appreciation to the 13 participating American Indian tribes/communities, the Indian Health Service, and the participants for their support and assistance. NR 25 TC 27 Z9 27 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2011 VL 34 IS 2 BP 363 EP 368 DI 10.2337/dc10-1680 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 722LO UT WOS:000287433900022 PM 21270194 ER PT J AU James, C Bullard, KM Rolka, DB Geiss, LS Williams, DE Cowie, CC Albright, A Gregg, EW AF James, Cherie Bullard, Kai McKeever Rolka, Deborah B. Geiss, Linda S. Williams, Desmond E. Cowie, Catherine C. Albright, Ann Gregg, Edward W. TI Implications of Alternative Definitions of Prediabetes for Prevalence in US Adults SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INCIDENT CARDIOVASCULAR EVENTS; DIABETES PREVENTION PROGRAM; LIFE-STYLE; GLYCATED HEMOGLOBIN; FASTING GLYCEMIA; RISK; DIAGNOSIS; MELLITUS; IMPACT AB OBJECTIVE-To compare the prevalence of prediabetes using A1C, fasting plasma glucose (FPG), and oral glucose tolerance test (OGTT) criteria, and to examine the degree of agreement between the measures. RESEARCH DESIGN AND METHODS-We used the 2005-2008 National Health and Nutrition Examination Surveys to classify 3,627 adults aged >= 18 years without diabetes according to their prediabetes status using A1C, FPG, and OGTT. We compared the prevalence of prediabetes according to different measures and used conditional probabilities to examine agreement between measures. RESULTS-In 2005-2008, the crude prevalence of prediabetes in adults >= 18 aged years was 14.2% for A1C 5.7-6.4% (A1C5.7), 26.2% for FPG 100-125 mg/dL (IFG100), 7.0% for FPG 110-125 mg/dL (IFG110), and 13.7% for OGTT 140-199 mg/dL (IGT). Prediabetes prevalence varied by age, sex, and race/ethnicity, and there was considerable discordance between measures of prediabetes. Among those with IGT, 58.2, 23.4, and 32.3% had IFG100, IFG110, and A1C5.7, respectively, and 67.1% had the combination of either A1C5.7 or IFG100. CONCLUSIONS-The prevalence of prediabetes varied by the indicator used to measure risk; there was considerable discordance between indicators and the characteristics of individuals with prediabetes. Programs to prevent diabetes may need to consider issues of equity, resources, need, and efficiency in targeting their efforts. C1 [Bullard, Kai McKeever; Rolka, Deborah B.; Geiss, Linda S.; Williams, Desmond E.; Albright, Ann; Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA. [James, Cherie] RTI Int, Atlanta Reg Off, Atlanta, GA USA. [Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD USA. RP Geiss, LS (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30333 USA. EM lgeiss@cdc.gov NR 24 TC 49 Z9 50 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2011 VL 34 IS 2 BP 387 EP 391 DI 10.2337/dc10-1314 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 722LO UT WOS:000287433900026 PM 21270196 ER PT J AU Bankoski, A Harris, TB McClain, JJ Brychta, RJ Caserotti, P Chen, KY Berrigan, D Troiano, RP Koster, A AF Bankoski, Andrea Harris, Tamara B. McClain, James J. Brychta, Robert J. Caserotti, Paolo Chen, Kong Y. Berrigan, David Troiano, Richard P. Koster, Annemarie TI Sedentary Activity Associated With Metabolic Syndrome Independent of Physical Activity SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR-DISEASE; UNITED-STATES; TIME; RISK; ADULTS; INDIVIDUALS; BEHAVIOR; OBESITY AB OBJECTIVE-This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults. RESEARCH DESIGN AND METHODS-Data were from 1,367 men and women, aged a >= 60 years who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES). Sedentary time during waking hours was measured by an accelerometer (<100 counts per minute). A sedentary bout was defined as a period of time >5 mm. A sedentary break was defined as an interruption in sedentary time (>= 100 counts per minute). Metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III criteria. RESULTS-On average, people spent 9.5 h (65% of wear time) as sedentary. Compared with people without metabolic syndrome, people with metabolic syndrome spent a greater percentage of time as sedentary (67.3 vs. 62.2%), had longer average sedentary bouts (17.7 vs. 16.7 min), had lower intensity during sedentary time (14.8 vs. 15.8 average counts per minute), and had fewer sedentary breaks (82.3 vs. 86.7), adjusted for age and sex (all P < 0.01). A higher percentage of time sedentary and fewer sedentary breaks were associated with a significantly greater likelihood of metabolic syndrome after adjustment for age, sex, ethnicity, education, alcohol consumption, smoking, BMI, diabetes, heart disease, and physical activity. The association between intensity during sedentary time and metabolic syndrome was borderline significant. CONCLUSIONS-The proportion of sedentary time was strongly related to metabolic risk, independent of physical activity. Current results suggest older people may benefit from reducing total sedentary time and avoiding prolonged periods of sedentary time by increasing the number of breaks during sedentary time. C1 [Bankoski, Andrea; Harris, Tamara B.; Caserotti, Paolo; Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bankoski, Andrea] George Mason Univ, Global & Community Hlth Dept, Fairfax, VA 22030 USA. [McClain, James J.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Brychta, Robert J.; Chen, Kong Y.] NIDDK, Bethesda, MD USA. [Koster, Annemarie] Maastricht Univ Med Ctr, Dept Internal Med, Sch Publ Hlth & Primary Care, Maastricht, Netherlands. RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM kostera@mail.nih.gov RI Koster, Annemarie/E-7438-2010; OI Troiano, Richard/0000-0002-6807-989X; Chen, Kong/0000-0002-0306-1904 FU National Institutes of Health, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 24 TC 150 Z9 155 U1 2 U2 32 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2011 VL 34 IS 2 BP 497 EP 503 DI 10.2337/dc10-0987 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 722LO UT WOS:000287433900047 PM 21270206 ER PT J AU Sacks, DB AF Sacks, David B. TI A1C Versus Glucose Testing: A Comparison SO DIABETES CARE LA English DT Review ID NUTRITION EXAMINATION SURVEY; IRON-DEFICIENCY ANEMIA; 3RD NATIONAL-HEALTH; DIABETES-MELLITUS; HEMOGLOBIN A(1C); BLOOD-GLUCOSE; BIOLOGICAL VARIATION; GLYCATED HEMOGLOBIN; TOLERANCE TESTS; HEPARINIZED PLASMA C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 NR 60 TC 115 Z9 119 U1 2 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2011 VL 34 IS 2 BP 518 EP 523 DI 10.2337/dc10-1546 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 722LO UT WOS:000287433900051 PM 21270207 ER PT J AU Gong, Q Gregg, EW Wang, J An, Y Zhang, P Yang, W Li, H Li, H Jiang, Y Shuai, Y Zhang, B Zhang, J Gerzoff, RB Roglic, G Hu, Y Li, G Bennett, PH AF Gong, Q. Gregg, E. W. Wang, J. An, Y. Zhang, P. Yang, W. Li, H. Li, H. Jiang, Y. Shuai, Y. Zhang, B. Zhang, J. Gerzoff, R. B. Roglic, G. Hu, Y. Li, G. Bennett, P. H. TI Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study SO DIABETOLOGIA LA English DT Article DE Diabetic retinopathy; Impaired glucose tolerance; Lifestyle intervention; Nephropathy; Neuropathy ID PIMA-INDIANS; VASCULAR-DISEASE; FOLLOW-UP; PREVALENCE; RETINOPATHY; MORTALITY; MELLITUS; PROGRAM; AGE; IGT AB We determined the effects of 6 years of lifestyle intervention in persons with impaired glucose tolerance (IGT) on the development of retinopathy, nephropathy and neuropathy over a 20 year period. In 1986, 577 adults with IGT from 33 clinics in Da Qing, China were randomly assigned by clinic to a control group or one of three lifestyle intervention groups (diet, exercise, and diet plus exercise). Active intervention was carried out from 1986 to 1992. In 2006 we conducted a 20 year follow-up study of the original participants to compare the incidence of microvascular complications in the combined intervention group vs the control group. Follow-up information was obtained on 542 (94%) of the 577 original participants. The cumulative incidence of severe retinopathy was 9.2% in the combined intervention group and 16.2% in the control group (p = 0.03, log-rank test). After adjusting for clinic and age, the incidence of severe retinopathy was 47% lower in the intervention group than the control group (hazard rate ratio 0.53, 95% CI 0.29-0.99, p = 0.048). No significant differences were found in the incidence of severe nephropathy (hazard rate ratio 1.05, 95% CI 0.16-7.05, intervention vs control, p = 0.96) or in the prevalence of neuropathy (8.6% vs 9.1%, p = 0.89) among the 20 year survivors. Lifestyle intervention for 6 years in IGT was associated with a 47% reduction in the incidence of severe, vision-threatening retinopathy over a 20 year interval, primarily due to the reduced incidence of diabetes in the intervention group. However, similar benefits were not seen for nephropathy or neuropathy. C1 [Gong, Q.; An, Y.; Yang, W.; Shuai, Y.; Zhang, B.; Li, G.] China Japan Friendship Hosp, Dept Endocrinol, Beijing 100029, Peoples R China. [Gregg, E. W.; Zhang, P.; Gerzoff, R. B.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Wang, J.; Jiang, Y.; Zhang, J.; Hu, Y.] Da Qing First Hosp, Dept Cardiol, Da Qing, Peoples R China. [Roglic, G.] World Hlth Org, Dept Chron Dis & Hlth Promot, Geneva, Switzerland. [Gong, Q.; Bennett, P. H.] NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA. RP Li, G (reprint author), China Japan Friendship Hosp, Dept Endocrinol, Beijing 100029, Peoples R China. EM guangwei_li@medmail.com.cn FU CDC/WHO [U58/CCU424123-01-02]; China-Japan Friendship Hospital; Da Qing First Hospital; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank the participants in the original Da Qing Diabetes Prevention Study and the Da Qing Diabetes Prevention Outcome Study. We thank L. Zhang and H. Zhang of the China-Japan Friendship Hospital for grading the fundus photographs. We thank M. M. Engelgau for assistance in acquiring funding and B.V. Howard for help in the design of the original study. We also acknowledge L. Kong, the China Ministry of Health, the leadership of the China-Japan Friendship Hospital, Da Qing First Hospital, the Da Qing City Health Bureau and the Beijing and West Pacific Regional Office of WHO for their general support. We thank W.C. Knowler, C.C. Mason, R.G. Nelson and S. Kobes of the Diabetes Epidemiology and Clinical Research Section, NIDDK, for statistical assistance. Special thanks are due to the late Professor X. Pan as this study would not have been possible without his leadership in the original Da Qing Diabetes Prevention Study. This study was supported by CDC/WHO Cooperative Agreement No. U58/CCU424123-01-02, China-Japan Friendship Hospital and Da Qing First Hospital. Q. Gong received a Mentor-based Postdoctoral Research Fellowship from the American Diabetes Association and partial support from Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The sponsors had no role in any aspect of the study design, in the collection, analysis and interpretation of data, or in the development of the manuscript. NR 27 TC 92 Z9 100 U1 1 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2011 VL 54 IS 2 BP 300 EP 307 DI 10.1007/s00125-010-1948-9 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703SO UT WOS:000286001800014 PM 21046360 ER PT J AU Jiang, XL Gonzalez, FJ Yu, AM AF Jiang, Xi-Ling Gonzalez, Frank J. Yu, Ai-Ming TI Drug-metabolizing enzyme, transporter, and nuclear receptor genetically modified mouse models SO DRUG METABOLISM REVIEWS LA English DT Review DE Transgenic; knockout; humanized; drug metabolism; pharmacokinetics; drug interaction; toxicity; cancer ID CANCER RESISTANCE PROTEIN; NADPH-CYTOCHROME-P450 REDUCTASE GENE; HEPATIC CYTOCHROME-P450 REDUCTASE; UDP-GLUCURONOSYLTRANSFERASE-1 UGT1 LOCUS; LIVER-SPECIFIC EXPRESSION; ORGANIC ANION TRANSPORT; MDR1A P-GLYCOPROTEIN; BLOOD-BRAIN-BARRIER; TRANSGENIC MICE; TARGETED DISRUPTION AB Determining the in vivo significance of a specific enzyme, transporter, or xenobiotic receptor in drug metabolism and pharmacokinetics may be hampered by gene multiplicity and complexity, levels of expression, and interaction between various components involved. The development of knockout (loss-of-function) and transgenic (gain-of-function) mouse models opens the door to the improved understanding of gene function in a whole-body system. There is also growing interest in the development of humanized mice to overcome species differences in drug metabolism and disposition. This review, therefore, aims to summarize and discuss some successful examples of drug-metabolizing enzyme, transporter, and nuclear-receptor genetically modified mouse models. These genetically modified mouse models have been proven as invaluable models for understanding in vivo function of drug-metabolizing enzymes, transporters, and xenobiotic receptors in drug metabolism and transport, as well as predicting potential drug-drug interaction and toxicity in humans. Nevertheless, concerns remain about interpretation of data obtained from such genetically modified mouse models, in which the expression of related genes is altered significantly. C1 [Yu, Ai-Ming] SUNY Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Yu, AM (reprint author), SUNY Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, 541 Cooke Hall, Buffalo, NY 14260 USA. EM aimingyu@buffalo.edu RI Jiang, Xiling/E-9197-2012 FU National Institute On Drug Abuse, National Institutes of Health (NIH; Bethesda, Maryland, USA [R01DA021172]; Pfizer (New York, New York, USA) FX AMY wants to thank the support (award number R01DA021172) from the National Institute On Drug Abuse, National Institutes of Health (NIH; Bethesda, Maryland, USA). XLJ is supported by a Pfizer (New York, New York, USA) fellowship. NR 139 TC 17 Z9 17 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD FEB PY 2011 VL 43 IS 1 BP 27 EP 40 DI 10.3109/03602532.2010.512294 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 734PO UT WOS:000288348000002 PM 20854191 ER PT J AU Kuhar, DT Henderson, DK AF Kuhar, David T. Henderson, David K. TI Pandemic (H1N1) 2009 and HIV Co-infection SO EMERGING INFECTIOUS DISEASES LA English DT Letter C1 [Kuhar, David T.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Henderson, David K.] NIH, Bethesda, MD 20892 USA. RP Kuhar, DT (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop A31, Atlanta, GA 30333 USA. EM dkuhar@cdc.gov NR 4 TC 0 Z9 0 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2011 VL 17 IS 2 BP 328 EP 328 DI 10.3201/eid1702.101775 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 722MM UT WOS:000287436400045 PM 21291627 ER PT J AU Eisenhofer, G Pacak, K Huynh, TT Qin, N Bratslavsky, G Linehan, WM Mannelli, M Friberg, P Grebe, SK Timmers, HJ Bornstein, SR Lenders, JWM AF Eisenhofer, Graeme Pacak, Karel Thanh-Truc Huynh Qin, Nan Bratslavsky, Gennady Linehan, W. Marston Mannelli, Massimo Friberg, Peter Grebe, Stefan K. Timmers, Henri J. Bornstein, Stefan R. Lenders, Jacques W. M. TI Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma SO ENDOCRINE-RELATED CANCER LA English DT Article AB Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with PPGLs and 846 subjects without PPGLs examined how catecholamine metabolomic profiles are impacted by hereditary background and relate to variable hormone secretion. Catecholamine secretion was assessed in a subgroup of 156 patients from whom tumour tissue was available for measurements of catecholamine contents. Among all analytes, the free catecholamine O-methylated metabolites measured in plasma showed the largest tumour-related increases relative to the reference group. Patients with tumours due to multiple endocrine neoplasia type 2 and neurofibromatosis type 1 (NF1) showed similar catecholamine metabolite and secretory profiles to patients with adrenaline-producing tumours and no evident hereditary background. Tumours from these three patient groups contained higher contents of catecholamines, but secreted the hormones at lower rates than tumours that did not contain appreciable adrenaline, the latter including PPGLs due to von Hippel-Lindau (VHL) and succinate dehydrogenase (SDH) gene mutations. Large increases of plasma dopamine and its metabolites additionally characterised patients with PPGLs due to the latter mutations, whereas patients with NF1 were characterised by large increases in plasma dihydroxyphenylglycol and dihydroxyphenylacetic acid, the deaminated metabolites of noradrenaline and dopamine. This analysis establishes the utility of comprehensive catecholamine metabolite profiling for characterising the distinct and highly diverse catecholamine metabolomic and secretory phenotypes among different groups of patients with PPGLs. The data further suggest developmental origins of PPGLs from different populations of chromaffin cell progenitors. C1 [Eisenhofer, Graeme; Qin, Nan] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Eisenhofer, Graeme; Bornstein, Stefan R.; Lenders, Jacques W. M.] Univ Dresden, Dept Med, D-01307 Dresden, Germany. [Pacak, Karel; Thanh-Truc Huynh] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. [Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, I-50139 Florence, Italy. [Friberg, Peter] Univ Gothenburg, Sahlgrenska Acad & Univ Hosp, Dept Clin Physiol, SE-41345 Gothenburg, Sweden. [Grebe, Stefan K.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Timmers, Henri J.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 GA Nijmegen, Netherlands. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands. RP Eisenhofer, G (reprint author), Univ Dresden, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM graeme.eisenhofer@uniklinikum-dresden.de RI Lenders, J.W.M./L-4487-2015; OI Mannelli, Massimo/0000-0002-8001-9857 FU Deutsche Forschungsgesellschaft (DFG) [515/6-1]; Center for Regenerative Therapies Dresden; Dresden Tumour Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Center for Cancer Research, National Cancer Institute, at the National Institutes of Health FX This work was supported by the Deutsche Forschungsgesellschaft (DFG grant no: 515/6-1), the Center for Regenerative Therapies Dresden and the Dresden Tumour Center. Support from the intramural programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Center for Cancer Research, National Cancer Institute, at the National Institutes of Health, was not in the form of any specific grant. NR 45 TC 44 Z9 44 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD FEB PY 2011 VL 18 IS 1 BP 97 EP 111 DI 10.1677/ERC-10-0211 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA V30ED UT WOS:000208798400012 PM 21051559 ER PT J AU Martiniova, L Perera, SM Brouwers, FM Alesci, S Abu-Asab, M Marvelle, AF Kiesewetter, DO Thomasson, D Morris, JC Kvetnansky, R Tischler, AS Reynolds, JC Fojo, AT Pacak, K AF Martiniova, Lucia Perera, Shiromi M. Brouwers, Frederieke M. Alesci, Salvatore Abu-Asab, Mones Marvelle, Amanda F. Kiesewetter, Dale O. Thomasson, David Morris, John C. Kvetnansky, Richard Tischler, Arthur S. Reynolds, James C. Fojo, Antonio Tito Pacak, Karel TI Increased uptake of [I-123]meta-iodobenzylguanidine, [F-18]fluorodopamine, and [H-3]norepinephrine in mouse pheochromocytoma cells and tumors after treatment with the histone deacetylase inhibitors SO ENDOCRINE-RELATED CANCER LA English DT Article ID CHROMOBACTERIUM-VIOLACEUM NO-968; MALIGNANT PHEOCHROMOCYTOMA; I-131 METAIODOBENZYLGUANIDINE; METASTATIC PHEOCHROMOCYTOMA; THYROID-CANCER; PHASE-II; SIGNAL THERAPY; MURINE MODEL; DEPSIPEPTIDE; EXPRESSION AB [I-131]meta-iodobenzylguanidine ([I-131]MIBG) is the most commonly used treatment for metastatic pheochromocytoma and paraganglioma. It enters the chromaffin cells via the membrane norepinephrine transporter; however, its success has been modest. We studied the ability of histone deacetylase (HDAC) inhibitors to enhance [I-123]MIBG uptake by tumors in a mouse metastatic pheochromocytoma model. HDAC inhibitors are known to arrest growth, induce differentiation and apoptosis in various cancer cells, and further inhibit tumor growth. We report the in vitro and in vivo effects of two HDAC inhibitors, romidepsin and trichostatin A, on the uptake of [H-3]norepinephrine, [I-123]MIBG, and [F-18]fluorodopamine in a mouse model of metastatic pheochromocytoma. The effects of both inhibitors on norepinephrine transporter activity were assessed in mouse pheochromocytoma (MPC) cells by using the transporter-blocking agent desipramine and the vesicular-blocking agent reserpine. HDAC inhibitors increased [H-3] norepinephrine, [I-123]MIBG, and [F-18]fluorodopamine uptake through the norepinephrine transporter in MPC cells. In vivo, inhibitor treatment resulted in significantly increased uptake of [F-18]fluorodopamine positron emission tomography (PET) in pheochromocytoma liver metastases (19.1 +/- 3.2% injected dose per gram of tumor (%ID/g) compared to liver metastases in pretreatment scans 5.9 +/- 0.6%; P < 0.001). Biodistribution analysis after inhibitors treatment confirmed the PET results. The uptake of [I-123]MIBG was significantly increased in liver metastases 9.5 +/- 1.1% compared to 3.19 +/- 0.4% in untreated control liver metastases (P < 0.05). We found that HDAC inhibitors caused an increase in the amount of norepinephrine transporter expressed in tumors. HDAC inhibitors may enhance the therapeutic efficacy of [I-131]MIBG treatment in patients with advanced malignant pheochromocytoma and paraganglioma. Endocrine-Related Cancer (2011) 18 143-157 C1 [Martiniova, Lucia; Perera, Shiromi M.; Brouwers, Frederieke M.; Marvelle, Amanda F.; Pacak, Karel] NIH, E Kennedy Shriver Natl Inst Child Human & Dev, Sect Med Neuroendocrinol, Bethesda, MD 20892 USA. [Alesci, Salvatore] NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, Intramural Sci PRGMS, NIH, Bethesda, MD 20892 USA. [Thomasson, David] Warren Grant Magnuson Clin Ctr, Lab Diagnost Radiol, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Martiniova, Lucia; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. [Tischler, Arthur S.] Tufts Univ, Dept Pathol, Sch Med & Tufts Med Ctr, Boston, MA 02111 USA. [Reynolds, James C.] NIH, Dept Nucl Med, Clin Ctr, Bethesda, MD 20892 USA. [Fojo, Antonio Tito] NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD USA. RP Pacak, K (reprint author), NIH, E Kennedy Shriver Natl Inst Child Human & Dev, Sect Med Neuroendocrinol, Bldg 10,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU NIH [R01-CA48017]; Pheo Para Alliance; National Institute of Child Health and Human Development; National Cancer Institute; National Institute of Biomedical Imaging and Bioengineering; National Institute of Mental Health at the National Institutes of Health; [APVV-0148-06] FX This research was supported in part by the NIH grant R01-CA48017 and a grant from the Pheo Para Alliance (to A S Tischler) and APVV-0148-06 (to R Kvetnansky). This work also was supported by the intramural program of the National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute of Biomedical Imaging and Bioengineering, and the National Institute of Mental Health at the National Institutes of Health. NR 69 TC 19 Z9 19 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD FEB PY 2011 VL 18 IS 1 BP 143 EP 157 DI 10.1677/ERC-10-0090 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 709LP UT WOS:000286439800015 PM 21098082 ER PT J AU Lee, HW Muniyappa, R Yan, X Yue, LQ Linden, EH Chen, H Hansen, BC Quon, MJ AF Lee, Ho-Won Muniyappa, Ranganath Yan, Xu Yue, Lilly Q. Linden, Ellen H. Chen, Hui Hansen, Barbara C. Quon, Michael J. TI Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys SO ENDOCRINOLOGY LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; DEPENDENT DIABETES-MELLITUS; FASTING PLASMA-GLUCOSE; REDUCES BLOOD-PRESSURE; GREEN TEA POLYPHENOL; METABOLIC SYNDROME; NONHUMAN-PRIMATES; ISLET AMYLOIDOSIS; MACACA-MULATTA; CHECK INDEX AB The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SI(Clamp) (r approximate to 0.4-0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies. (Endocrinology 152: 414-423, 2011) C1 [Lee, Ho-Won; Muniyappa, Ranganath; Chen, Hui; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Yan, Xu; Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Linden, Ellen H.; Hansen, Barbara C.] Univ S Florida, Obes Diabet & Aging Res Ctr, Dept Pediat, Coll Med, St Petersburg, FL 33701 USA. [Linden, Ellen H.; Hansen, Barbara C.] Univ S Florida, Dept Internal Med, Coll Med, St Petersburg, FL 33701 USA. RP Lee, HW (reprint author), NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. RI Hansen, Barbara/J-8723-2012; OI Hansen, Barbara/0000-0001-9646-3525; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU National Center for Complementary and Alternative Medicine, National Institutes of Health; American Diabetes Association FX This work was supported in part by the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health, and in part by a Clinical Research Award from the American Diabetes Association (to M.J.Q.). The primate colony support was via National Institutes of Health National Institute on Aging N01AG3 1012 and continues under National Institutes of Health HHSN263200800022C, institutional, and private funds (to B.C.H.). NR 42 TC 14 Z9 14 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2011 VL 152 IS 2 BP 414 EP 423 DI 10.1210/en.2010-1164 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 709FA UT WOS:000286422100012 PM 21209021 ER PT J AU Vlaanderen, J Lan, Q Kromhout, H Rothman, N Vermeulen, R AF Vlaanderen, Jelle Lan, Qing Kromhout, Hans Rothman, Nathaniel Vermeulen, Roel TI Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE acute lymphocytic leukemia; benzene; chronic lymphocytic leukemia; Hodgkin lymphoma; leukemia; meta-analysis; multiple myeloma; non-Hodgkin lymphoma; occupational exposure ID NON-HODGKIN-LYMPHOMA; PETROLEUM DISTRIBUTION WORKERS; INDUSTRY WIDE MORTALITY; DOSE-RELATED INCIDENCE; OIL REFINERY WORKERS; MULTIPLE-MYELOMA; FOLLOW-UP; UNITED-STATES; HEMATOLOGIC NEOPLASMS; INTERLYMPH-CONSORTIUM AB BACKGROUND: The use of occupational cohort studies to assess the association of benzene and lymphoma is complicated by problems with exposure misclassification, outcome classification, and low statistical power. OBJECTIVE: We performed meta-analyses of occupational cohort studies for five different lymphoma categories: Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). DATA EXTRACTION: We assessed three study quality dimensions to evaluate the impact of study quality variations on meta-relative risks (mRRs): stratification by the year of start of follow-up, stratification by the strength of the reported acute myelogenous leukemia association, and stratification by the quality of benzene exposure assessment. DATA SYNTHESIS: mRRs for MM, ALL, and CLL increased with increasing study quality, regardless of the study quality dimension. mRRs for NHL also increased with increasing study quality, although this effect was less pronounced. We observed no association between occupational benzene exposure and HL. CONCLUSIONS: Our meta-analysis provides support for an association between occupational benzene exposure and risk of MM, ALL, and CLL. The evidence for an association with NHL is less clear, but this is likely complicated by the etiologic heterogeneity of this group of diseases. Further consideration of the association between benzene and NHL will require delineation of risks by NHL subtype. C1 [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3584 CK Utrecht, Netherlands. [Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands. EM R.C.H.Vermeulen@uu.nl RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU European Union [FOOD-CT-2005-513943] FX This work was performed as part of the work package "Integrated Risk Assessment" of the Environmental Cancer Risk, Nutrition, and Individual Susceptibility Network of Excellence, operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (FOOD-CT-2005-513943). NR 99 TC 41 Z9 44 U1 0 U2 14 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2011 VL 119 IS 2 BP 159 EP 167 DI 10.1289/ehp.1002318 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 714IP UT WOS:000286803400016 PM 20880796 ER PT J AU Metcalf, CJE Klepac, P Ferrari, M Grais, RF Djibo, A Grenfell, BT AF Metcalf, C. J. E. Klepac, P. Ferrari, M. Grais, R. F. Djibo, A. Grenfell, B. T. TI Modelling the first dose of measles vaccination: the role of maternal immunity, demographic factors, and delivery systems SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Mathematical modelling; measles (rubeola); vaccine policy development ID RUBELLA MMR VACCINE; AGE; MUMPS; EPIDEMICS; DYNAMICS; INFANTS; IMMUNOGENICITY; TRANSMISSION; ANTIBODIES; EFFICACY AB Measles vaccine efficacy is higher at 12 months than 9 months because of maternal immunity, but delaying vaccination exposes the children most vulnerable to measles mortality to infection. We explored how this trade-off changes as a function of regionally varying epidemiological drivers, e. g. demography, transmission seasonality, and vaccination coverage. High birth rates and low coverage both favour early vaccination, and initiating vaccination at 9-11 months, then switching to 12-14 months can reduce case numbers. Overall however, increasing the age-window of vaccination decreases case numbers relative to vaccinating within a narrow age-window (e. g. 9-11 months). The width of the age-window that minimizes mortality varies as a function of birth rate, vaccination coverage and patterns of access to care. Our results suggest that locally age-targeted strategies, at both national and sub-national scales, tuned to local variation in birth rate, seasonality, and access to care may substantially decrease case numbers and fatalities for routine vaccination. C1 [Metcalf, C. J. E.; Klepac, P.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Ferrari, M.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Ferrari, M.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Grais, R. F.] Epictr, Paris, France. RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Eno Hall, Princeton, NJ 08544 USA. EM cmetcalf@princeton.edu FU Bill and Melinda Gates Foundation; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We thank Justin Lessler and two anonymous reviewers for comments on the manuscript. This work was funded by the Bill and Melinda Gates Foundation (C.J.E.M., P.K., B.T.G.); B.T.G. and M.F. were also supported by the Research and Policy for Infectious Disease Dynamics Program (RAPIDD) of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 29 TC 9 Z9 9 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD FEB PY 2011 VL 139 IS 2 BP 265 EP 274 DI 10.1017/S0950268810001329 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 703WU UT WOS:000286012800013 PM 20525415 ER PT J AU Bae, EH Theodore, WH Fregni, F Cantello, R Pascual-Leone, A Rotenberg, A AF Bae, Erica Hyunji Theodore, William H. Fregni, Felipe Cantello, Roberto Pascual-Leone, Alvaro Rotenberg, Alexander TI An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Repetitive transcranial magnetic stimulation; Epilepsy; Placebo ID REFRACTORY EPILEPSY; CORTICAL DYSPLASIA; TRIAL; EEG AB Objective: Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool in epilepsy. In recent years, several open-label trials have shown an encouraging reduction in seizure frequency in patients with epilepsy. However, the data from controlled trials are mixed with respect to antiepileptic rTMS efficacy, and the field would benefit from further carefully controlled trials. Prior to initiating new trials, it is important assess the magnitude of the placebo effect of presently used sham rTMS methods. Methods: We systematically analyzed individual subject data from three placebo-controlled trials and measured the placebo effect at follow-up intervals of 2, 4, and 8 weeks after sham rTMS treatment. Given the relatively small subgroup sample size, placebo condition data were pooled for analysis. Results: Three methods for sham rTMS were employed in the reviewed studies: (1) coil positioning orthogonal to the scalp, (2) a spring-loaded sham coil, and (3) a double active-sham coil. The placebo response overall was consistently low across follow-up intervals, both for median change in seizure frequency (Kruskal-Wallis, P > 0.4, df=2) and for responder (defined as >= 50% seizure frequency reduction) rate (Fisher's exact rest, P > 0.9, df = 2). The aggregate effect of the placebo condition was a 0-2% median seizure reduction rate and a responder rate of 16-20%. Conclusion: We anticipate that these data will contribute to future power analysis as well as selection and design of sham rTMS methods for controlled rTMS trials. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bae, Erica Hyunji; Rotenberg, Alexander] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. [Bae, Erica Hyunji; Fregni, Felipe; Pascual-Leone, Alvaro; Rotenberg, Alexander] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Theodore, William H.] NIH, Bethesda, MD 20892 USA. [Fregni, Felipe] Harvard Univ, Sch Med, Lab Neuromodulat, Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Cantello, Roberto] Amedeo Avogadro Univ, Dept Clin & Expt Med, Neurol Sect, Novara, Italy. RP Rotenberg, A (reprint author), Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp, Boston, MA 02115 USA. EM alexander.rotenberg@childrens.harvard.edu RI Cantello, Roberto/L-3786-2016 OI Cantello, Roberto/0000-0001-6999-5729 FU Siegel Family Fund for Epilepsy Research; National Institutes of Health [K24 RR018875, UL1 RR025758] FX A.R. acknowledges the Siegel Family Fund for Epilepsy Research for support. A.P.L. received support through National Institutes of Health Grants K24 RR018875 and UL1 RR025758. NR 13 TC 16 Z9 16 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD FEB PY 2011 VL 20 IS 2 BP 355 EP 359 DI 10.1016/j.yebeh.2010.12.005 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 727WN UT WOS:000287833700033 PM 21216200 ER PT J AU Rossler, W Angst, J Gamma, A Haker, H Stulz, N Merikangas, KR Ajdacic-Gross, V AF Roessler, Wulf Angst, Jules Gamma, Alex Haker, Helene Stulz, Niklaus Merikangas, Kathleen R. Ajdacic-Gross, Vladeta TI Reappraisal of the interplay between psychosis and depression symptoms in the pathogenesis of psychotic syndromes: results from a twenty-year prospective community study SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Subclinical psychosis; Schizotypy; Schizotypal personality disorder; Depression; Community study; Epidemiological cohort ID GENERAL-POPULATION; SCHIZOTYPAL PERSONALITY; SEPARATE DISEASES; ZURICH COHORT; SCHIZOPHRENIA; EXPERIENCES; MODELS; DISORDER; EPISODES; SCL-90 AB The interplay of psychotic and affective symptoms is a crucial challenge in understanding the pathogenesis of psychosis. In this study, we analyzed the interplay between two subclinical psychosis symptoms dimensions, and one depression symptoms dimension, using longitudinal data from Zurich. The Zurich study started in 1979 with a representative sample of 591 participants who were aged 20/21. Follow-up interviews were conducted at age 23, 28, 30, 35, and 41. The psychiatric symptoms were assessed with a semi-structured interview and the SCL 90-R. In this study, we analyzed three SCL-90-R subscales: the depression symptoms dimension and two distinct symptoms dimensions of subclinical psychosis, one representing a schizophrenia nuclear symptom dimension, the other representing a schizotypal symptoms dimension. Modeling was done with hybrid latent growth models, thereby including simultaneous and cross-lagged effects. The interplay between the two subclinical psychosis symptoms dimensions and the depression symptoms dimension includes several intertwined pathways. The schizotypal symptoms dimension has strong direct effects on the schizophrenia nuclear symptoms dimension, but also on the depression symptoms dimension. The latter has for its part an effect on the schizophrenia nuclear symptoms dimension. The main driving force within the dynamic interplay between depression and psychosis symptoms is a schizotypal symptoms dimension, which represents social and interpersonal deficiencies, ideas of reference, suspiciousness, paranoid ideation, and odd behavior. It does not only directly influence subclinical nuclear schizophrenia symptoms but also the symptoms of depression. C1 [Roessler, Wulf; Angst, Jules; Gamma, Alex; Haker, Helene; Stulz, Niklaus; Ajdacic-Gross, Vladeta] Univ Zurich, Psychiat Univ Hosp, Dept Gen & Social Psychiat, CH-8021 Zurich, Switzerland. [Roessler, Wulf] Swiss Fed Inst Technol, Zurich, Switzerland. [Merikangas, Kathleen R.] NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Rossler, W (reprint author), Univ Zurich, Psychiat Univ Hosp, Dept Gen & Social Psychiat, Militarstr 8, CH-8021 Zurich, Switzerland. EM roessler@dgsp.uzh.ch OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237 FU Swiss National Science Foundation [32-50881.97] FX The study was supported by the Swiss National Science Foundation (grant # 32-50881.97). NR 46 TC 5 Z9 5 U1 3 U2 16 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD FEB PY 2011 VL 261 IS 1 BP 11 EP 19 DI 10.1007/s00406-010-0123-0 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 712KI UT WOS:000286665200003 PM 20625755 ER PT J AU Ho, M Kim, H AF Ho, Mitchell Kim, Heungnam TI Glypican-3: A new target for cancer immunotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Glypicans; Immunotherapy; Biological markers; Liver neoplasms; Melanoma; Ovarian neoplasms; Endodermal sinus tumour; Neuroblastoma; Wilms tumour ID HUMAN HEPATOCELLULAR-CARCINOMA; GOLABI-BEHMEL-SYNDROME; DEVELOPMENTALLY-REGULATED TRANSCRIPT; HUMAN LIVER-CANCER; CLEAR-CELL; ONCOFETAL PROTEIN; TUMOR-MARKER; MOUSE MODEL; 3 ANTIBODY; EXPRESSION AB Hepatocellular carcinoma (HCC) remains a common malignant cancer worldwide. There is an urgent need to identify new molecular targets for the development of novel therapeutic approaches. Herein, we review the structure, function and biology of glypican-3 (GPC3) and its role in human cancer with a focus on its potential as a therapeutic target for immunotherapy. GPC3 is a cell-surface protein that is over-expressed in HCC. Loss-of-function mutations of GPC3 cause Simpson-Golabi-Behmel syndrome (SGBS), a rare X-linked over-growth condition. GPC3 binds Wnt and Hedgehog (Hh) signalling proteins. GPC3 is also able to bind basic growth factors such as fibroblast growth factor 2 through its heparan sulphate glycan chains. GPC3 is a promising candidate for liver cancer therapy given that it shows high expression in HCC. An anti-GPC3 monoclonal antibody has shown anti-cancer activity in mice and its humanised IgG molecule is currently undergoing clinical evaluation in patients with HCC. There is also evidence that soluble GPC3 may be a useful serum biomarker for HCC. Published by Elsevier Ltd. C1 [Ho, Mitchell; Kim, Heungnam] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5002, Bethesda, MD 20892 USA. EM homi@mail.nih.gov RI Ho, Mitchell/F-5059-2015 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. We thank the NIH Fellows Editorial Board for their review of the manuscript, and Yen Phung and Anna Mazzuca for editorial assistance. 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 organisations imply endorsement by the US Government. NR 52 TC 54 Z9 58 U1 3 U2 33 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 2011 VL 47 IS 3 BP 333 EP 338 DI 10.1016/j.ejca.2010.10.024 PG 6 WC Oncology SC Oncology GA 727ER UT WOS:000287780900001 PM 21112773 ER PT J AU Artym, VV Matsumoto, K Mueller, SC Yamada, KM AF Artym, Vira V. Matsumoto, Kazue Mueller, Susette C. Yamada, Kenneth M. TI Dynamic membrane remodeling at invadopodia differentiates invadopodia from podosomes SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE Invadopodia; Podosomes; Cortactin; Focal adhesions; Invasion ID EXTRACELLULAR-MATRIX DEGRADATION; ADHESION STRUCTURES; CELL STRUCTURES; INVASION; OSTEOCLASTS; CORTACTIN; FIBROBLASTS; SITES; ORGANIZATION; PROTEINS AB Invadopodia are specialized actin-rich protrusions of metastatic tumor and transformed cells with crucial functions in ECM degradation and invasion. Although early electron microscopy studies described invadopodia as long filament-like protrusions of the cell membrane adherent to the matrix, fluorescence microscopy studies have focused on invadopodia as actin-cortactin aggregates localized to areas of ECM degradation. The absence of a clear conceptual integration of these two descriptions of invadopodial structure has impeded understanding of the regulatory mechanisms that govern invadopodia. To determine the relationship between the membrane filaments identified by electron microscopy and the actin-cortactin aggregates of invadopodia, we applied rapid live-cell high-resolution TIRF microscopy to examine cell membrane dynamics at the cortactin core of the invadopodia of human carcinoma cells. We found that cortactin docking to the cell membrane adherent to 2D fibronectin matrix initiates invadopodium assembly associated with the formation of an invadopodial membrane process that extends from a ventral cell membrane lacuna toward the ECM. The tip of the invadopodial process flattens as it interacts with the 2D matrix, and it undergoes constant rapid ruffling and dynamic formation of filament-like protrusions as the invadopodium matures. To describe this newly discovered dynamic relationship between the actin-cortactin core and invadopodial membranes, we propose a model of the invadopodial complex. Using TIRF microscopy, we also established that - in striking contrast to the invadopodium - membrane at the podosome of a macrophage fails to form any process- or filament-like membrane protrusions. Thus, the undulation and ruffling of the invadopodial membrane together with the formation of dynamic filament-like extensions from the invadopodial cortactin core defines invadopodia as invasive superstructures that are distinct from the podosomes. (C) 2010 Elsevier GmbH. All rights reserved. C1 [Artym, Vira V.; Matsumoto, Kazue; Yamada, Kenneth M.] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Artym, Vira V.; Mueller, Susette C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. RP Artym, VV (reprint author), NIDCR, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Room 408, Bethesda, MD 20892 USA. EM vartym@mail.nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU NCI [K99CA129205]; NIH/NIDCR [DE 000719]; NIH [R01 CA112673] FX This work was supported by Pathway to Independence Award K99CA129205 from NCI (V.V.A.), NIH/NIDCR Intramural project DE 000719 (K.M.Y.), and NIH R01 CA112673 (S.C.M.). NR 26 TC 31 Z9 31 U1 2 U2 13 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD FEB-MAR PY 2011 VL 90 IS 2-3 BP 172 EP 180 DI 10.1016/j.ejcb.2010.06.006 PG 9 WC Cell Biology SC Cell Biology GA 733UG UT WOS:000288288100010 PM 20656375 ER PT J AU Windelinckx, A De Mars, G Huygens, W Peeters, MW Vincent, B Wijmenga, C Lambrechts, D Delecluse, C Roth, SM Metter, EJ Ferrucci, L Aerssens, J Vlietinck, R Beunen, GP Thomis, MA AF Windelinckx, An De Mars, Gunther Huygens, Wim Peeters, Maarten W. Vincent, Barbara Wijmenga, Cisca Lambrechts, Diether Delecluse, Christophe Roth, Stephen M. Metter, E. Jeffrey Ferrucci, Luigi Aerssens, Jeroen Vlietinck, Robert Beunen, Gaston P. Thomis, Martine A. TI Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B) as a muscle strength gene SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE complex trait; combined linkage and association analyses; family-based association; genotype/phenotype association ID GROWTH-FACTOR-BETA; MYOSTATIN PATHWAY GENES; FAMILY-BASED TESTS; WIDE LINKAGE SCAN; SKELETAL-MUSCLE; QUANTITATIVE TRAITS; MUSCULAR STRENGTH; MESSENGER-RNA; ASSOCIATION; MEN AB Muscle strength is important in functional activities of daily living and the prevention of common pathologies. We describe the two-staged fine mapping of a previously identified linkage peak for knee strength on chr12q12-14. First, 209 tagSNPs in/around 74 prioritized genes were genotyped in 500 Caucasian brothers from the Leuven Genes for Muscular Strength study (LGfMS). Combined linkage and family-based association analyses identified activin receptor 1B (ACVR1B) and inhibin beta C (INHBC), part of the transforming growth factor beta pathway regulating myostatin - a negative regulator of muscle mass - signaling, for follow-up. Second, 33 SNPs, selected in these genes based on their likelihood to functionally affect gene expression/function, were genotyped in an extended sample of 536 LGfMS siblings. Strong associations between ACVR1B genotypes and knee muscle strength (P-values up to 0.00002) were present. Of particular interest was the association with rs2854464, located in a putative miR-24-binding site, as miR-24 was implicated in the inhibition of skeletal muscle differentiation. Rs2854464 AA individuals were similar to 2% stronger than G-allele carriers. The strength increasing effect of the A-allele was also observed in an independent replication sample (n=266) selected from the Baltimore Longitudinal Study of Aging and a Flemish Policy Research Centre Sport, Physical Activity and Health study. However, no genotype-related difference in ACVR1B mRNA expression in quadriceps muscle was observed. In conclusion, we applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength. European Journal of Human Genetics (2011) 19, 208-215; doi:10.1038/ejhg.2010.173; published online 10 November 2010 C1 [Windelinckx, An; De Mars, Gunther; Huygens, Wim; Peeters, Maarten W.; Vincent, Barbara; Delecluse, Christophe; Beunen, Gaston P.; Thomis, Martine A.] Katholieke Univ Leuven, Res Ctr Exercise & Hlth, Dept Biomed Kinesiol, Fac Kinesiol & Rehabil Sci, B-3001 Leuven, Belgium. [Wijmenga, Cisca] Univ Med Ctr Utrecht, Dept Med Genet, Complex Genet Sect, Utrecht, Netherlands. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium. [Roth, Stephen M.] Univ Maryland, Sch Publ Hlth, Dept Kinesiol, College Pk, MD 20742 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Aerssens, Jeroen] Tibotec Bvba, Dept Translat Med Res, Mechelen, Belgium. [Vlietinck, Robert] Katholieke Univ Leuven, Fac Med, Dept Human Genet, Clin Genet Sect, B-3001 Leuven, Belgium. RP Thomis, MA (reprint author), Katholieke Univ Leuven, Res Ctr Exercise & Hlth, Dept Biomed Kinesiol, Fac Kinesiol & Rehabil Sci, Tervuursevest 101, B-3001 Leuven, Belgium. EM Martine.Thomis@faber.kuleuven.be RI Verdrengh, Evelien/H-4571-2012; Wijmenga, Cisca/D-2173-2009; OI Wijmenga, Cisca/0000-0002-5635-1614; Roth, Stephen/0000-0002-7841-3695 FU KU Leuven [OT/04/44, OT/98/39]; Research Foundation Flanders (FWO) [G.0496.05]; FWO [G.0496.05]; National Institute on Aging, National Institutes of Health [AG022791]; Flemish Government FX AW and WH were funded by the Research Fund of the KU Leuven (OT/04/44 and OT/98/39, respectively). The Research Foundation Flanders (FWO) funded GDM by grant G.0496.05 and MP as post-doctoral researcher. The fine mapping phase of the LGfMS is funded by OT/04/44 and FWO grant G.0496.05. The BLSA research was conducted as a component of the Intramural Research Program of the National Institute on Aging and further supported by AG022791 from the National Institutes of Health. Strength phenotyping of the SPAH cohort was supported by the Flemish Government in the Flemish Policy Research Centre Sport, Physical Activity and Health and genotyping by a FWO Research grant to Martine Thomis. We thank Ivo Salden for his support during the preparation of DNA samples, Ruben van 't Slot, Bart Claes, Gilian Peuteman, Ricardo Lima and Andrew Ludlow for the genotyping, Monique Ramaekers and Els Van den Eede for assistance in the biopsy study and Karolina Szlufcik for support during the mRNA expression analyses. We would like to dedicate this paper to Gunther De Mars, who deceased on 28/02/2010 (age 34) and greatly contributed to the LGfMS study and to earlier versions of this manuscript. NR 47 TC 12 Z9 14 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2011 VL 19 IS 2 BP 208 EP 215 DI 10.1038/ejhg.2010.173 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 705YK UT WOS:000286176500016 PM 21063444 ER PT J AU Tripathi, L Singh, R Stables, JP AF Tripathi, Laxmi Singh, Ranjit Stables, James P. TI Design & synthesis of N '-[substituted] pyridine-4-carbohydrazides as potential anticonvulsant agents SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE N '-[substituted]pyridine-4-carohydrazides; Anticonvulsant activity; Neurotoxicity; Computational study ID MAXIMAL ELECTROSHOCK SCREEN; ANTIEPILEPTIC DRUGS; ARYL SEMICARBAZONES; PHARMACOPHORE; DISCOVERY; TARGETS AB A series of N'-[substituted] pyridine-4-carbohydrazides were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was established after intraperitoneal administration in three seizure models, which include MES, scMET and 6 Hz model. The most active compound of the series was N'-[4-(4-fluorophenoxy)benzylidene]pyridine-4-carbohydrazide PCH 6, which showed a MES ED50 value of 128.3 mg/kg and 6 Hz ED50 value of 53.3 mg/kg in mice. The median toxic dose (TD50) was 343.6 mg/kg, providing compound PCH 6 with a protection index of 2.67 in the MES test and 6.44 in 6 Hz test. A computational study was also carried out, including calculation of pharmacophore pattern, prediction of pharmacokinetic properties and docking studies. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Tripathi, Laxmi; Singh, Ranjit] Shobhit Univ, Sch Pharmaceut Sci, Meerut 250110, Uttar Pradesh, India. [Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Tripathi, L (reprint author), Shobhit Univ, Sch Pharmaceut Sci, Meerut 250110, Uttar Pradesh, India. EM tripathilaxmi@rediffmail.com NR 27 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD FEB PY 2011 VL 46 IS 2 BP 509 EP 518 DI 10.1016/j.ejmech.2010.11.030 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 725AL UT WOS:000287617500006 PM 21167624 ER PT J AU Balboni, G Salvadori, S Marczak, ED Knapp, BI Bidlack, JM Lazarus, LH Peng, XM Si, YG Neumeyer, JL AF Balboni, Gianfranco Salvadori, Severo Marczak, Ewa D. Knapp, Brian I. Bidlack, Jean M. Lazarus, Lawrence H. Peng, Xuemei Si, Yu Gui Neumeyer, John L. TI Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Bifunctional ligands; Dmt-Tic pharmacophore; Opioid receptors ID DESIGNED MULTIPLE LIGAND; BIVALENT LIGANDS; INVERSE AGONISM; RECEPTORS; ANTAGONIST; ANALOGS; NALTRINDOLE; EVOLUTION; BINDING AB Bifunctional ligands containing an ester linkage between morphine and the delta-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the mu, delta and kappa opioid receptors determined. Bifunctional ligands containing or not a spacer of beta-alanine between the two pharmacophores lose the mu agonism deriving from morphine becoming partial p agonists mu or mu antagonists 5. Partial kappa agonism is evidenced only for compound 4. Finally, both compounds showed potent delta antagonism. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. [Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. [Salvadori, Severo] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. [Knapp, Brian I.; Bidlack, Jean M.] Univ Rochester, Dept Pharmacol & Physiol, Sch Med & Dent, Rochester, NY 14642 USA. [Marczak, Ewa D.; Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Peng, Xuemei; Si, Yu Gui; Neumeyer, John L.] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. RP Balboni, G (reprint author), Univ Cagliari, Dept Toxicol, Via Osped 72, I-09124 Cagliari, Italy. EM gbalboni@unica.it; jneumeyer@mclean.harvard.edu OI SALVADORI, Severo/0000-0002-8224-2358 FU NIH [RO1-DA14251, K05-DA 00360]; University of Cagliari; University of Ferrara; NIEHS FX This work was supported in part by NIH Grants RO1-DA14251 (to J.L.N.), K05-DA 00360 (to J.M.B.), University of Cagliari (to G.B.), University of Ferrara (to S.S.), and the Intramural Research Program of the NIH and NIEHS (to L.H.L.). NR 27 TC 9 Z9 10 U1 0 U2 8 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD FEB PY 2011 VL 46 IS 2 BP 799 EP 803 DI 10.1016/j.ejmech.2010.12.001 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 725AL UT WOS:000287617500036 PM 21216504 ER PT J AU Michalski, MH Chen, XY AF Michalski, Mark H. Chen, Xiaoyuan TI Molecular imaging in cancer treatment SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Molecular imaging; Therapy response; Metabolism; Proliferation; Angiogenesis; Hypoxia; Apoptosis ID POSITRON-EMISSION-TOMOGRAPHY; ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; INTEGRIN ALPHA(V)BETA(3) EXPRESSION; MATRIX-METALLOPROTEINASE INHIBITORS; FACTOR RECEPTOR EXPRESSION; HYPOXIC TISSUE TRACER; IN-VIVO DETECTION; BREAST-CANCER; TUMOR HYPOXIA AB The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. C1 [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Michalski, Mark H.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU NIH, NIBIB FX This research was supported by the Intramural Research Program of the NIH, NIBIB. NR 203 TC 48 Z9 53 U1 5 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD FEB PY 2011 VL 38 IS 2 BP 358 EP 377 DI 10.1007/s00259-010-1569-z PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 706GC UT WOS:000286205000018 PM 20661557 ER PT J AU Huff, J AF Huff, James TI Occupational cancer and social inequities SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID PRIMARY PREVENTION C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD FEB PY 2011 VL 21 IS 1 BP 129 EP 129 DI 10.1093/eurpub/ckq026 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 709TA UT WOS:000286463100023 PM 20375025 ER PT J AU Kleykamp, BA Jennings, JM Eissenberg, T AF Kleykamp, Bethea A. Jennings, Janine M. Eissenberg, Thomas TI Effects of Transdermal Nicotine and Concurrent Smoking on Cognitive Performance in Tobacco-Abstinent Smokers SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; tobacco; smoking; cognition; performance ID REPLACEMENT THERAPY; CIGARETTE-SMOKING; WORKING-MEMORY; PSYCHOMOTOR PERFORMANCE; ADMINISTERED NICOTINE; WITHDRAWAL SYNDROME; NEVER-SMOKERS; PATCH; CESSATION; ATTENTION AB Smokers experience cognitive decrements during tobacco abstinence and boosts in performance on resumption of smoking. Few studies have examined whether smoking cessation treatments such as transdermal nicotine (TN) ameliorate these decrements or attenuate the cognitive effects of smoking. Identifying the effects of nicotine on these tobacco-related changes in performance could guide the development of more efficacious treatments. The purpose of this double-blind, randomized, laboratory study was to use process-specific cognitive tasks to examine the effects of TN and tobacco smoking on attention and working memory in overnight-abstinent smokers (N = 124; 54 women). Each participant completed 4 sessions lasting 6.5 hr corresponding to 0-, 7-, 14-, or 21-mg TN doses, and smoked a single cigarette 4 hr after TN administration. Outcome measures were administered before and after smoking and included tasks measuring attention (alerting, orienting, and executive function), working memory (verbal and spatial), and psychomotor function. Analysis of variance (p < .05) revealed that TN improved verbal and spatial working memory performance, as well as psychomotor function. Smoking, independent of TN dose, improved alerting, verbal working memory, and psychomotor function. Lastly, TN partially attenuated the effects of smoking on some working memory outcomes. These findings lend evidence to the idea that TN ameliorates some abstinence-related cognitive decrements and suggest that TN does not completely attenuate the cognitive effects of a concurrently smoked cigarette. Consequently, TN's efficacy as a smoking cessation treatment might be improved if these limitations are better addressed by either modifying or supplementing existing treatments. C1 [Kleykamp, Bethea A.] NIDA, Nicotine Psychopharmacol Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Jennings, Janine M.] Wake Forest Univ, Dept Psychol, Winston Salem, NC 27109 USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA 23284 USA. RP Kleykamp, BA (reprint author), NIDA, Nicotine Psychopharmacol Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd,Room 01A941, Baltimore, MD 21224 USA. EM annie.kleykamp@nih.gov FU Public Health Service [R01DA11082, F31DA017437] FX Portions of this work were presented at the 11th and 12th Annual Meetings of the Society for Research on Nicotine and Tobacco and the 67th and 68th Annual Meetings of the College on Problems of Drug Dependence. This work was supported by Public Health Service Grants R01DA11082 and F31DA017437. This article is based on dissertation research that was conducted, completed, and defended at Virginia Commonwealth University by Bethea A. Kleykamp under the guidance of Thomas Eissenberg. NR 61 TC 8 Z9 8 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2011 VL 19 IS 1 BP 75 EP 84 DI 10.1037/a0022417 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 722WM UT WOS:000287466000008 PM 21341925 ER PT J AU Aguilera, G AF Aguilera, Greti TI HPA axis responsiveness to stress: Implications for healthy aging SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Neurobiology and Neuroendocrinology of Aging CY JUL 25-30, 2010 CL Bregenz, AUSTRIA DE Stress; Hypothalamic pituitary adrenal axis (HPA); Corticotropin releasing hormone (CRH); Vasopressin (VP); Glucocorticoids ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; FACTOR MESSENGER-RNA; GLUCOCORTICOID-RECEPTOR GENE; AGE-RELATED-CHANGES; PARAVENTRICULAR NUCLEUS; ADRENOCORTICOTROPIN SECRETION; SUPRACHIASMATIC NUCLEI; FISCHER-344 RATS; CIRCADIAN-RHYTHM AB The major neuroendocrine response mediating stress adaptation is activation of the hypothalamic pituitary adrenal axis, with stimulation of corticotropin releasing hormone (CRH) and vasopressin (VP) from parvocellular neurons of the hypothalamic paraventricular nucleus, leading to stimulation of pituitary ACTH secretion and increases in glucocorticoid secretion from the adrenal cortex. Basal production and transient increases during stress of glucocorticoids and its hypothalamic regulators are essential for neuronal plasticity and normal brain function. While activation of the HPA axis is essential for survival during stress, chronic exposure to stress hormones can predispose to psychological, metabolic and immune alterations. Thus, prompt termination of the stress response is essential to prevent negative effects of inappropriate levels of CRH and glucocorticoids. This review addresses the regulation of HPA axis activity with emphasis on the mechanisms of termination of CRH transcription, which is a critical step in this process. In addition, the actions by which glucocorticoids, CRH and VP can affect the aging process will be discussed. Published by Elsevier Inc. C1 [Aguilera, Greti] NIH, Eunice Kennedy Shiver Inst Child Hlth & Human Dev, Program Dev Endocrinol & Genet, Sect Endocrine Physiol, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Psysiol DEB, CRC, NIH Bldg 10,Rm 11E-3330 10 Ctr Dr, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov FU Intramural NIH HHS [Z01 HD000631-18, Z99 HD999999] NR 89 TC 72 Z9 75 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD FEB-MAR PY 2011 VL 46 IS 2-3 SI SI BP 90 EP 95 DI 10.1016/j.exger.2010.08.023 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 720OQ UT WOS:000287290400002 PM 20833240 ER PT J AU DeJesus, CE Egen, J Metzger, M Alvarez, X Combs, CA Malide, D Yu, ZX Tian, X Donahue, RE AF DeJesus, Catherine E. Egen, Jackson Metzger, Mark Alvarez, Xavier Combs, Christian A. Malide, Daniela Yu, Zu Xi Tian, Xin Donahue, Robert E. TI Transient neutropenia after granulocyte-colony stimulating factor administration is associated with neutrophil accumulation in pulmonary vasculature SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID G-CSF; DONORS; MACROPHAGES; SPLEEN; LUNGS AB Objective. To better define the nature of the transient neutropenia shortly following granulocyte-colony stimulating factor (G-CSF) administration. Materials and Methods. To evaluate the disappearance of neutrophils, we investigated neutrophil trafficking. Ratios of neutrophil number to background cellularity for C57BL/6 LysM-EGFP knock-in mice and rhesus macaques were determined in the lung, liver, spleen, and kidney after G-CSF administration. Results. For the C57BL/6 LysM-EGFP knock-in mice, the enhanced green fluorescent protein expression (EGFP(+)) cells increased in the lung and spleen within 15 minutes of administering 50 mu g/kg G-CSF subcutaneously, and continued to increase in the lung and spleen from 15 minutes to 30 minutes. At 240 minutes, the pulmonary infiltrate declined to a level comparable to the level at 15 minutes, while in the spleen EGFP(+) cells continued to increase. For rhesus macaques, CD18(+) cells also significantly increased in the lung 30 minutes after administration of 10 mu g/kg G-CSF subcutaneously compared to the control level. Conclusions. These results suggest that the transient neutropenia following G-CSF administration in the mouse and nonhuman primate is associated with an accumulation of neutrophils within pulmonary and splenic vasculature. Published by Elsevier Inc. on behalf of the ISEH - Society for Hematology and Stem Cells. C1 [DeJesus, Catherine E.; Metzger, Mark; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD 20850 USA. [Egen, Jackson] NIAID, Bethesda, MD 20892 USA. [Alvarez, Xavier] Tulane Natl Primate Res Ctr, Covington, LA USA. [Combs, Christian A.; Malide, Daniela] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Yu, Zu Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Donahue, RE (reprint author), NHLBI, Hematol Branch, NIH, 5 Res Court, Rockville, MD 20850 USA. EM donahuer@nhlbi.nih.gov OI Egen, Jackson/0000-0003-2053-0837 FU National Institutes of Health (NIH), National Heart, Lung, and Blood Institute; NIH [RR00164] FX The authors wish to thank the veterinary and laboratory animal staff at 5 Research Court and National Insitute of Allergy and Infectious Diseases (Bethesda, MD, USA) for maintaining the animals used in this study. In addition, we would like the veterinary pathology staff of the Division of Veterinary Resources for their help in performing the necropsies. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute. Xavier Alvarez is supported partially by NIH grant RR00164 to the Tulane National Primate Research Center. NR 21 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2011 VL 39 IS 2 BP 142 EP 150 DI 10.1016/j.exphem.2010.11.004 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 716JE UT WOS:000286964100002 PM 21087652 ER PT J AU Dodson, HC Lyda, TA Chambers, JW Morris, MT Christensen, KA Morris, JC AF Dodson, Heidi C. Lyda, Todd A. Chambers, Jeremy W. Morris, Meredith T. Christensen, Kenneth A. Morris, James C. TI Quercetin, a fluorescent bioflavanoid, inhibits Trypanosoma brucei hexokinase 1 SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Trypanosoma brucei; Hexokinase; Quercetin; Glycolysis ID BLOOD-STREAM FORM; AGENT LONIDAMINE; TUMOR-CELLS; ANTI-TUMOR; GLYCOLYSIS; MITOCHONDRIA; EXPRESSION; FLAVONOIDS; APOPTOSIS; IMPORT AB Hexokinases from the African trypanosome, Trypanosome brucei, are attractive targets for the development of anti-parasitic drugs, in part because the parasite utilizes glycolysis exclusively for ATP production during the mammalian infection. Here, we have demonstrated that the bioflavanoid quercetin (QCN), a known trypanocide, is a mixed inhibitor of Trypanosome brucei hexokinase 1 (TbHK1) (IC(50) = 4.1 +/- 0.8 mu M). Spectroscopic analysis of QCN binding to TbHK1, taking advantage of the intrinsically fluorescent single tryptophan (Trp177) in TbHK1, revealed that QCN quenches emission of Trp177, which is located near the hinge region of the enzyme. ATP similarly quenched Trp177 emission, while glucose had no impact on fluorescence. Supporting the possibility that QCN toxicity is a consequence of inhibition of the essential hexokinase, in live parasites QCN fluorescence localizes to glycosomes, the subcellular home of TbHK1. Additionally, RNAi-mediated silencing of TbHK1 expression expedited QCN induced death, while over-expressing TbHK1 protected trypanosomes from the compound. In summary, these observations support the suggestion that QCN toxicity is in part attributable to inhibition of the essential TbHK1. (C) 2010 Elsevier Inc. All rights reserved. C1 [Dodson, Heidi C.; Lyda, Todd A.; Chambers, Jeremy W.; Morris, Meredith T.; Morris, James C.] Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. [Christensen, Kenneth A.] Clemson Univ, Dept Chem, Clemson, SC 29634 USA. [Lyda, Todd A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Chambers, Jeremy W.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. RP Morris, JC (reprint author), Clemson Univ, Dept Biochem & Genet, 214 BRC,51 New Cherry St, Clemson, SC 29634 USA. EM jmorri2@clemson.edu RI Christensen, Kenneth/D-3460-2017; OI Chambers, Jeremy/0000-0002-6143-3091 FU US National Institutes of Health [1R15AI075326] FX The authors would like to thank Stephen Carek and Tom Caldwell for their technical assistance. This work was supported in part by the US National Institutes of Health 1R15AI075326 to JCM. NR 32 TC 14 Z9 14 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD FEB PY 2011 VL 127 IS 2 BP 423 EP 428 DI 10.1016/j.exppara.2010.10.011 PG 6 WC Parasitology SC Parasitology GA 712CW UT WOS:000286643300016 PM 20971104 ER PT J AU Davis, CD Milner, JA AF Davis, Cindy D. Milner, John A. TI Vitamin D and colon cancer SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE colon cancer; CYP24A1; CYP27B1; vitamin D; vitamin D receptor ID D-RECEPTOR EXPRESSION; EPITHELIAL-CELL PROLIFERATION; RANDOMIZED CLINICAL-TRIAL; CALCIUM-SENSING RECEPTOR; COLORECTAL ADENOMA RISK; DIETARY CALCIUM; UNITED-STATES; SERUM 25-HYDROXYVITAMIN-D; CARCINOMA-CELLS; PROSPECTIVE COHORT AB A wealth of scientific evidence supports a role for vitamin D in decreasing colorectal cancer incidence, and possibly mortality. This reduction in risk is related to inhibition of cellular proliferation and stimulation of differentiation. The minimal amount and duration needed to bring about these effects necessitate additional studies. Furthermore, a critical evaluation of physiologically relevant biomarkers of vitamin D status, including 25-hydroxyvitamin D, is needed. Several dietary components and the balance between energy intake and expenditure influence vitamin D metabolism. Scientists need to identify confounders and modifiers of the biological response to vitamin D, including dietary factors, lifestyle factors such as exercise, race or ethnicity, and genetic background. C1 [Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA. RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3159,MSC 7328, Rockville, MD 20892 USA. EM davisci@mail.nih.gov NR 122 TC 9 Z9 10 U1 0 U2 6 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD FEB PY 2011 VL 5 IS 1 BP 67 EP 81 DI 10.1586/EGH.10.89 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861SL UT WOS:000298039400013 PM 21309673 ER PT J AU Dey, AK Srivastava, IK AF Dey, Antu K. Srivastava, Indresh K. TI Novel adjuvants and delivery systems for enhancing immune responses induced by immunogens SO EXPERT REVIEW OF VACCINES LA English DT Review DE adjuvant; immunogen; MF59; MPL; nanoemulsions; PAMPs; PLG microparticles; PRR; SMIP ID MONOPHOSPHORYL-LIPID-A; HEPATITIS-B-VACCINE; HEAT-LABILE ENTEROTOXIN; VIRUS-LIKE PARTICLES; CELLS IN-VIVO; RECONSTITUTED INFLUENZA VIROSOMES; IMMUNOSTIMULATING COMPLEX ISCOM; ADP-RIBOSYLTRANSFERASE ACTIVITY; CROSS-PROTECTIVE IMMUNITY; SERUM ANTIBODY-RESPONSE AB Vaccines are the most important preventive measure against infectious diseases. In developing an effective vaccine, besides the primary challenge of identifying the most relevant immunogen and efficient regime of immunization, selection of a potent adjuvant and delivery method is equally critical. The formulation of immunogens with different adjuvants may affect the affinity maturation of antibody responses differently, suggesting that the structure of specific epitopes within the immunogen may be influenced by different adjuvants. Thus, developing adjuvants that can efficiently activate both the innate and adaptive arms of the immune system is a major challenge for vaccine researchers. The use of novel adjuvants in combination with novel immunogen design holds great promise towards the goal of enhancing the potency, breadth and durability of vaccines. This article summarizes the different immunopotentiators (and immunomodulators) as well as the delivery systems that are available for vaccine generation and the types of immune responses that each of them induces. Also discussed are adjuvants that have a combination of both immunomodulatory and delivery properties. C1 [Dey, Antu K.; Srivastava, Indresh K.] Novartis Vaccines & Diagnost Inc, Cambridge, MA 02139 USA. RP Srivastava, IK (reprint author), NIAID, VPPL, Vaccine Res Ctr, NIH, 942 Clopper Rd, Gaithersburg, MD 20877 USA. EM srivastavai@mail.nih.gov RI Dey, Antu/A-1305-2013 FU National Institute of Allergy and Infectious Diseases, NIH (Bethesda, MD, USA) [AI-9536Z, I-AI-05397, 5PO1-AI48225-03] FX Some of the work reported in this article was supported by grants and contracts (AI-9536Z, I-AI-05397 and 5PO1-AI48225-03) from the National Institute of Allergy and Infectious Diseases, NIH (Bethesda, MD, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 272 TC 33 Z9 36 U1 2 U2 14 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD FEB PY 2011 VL 10 IS 2 BP 227 EP 251 DI 10.1586/ERV.10.142 PG 25 WC Immunology SC Immunology GA 732NM UT WOS:000288192200014 PM 21105782 ER PT J AU Wang, Y Wang, VM Chan, CC AF Wang, Y. Wang, V. M. Chan, C-C TI The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment SO EYE LA English DT Review DE age-related macular degeneration; inflammation; corticosteroid; nonsteoridal anti-inflammatory drug; immunosuppressant; biologics ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; RANDOMIZED CLINICAL-TRIAL; CHLAMYDIA-PNEUMONIAE INFECTION; PIGMENT EPITHELIAL DETACHMENT; CHOROIDAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; TRIPLE THERAPY; RHEUMATOID-ARTHRITIS; RETINAL DEGENERATION; ENDOTHELIAL-CELLS AB Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. Eye (2011) 25, 127-139; doi: 10.1038/eye.2010.196; published online 24 December 2010 C1 [Wang, Y.; Wang, V. M.; Chan, C-C] NEI, Immunol Lab, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. [Wang, Y.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China. RP Chan, CC (reprint author), NEI, Immunol Lab, Immunopathol Sect, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016 FU NEI FX The NEI Intramural Research Program provided the funding support. Mrs Pamela Sieving provided helpful editing assistance. NR 108 TC 45 Z9 50 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD FEB PY 2011 VL 25 IS 2 BP 127 EP 139 DI 10.1038/eye.2010.196 PG 13 WC Ophthalmology SC Ophthalmology GA 719FR UT WOS:000287187300001 PM 21183941 ER PT J AU Wang, XQ Hawkins, BT Miller, DS AF Wang, Xueqian Hawkins, Brian T. Miller, David S. TI Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier SO FASEB JOURNAL LA English DT Article DE P-glycoprotein; multidrug resistance-associated protein 2; breast cancer resistance protein; dioxin; brain capillaries ID CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN; ENDOTHELIAL-CELLS; DNA-BINDING; IN-VITRO; ALPHA-NAPHTHOFLAVONE; DRUG TRANSPORTER; ABC TRANSPORTERS; CYTOCHROMES P450; DIOXIN RECEPTOR AB Many widespread and persistent organic pollutants, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), activate the aryl hydrocarbon receptor (AhR), causing it to translocate to the cell nucleus, where it transactivates target genes. AhR's ability to target the blood-brain barrier is essentially unexplored. We show here that exposing isolated rat brain capillaries to 0.05-0.5 nM TCDD roughly doubled transport activity and protein expression of P-glycoprotein, an ATP-driven drug efflux pump and a critical determinant of drug entry into the CNS. These effects were abolished by actinomycin D or cycloheximide or by the AhR antagonists resveratrol and alpha-naphthoflavone. Brain capillaries from TCDD-dosed rats (1-5 mu g/kg, i.p.) exhibited increased transport activity and protein expression of 3 xenobiotic efflux pumps, P-glycoprotein, multidrug resistance-associated protein 2, and breast cancer resistance polypeptide, as well as expression of Cyp1a1 and Cyp1b1, both AhR target genes. Consistent with increased P-glycoprotein expression in capillaries from TCDD-dosed rats, in situ brain perfusion indicated significantly reduced brain accumulation of verapamil, a P-glycoprotein substrate. These findings suggest a new paradigm for the field of environmental toxicology: toxicants acting through AhR to target xenobiotic efflux transporters at the blood-brain barrier and thus reduce brain accumulation of CNS-acting therapeutic drugs.-Wang, X., Hawkins, B. T., Miller, D. S. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J. 25, 644-652 (2011). www.fasebj.org C1 [Wang, Xueqian; Hawkins, Brian T.; Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov OI Hawkins, Brian/0000-0001-6719-5402 FU National Institute of Environmental Health Sciences, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 50 TC 42 Z9 44 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2011 VL 25 IS 2 BP 644 EP 652 DI 10.1096/fj.10-169227 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 713GZ UT WOS:000286724800022 PM 21048045 ER PT J AU Deng, YM Edin, ML Theken, KN Schuck, RN Flake, GP Kannon, MA DeGraff, LM Lih, FB Foley, J Bradbury, JA Graves, JP Tomer, KB Falck, JR Zeldin, DC Lee, CR AF Deng, Yangmei Edin, Matthew L. Theken, Katherine N. Schuck, Robert N. Flake, Gordon P. Kannon, M. Alison DeGraff, Laura M. Lih, Fred B. Foley, Julie Bradbury, J. Alyce Graves, Joan P. Tomer, Kenneth B. Falck, John R. Zeldin, Darryl C. Lee, Craig R. TI Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice SO FASEB JOURNAL LA English DT Article DE CYP2J2; CYP2C8; EPHX2; EETs; eicosanoids; inflammation ID NF-KAPPA-B; ACUTE LUNG INJURY; ACUTE PSEUDOMONAS PNEUMONIA; BLOOD-PRESSURE REGULATION; ARACHIDONIC-ACID; CYTOCHROME-P450 EPOXYGENASES; CORONARY-ARTERIES; EPOXYEICOSATRIENOIC ACIDS; THERAPEUTIC TARGET; MOLECULAR-CLONING AB Cytochrome P-450 (CYP)-derived epoxyeicosatrienoic acids (EETs) possess potent anti-inflammatory effects in vitro. However, the effect of increased CYP-mediated EET biosynthesis and decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on vascular inflammation in vivo has not been rigorously investigated. Consequently, we characterized acute vascular inflammatory responses to endotoxin in transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases and mice with targeted disruption of Ephx2. Compared to wild-type controls, CYP2J2 transgenic, CYP2C8 transgenic, and Ephx2(-/-) mice each exhibited a significant attenuation of endotoxin-induced activation of nuclear factor (NF)-kappa B signaling, cellular adhesion molecule, chemokine and cytokine expression, and neutrophil infiltration in lung in vivo. Furthermore, attenuation of endotoxin-induced NF-kappa B activation and cellular adhesion molecule and chemokine expression was observed in primary pulmonary endothelial cells isolated from CYP2J2 and CYP2C8 transgenic mice. This attenuation was inhibited by a putative EET receptor antagonist and CYP epoxygenase inhibitor, directly implicating CYP epoxygenase-derived EETs with the observed anti-inflammatory phenotype. Collectively, these data demonstrate that potentiation of the CYP epoxygenase pathway by either increased endothelial EET biosynthesis or globally decreased EET hydrolysis attenuates NF-kappa B-dependent vascular inflammatory responses in vivo and may serve as a viable anti-inflammatory therapeutic strategy.-Deng, Y., Edin, M. L., Theken, K. N., Schuck, R. N., Flake, G. P., Kannon, M. A., DeGraff, L. M., Lih, F. B., Foley, J., Bradbury, J. A., Graves, J. P., Tomer, K. B., Falck, J. R., Zeldin, D. C., Lee, C. R. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J. 25, 703-713 (2011). www.fasebj.org C1 [Deng, Yangmei; Theken, Katherine N.; Schuck, Robert N.; Kannon, M. Alison; Lee, Craig R.] UNC, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA. [Edin, Matthew L.; Flake, Gordon P.; DeGraff, Laura M.; Lih, Fred B.; Foley, Julie; Bradbury, J. Alyce; Graves, Joan P.; Tomer, Kenneth B.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Div Intramural Res, Res Triangle Pk, NC USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. RP Lee, CR (reprint author), UNC, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, CB 7569,Kerr Hall, Chapel Hill, NC 27599 USA. EM craig_lee@unc.edu RI Theken, Katherine/H-1098-2012; Tomer, Kenneth/E-8018-2013; OI Falck, John/0000-0002-9219-7845; Edin, Matthew/0000-0002-7042-500X; Lee, Craig/0000-0003-3595-5301 FU American Foundation for Pharmaceutical Education; NIH [GM31278, GM088199, P30 DK34987]; Robert A. Welch Foundation; NIH, NIEHS [Z01 ES050167, Z01 ES025034]; American Heart Association FX This publication was made possible by a predoctoral fellowship from the American Foundation for Pharmaceutical Education to K.N.T., NIH grant GM31278 and support from the Robert A. Welch Foundation to J.R.F., funds from the Intramural Research Program of the NIH, NIEHS, to K. B. T. (Z01 ES050167) and D.C.Z. (Z01 ES025034), a Beginning Grant-in-Aid from the American Heart Association and NIH grant GM088199 to C. R. L., and NIH grant P30 DK34987. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, National Institute of General Medical Sciences, or NIH. D. C. Z. is a coinventor on U.S. Patent No. 6,531,506 B1 (issued March 11, 2003), Inhibition of Epoxide Hydrolases for the Treatment of Hypertension, and on U. S. Patent No. 6,916,843 B1 (issued July 12, 2005), Anti-inflammatory Actions of Cytochrome P450 Epoxygenase-Derived Eicosanoids. No other authors declare conflicts of interest. NR 52 TC 67 Z9 68 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2011 VL 25 IS 2 BP 703 EP 713 DI 10.1096/fj.10-171488 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 713GZ UT WOS:000286724800028 PM 21059750 ER PT J AU Beydoun, HA Sicignano, N Beydoun, MA Bocca, S Stadtmauer, L Oehninger, S AF Beydoun, Hind A. Sicignano, Nicholas Beydoun, May A. Bocca, Silvina Stadtmauer, Laurel Oehninger, Sergio TI Pubertal development of the first cohort of young adults conceived by in vitro fertilization in the United States SO FERTILITY AND STERILITY LA English DT Article DE Body mass index; infertility; in vitro fertilization; puberty ID CHILDREN BORN; ASSISTED REPRODUCTION; CONCEPTION; PARENTS; HEALTH AB Objective: To characterize pubertal development of the first generation of young adults born as a result of in vitro fertilization (IVF). Demographic, clinical, and body size characteristics were examined regarding developmental milestones. Design: Cross-sectional. Setting: Academic center. Patient(s): Young adults (18-26 years) conceived by IVF (no gamete/embryo manipulation) 1981-1990. Intervention(s): Self-administered questionnaire. Main Outcome Measure(s): Age at puberty onset, body size. Result(s): Of 560 eligible young adults, 173 completed the survey (response rate 30.9%). We analyzed data on 166 respondents (71 male and 95 female). No cases of delayed or precocious puberty were observed in the study sample. As expected, age at puberty onset was significantly higher among male subjects (12.3 years) compared with female subjects (11.5 years). A few developmental milestones were predicted by maternal age and infertility diagnoses. For both genders, a direct association was noted between age at puberty onset and height achieved in young adulthood. Structural equation models suggested an inverse relationship of female gender with age at puberty onset and body mass index. Conclusion(s): In vitro fertilization-conceived young adults did not exhibit pubertal abnormalities. Female gender and age at puberty onset independently predicted body mass index of IVF offspring in young adulthood. (Fertil Steril (R) 2011;95:528-33. (C)2011 by American Society for Reproductive Medicine.) C1 [Bocca, Silvina; Stadtmauer, Laurel; Oehninger, Sergio] Eastern Virginia Med Sch, Jones Inst Reprod Med, Norfolk, VA 23507 USA. [Beydoun, Hind A.; Sicignano, Nicholas] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA. [Beydoun, May A.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Oehninger, S (reprint author), Eastern Virginia Med Sch, Jones Inst Reprod Med, 601 Colley Ave,4th Floor, Norfolk, VA 23507 USA. EM oehninsc@evms.edu FU National Institute on Aging, National Institutes of Health FX Supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 26 TC 9 Z9 9 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2011 VL 95 IS 2 BP 528 EP 533 DI 10.1016/j.fertnstert.2010.04.057 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 709EA UT WOS:000286419000022 PM 20547390 ER PT J AU Nieman, LK Blocker, W Nansel, T Mahoney, S Reynolds, J Blithe, D Wesley, R Armstrong, A AF Nieman, Lynnette K. Blocker, Wendy Nansel, Tonja Mahoney, Sheila Reynolds, James Blithe, Diana Wesley, Robert Armstrong, Alicia TI Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study SO FERTILITY AND STERILITY LA English DT Article DE Selective progestin receptor modulator; ulipristal acetate; fibroids; UFS-QOL ID QUALITY-OF-LIFE; GONADOTROPIN-RELEASING-HORMONE; PROGESTERONE-RECEPTOR MODULATORS; LOW-DOSE MIFEPRISTONE; CONTROLLED-TRIAL; LEIOMYOMATA TREATMENT; WOMEN; DIAGNOSIS; AGONIST; MYOMAS AB Objective: To evaluate the efficacy and tolerability of the P receptor modulator CDB-2914 (Ulipristal, CDB). Design: Randomized, placebo-controlled double-blind clinical trial. Setting: Clinical research center. Patient(s): Premenopausal women with symptomatic uterine fibroids. Intervention(s): Once-daily oral CDB (10 or 20 mg) or placebo (PLC) for 12 weeks (treatment 1). A second 3-month treatment with CDB (treatment 2) was offered. A computer-generated blocked randomization was used. Main Outcome Measure(s): Magnetic resonance imaging (MRI)-determined total fibroid volume (TFV) change was the primary outcome; amenorrhea and quality of life (QOL) were secondary end points. Result(s): Treatment 1 TFV increased 7% in the PLC group, but decreased 17% and 24% in the CDB10 and CDB20 groups. The TFV decreased further in treatment 2 (-11%). Amenorrhea occurred in 20/26 women taking CDB and none on PLC. Ovulation resumed after CDB. Hemoglobin improved only with CDB (11.9 +/- 1.5 to 12.9 +/- 1.0 g/dL) as did the Fibroid QOL Questionnaire symptom severity, energy/mood, and concern subscores, and overall QOL scores. The CDB was well tolerated, with no serious adverse events. Adverse events were unchanged during treatments. Conclusion(s): Administration of CDB-2914 for 3-6 months controls bleeding, reduces fibroid size, and improves QOL. (Fertil Steril(R) 2011;95:767-72. (C) 2011 by American Society for Reproductive Medicine.) C1 [Nieman, Lynnette K.; Blocker, Wendy; Mahoney, Sheila; Armstrong, Alicia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Nansel, Tonja] NICHHD, Div Epidemiol Stat & Populat Res, Bethesda, MD 20892 USA. [Reynolds, James] Mark O Hatfield Clin Res Ctr, Dept Radiol, Bethesda, MD USA. [Blithe, Diana] NICHHD, Contracept & Reprod Hlth Branch, Bethesda, MD 20892 USA. [Wesley, Robert] NIH, Biostat & Clin Epidemiol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM NiemanL@nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD; Laboratoire HRA-Pharma, Paris, France FX Supported by in part by the Intramural Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and by the National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD. Under a Cooperative Research and Development Agreement, Laboratoire HRA-Pharma, Paris, France, provided study drug and placebo as well as salary support for one member of the research team. The research team analyzed the data and drafted the manuscript, and Laboratoire HRA-Pharma agreed to the final submission, NCT00290251. NR 32 TC 44 Z9 49 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2011 VL 95 IS 2 BP 767 EP U769 DI 10.1016/j.fertnstert.2010.09.059 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 709EA UT WOS:000286419000071 PM 21055739 ER PT J AU Davis, RM Matsumoto, S Bernardo, M Sowers, A Matsumoto, KI Krishna, MC Mitchell, JB AF Davis, Ryan M. Matsumoto, Shingo Bernardo, Marcelino Sowers, Anastasia Matsumoto, Ken-Ichiro Krishna, Murali C. Mitchell, James B. TI Magnetic resonance imaging of organic contrast agents in mice: capturing the whole-body redox landscape SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Magnetic resonance imaging; Nitroxides; Redox; Radioprotection; Electron paramagnetic resonance spectroscopy; Free radicals ID IN-VIVO MEASUREMENT; SUPEROXIDE-DISMUTASE; SOLUBLE NITROXIDES; MURINE TUMOR; TEMPOL; OXYGEN; AMIFOSTINE; RADIOTHERAPY; METABOLISM; PROTECTION AB Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6-7.2 mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO(2) in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO(2) is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo. Published by Elsevier Inc. C1 [Davis, Ryan M.; Matsumoto, Shingo; Sowers, Anastasia; Krishna, Murali C.; Mitchell, James B.] NIH, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bernardo, Marcelino] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Bernardo, Marcelino] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Matsumoto, Ken-Ichiro] Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 260, Japan. RP Davis, RM (reprint author), NIH, Radiat Biol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM davisrm2@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We thank Dr. Pete Choyke for his provision of imaging resources. We thank Dr. Brenda Klaunberg for her assistance in identifying murine tissues on MR images. NR 45 TC 26 Z9 27 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2011 VL 50 IS 3 BP 459 EP 468 DI 10.1016/j.freeradbiomed.2010.11.028 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 722JX UT WOS:000287429600006 PM 21130158 ER PT J AU Ko, SU Ling, SM Schreiber, C Nesbitt, M Ferrucci, L AF Ko, Seung-uk Ling, Shari M. Schreiber, Catherine Nesbitt, Mark Ferrucci, Luigi TI Gait patterns during different walking conditions in older adults with and without knee osteoarthritis-Results from the Baltimore Longitudinal Study of Aging SO GAIT & POSTURE LA English DT Article DE Gait; Knee osteoarthritis; Challenging walking; Mechanical work expenditure ID MUSCLE; STRATEGIES; FATIGUE; HIP AB Biomechanical analysis of lower extremity activities while walking at different speeds and in challenging conditions may help to identify specific gait patterns associated with knee osteoarthritis (knee-OA). We hypothesized that individuals with asymptomatic knee-OA have lower ankle activity, while individuals with symptomatic knee-OA have similar or higher ankle activity compared to individuals without knee-OA, and that such differences are enhanced during challenging gait tasks. We tested this hypothesis by examining gait characteristics in multiple gait tasks using data from 153 Baltimore Longitudinal Study of Aging (BLSA) participants (112 without knee-OA, 41 with knee-OA: 53-87 years, 52% women). All participants who could walk unassisted were evaluated in the BLSA gait lab while walking at self-selected speed (usual-walking), at maximum speed (fast-walking) and again at self-selected speed after 30-min of walking activities (usual-walking-after-30 min). Knee range of motion was lower for knee-OA participants in the fast-walking and usual-walking-after-30 min tasks (p < 0.030). Ankle range of motion for symptomatic knee-OA was greater compared to asymptomatic knee-OA for all walking tasks (p < 0.050). Symptomatic knee-OA had greater generative MWE of the ankle compared to asymptomatic knee-OA (p = 0.034), while keeping similar absorptive MWE of the knee when compared to no-OA controls (p = 0.151). Symptomatic knee-OA individuals seem to adapt an ankle kinematic gait pattern aimed at avoiding knee pain, by enhancing forward propulsion so to minimize knee joint load. Whether these conditions represent subsequent steps in the causal pathway from knee-OA to changes in gait is still not clear. Published by Elsevier B.V. C1 [Ko, Seung-uk] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. RP Ko, SU (reprint author), Harbor Hosp, NIA, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA. EM kos2@mail.nih.gov FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the National Institute on Aging. NR 21 TC 12 Z9 13 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD FEB PY 2011 VL 33 IS 2 BP 205 EP 210 DI 10.1016/j.gaitpost.2010.11.006 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 737LF UT WOS:000288569600011 PM 21145241 ER PT J AU Lochhead, P Frank, B Hold, GL Rabkin, CS Ng, MTH Vaughan, TL Risch, HA Gammon, MD Lissowska, J Weck, MN Raum, E Muller, H Illig, T Klopp, N Dawson, A McColl, KE Brenner, H Chow, WH El-Omar, EM AF Lochhead, Paul Frank, Bernd Hold, Georgina L. Rabkin, Charles S. Ng, Michael T. H. Vaughan, Thomas L. Risch, Harvey A. Gammon, Marilie D. Lissowska, Jolanta Weck, Melanie N. Raum, Elke Mueller, Heiko Illig, Thomas Klopp, Norman Dawson, Alan McColl, Kenneth E. Brenner, Hermann Chow, Wong-Ho El-Omar, Emad M. TI Genetic Variation in the Prostate Stem Cell Antigen Gene and Upper Gastrointestinal Cancer in White Individuals SO GASTROENTEROLOGY LA English DT Article DE Stomach Cancer; Esophageal Cancer; Genetic Polymorphisms; Cancer Genetics ID CHRONIC ATROPHIC GASTRITIS; HELICOBACTER-PYLORI INFECTION; INCREASED RISK; STOMACH-CANCER; GLEASON SCORE; OLDER-ADULTS; LY-6 FAMILY; CARCINOMA; EXPRESSION; ADENOCARCINOMA AB BACKGROUND & AIMS: An association between gastric cancer and the rs2294008 (C > T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals. METHODS: We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables. RESULTS: Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9). CONCLUSIONS: The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers. C1 [El-Omar, Emad M.] Univ Aberdeen, Div Appl Med, Sch Med & Dent, Inst Med Sci,Gastrointestinal Res Grp, Aberdeen AB25 2ZD, Scotland. [Frank, Bernd; Weck, Melanie N.; Raum, Elke; Mueller, Heiko; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Rabkin, Charles S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Vaughan, Thomas L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Div Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Illig, Thomas; Klopp, Norman] Res Ctr Environm & Hlth, Inst Epidemiol, Neuherberg, Germany. [McColl, Kenneth E.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. RP El-Omar, EM (reprint author), Univ Aberdeen, Div Appl Med, Sch Med & Dent, Inst Med Sci,Gastrointestinal Res Grp, Foresterhill, Aberdeen AB25 2ZD, Scotland. EM e.el-omar@abdn.ac.uk RI Brenner, Hermann/B-4627-2017; OI Brenner, Hermann/0000-0002-6129-1572; Lissowska, Jolanta/0000-0003-2695-5799 FU Baden-Wuerttemberg Ministry of Science, Research, and the Arts; Scottish Government Chief Scientist Office; United States Public Health Service [U01-CA57983, U01-CA57949, U01-CA57923, P30ES10126]; National Cancer Institute, National Institutes of Health, and Department of Health and Human Services [N02-CP40501, N01-CN05230] FX Supported by grants from the Baden-Wuerttemberg Ministry of Science, Research, and the Arts for The ESTHER study baseline examination and the German analyses on atrophic gastritis; by a Scottish Government Chief Scientist Office fellowship (to P. L.); by the United States Public Health Service (U01-CA57983, U01-CA57949, U01-CA57923, P30ES10126) for the US multicenter esophageal and gastric cancer study; and by the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services (N02-CP40501, N01-CN05230). NR 52 TC 41 Z9 41 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 435 EP 441 DI 10.1053/j.gastro.2010.11.001 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600022 PM 21070776 ER PT J AU Schwarz, KB Gonzalez-Peralta, RP Murray, KF Molleston, JP Haber, BA Jonas, MM Rosenthal, P Mohan, P Balistreri, WF Narkewicz, MR Smith, L Lobritto, SJ Rossi, S Valsamakis, A Goodman, Z Robuck, PR Barton, BA AF Schwarz, Kathleen B. Gonzalez-Peralta, Regino P. Murray, Karen F. Molleston, Jean P. Haber, Barbara A. Jonas, Maureen M. Rosenthal, Philip Mohan, Parvathi Balistreri, William F. Narkewicz, Michael R. Smith, Lesley Lobritto, Steven J. Rossi, Stephen Valsamakis, Alexandra Goodman, Zachary Robuck, Patricia R. Barton, Bruce A. CA Peds-C Clinical Res Network TI The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C SO GASTROENTEROLOGY LA English DT Article DE Antiviral Therapy; Pediatric Liver Disease; Multicenter Pediatric Trial ID ALPHA-2B PLUS RIBAVIRIN; VIROLOGICAL RESPONSE RATES; VIRUS-INFECTION; PEGYLATED INTERFERON; INITIAL TREATMENT; EFFICACY; SAFETY; TRIAL; PHARMACOKINETICS; THERAPY AB BACKGROUND & AIMS: Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases the efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5 to 17 years old with chronic hepatitis C. METHODS: HCV RNA-positive children from 11 university medical centers were randomly assigned to receive either PEG alfa-2a (PEG-2a; 180 mu g/1.73 m(2) body surface area, subcutaneously each week; n = 55) and ribavirin (15 mg/kg orally in 2 doses daily) or PEG-2a and placebo (n = 59) for 48 weeks. The primary end point was sustained virologic response (SVR; lack of detectable HCV RNA at least 24 weeks after stopping therapy). RESULTS: SVR was achieved in 53% of children treated with PEG-2a and ribavirin, compared with 21% of children who received PEG-2a and placebo (P < .001). Early virologic response (HCV RNA reduction >2 log(10) IU at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year 2 follow-up visit; the durability of virologic response was 100% in both groups. CONCLUSIONS: The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents. C1 [Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Gastroenterol & Nutr, Baltimore, MD 21205 USA. [Valsamakis, Alexandra] Johns Hopkins Univ, Sch Med, Johns Hopkins Clin Virol Lab, Baltimore, MD USA. [Gonzalez-Peralta, Regino P.] Univ Florida, Coll Med, Dept Pediat, Sect Hepatol & Liver Transplantat, Gainesville, FL USA. [Gonzalez-Peralta, Regino P.] Shands Childrens Hosp, Gainesville, FL USA. [Murray, Karen F.] Seattle Childrens Hosp, Div Gastroenterol & Hepatol, Seattle, WA USA. [Molleston, Jean P.] Indiana Univ Sch Med, Sect Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN USA. [Haber, Barbara A.] Univ Penn, Childrens Hosp Philadelphia, Clin & Translat Sci Award Res Ctr, Philadelphia, PA 19104 USA. [Jonas, Maureen M.] Childrens Hosp Boston, Div Gastroenterol, Boston, MA USA. [Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Mohan, Parvathi] Childrens Natl Med Ctr, Div Gastroenterol Hepatol & Nutr, Washington, DC 20010 USA. [Balistreri, William F.] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Narkewicz, Michael R.] Univ Colorado, Sect Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Narkewicz, Michael R.] Childrens Hosp, Aurora, CO USA. [Smith, Lesley; Lobritto, Steven J.] Columbia Univ, Med Ctr, New York, NY USA. [Rossi, Stephen] Roche Mol Syst, Pleasanton, CA USA. [Goodman, Zachary] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Robuck, Patricia R.] NIDDK, NIH, Washington, DC USA. [Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. RP Schwarz, KB (reprint author), Brady 320,600 N Wolfe St, Baltimore, MD 21287 USA. EM kschwarz@jhmi.edu OI Barton, Bruce/0000-0001-7878-8895 FU Roche; Bristol-Myers Squibb; Gilead; Novartis; Boehringer-Ingelheim; Digestive Care Inc; National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration [1UO1DK067767-01]; National Institutes of Health/National Center for Research Resources Colorado CTSI [UL1 RR025780]; Children's Hospital, Aurora [M01-RR-02172]; Children's Hospital Boston, Boston, MA [M01-RR-01271]; University of California, San Francisco, CA [5-M01-RR-020359-01]; Children's National Medical Center, Washington, DC [M01-RR-00645]; Columbia University Medical Center, New York, NY [M01-RR-00082]; University of Florida, Gainesville, FL [M01-RR-00037]; University of Washington, Seattle, WA [5-M01-RR-000240]; Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA [U01-DK-067767-02]; Johns Hopkins Medical Center, Baltimore, MD [M01-RR-08084]; University of Cincinnati, Cincinnati, OH; Indiana University, Indianapolis, IN [M01-RR-00750]; [M01-RR-00069] FX The authors disclose the following: Dr Schwarz is supported by Roche (grant/research support), Bristol-Myers Squibb (grant/research support), Gilead (grant/research support), and Novartis (consultant). Dr Gonzalez-Peralta is supported by Boehringer-Ingelheim (grant/research support), Roche (grant/research support), Bristol Myers-Squibb (grant/research support), and Novartis (consultant). Dr Murray is supported by Roche (grant/research support), Bristol-Myers Squibb (grant/research support), and Novartis. Dr Molleston, Dr Haber, Dr Jonas, Dr Rosenthal, Dr Smith, Dr Lobritto, and Dr Valsamakis are supported by Roche (grant/research support). Dr Mohan is supported by Roche (grant/research support) and Gilead (grant/research support). Dr Balistreri is supported by Digestive Care Inc (consultant) and Roche (grant/research support). Dr Narkewicz is supported by Novartis (consultant) and Roche (grant/research support). Dr Rossi is an employee of Roche Molecular Systems. The remaining authors disclose no conflicts.; Supported by a cooperative agreement between the National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration (contract no. 1UO1DK067767-01. CRC) and in part by National Institutes of Health/National Center for Research Resources Colorado CTSI grant no. UL1 RR025780 and the following study sites: M01-RR-00069, Children's Hospital, Aurora, CO; M01-RR-02172, Children's Hospital Boston, Boston, MA; M01-RR-01271, University of California, San Francisco, CA; 5-M01-RR-020359-01, Children's National Medical Center, Washington, DC; M01-RR-00645, Columbia University Medical Center, New York, NY; M01-RR-00082, University of Florida, Gainesville, FL; M01-RR-00037, University of Washington, Seattle, WA; 5-M01-RR-000240, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA; U01-DK-067767-02, Johns Hopkins Medical Center, Baltimore, MD; M01-RR-08084, University of Cincinnati, Cincinnati, OH; and M01-RR-00750, Indiana University, Indianapolis, IN. The contents of this report are the authors' sole responsibility and do not necessarily represent the official views of the National Institutes of Health. Additional support was provided by Hoffmann-La Roche for study medications, the data coordinating center, and central laboratory costs. NR 34 TC 51 Z9 54 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 450 EP U148 DI 10.1053/j.gastro.2010.10.047 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600024 PM 21036173 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, Constance E. Everhart, James E. TI Gallstone Disease Is Associated With Increased Mortality in the United States SO GASTROENTEROLOGY LA English DT Article DE Gallstone Disease; Epidemiology; Gallbladder; Cholelithiasis ID GALLBLADDER-DISEASE; CARDIOVASCULAR-DISEASE; CANCER; POPULATION; CHOLECYSTECTOMY; CHOLELITHIASIS; CONSUMPTION; INSULIN; COFFEE; LIVER AB BACKGROUND & AIMS: Gallstones are common and contribute to morbidity and health care costs, but their effects on mortality are unclear. We examined whether gallstone disease was associated with overall and cause-specific mortalities in a prospective national population-based sample. METHODS: We analyzed data from 14,228 participants in the third US National Health and Nutrition Examination Survey (20-74 years old) who underwent gallbladder ultrasonography from 1988 to 1994. Gallstone disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. The underlying cause of death was identified from death certificates collected through 2006 (mean follow-up, 14.3 years). Mortality hazard ratios (HR) were calculated using Cox proportional hazards regression analysis to adjust for multiple demographic and cardiovascular disease risk factors. RESULTS: The prevalence of gallstones was 7.1% and of cholecystectomy was 5.3%. During a follow-up period of 18 years or more, the cumulative mortality was 16.5% from all causes (2389 deaths), 6.7% from cardiovascular disease (886 deaths), and 4.9% from cancer (651 deaths). Participants with gallstone disease had higher all-cause mortality in age-adjusted (HR = 1.3; 95% confidence interval [CI]: 1.2-1.5) and multivariate-adjusted analysis (HR = 1.3; 95% CI: 1.1-1.5). A similar increase was observed for cardiovascular disease mortality (multivariate-adjusted HR = 1.4; 95% CI: 1.2-1.7), and cancer mortality (multivariate-adjusted HR = 1.3; 95% CI: 0.98 - 1.8). Individuals with gallstones had a similar increase in risk of death as those with cholecystectomy (multivariate-adjusted HR = 1.1; 95% CI: 0.92-1.4). CONCLUSIONS: In the US population, persons with gallstone disease have increased mortality overall and mortalities from cardiovascular disease and cancer. This relationship was found for both ultrasound-diagnosed gallstones and cholecystectomy. C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Everhart, James E.] NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700001G] FX This work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G). NR 29 TC 43 Z9 48 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 508 EP 516 DI 10.1053/j.gastro.2010.10.060 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600030 PM 21075109 ER PT J AU Veerapu, NS Raghuraman, S Liang, TJ Heller, T Rehermann, B AF Veerapu, Naga Suresh Raghuraman, Sukanya Liang, T. Jake Heller, Theo Rehermann, Barbara TI Sporadic Reappearance of Minute Amounts of Hepatitis C Virus RNA After Successful Therapy Stimulates Cellular Immune Responses SO GASTROENTEROLOGY LA English DT Article DE Interferon; IFN; Liver Disease; Virology ID BLOOD MONONUCLEAR-CELLS; ALANINE AMINOTRANSFERASE LEVELS; SUSTAINED VIROLOGICAL RESPONSE; HCV RNA; OCCULT INFECTION; CULTURE; LIVER; PERSISTENCE; INTERFERON; RIBAVIRIN AB BACKGROUND & AIMS: Several studies have reported hepatitis C virus (HCV) RNA sequences in the circulation after treatment-induced or spontaneous recovery. We investigated whether the HCV RNA represents persistence of HCV infection or reinfection. METHODS: We studied 117 patients who recovered from HCV infection (98 following therapy and 19 spontaneously). A reverse-transcription polymerase chain reaction assay was used to detect the 5'-untranslated region of HCV. T-cell responses were studied by enzyme-linked immunospot for interferon-gamma. RESULTS: Plasma samples from 15% of treatment-recovered patients and no spontaneously recovered patient tested positive for HCV RNA. Lymphocytes from 3 patients who responded to therapy and 1 who recovered spontaneously tested positive. The frequency of HCV RNA detection in plasma correlated inversely with the time after the end of treatment. Post-treatment HCV 5'-untranslated region sequences matched pretreatment sequences in 85% of cases. T-cell responses were significantly greater at time points with detectable trace amounts of HCV RNA than at time points without detectable HCV RNA (P = .035) and were primarily against nonstructural HCV antigens. The immune hierarchy was preserved over 5 years in patients whose post-treatment HCV RNA sequences matched pretreatment sequences, indicating HCV RNA persistence. An altered immune hierarchy with dominant immune responses, shifting from nonstructural to structural antigens, was observed in a single patient whose post-treatment HCV genotype differed from that of the pretreatment genotype, indicating HCV reinfection. CONCLUSIONS: Trace amounts of HCV RNA of pretreatment sequence persisted and reappeared sporadically in the circulation within 8 years after recovery from hepatitis C but not thereafter, indicating that patients are cured of HCV infection. Reappearance of HCV RNA induced HCV-specific T-cell responses. C1 [Veerapu, Naga Suresh; Raghuraman, Sukanya; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16C, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Veerapu, Naga Suresh/F-4338-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 34 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 676 EP U422 DI 10.1053/j.gastro.2010.10.048 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600046 PM 21040725 ER PT J AU Kim, AY Kuntzen, T Timm, J Nolan, BE Baca, MA Reyor, LL Berical, AC Feller, AJ Johnson, KL Zur Wiesch, JS Robbins, GK Chung, RT Walker, BD Carrington, M Allen, TM Lauer, GM AF Kim, Arthur Y. Kuntzen, Thomas Timm, Joerg Nolan, Brian E. Baca, Melanie A. Reyor, Laura L. Berical, Andrew C. Feller, Andrea J. Johnson, Kristin L. Zur Wiesch, Julian Schulze Robbins, Gregory K. Chung, Raymond T. Walker, Bruce D. Carrington, Mary Allen, Todd M. Lauer, Georg M. TI Spontaneous Control of HCV Is Associated With Expression of HLA-B*57 and Preservation of Targeted Epitopes SO GASTROENTEROLOGY LA English DT Article DE CD8 T Cell; HLA-B57; Spontaneous Clearance; Viral Escape ID C VIRUS-INFECTION; T-CELL RESPONSES; ANTIGEN CLASS-I; DISEASE PROGRESSION; IMMUNE-RESPONSES; HIV-INFECTION; P24 GAG; EVOLUTION; HLA; ALLELES AB BACKGROUND & AIMS: HLA class I alleles are linked to spontaneous control of hepatitis C virus (HCV) and human immunodeficiency virus-1, but for HCV the roles of particular alleles and corresponding CD8(+) T-cell responses remain incompletely defined. We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses. METHODS: In a cohort of HCV individuals, we determined HLA class I alleles, HCV outcomes, T-cell responses, and examined sequence data for mutational changes within key epitopes. RESULTS: Carriage of HLA-B*57 was associated with a higher rate of viral clearance (risk ratio = 2.0; 95% confidence interval: 1.2-3.4), while HLA-B*08 was associated with a lower rate (risk ratio = 0.34; 95% confidence interval: 0.1-0.9]. Two HLA-B*57-restricted T-cell epitopes were targeted in spontaneous clearance; subjects with chronic viremia expressing HLA-B*57 harbored HCV strains with a high frequency of mutations in key residues. HLAB*57-mediated escape was supported by diminished immune recognition of these variants and acute HCV infection revealing viral evolution toward less recognized variants. Analysis of a genotype 1b strain from a single-source HCV outbreak in which HLA-B*57 was not protective revealed sequence variations that interfere with immunogenicity, thereby preventing HLA-B*57-mediated immune pressure. CONCLUSIONS: Our data indicate a role of HLA-B*57-restricted CD8(+) T-cell responses in mediating spontaneous clearance and evolution in HCV infection, and viral strains containing epitope variants that are less recognized abrogate the protective effects of HLA-B*57. The finding that HLAB*57-mediated antiviral immunity is associated with control of both human immunodeficiency virus-1 and HCV suggests a common shared mechanism of a successful immune response against persistent viruses. C1 [Kim, Arthur Y.; Reyor, Laura L.; Johnson, Kristin L.; Robbins, Gregory K.; Walker, Bruce D.; Allen, Todd M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Nolan, Brian E.; Reyor, Laura L.; Chung, Raymond T.; Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Kim, Arthur Y.; Kuntzen, Thomas; Baca, Melanie A.; Berical, Andrew C.; Feller, Andrea J.; Walker, Bruce D.; Carrington, Mary; Allen, Todd M.] Ragon Inst MGH Massachusetts Inst Technol & Harva, Boston, MA USA. [Timm, Joerg] Univ Essen Gesamthsch, Inst Virol, Essen, Germany. [Zur Wiesch, Julian Schulze] Univ Med Ctr Hamburg Eppendorf, Div Med, Hamburg, Germany. [Zur Wiesch, Julian Schulze; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Kim, AY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, GRB-504, Boston, MA 02114 USA. EM akim1@partners.org RI Robbins, Gregory/F-7988-2011; Allen, Todd/F-5473-2011 FU National Institutes of Health [AI 054379, AI 066345, AI 031563, AI 042851, AI 067926, AI 069939, DK 078772, AI 062435]; Harvard Medical School Center for AIDS Research [P30 AI060354]; Campbell Foundation; Liver Foundation; Doris Duke Charitable Foundation; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft [DFG KU2250/1-1] FX This work was funded by the National Institutes of Health (AI 054379 to AYK, AI 066345 to AYK, GML, TMA, BDW; AI 031563, AI 042851 and AI 054379 to BDW; AI 067926 to TMA; AI 069939 and DK 078772 to RTC, AI 062435 to GKR), the Harvard Medical School Center for AIDS Research (P30 AI060354), the Campbell Foundation (GML), the Liver Foundation (GML), the Doris Duke Charitable Foundation and Howard Hughes Medical Institute (BDW), Deutsche Forschungsgemeinschaft grant DFG KU2250/1-1 (TK). NR 32 TC 66 Z9 72 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2011 VL 140 IS 2 BP 686 EP U434 DI 10.1053/j.gastro.2010.09.042 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 711LR UT WOS:000286593600047 PM 20875418 ER PT J AU Wohr, M Roullet, FI Crawley, JN AF Woehr, M. Roullet, F. I. Crawley, J. N. TI Reduced scent marking and ultrasonic vocalizations in the BTBR T plus tf/J mouse model of autism SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Autism; communication; mice; olfaction; scent marking; social behavior; ultrasonic vocalizations ID MICE MUS-DOMESTICUS; BENZODIAZEPINE RECEPTOR COMPLEX; MALE HOUSE MICE; URINE MARKING; INDIVIDUAL RECOGNITION; INBRED STRAINS; SEX-PHEROMONE; C57BL/6J MICE; SOCIAL-STATUS; T+TF/J MICE AB Qualitative impairments in communication, such as delayed language and poor interactive communication skills, are fundamental to the diagnosis of autism. Investigations into social communication in adult BTBR T+tf/J (BTBR) mice are needed to determine whether this inbred strain incorporates phenotypes relevant to the second diagnostic symptom of autism, communication deficits, along with its strong behavioral phenotypes relevant to the first and third diagnostic symptoms, impairments in social interactions and high levels of repetitive behavior. The aim of the present study was to simultaneously measure female urine-elicited scent marking and ultrasonic vocalizations in adult male BTBR mice, in comparison with a standard control strain with high sociability, C57BL/6J (B6), for the assessment of a potential communication deficit in BTBR. Adult male BTBR mice displayed lower scent marking and minimal ultrasonic vocalization responses to female urine obtained from both B6 and BTBR females. Lower scent marking and ultrasonic vocalizations in a social setting by BTBR, as compared with B6, are consistent with the well-replicated social deficits in this inbred mouse strain. Our findings support the interpretation that BTBR incorporate communication deficits, and suggest that scent marking and ultrasonic vocalizations offer promising measures of interest in social cues that may be widely applicable to investigations of mouse models of autism. C1 [Woehr, M.] Univ Marburg, D-35032 Marburg, Germany. [Woehr, M.; Roullet, F. I.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Wohr, M (reprint author), Univ Marburg, Gutenbergstr 18, D-35032 Marburg, Germany. EM markus.woehr@staff.uni-marburg.de FU National Institute of Mental Health FX This work was supported by the National Institute of Mental Health Intramural Research Program. NR 68 TC 68 Z9 69 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 EI 1601-183X J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD FEB PY 2011 VL 10 IS 1 BP 35 EP 43 DI 10.1111/j.1601-183X.2010.00582.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 709VG UT WOS:000286468900005 PM 20345893 ER PT J AU Scattoni, ML Ricceri, L Crawley, JN AF Scattoni, M. L. Ricceri, L. Crawley, J. N. TI Unusual repertoire of vocalizations in adult BTBR T plus tf/J mice during three types of social encounters SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Autism; communication; social approach; social motivation; ultrasonic vocalizations ID ULTRASONIC VOCALIZATIONS; FEMALE MICE; MUS-MUSCULUS; AUTISTIC-CHILDREN; INBRED STRAINS; MOUSE MODELS; T+TF/J MICE; HOUSE MICE; BEHAVIOR; COMMUNICATION AB BTBR T+tf/J (BTBR) is an inbred mouse strain that displays social deficits and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. We previously reported an unusual pattern of ultrasonic vocalizations in BTBR pups that may represent a behavioral homolog to the second diagnostic symptom of autism, impaired communication. This study investigated the social and vocal repertoire in adult BTBR mice, to evaluate the role of ultrasonic vocalizations in multiple social situations at the adult stage of development. Three different social contexts were considered: male-female, male-male (resident-intruder) and female-female interactions. Behavioral responses and ultrasonic vocalizations were recorded for BTBR and for the highly social control strain C57BL/6J (B6). No episodes of overt fighting or mating were observed during the short durations of the three different experimental encounters. BTBR displayed lower levels of vocalizations and social investigation in all three social contexts as compared with B6. In addition, the correlation analyses between social investigation and ultrasonic vocalization emission rate showed that in B6 mice, the two variables were positively correlated in all the three different social settings, whereas in BTBR mice, the positive correlation was significant only in the male-female interactions. These findings strongly support the value of simultaneously recording two aspects of the mouse social repertoire: social motivation and bioacoustic communication. Moreover, our findings in adults are consistent with previous results in pups, showing an unusual vocal repertoire in BTBR as compared with B6. C1 [Scattoni, M. L.; Ricceri, L.] Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Scattoni, M. L.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Scattoni, ML (reprint author), Ist Super Sanita, Neurotoxicol & Neuroendocrinol Sect, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM marialuisa.scattoni@iss.it RI Scattoni, Maria Luisa/K-4116-2016 OI Scattoni, Maria Luisa/0000-0002-6659-0280 FU National Institute of Mental Health; Istituto Superiore di Sanita [530F/52] FX We are grateful for the excellent technical contributions of our students Maria Adelaide Marconi, Ludovica De Benedetti, Gloria Matte Bon, ISS, and Mark Harris, NIMH. Special thanks go to Professor Stefan Brudzynsky, Brock University, Dr Markus Wohr, University of Marburg, and Raimund Specht, Avisoft Bioacoustics, for their expert advice concerning the unstructured call categorization. We thank Adam Katz, NIMH, for the editing of the supplementary movies. This work was supported by the National Institute of Mental Health Intramural Research Program and Istituto Superiore di Sanita 530F/52 'Neurobehavioral phenotyping of genetically modified mouse models of mental retardation'. NR 59 TC 100 Z9 102 U1 4 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD FEB PY 2011 VL 10 IS 1 BP 44 EP 56 DI 10.1111/j.1601-183X.2010.00623.x PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 709VG UT WOS:000286468900006 PM 20618443 ER PT J AU Coutellier, L Logemann, A Kuo, J Rusnak, M Usdin, TB AF Coutellier, L. Logemann, A. Kuo, J. Rusnak, M. Usdin, T. B. TI TIP39 modulates effects of novelty-induced arousal on memory SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Noradrenergic system; novelty-induced arousal; short-term memory; TIP39; working memory ID OBJECT RECOGNITION MEMORY; ADRENAL STRESS HORMONES; TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; PARATHYROID-HORMONE-2 RECEPTOR; EMOTIONAL AROUSAL; LOCUS-COERULEUS; MICE; BRAIN; COGNITION AB Tuberoinfundibular peptide of 39 residues (TIP39) is a neuropeptide localized to neural circuits subserving emotional processing. Recent work showed that mice with null mutation for the gene coding TIP39 (TIP39-KO mice) display increased susceptibility to environmental provocation. Based on this stressor-dependent phenotype, the neuroanatomical distribution of TIP39, and knowledge that novelty-induced arousal modulates memory functions via noradrenergic activation, we hypothesized that exposure to a novel environment differently affects memory performance of mice with or without TIP39 signaling, potentially by differences in sensitivity of the noradrenergic system. We tested TIP39-KO mice and mice with null mutation of its receptor, the parathyroid hormone 2 receptor (PTH2-R), in tasks of short-term declarative and social memory (object recognition and social recognition tests, respectively), and of working memory (Y-maze test) under conditions of novelty-induced arousal or acclimation to the test conditions. Mice lacking TIP39 signaling showed memory impairment selectively under conditions of novelty-induced arousal. Acute administration of a PTH2-R antagonist in wild-type mice had a similar effect. The restoration of memory functions in TIP39-KO mice after injection of a beta-adrenoreceptor-blocker, propranolol, suggested involvement of the noradrenergic system. Collectively, these results suggest that the TIP39/PTH2-R system modulates the effects of novelty exposure on memory performance, potentially by acting on noradrenergic signaling. C1 [Coutellier, L.; Logemann, A.; Kuo, J.; Rusnak, M.; Usdin, T. B.] NIMH, Sect Fundamental Neurosci, NIH, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, NIH, 35 Convent Dr,Room 1B-215, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov FU NIH, National Institute of Mental Health FX We thank Jim Pickel for generation of knockout mice, Elka Scordalakes and Eugene Dimitrov for help and advice, and Andrew Holmes for advice and helpful comments on the manuscript. This research was supported by the Intramural Program of the NIH, National Institute of Mental Health. The authors declare that there are no potential conflicts of interest. NR 44 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD FEB PY 2011 VL 10 IS 1 BP 90 EP 99 DI 10.1111/j.1601-183X.2010.00643.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 709VG UT WOS:000286468900010 PM 20796031 ER PT J AU Yang, JD Sun, ZF Hu, CL Lai, JP Dove, R Nakamura, I Lee, JS Thorgeirsson, SS Kang, KJ Chu, IS Roberts, LR AF Yang, Ju Dong Sun, Zhifu Hu, Chunling Lai, Jinping Dove, Rebecca Nakamura, Ikuo Lee, Ju-Seog Thorgeirsson, Snorri S. Kang, Koo Jeong Chu, In-Sun Roberts, Lewis R. TI Sulfatase 1 and Sulfatase 2 in Hepatocellular Carcinoma: Associated Signaling Pathways, Tumor Phenotypes, and Survival SO GENES CHROMOSOMES & CANCER LA English DT Article ID IQGAP1 INTEGRATES CA2+/CALMODULIN; HEPARAN-SULFATE; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; BREAST-CANCER; GROWTH; HSULF-1; CELLS; EXPRESSION; BINDING AB The heparin-degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) have opposing effects in hepatocarcinogenesis despite structural similarity. Using mRNA expression arrays, we analyzed the correlations of SULF expression with signaling networks in human hepatocellular carcinomas (HCCs) and the associations of SULF expression with tumor phenotype and patient survival. Data from two mRNA microarray analyses of 139 and 36 HCCs and adjacent tissues were used as training and validation sets. Partek and Metacore software were used to identify SULF correlated genes and their associated signaling pathways. Associations between SULF expression, the hepatoblast subtype of HCC, and survival were examined. Both SULF1 and 2 had strong positive correlations with periostin, IQGAP1, TGFB1, and vimentin and inverse correlations with HNF4A and IQGAP2. Genes correlated with both SULFs were highly associated with the cell adhesion, cytoskeletal remodeling, blood coagulation, TGFB, and Wnt/beta-catenin and epithelial mesenchymal transition signaling pathways. Genes uniquely correlated with SULF2 were more associated with neoplastic processes than genes uniquely correlated with SULF1. High SULF expression was associated with the hepatoblast subtype of HCC. There was a bimodal effect of SULF1 expression on prognosis, with patients in the lowest or highest tertile having a worse prognosis than those in the middle tertile. SULFs have complex effects on HCC signaling and patient survival. There are functionally similar associations with cell adhesion, ECM remodeling, TGFB, and WNT pathways, but also unique associations of SULF1 and SULF2. The roles and targeting of the SULFs in cancer require further investigation. (C) 2010 Wiley-Liss, Inc. C1 [Yang, Ju Dong; Hu, Chunling; Lai, Jinping; Dove, Rebecca; Nakamura, Ikuo; Roberts, Lewis R.] Mayo Clin, Miles Shirley Fiterman Ctr Digest Dis, Coll Med, Rochester, MN 55905 USA. [Yang, Ju Dong; Sun, Zhifu; Hu, Chunling; Lai, Jinping; Dove, Rebecca; Nakamura, Ikuo; Roberts, Lewis R.] Mayo Clin, Ctr Canc, Rochester, MN 55905 USA. [Sun, Zhifu] Mayo Clin, Dept Biomed Stat & Informat, Coll Med, Rochester, MN 55905 USA. [Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. [Kang, Koo Jeong] Keimyung Univ, Sch Med, Taegu, South Korea. [Chu, In-Sun] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Taejon, South Korea. RP Roberts, LR (reprint author), Mayo Clin, Miles Shirley Fiterman Ctr Digest Dis, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM chu@kribb.re.kr; Roberts.lewis@mayo.edu OI Sun, Zhifu/0000-0001-8461-7523; Roberts, Lewis/0000-0001-7885-8574 FU National Institutes of Health [CA100882, CA128633]; Mayo Clinic Center for Cell Signaling in Gastroenterology [NIDDK P30DK084567]; Mayo Clinic Cancer Center; Mayo Foundation; 21C Frontier Functional Human Genome Project [MEST FG-4-2]; KRIBB FX Supported by: National Institutes of Health, Grant numbers: CA100882, CA128633; Mayo Clinic Center for Cell Signaling in Gastroenterology, Grant number: NIDDK P30DK084567; Mayo Clinic Cancer Center; Mayo Foundation; 21C Frontier Functional Human Genome Project (MEST FG-4-2); KRIBB. NR 50 TC 21 Z9 22 U1 0 U2 18 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2011 VL 50 IS 2 BP 122 EP 135 DI 10.1002/gcc.20838 PG 14 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 693ZL UT WOS:000285263800006 PM 21104785 ER PT J AU Lacey, JV Yang, HN Gaudet, MM Dunning, A Lissowska, J Sherman, ME Peplonska, B Brinton, LA Healey, CS Ahmed, S Pharoah, P Easton, D Chanock, S Garcia-Closas, M AF Lacey, James V., Jr. Yang, Hannah Gaudet, Mia M. Dunning, Alison Lissowska, Jolanta Sherman, Mark E. Peplonska, Beata Brinton, Louise A. Healey, Catherine S. Ahmed, Shahana Pharoah, Paul Easton, Douglas Chanock, Stephen Garcia-Closas, Montserrat TI Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a population-based case-control study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE SNPs; Uterine cancer; Epidemiology; Haplotypes ID COWDEN-SYNDROME; HIGH-FREQUENCY; BREAST-CANCER; MUTATIONS; RISK; CARCINOMA; PATHWAY; VARIANTS; EPIDEMIOLOGY; ASSOCIATION AB Objective. We assessed whether common genetic variation in PTEN, PIK3CA,AKT1, MLH1, and MSH2-genes that reportedly are frequently altered in endometrial cancer-was associated with risk of endometrial cancer. Methods. Using data from a population-based case-control study in Poland (PECS) of 417 cases and 407 matched controls, we genotyped 76 tagging single nucleotide polymorphisms (tagSNPs; located in or within 10 kb upstream or 5 kb downstream of the gene of interest, minor allele frequency >=5% among various ethnic groups, and not already represented by another tagSNP at a LD of r(2) >=0.80) on an Illumina Custom Infinium iSelect assay that included over 29,000 SNPs in 1316 genes. For individual SNPs, we used unconditional logistic regression models, adjusted for age and site, to generate odds ratios (ORs) and 95% confidence intervals (CIs). To replicate the one statistically significant association in PECS, we independently genotyped that tagSNP among 1141 endometrial cancer cases and 2275 controls from the SEARCH study in the UK. We assessed haplotypes via extended haplotype blocks and the sequential haplotype scan method. Results. The rs2677764 tagSNP in PIK3CA was statistically significantly associated with endometrial cancer in PECS (OR = 1.42, 95% Cl, 1.03-1.95; P = 0.03) but not SEARCH (OR=0.98, 95% Cl = 0.82-1.17). Of the 25 haplotypes observed in at least 5% of cases and controls in PECS, only 1, in PIK3CA, was statistically significantly associated with endometrial cancer (OR=1.39, 95% Cl. 1.00-1.93). All haplotype global p-values were null. Conclusion. Common genetic variation in PTEN, PIK3CA, AIM MLH1, or MSH2 was not statistically significantly associated with endometrial cancer. Published by Elsevier Inc. C1 [Lacey, James V., Jr.; Yang, Hannah; Gaudet, Mia M.; Lissowska, Jolanta; Sherman, Mark E.; Peplonska, Beata; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Dunning, Alison; Healey, Catherine S.; Ahmed, Shahana; Pharoah, Paul] Univ Cambridge, Canc Res UK Human Canc Genet Res Grp, Dept Oncol, Cambridge, England. [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. [Easton, Douglas] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England. [Chanock, Stephen] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chanock, Stephen] NCI, Lab Translat Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lacey, JV (reprint author), 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jlacey@coh.org RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166 FU National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX Supported by the Intramural Research Program of the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. NR 32 TC 7 Z9 9 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2011 VL 120 IS 2 BP 167 EP 173 DI 10.1016/j.ygyno.2010.10.016 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 715CA UT WOS:000286856800002 PM 21093899 ER PT J AU Kamath, GS Zareba, W Delaney, J Koneru, JN McKenna, W Gear, K Polonsky, S Sherrill, D Bluemke, D Marcus, F Steinberg, JS AF Kamath, Ganesh S. Zareba, Wojciech Delaney, Jessica Koneru, Jayanthi N. McKenna, William Gear, Kathleen Polonsky, Slava Sherrill, Duane Bluemke, David Marcus, Frank Steinberg, Jonathan S. TI Value of the signal-averaged electrocardiogram in arrhythmogenic right ventricular cardiomyopathy/dysplasia SO HEART RHYTHM LA English DT Article DE Arrhythmogenic right ventricular cardiomyopathy/dysplasia; Signal-averaged electrocardiogram ID TERM-FOLLOW-UP; RISK STRATIFICATION; MAGNETIC-RESONANCE; LATE POTENTIALS; DYSPLASIA/CARDIOMYOPATHY; DYSPLASIA; DIAGNOSIS; TACHYCARDIA; CRITERIA; ARRHYTHMIAS AB BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited disease that causes structural and functional abnormalities of the right ventricle (RV). The presence of late potentials as assessed by the signal-averaged electrocardiogram (SAECG) is a minor task force criterion. OBJECTIVE The purpose of this study was to examine the diagnostic and clinical value of the SAECG in a large population of genotyped ARVC/D probands. METHODS We compared the SAECGs of 87 ARVC/D probands (age 37 +/- 13 years, 47 males) diagnosed as affected or borderline by task force criteria without using the SAECG criterion with 103 control subjects. The association of SAECG abnormalities was also correlated with clinical presentation, surface ECG, ventricular tachycardia (VT) inducibility at electrophysiologic testing, implantable cardioverter-defibrillator therapy for VT, and RV abnormalities as assessed by cardiac magnetic resonance imaging (cMRI). RESULTS Compared with controls, all three components of the SAECG were highly associated with the diagnosis of ARVC/D (P <.001). They include the filtered QRS duration (97.8 +/- 8.7 ms vs 119.6 +/- 23.8 ms), low-amplitude signal (24.4 +/- 9.2 ms vs 46.2 +/- 23.7 ms), and root mean square amplitude of the last 40 ms of the QRS (50.4 +/- 26.9 +/- mu V vs 27.9 +/- 36.3 mu V). The sensitivity of using SAECG for diagnosis of ARVC/D was increased from 47% using the established 2 of 3 criteria (i.e., late potentials) to 69% by using a modified criterion of any 1 of 3 criteria, while maintaining a high specificity of 95%. Abnormal SAECG as defined by this modified criterion was associated with a dilated RV volume and decreased RV ejection fraction detected by cMRI (P <.05). SAECG abnormalities did not vary with clinical presentation or reliably predict spontaneous or inducible VT and had limited correlation with ECG findings. CONCLUSION Using 1 of 3 SAECG criteria contributed to increased sensitivity and specificity for the diagnosis of ARVC/D. This finding is incorporated in the recent modification of the task force criteria. C1 [Steinberg, Jonathan S.] St Lukes Hosp, Div Cardiol, Al Sabah Arrhythmia Inst, New York, NY 10025 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Zareba, Wojciech; Polonsky, Slava] Univ Rochester, Sch Med, Rochester, NY USA. [McKenna, William] Heart Hosp, London, England. [Gear, Kathleen; Marcus, Frank] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. [Sherrill, Duane] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Bluemke, David] NIH Clin Ctr, Bethesda, MD USA. [Steinberg, Jonathan S.] Roosevelt Hosp, Div Cardiol, Al Sabah Arrhythmia Inst, New York, NY 10025 USA. RP Steinberg, JS (reprint author), St Lukes Hosp, Div Cardiol, Al Sabah Arrhythmia Inst, 1111 Amsterdam Ave, New York, NY 10025 USA. EM jss7@columbia.edu RI McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute (NHLBI) [U01 HL65594, HL65652, HL65691] FX Funded by National Heart, Lung, and Blood Institute (NHLBI) Grants U01 HL65594, HL65652, and HL65691. Dr. Steinberg is the Al-Sabah Endowed Director of the Arrhythmia Institute at St. Luke's and Roosevelt Hospitals. NR 43 TC 24 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2011 VL 8 IS 2 BP 256 EP 262 DI 10.1016/j.hrthm.2010.10.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 712GC UT WOS:000286652900018 PM 20933608 ER PT J AU Guo, XC Zhang, Y Li, J Ma, JC Wei, ZL Tan, WJ O'Brien, SJ AF Guo, Xiuchan Zhang, Yong Li, Ji Ma, Jingchen Wei, Zuli Tan, Wenjie O'Brien, Stephen J. TI Strong Influence of Human Leukocyte Antigen (HLA)-DP Gene Variants on Development of Persistent Chronic Hepatitis B Virus Carriers in the Han Chinese Population SO HEPATOLOGY LA English DT Article ID CHRONIC VIRAL-HEPATITIS; HEPATOCELLULAR-CARCINOMA; INFECTIOUS-DISEASES; ASSOCIATION; HLA; POLYMORPHISMS; CLEARANCE; SUSCEPTIBILITY; BINDING; KOREA AB Chronic hepatitis B virus (HBV) infection is a major health issue, especially in Asia. A recent genome-wide association study (GWAS) implicated genetic variants in the human leukocyte antigen (HLA)-DP locus associated with chronic hepatitis B in Japanese and Thai populations. To confirm whether the polymorphisms at the HLA-DP genes are associated with persistent chronic HBV infection in Han Chinese, we conducted an independent casecontrol study using 521 persistent chronic HBV carriers and 819 controls that included 571 persons with HBV natural clearance and 248 never HBV-infected (healthy) individuals. Eleven single nucleotide polymorphisms (SNPs) in a region including HLA-DPA and HLA-DPB and an adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA-DR13 locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at HLA-DP showed a strong association with persistent chronic HBV carrier status (P = 1.82 X 10(-12) to 0.01). We also stratified the analysis by HBV clearance status to test the association between these polymorphisms and HBV natural clearance; similar results were obtained (P = 2.70 x 10(-1)1 to 0.003). Included SNPs define highly structured haplotypes that were also strongly associated with HBV chronic infection (block 1: odds ratio [OR] = 0.54, P = 8.73 x 10(-7); block 2: OR = 1.98, P = 1.37 x 10(-10)). These results further confirm that genetic variants in the HLA-DP locus are strongly associated with persistent HBV infection in the Han Chinese population. (HEPATOLOGY 2011;53:422-428) C1 [Guo, Xiuchan] Wenzhou Med Coll, Zhejiang Prov Key Lab Med Genet, Sch Lab Med & Life Sci, Wenzhou, Zhejiang, Peoples R China. [Guo, Xiuchan; Zhang, Yong] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Inst Viral Dis Control & Prevent, Beijing, Peoples R China. [Guo, Xiuchan; Li, Ji; O'Brien, Stephen J.] NCI, Lab Genom Divers, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Ma, Jingchen] Hebei Prov Ctr Dis Control & Prevent, Shijiazhuang, Peoples R China. [Wei, Zuli] Luohes Ctr Dis Control & Prevent, Luohe City, Henan, Peoples R China. [Tan, Wenjie] Chinese Ctr Dis Control & Prevent, Biotech Ctr Viral Dis Emergency, Inst Viral Dis Control & Prevent, Beijing, Peoples R China. RP Guo, XC (reprint author), Wenzhou Med Coll, Zhejiang Prov Key Lab Med Genet, Sch Lab Med & Life Sci, Wenzhou, Zhejiang, Peoples R China. EM xguo1@cdc.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX Funded in whole or in part with federal fiends 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 U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 82 Z9 96 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2011 VL 53 IS 2 BP 422 EP 428 DI 10.1002/hep.24048 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 715BO UT WOS:000286855600008 PM 21274863 ER PT J AU Nelson, JE Wilson, L Brunt, EM Yeh, MM Kleiner, DE Unalp-Arida, A Kowdley, KV AF Nelson, James E. Wilson, Laura Brunt, Elizabeth M. Yeh, Matthew M. Kleiner, David E. Unalp-Arida, Aynur Kowdley, Kris V. CA Nonalcoholic Steatohepatitis Clini TI Relationship Between the Pattern of Hepatic Iron Deposition and Histological Severity in Nonalcoholic Fatty Liver Disease SO HEPATOLOGY LA English DT Article ID NF-KAPPA-B; HEREDITARY HEMOCHROMATOSIS PROTEIN; KUPFFER CELLS; HEPCIDIN EXPRESSION; OXIDATIVE STRESS; GENETIC HEMOCHROMATOSIS; MOLECULAR-MECHANISM; INSULIN-RESISTANCE; STEATOHEPATITIS; HFE AB Previous studies examining the relationship between hepatic iron deposition and histological severity in nonalcoholic fatty liver disease (NAFLD) have been inconclusive. The goal of this study was to examine the relationship between hepatic iron deposition and liver histology in 849 patients enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Hepatic iron staining was performed in a central laboratory, and the stains were scored for grade and cellular and parenchymal localization by a central pathology committee; the relationship between the grade and pattern of iron deposition and the clinical, laboratory, and histological variables was examined with univariate and multivariate analyses. Stainable hepatic iron was present in 293 of 849 patients (34.5%) in one of three histological patterns: a hepatocellular (HC) pattern [63/849 (7.4%)], a reticuloendothelial system (RES) cell pattern [91/849 (10.7%)], or a mixed RFS/HC pattern [139/849 (16.4%)]. Patients with the RES iron-staining pattern were more likely to have advanced fibrosis compared to those with those with HC iron (P = 0.01). Patients with RES iron were also more likely to have advanced histological features such as fibrosis (P = 0.049), portal inflammation (P = 0.002), HC ballooning (P = 0.006), and definite nonalcoholic steatohepatitis (P = 0.007) compared to those with patients with HC or mixed iron patterns. The presence of RES iron (odds ratio = 1.60, 95% confidence interval = 1.10-2.33, P = 0.015) was independently associated with advanced hepatic fibrosis on multiple regression analysis after adjustments for age, gender, diabetes status, and body mass index. Conclusion: The presence and pattern of hepatic iron deposition are associated with distinct histological features in patients with NAFLD and may have implications for pathophysiology and therapy. (HEPATOLOGY 2011;53:448-457) C1 [Kowdley, Kris V.] Virginia Mason Med Ctr, Ctr Liver Dis, Inst Digest Dis, Seattle, WA 98101 USA. [Nelson, James E.; Kowdley, Kris V.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. [Wilson, Laura; Unalp-Arida, Aynur] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Brunt, Elizabeth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Yeh, Matthew M.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Kowdley, KV (reprint author), Virginia Mason Med Ctr, Ctr Liver Dis, Inst Digest Dis, 1201 9th Ave, Seattle, WA 98101 USA. EM kkowdley@benaroyaresearch.org OI Kleiner, David/0000-0003-3442-4453 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institute of Child Health and Human Development; National Institutes of Health [DK-02957]; General Clinical Research Centers [UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, ULIRR02501401, M01RR000065, M01RR020359]; National Cancer Institute FX The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713) and by the National Institute of Child Health and Human Development. Kris V Kowdley is supported by the National Institutes of Health (K24 grant DK-02957). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards to conduct studies for the Nonalcoholic Steatohepatitis Clinical Research Network (grants UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, ULIRR02501401, M01RR000065, and M01RR020359). This work was supported in part by the Intramural Research Program of the National Cancer Institute. NR 50 TC 78 Z9 85 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2011 VL 53 IS 2 BP 448 EP 457 DI 10.1002/hep.24038 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 715BO UT WOS:000286855600011 PM 21274866 ER PT J AU Ohmine, K Li, Y Bauer, TR Hickstein, DD Russell, DW AF Ohmine, Ken Li, Yi Bauer, Thomas R., Jr. Hickstein, Dennis D. Russell, David W. TI Tracking of Specific Integrant Clones in Dogs Treated with Foamy Virus Vectors SO HUMAN GENE THERAPY LA English DT Article ID NIJMEGEN-BREAKAGE-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; NOD/SCID-REPOPULATING CELLS; HEMATOPOIETIC STEM-CELLS; RETROVIRAL GENE MARKING; LONG-TERM; THERAPY; ACTIVATION; TRANSDUCTION AB Vector integration can lead to proto-oncogene activation and malignancies during hematopoietic stem cell gene therapy. We previously used foamy virus vectors to deliver the CD18 gene under the control of an internal murine stem cell virus promoter and successfully treated dogs with canine leukocyte adhesion deficiency. Here we have tracked the copy numbers of 11 specific proviruses found in these animals for 36-42 months after transplantation, including examples within or near proto-oncogenes, tumor suppressor genes, and genes unrelated to cancer. We found no evidence for clonal expansion of any of the clones, including those with proviruses in the MECOM gene (MDS1-EVI1 complex). These results suggest that although foamy virus vectors may integrate near proto-oncogenes, this does not necessarily lead to clonal expansion and malignancies. Additionally, we show that copy number estimates of these specific proviruses based on linker-mediated PCR results are different from those obtained by quantitative PCR, but can provide a qualitative assessment of provirus levels. C1 [Ohmine, Ken; Li, Yi; Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. [Bauer, Thomas R., Jr.; Hickstein, Dennis D.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Russell, David W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. RP Russell, DW (reprint author), Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. EM hicksted@mail.nih.gov; drussell@u.washington.edu FU U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research; U.S. National Institutes of Health [HL53750, HL085107] 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, and by U.S. National Institutes of Health grants HL53750 and HL085107. We thank Laura Tuschong for processing blood samples and Mehreen Hai for assistance with LM-PCR. NR 45 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB PY 2011 VL 22 IS 2 BP 217 EP 224 DI 10.1089/hum.2010.072 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 722PQ UT WOS:000287447200012 PM 20738155 ER EF